Objective: To analyze the etiological surveillance results of influenza-like illness (ILI) cases in Jiangsu Province, and investigate the distribution characteristics of different influenza virus types, so as to provide the evidence for improving influenza prevention and control measures. Methods: Influenza laboratory testing data for sentinel surveillance of ILI cases in Jiangsu Province from 2019 to 2024 were collected through the China Influenza Surveillance Information System. The positive detection rate of influenza virus was calculated, and descriptive analysis was performed to characterize the distribution of different influenza virus types. Using the farthest neighbor linkage method, influenza virus positive detection rates clustering was analyzed by year and week. Clusters were defined based on inter-cluster distance, and the intensity of the positive detection rate was visualized through color gradients in the clustering heatmap. Results: From 2019 to 2024, a total of 183 878 ILI specimens were collected in Jiangsu Province. Among them, 20 059 specimens tested positive for influenza virus, corresponding to an overall positive detection rate of 10.91%, and an average annual positive detection rate of 10.89%. The primary circulating influenza virus types were influenza A H3N2 subtype, accounting for 40.92%, followed by influenza B Victoria linage at 34.00%, and influenza A H1N1 subtype at 24.80%. Influenza B Yamagata linage was not detected throughout the five-year period. Influenza A H3N2 subtype predominated during two distinct periods: from January to March 2019, and from June 2022 to December 2023. Influenz B Victoria linage was the dominant type from April 2019 to May 2022 and again from January to April 2024. Influenza A H1N1 subtype emerged as the primary type from May to December 2024. Year-based clustering analysis grouped the annual positive detection rates from 2019 to 2024 into three clusters. The closest cluster distance was observed between 2019 and 2024. The highest annual positive detection rate occurred in 2023. Both influenza A H3N2 and H1N1 subtype each formed a single cluster, with their peak positive detection rates also recorded in 2023. Influenza B Victoria lineage was separated into two clusters, with its highest positive detection rate occurring in 2020. Week-based clustering analysis revealed that influenza virus detection was concentrated in weeks 47 to 52 and weeks 1 to 15. More specifically, the positive detection rates for influenza A H3N2 subtype peaked during weeks 30 to 34 and weeks 42 to 52; for influenza A H1N1 subtype, during weeks 9 to 15 and weeks 51 to 52; and for influenza B Victoria lineage, during weeks 1 to 11 and weeks 50 to 52. Conclusions From 2019 to 2024, the average annual positive detection rate of influenza virus in Jiangsu Province remained relatively low. Influenza activity characterized by the alternating circulation of influenza A H1N1 subtype, influenza A H3N2 subtype, and influenza B Victoria linage. It is necessary to maintain the surveillance sensitivity for the influenza B Yamagata lineage.

ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. ConclusionIn patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.

ObjectiveTo investigate the association of liver fibrosis scores and inflammation markers with gallstones in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， as well as the mediating role of liver fibrosis scores in the relationship between inflammation markers and gallstones. MethodsA total of 14 567 patients who received physical examination and were diagnosed with MAFLD in Subei People’s Hospital from January 2014 to June 2023 were enrolled in this study， and according to the results of abdominal color Doppler ultrasound， they were divided into gallstone group with 1 724 patients and non-gallstone group with 12 843 patients. Related clinical data were collected from all patients， including demographic data， medical history， family history， physical examination， Color Doppler ultrasound， and biochemical parameters. The biomarkers associated with metabolic disorders and insulin resistance included triglyceride-glucose index （TyG）， TyG-body mass index （BMI） index， atherogenic index of plasma （AIP）， and non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio （NHHR）； the biomarkers associated with inflammation and nutritional status included neutrophil-to-lymphocyte ratio （NLR）， neutrophil percentage-to-albumin ratio （NPAR）， and monocyte-to-lymphocyte ratio （MLR）； the biomarkers for assessing liver fibrosis degree and liver function included albumin-bilirubin （ALBI） score， NAFLD fibrosis score （NFS）， fibrosis-4 （FIB-4） index， and aspartate aminotransferase-to-platelet ratio index （APRI）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Multivariate Logistic regression analysis， restricted cubic spline analysis， and mediating effect analysis were used to assess the association of liver fibrosis markers and inflammation markers with the risk of gallstones. ResultsThe prevalence rate of gallstones was 11.8% among the MAFLD patients. There were significant differences between the gallstone group and the non-gallstone group in sex， age， smoking history， diabetes， hypertension， lymphocytes， platelets， glucose， albumin， serum uric acid， alanine aminotransferase， aspartate aminotransferase， red blood cell， NLR， NPAR， MLR， NFS， FIB-4 index， and ALBI score （all P<0.05）. The multivariate Logistic regression analysis showed that NLR （odds ratio ［OR］=1.091， 95% confidence interval ［CI］： 1.028　—　1.160， P<0.05）， NPAR （OR=1.073， 95%CI： 1.042　—　1.105， P<0.05）， MLR （OR=1.142， 95%CI： 1.057　—　1.232， P<0.05）， NFS （OR=1.239， 95%CI： 1.190　—　1.291， P<0.05）， and FIB-4 index （OR=1.326， 95%CI： 1.241　—　1.417， P<0.05） were influencing factors for the prevalence rate of gallstones. The restricted cubic spline analysis showed a significant non-linear association between NFS/FIB-4 index and the risk of gallstone （non-linear P<0.05）. The mediating effect analysis further showed that the association of NLR， MLR， and NPAR with gallstones was partially mediated by NFS or FIB-4 index， with a mediating effect accounting for 36.79%、28.09%、29.67% and 18.31%、17.70、11.57%， respectively. ConclusionNFS and FIB-4 index have a non-linear association with the prevalence rate of gallstones in MAFLD patients， and they also mediate the association of NLR， NPAR， and MLR with the risk of gallstone.

