Atrial fibrillation (AF) is highly prevalent in nonagenarians (≥ 90 years). However, this group is often excluded from clinical trials, leaving limited real-world evidence on oral anticoagulant (OAC) use, safety, and efficacy. This study sought to investigate the usage patterns, predictors, and in-hospital outcomes of OAC therapy in nonagenarian patients with AF to provide real-world evidence to inform clinical decision-making. A retrospective single-center analysis was conducted on 290 nonagenarian AF patients (Beijing Hospital, 2018–2024). Patients were grouped as OAC (n = 89) or non-OAC (n = 201). Primary endpoints: In-hospital stroke/SE (efficacy) and major bleeding (ISTH criteria; safety). Secondary endpoints included in-hospital composite efficacy, net clinical benefit (stroke/SE/major bleeding/all-cause death), and all-cause death. Multivariate logistic regression identified OAC predictors; OAC temporal trends were analyzed. The overall OAC utilization rate was 30.69

BackgroundImmunoglobulin A nephropathy (IgAN) is not only the most common primary glomerular disease but also a chronic inflammatory condition associated with increased cardiometabolic risk through the cardiorenal axis. Persistent proteinuria and progressive renal dysfunction are linked to adverse cardiovascular and metabolic outcomes and may complicate the delivery of long-term lifestyle and nutritional risk–modifying strategies. Telitacicept, a dual BAFF/APRIL inhibitor, has emerged as a targeted immunomodulatory therapy for IgAN, yet the clinical evidence remains heterogeneous.MethodsWe conducted a scoping review of clinical studies evaluating telitacicept in biopsy-confirmed IgAN. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to 2 January 2026. Randomized and observational studies reporting renal outcomes were included. When available, cardiometabolic- and nutrition-related variables (e.g., blood pressure, lipid profile, uric acid, body weight/BMI, inflammatory markers, and lifestyle/nutritional counseling) were also captured.ResultsTwenty-four studies were identified, including one randomized controlled trial, 16 observational studies, and seven case reports/series. Across studies, telitacicept consistently reduced proteinuria (approximately 49–87%) while maintaining stable estimated glomerular filtration rate. Additional reported benefits included improvements in serum albumin-likely reflecting reduced urinary protein loss—and glucocorticoid-sparing effects. The therapy was generally well tolerated, with predominantly mild adverse events. Notably, cardiometabolic and nutritional endpoints were inconsistently reported across the current literature, limiting definitive conclusions regarding these outcomes.ConclusionCurrent evidence suggests that telitacicept may offer a promising targeted therapeutic option for IgAN by achieving sustained proteinuria reduction and renal function stabilization. From a clinical practice perspective, improved renal and inflammatory control may facilitate the implementation of long-term nutritional and metabolic risk–modifying strategies in high-risk IgAN populations; however, direct evidence linking telitacicept to cardiometabolic or nutritional endpoints remains scarce. Larger, long-term randomized studies incorporating prespecified cardiometabolic and nutritional outcomes are warranted.

Gastric precancerous lesions (GPLs) are a pivotal stage in the gastritis-gastric cancer sequence, and the absence of effective treatments presents a clinical challenge. Veratramine is a natural anti-inflammatory and analgesic steroid alkaloid; however, its effects on GPLs and the mechanisms have remained unexplored. This study investigated the effects of veratramine on GPLs using 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG)-induced GES-1 cells and rat models, utilizing RNA-seq to elucidate the underlying mechanisms. In vitro, veratramine inhibited malignant cells (MC) proliferation, induced apoptosis, and triggered G0/G1 cell cycle arrest. It also suppressed epithelial-mesenchymal transition (EMT), migration, and invasion by upregulating E‑cadherin and downregulating Slug and vimentin. Transcriptomic and molecular docking analyses highlighted the Wnt/β-catenin pathway as a key target, regulated via DDX60, MUC1, APOL1, and MSH5. Veratramine reduced Wnt10B, β-catenin, and cyclin D1 expression and blocked β‑catenin nuclear translocation; these effects were reversed by the Wnt activator BML-284. In vivo, treatment with veratramine ameliorated the GPLs-induced pathological changes in rats. It restored body weight and preserved gastric mucosal integrity, as evidenced by intact glandular and cellular morphology, reduced hyperplasia, and attenuated intestinal metaplasia. These improvements were associated with a modulation of key molecular markers, specifically a decrease in the expression of N-cadherin, Wnt10B, and β-catenin, alongside an increase in E-cadherin expression in gastric tissues. These results collectively indicate that veratramine exerts its therapeutic effects against GPLs primarily by suppressing the Wnt/β-catenin signaling pathway. Taken together, our findings suggest that veratramine is a promising candidate small-molecule drug for the treatment of GPLs.

Andrographolide, a natural labdane diterpenoid lactone isolated from Andrographis paniculata, possesses diverse pharmacological properties such as anti-tumor, anti-inflammatory, antiviral, and immunomodulatory activities, rendering it a promising candidate for therapeutic development. In this study, pharmacokinetic profiles, excretion features, and metabolism of andrographolide were systematically investigated in rats using a liquid chromatography/mass spectrometry (LC/MS)-based approach. Following intravenous and oral administration, andrographolide exhibited high elimination and moderate bioavailability. Excretion study revealed that less than 5% of the administered dose was eliminated in its parent form in urine and feces. Metabolic profiling identified a total of 39 analytes, among which 34 were sulfated conjugates—establishing sulfation as the most structurally diverse metabolic pathway of andrographolide in rats. A novel MS/MS fragmentation workflow was established, which enabled the unambiguous discrimination of four sulfation modification sites: O-sulfation at the C3 and C19 positions, and C-sulfation at the C12 and C14 positions. Collectively, this comprehensive study delineates the complete in vivo disposition of andrographolide in rats and clarifies the site-specific sulfation rules of its metabolites.

