ObjectiveThis study aims to elucidate the potential mechanism of Zuojinwan in improving liver fibrosis through hepatic tissue metabolomics analysis. MethodsTwenty-four mice were randomly allocated into normal group， model group ， positive drug group （silymarin， 100 mg·kg^-1）， and Zuojinwan group （Zuojinwan solution， 2.5 g·kg^-1）， with per group six mice. Liver fibrosis model was induced via intraperitoneal injection of olive oil solution with 10% carbon tetrachloride （CCl₄） （0.5 μL·g^-1， three times weekly for 8 weeks） in all groups except the normal group. During the final 4 weeks， the silymarin group received silymarin （100 mg·kg^-1） by gavage thrice weekly， while the Zuojinwan group was administered Zuojinwan solution （2.5 g·kg^-1） under the same regimen. After the last administration， the levels of liver fibrosis indicators and liver injury markers in serum were detected. The pathological morphological changes of the liver tissues were observed. The levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and Collagen Ⅰ（ColⅠ） were detected. Metabolomics was analyzed on mice's liver tissues. The mice's serum was collected for metabolomics analysis. ResultsCompared with the model group， Zuojinwan significantly improved indicators related to liver fibrosis and liver injury. Compared with the normal group， the model group showed significantly elevated levels of fibrosis markers such as laminin （LN）， hyaluronic acid （HA）， procollagen typeⅢ （PC-Ⅲ）， and type Ⅳ Collagen （Ⅳ-C）， while liver injury indicators such as alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， lactate dehydrogenase （LDH）， and total bilirubin （TBIL）， exhibited a marked upward trend （P<0.05）. Compared with the model group， the silymarin group showed a significant decrease in the aforementioned indicators （P<0.05）. Notably， compared with the model group， the Zuojinwan group exhibited a significant reduction in all these indicators （P<0.05）， with efficacy comparable to that of the silymarin group. Zuojinwan reduced mRNA and protein levels of α-SMA and ColⅠ in the liver tissue. Metabolomics results revealed that compared with the model group， Zuojiinwan significantly reduced levels of glucose metabolism-related metabolites such as D-fructose 1，6-bisphosphate （FBP）， nicotinamide adenine dinucleotide phosphate （NADPH）， sodium beta-D-fructose 6-phosphate （F6P）， dihydroxyacetone phosphate （DHAP）， fumaric acid， and D-glucose 6-phosphate （G6P） （P<0.05）. Serum enzyme-linked immunosorbent assay （ELISA） was used to detect glucose metabolism indicators and further validate the regulatory effect of Zuojinwan on glucose metabolism. ConclusionThese results suggest that Zuojinwan may improve liver fibrosis by regulating the dysregulated levels of glucose metabolism during the progression of liver fibrosis.

Objective: To analyze the school tuberculosis (TB) outbreaks and preventive treatment in Hefei from 2022 to 2024, so as to provide reference for TB prevention and control in schools. Methods: Data were collected on all school based TB outbreaks occurring during 2022-2024 in Hefei, defined as ≥2 epidemiologically linked TB cases within the same school during a single semester. Statistical analyses were performed using the Chi square test. Results: Close contacts exhibited significantly higher TB incidence (2.88%) and latent mycobacterium tuberculosis infection (LTBI) rates (13.80%) in the school TB outbreaks, compared to non close contacts (0.12% and 2.63%, respectively). Among close contacts, secondary school students showed lower TB incidence (0.48%) and LTBI prevalence (3.42%) than both primary school or younger children (0.68%, 6.95%) and college students ( 0.78% , 6.50%), with statistically significant differences ( χ 2=360.91, 6.37; 791.71, 102.03, all P <0.05). The proportion of LTBI individuals recommended for preventive therapy was higher in primary school or younger groups (98.59%) than in secondary (95.25%) or college students (86.34%) ( χ 2=25.86, P <0.01). However, among those recommended, close contacts had higher uptake (85.82%) and completion rates (87.25%) of preventive therapy than non close contacts (69.63% and 70.57%); similarly, secondary school students demonstrated higher uptake (91.21%) and completion rates (86.45%) compared to primary school or younger (88.57%, 83.87%) and college students (57.28%, 64.08%) ( χ 2=30.52, 26.72; 125.17, 38.84, all P <0.01). Subsequent TB incidence among LTBI close contacts (13.30%) and among those who did not complete preventive therapy (22.73%) were significantly higher than among non close contacts (2.80%, 2.41%), respectively ( χ 2=32.19, 13.87, both P <0.05). Conclusions In school TB outbreaks, close contacts face higher LTBI prevalence and subsequent TB risk than non close contacts. College students show notably low adherence to preventive therapy. It is necessary to take targeted measures to improve the compliance of preventive measures among students.

