OBJECTIVE To explore the ameliorative effect and potential mechanism of vitexin on inflammation in ulcerative colitis （UC） mice. METHODS The UC mice model was established by continuous administration of 3% dextran sulfate sodium solution for 5 days. Mice with successful modeling were randomly divided into UC group， vitexin low- and high-dose groups （vitexin-L and vitexin-H groups， 40， 80 mg/kg）， mesalazine group （400 mg/kg）， and vitexin-H+recombinant Jagged canonical Notch ligand 1 （rJagged-1） group （vitexin-H+rJagged-1 group， 80 mg/kg vitexin+1 mg/kg rJagged-1）， with 12 mice in each group. Another 12 normal mice were used as the control （CK） group. Mice in each group were administered the corresponding drugs or the corresponding drugs and normal saline by gavage and intraperitoneal injection once daily for 7 consecutive days. General conditions were observed during the experiment. At 24 h after the last administration， the disease activity index （DAI） score was evaluated. Colonic histopathological morphology was observed and scored. Macrophage polarization levels in the spleen and colon tissues were measured. The protein expressions of interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）， transforming growth factor-β 1 （TGF-β 1 ）， Jagged-1， Notch1 and Notch intracellular domain （NICD） in colonic tissues were determined. RESULTS Compared with the UC group， the symptoms （reduced food and water intake， dull fur， etc.） and pathological changes （epithelial cell shedding， inflammatory cell infiltration， etc.） were significantly improved in the vitexin-L， vitexin-H and mesalazine groups. DAI scores， colonic histopathological scores， M1 macrophage contents in spleen tissue， M1/M2 macrophage ratios， M1 macrophage proportions in colon tissue， and protein expressions of IL-6， TNF-α， Jagged-1， Notch1 and NICD in colon tissue were significantly decreased （ P ＜0.05）. Meanwhile， the M2 macrophage contents in spleen tissue， M2 macrophage proportions in colon tissue， and protein expressions of IL-10 and TGF-β 1 in colon tissue were significantly increased （ P ＜0.05）. Moreover， the improvement effects in the vitexin-H and mesalazine groups were significantly superior to those in the vitexin-L group （ P ＜0.05）. Compared with the vitexin-H group， the above symptoms and pathological changes were aggravated， and all quantitative indicators were significantly reversed in the vitexin-H+rJagged-1 group （ P ＜0.05）. CONCLUSIONS Vitexin can ameliorate the inflammation of UC mice， which is associated with its inhibition of the Jagged-1/Notch1 pathway and regulation of macrophage polarization （inhibition of M1-type polarization and promotion of M2-type polarization）.

ObjectiveTo explore the complex network relationships among pain, kinesiophobia, social participation and knee function in patients after total knee arthroplasty (TKA), and to analyze the moderating effects of different socio-structural factors on the rehabilitation network from an ethical equity perspective. MethodsA convenience sampling method was used to select 291 patients who underwent TKA in Qilu Hospital of Shandong University from May to July, 2023. Pain was assessed using Numerical Rating Scale, kinesiophobia with Chinese short version of the Tampa Scale for Kinesiophobia, social participation with Impact on Participation and Autonomy Questionnaire, and knee function with Hospital for Special Surgery Knee Score. A partial correlation network among pain, kinesiophobia, social participation and knee function was constructed using Graphical Least Absolute Shrinkage and Selection Operator. Key variables were identified through node centrality and bridge centrality analysis. Network Comparison Tests (NCT) were used to analyze network differences among subgroups based on different socio-structural characteristics. ResultsIn the network model, the nodes with the highest strength centrality were indoor participation, activity behavior and activity pain. Bridge centrality analysis indicated that activity pain, knee function, indoor participation and activity cognition were key bridge nodes. NCT revealed no significant differences in overall network structure or global strength among subgroups based on residence, education level or payment method (P > 0.05). However, significant differences in edge weights were found for specific edges such as activity cognition-activity behavior and knee function-indoor participation (P < 0.05). ConclusionThere is a network of interactions among pain, kinesiophobia, social participation and knee function in patients after TKA, with nodes such as indoor participation and activity pain playing key roles in the rehabilitation process. Although the overall rehabilitation network is similar across different socio-structural groups, variations exist in specific relational pathways among patients from rural areas, those with lower education levels, and those with out-of-pocket payment. This suggests that clinical rehabilitation interventions should focus on these core nodes and implement targeted support strategies for socio-structurally disadvantaged groups to promote rehabilitation equity.