Traditional pharmacovigilance (PV) relies heavily on spontaneous reporting systems (SRS), which remain vulnerable to under-reporting and limited mechanistic insight. Artificial intelligence (AI) and real-world data (RWD) offer opportunities to strengthen signal detection, risk prediction, and translational safety assessment, but most applications remain at retrospective development or early implementation stages. We conducted a structured narrative scoping review with critical appraisal, reported using PRISMA-ScR. Literature from 2010 to 2026 was identified through expert review, reference chaining, and regulatory sources. English-language publications on AI or machine learning in clinical pharmacovigilance with real-world data were synthesized thematically across data sources, analytical methods, validation strategies, and implementation challenges. RWD ecosystems-including electronic health records (EHRs), administrative claims, multi-omics, and global SRS-can be integrated with supervised ML, natural language processing (NLP), graph neural networks (GNNs), and federated learning (FL) for diverse PV tasks. Reported area under the receiver operating characteristic curve (AUROC) values often exceed 0.90 in internal validation, yet external validation, calibration, decision-curve analysis, and prospective implementation evidence remain inconsistently reported. Common data models such as the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) and FL architectures improve interoperability and privacy-preserving collaboration. Causal and explainable AI methods are emerging but require explicit assumptions and mechanistic confirmation before regulatory-grade causal claims. AI-enabled PV is transitioning from association-focused surveillance toward prediction, mechanistic interpretation, and implementation science, yet widespread clinical or regulatory adoption requires transparent reporting (e.g., TRIPOD + AI, PROBAST), rigorous external and prospective validation, clear separation of association from causation, clinically interpretable outputs, sustained human oversight, and governance within harmonizing regulatory frameworks.

The FAERS database is a vital tool for identifying adverse drug reactions (ADRs). However, data mining in FAERS faces significant challenges, including data quality issues (e.g., integrity, consistency, and completeness) and limitations in traditional model selection. These issues can introduce biases and affect the reliability of safety signal detection. This review critically analyzes the current state and limitations of FAERS data mining, particularly by briefly comparing it with other mainstream global databases to contextualize its unique challenges. It then proposes optimization strategies, focusing on improved data preprocessing, algorithm refinement, and the integration of emerging technologies. We emphasize the potential of Artificial Intelligence (AI) and multi-source data fusion to enhance detection sensitivity, accelerate the risk signal identification cycle, and address challenges in data-limited scenarios, such as rare diseases. We recommend promoting database standardization, strengthening validation, and formulating policy changes to fully realize FAERS's potential for precision pharmacovigilance.

Given the narrow therapeutic window, high inter-individual variability, and inherent risks of Narrow Therapeutic Index Drugs (NTIDs), this study systematically analyzes global NTID regulatory policies to explore pathways for optimizing China’s lifecycle management system. The ultimate goals are to ensure clinical medication safety and promote the healthy development of the generic drug industry. This research conducts a systematic comparative policy review and narrative synthesis of the current regulatory landscape of NTIDs in China, covering both pre-market and post-market stages. We systematically identified and screened regulatory documents, technical guidelines, and policy statements from major international jurisdictions, including the United States Food and Drug Administration (USFDA), the European Medicines Agency (EMA), Health Canada, and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). The analysis focused on four core pillars: catalog status, bioequivalence (BE) requirements, generic substitution policies, and post-market risk monitoring. China’s NTID regulatory system currently under development but has not yet formed a comprehensive, systematic, and dynamically updated framework. Globally, regulatory bodies generally impose stricter lifecycle controls, particularly by narrowing BE acceptance intervals (e.g., AUC to 90.00–111.11

ObjectiveTo mine tacrolimus-related adverse event signals affecting the cardiovascular system based on an international authoritative database, aiming to provide a reference for clinical safe drug use.MethodsAdverse event reports with tacrolimus as the primary suspected drug were retrieved and extracted from the U.S. Food and Drug Administration Adverse Event Reporting System(FAERS) database from January 1, 2004, to September 30, 2024, with a focus on cardiovascular system-related adverse events. Adverse events were categorized using the system organ class(SOC) and preferred terms(PTs) from the Medical Dictionary for Regulatory Activities(MedDRA). Signal mining for cardiovascular system-related adverse drug events(ADEs) was performed using the information component(IC), empirical Bayesian geometric mean(EBGM), and reporting odds ratio(ROR) methods.ResultsA total of 58 357 ADE reports with tacrolimus as the primary suspected drug were retrieved, of which 3173 were related to cardiovascular system disorders. The top five most frequently reported cardiovascular adverse events were hypertension, cardiac arrest, heart failure, myocardial infarction, and atrial fibrillation. ADE signal detection identified correlations between tacrolimus and hypertension, cardiac arrest, heart failure, ventricular hypertrophy, cardiomyopathy, and cardiac hypertrophy. Regarding the outcomes of cardiovascular adverse events, "hospitalization or prolongation of existing hospitalization" was the most common(34.74%), followed by "death"(29.44%).ConclusionsTacrolimus carries the risk of inducing various cardiovascular diseases. In clinical practice, when using tacrolimus, attention should be paid to the patient's underlying diseases and concomitant medications, adverse reactions should be closely monitored during the initial and long-term treatment phases, and the dosage should be adjusted in a timely manner to ensure patient safety during long-term therapy.

Chronic and subchronic toxicity are very important endpoints for evaluating the long-term and medium-term toxicity of chemical substances. However, due to the complex mechanism and diverse chemical structures, developing effective computer models remains a significant challenge. In this study, we developed ChronicDPipredictor, an interpretable machine learning framework for chemical chronic and subchronic toxicity assessment. Among three fingerprint representations (MACCS, PubChem, and KRFP), models based on MACCS fingerprints achieved the best performance, with accuracies up to 0.82 for chronic and 0.80 for subchronic toxicity in three-class classification. When using these three-class models for the binary classification of toxic and non-toxic substances, the overall prediction accuracy for the chronic toxicity and subchronic toxicity of the compounds reached 0.93 and 0.83 respectively, also showing excellent predictive ability. The SHAP analysis was applied to enhance interpretability. We implemented the ChronicDPipredictor framework as a web-server for predicting the chronic and subchronic toxicity of compounds, which can be freely accessed and used via http://ChronicDPi.sapredictor.cn/ . Furthermore, we systematically extracted structural alerts (18 for chronic toxicity and 7 for subchronic toxicity) from KRFP fingerprints. Several representative alerts, such as nitrobenzene, phenylhydrazine, and triazole derivatives, were supported by established toxicological mechanisms, including oxidative stress, DNA damage, enzyme inhibition, and metabolic disruption. This study provides an interpretable and practical method for assessing chronic and subchronic toxicity, which is quite helpful for the risk assessment of compound repeated-dose toxicity.

