Background:China's National Centralized Drug Procurement (NCDP) policy has substantially reduced the cost of essential medicines, yet concerns persist regarding the real-world therapeutic equivalence of NCDP-procured drugs compared to their non-NCDP counterparts. This study aimed to systematically evaluate, using real-world data, the comparative efficacy and safety of NCDP-procured versus non-NCDP oxaliplatin in patients with advanced pancreatic cancer. Methods:This single-center retrospective cohort study enrolled patients with unresectable or metastatic pancreatic cancer who received first-line mFOLFIRINOX between May 2022 and March 2025. Patients were stratified into NCDP and non-NCDP groups based on the procurement source of oxaliplatin. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Safety was assessed by the incidence of adverse drug reactions (ADRs). Results:Among 168 enrolled patients (NCDP, n=77; non-NCDP, n=91), no significant between-group differences were observed in ORR (9.1% vs. 13.2%, P=0.47), disease control rate (57.1% vs. 63.7%, P=0.43), or median PFS [6.5 vs. 6.0 months; adjusted hazard ratio (HR) =1.034, 95% confidence interval (CI): 0.691-1.547, P=0.87]. However, the NCDP group exhibited significantly lower incidences of elevated aspartate aminotransferase (AST) (28.6% vs. 45.1%, P=0.04) and grade ≥3 anemia (2.6% vs. 15.4%, P=0.007), which remained significant after multivariable adjustment. After propensity score matching, baseline characteristics were well-balanced between groups (all P>0.10), and the primary findings remained consistent. The unit price of NCDP oxaliplatin (¥ 76/vial) was 45% of the price of the non-NCDP agent (¥ 170/vial), representing substantial cost savings. Conclusions:NCDP-procured oxaliplatin demonstrated comparable efficacy to non-NCDP alternatives in advanced pancreatic cancer, with a more favorable safety profile for specific hepatic and hematologic toxicities. These real-world findings support the translation of the national procurement policy into clinical practice, offering significant cost savings without compromising patient outcomes.

BACKGROUND:Peripheral neuropathic pain (pNP) is a prevalent and complex clinical condition that presents significant therapeutic challenges, with pharmacological options demonstrating variable efficacy and safety. OBJECTIVE:To establish expert consensus recommendations on the clinical use of pregabalin in the management of diverse pNP conditions. METHODS:A multidisciplinary panel of Chinese experts from orthopedics, pain management, neurology, oncology, dermatology, and pharmacy conducted a comprehensive literature review and synthesized clinical evidence to formulate consensus-based recommendations. RESULTS:Pregabalin, a second-generation calcium channel regulator, demonstrated broad efficacy across multiple pNP conditions, including postherpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), neuropathic cancer pain (NCP), postoperative and post-traumatic neuralgia, and trigeminal neuralgia (TN). In PHN, pregabalin significantly reduced pain intensity and improved sleep quality. In DPN, it provided consistent analgesia with improved pain scores and good tolerability. In NCP, pregabalin effectively alleviated pain, showed no significant drug-drug interactions, and was safely co-administered with chemotherapy. It was also effective in postoperative and post-traumatic neuralgia, although caution is warranted in cases of traumatic neuroma. In TN, pregabalin exhibited favorable low-dose efficacy, particularly in elderly patients, with minimal adverse effects. However, cautious use is advised in patients with nerve compression syndromes, such as carpal tunnel syndrome, and in individuals with a history of substance abuse. CONCLUSIONS:This consensus highlights pregabalin as an effective and generally well-tolerated therapeutic option for a broad range of pNP conditions. These recommendations provide clinically relevant guidance for optimizing pregabalin use, particularly within the Chinese healthcare context.

There are currently six ALK inhibitors available for the first-line treatment of patients diagnosed with ALK-positive advanced non-small cell lung cancer (NSCLC). However, clinicians face challenges in selecting the most appropriate drug for treatment. We have collated pertinent evaluative evidence and undertaken a multifaceted assessment of the enrolled medications across five critical dimensions: safety, efficacy, pharmaceutical properties, drug economy, and other properties. This comprehensive analysis aims to furnish a robust foundation for the selection and clinical deployment of pharmaceuticals, thereby advocating for the judicious and rational utilization of medications in clinical practice. Upon conducting an exhaustive evaluation, we determined that the aggregate scores for all ALK inhibitors under review surpassed the threshold of 75 points, with brigatinib distinguishing itself as the top performer in terms of overall scoring. Considering that safety, efficacy, and pharmacological properties are paramount in the comprehensive clinical appraisal of pharmaceuticals, lorlatinib emerged with the highest score when evaluated solely on these three critical criteria. Through an extensive evaluation of ALK inhibitors, it has been determined that each ALK inhibitor possesses unique strengths across a spectrum of five distinct dimensions. Notably, when evaluating both the comprehensive scores across all five dimensions and the focused scores for the top three dimensions, third-generation inhibitors consistently ranked as the optimal choice. Healthcare organizations can leverage these findings to assess and select ALK inhibitors that align with their specific requirements, utilizing the comparative rankings and scores across various dimensions to inform their selection process.

