Weaning failure in mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remains a critical ICU challenge that substantially increases mortality. Although point-of-care diaphragmatic ultrasound is widely proposed to guide weaning decisions, its diagnostic accuracy remains uncertain, and the optimal parameter for this high-risk population has yet to be established. We systematically searched eight databases through April 5, 2026, for studies evaluating diaphragmatic ultrasound for predicting weaning outcomes in AECOPD. After methodological quality was appraised with the QUADAS-2 tool. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR + and LR−), and diagnostic odds ratios were estimated using bivariate random-effects models, and overall diagnostic performance was summarized by the area under the summary receiver operating characteristic curve. Fagan nomograms were constructed to illustrate changes from pre-test to post-test probability. Threshold effects and heterogeneity were assessed using Spearman correlation and the Q test with the I² statistic, respectively. Exploratory meta-regression, leave-one-out sensitivity analyses, and Deeks’ test were used to investigate sources of heterogeneity, assess result stability, and evaluate funnel-plot asymmetry. Twenty-three studies comprising 2,000 patients (1,310 successes, 690 failures) were included. Of 14 distinct ultrasound parameters identified, four provided sufficient data for quantitative synthesis. Diaphragmatic excursion (DE, n = 16) showed the most robust and balanced performance, with a pooled sensitivity of 0.85, specificity of 0.85, and an AUC of 0.92. Diaphragm thickening fraction (DTF, n = 13) also showed good accuracy (sensitivity 0.84, specificity 0.77, AUC 0.88). The diaphragmatic rapid shallow breathing index (D-RSBI, n = 8) showed high specificity (0.88) but moderate sensitivity (0.74; AUC 0.85), whereas diaphragmatic contraction velocity (DCV, n = 4) showed only moderate accuracy (AUC 0.70). Substantial heterogeneity was observed for DE, DTF, and D-RSBI. Diaphragm ultrasound, particularly DE, may provide useful prognostic information for weaning outcomes in mechanically ventilated patients with AECOPD, while D-RSBI may help identify patients at high risk of weaning failure. However, given the small, predominantly single-centre studies, post hoc study-specific thresholds, substantial heterogeneity, and geographical concentration of the evidence, these findings represent apparent prognostic performance rather than externally validated diagnostic accuracy. Diaphragm ultrasound should therefore be used as an adjunct rather than the sole basis for weaning decisions, pending multicentre external validation and interventional trials demonstrating improved patient-important outcomes.

Background Asthma is a chronic inflammatory airway disease characterized by airway remodeling and hyperresponsiveness. Angiogenesis is a key contributor to airway remodeling and disease progression. Rhizoma Dioscoreae Nipponicae (RDN), a traditional Chinese medicine, has shown anti-inflammatory and anti-angiogenic potential, but its effects on asthma-associated airway remodeling remain unclear. Methods The chemical profile of the RDN extract was characterized using UHPLC-Q Exactive Orbitrap MS/MS. An ovalbumen-induced mouse model of asthma and C166 mouse endothelial cells were used to examine the effects of RDN treatment. Histopathological changes were assessed using H&E and Masson's trichrome staining. mRNA and protein expression levels of key components in the mTOR/4EBP1/HIF-1α/VEGF signaling pathway were analyzed by qPCR and Western blot. Results UHPLC-Q Exactive Orbitrap MS/MS analysis tentatively annotated 2509 constituents and demonstrated good batch-to-batch chemical consistency of the RDN extract. Compared with the model group, RDN treatment significantly reduced the airway inflammation score by approximately 39.5% (P < 0.01), an effect comparable to that of prednisone. It also decreased the collagen area ratio by approximately 62.7% (P < 0.05). RDN also significantly decreased the protein levels of mTOR, 4EBP1, HIF-1α, and VEGF in both lung tissue and C166 cells (P < 0.05). Conclusion RDN alleviated airway inflammation and remodeling at the histopathological level, and these effects were associated with downregulation of markers within the mTOR/4EBP1/HIF-1α/VEGF pathway. These findings suggest that RDN may be a promising therapeutic agent for ameliorating airway remodeling in asthma. Future studies incorporating analyses of phosphorylation states are warranted to further clarify the underlying mechanisms.

