Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Background and purpose:The resistance of pancreatic cancer to albumin-bound paclitaxel affects the therapeutic effect and prognosis.Signal transducer and activator of transcription 3(STAT3)is one of the important molecules regulating the chemotherapy sensitivity of cancer cells.The liposome BP1003 targeting the antisense oligonucleotide of STAT3 mRNA can inhibit the expression of STAT3 and increase the chemotherapy sensitivity.However,the effect of BP1003 on the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel remains unclear.The purpose of this study was to investigate the effects of liposome binding antisense oligonucleotide BP1003 on albumin-bound paclitaxel sensitivity in pancreatic cancer cells by inhibiting STAT3.Methods:Pancreatic cancer cell lines PANC-1 and ASPC-1 were cultured.They were divided into control group(without drugs),BP1003 group(200 μg/mL BP1003 intervention),different concentrations of albumin-bound paclitaxel group(5,10,20 nmol/L albumin-bound paclitaxel intervention),BP1003+different concentrations of albumin-bound paclitaxel group(200 μg/mL BP1003 combined with 5,10,20 nmol/L albumin-bound paclitaxel intervention).The proliferation viability,apoptotic rate and the protein expression levels of STAT3,STAT4,STAT6,Bcl-2,Bax and c-Myc were detected.The transplanted tumor model was established by subcutaneous injection of PANC-1 and ASPC-1 cell suspension in nude mice,which were divided into control group(normal saline intervention),BP1003 group(25 mg/kg BP1003 intervention,once every 2 weeks)and albumin-bound paclitaxel group(10 mg/kg albumin-bound paclitaxel,once a week),BP1003+albumin-bound paclitaxel group(25 mg/kg BP1003 intervention,once every 2 weeks combined with 10 mg/kg albumin-bound paclitaxel,once a week).Four weeks later,the graft volume and mass were measured,and the protein expression levels of STAT3,Bcl-2,Bax and c-Myc were detected.Results:The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003 group and albumin-bound paclitaxel group were higher than those in the control group,while the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in control group(P＜0.05).There was no significant difference in the expression levels of STAT4 and STAT6 in PANC-1 and ASPC-1 cells between BP1003 group and the control group(P＞0.05).The apoptotic rate and the protein expression levels of Bax of PANC-1 and ASPC-1 cells in BP1003+different concentrations of albumin-bound paclitaxel groups were higher than those in different concentrations of albumin-bound paclitaxel groups,and the proliferation viability and protein expression levels of STAT3,Bcl-2 and c-Myc were lower than those in different concentrations of albumin-bound paclitaxel groups(P＜0.05).The volume and mass of transplanted tumor and the protein expression levels of STAT3,Bcl-2 and c-Myc of nude mice in BP1003 group,albumin-bound paclitaxel group and BP1003+albumin-bound paclitaxel group were all lower compared with the control group,the protein expression level of Bax was higher compared with the control group(P＜0.05),and the above changes in BP1003+albumin-bound paclitaxel group were more significant compared with BP1003 and albumin-bound paclitaxel group.Conclusion:BP1003 increases the sensitivity of pancreatic cancer cells to albumin-bound paclitaxel by inhibiting the expression of STAT3.