ObjectiveTo investigate the therapeutic effect of sitravatinib on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice. MethodsA total of 30 male C57BL/6J mice， aged 8 weeks， were randomly divided into control group， CCl₄ model group， and low- （5 mg/kg）， middle- （10 mg/kg）， and high-dose （20 mg/kg） sitravatinib groups. All mice except those in the control group were given intraperitoneal injection of CCl₄ for 4 consecutive weeks to induce liver fibrosis， and since the first day of modeling， the mice in the low-， middle-， and high-dose sitravatinib groups were given sitravatinib at the corresponding dose by gavage every day. The serum levels of total cholesterol （TC）， triglyceride （TG）， and alanine aminotransferase （ALT） were measured for the mice in each group； hepatic hydroxyproline content was measured； HE staining， Masson staining， and Sirius Red staining were used to observe liver histopathological changes； quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of α-smooth muscle actin （α-SMA） and collagen type I alpha 1 （Col1a1） in liver tissue. The therapeutic effect of sitravatinib was assessed based on the above results. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had significant increases in the levels of TC， TG， and ALT （all P<0.05）， and there were no significant differences in the levels of TC， TG， and ALT between the model group and the low-， middle-， and high-dose sitravatinib groups （all P>0.05）. Hepatic hydroxyproline content decreased after sitravatinib intervention， with a significant difference between the middle-/high-dose sitravatinib groups and the CCl₄ model group （both P<0.05）. Histopathological staining showed that the sitravatinib treatment groups had a reduction in collagen deposition， along with thinning and fragmentation of fibrous septa， and in the high-dose sitravatinib group， 4 mice had a fibrosis stage of S0—S1 and 2 mice had a fibrosis stage of S2—S3， suggesting a certain degree of alleviation of liver fibrosis degree compared with the CCl₄ model group （mainly S3—S4）. The measurement of related molecules showed that sitravatinib downregulated the mRNA and protein expression levels of α-SMA and Col1a1 （all P<0.05）. ConclusionSitravatinib can effectively alleviate CCl₄-induced liver fibrosis in mice， possibly by inhibiting hepatic stellate cell activation and collagen synthesis.

Drawing on recent advances in modern fascial anatomy and biomechanics， this paper interprets the biomechanical implications of yin-yang balance at the physical level from the perspective of holistic force lines. It posits that holistic force lines represent the functional expression of mechanical load transmission and integration within the myofascial network； the channel sinews system and myofascial chains exhibit significant similarities in terms of their distribution， functional attributes， and principles of holistic regulation， and can thus be understood as structural-functional carriers of yin-yang balance. Accordingly， this paper provides a biomechanical interpretation of the yin-yang relationship from four aspects， including interdependence， mutual restriction， dynamic balance through waxing and waning， and mutual transformation， proposing that in a healthy state， the body relies on the continuous integration， distribution， and readjustment of the myofascial tension network to maintain overall coordination， whereas disease states are often associated with compensatory transmission of local tension abnormalities along holistic force lines， the accumulation of imbalances， and structural rigidity. The holistic force-line perspective provides a biomechanical explanatory framework for the theory of yin-yang balance and offers a new theoretical basis for clinical diagnosis and treatment to shift from empirical holistic balancing toward holistic force-line balancing based on posture， function， and tension transmission pathways.

Incretin-based drugs have demonstrated significant clinical value in weight management and the treatment of metabolic diseases by mimicking or enhancing endogenous incretin signaling. These agents primarily target multiple receptors including glucagon-like peptide-1， glucose-dependent insulinotropic polypeptide， and glucagon， exerting weight-reducing effects through multiple mechanisms such as central appetite regulation， gastrointestinal function modulation， and peripheral metabolic improvement， while further ameliorating blood glucose， blood lipids， fatty liver， and cardiorenal metabolic risks. This review focuses on incretin-based drugs， systematically summarizing the key clinical application points and relevant research progress of domestically marketed and investigational candidate drugs in the field of weight reduction. Available evidence indicates that semaglutide and tirzepatide demonstrate substantial weight reduction with multiple metabolic benefits； domestic innovative drugs represented by mazdutide and ecnoglutide also exhibit favorable weight-reducing effects and safety profiles. Regarding safety， these agents are generally well-tolerated， with the most common adverse reactions being mild-to-moderate gastrointestinal events， while potential risks including gallbladder events， pancreatitis， and mood changes require attention. In special populations， individualized assessment is warranted for use in children， elderly people， and pregnant women. Future research should focus on the screening of predictive biomarkers for efficacy， the development of long-acting oral formulations， and the accumulation of long-term safety follow-up data.