Background:Tuberculosis (TB) remains a leading opportunistic infection in immunocompromised hosts. Disruption of host-pathogen interactions under cumulative immunosuppression may result in atypical extrapulmonary disease with indolent clinical manifestations and tumor-mimicking radiologic features, leading to substantial diagnostic delay. Case presentation:A 67-year-old man with Crohn's disease on cumulative immunosuppressive therapy, including biologics and a Janus kinase inhibitor, developed progressive mediastinal lymphadenopathy and a paravertebral mass with associated vertebral destruction on chest computed tomography, despite prior completion of isoniazid prophylaxis for latent TB infection. The aggressive, tumor-like imaging appearance raised a strong suspicion of metastatic malignancy. Conventional endobronchial ultrasound-guided transbronchial needle aspiration was nondiagnostic. As a salvage diagnostic approach, endobronchial ultrasound-guided tunneling biopsy obtained histological core tissue from a subcarinal lymph node. Although histopathology showed nonspecific fibrous changes without identifiable acid-fast bacilli, Xpert MTB/RIF testing detected Mycobacterium TB complex DNA at trace levels. A diagnosis of mediastinal tuberculous lymphadenitis complicated by a paravertebral cold abscess and secondary vertebral osteomyelitis was ultimately established. The patient subsequently showed marked radiological improvement with standard anti-TB therapy. Conclusion:This case illustrates how cumulative immunosuppression can profoundly alter host immune responses to Mycobacterium TB, resulting in tumor-like extrapulmonary disease and diagnostic ambiguity. Integration of advanced tissue acquisition with molecular testing may be essential for diagnosing TB when disrupted host-pathogen interactions limit conventional diagnostic yield.

OBJECTIVE:Body mass index (BMI) fails to distinguish fat from lean mass, capture fat distribution, or reflect metabolic dysfunction and adipose inflammation, limiting its utility in obesity-related asthma. A framework integrating morphological, metabolic, and inflammatory indicators may offer a more biologically relevant approach. METHODS:We systematically searched PubMed, Embase, and Web of Science up to April 10, 2026, including population-based studies, imaging/body composition analyses, and mechanistic studies reporting asthma risk, phenotypes, lung function, control, or exacerbations. RESULTS:BMI alone insufficiently predicts asthma outcomes. Central and upper-body anthropometric indices (waist-to-height ratio, neck circumference, weight-adjusted waist index) show stronger, BMI-independent associations with asthma onset, poor control, and lung function decline. Body composition distinguishes fat versus lean mass effects; visceral adipose tissue and dysanapsis capture mechanical/developmental pathways. Metabolic abnormalities (dyslipidemia, small dense LDL, triglyceride-glucose index) correlate with airway resistance and exacerbation risk, often independent of total adiposity. Leptin is elevated and adiponectin (ADPN) reduced in asthma; the leptin/ADPN ratio and interleukin-6 identify a metabolically driven, non-type 2 phenotype poorly captured by BMI. These three dimensions offer complementary biomarkers for risk stratification, phenotyping, and monitoring treatment response. CONCLUSIONS:Assessing obesity-related asthma should move beyond a BMI-centered approach toward an integrated morphology-metabolism-inflammation framework, enhancing early identification, endotype-based stratification, and personalized management. Longitudinal studies are needed to validate multi-indicator scoring systems and establish standardized cutoffs.

BackgroundAs a heterogeneous disease, chronic obstructive pulmonary disease (COPD) presents with eosinophil driven type 2 inflammation in some patients. Monoclonal antibodies targeting this pathway have shown promising therapeutic effects in related COPD clinical trials, but updated evidence on their efficacy and safety is still needed, specifically in strictly defined eosinophilic COPD patients.MethodsThis study searched 8 databases from inception to March 17, 2026, for randomized controlled trials (RCTs) comparing type 2 mAbs vs. placebo in eosinophilic COPD, defined as a blood eosinophil count (BEC) ≥300 cells/μL. The primary outcome was the annual rate of moderate-to-severe exacerbations; secondary outcomes covered changes in pre-bronchodilator forced expiratory volume in 1 s (pre-BD FEV1), St. George's Respiratory Questionnaire (SGRQ) score, Evaluating Respiratory Symptoms in COPD (E-RS: COPD) score, and safety-related events. A random effects model in RevMan was used for analysis. Risk of bias was assessed with the RoB 2.0 tool, and the certainty of evidence with the GRADE approach.Results6 RCTs (pooled into 5 research units, as METREX and METREO were combined) involving 3,171 participants were included. Type 2 mAbs reduced the annual rate of moderate-to-severe exacerbations vs. placebo (RR = 0.73, 95% CI 0.66 to 0.80), with consistent subgroup efficacy. Among secondary outcomes, pre-bronchodilator FEV1 improved by 61.97 mL (95% CI 5.09 to 118.85). SGRQ score decreased by −3.16 points (95% CI −4.54 to −1.79). E-RS: COPD score decreased by −0.67 points (95% CI −1.20 to −0.14). There was no statistically significant difference between the treatment group and placebo group in the incidence of adverse events. Evidence certainty was high to moderate, downgraded due to indirectness and inconsistency.ConclusionsIn eosinophilic COPD patients, type 2 mAbs reduce moderate-to-severe exacerbations without additional safety signals. Improvements in lung function and quality of life were statistically significant but modest. The symptom benefit was also statistically significant, but should be interpreted with caution given the non-robust sensitivity analysis. This evidence supports the use of type 2 mAbs as an add on treatment for these patients. Future studies should establish a uniform clinical threshold and integrate multiple biomarkers for precision phenotyping.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261334527, identifier: CRD420261334527.