Among very older patients with atrial fibrillation (AF), the frequency of inappropriate direct oral anticoagulant (DOAC) dosing, associated factors, and temporal trends in practice are unknown. This retrospective study included consecutive inpatients aged 80 years or older with a discharge diagnosis of atrial fibrillation who were prescribed DOACs at discharge from Beijing Hospital between January 2018 and August 2023. Patients were stratified into underdosed, overdosed, or recommended dosing groups. Logistic regression analysis was performed to identify risk factors associated with inappropriate dosing, and temporal trends were evaluated using the Cochran–Mantel–Haenszel test. Among 676 inpatients aged ≥ 80 years with AF (mean age 84.4 ± 3.5 years; 53.1

Background: Hypertension is one of the most prevalent disorders encountered in medical practice, yet effective pharmacotherapy options for resistant hypertension are limited. In this meta-analysis, we aimed to evaluate the efficacy and safety of aprocitentan in treating hypertension. Methods: We searched PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library databases from inception to June 3, 2024, for randomized controlled trials (RCTs) that compared the efficacy and safety between aprocitentan and placebo in treating hypertension. According to the dosage of aprocitentan, the study was divided into a low-dose group (10–12.5 mg), medium-dose group (25 mg), and high-dose group (50 mg). Results: This meta-analysis included five RCTs, which incorporated 1224 patients, and displayed that aprocitentan can reduce the mean sitting systolic blood pressure (msSBP) [(low dose subgroup: mean difference (MD): –3.85 mmHg; 95% confidence interval (CI): –7.47 to –0.23; p = 0.040; medium dose group: MD: –5.56 mmHg; 95% CI: –10.69 to –0.44; p = 0.030)], mean sitting diastolic blood pressure (msDBP) (low dose subgroup: MD: –3.95 mmHg; 95% CI: –4.06 to –3.85; p < 0.001; medium dose group: MD: –4.75 mmHg; 95% CI: –5.91 to –3.60; p < 0.001), 24-hour ambulatory systolic blood pressure (maSBP) (low dose group: MD: –4.18 mmHg; 95% CI: –4.32 to –4.04; p < 0.001; medium dose group: MD: –5.89 mmHg; 95% CI: –6.03 to –5.75; p < 0.001), and 24-hour ambulatory diastolic blood pressure (maDBP) (low dose group: MD: –4.33 mmHg; 95% CI: –4.42 to –4.24; p < 0.001; medium dose group: MD: –5.82 mmHg; 95% CI: –5.91 to –5.73; p < 0.001). In the high-dose group, there was no difference between the aprocitentan and placebo groups in the msSBP (MD: –4.83 mmHg; 95% CI: –11.44 to 1.79; p = 0.150). Meanwhile, the safety profile of aprocitentan was good, and no significant differences in the frequency of adverse events (AEs) and serious adverse events (SAEs) were observed compared to the placebo. Conclusions: Aprocitentan significantly reduces blood pressure and has a good safety profile. However, it is worth noting that high doses of aprocitentan (50 mg) did not yield better blood pressure-lowering effects.