BACKGROUND:Immune thrombocytopenic purpura (ITP) in adults typically develops slowly and insidiously. The ITP medications might be linked to psychological disorders, but the connection is not well-understood. OBJECTIVE:This study aimed to examine the association between ITP medication use and the risk of depression among participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. METHODS:Using data from 70 190 NHANES participants, we conducted a cross-sectional study, excluding individuals under 18 years, with hypertension, HIV, hepatitis C, and various comorbidities. A total of 17 299 individuals were included in the analysis of this study. We identified 2 populations within this study: those using ITP medications, including prednisone, dexamethasone, and rituximab and those not using ITP drugs. Depression status was assessed using the Patient Health Questionnaire-9 (PHQ-9), and the relationship between ITP medication use and depression was analyzed through multivariate logistic regression. RESULTS:There was no significant association between ITP medication use and an increased risk of depression after adjusting for demographic and health-related variables. Notably, among the study participants, 1.8% of the non-depressed population were on ITP medication compared with 0.3% in the depressed population. The analysis revealed varying depression risks associated with different sociodemographic factors. For instance, the correlation between ITP medication and depression risk was influenced by a combination of age, race, income, and smoking status. CONCLUSION AND RELEVANCE:The study suggests that ITP medication use does not independently increase the risk of depression. This finding is crucial for guiding clinical decisions and managing patient expectations regarding ITP treatment and its psychological impacts.

目的 基于临床案例探讨细胞色素P4502D6(CYP2D6)*15等位基因突变对曲马多用药的指导意义.方法 基于荧光聚合酶链反应-毛细管电泳法检测CYP2D6基因第1外显子区的单核苷酸多态性(SNP)情况.进一步地通过检索遗传药理学知识库(PharmGKB)中CYP2D6等位基因分布频率、酶活性及临床功能状态等信息确证该患者基因型和表型.结果 患者CYP2 D6基因携带有1个活性降低的*10拷贝,1个无功能活性的*15拷贝及功能尚未明确的*43拷贝.结论 该患者携带有*10/*15二倍体多态性,属于中间代谢型,理论上认为常规剂量曲马多体内活性代谢产物转化效率较低,治疗可能达不到预期疗效.

The abuse of opioids has become one of the most serious concerns in the world. Opioid use can cause serious adverse reactions, including respiratory depression, postoperative nausea and vomiting, itching, and even death. These adverse reactions are also important complications of clinical application of opioid drugs that may affect patient safety and recovery. Due to the fear of adverse reactions of opioids, clinicians often do not dare to use opioids in an adequate or appropriate amount, thus affecting the clinical medication strategy and the quality of treatment for patients. The prediction of adverse reactions to opioids is one of the most concerned problems in clinical practice. At present, the correlation between gene polymorphism and the efficacy of opiates has been widely studied and preliminarily confirmed, but the research on the effect of gene polymorphism on the adverse reactions of opiates is relatively limited. Existing studies have made encouraging progress in predicting the incidence and severity of adverse opioid reactions and clinical management by using genetic testing, but most of these studies are single-center, small-sample clinical studies or animal experiments, which have strong limitations. When the same receptor or enzyme is studied by different experimental methods, different or even opposite conclusions can be drawn. These phenomena indicate that the correlation between gene polymorphism and adverse opioid reaction still needs further research and demonstration. At present, it is still too early to use genetic testing to predict opioid adverse reactions in clinic. In this paper, the correlation between gene polymorphism and adverse opioid reactions and a small number of clinical applications were reviewed in terms of pharmacokinetics and pharmacodynamics, in order to provide some suggestions for future research and clinical drug decision making.