Systemic lupus erythematosus(SLE)complicated refractory immune thrombocytopenia(ITP)is mainly characterized by persistent severe thrombocytopenia and bleeding.Currently,there are no guidelines for treating such ITP.Hereby we reported a patient diagnosed with SLE with more than 10 years history of anemia and thrombocytopenia.This patient had been treated by various immunity inhibitors,such as corticosteroids,cyclosporine,mycophenolate mofetil,azathioprine,tofacitinib and telitacicept,but there was no obvious effect.The platelet count continued to be below 50×109/L.However,when serum cyclosporine trough level between 100 and 150 ng/mL,the clinical efficacy was improved and the platelet count was above 100×109/L.The patient was followed up for more than 6 months,and no recurrence of disease was found.Cyclosporine combined with low-dose glucocorticoid is safe and effective for SLE associated ITP.Therapeutic drug monitoring is a powerful tool for improving clinical efficacy and ensuring drug safety.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective:To analyze the clinical phenotypes and genetic characteristics of pediatric patients with neurofibromatosis type 1 (NF1).Methods:A cross-sectional study was adopted. Clinical and imaging data of 25 pediatric patients diagnosed as having NF1 in Department of Pediatric Neurology, Linyi People's Hospital Affiliated to Shandong Second Medical University from January 2024 to July 2025 were collected. Whole exome sequencing and Sanger sequencing were used to conduct genetic testing on the pediatric patients and his/her parents. Protein 3D modeling of the domestic and foreign unreported variations was conducted using SWISS-MODEL software.Results:Among the 25 pediatric patients with NF1, 14 were male (56%) and 11 were female (44%), with age ranging from 8 months to 18 years. All pediatric patients exhibited café-au-lait macules, and 7 (28%) presented with plexiform neurofibromas. Genetic test identified 4 types of NF1 variants: nonsense variant ( n=11, 44%), frameshift variant ( n=9, 36%), missense variant ( n=3, 12%), and splice-site variant ( n=2, 8%). Importantly, 5 novel NF1 variants were discovered, including c.3455T>A, c.3709dupG, c.2665_2684del, c.7092_7095delinsTA, and c.3260del. Three pediatric patients inherited NF1 variant from their parents, while the remaining 22 harbored de novo mutation. Conclusion:NF1 exhibits a broad clinical spectrum, primarily affecting the skin and nervous system; this study identifies 5 previously unreported variants, expanding the genetic profile of NF1.

Aim To observe the mechanism of salvian-olic acid B(SalB)against oxygen glucose deprivation/re-oxygenation(OGD/R)injury in H9c2 cardiomyo-cytes.Methods The protective concentration of SalB against OGD/R-injured H9c2 cardiomyocytes was screened by CCK-8 assay.The levels of lactate dehy-drogenase(LDH),aspartate transaminase(AST)and creatine kinase(CK)were detected by ELISA kit.The mechanism of action of SalB on OGD/R-injured H9c2 cardiomyocytes was explored using high-through-put sequencing of the transcriptome.The binding of SalB to differential proteins was assessed using molecu-lar docking assays.Fatty acid content was determined using free fatty acid kits.The relative expressions of mRNA and protein of differential genes were verified by RT-qPCR and Western blot.The causal relationship between the target of action of SalB and heart failure was examined by Mendelian randomization experiment.Results SalB protected OGD/R-injured H9c2 cardio-myocytes and significantly reduced the levels of CK,LDH and AST compared with the blank control group.One hundred differential genes were screened by tran-scriptome sequencing,which were mainly involved in fatty acid elongation,central carbon metabolism of cancer,tryptophan metabolism pathways.Molecular docking showed that SalB had good binding energy to differential proteins.The mRNA and protein expression of core differential genes Elovl6,Echs1 and Acot1 were consistent with the transcriptome sequencing results.SalB reduced fatty acidsafter OGD/R injury.Mende-lian randomization experiments suggested that SalB might reduce the risk of heart failure through fatty acid metabolism,thereby reducing the risk of heart failure.Conclusion SalB can protect H9c2 cardiomyocytes after OGD/R injury by down-regulating Elovl6,Echs1 and Acot1 expression through the fatty acid metabolism pathway.

Objective To screen and analyze biomarkers of comorbidity in nonalcoholic fatty liver disease(NAFLD)and colorectal cancer(CRC)based on bioinformatics so as to explore the mechanism of comorbidity.Methods After data related to NAFLD and CRC were downloaded from the public database(GEO),gene set enrichment analysis(GSEA)was performed for all genes to screen the expression pathways,and the common differentially expressed genes of both genes were annotated by GO and KEGG functions.Subsequently,PPI protein interaction network was constructed using STRING online database to screen key genes,and transcription factor-gene regulatory network was constructed based on key genes,and biomarker genes were identified using LASSO regression.Finally,the transcription factor prediction analysis of key genes and SCD was conducted through Network Analyst database,and the transcription factor network was constructed.Results GSEA analysis revealed that signaling pathways such as TNF-α and IL-6-JAK-STAT3 were activated in NAFLD patients.The 17 common differentially expressed genes were mainly enriched in biological processes such as bivalent inorganic cation homeostasis and neutrophil chemotaxis in GO analysis.KEGG pathway analysis showed that common differentially expressed genes were mainly concentrated in IL-17 signaling pathway.The protein interaction network screened out five key genes:TREM1,FPR1,IL1RN,S100A9,and S100A8.IL1RN and SCD,identified by LASSO regression,were validated as biomarker genes using external datasets and immunohistochemistry data from the human protein atlas(HPA)database,showing high expression in CRC tissues.A transcription factor-key comorbidity gene regulatory network was constructed using Network Analyst.Conclusion The genes for comorbidities between NAFLD and colorectal cancer discovered by bioinformatics reveal the potential pathogenesis of comorbidities,and provide ideas for cancer screening and early diagnosis of colorectal cancer in NAFLD patients.

