OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.

ObjectiveTo investigate the effect of the multidisciplinary team （MDT） management model in improving the prognosis of patients with cirrhotic portal hypertension. MethodsA total of 86 patients with cirrhotic portal hypertension who were admitted to Shenzhen Third People’s Hospital from May 2022 to July 2024 were enrolled， and according to whether the MDT treatment regimen was implemented， they were divided into execution group with 51 patients and non-execution group with 35 patients. Baseline clinical data were collected， and the patients were observed in terms of gastrointestinal bleeding， hepatic encephalopathy， liver cancer， and death from admission to the end of follow-up （January 2025）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves for the cumulative incidence rates of endpoint events （gastrointestinal bleeding， hepatic encephalopathy， liver cancer， and death）， and the Log-rank test was used for comparison between groups. The Cox proportional-hazards regression model analysis was used to investigate the effect of MDT management on the prognosis of patients. ResultsThere were significant differences between the execution group and the non-execution group in diameter of the portal vein （t=1.216， P=0.017） and ascites （χ²=4.515， P=0.034） at baseline. The patients were followed up for 14.6±6.2 months， and the survival curve analysis showed that there was a significant difference in the cumulative incidence rate of gastrointestinal bleeding between the two groups （χ²=4.573， P=0.024）， while there were no significant differences in the incidence rates of other outcome events between the two groups （all P>0.05）. The Cox regression analysis showed that the execution group had a reduced risk of gastrointestinal bleeding （hazard ratio=0.262， 95% confidence interval： 0.110 — 0.630， P=0.003）. ConclusionImplementation of the MDT treatment regimen can significantly reduce the short-term risk of gastrointestinal bleeding in patients with cirrhotic portal hypertension， while its long-term benefits require further follow-up verification.