infection or allergic constitution. In recent years, many studies have attempted to explore the effects of human microbiome-based interventions on the regulation of host immunity and the prevention of respiratory tract infections. However, the heterogeneous and inconsistent reproducibility between studies resulted in inconsistent opinions among physicians in terms of the recommendation of probiotics to patients. As an evidence-based research method recommended by academia in recent years, probiotic finished product research is an effective method to promote the development of probiotics industry. The research results are more consistent with the clinical outcomes in a realworld setting and hence conducive to experts' clinical use and also inform consumer decisions. This expert panel suggests that the upper respiratory tract probiotic Bactoblis can be a valuable tool for physicians to recommend to patients in addition to standard drug therapy. This recommendation is based on its successful application in clinical practice in China and Europe, positive patient feedback, and evidence from multiple clinical trials limited to those where a single finished product was admistered to subjects. The panel also encourages physicians to explore new research areas related to respiratory microbiota, believing that such interventions hold great potential for improved disease management and enhancing patients' quality of life.Expert ConsensusComplementary use together with standard treatment to ameliorate disease when standard therapy does not improve health conditions effectively Complementary use together with standard treatment to ameliorate disease when standard therapy does not improve health conditions effectivelyThe upper respiratory tract is a crucial site for host defense, as it is home to bacterial communities that both modulate host immune defense and serve as a reservoir of potential pathogens. During the first few years of life, much like the gastrointestinal tract microbiome, nasopharyngeal microbiota in young children changes from an immature state to a more diverse state as it matures to resemble the adult microbiota, resulting in a higher risk of respiratory illness in young children [1]. According to a systematic analysis on respiratory infections for 33 provinces in China from 1990 to 2019, a consistently increasing trend in the number of RTi cases was observed. RTi cases in 2019 was 3%, 5% and 11% higher than that in 2010, 2000 and 1990, respectively. The incidence rate of URTis was the largest in younger children indicating that the future URTi and LRTi prevention strategies should focus on the maternal and child health, especially in young children [2]. URTIs, although they are generally mild and resolve spontaneously, can significantly impact the quality of life, school attendance of children work absence for caregivers. Paediatricians andcaregivers require prevention strategies to reduce the recurrence incidence in children prone to frequent RTIs to reduce medical visits. Risk factors that are significantly associated through odds ratio (OR) with recurrent respiratory tract infection include asthma(OR = 8.31 (P < 0.001)), allegry (OR = 2.31 (P < 0.001)), initial use of antibiotics (OR = 1.72 (P < 0.001)), breastfeeding duration < 6months (OR = 1.24 (P<0.002)), and maternal body mass index 1.19 (P < 0.001) [4]. In general, distinct microbial maturation patterns involved with early asymptomatic respiratory viral presence and dynamics in gene expression profiles [5], translate into either a beneficial microbiota or susceptibililty to RTI development and/or asthma and/or allergic rhinitis. A "three-hit" model for chronic RTI development begins with an establishment of non-beneficial respiratory microbiota as the first hit, suffering RTi with varying degree of severity as second hit, and progression to a long-term inflammatory airway status as the third hit [6]. The strategies for managing pediatric recurrent respiratory tract infections (RRTi) can be built on several key approaches. One approach focuses on modulating non-specific immune responses to strengthen the body's natural defenses against infectious agents. Another involves enhancing specific immune responses to directly combat respiratory pathogens. Additionally, managing inflammation through anti-inflammatory responses can help reduce infection-or pathogeninduced airway inflammation. Modulating respiratory microflora through the administration of probiotics that colonize the airway is also promising. This approach aims to improve the interaction between host commensal bacteria and the immune system, ultimately reducing susceptibility to RRTi.To date, unnecessary antibiotics are widely prescribed for pediatric RTIs and most pediatric patients with RTIs do not receive guideline-recommended antibiotic classes in Chinese primary healthcare facilities [7],. Meanwhileparents often resort to self-medication with antibiotics to their children in China [8]. Unfortunately, microbiome recovery lost diversity after short courses of antibiotics and can be delayed by Azithromycin, the long-term effect of altered diversity, resistance and composition is considered as "antibiotic scarring" [9].Well documented evidence suggests that early antibiotic exposure affects the development of infant gut microbiota and the disturbances in host increase the susceptibility to variety of diseases later in life including respiratory infections.[10],In addition, antibiotic use in early life preferentially impairs the development of lung mucosal-associated invariant T (MAIT) cell which plays an important role in recognizing a broad array of respiratory pathogens [11].Antibiotic-induced microbial disruption in early life can be exacerbated by the vertical transmission of resistance genes from mother to offspring during pregnancy and lactation, and [12], is associated with higher risks of childhood metabolic disorders [13], neurobehavioral conditions including autism spectrum disorder, intellectual disorder, language disorder, epilepsy [14], and Juvenile Idiopathic Arthritis (JIA) [15].Although most recent reviews reveal the variable outcomes, knowledge gaps and insufficient evidence to recommend probiotic for prevention or management of RTi conditions [16][17][18][19], specific formula with consistent positive clinical results should be recommended, and be considered as a possible supportive approach in selected patients to improve their quality of life and reduce the burden of RTIs.Oropharyngeal probiotics, Bactoblis has clinical and real-world evidence for indications of selected Therefore, it is extremely important for healthcare professionals to be properly educated and updated on the knowledge of oropharyngeal probiotics even though their awareness towards gut probiotic has been well-established [21], with the purpose of assisting pediatricians or practitioners who are willing to offer their patients an alternative option to safely and effectively manage their respiratory conditions and appropriately recommend the use of oropharyngeal probiotics. The following professional recommendations are meant to be broadly applicable and should be viewed as the preferred alternative and adjunctive approach. However, they are not meant to replace standard approaches and clinical management strategies depend on individual clinical scenarios. This project aims to support decision-making in respiratory health based on scientific evidence and the daily life of both the pediatric patients with respiratory infections and their care-givers.A meeting of our consensus panal consisting of clinical and scientific experts (with specialties in paediatrics, obstetrician and gynecologist, oncologist, pharmacist, immunology and microbiology scientists) was convened to review, examine, select and synthesize 38 evidence-based publications on oropharyngeal probiotics, and organized them into 2 main topics, which are the existing evidencebased science and the recommendation for future researches, respectively. Participants in the meeting jointly considered key questions and generated and approved the outcomes hereby summarized.We hope that this consensus statement will provide consensus views on the appropriate use of oropharyngeal probiotic, and recommendations for future research associated with oropharyngeal probiotics and human respiratory health. societies and group of experts technically reviewed 10 clinical trials conducted with oropharyngeal probiotics with documented efficacy for management of RRTi published since 2012 with a total of 832 children participating.Oropharyngeal probiotic Bactoblis was given in the form of slowly dissolving oral lozenges, to be administered before bedtime after brushing teeth every evening and subjects were required to suck the lozenge until fully dissolved (approximately 4-5 min) and making sure that the lozenge was not chewed or directly swallowed. They were suggested not to drink or swallow any substance for at least 1 hour after the administration of oropharyngeal probiotic lozenges. If the subjects were prescribed with antibiotics by study practitioners during RTIs, they are requested to continuously take the oropharyngeal probiotics during the days taking antibiotics, but making sure that oropharyngeal probiotics and antibiotics had been taken two hours apart.Oropharyngeal probiotics with recommendations for use in clinical practices were discussed based on the evaluation of 10 trials in terms of population, burden of RRTi, current treatment strategies, probiotic dose and administration schedule. Overall, oropharyngeal probiotic, as a general group, reduced the risk of developing new episodes of respiratory tract infections and antibiotic exposure in children with RRTi. A conditional recommendation based on level 2 evidence criteria graded by study type of randomized trials with consistent effect according to the latest World Gastroenterology Organisation Global Guidelines: Probioticcs and Prebiotics 2024 [22], on the adjunctive use of oropharyngeal probiotics supportive of standard treatment in children with recurrent respiratory tract infections was made, in the context of the corresponding 10 clinical trials. Most of the 10 trials are homogeneous in regards to study subjects, dosage, the schedule of administration and formulation, oropharyngeal probiotic Bactoblis has been found to have a good safety profile. These findings revealed that compared to controls, people with a history of recurrent RTIs receiving oropharyngeal probiotic Bactoblis had a significantly lower risk of new episodes of RTi during the study period reduced by around 90%, the protective benefit was observed during both the intervention period and maintained several months after the end of intervention. The risk of antibiotic exposure was significantly higher among controls than among subjects administrating oropharyngeal probiotic Bactoblis. Limitation of the 10 studies were the use of non-blinded method and that the pathogen type and severity of RTIs were not defined by molecular tests and RTi-related quality of life, the type of antibiotic used by the subjects were not described in the article, and the size of the studies was generally small. However, the baseline clinical characteristics of the enrolled subjects were precisely defined in all of 10 trials. Among the 10 trials, 6 were published in English of which 5 were carried out in Europe and 1 was carried out in China, 4 were carried out in Ukraine and published in Ukrainian with the abstract in English and in most cases were publish in Ukrainian journals. Clinical studies evidencing that oropharyngeal probiotic Bactoblis can provide clinical benefit on recurrent RTi management are listed in Table 1.Otitis media that represents a significant burden on children, their families, and the healthcare system is the major cause of hearing loss and serious life-long sequelae, such as behavior, attention [34], anxiety, learning and speech-language problems in early and late childhood [35], if left their chronic and recurrent otitis media untreated. Chronic and recurrent otitis media are recalcitrant to current therapies due to the formation of biofilms and intracellular biofilm pods by otopathogens on the middle ear mucosa and within the middle ear fluid [36]. antibiotics are generally used empirically for treating chronic suppurative otitis media, which may lead to the emergence of resistant bacterial strains [37]. In addition, official recommendations differ regarding tympanostomy-tube placement that could favoring the time to a first episode of acute otitis media and various episode-related clinical findings in young children with recurrent acute otitis media, but the rate of acute otitis media episodes, the percentage of episodes considered to be severe, and antimicrobial resistance among respiratory isolates were not significantly lower than with medical management [38]. Relative abundances of potential pathogens such as Haemophilus influenzae, Streptococcus pneumonia and Moraxella catarrhalis in the upper respiratory tract, might lead to further investigation into new preventive measurements for acute, secretory and recurrent otitis media [39]. 7 studies with evidence for oropharyngeal probiotic formula, Bactoblis, providing a clinical benefit for otitis media management are listed in Table 2.Respiratory viral infections are the most common type of acute respiratory infection, predisposing patients to secondary bacterial infections that often have a more severe clinical course, antiviral immune responses induced by acute RTi are associated with dysbiosis in the respiratory tract, which in turn alter subsequent immune function against secondary bacterial infection or the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. [45],Increased microbial diversity and growth rates of specific pathogens in upper respiratory tract was observed, oropharyngeal microbiota is type-specifically disrupted by the infection of influenza A virus (FluA), influenza B virus (FluB), respiratory syncytial virus (RSV), and human rhinovirus (HRV) [46], as well as Omicron or other variant of SARS-CoV-2 viruses [47].Non-pathogenic commensal organisms colonized at nasopharynx and oropharynx possess the ability to interfere with the growth of potential pathogens such as S. pneumoniae, H. influenzae and M. catarrhalis, the carriage of which increases during nasopharyngitis or pharyngitis , as well as symptomatic and asymptomatic viral URTi [48]. Even though respiratory microbiota is shaped during the critical window of early life, season and RTIs, evidence indicates a reduced niche differentiation preceding confirmed RTIs, this loss of ecological topography is further augmented by start of daycare and linked to consecutive development of symptomatic RTIs [49]. In summary, restoring the loss of topography is linked to the prevention of subsequent development of RTi episodes. 4 Studies suggesting the clinical benefit on preventing acute RTi via administration of oropharyngeal probiotic Bactoblis are listed in Table 3.Repeated use of antibiotics is common during the treatment of tonsillitis, and prior antibiotic use is a major contributor to subsequent antibiotic prescribing[51], except recurrent antibiotic prescription, tonsillectomy remains a common pediatric surgery for recurrent and chronic tonsillitis, or recurrent otitis media, however, severe postoperative pain is common and some patients will have postoperative complications of bleeding[52], importantly, a cohort study of 1.2 million patients followed for up to 30 years showed that childhood adenoidectomy or tonsillectomy was associated with a significantly increased relative risk of respiratory infections and allergies later in life, increases in long-term absolute disease risks were considerably larger than changes in risk for the disorders these surgeries aim to treat, suggesting that it is important to consider long-term risks when making decisions to perform tonsillectomy or adenoidectomy [53]. Children who had adenoidectomy for adenoid-related diseases are mostly due to obstructive sleep-disordered breathing, otitis media with effusion, and chronic sinusitis, while respiratory pathogens H. influenzae, S. aureus, S. pneumoniae and M. catarrhalis are commonly found in adenoid [54]. Surgical removal of adenoids and tonsils to treat obstructed breathing or recurrent middle-ear infections remain common pediatric procedures, however, meta-analysis of current literature included more than a thousand subjects demonstrated that pediatric sleep apnea is often not cured by tonsillectomy and adenoidectomy [55]. Chronic adenoiditis occurs frequently in children, and it is complicated by the subsequent development of recurrent or chronic middle ear diseases, such as recurrent acute otitis media, persistent otitis media with effusion and chronic otitis media who fail to respond to traditional antibiotic therapy, which may predispose a child to long-term functional sequalae and auditory impairment [56].In the treatment of children with chronic adenoiditis, it is necessary to take into account the features of the normal microbiota of the nasopharynx, by acting on opportunistic and pathogenic microorganisms, favorable conditions for stimulating the growth and development of representatives of the indigenic microbiota can be created, which in turn will contribute to the patient's speedy recovery from chronic adenoiditis and absence of relapses [57]. Further investigation of individual microbiomes in a longitudinal design with implantation of protective oropharyngeal probiotic may have a potential to lead to new strategies as an alternative to adenoidectomy. 4 Studies demonstrating that oropharyngeal probiotic Bactoblis can provide clinical benefit on chronic adenoiditis and tonsillitis management are listed in Table 4.The microbiota of the tonsils removed from PFAPA patients differed significantly from those of the non-PFAPA patients, indicating that tonsillar microbiota may play a role in triggering the inflammatory processes that lead to symptoms of PFAPA [61] , further, the tonsil dysbiosis may be associated with altered antimicrobial peptide expression on tonsil surface epithelium as in other autoinflammatory diseases which was not evident in recurrent tonsillitis [62]. 2 Studies evidencing that oropharyngeal probiotic Bactoblis can provide clinical benefit on PFAPA management is listed in Table 5. To restore the beneficial nasopharyngeal microbiota could be an alternative approach for selfmanagement in pediatric patients with allergic respiratory conditions. Evidence from observational studies of children attending daycare revealed that nasopharyngeal probiotics Bactoblis administration in children was associated with an increased abundance of commensal S. salivarius in saliva and a lower abundance of otopathogens, Moraxella, in nasopharynx which is strongly associated with the exacerbation of asthma [72] . More research on oropharyngeal microflora intervention might will help improve the quality of life for people with allergic rhinitis and reduce the risk of developing respiratory infections during high allergy seasons.Despite decades of research, systemic autoimmune diseases (SADs) continue to be a major global health concern and the etiology of these diseases is still not clear. The World Health Organization (WHO) and The International Labour Organization (ILO) have healthcare workers are at risk for work-related rhinitis and asthma. For example, high prevalence rates of occupational asthma are found in nurses (10.7%) in Japan according to the Japanese Guidelines for Occupational Allergic Diseases published in 2020 [85] ,a review of cross-sectional studies indicated that occupational rhinitis affects 10~60% of healthcare workers, while the occupational anaphylaxis was most frequently triggered by natural rubber latex, chemicals, disinfectants and medications [86] . The inflammatory response of allergic rhinitis continues to interact with the imbalance of nasal flora. Exposure to allergens will induce changes in the bacterial flora of the nasal mucosa, leading to acute sinusitis and nasal eosinophilia, leading to more serious nasal symptoms, which will reduce the quality of life[71]. In addition to occupation-related allergens, the adhesion or colonization of specific opportunistic pathogens in the nasal mucosa is also an important risk factor for inducing chronic airway inflammation leading to allergic respiratory diseases[87].It has been reported that the oropharyngeal colonization of Streptococcus pneumoniae and haemophilus influenzae in health care workers working in hospitals is as high as 2 times comparing to non-healthcare workers [88][89] , it was also documented a higher prevalence of Methicillin-resistant S. aureus (MRSA) nasal colonization in healthcare workers [90], medical laboratory staff due to direct and dense contact with the pathogens, and those living with hospital staff, the isolates also appeared more virulent while all isolates were β-lactamases positive [91],another study indicated that the carriage rates of S. aureus and MRSA among surgical HCW (32.4%) and nurses (30.8%) were relatively higher, while the highest MRSA rate was detected in nurses [92].The presence of Staphylococcus spp. was more prevalently on the hands of HCWs working in the internal medicine ward and the surgical ward, which is about 6 times compared to personnel in neonatal unit, while those with multi-drug resistant or extensively drug resistant strains were isolated[93], it was also demonstrated that Staphylococcus spp. were most frequently (40%) isolated from the cellphones of hospital staff, while Gram-positive isolates were all susceptible to the antibiotic used and Gram-negative isolates were all resistant to ceftazidime [94]. The establishment of a balanced and healthier respiratory microflora through the intervention of oropharyngeal probiotics among health care workers and their families is expected to help protect their long term respiratory health, and reduce the risk of transmission of resistance genes to their family members. The rise of antibiotic resistance and a dwindling antimicrobial pipeline have been recognized as emerging threats to public health [99]. Enormous therapeutic challenges may present in specific groups of children who have higher risk acquiring antibiotic resistant genes. For example, major proportion of pneumococci isolated from the nasopharyngeal aspirates of the inpatient children with The panel conducted a technical review of evidence-based clinical review and completed the first expert consensus on the adjuvant use of oropharyngeal probiotics for the management of pediatric respiratory tract infections and otitis media based on the clinical studies that explicitly labeled the use of evidence-based finished formulas rather than formula with only strains described of which the clinical benefit is undefined.The consensus process aims to help more doctors understand how to use the evidence-based oropharyngeal probiotic Bactoblis as dietary supplement, an assistive tool, to be adjunctively used with standard treatment and help their patients better manage their respiratory health, especially for the refractory pediatric recurrent and chronic respiratory tract infections, such as recurrent and suppurative otitis media, recurrent tonsillitis, chronic adenoiditis, etc., adjuvant or prophylactically supplemented with oropharyngeal probiotics can safely reduce the incidence of respiratory tract infections and shorten the course of infectious episodes. Meanwhile, children and parents or their caregivers can also be benefited from the reduced absence from school due to illness, absence due to care-giving, and reduced need for prescriptions of antibiotics and antiviral drugs. This expert consensus can be considered as a widely applicable strategy for self-health management that is accepted according to the patient's active will. The recommendation of oropharyngeal probiotics is not intended to replace any standard treatment. The expert consensus provided by this panel serves only as a reference to best practice, and the diagnosis and treatment of the disease is determined by the physician on a case-by-case basis.The [15] KINDGREN E,LUDVIGSSON J.Infections and antibiotics during fetal life and childhood and their relationship to juvenile idiopathic arthritis:a prospective cohort study[J].Pediatr Rheumatol,2021,19(1):145. [23] .3-12 Among 65 children with a history of recurrent streptococcal respiratory infections, 45 were treated with oropharymgeal probiotics for 90 days, and the remaining 20 subjects that did not take any probiotics served as recurrent control group. Another 17 children without recurrent respiratory infections were served as healthy control group. The incidence of streptococcal pharyngotonsil infection decreased by 92% (p<0.0001) compared to that of previous year during the 90-day oropharyngeal probiotic administration, while it increased by 39% (p<0.001) in children of recurrent control group, in contrast, there was a non-significant increase of 29% in the incidence of streptococcal pharyngotonsil infection among healthy control children compared to that of previous year. During the 6-month follow-up period, children with recurrent streptococcal respiratory infections who received oropharyngeal probiotics experienced a significant reduction of 66% (p=0.0278) in the incidence of pharyngeal tonsillitis compared to children in the recurrent control group.Pierro et al [24] .2013 40 18-65 20 adult patients with streptococcal recurrent pharyngitis or tonsillitis were treated with oropharyngeal probiotics for 90 days as probiotic group and 20 of whom did not take probiotics as a control group. The incidence of pharyngeal tonsillitis in adults during oropharyngeal probiotic administration decreased by 84% (p<0.001) comparing with that of previous year, while it increased slightly by 14% (p<0.001) in control patients; During the 6 months of follow-up period, the incidence of pharyngeal tonsillitis in probiotic group was 62% lower than that in the control group (p=0.0389).Pierro et 2014 b 60 3-13 The prevalence of streptococcal pharyngotonsillitis decreased significantly by 96.8% (p<0.001) during 90 days of oropharyngeal probiotics administration compared with the same quarter of the previous year in children with al [25] .recurrent streptococcal pharyngotonsillitis, while the prevalence of viral pharyngeal tonsillitis was significantly reduced by 80% (p<0.01), the prevalence of streptococcal pharyngotonsillitis and viral pharyngotonsillitis in the control group was not significantly different from that in the previous year. Further, the days of medication, absent from school for children, and absent from work for parents due to caregiving to their children were reduced during the study.Pierro et al [26] .3-10 48 children with recurrent streptococcal adenoiditis were given oropharyngeal probiotics for 90 days, and another 76 children without recurrent adenoiditis were enrolled as healthy controls. The prevalence of adenoiditis in children was significantly reduced by 89.6% (P<0.01) during oropharyngeal probiotic administration compared to that in the previous year, while it increased by 33.3% non-significantly in healthy controls. Prevalence of various respiratory tract infections in children was significantly lower during oropharyngeal probiotics administration compared with that of healthy controls, including a 93% (P<0.01) reduction in bronchitis, a 76% (P<0.01) reduction in viral pharyngitis, a 69% (P<0.05) reduction in rhinitis, a 95% (P<0.01) reduction in influenza, a 93% (P<0.01) reduction in laryngitis, and a 100% (P<0.01) reduction in acute otitis media.Grego ri et al [27] .2016 b 130 3-776 children with recurrent streptococcal pharyngotonsil were treated with oropharyngeal probiotics for 90 days, and 54 children took no probiotics as a control group, and were followed up for 9 months. During the one-year observation period, administration of oropharyngeal probiotics for 3 months significantly reduced the prevalence of streptococcal pharyngotonsil infection by 82% compared to children in the control group (p<0.001).Kryuc hko et al [28] .2017 66 3-10 Pediatric outpatients were classified as three subgroups according to the diagnosis, including 26 in the recurrent pharyngotonsil infection group, 22 in chronic adenoid or tonsil hypertrophy group, and 18 in beta-Hemolytic Group A Streptococcus (BHSGA) infection group, and children in each subgroup were further assigned to take oropharyngeal probiotics for 30 days or to take no probiotic as controls, and then been followed up for 5 months. In the BHSGA subgroup, the prevalence of BHSGA pharyngotonsil infection in children taking oropharyngeal probiotics during the study period was 90% lower than that in the previous year (p<0.001), was 86% less than that in control children (p< 0.001); In chronic adenoid or tonsil hypertrophy subgroup, oropharyngeal probiotics in combination with medication significantly improved the severity of chronic adenoiditis-associated symptoms, such as nasal dyspnea, mouth breathing and snoring during sleep, cough (mainly at night and in the morning), nasal congestion, and hearing loss by about 2 times, compared with children using only a drug prescription; In recurrent pharyngotonsil infection subgroup, significant changes in the pharyngeal microbiome composition were observed during oropharyngeal probiotic administration, especially the decrease in the detection rates of pathogenic haemophilus, staphylococcus aureus, Streptococcus pneumoniae, and streptococcus pyogenes, whether been compared to the time before the study started or been compared with