Nanomedicine-based photodynamic therapy (PDT) for melanoma treatment has attracted great attention. However, the complex design of polymer nanoparticles and high doses of photosensitizers used in intravenous injections (for sufficient accumulation of drugs in tumor lesions) pose a huge challenge to the commercialization and further clinical application. Herein, we fabricated the carrier-free nanoassemblies of a chlorin e6 (L-Ce6 NAs)-integrated fast-dissolving microneedles patch (L-Ce6 MNs) enriching only about 3 μg of Ce6 in the needle tips via a facile fabrication method. The L-Ce6 MNs had sufficient mechanical strength to penetrate the skin and facilitated the transportation of L-Ce6 NAs to a depth of 200-500 μm under the skin, thereby achieving efficient and accurate drug delivery to tumor lesions. In a xenograft mouse melanoma model, the L-Ce6 MNs-based PDT with low dose of Ce6 (0.12 mg/kg) exerted efficient ablation of the primary lesions in situ through reactive oxygen species (ROS) generation. More importantly, a significant abscopal effect was also elicited by activating immunogenic cell death (ICD) and releasing danger-associated molecular patterns (DAMPs), which in turn promoted dendritic cells (DCs) maturation and the subsequent antigen presentation, thereby facilitating the T-cell-mediated immune response without synergetic immunotherapies. Collectively, our findings indicate the facile, controllable, and fast-dissolving microneedles patch with a low dose of photosensitizers presented great therapeutic potential for enhanced photoimmunotherapy.

Background:Irritable bowel syndrome (IBS) is a common gastrointestinal disease. Emerging studies have demonstrated that microRNAs (miRNAs) are commonly dysregulated in patients with IBS, and aberrant miRNAs are implicated in IBS occurrence. Although miR-155-5p participates in inflammatory bowel disease (IBD) and intestinal barrier dysfunction, the role of miR-155-5p in IBS is unclear.Methods:In the present study, colon samples were obtained from IBS patients and IBS mice induced by trinitrobenzenesulfonic acid (TNBS), and the levels of miR-155-5p, claudin-1 (CLDN1), and zonula occludens-1 (ZO-1) were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical analysis. The regulatory role of miR-155-5p in CLDN1 and ZO-1 expression was validated using dual luciferase reporter assay.Results:We found that miR-155-5p levels were upregulated in colon samples of IBS patients and mice compared with healthy subjects and normal mice, respectively. Meanwhile, the levels of CLDN1 and ZO-1 were decreased in colon samples of IBS patients and mice. Importantly, forced expression of miR-155-5p inhibited CLDN1 and ZO-1 expression. In IBS mice, intraperitoneal injection with miR-155-5p inhibitor increased CLDN1 and ZO-1 expression in intestinal mucosal epithelium, enhanced visceral response thresholds, and decreased myeloperoxidase (MPO) activity.Conclusions:In summary, these results suggested that miR-155-5p participated in the pathogenesis of IBS, at least in part by inhibiting CLDN1 and ZO-1 expression, indicating that miR-155-5p may be a potential therapeutic target for IBS.

随着"精准用药"概念的提出,基因多态性对药物疗效的影响受到广泛关注,目前基因检测已成为评估药物疗效、预防药物不良反应的重要手段.临床用药实践证明在传统经验用药模式下镇痛药物的治疗效果个体差异明显,本文基于基因多态性对神经病理性疼痛镇痛药物的个体化用药予以综述,旨在为镇痛药物的合理安全用药提供参考,为医院药学部门开展药物基因检测提供理论依据.

Background Pain is a common symptom among cancer patients and directly affects their prognosis. As the leading drug for pain management, opioids are widely prescribed. So it is necessary to get people a correct understanding and application of opioids. In order to examine whether the use of high-dose opioids might affect survival and quality of life, this retrospective cohort study was performed to explore the outcomes of patients receiving high-dose opioids for pain management in a first-class tertiary hospital in China. Methods We retrospectively searched medical records of inpatients and outpatients with pain who were treated with opioids in The First Affiliated Hospital, Zhejiang University School of Medicine from July to December 2021. Forty-three cases who were treated with high-dose opioids meeting inclusion criteria. Among these patients, 37 had cancer pain and 6 had neuropathic pain. All patients had regular follow-up when readmission until to April 7, 2022. Medical records of patients on high-dose opioids (equivalent to morphine ≥300 mg/d) was collected, including numerical rating scale (NRS), Karnofsky performance score (KPS), survival and adverse drug reactions (ADRs). Pain relief, quality of life, survival, and ADRs of patients after pain treatment were analyzed and evaluated. Results The NRS score was significantly reduced and pain was relieved after high-dose opioid treatment. The before and after average NRS score of cancer pain was 5.2±1.6 vs. 2.2±1.1 points (P<0.001), neuropathic pain was 5.0±2.2 vs. 1.3±1.2 points (P<0.05), respectively. Although there is no statistical difference, quality of life showed a trend of improvement compared with before treatment. The before and after average KPS scores of cancer pain patients was 55.7±17.3 vs. 62.4±20.0, and neuropathic pain patients was 71.7±9.0 vs. 83.3±4.7. There were no intolerable ADRs. The median survival time was 238 days and 83 days in patients with cancer pain who received high-dose opioids and ultra-high dose opioids (equivalent to morphine ≥600 mg/d). Conclusions Multimodal high-dose opioid pain treatments are important approaches to effectively relieve moderate to severe pain and improve the quality of life of patients. This study provides a clinical basis for future pain treatment with high-dose opioids.

