Objective: To establish a rapid, accurate, and decentralized workflow for bacterial whole-genome sequencing (WGS) and risk profiling within the shelf-life of platelet concentrates, and to characterize the species, virulence, antimicrobial resistance (AMR), and immune evasion mechanisms of co-existing bacteria in qualified platelet products, thereby providing a scientific basis for transfusion safety assessment. Methods: Three units of platelet concentrates, which tested negative by routine bacterial screening, were collected from the Chengdu Blood Center between May and June 2025. Samples were enriched at 37℃under six aerobic and nine anaerobic conditions for 7 days. Using a culturomics strategy, aliquots were plated for isolation on days 1, 3, 5, and 7 to obtain cultivable isolates, with negative culture controls included to exclude contamination. High-molecular-weight genomic DNA was extracted via mechanical grinding, purified, and size-selected. Sequencing libraries were constructed and sequenced on the G-seq500 single-molecule nanopore sequencing platform. Genomes were assembled using Flye and polished with NextPolish, with quality evaluated by BUSCO and CheckM. Taxonomic identification was performed using GTDB-Tk. Functional annotation and database comparisons were conducted to analyze virulence factors, AMR genes, and genes related to immune evasion and environmental adaptation. Results: Viable bacteria were successfully isolated from all three qualified platelet units within their shelf life. The isolates were identified as Bacillus albus, Niallia taxi, and Staphylococcus warneri. Nanopore sequencing generated 92 227-109 813 reads (totaling 680-758 Mb) with an N50 of 7 625-8 584 bp and Q20/Q30 scores of 97%/93%, respectively. All three genomes were assembled into complete circular chromosomes with 1-3 plasmids, achieving >93% completeness. Functional analysis revealed that B. albus carried multiple hemolysins, metalloproteases, and multidrug resistance genes, indicating the highest potential pathogenicity and AMR risk. S. warneri exhibited a typical multidrug resistance profile and regulatory network characteristic of coagulase-negative staphylococci, suggesting intermediate virulence. N. taxi harbored few canonical virulence factors and lacked functional AMR determinants, presenting a "low-virulence, low-resistance" profile. Notably, all three strains were enriched in genes encoding antimicrobial peptide resistance systems (e.g., dltABCD, mprF, GraRS, BceAB) and antioxidant enzymes, suggesting a strong capacity to withstand immune stress in the blood environment. Conclusion: Viable bacteria can be recovered from qualified platelet concentrates that test negative by routine screening. Nanopore WGS enables rapid strain-level identification and comprehensive risk profiling of virulence, resistance, and immune adaptation traits. The functional repertoires of these "co-existing" isolates range from environmental adaptation to potential pathogenicity, representing an underappreciated risk for transfusion-transmitted infections in susceptible recipients.

ObjectiveTo explore the factors influencing home-based rehabilitation exercise and the needs for digital interventions among patients with spinal muscular atrophy (SMA), based on the behavior change wheel (BCW), and to provide evidence for the development of digital home-based rehabilitation interventions. MethodsA two-phase qualitative study was conducted from December, 2024 to March, 2025. Using convenience sampling, 14 participants were recruited, including patients with SMA, primary caregivers, rehabilitation professionals, clinicians, a patient organization representative and a health policy expert. In phase 1, semi-structured individual interviews were conducted with seven participants, including patients, caregivers and a patient organization representative, to identify factors influencing home-based rehabilitation exercise and unmet needs. In phase 2, a focus group involving 12 stakeholders was conducted, including five participants who had participated in phase 1, to explore requirements for the functions, knowledge content and interface design of a digital intervention, five of them had participated in phase 1. Overall, the two phases involved 14 individual participants, accounting for 19 participant-instances. Thematic analysis was performed using both deductive and inductive approaches, guided by the capability-opportunity-motivation-behavior (COM-B) model. ResultsSix themes were identified. phase 1 showed that patients with SMA experienced inadequate continuity of rehabilitation services and limited access to professional rehabilitation resources, with interruptions in institution-based rehabilitation coexisting with declining adherence to home-based exercise. Home-based rehabilitation exercise was jointly influenced by capability-, opportunity- and motivation-related factors, including limited capabilities of patients and caregivers, constraints in time and supportive conditions and insufficient goals, feedback, and incentives. Individualized rehabilitation plans and professional guidance were the major unmet needs. phase 2 showed that the core functions of a digital intervention should include individualized exercise plans, professional guidance and feedback, reminders and incentives, safety monitoring, remote assessment, and privacy and permission management. Core knowledge content should include stratified exercise guidance, caregiving skills, recognition of abnormal conditions, and information on when and how to seek help. The interface should be simple, impose a low user burden and accommodate different types of users. ConclusionHome-based rehabilitation exercise among patients with SMA is jointly influenced by multiple capability-, opportunity- and motivation-related factors. Digital interventions should prioritize individualized rehabilitation plans, professional guidance and sustained behavioral support. These findings may inform the development of a digital home-based rehabilitation intervention prototype for patients with SMA; its feasibility, safety, clinical effectiveness and economic value require further evaluation.