Sweroside, a natural secoiridoid glycoside derived from various medicinal plants, is known for its anti-tumor, anti-inflammatory, and hepatoprotective properties. However, its pharmacological significance is not fully supported by its low systemic exposure. In this study, a de novo strategy was proposed to investigate the metabolism of sweroside in rats, including drug administration, sample pretreatment, ultra-high-performance liquid chromatography/Quadrupole-Exactive mass spectrometry data acquisition, data processing, and semi-quantitative analysis. First, following oral administration of sweroside to rats, plasma, urine, and feces were collected, and respectively mixed using the area-under-the-curve pooling method. Secondly, data-dependent, dynamic exclusion, and parallel reaction monitoring scan modes were employed to build a tandem mass spectra database. Using a neutral loss fragment-based method, target metabolites were effectively filtered. As a result, sweroside was demonstrated to be extensively metabolized, while 18 metabolites were identified and nine of them were newly reported. Sweroside predominantly underwent phase II metabolism, including glycosylation, sulfonation, glucuronidation, and deglycosylation, and were primarily excreted via the kidney. Notably, N-heterocyclization (M7 and M10) was likely catalyzed by intestinal bacteria. This study not only elucidates the in vivo drug elimination of sweroside but also offers an efficient approach for profiling the metabolism of specific molecules.