Objective To fabricate a large-diameter vascular graft with a pore size gradient structure mimicking that of natural blood vessels, using poly-L-lactic acid (PLLA) and polycaprolactone (PCL) as base materials through electrospinning and ultrasonic pore-forming techniques, and to evaluate its application potential. Methods A three-layered tubular graft was fabricated from a PCL/PLLA blend (mass ratio 6 : 4) via electrospinning, followed by an ultrasonic pore-forming process to create a gradient porosity. The resulting graft (diameter: 2 cm, length: 4 cm) was implanted into the descending thoracic aorta of an experimental pig using an end-to-end anastomosis. Graft patency and anastomotic sites were monitored by computed tomography angiography (CTA) at 1 and 6 weeks post-surgery. After 2 months, the graft was explanted for systematic evaluation of vascular regeneration and repair through gross examination, histopathology (H&E and elastic fiber staining), immunohistochemistry [for ETS-related gene (ERG), Actin, and Vimentin], and scanning electron microscopy (SEM). Results Postoperative CTA confirmed excellent graft patency at both 1 and 6 weeks, with no evidence of thrombosis or anastomotic stenosis. Gross examination of the 2-month explant revealed a smooth luminal surface covered by neotissue. Histopathological analysis demonstrated that the graft successfully induced the formation of a three-layered structure resembling a native vessel wall, comprising endothelial cells, smooth muscle cells, and fibroblasts. Immunohistochemistry further verified coverage of the luminal surface by endothelial cells (ERG-positive), along with the presence of neosmooth muscle (Actin-positive) and fibroblasts (Vimentin-positive). Endothelial cells were observed adhering to the inner surface of the artificial vessel under SEM. Conclusion The biomimetic, three-layered PLLA/PCL large-diameter vascular graft, constructed via electrospinning and ultrasonic pore-forming, exhibits excellent short-term patency and biocompatibility in a large animal model. More importantly, it demonstrates a significant potential to promote host cell infiltration and achieve in situ regeneration of a three-layered vascular wall structure, providing a promising experimental basis for the development of next-generation functional vascular substitutes.

ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction （清肠温中方， QWD） in treating ulcerative colitis （UC）. MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group （n=45） and a conventional group （n=55） using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established， the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group， a pseudo-germ-free QWD group， and a pseudo-germ-free mesalazine group， with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group （n=10）， as well as a conventional model group， a conventional QWD group， and a conventional mesalazine group， with 15 mice in each group. Except for the normal control group， acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment， mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/（kg·d） by gavage with deionized water， while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/（kg·d） by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment， six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight， and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota， including operational taxonomic units （OTUs）， Shannon index， Observed_species index， and phylogenetic diversity （PD whole tree）. On day 39， body weight was measured in all groups， and the disease activity index （DAI） was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin （HE） staining， and histological injury scores were determined. In addition， the expression levels of mucopolysaccharides and mucin 2 （MUC2） in colonic tissues were measured. ResultsOn day 25， there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group （P＞0.05）. Compared to the conventional microbiota group， the pseudo-germ-free group showed significantly reduced OTUs， Shannon index， Observed_species index， and PD whole tree （P＜0.01）. On day 39， compared to the normal control group， mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI， along with increased colon wet weight， shortened colon length， markedly elevated histopathological scores， and reduced expression of mucopolysaccharides and MUC2 （P＜0.01）. In contrast， no significant differences were observed in these parameters in the pseudo-germ-free model group （P＞0.05）. Compared to the conventional model group， the conventional QWD group showed significant improvement in all measured parameters， whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight （P＜0.01）. No statistically significant differences were observed among the pseudo-germ-free model group， the pseudo-germ-free QWD group， and the pseudo-germ-free mesalazine group （P＞0.05）. ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora， thereby exerting a therapeutic effect on acute UC.