As a new type of model organism， zebrafish is gradually gaining prominence in the field of scientific research. The unique biological characteristics and advantages of zebrafish make them play an increasingly important role in the quality evaluation of traditional Chinese medicine. Compared with other common experimental animals， zebrafish have a fast reproductive and growth speed and high embryo transparency， making them an ideal model for evaluating the quality of traditional Chinese medicine. This provides a new perspective and method for research on traditional Chinese medicine. With the growing global interest in traditional Chinese medicine， it has become crucial to find scientific and accurate methods to evaluate the quality and effectiveness of traditional Chinese medicine. The introduction of the zebrafish model has brought new breakthroughs in the quality evaluation of traditional Chinese medicine. To further promote the application of zebrafish in evaluating the quality of traditional Chinese medicine， this article systematically searched and sorted out the previous studies related to the application of zebrafish for this purpose since 2023. The commonly used disease models and indicators of zebrafish in evaluating the effectiveness of traditional Chinese medicine， as well as the mechanism of zebrafish in exploring the active ingredients of traditional Chinese medicine， were primarily reviewed. The application of zebrafish in evaluating the safety of traditional Chinese medicine and the typical examples in ensuring the quality of traditional Chinese medicine were demonstrated. The limitations encountered by zebrafish models in evaluating the quality of traditional Chinese medicine were highlighted. The resolution of these problems will help further improve the accuracy and reliability of zebrafish in evaluating the quality of traditional Chinese medicine. The article discussed the evaluation of effectiveness， safety， and quality control of zebrafish applied in traditional Chinese medicine， so as to provide a reference for establishing standards for traditional Chinese medicine and promoting its modernization in the future.

ObjectiveBased on the zebrafish model， the hepatotoxicity and anti-osteoporotic activity of evodiamine （EVO） were studied. The mechanism of EVO in treating osteoporosis was explored by using network pharmacology and real-time polymerase chain reaction（Real-time PCR）. MethodsThree days after fertilization （3 dpf）， zebrafish were randomly selected and exposed to different concentrations of EVO solution for 96 hours. The mortality rate of zebrafish at different concentrations was calculated at the exposure endpoint， and a "dose-toxicity" curve was drawn. The 10% lethal concentration （LC₁₀） was calculated. Liver phenotype， acridine orange staining， and pathological tissue sections of liver-transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP））］ were used to confirm hepatotoxicity of EVO. On this basis， prednisolone was used to create a model of osteoporosis in zebrafish. The skull development， area of the skull stained by alizarin red， and cumulative optical density were used as indicators to evaluate the anti-osteoporotic activity of EVO in a safe dose. Based on network pharmacology， the mechanism of action of EVO in the treatment of osteoporosis was predicted and verified through Real-time PCR. ResultsThe LC₁₀ of EVO on zebrafish （7 dpf） was determined to be 0.4 mg·L^-1. Compared with the control group， sublethal concentrations （10=0.36 mg·L^-1 and 1/2LC₁₀=0.18 mg·L^-1） significantly decreased the fluorescence area of zebrafish liver （P<0.05，P<0.01） and increased the number of liver cell apoptosis. The arrangement of liver tissue was disordered and loose， and the vacuole was obvious， especially in the 0.36 mg·L^-1 group. Compared with the control group， under safe dose conditions， 0.08 and 0.02 mg·L^-1 of EVO had no significant effect on the liver. Prednisolone administration significantly reduced the mineralization area and cumulative optical density of zebrafish skulls （P<0.01） compared with the control group. The mineralization area and cumulative optical density of zebrafish skulls in the 0.08 and 0.02 mg·L^-1 groups of EVO were significantly increased compared with the model group （P<0.01）. Network pharmacology prediction suggested that EVO may regulate key targets such as avian sarcoma viral oncogene homolog （SRC）， signal transducer and activator of transcription 3 （STAT3）， interleukin-8 （CXCL8） and tyrosine kinase receptor 2 （ERBB2） to regulate signaling pathways related to lipid and atherosclerosis in diabetic complications， as well as the regulation of inflammatory mediators of tryptophan （TRP） channels. Real-time PCR experiment results indicated that EVO could regulate the above-mentioned targets， as well as genes related to osteoblasts and osteoclasts. ConclusionExcessive doses of EVO can lead to hepatotoxicity in zebrafish. Under safe dosage conditions， EVO can regulate relevant targets to exert anti-osteoporotic activity， providing a reference for the clinical safe use of EVO and ideas for the development of new drugs for osteoporosis.

