Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

OBJECTIVE To evaluate the efficacy and safety of cadonilimab plus chemotherapy in patients with advanced gastric adenocarcinoma or adenocarcinoma of gastroesophageal junction （AEG） with intermediate， low， or no human epidermal growth factor receptor 2 （HER2） expression. METHODS Patients with advanced gastric adenocarcinoma or AEG with intermediate， low， or no HER2 expression who were treated at Liaoning Cancer Hospital between October 1， 2024 and June 30， 2025 were retrospectively included. According to the treatment regimen received， the patients were divided into group A [cadonilimab plus oxaliplatin and capecitabine （XELOX）， n ＝54 ] ， group B （sintilimab plus XELOX， n ＝68）， and group C （tislelizumab plus XELOX， n ＝49）. Short-term efficacy after 4 cycles of treatment， survival outcomes， and adverse events were compared among the three groups. Cox regression and Logistic regression analyses were further performed to evaluate the effects of the treatment regimen and baseline data on survival outcomes and the risk of grade 3-4 treatment related adverse events （TRAEs）. RESULTS No statistically significant differences in objective response rate or disease control rate were observed among the three groups （ P ＞0.05）. The median progression-free survival was 7.56 （5.62， 8.11） months in group A， 7.23 （5.33， 8.23） months in group B， and 7.33 （5.42， 8.19） months in group C， with no statistically significant difference among the three groups （ P ＞0.05）. The median overall survival （mOS） was 11.67 （8.82， 13.88） months in group A， 9.78 （6.82， 12.73） months in group B， and 9.69 （6.78， 12.66） months in group C. The mOS was significantly longer in group A than in group B and group C （ P ＜0.05）， whereas no statistically significant difference was observed between group B and group C （ P ＞0.05）. The correlation analysis indicated that treatment regimen， Eastern Cooperative Oncology Group performance status （ECOG PS）， number of metastatic organs， and peritoneal metastasis may be associated with overall survival （OS）. No significant association was observed between treatment regimen and the risk of grade 3-4 TRAEs. The incidences of grade 1-2 or grade 3-4 TRAEs did not differ significantly among the three groups （ P ＞0.05）. CONCLUSIONS In patients with advanced gastric adenocarcinoma or AEG with intermediate， low， or no HER2 expression， cadonilimab plus XELOX may provide a more significant OS benefit with a safety profile comparable to that of sintilimab or tislelizumab plus XELOX. Further studies with larger sample sizes are required to validate these findings.

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.

Objective:To explore the interrelationship between brain functional networks and features in functional magnetic resonance imaging(fMRI)of patients with Alzheimer's disease(AD),and to construct mixed-function networks(MFN),and apply them in machine learning classification models to improve the accuracy of AD classification.Methods:102 AD patients and 227 healthy subjects in the Alzheimer's Neuroimaging Initiative(ADNI)dataset were retrospectively analyzed.The partial correlation brain network of the blood oxygen level dependent(BOLD)signal was calculated and fused with low-frequency wave amplitude(ALFF),fractional low-frequency wave amplitude(fALFF)and local consistency(ReHo)features to construct MFN.Network topology parameters were extracted,and a variety of machine learning classification models were constructed based on MFN topological parameters,accuracy,precision,recall and area under the curve(AUC)were used to evaluate the predictive efficiency of the models.Results:By constructed MFN and calculated intra group to inter group ratio(IIGR),35 features could be obtained from ALFF,fALFF and ReHo feature topological parameter analysis,after rank sum test and FDR correction,there were statistical differences among 28 features(P＜0.05).The classification results show that,all the five classifiers have high classification performance on the test data set.The accuracy,precision and recall rates of random forest(RF),adaptive lifting algorithm(AdaBoost),guided aggregation algorithm(Bagging)and support vector machine(SVM)were all 99.7％,and the AUC values were up to 100％,99.5％,99.1％and 99.5％,respectively.The accuracy(98.5％),precision(98.5％),recall(98.5％),and AUC(99.1％)of the multi-layer perceptron(MLP)were slightly lower than other models,but remained excellent.It was worth noting that RF has the highest AUC value of all models at 100.0％,while Bagging has the lowest AUC value(99.1％)in the integrated approach.The results of performance comparison show that,MFN classification model can significantly improve the recognition and classification of AD disease,and greatly improve the performance of various indicators of the classifier.The results showed that,MFN classification model was superior to intelligent classification based fusion,DBN-based multitask learning,PVT-TSVM,unsupervised learning and clustering,SVM and SVM of degree 3 polynomial kernel function in key indicators such as accuracy(99.13％),AUC(99.42％),recall rate(99.46％)and specificity(99.42％)with plasma proteins,machine learning algorithms.It was further proved that MFN classification model has good generalization ability and robustness in AD disease classification.Conclusion:The AD classification model constructed based on brain mixed function network topology parameters and machine learning can improve the accuracy of AD classification.