Background:Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and a major public health issue in China. This study aims to develop a COPD predictive model and conduct risk stratification for key indicators not included. Methods:We collected data from inpatients and outpatients with COPD and non-COPD who were hospitalized between January 2018 and December 2022 at three different hospitals. The data were divided into a training set and an internal validation set, using logistic regression to build a COPD predictive model and perform internal validation. External validation of the model was performed using data from two additional units for the period November 2019 to June 2022. Results:A total of 1,056 cases were included: 740 in the training set, 316 in the internal validation set, and 408 in the external validation set. Six risk factors were identified: age (OR = 1.05, 95% CI: 1.02-1.08), second-hand smoke exposure (OR = 8.27, 95% CI: 2.70-25.34), cough (OR = 23.52, 95% CI: 12.64-43.77), "occasional episodes of wheezing that are mild and do not interfere with sleep or activity" (OR = 6.06, 95% CI: 2.59-14.19), "bouts of wheezing that worsen with movement" (OR = 21.40, 95%CI: 10.32-44.37), and "persistent episodes of wheezing, occurring at rest, unable to lie down" (OR = 10.97, 95% CI: 1.02-118.28). The predictive model equation was: y = -5.920 + 0.047 (age) + 2.113 (smoke exposure) + 3.158 (cough) + 1.801 (wheezing 1) + 3.063 (wheezing 2) + 2.396 (wheezing 3). The model achieved 94.1% accuracy, 98.5% sensitivity, and 89.2% specificity, with an AUC of 0.976 (internal) and 0.691 (external). The critical cut-off value was 0.258. Conclusion:We have successfully developed a model for the diagnosis of COPD. The predictive model equation was: y = -5.920 + 0.047 (age) + 2.113 (smoke exposure) + 3.158 (cough) + 1.801 (wheezing 1) + 3.063 (wheezing 2) + 2.396 (wheezing 3).

[This corrects the article DOI: 10.3389/fpubh.2025.1571499.].

BACKGROUND:Oxidative stress is crucial in the immune response and airway inflammatory process associated with asthma. While the relationship between dietary antioxidants and asthma remains debated in observational studies, this study uses two-sample Mendelian randomization (MR) to explore a potential causal link. METHODS:We acquired six distinct categories of absolute circulating antioxidants and five different types of metabolic circulating antioxidants from the most recent genome-wide association study data of the European population, including vitamin A (retinol), vitamin C (ascorbic acid), vitamin E (tocopherol), β-carotene, lycopene, and urate. The latest data regarding asthma was obtained from the FinnGen database. We utilized single nucleotide polymorphisms as instrumental variables to conduct five MR methods. To confirm the accuracy of the results, additional sensitivity analyses were performed to eliminate any potential confounding factors, such as heterogeneity and pleiotropy. RESULTS:MR and sensitivity analyses revealed an association between circulating urate and asthma, suggesting a potential increase in asthma risk (OR = 1.090; 95% CI = 1.030-1.150; p = 0.004). No causal relationship was found for other antioxidants. CONCLUSIONS:This MR analysis suggested that genetically determined circulating urate may increase asthma risk. Further large-scale randomized controlled trials and mediated MR analysis are needed to explore underlying mechanisms.