The escalating phenomenon of global population aging is posing multi-dimensional challenges to society, the economy and medical healthcare system.Among the significant health threats to the elderly population are cardiovascular diseases(CVD)and cognitive frailty(CF), both of which profoundly affect the quality of life and increase the risks of adverse health outcomes, including disability, hospitalization, and death.The concurrent presence of CVD and CF in elderly patients is prevalent, as these conditions share many common risk factors and underlying pathophysiological mechanisms, such as atherosclerosis, microcirculation dysfunction, and inflammation, which interact to perpetuate a vicious cycle.Notably, CF exhibits a certain degree of reversibility; thus, the implementation of a diagnosis and treatment paradigm that incorporates "comprehensive geriatric assessment and geriatric interdisciplinary teams" should be established as a conventional management strategy for elderly patients affected by both CVD and CF.Cognitive digital therapeutics, along with personalized exercise prescriptions based on cardiopulmonary exercise tests, may represent more appropriate precision interventions for these patients.Consequently, there is a necessity for further in-depth research in this area moving forward.

Objective:To explore application value of a constructed predictive model of quantitative parameters of contrast-enhanced ultrasound(CEUS)combined with immunohistochemical indicators in assessing the curative efficacy of neoadjuvant chemotherapy(NAC)for breast cancer,so as to provide objective basis for clinically individual treatment decisions.Methods:The CEUS quantitative parameters were used to combine with immunohistochemical indicators to construct predictive model,and this study adopted prospective cohort design.A total of 93 patients who were preliminarily diagnosed as breast cancer at Affiliated Hospital of Jiangnan University during June 2022 and June 2023 were included in this study.According to the pathologically relieve condition,they were divided into significant response group(41 cases)and non-significant response group(52 cases).All of them received NAC with docetaxel/doxorubicin/cyclophosphamide(TAC).Before treatment,the peak intensity(PI),time-to-peak(TTP),and wash-in rate(WIR)of them were obtained through CEUS,and all of patients underwent immunohistochemical examination to detect the expressions of immunohistochemical indicators included estrogen receptor(ER),progesterone receptor(PR),human epidermal growth factor receptor 2(HER2)and Ki-67 proliferation index.The Miller-Payne grade G4-G5 was used as the standard of pathological complete response(pCR).Multivariate logistic regression was adopted to screen independent predictors,and construct a jointly predictive model,and verify effectiveness by Bootstrap resampling method.Results:The PI value of significant response group was(22.7±4.1)dB,which was significantly higher than(18.3±3.6)dB of non-significant response group,and the difference was significant(t=5.437,P<0.001).The TTP of significant response group was(14.2±2.8)s,which was shorter than(18.6±3.1)s of non-significant response group,and the difference was significant(t=7.152,P<0.05).The wash-in rate(WIR)of significant response group was(1.61±0.43)dB/s,which was significantly higher than(0.98±0.37)dB/s of non-significant response group,and the difference was significant(t=7.893,P<0.001).In the immunohistochemical indicators,the positive HER2 and high Ki-67 expression significantly correlated with pathological response.In the results of positive HER2,there were 17 cases(41.5%)in 41 patients of significant response group,and there were 9 cases(17.3%)in non-significant response group,and the positive HER2 of significant response group was higher than that of non-significant response group,and the difference was significant(x2=7.326,P<0.05).For patients whose Ki-67 were larger or equal to 20%,the positive rate of significant response group was 75.6%(31 cases),which was higher than 57.7%(30 cases)of non-significant response group.For patients whose Ki-67 were less than 20%,the positive rate of significant response group was 24.4%(10 cases),which was significantly higher than 42.3%(22 cases)of non-significant response group,and the difference was significant(x2=3.921,P<0.05).Multivariate analysis indicated that TTP≤15 s,WIR≥1.5 dB/s,and positive HER2 were respectively independent predictors(OR=4.23,3.76,2.91,P<0.05).The area under curve(AUC)value of receiver operating characteristic(ROC)curve of joint model was 0.89(95%CI:0.83-0.95),and the sensitivity and specificity of that were respectively 92.7%and 80.8%,which were significantly better than each single parameter.Decision curve analysis indicated that the net benefit value of joint model increased by 21.3%-28.6%than conventional strategy when threshold probabilities was 15%-60%.Conclusion:CEUS quantitative parameters(TTP,WIR)that combine with HER2 status can construct predictive model with high-precision and low-cost for NAC curative efficacy,which synergistic effect in dynamic perfusion assessment and molecularly pathological characteristic can provide new paradigm for precision treatment in breast cancer.This mode has excellent clinical applicability,and can effectively identify chemosensitive populations and optimize decision-making process of treatment.