Aim To investigate the therapeutic effect of newly formulated Tadalafil tablets on liver fibrosis in mice induced by carbon tetrachloride(CCl4)and its impact on the activation of hepatic stellate cells(HSCs).Methods Liver fibrosis model was estab-lished by intraperitoneally injecting 20％CCl4 corn oil solution twice a week for eight weeks.After four weeks of modeling,the treatment group was administered ei-ther the newly formulated Tadalafil tablets(1.0 mg·kg-1)or the Cialis(2.5 mg·kg-1)via gavage for the remaining four weeks.We assessed the effects of Tadalafil on collagen deposition,tissue structural dam-age,and HSCs activation markers in the fibrotic liver of mice using serum biochemical analysis,histopathologi-cal staining,and Western blotting following the treat-ment period.LX-2 cells were cultured and treated with tadalafil after TGF β1 stimulation,and the effects of tadalafil on LX-2 cell activation were assessed via Western blot.Results Compared to the normal mice,the model group mice exhibited a significantly higher liver-specific index,increased liver function indicators,and notable hepatocyte necrosis.Additionally,liver lobules were damaged,accompanied by severe infiltra-tion of inflammatory cells.Both smooth muscle actin(α-SMA)and fibronectin(Fn)were elevated,serving as markers of HSCs activation.As a result of treatment with the newly formulated Tadalafil tablets,liver tissue damage was significantly reduced,transaminase levels decreased,necrosis and inflammatory cell infiltration were reduced,and collagen fiber deposition was allevia-ted,and α-SMA and Fn expression was reduced.It was worth noting that low-dose newly formulated Tadalafil tablets were found to be as effective as high-dose Cia-lis.In a cellular model,Tadalafil significantly inhibited the activation of LX-2 cells and reduced the expression of proteins related to cell activation.Conclusions The newly formulated Tadalafil tablets can significantly inhibit HSCs activation,reduce extracellular matrix(ECM)deposition,improve liver fibrosis and liver function damage caused by CCl4.This new formulation offers a significant advantage over Cialis in terms of ef-fectiveness,with a lower effective dose.

Medical ultrasound technology is widely used for diagnosis and therapy in clinical practice.Ultrasound probes,which are directly contact with patients,pose a potential risk of pathogen transmission.This expert consen-sus was developed by a multidisciplinary team based on international guidelines,standards in China,and the results of a national survey,aiming to reduce the risk of healthcare-associated infection through standardizing reprocessing of medical ultrasound probes,and formulating consensus recommendations with the Delphi method.The consensus clarifies the reprocessing principles for three types of ultrasound probes of different infection risks:external-use ul-trasound probes,interventional percutaneous ultrasound probes,and internal-use ultrasound probes,puts forward systematic suggestions on the reprocessing standards and disinfection levels of ultrasound probe isolation covers and coupling agents,the reprocessing procedures and methods of ultrasound probes,as well as architectural layout and management of reprocessing,so as to provide a scientific prevention and control framework for ensuring ultrasound diagnosis and therapy safety.

Objective To preliminarily explore the safety of collecting colostrum in the third trimester,and to evaluate postpartum breastfeeding in pregnant women with hyperglycemia during pregnancy.Methods Pregnant women with hyperglycemia during pregnancy who had prenatal examinations in Obstetrics and Gynecology Hospital,Fudan University from Jul to Nov 2022 were prospectively divided into the colostrum collection group(n=52)in the third trimester and the control group(n=55)by randomized controlled grouping method.The t-test,χ2 test,Fisher's exact probability method and rank sum test were used for statistical analysis of the data to compare the delivery outcomes,neonatal outcomes and postpartum breastfeeding status between the two groups.Results There were no significant differences in the gestational weeks at delivery,delivery methods,breastfeeding rates at 42 days postpartum and 4 months postpartum between the two groups of pregnant women with hyperglycemia during pregnancy.There were also no significant differences in the Apgar scores at 1 minute and 5 minutes after birth and the neonatal hospitalization rate.The proportion of formula milk as the first supplementary feeding after delivery and the delayed lactation rate at 3 days postpartum in the colostrum collection group were significantly lower than those in the control group(P<0.05).The exclusive breastfeeding rates at 24 hours postpartum and 3 days postpartum in the colostrum collection group were significantly higher than those in the control group(P<0.05).Conclusion Collecting colostrum in the third trimester among pregnant women with hyperglycemia during pregnancy is safe,and it can reduce the rate of supplementary feeding with formula milk after delivery,and increase the exclusive breastfeeding rates at 24 hours postpartum and 3 days postpartum.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To investigate the effect of curcumin on blood glucose levels in pregnant women at high risk of Gestational Diabetes Mellitus(GDM).Methods:One hundred and twenty-four pregnant women with high-risk factors for GDM were included in a cross-sectional study according to the inclusion and exclusion criteria.After undergoing an Oral Glucose Tolerance Test,participants were divided into the GDM group(n=61)and the non-GDM group(n=63).Subsequently,a randomized controlled trial was performed to compare Fasting Plasma Glucose(FPG)levels between the control group(n=8)and the intervention group(n=8).Results:The cross-sectional study revealed that the GDM group had significantly higher rates of pre-pregnancy BMI ≥ 24 kg/m2,early pregnancy HbA1c≥5.7％,impaired fasting glucose or glucose tolerance,and lack of exercise compared to the non-GDM group(P＜0.05).FPG levels in the GDM group were significantly higher than those in the non-GDM group at all stages of pregnancy.Multivariable linear regression analysis showed that the impact of high-risk factors on FPG gradually diminished as pregnancy progressed.In the randomized controlled experiment,all cases in the control group developed GDM;one case in the curcumin intervention group did not,whose intervention time was the earliest and longest.Pearson correlation analysis indicated a positive correlation between the duration of curcumin intervention and changes in FPG values,although the correlation was not statistically significant(P＞0.05).By the descriptive statistical analysis,within-group comparisons showed no significant differences in the median and percentiles of FPG values between the control group in late pregnancy and early pregnancy.However,the median and percentiles of FPG values were significantly lower post-intervention compared to curcumin pre-intervention.Between-group comparisons revealed that the mean FPG in the curcumin intervention group decreased significantly more than in the control group.These results suggested that curcumin might have a potential impact on FPG.No significant differences were observed in neonatal outcomes between the curcumin intervention and control groups.Conclusions:Pregnant women with high risk factors for GDM should be paid enough attention in clinical practice.All these results have demonstrated that curcumin has a positive regulatory effect on FPG in patients with GDM,which may provide a new adjunctive method for the treatment of GDM.