While nutritional factors have been suggested to influence cancer risk, the role of carnitine—a nutrient involved in fatty acid metabolism—remains controversial across cancer types. Emerging evidence indicates that carnitine’s anti-inflammatory and metabolic properties might influence carcinogenesis, but its site-specific associations are yet to be fully elucidated. We conducted a Mendelian randomization (MR) study to assess the causal relationship between genetically predicted serum carnitine levels and 12 site-specific cancers. Genetic variants associated with serum carnitine were used as instrumental variables to minimize confounding factors. Causal estimates were derived using inverse-variance weighted regression as the primary method, complemented by four regression methods. Furthermore, sensitivity analyses were applied to ensure the robustness and reliability of results. The MR analysis showed no significant causal associations between carnitine levels and 11 types of cancer. However, a modest positive causal relationship was identified between carnitine and pancreatic cancer (OR = 1.085, 95

Acute respiratory infections (ARIs) remain a major contributor to global morbidity and mortality, with diverse viral and bacterial pathogens varying across age groups. We conducted a multicenter, active surveillance study in Zhejiang Province, China, from November 2023 to November 2024, enrolling 31 490 patients with ARIs, including 6354 pneumonia cases. Specimens were tested for 13 respiratory pathogens, including 10 viruses and 3 bacteria, by polymerase chain reaction. The detection rate was calculated. Generalized additive models were used to explore the nonlinear relationship between age and detection rate, and modified Poisson regression was performed to evaluate pathogen infection and co-infection patterns associations with pneumonia risk. Overall, 57.49% of patients tested positive for at least one pathogen. Influenza virus (16.35%), Streptococcus pneumoniae (11.83%), and SARS-CoV-2 (9.04%) were the most frequently detected pathogens. Among pneumonia patients, Mycoplasma pneumoniae (M. pneumoniae) was predominant (24.80%), especially in adolescents (54.24%). Several pathogens exhibited distinct age-specific detection trends, with pediatric peaks for most viruses, adolescent predominance for IFV and M. pneumoniae, and higher detection of SARS-CoV-2 in older adults. Certain pathogens, such as RSV and M. pneumoniae, were positively associated with pneumonia. Co-infections were identified in 12.58% of patients, with the highest rate in children (22.80%), and viral-bacterial co-infections being the most common patterns (8.94%). Bacterial-related co-infection patterns were positively associated with pneumonia. These findings reveal distinct age-specific patterns of pathogen detection and co-infection in ARIs and support the need for age-targeted prevention strategies, including vaccination, optimized antibiotic use, and integrated surveillance approaches in the postpandemic era.

Influenza vaccination is an effective measure to prevent and control influenza, and countries worldwide consider older people a key recommended population for influenza vaccination. From 2020, Zhejiang Province has provided free influenza vaccination to anyone aged ≥70 years as part of its livelihood projects. In certain counties, the program is also offered to those aged ≥60 years. This measure has made influenza vaccination more convenient and has advanced the strategy for acceptance of influenza vaccines and improved readiness for a pandemic. Furthermore, it serves as an example for other Chinese provinces looking to implement free influenza vaccination programs.

BACKGROUND:This study aimed to evaluate the synergistic effect of salidroside and pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD) complicated by lower extremity deep vein thrombosis (LEDVT). METHODS:Eighty-two patients with COPD and LEDVT were randomly assigned to a control group (n = 41; low-molecular-weight heparin calcium plus pulmonary rehabilitation) or a combined group (n = 41; pulmonary rehabilitation plus salidroside). Clinical efficacy, hemorheological parameters, and serum hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) levels were compared. RESULTS:The total effective rate was higher in the combined group (95.12 %) than in the control group (75.61 %; P = 0.045), with no difference in adverse event incidence (17.07 % vs 9.76 %; P = 0.331). After 14 days, the combined group showed greater improvement in swelling, pain, skin temperature, and Homans's sign (all P < 0.05). Hemorheological parameters improved more significantly, including plasma viscosity (0.70 ± 0.08 vs 1.25 ± 0.30 mPa s), high-shear viscosity (4.10 ± 0.22 vs 5.00 ± 0.45 mPa s), and low-shear viscosity (7.84 ± 0.20 vs 10.93 ± 0.43 mPa s; all P < 0.001). HIF-1α levels were lower and VEGF levels higher in the combined group (both P < 0.001). CONCLUSION:Salidroside combined with pulmonary rehabilitation significantly improved clinical outcomes, oxygenation, and endothelial repair in COPD with LEDVT, likely via modulation of the HIF-1α/VEGF pathway, without increasing adverse effects.