Objective:To evaluate the impact of adverse health conditions, including multimorbidity, frailty, malnutrition, cognitive impairment, and polypharmacy, on clinical outcomes in older people with atrial fibrillation (AF). Patients and Methods:This prospective cohort study focused on patients aged 65 years and older with AF. They were admitted to the hospital between September 2018 and April 2019 and followed up for 1 year. We evaluated these participants for adverse health conditions including multimorbidity, frailty, malnutrition, cognitive impairment, and polypharmacy. The primary clinical outcome measured was a combination of all-cause mortality or rehospitalization. Results:197 older patients (≥65 years) with AF (mean age, 77.5±7.1 years; 57.4% men) were enrolled. During 1-year follow-up, Primary endpoint events (all-cause mortality or rehospitalization) occurred in 82 patients (41.6%). Compared with the non-event group, the Charlson comorbidity index (CCI) was higher (2.5±1.9 vs 1.7±1.3, p=0.004), more heart failure (32.9% vs 17.4%, p=0.01) and chronic kidney disease (17.1% vs 7.0%, p=0.03), with lower systolic blood pressure (125.3±18.3 mmHg vs 132±17.9 mmHg, p=0.005) in the event group. On multivariate Cox regression showed that the CCI was associated with a higher odds ratio of the composite outcome of all-cause mortality and rehospitalization (HR: 1.26; 95% CI: 1.02-1.56, p=0.03). Other adverse health conditions showed no significant association with the composite outcome of all-cause mortality and rehospitalization. Conclusion:Among adverse health conditions in older people with AF, multimorbidity appears to be a significant determinant of adverse clinical outcomes. Clinical Trial Registration:ChiCTR1800017204; date of registration: 07/18/2018.