Objective:To investigate the role of dynamic changes in liver stiffness measurement (LSM) in predicting liver-related end-point events (LREs) occurrence in patients with chronic hepatitis B (CHB) with liver fibrosis during long-term antiviral therapy.Methods:Data were collected from CHB patients whose liver biopsy results showed Metavir fibrosis stage F2～F4 or clinically diagnosed cirrhosis. Entecavir antiviral therapy was mainly administered. Follow-up was conducted once every six months. Clinical data such as demographic information, blood routine tests, liver biochemical parameters, HBV virological and serological test results, and LSM were collected. Dynamic changes in LSM were categorized into four types based on LSM levels before treatment (0y) and following two years of antiviral therapy (2y) : (1) LSM 0y < 10 kPa and LSM 2y < 10 kPa, i.e., LSM persisted < 10 kPa; (2) LSM 0y < 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM increased to ≥ 10 kPa; (3) LSM 0y ≥ 10 kPa and LSM 2y < 10 kPa, i.e., LSM decreased to < 10 kPa; (4) LSM 0y ≥ 10 kPa and LSM 2y ≥ 10 kPa, i.e., LSM persisted ≥ 10 kPa. The predictive role of the dynamic changes of LSM in the occurrence of LREs was analyzed. The Wilcoxon rank-sum test was used for quantitative data. Fisher's exact test was used for categorical data. Multivariate analysis was performed using the Cox proportional hazards regression model. Survival curves were plotted and compared using the Kaplan-Meier. Results:A total of 713 CHB cases with liver fibrosis were included, among whom 512 had cirrhosis. The cumulative incidence of LREs following two years of antiviral therapy was low in patients with LSM 0y < 10 kPa during follow-up (all patients: LSM persisted < 10 kPa 1.6% vs. LSM increased to ≥ 10 kPa 0%; cirrhosis subgroup: LSM persisted < 10 kPa 0% vs. LSM increased to ≥ 10 kPa 0%). The 5-year cumulative incidence of LREs following two years of antiviral treatment was significantly higher in patients with LSM0y ≥ 10 kPa than in those with LSM persisting ≥ 10 kPa and those with LSM decreasing to < 10 kPa during follow-up (all patients: LSM persisted ≥ 10 kPa 12.4% vs. LSM decreased to < 10 kPa 3.6%; cirrhosis subgroup: LSM persisted ≥ 10 kPa 12.6% vs. LSM decreased to < 10 kPa 4.3%). Patients with LSM persisting at ≥ 10 kPa had a significantly increased risk of LREs following two years of antiviral treatment compared with those whose LSM decreased to <10 kPa during follow-up after adjusting for age, gender, baseline body mass index, platelet count, and alanine aminotransferase (all patients, aHR=2.96, 95% CI: 1.41～6.24, P=0.005; cirrhosis subgroup, aHR=2.74, 95% CI:1.26～5.95, P=0.011). Conclusions:LSM<10 kPa before antiviral treatment had a lower risk of liver-related endpoint events following two years of treatment among CHB patients with liver fibrosis. LSM ≥10 kPa before antiviral treatment and LSM persisted ≥10 kPa two years following treatment had a significantly higher occurrence risk of liver-related endpoints than LSM<10 kPa following treatment among CHB patients with liver fibrosis.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Objective:To summarize the clinical characteristics of focal cerebral arteriopathy (FCA) in children, and to analyze its influencing factor of prognosis.Methods:A retrospective cohort study was conducted. Clinical data from 40 children with FCA who were hospitalized at the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from September 2015 to August 2024 were collected. A centralized follow-up was conducted in October 2024 via outpatient clinics or the internet. The pediatric stroke outcome measure (PSOM) was used to evaluate their outcomes. Based on the PSOM, the children were further divided into a group with normal neurological function and another group with abnormal neurological function. Differences between groups were analyzed using the Mann-Whitney U test and Fisher exact test. Univariate Logistic regression analysis was performed to identify the influencing factors for neurological outcomes in children with FCA. Results:A total of 40 children were included, with 20 males and 20 females, and the onset age of 9.2 (6.8, 12.5) years. Among them, 12 cases (30%) had a history of varicella within 1 year before onset. There were 23 cases (58%) presenting with transient ischemic attack (TIA) or recurrent fluctuating symptoms of onset, while 3 cases (8%) developed progressive stroke within the first month of onset. The M1 segment of the middle cerebral artery was the most commonly affected vascular site, with a total of 16 cases (40%). Arterial occlusion occurred in 8 cases (20%). Lumbar puncture was completed in 36 children, and white blood cell counts in cerebrospinal fluid was increased in 6 cases. All 23 patients who completed magnetic resonance vessel wall imaging (VWI) showed circular enhancement of the arterial wall. A total of 28 patients (70%) received antiplatelet or anticoagulation therapy, and 16 patients (40%) received hormone therapy. At admission, the pediatric National Institute of Health Stroke Scale (PedNIHSS) score was 6.0 (2.0, 8.8) points, which decreased to 0.5 (0, 3.0) points at discharge. The follow-up duration was 1.6 (0.8, 4.9) years, with 1 case lost to follow-up. There was 1 case presenting with recurrence course manifesting as TIA. Among the 39 cases who completed the follow-up, 23 cases (59%) were assessed as neurologically normal by PSOM, while 16 cases (41%) were assessed as neurologically abnormal. Among the 29 cases who completed the imaging review, magnetic resonance angiography (MRA) review in 23 cases indicated stability or improvement in the original arterial stenosis, with 6 cases experiencing transient worsening of arterial stenosis early in the disease course (within 2 months), which later improved. Arterial stenosis progression occurred in 6 cases at the final review of 29 cases who completed the imaging review, with 1 case developing progressive cerebral arteriopathy. The proportion of patients with headache, altered consciousness, and aphasia in the abnormal neurological function group, as well as the PedNISS scores at admission and discharge, were all higher than those in the normal neurological function group (all P<0.05). Univariate Logistic regression analysis revealed that only a PedNISS score>6 points at onset was an influencing factor for abnormal neurological function ( OR=20.58, 95% CI 3.93-107.70, P<0.001). Conclusions:Childhood FCA often presents with fluctuating onset, and the proximal segment of the middle cerebral artery is frequently affected. Progression of arterial stenosis is common within 2 months of the disease course, but clinical progression and new ischemic lesions are uncommon. Most patients have a favorable long-term prognosis. PedNIHSS score>6 points at admission is related to abnormal neurological function outcomes.