氢吗啡酮是吗啡的半合成衍生物,有镇痛效果好、起效快、代谢产物无活性等优点,在中重度急慢性疼痛中应用日益广泛 [1].有研究表明,氢吗啡酮滥用风险高于吗啡,临床使用时需注意监测滥用、误用和依赖的迹象 [2].本文对1例带状疱疹后神经痛(PHN)患者使用盐酸氢吗啡酮注射液致药物依赖的原因和处置进行分析,并提出建议,旨在为临床防治阿片类药物依赖提供参考.

Background: Polymyxin B (PMB) is a basic cyclic polypeptide antibiotic produced by Bacillus polymyxa, and is one of the last options for treating multi-drug-resistant negative bacterial infections in clinical practice. In recent years, many population pharmacokinetic studies of PMB have been conducted. This paper sought to comprehensively summarize the characteristics of population pharmacokinetic models of PMB and provide a theoretical basis for the individualized use of PMB. Methods: In this review, we systematically searched the PubMed and Embase databases to find articles on population pharmacokinetic models published from database establishment to August 2021. Results: A total of 10 studies were included in this review, including studies on various types of severe infections caused by multi-drug-resistant bacteria, hospital-acquired infections with fibrosis and other male and female populations, and a study of 2 continuous renal replacement therapy (CRRT) patients, aged 16-94 years, who received PMB doses of 10-360 mg/day (0.13-3.45 mg/kg/day), at an administration time of 0.5-6 hours. First-order linear elimination was used in all the studies; a 1-compartment model was used in 5 studies, and a 2-compartment model was used in 5 studies. The most common covariates were creatinine clearance (CrCL) and body weight. Discussion: Although these studies included several covariates and total clearance (CL) was close, but the external validation of some models was poorly correlated between the actual and predicted value. Novel or potential covariates represent important directions for further study.

Although the strategy for administering antibodies orally for inflammatory bowel disease (IBD) treatment has been proposed, the rational design for efficient delivery system is still a challenge, restricted by poor drug loading and nonspecific distribution. In this study, we developed an inflammatory microenvironment-responsive nanocomplex (IFXSS@HA or IFXTK@HA) for oral administration of Infliximab (IFX) for IBD treatment using self-crosslinking technology, which was developed by reactive oxygen species-responsive cross-linkers and fabricated with hyaluronic acid. The nanocomplex is a "carrier-free" antibody backpack with a high drug loading (>90%), inflammation targeting, and bioresponsive controlled release. The results of preliminary in vivo studies indicated that the nanocomplex showed an extended retention time and caused an increased antibody accumulation in the inflamed intestinal tissues based on hyaluronic acid functionalization and responsive controlled release within the inflammation site, exhibiting great efficacy by reducing intestinal inflammation and systemic exposure. This study provided a rational design for an oral delivery system of antibodies, explored the design of the combination of vehicle and functionalization, and showed a strategy for the oral administration of antibodies in IBD treatment.

Objective Our study aimed to evaluate the influence of methylenetetrahydrofolate reductase ( MTHFR ) polymorphism on the clinical features and therapeutic effects in patients with migraine. Methods The data of 135 patients with migraine were collected from January 2021 to December 2021. The MTHFR C677T polymorphism was analyzed. The pain intensity was evaluated using a numerical rating scale (NRS) during treatment. The levels of folic acid, homocysteine (Hcy), vitamin B12, interleukin-2 (IL-2), IL-4, and ferritin, and changes of NRS were compared between folic acid and conventional treatment groups stratified by different genotypes of MTHFR in migraine patients. Results The levels of Hcy and ferritin in male patients were higher than that in female patients ( P < 0.05); Compared with CC and CT genotype groups, the TT genotype group showed significantly higher Hcy levels ( P < 0.05) and lower folic acid levels ( P < 0.05); In both folic acid and conventional treatment groups, a significant decrease in NRS score was observed in different genotypes post-treatment ( P < 0.05). Patients with TT genotype in the folic acid treatment group showed better therapeutic efficacy than conventional treatment group ( P < 0.05). There is no significant difference in the therapeutic efficacy in other genotypes between the two groups ( P > 0.05). Conclusion The MTHFR C677T genotyping may provide a new method to guide and optimize individualized medication for migraine patients.