Background SGLT2 inhibitor (SGLT2i) may reduce the risk of contrast-induced acute kidney injury (CI-AKI) in patients with type 2 diabetes mellitus (T2DM) with chronic coronary syndrome (CCS) undergoing angiography. However, the evidence is still inconclusive. We aimed to conduct a real world study and systematically review to provide updated and larger-scale evidence. Study design: Ambispective Cohort Study and Meta-analysis. Setting & population: Patients with T2DM and CCS. Methods The data was obtained from December 2017 to July 2024. Propensity score techniques were applied to enhance between-group comparability. We analyzed CI-AKIESUR and CI-AKIKDIGO and conducted subgroup analyses based on the types of angiographic procedures, including percutaneous coronary interventions (PCI), coronary arteriography (CAG), and Coronary Computed Tomographic Angiography (CCTA). We retrieved similar cohort studies from the literature to perform a meta-analysis. Results from trials reporting CI-AKIESUR and/or CI-AKIKDIGO rates among patients randomized to SGLT2i versus placebo were also meta-analysed. Results A total of 2,350 patients receiving dapagliflozin and 16,251 patients did not receiving any SGLT2i were included before PSM. 2,071 SGLT2i users were matched with 2,071 control patients. The incidence of primary outcome 1 and 2 were both significant lower in SGLT2i group than in the control group, which were both confirmed before and after PSM analysis. Subgroup analysis showed that the incidence of CI-AKI in the SGLT2i group was significantly lower after either PCI, CAG or CCTA. The meta-analysis of cohort studies further confirmed this result, that is, the rate of CI-AKI occurrence after angiography in the SGLT2i group was significantly lower than in the control group regardless of which criterion for CI-AKI was used. Limitations Results may be limited by single-center nature, inevitable sample selection bias, etc. and subgroup analysis of angiography operation types was conducted. Conclusion In real-world T2DM patients, SGLT2i was associated with lower CI-AKI risk. Clinical trial registration: Chinese Clinical Trial Registry, identifier: ChiCTR2300076484

本文报道1例心电图表现为宽QRS波和窄QRS波两种形式心动过速的病例，通过详细的病史询问及完善相关检查后诊断为普罗帕酮导致心房扑动1∶1下传伴宽QRS波心动过速，为宽QRS波心动过速的鉴别诊断以及抗心律失常药物合理应用提供一定的经验。