ObjectiveTo investigate the influenza vaccination coverage among kindergarten and primary school children in Zhejiang Province in 2023 and analyze the influencing factors, and to provide the basis for improving the effect of influenza vaccination in children. MethodsA multi-stage random cluster sampling method was used to select 3 681 parents of children from 10 primary schools and kindergartens based on economic level and geographical distribution in Zhejiang Province, who participated in an online questionnaire survey, including basic information about the children and their parents, parents’ knowledge about influenza, and their willingness to vaccination. ResultsAmong the 3 681 parents surveyed, 33.82% (1 245/3 681) reported that their children received influenza vaccination in 2023. Multivariate logistic regression analysis showed that factors contributing to children’s influenza vaccination included both parents [adjusted OR (95%CI): 1.56 (1.32‒1.84)] and children [6.04 (5.04‒7.27)] having a history of influenza vaccination, parents’ conviction the influenza vaccine could protect children from severe diseases [1.43 (1.19‒1.74)], and the willingness of most parents would let their children get vaccinated [1.40 (1.13‒1.74)]. In contrast, vaccine hesitancy among parents [0.55 (0.43‒0.69)] and the belief that influenza is just a common cold [0.80 (0.65‒1.00)] were hindering factors. ConclusionThe influenza vaccination coverage among children is insufficient. Both the vaccination history of parents and children, as well as parents’ correct understanding of influenza and the effectiveness of influenza vaccine, significantly influence the influenza vaccination status in children. Efforts to address vaccine hesitancy and misconceptions about influenza are essential to improve vaccination rates.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective:To discuss the infection status and clinical outcomes in the patients with bullous pemphigoid(BP),and to analyze the risk factors for infection in hospitalized BP patients,as well as to construct and evaluate the risk prediction model.Methods:A total of 126 patients first diagnosed with BP were selected.According to the occurrence of infection,the patients were divided into infection group(52 cases)and non-infection group(74 cases).The infection status and outcomes of the patients in two groups were recorded;statistical analysis was performed on the general data,laboratory examination results,FRAIL scale scores for frailty screening,NRS2002 scores,and skin lesion severity of the patients in two groups;multivariate Logistic regression model was used to identify the risk factors for infection in the patients;the goodness-of-fit test was used to evaluate the model;receiver operating characteristic(ROC)curve was used to evaluate the predictive value of the model for infection.Results:Among the 126 hospitalized BP patients,52 cases had infection,with an infection rate of 41.27％.The mortality rate of the patients in infection group was higher than that in non-infection group(P＜0.05),and the remission rate of the patients in non-infection group was higher than that in infection group(P＜0.05).The FRAIL scale score for frailty screening,NRS2002 score,serum albumin level,prealbumin level,number of hospitalization,skin lesion severity,and time of hospital stay of the patients in infection group were significantly higher than those in non-infection group(P＜0.05).The multivariate Logistic regression analysis results derived the regression equation:Logistic(P)=-7.63+0.922× skin lesion severity+2.565×FRAIL scale score for frailty screening+1.214×NRS2002 score.The area under the curve of the Logistic regression model was 0.916.Conclusion:The FRAIL scale score for frailty screening,NRS2002 score,and skin lesion severity are the risk factors for infection in the hospitalized BP patients.The constructed infection risk prediction model based on these factors has good predictive value and may provide new ideas for the prevention and control of infection in the hospitalized BP patients.

Objective To investigate the feasibility of selectively omitting ureteral stent placement after ureteroscopic lithotripsy(URL).Methods A total of 118 patients with distal ureteral calculi undergoing URL from 2021 to 2024 were enrolled.Patients were divided into a control group(indwelling ureteral stent for 2 weeks,n=86)and an observation group(no ureteral stent placement,n=32).General data,operation time,hospital stay,and total medical costs were compared between the two groups.Patients were followed 2 weeks postoperatively for assessment of flank pain visual analogue scale(VAS)scores,bladder irritation symptoms,hematuria,and incidence of urinary tract infection.Hydronephrosis was evaluated by ultrasonography 3 months after surgery.Results There was no significant difference in the general information and operation time between the two groups(P>0.05).The length of hospital stay and total treatment cost in the observa-tion group were significantly lower than those in the control group(P<0.05).Two weeks after surgery,the VAS scores of low back pain on the affected side and occurrence rates of bladder irritation symptoms,hematu-ria,and urinary tract infection in the observation group were significantly lower than those in the control group(P<0.01).Three months after operation,no hydronephrosis was observed in both groups.Conclusion It is safe and feasible to avoid indwelling ureteral stent after URL in appropriate cases.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.