The proteasome inhibitor bortezomib (BTZ) is a first-line antitumor drug, mainly used for multiple myeloma treatment. However, BTZ shows prominent toxicity in the peripheral nervous system, termed BTZ-induced peripheral neuropathy (BIPN). BIPN is characterized by neuropathic pain, resulting in a dose reduction or even treatment withdrawal. To date, the pathological mechanism of BIPN has not been elucidated. There is still no effective strategy to prevent or treat BIPN. This review summarizes the pathological mechanisms of BIPN, which involves the pathological changes of Schwann cells, neurons, astrocytes and macrophages. A better knowledge of the pathological mechanisms of BIPN would provide new ideas for therapeutic interventions of BIPN patients.

BACKGROUND:The spread of carbapenem-resistant Gram-negative bacteria poses a substantial threat to morbidity and mortality worldwide, which is mainly attributed to the overuse of carbapenem. This study aimed to evaluate the use of a quality control circle (QCC) in controlling the overuse of carbapenems and improving the state of carbapenem resistance at a Chinese tertiary teaching hospital.METHODS:A pharmacist-led multidisciplinary QCC project was carried out and the plan-do-check-act (PDCA) method was applied for 12 months. The data on carbapenem consumption, bacterial identification, and antibacterial susceptibility testing were collected to evaluate the effect of this project.RESULTS:The antibiotics use density (AUD) of carbapenems exhibited a decreasing trend over time (P<0.001), and the AUD of meropenem, imipenem, and biapenem decreased by 30.20%, 42.45%, and 78.05% after the intervention, respectively. The total AUD of carbapenems decreased from 7.37 to 3.96, which included the decrease in the irrational use of carbapenems by 1.61, accounting for 47.21% of the total. Moreover, the positive correlations were discovered between the resistance rate of carbapenem-resistant Klebsiella pneumonia (CRKP)/Acinetobacter baumannii (CRAB) and the AUD of carbapenems (P<0.05). The resistance rate of CRKP and CRAB decreased from 51.93% and 89.21% to 32.94% and 60.66%, respectively, following QCC project implementation.CONCLUSIONS:This is the first study to highlight the success of a multifaceted intervention QCC project and PDCA method, which led to a significant reduction in the AUD and resistance rate of carbapenems. QCC is a feasible and effective management tool for improving the quality of carbapenem use in medical institutions.

目的 对低剂量地西他滨皮下注射治疗骨髓增生异常综合征的国内外研究进展进行综述.方法 在Pubmed、中国知网、万方等数据资源库检索近年国内外相关文献,阐明地西他滨治疗骨髓增生异常综合征的作用机制,并对低剂量皮下注射的疗效及安全性进行总结与评价.结果 低剂量地西他滨皮下注射能靶向抑制DNA甲基转移酶活性,在发挥抗肿瘤效应同时减轻细胞毒性.与常规静脉给药方案相比,其疗效肯定、作用安全、给药方便、耐受性良好,同时可降低用药剂量、减轻经济负担,提高患者生存质量.结论 低剂量地西他滨皮下注射对不能耐受高剂量化疗与无法接受造血干细胞移植的患者而言或可成为一种较优的治疗选择,具有广阔的应用前景,其联合用药方案值得深入探索研究.

目的 加强对药物临床试验经费的管理,提高临床试验的质量.方法 归纳分析临床试验经费管理过程中存在的问题,结合文献与实践探索,提出对策建议.结果 科学规范地管理药物临床试验经费,可以保障受试者、研究者及研究机构的合法权益.结论 完善临床试验经费管理体系,加强信息化管理,可进一步提高临床试验管理水平,确保临床试验质量.

The anti-tumor necrosis factor-α (anti-TNF-α) blocker, has shown great efficacy for the treatment of inflammatory bowel disease (IBD). However, systemic exposure to it can cause considerable safety problems due to reduced suppression of the systemic immune response and loss of response to the production of anti-drug antibodies. Thus, we try to devise a targeted vehicle system for oral administration of anti-TNF-α antibodies for the treatment of IBD. In the present study, we developed an oral Infliximab (IFX) loaded nano-in-microparticles, based on chitosan (CS)/carboxymethyl chitosan (CMC) and alginate (Alg), which could protect IFX from the harsh environment of the gastrointestinal tract and produce targeted drug delivery to the inflamed intestine. In vivo studies demonstrated that the IFX loaded nano-in-micro vehicle can alleviate colitis by ameliorating inflammation and maintaining the intestinal epithelial barrier.