ObjectiveTo investigate the association of single nucleotide polymorphisms (SNPs) of various genes known to influence mean daily warfarin dose (MDWD) in the Han Chinese population.MethodsThe study is a systematic review and meta-analysis. Selected studies retrieved by searching Pubmed, Embase (Ovid), Medline, CNKI, Wanfang data, and SinoMed (from their inception to 31 August 2022) for the cohort studies assessing genetic variations that may possibly influence MDWD in Chinese patients were included.ResultA total of 46 studies including a total of 10,102 Han Chinese adult patients were finally included in the meta-analysis. The impact of 20 single nucleotide polymorphisms (SNPs) in 8 genes on MDWD was analyzed. The significant impact of some of these SNPs on MDWD requirements was demonstrated. Patients with CYP4F2 rs2108622 TT, EPHX1 rs2260863 GC, or NQO1 rs1800566 TT genotype required more than 10% higher MDWD. Furthermore, patients with ABCB1 rs2032582 GT or GG, or CALU rs2290228 TT genotype required more than 10% lower MDWD. Subgroup analysis showed that patients with EPHX1 rs2260863 GC genotype required 7% lower MDWD after heart valve replacement (HVR).ConclusionThis is the first systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) of various genes known to influence MDWD besides CYP2C9 and VKORC1 in the Han Chinese population. CYP4F2 (rs2108622), GGCX (rs12714145), EPHX1 (rs2292566 and rs2260863), ABCB1 (rs2032582), NQO1 (rs1800566), and CALU (rs2290228) SNPs might be moderate factors affecting MDWD requirements.Registered informationPROSPERO International Prospective Register of Systematic Reviews (CRD42022355130).

目的:快速评估丁苯酞治疗缺血性脑血管病的有效性、安全性和经济性,为临床和决策者提供参考.方法:检索中英文数据和国内外卫生技术评估(HTA)机构官方网站,如中国知网、万方数据库、PubMed、EMBase以及the Cochrane Library等,纳入丁苯酞治疗缺血性脑血管病的HTA报告、系统评价/Meta分析和药物经济学研究,采用定性描述的方法汇总纳入的研究.结果:最终纳入39篇文献,包括系统评价/Meta分析22篇、药物经济学研究15篇以及同时进行Meta分析和药物经济学研究的文献2篇.汇总分析结果显示,丁苯酞与其他改善循环的药物相比,或在常规治疗的基础上进行添加治疗,均可以提高缺血性脑血管病的治疗有效率,同时可改善美国国立卫生研究院卒中量表评分、Barthel指数评定量表评分、日常生活活动量表评分、中国卒中评分量表评分以及检查检验指标水平.丁苯酞干预组的不良反应总发生率与对照组相近,但在对肝功能的影响方面可能具有一定风险,临床在应用过程中应予以注意.药物经济性方面,与对照组相比,丁苯酞干预组是否具有较好的经济性还尚无统一结论.结论:丁苯酞治疗缺血性脑血管病具有良好的有效性、安全性,但其经济性有待进一步评价.

Objective:To investigate the use of non-vitamin K antagonist oral anticoagulant (NOAC) in very old patients with nonvalvular atrial fibrillation (NVAF) .Methods:We retrospectively enrolled very old (≥85 years old) in patients with NVAF who received NOAC treatment in Department of Cardiology, Beijing Hospital from October 2018 to October 2021, and were divided into a underdose group and non-underdose group according to NOAC prescription. Baseline data on demographic characteristics, atrial fibrillation, comorbidity, and combined drugs were collected. The study endpoint was the outcome during hospitalization, including length of stay, death, and bleeding events, for comparative analysis.Results:A total of 219 consecutive very old inpatients [aged (87.4±2.4) years, 85-97 years old, 49.8% (109/219) women] with NVAF were included, with the CHA 2DS 2-VASc score 6.0±1.5 and HAS-BLED score 1.8±0.8. Among them, 144 (65.8%, 144/219) were taking underdosed NOAC. Compared with non-underdosed patients, those with underdosed were more older [ (87.4±2.5) years vs. (86.8±2.0) years, P=0.012] , and had lower albumin level [ (35.8±4.3) g/L vs. (37.0±3.8) g/L, P=0.048] , and fewer clinical related non-major bleeding events during hospitalization (0 vs. 6.7%, P=0.002) , whereas no significant differences in hospital stay, death and major bleeding events. In multivariable regression analyses, older age was associated with underdosing NOAC ( OR=1.17, 95% CI 1.02-1.35, P=0.029) . Conclusion:Underdosed NOAC in very old patients with NVAF is very common. Patients with underdosed were older, had a lower albumin level, more taking antiplatelet drugs, had fewer clinical related non-major bleeding events during hospitalization. Older age was an independent risk factor of the NOAC underdosage.

目的:从有效性、安全性、经济性、创新性、适宜性和可及性 6 个维度,对左卡尼汀口服溶液进行药品临床综合评价研究.方法:系统检索PubMed、Embase、the Cochrane Library、中国知网、万方数据库和中国生物医学文献数据库和CRDWeb等数据库(检索时限为建库至 2020 年 10 月),通过快速卫生技术评估的方法对左卡尼汀口服溶液的有效性、安全性和经济性进行分析.检索国家药品监督管理局、国家药品监督管理局药品审评中心等专业网站、各国药典及药品说明书,对药品的创新型、适宜性和可及性进行分析.结果:有效性与安全性方面,左卡尼汀口服溶液可显著改善非酒精性脂肪肝、血液透析、2 型糖尿病、2 型糖尿病合并血脂异常、高脂血症、高龄等疾病和人群的空腹血糖、三酰甘油、高密度脂蛋白水平和胰岛素抵抗情况;缓解神经源性疼痛症状;降低C反应蛋白、白细胞介素 6 等炎症标志物及肝酶水平;改善男性不育症状;对心血管疾病二级预防的全因死亡等结局也显示出较好的改善效果.安全性数据有待补充.经济性方面,该药已被纳入 2020 年国家医保目录,尚无针对该药的经济学研究.该药的溶液工艺已获得专利,但无其他创新性特征.适宜性方面,左卡尼汀口服溶液较注射剂型有更好的依从性.可及性方面,国产药品生产企业所在地包括 5 个省、直辖市,集中于东北部.结论:左卡尼汀口服溶液在内分泌等多个系统的疾病中具有较好效果,适宜性和可及性适中,安全性和经济性有待进一步研究.