There are estimated to be over one billion human infections of Toxoplasma gondii worldwide. However, significant spatial heterogeneity exists across countries and regions. For this study, a total of 2,943 participants were enrolled between 2019 and 2023 in Zhejiang Province, southeastern China including 519 animal contact workers, 1,722 people from the general population, and 702 blood donors. Anti-T. gondii IgG and IgM in sera were assessed using an enzyme-linked immunosorbent assay. The overall seroprevalence of IgG and IgM was 4.08% and 0.41%, respectively. IgG positivity was highest in the (50, 60] years age group (5.47%, 29/530), while IgM was found in the (60, 70] years age group (1.21%, 3/247). The general population showed the lowest IgG seroprevalence (1.68%) compared to animal contact workers (10.40%) and blood donors (5.27%) (p < 0.001). Patterns of T. gondii IgG prevalence varied by participant type. Increasing seroprevalence with age was observed among animal contact workers, indicating a cumulative effect, while frequency was highest in the (50, 60] and (30, 40] age groups in the general population and blood donors, respectively. Animal contact workers with two types of animal exposure had higher IgG positivity rates (13.16%) than those with one type (8.50%). Occupational exposure to cattle was associated with the highest frequency of IgG (12.69%), followed by pigs (9.69%), and sheep (8.85%). This study provides critical insights into the epidemiological characteristics of T. gondii infections across distinct population groups in Eastern China.

RATIONALE:Cough variant asthma (CVA) is one of the primary causes of chronic cough, significantly impacting quality of life. Although inhaled corticosteroids-long-acting beta agonists are the first-line treatment, their limitations-such as prolonged treatment duration, high relapse rates after discontinuation, and suboptimal efficacy in some patients-highlight the need to explore alternative treatment options. Traditional Chinese medicine (TCM), with its holistic framework, syndrome differentiation-based treatment, and emphasis on preventing relapse, offers a promising strategy for complementary therapy. This case report aims to evaluate the potential efficacy of personalized TCM protocols for CVA patients who have not responded to conventional treatment. PATIENT CONCERNS:A CVA patient with poor medication compliance developed persistent airway inflammation after an upper respiratory tract infection, resulting in worsening of existing cough symptoms and poor response to standard western medical treatment. DIAGNOSES:The patient was diagnosed with CVA, and the Chinese medicine diagnosis was cough and wind-heat offending the lung syndrome. INTERVENTIONS:The patient received a Chinese medicine decoction. The principle of TCM treatment is to clear heat, dispel wind, relieve the pharynx, and relieve cough. OUTCOMES:After 2 weeks of Chinese medicine treatment, the patient's visual analogue scale, cough evaluation test, Leicester cough questionnaire, and traditional Chinese medicine criteria scores improved. All key indicators reflecting small airway function (forced expiratory flow at 50% of vital capacity, forced expiratory flow at 75% of vital capacity, and maximal mid-expiratory flow) showed sustained and clinically significant improvements. Additionally, the treatment process was safe, with no adverse reactions or abnormal changes in liver, kidney, or hematological parameters observed. Overall, this TCM treatment was safe and effective for this CVA patient. LESSONS:This case demonstrates the potential of TCM as a viable option for managing CVA, particularly in cases suboptimally controlled by conventional therapy. The "one person, one prescription" approach, targeting both pathogenic factors and systemic regulation, may address the multifactorial nature of CVA and contribute to sustained remission. Rigorous larger-scale studies are warranted to validate these findings.

The present study elucidated cuproptosis-related molecular clusters involved in ischemic stroke and developed predictive models. Transcriptomic and immunological profiles of ischemic stroke-related datasets were extracted from the Gene Expression Omnibus database. Next, we conducted weighted gene co-expression network analysis to determine cluster-specific differentially expressed genes (DEGs). Models such as random forest and eXtreme gradient boosting (XGB) were evaluated to select the best prediction performance model. Subsequently, we validated the model’s predictive efficiency by using nomograms, decision curve analysis, calibration curves, and receiver operating characteristic curve analysis with an external dataset. We identified two cuproptosis-related clusters involved in ischemic stroke. The DEGs in Cluster 2 were closely associated with amino acid metabolism, various immune responses, and cell proliferation pathways. The XGB model showed lower residuals, a smaller root mean square error, and a greater area under the curve value (AUC = 0.923), thus exhibiting the best discriminative performance. The AUC value for the external validation dataset was 0.921, thus confirming the high performance of the model. NFE2L2, NLRP3, GLS, LIPT1, and MTF1 were identified as potential cuproptosis predictors, thus shedding new light on ischemic stroke pathogenesis and heterogeneity.