Objective:To explore the genetic testing outcomes of a fetal family with Thyroid secretion disorder type 5 (TDH5) and familial Neurofibromatosis type 1 (NF1), and to clarify the association between clinical manifestations and genetic variations.Methods:One case of a TDH5 combined with familiar NF1 fetus treated at Gansu Maternal and Child Health Hospital in January 2024 was selected as the research subject. The clinical and family history data of the fetus were collected by retrospective research method. 10-15 mL of fetal amniotic fluid, and 2-3 mL of peripheral blood from the parents, sister, and grandfather of the fetus were collected, and genomic DNA was extracted for trio whole-exome sequencing (trio-WES). The Sanger sequencing was utilized to validate candidate variants for family verification. According to the Standards and Guidelines for the Interpretation and Reporting of Sequence Variants of the American Society of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG guidelines), the pathogenicity of the detected variants was classified. This study has been approved by the Medical Ethics Committee of Gansu Maternal and Child Health Hospital [Ethics No.(2021)GSFY(65)].Results:The fetal ultrasound indicated the nuchal translucency (NT) thickening, and the thyroid function test results of the sister showed an increase in thyroid stimulating hormone and a decrease in free thyroid hormone. Simultaneously, there were cafe-au-lait macules of various sizes in multiple parts of the body of the sister, and the mother had a similar cafe-au-lait macules phenotype. The trio-WES results revealed that there was a c. 413dupA(p.Tyr138*) frameshift mutation in exon 4 and c. 573G>A(p.Trp191*) nonsense mutation in exon 5 of the fetal DUOXA2, which were inherited from the mother and father, respectively. In accordance with the ACMG guidelines, they were classified as pathogenic variant (PVS1+ PM2_Supporting+ PM3) and likely pathogenic variant (PVS1+ PM2_Supporting), respectively. And the nonsense mutation c. 6972C>A(p.Tyr2264*) was detected in exon 46 of the NF1 in the fetus, inherited from the mother. The genetic testing results of the first sister and proband in this case were consistent, and the DUOXA2 and NF1 of the second sister were both wild-type. According to the ACMG guidelines, c.6972C>A(p.Tyr2264*) was classified as pathogenic variant (PVS1+ PS4_Supporting+ PP4+ PM2_Supporting). Conclusion:The mutations in the DUOXA2 gene c. 413dupA(p.Tyr138*) and c. 573G>A(p.Trp191*), and the NF1 gene c. 6972C>A(p.Tyr2264*) might be the genetic causes of TDH5 combined with familiar NF1 in proband. The discovery of the DUOXA2 gene c. 573G>A(p.Trp191*) enriches the spectrum of pathogenic gene variations.

The red doctor spirit is the advanced culture of the Communist Party of China formed under a specific historical and cultural background. It can be summarized as “political firmness， excellent technology， working hard， and healing the wounded and rescuing the dying.” This content has many hidden similarities and integrations with the goal of cultivating humanistic literacy for medical students in military medical universities. This paper aimed to identify the important connection points between the red doctor spirit and the contents and goals of medical humanities teaching， as well as integrate the red doctor spirit into medical humanities teaching by various dimensions， including systematic reconstruction of textbook content， immersive innovation in teaching form， three-dimensional support in resource construction， and innovative implementation of narrative medicine teaching. It also further explored the extension of the red doctor spirit in military medical humanistic literacy， namely， revolutionary humanism and revolutionary heroism， thereby enhancing the effectiveness of medical humanistic teaching.

OBJECTIVES: To explore the association of the expression of WW domain-containing ubiquitin E3 ligase 1 (WWP1) with immune infiltration in tumor microenvironment (TME) of ovarian cancer. METHODS: Ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were used to analyze the association of WWP1 expression with patient prognosis. TISCH2 was utilized to analyze the changes in immune cell subtypes in TME of metastatic tumor and after chemotherapy. The impact of WWP1 on immune cell infiltration, somatic copy number alterations of WWP1 and evolution of immune cell subtypes was evaluated using TIMER and TIGER pseudo-time analysis. A deep learning model was used to analyze TCGA pathological images to investigate the effect of WWP1 on TME of ovarian cancer. RNA-seq analysis was conducted to identify the differentially expressed genes in WWP1-overexpressing SKOV3 cells and validate immune infiltration. Multicolor immunofluorescence assay was used to analyze the immune markers in SKOV3 and SKOV3/DDP cell xenografts in nude mice. RESULTS: The patients with high WWP1 expression levels had significantly lower overall survival rate (P=0.0012). High WWP1 expression levels and Stage IV disease were both associated with a poor prognosis (P<0.05). In metastatic ovarian cancer or after chemotherapy, the percentages of malignant tumor cells and tumor-associated fibroblasts increased in the TME, accompanied by elevated WWP1 levels. WWP1 expression level was positively correlated with pro-tumorigenic immunosuppressive cells (r=0.1323-0.3955, P<0.05) and negatively with tumor-inhibiting immune cells (r=-0.1949- -0.1333, P<0.05). Specific copy number alterations of WWP1 also influenced CD8⁺ T cell percentage and neutrophil infiltration levels in the TME. RNA-seq analysis of WWP1-overexpressing SKOV3 cells and immunofluorescence assay of the tumor-bearing mice yielded findings consistent with those of bioinformatics analysis. CONCLUSIONS WWP1 may serve as a prognostic biomarker and a potential target for immune regulation in the TME of ovarian cancer.
Female ; Ovarian Neoplasms/genetics* ; Humans ; Ubiquitin-Protein Ligases/metabolism* ; Tumor Microenvironment/immunology* ; Animals ; Mice ; Cell Line, Tumor ; Mice, Nude ; Prognosis ; Gene Expression Regulation, Neoplastic