Objective To analyze the clinical characteristics,treatment and prognosis of patients undergoing the maintenance hemodialysis and treatment-naive tuberculosis and to explore the prognostic factors,so as to provide a reference for the clinical treatment of patients undergoing hemodialysis due to tuberculosis.Methods The clinical data of 70 patients undergoing hemodialysis with treatment-naive tuberculosis admitted to the Third People's Hospital of Kunming from October 31,2020～October 31,2023 were retrospectively collected,the clinical characteristics of the patients were analyzed,and the occurrence of adverse reactions,treatment outcomes and prognostic factors were observed.Results Among the 70 patients,pulmonary tuberculosis was the primary type(64 cases,accounting for 91.43％),and extrapulmonary tuberculosis was also quite common(56 cases,accounting for 80.00％).The most widely used anti-tuberculosis regimen was isoniazid,rifampicin,ethambutol,and moxifloxacin in a four-drug combination;During the anti-tuberculosis treatment,55 patients(78.57％)improved.A total of 13 adverse reactions occurred in 11 patients(15.71％),and the most common ones were itching,rash and blurred vision.The hemoglobin,lymphocyte count and CD8+T lymphocyte count in the treatment improvement group were higher than those in the ineffective group(P<0.05).Conclusion Dialysis patients have a high risk of tuberculosis infection,mainly pulmonary tuberculosis,and extrapulmonary tuberculosis is more common.78.57％of the patients hare improved after the tuberculosis treatment,but the overall prognosis is poor,and the low hemoglobin level is associated with ineffective treatment.

With the increasing difficulty of traditional chemical drug research and development,peptide drugs have gradually become a hot spot in drug research and development due to their advantages of high specificity,significant efficacy,easy metabolism and low toxicity.This review systematically expounds the physicochemical properties,main advantages and limitations of peptide drugs,and summarizes the currently common strategies for structural modification and delivery.It focuses on the application and target of approved peptide drugs in various diseases such as diabetes,cancer,bacterial and viral infections,multiple sclerosis,and osteoporosis.Furthermore,the research analyzes the challenges in the research and development of peptide drugs,including poor in vivo stability,low bioavailability,and limited routes of administration.It also discusses the prospects of new technologies based on molecular modification,nanodelivery systems,and computer-aided design.In summary,peptide drugs have shown unique advantages in multi-field therapy,but they still need to break through bottlenecks in preparation,delivery and drug resistance to provide new ideas and directions for future precision therapy.