ObjectiveTo explore the mechanisms of Qingchang Wenzhong Decoction （清肠温中方， QWD） in treating ulcerative colitis （UC）. MethodsA total of 100 male C57BL/6J mice were assigned to a pseudo-germ-free group （n=45） and a conventional group （n=55） using a random number table. Pseudo-germ-free model was established by giving antibiotic treatment and subsequently subjected to acute UC induction. After the model was successfully established， the 45 pseudo-germ-free acute UC mice were randomly allocated to a pseudo-germ-free model group， a pseudo-germ-free QWD group， and a pseudo-germ-free mesalazine group， with 15 mice in each group. The 55 conventional mice were randomly divided into a normal control group （n=10）， as well as a conventional model group， a conventional QWD group， and a conventional mesalazine group， with 15 mice in each group. Except for the normal control group， acute UC models were established in all other groups. Mice in the control group received no intervention. From day 32 of the experiment， mice in the pseudo-germ-free QWD group and the conventional QWD group were administered with QWD granules at a dose of 9.71 g/（kg·d） by gavage with deionized water， while those in the pseudo-germ-free mesalazine group and the conventional mesalazine group were given mesalazine enteric-coated tablets at a dose of 151.67 mg/（kg·d） by gavage. Mice in the remaining groups received an equal volume of deionized water once daily for 7 consecutive days. On day 25 of the experiment， six mice were randomly selected from both the pseudo-germ-free group and the conventional group to measure body weight， and fecal samples were collected for 16S rDNA sequencing to compare differences in gut microbiota， including operational taxonomic units （OTUs）， Shannon index， Observed_species index， and phylogenetic diversity （PD whole tree）. On day 39， body weight was measured in all groups， and the disease activity index （DAI） was evaluated. Colon length and colon wet weight were recorded. Histopathological changes in colonic tissues were assessed by hematoxylin and eosin （HE） staining， and histological injury scores were determined. In addition， the expression levels of mucopolysaccharides and mucin 2 （MUC2） in colonic tissues were measured. ResultsOn day 25， there was no significant difference in body weight between the pseudo-germ-free group and the conventional microbiota group （P＞0.05）. Compared to the conventional microbiota group， the pseudo-germ-free group showed significantly reduced OTUs， Shannon index， Observed_species index， and PD whole tree （P＜0.01）. On day 39， compared to the normal control group， mice in the conventional model group showed a significant decrease in the body weight and an increase in DAI， along with increased colon wet weight， shortened colon length， markedly elevated histopathological scores， and reduced expression of mucopolysaccharides and MUC2 （P＜0.01）. In contrast， no significant differences were observed in these parameters in the pseudo-germ-free model group （P＞0.05）. Compared to the conventional model group， the conventional QWD group showed significant improvement in all measured parameters， whereas the conventional mesalazine group showed reductions only in DAI scores and colon wet weight （P＜0.01）. No statistically significant differences were observed among the pseudo-germ-free model group， the pseudo-germ-free QWD group， and the pseudo-germ-free mesalazine group （P＞0.05）. ConclusionQWD may promote the reconstruction of the intestinal mucus barrier by regulating the intestinal flora， thereby exerting a therapeutic effect on acute UC.

OBJECTIVE To evaluate the cost-effectiveness of brivaracetam （BRV） versus perampanel （PER） as add-on therapy for drug-resistant focal epilepsy in adults from the perspective of the Chinese healthcare system.METHODS A Markov model was established to simulate the progression of drug-resistant focal epilepsy in adults， with a simulation cycle of 5 months， a time horizon of 44 years， and a discount rate of 4.5%. Clinical data required for the model were derived from the phase Ⅲ clinical trial of BRV and a post hoc analysis of PER； cost data and utility data were obtained from Yaozh and related literature. The willingness-to-pay （WTP） threshold was set at twice China’s 2025 per capita gross domestic product （GDP） [199 330 yuan per quality-adjusted life year （QALY）]， and a cost-effectiveness analysis was adopted to compare the cost-effectiveness of the regimens. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the stability of the base-case analysis conclusions.RESULTS The incremental cost-effectiveness ratio （ICER） of BRV 50 mg/d as an add-on therapy versus PER 8 mg/d was 44 823.08 yuan/QALY， which was below the WTP threshold； the ICER of BRV 200 mg/d versus PER 12 mg/d was 238 783.00 yuan/QALY， which was above the WTP threshold. In the one-way sensitivity analysis， the direct medical cost of seizures ≥53 times/year and the health utility value of a seizure-free state per year had a relatively large impact on the two ICER results mentioned above， respectively. Probabilistic sensitivity analysis indicated that the above results were robust.CONCLUSIONS For the selection of add-on therapy for drug-resistant focal epilepsy in adults in China， when twice China’s per capita GDP is used as the WTP threshold， BRV 50 mg/d has a cost-effectiveness advantage over PER 8 mg/d， whereas BRV 200 mg/d not have a cost-effectiveness advantage over PER 12 mg/d.