IntroductionMultiple targets are considered as the causes of ambient fine particulate matter [aerodynamic diameters of < 2.5 μm (PM2.5)] induced lung function injury. Qiju granules are derived from the traditional Chinese medicine (TCM) formula known as Qi-Ju-Di-Huang-Wan (Lycium, Chrysanthemum, and Rehmannia Formula, QJDHW), which has been traditionally used to treat symptoms such as cough with phlegm, dry mouth and throat, and liver heat. This treatment approach involves attenuating inflammation, oxidative stress, and fibrosis response. This study investigated the effects of Qiju granules on protecting lung function against PM2.5 exposure in a clinical trial.MethodsA randomized, double-blinded, and placebo-controlled trial was performed among 47 healthy college students in Hangzhou, Zhejiang Province in China. The participants were randomly assigned to the Qiju granules group or the control group based on gender. Clinical follow-ups were conducted once every 2 weeks during a total of 4 weeks of intervention. Real-time monitoring of PM2.5 concentrations in the individually exposed participants was carried out. Data on individual characteristics, heart rate (HR), blood pressure (BP), and lung function at baseline and during the follow-ups were collected. The effects of PM2.5 exposure on lung function were assessed within each group using linear mixed-effect models.ResultsIn total, 40 eligible participants completed the scheduled follow-ups. The average PM2.5 level was found to be 64.72 μg/m3 during the study period. A significant negative correlation of lung function with PM2.5 exposure concentrations was observed, and a 1-week lag effect was observed. Forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), forced expiratory flow at 75% of forced vital capacity (FVC) (FEF75), forced expiratory flow at 50% of FVC (FEF50), and forced expiratory flow at 25% of FVC (FEF25) were significantly decreased due to PM2.5 exposure in the control group. Small airway function was impaired more seriously than large airway function when PM2.5 exposure concentrations were increased. In the Qiju granules group, the associations between lung function and PM2.5 exposure were much weaker, and no statistical significance was observed.ConclusionThe results of the study showed that PM2.5 exposure was associated with reduced lung function. Qiju granules could potentially be effective in protecting lung functions from the adverse effects of PM2.5 exposure.Clinical Trial Registrationidentifier: ChiCTR1900021235.

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a common, preventable, and treatable disease. Traditional Chinese Medicine (TCM) has shown promising potential in COPD treatment. and we conducted a multi-center RCT to evaluate the effectiveness of TCM-based therapy in stable COPD patients.MethodsIn this multicenter, double-blind RCT, a total of 200 patients were supposed to be assigned to either trial or control group randomly. Both groups received Tiotropium (18 μg) from month 0 to month 12. Trial group received additional TCM granules, while control group received a placebo from month 0 to month 6. Symptom assessment, total effective rate, lung function measurements, hospitalization rates, and quality of life were evaluated at month 0, month 6, and month 12. Adverse events were assessed at month 12.ResultsOf the initial 105 patients (aged 40–80) who completed the study, 51 were in trial group and 54 were in control group. At month 6, significant differences were observed between two groups in total effective rate (p = 0.020), sputum score (p = 0.047), changes in FVC% (p = 0.047) and FEV1 (p = 0.046). At month 12, significant differences were observed in sputum score (p = 0.020), FVC (p = 0.042), and change in FEV1 (p = 0.013). Compared to baseline, they both demonstrated improvements in symptoms, acute exacerbation, lung function, quality of life, and exercise tolerance.ConclusionTCM treatment effectively improved total effective rate, sputum symptom, FVC%, FEV1, and exhibited prolonged efficacy in improving sputum symptoms and FEV1 in stable COPD patients.Clinical trial registration:https://www.chictr.org.cn/showproj.html?proj=6029 identifier ChiCTR-TRC-13003531.