Objective To compare the anti fungal efficacy and safety of amphotericin B cholesteryl sulfate complex(amphotericin B colloidal dispersion,ABCD)and amphotericin B for injection(amphotericin B deoxycholate,AmB-D)in the treatment of AIDS complicated with talaromycosis(TSM).Methods A total of 80 patients who were diagnosed with AIDS and complicated with TSM from December 2021 to January 2024 in Department of Infection,Kunming Third People's Hospital were included in the study.The patients were randomized to receive ABCD(n=40)via intravenous infusion or AmB-D(control,n=40)via Ⅳ infusion protected from light.The overall treatment efficacy rate,CD4+T lymphocyte count,routine blood tests,liver and kidney function tests,K+concentration,and the incidence of adverse drug reactions(ADR)during study were compared between the two treatment groups.Results The overall efficacy rate was 87.5％(35/40)in ABCD group and 80.0％(32/40)in the control(AmB-D)group(P＞0.05).WBC,hemoglobin,and platelet count were significantly higher after treatment compared with pretreatment levels(P＜0.05)in both groups.The CD4+T lymphocyte count was higher after treatment compared with pretreatment levels in both groups.And the CD4+T lymphocyte count in ABCD group was significantly higher than that in the control group(P＜0.05).The levels of total bilirubin,aspartate aminotransferase,alanine aminotransferase,blood urea nitrogen,and serum creatinine increased after treatment in both groups.Blood urea nitrogen and serum creatinine increased significantly in control group compared with ABCD group(P＜0.05).After treatment,serum K+concentration decreased significantly in control group compared with the pretreatment level and compared with ABCD group(P＜0.05).The incidence of adverse events in ABCD group was significantly lower than that in the control group.The time to renal injury was delayed significantly(P＜0.05).Conclusions In the treatment of AIDS complicated with TSM,the efficacy of ABCD was comparable to AmB-D.The incidence of hepatic impairment did not show significant difference between ABCD and AmB-D.However,ABCD is associated with less renal impairment,lower incidence of adverse events,and better safety,which is valuable for clinical use.

Objective To investigate the efficacy of voriconazole in the treatment of pulmonary tuberculosis complicated with chronic pulmonary aspergillosis(CPA)based on CYP2C19 gene polymorphism detection and examine the factors affecting the efficacy for improving targeted therapy in clinical practice.Methods A total of 207 patients with pulmonary tuberculosis complicated with CPA treated in the Third People's Hospital of Kunming from December 2018 to November 2022 were randomly assigned to an observation group(105 cases)or a control group(102 cases).The patients in the control group received standard voriconazole treatment,while the patients in the observation group had their voriconazole regimen tailored based on CYP2C19 genotyping results.Plasma drug concentration levels,efficacy,and safety were compared between the two groups and in terms of CYP2C19 genotypes.Logistic regression analysis was used to identify the factors affecting treatment efficacy.Results The observation group showed significantly higher plasma voriconazole concentrations and overall antifungal efficacy compared to the control group(P＜0.05).In the observation group,CYP2C19 genotyping identified 37 extensive metabolizers(EM),47 intermediate metabolizers(IM),and 21 poor metabolizers(PM).Plasma concentration of voriconazole did not show significant difference between EM and IM(P＞0.05),but both PM and IM were associated with significantly lower plasma concentration of voriconazole than PM(P＜0.05).The clinical efficacy rate was 100％for PM,91.5％for IM,and 83.8％for EM(P＜0.05).The incidence of adverse events did not show significant difference among the three genotypes(P＞0.05).Logistic regression analysis revealed that lung cavitation,hypoalbuminemia,and agranulosis were significantly correlated with therapeutic efficacy(P＜0.05).Conclusions CYP2C19 gene polymorphism detection is valuable in clinical practice.It can inform anti-aspergillus therapy with voriconazole to effectively improve symptoms and clinical efficacy in patients with pulmonary tuberculosis complicated with CPA.Meanwhile,clinicians should be aware of the factors such as hypoproteinemia,agranulocytosis,and lung cavitation that may affect the efficacy of voriconazole.