Objective:To explore the clinical characteristics of biliary system diseases complicated by severe acute pancreatitis(SAP) and the risk factors.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on the clinical data of 159 SAP patients admitted to the Department of Pancreatic and Biliary Surgery,the First Affiliated Hospital of Harbin Medical University from January 2019 to October 2024. There were 105 male cases, 54 female cases;aged (42.3±10.8)years (range:20 to 71 years). Grouping was performed according to the presence or absence of concurrent acute acalculous cholecystitis (AAC) and biliary stricture. There were 58 cases in the AAC group,including 40 males and 18 females;aged (43.8±10.6) years (range:28 to 71 years);101 cases in the non-AAC group,including 64 males and 37 females;aged (41.5±10.8) years (range:20 to 64 years);there were statistically significant differences between the two groups in terms of admission total bilirubin,Balthazar-CTSI score,fasting time,and the proportions of concurrent shock and sepsis (all P<0.05);the time from onset of SAP to diagnosis of AAC( M (IQR)) was 10.5 (13.3) days (range: 3 to 34 days). There were 15 cases in the biliary stricture group,including 13 males and 2 females;age (46.5±10.0) years (range:33 to 63 years);141 cases in the non-biliary stricture group,including 89 males and 52 females;age (41.9±10.8) years (range: 20 to 71 years); there were statistically significant differences between the two groups in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis (all P<0.05);the time from the onset of SAP to the diagnosis of biliary stenosis in patients with biliary stenosis was 2.0 (3.0) months (range: 1 to 19 months). Univariate analysis was performed using independent sample t-test, Mann-Whitney U test, χ 2 test,or Fisher′s exact probability method,and variables with P<0.05 in univariate analysis were included in multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic and predictive value of the multivariate logistic regression model for AAC and biliary stricture. Results:There were statistically significant differences in fasting time,Balthazar-CTSI score,admission total bilirubin,and the proportions of concurrent shock and sepsis between the AAC group and non-AAC group ( P<0.05). Multivariate logistic analysis showed that admission total bilirubin ( OR=1.033,95% CI: 1.010 to 1.058, P=0.004),Balthazar-CTSI score ( OR=1.276,95% CI: 1.036 to 1.572, P=0.022),fasting time ( OR=1.127,95% CI: 1.044 to 1.216, P=0.002), and sepsis ( OR=4.033, 95% CI: 1.419 to 11.462, P=0.009) were independent risk factors for AAC complicated by SAP. The area under the curve (AUC) of the ROC curve was 0.820 (95% CI: 0.752 to 0.888). There were statistically significant differences in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis between the biliary stricture group and non-biliary stricture group ( P<0.05). Multivariate logistic analysis showed that infected pancreatic necrosis ( OR=7.376,95% CI:1.566 to 37.750, P=0.012) and pancreatic head necrosis ( OR=3.898,95% CI:1.180 to 12.877, P=0.026) were independent risk factors for biliary stricture complicated by SAP. The AUC of the ROC curve was 0.806 (95% CI:0.715 to 0.898). Conclusions:AAC typically occurs in the early stage of SAP,and biliary stricture usually occurs in the late stage of SAP. Admission total bilirubin,Balthazar-CTSI score,fasting duration,and concurrent sepsis are independent risk factors for AAC complicating SAP. Infected pancreatic necrosis and pancreatic head necrosis are independent risk factors for biliary stricture complicating SAP.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index