Rationale:Proto-oncogene-oriented targeted therapy has limited benefits in elderly patients with multiple primary tumors. Patient concerns:A woman with anaplastic lymphoma kinase-positive lung adenocarcinoma developed acquired resistance after 3 years of targeted therapy with crizotinib. Diagnoses:Diagnosis of unexpected subsequent primary gallbladder tumor. Interventions:Lenvatinib was administered therapeutically. Meanwhile, next-generation sequencing results before and after crizotinib treatment were analyzed by comparing the tumor-driving mutation genes with bioinformatics methods. Outcomes:The patient died of ascites and liver failure. Furthermore, bypass activation was found to be the main reason for acquired drug resistance for this patient, and the abnormal expression of tumor suppressor genes and senescence-related genes was the likely cause of the second primary tumor. Lessons:A bioinformatic comparison of pre- and post-treatment sequencing in elderly oncology patients is of interest. Conclusions:For diagnosing, precision bioinformatics analysis and repeat biopsy are equally valuable. For therapy, potential therapy such as p53 gene replacement therapy and CAR-T therapy need to be practiced for senescence-related conditions.

Xuanbai Chengqi Decoction (XBCQD), a classic traditional Chinese medicine, has been widely used to treat COVID-19 in China with remarkable curative effect. However, the chemical composition and potential therapeutic mechanism is still unknown. Here, we used multiple open-source databases and literature mining to select compounds and potential targets for XBCQD. The COVID-19 related targets were collected from GeneCards and NCBI gene databases. After identifying putative targets of XBCQD for the treatment of COVID-19, PPI network was constructed by STRING database. The hub targets were extracted by Cytoscape 3.7.2 and MCODE analysis was carried out to extract modules in the PPI network. R 3.6.3 was used for GO enrichment and KEGG pathway analysis. The effective compounds were obtained via network pharmacology and bioinformatics analysis. Drug-likeness analysis and ADMET assessments were performed to select core compounds. Moreover, interactions between core compounds and hub targets were investigated through molecular docking, molecular dynamic (MD) simulations and MM-PBSA calculations. As a result, we collected 638 targets from 61 compounds of XBCQD and 845 COVID-19 related targets, of which 79 were putative targets. Based on the bioinformatics analysis, 10 core compounds and 34 hub targets of XBCQD for the treatment of COVID-19 were successfully screened. The enrichment analysis of GO and KEGG indicated that XBCQD mainly exerted therapeutic effects on COVID-19 by regulating signal pathways related to viral infection and inflammatory response. Meanwhile, the results of molecular docking showed that there was a stable binding between the core compounds and hub targets. Moreover, MD simulations and MM-PBSA analyses revealed that these compounds exhibited stable conformations and interacted well with hub targets during the simulations. In conclusion, our research comprehensively explained the multi-component, multi-target, and multi-pathway intervention mechanism of XBCQD in the treatment of COVID-19, which provided evidence and new insights for further research.

Abstract Background Traditional Chinese exercise as a new pulmonary rehabilitation technique has been increasingly used and achieved good results in pulmonary rehabilitation of chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the protective effects of Liuzijue on exercise tolerance, lung function, and quality of life in patients with COPD. Methods This study is a multicenter, non-randomized, prospective study. Patients will be divided into a control group (CG) and a Liuzijue group (LG) based on their willingness to learn Liuzijue. None of the outcome assessors will know the grouping of patients. Participants in this study will be collected from stable COPD patients who are outpatients or inpatients in 3 centers in China since September 2021. Patients will meet the diagnostic criteria for GOLD stage I-II COPD (FEV1% ≥ 0.5 and FEV1/FVC < 0.7) and be aged 40 years or older. Patients voluntarily will take part in the clinical study and sign an informed consent form. All participants will follow their existing medication. For LG patients, Liuzijue training has been added. Patients will practice Liuzijue for more than 30 minutes a day, more than 5 days a week, and adhere to the training for 3 months. Outcome indicators are 6-minute walk test (6MWT), lung function (FEV1%, FEV1/FVC, MMEF, PEF), modified British Medical Research Council (mMRC) score, COPD assessment test score (CAT), acute exacerbations and changes in drug treatment. Discussion This study quantified the effect of Liuzijue on the pulmonary rehabilitation of COPD patients in the stable phase of the disease, and provided a basis for the use of Liuzijue in COPD patients. Trial registration Chinese clinical trial registry, ChiCTR2100048945. Date: 2021-07-19. http://www.chictr.org.cn/showproj.aspx?proj=129094