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

Aim To perform high-throughput screen-ing of immunomodulatory traditional Chinese medicine(TCMs)based on an in vitro B cell differentiation-antibody secretion model,identifying active herbal candidates with immune-enhancing properties to pro-vide novel therapeutic options and theoretical support for influenza virus treatment in immunocompromised in-dividuals.Methods B cells were stimulated with dif-ferent concentrations of cytosine-phosphate-guanine oli-godeoxynucleotide 2006(CpG)and nterleukin-2(IL-2)to promote proliferation,differentiation,and anti-body secretion,and the effects of varying concentra-tions of the solvent DMSO were also evaluated.The op-timal conditions for the B cell differentiation-anti-body secretion model were determined based on the se-cretion levels of three antibody isotypes.The feasibility of the model was further validated using rapamycin,a known B cell function inhibitor.On this basis,a high-throughput screening platform for immunomodulatory a-gents was optimized and established.Subsequently,the immune-enhancing activity of 465 polarity extract from TCMs was evaluated.Results The optimal con-ditions for the model were determined as 2 mg·L-1 CpG,1.67 × 106 nkat·L-1 IL-2,and DMSO with a volume fraction of 0.1％.Rapamycin effectively inhib-ited B cell differentiation into plasmablast and signifi-cantly reduced antibody production,indicating the reli-ability of the model.Multiple rounds of screening re-vealed that the dichloromethane extract of licorice,the dichloromethane extract of Vinegar-processed Curcumae Rhizoma,the cyclohexane extract of Honey-prepared Radix Asteris,and the aqueous extract of Siphonostegia chinensis Benth were identified to significantly promote both B cell proliferation and differentiation and anti-body secretion at a concentration of 600 μg·L-1.Conclusion This study successfully optimizes an in vitro B cell differentiation-antibody secretion model and identifies several TCM extracts,including licorice,with potential immune-enhancing activity.

Objective:To investigate the correlation between transabdominal bowel ultrasongraphy (TBUS) parameters and disease activity of ulcerative colitis (UC).Methods:The results of TBUS, endoscopy and laboratory tests of 68 UC patients (108 examinations) who visited the Department of Gastroenterology of the Second Hospital (Eastern Campus) of Hebei Medical University From January 2022 to February 2024 were retrospectively analyzed. According to Mayo endoscopic score (MES), there were 10 cases of remission (MES=0) and 98 cases of active phase (MES>0); patients in active phase further classified into 16 cases of mild (MES=1), 19 cases of moderate (MES=2), and 63 cases of severe (MES=3). The TAUS parameters were compared between patients in remission and active phases. Spearman rank correlation analysis was used to analyze the correlation between the TBUS parameters including bowel wall thickness (BWT), Limberg score, wall layer stratification, fat wrapping and endoscopic activity score, laboratory inflammatory indicators. Receiver operating characteristic curve (ROC) analysis was applied to evaluate the predictive efficacy of the TBUS parameters and laboratory inflammatory indicators in identifying remission under endoscopy. Independent sample t-test and Fisher′s exact probability method were used to compare the two groups. Results:The BWT of patients in remission was significantly thinner than that of patients in active phase ((2.99±0.41) mm vs. (5.66±1.57) mm, t=-5.34, P<0.001). The proportions of patients in remisson with Limberg score ≤2, normal wall layer stratification, and absence of fat wrapping were significantly higher than those of patients in active phase (10/10 vs. 34/98, 10/10 vs. 48/98, 10/10 vs. 41/98, Fisher′s exact test, P<0.001, =0.002, =0.001). BWT, Limberg score, wall layer stratification, and fat wrapping were positively correlated with MES ( r=0.676, 0.677, 0.441, and 0.493, all P<0.001). BWT and Limberg score were moderate positively correlated with C-hypersensitive reactive protein, erythrocyte sedimentation rate and fecal calprotectin (BWT: r=0.561, 0.420 and 0.458, all P<0.001; Limberg score: r=0.576, 0.469 and 0.403, all P<0.001), and were negatively correlated with serum albumin and hemoglobin (BWT: r=-0.604 and -0.453, both P<0.001; Limberg score: r=-0.573 and -0.532, both P<0.001). The results of ROC analysis showed that BWT achieved the best predictive efficacy in identifying endoscopic remission, and the best cut-off value was 3.45 mm (area under the curve was 0.972, 95% confidence interval: 0.944 to 1.000, P<0.001), with a sensitivity of 93.9% and specificity of 100.0%. Conclusions:TBUS parameters can accurately reflect disease activity in UC. It is a powerful tool for UC monitoring. The BWT<3.45 mm is the best cut-off value in prediction of endoscopic remission.