Objective To analyze the newly reported HIV-1 infection in several prefectures of Hubei Province，and analyze its influencing factors. Methods The limiting antigen avidity enzyme immunoassay(LAg-avidity EIA,LAg) was conducted on HIV-1 positive samples confirmed by Western blot of Hubei in 2017-2022. The demographic characteristics of the newly infected samples were analyzed by χ2 test.Logistic regression model was used to analyze influencing factors of new infection rate and predict the factors associated with the HIV-1 recent infection. Results There were 403 new cases of HIV-1 from 2017 to 2022 in several prefectures of Hubei Province, of which 77 were newly infected sorted by LAg,with a new infection rate of 19.11%. The newly confirmed HIV-1 persons of whom aged ≤24 years (40.00% new infection ratio), unmarried (29.41%), college or above (31.37%), and from Voluntary counseling and testing testing(VCT) clinics (40.00%) had a higher proportion of new infections, and the difference was statistically significant. Multivariate Logistic regression analysis showed that age ≤24 years old (aOR=4.346,95%CI: 1.342-14.075) and screening from the VCT clinic (aOR=6.761,95%CI: 1.460-31.319) were more likely to be newly infected. Conclusion The proportion of new HIV infection in several prefectures of Hubei province is relatively low in recent years.Further effective publicity and intervention measures for young students and the construction of VCT clinic should be continuously promoted to achieve early diagnosis and treatment.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a major cause of chronic kidney disease and kidney failure. IgAN exhibits marked heterogeneity in clinical presentation, histopathology, and pathogenic mechanisms, contributing to variable treatment responses and prognosisamong patients. Precise risk assessment and individualized intervention are therefore of critical importance. This review systematically traces the evolution of IgAN management from traditional risk stratification toward biomarker-driven precision medicine. We first review the clinical utility and limitations of established risk stratification tools, including the KDIGO guidelines, the Oxford MEST-C classification, and the International IgAN Prediction Tool. We then discuss emerging biomarkers closely linked to disease pathogenesis, including galactose-deficient IgA1 (Gd-IgA1), anti-Gd-IgA1 autoantibodies, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and complement components, as well as the targeted therapies they have informed. In addition, urinary biomarkers and multi-omics approaches show promise for dynamic disease monitoring and individualized risk stratification.

OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

Objective: To investigate the factors affecting cognition and vaccination willingness to receive human papilloma virus (HPV) vaccine among male university students, so as to provide a basis for formulating health education and promotion strategies for HPV vaccination in males. Methods: From March to June 2025, a convenience sampling method was used to recruit full-time male undergraduate students from 23 universities in Zhejiang Province. Self-administered questionnaires were employed to collect information on participants' basic demographics, sexual behaviors, knowledge of HPV and HPV vaccines, and willingness to receive HPV vaccination. Multivariable logistic regression model was used to analyze the influencing factors for vaccination willingness to receive HPV vaccine among male university students. Results: A total of 402 male university students were surveyed, with a mean age of (20.20±1.95) years. Among them, 65 participants reported having engaged in sexual behavior, accounting for 16.17%. Additionally, 192 students perceived themselves to be at relatively high risk of HPV infection, accounting for 47.76%. Knowledge of HPV and the HPV vaccine was reported by 227 participants, corresponding to an awareness rate of 56.47%. Willingness to receive HPV vaccine was expressed by 242 individuals, reflecting a vaccination willingness rate of 60.20%. Multivariable logistic regression analysis showed that male university students who were medical majors (OR = 3.404, 95% CI: 1.396-8.301), had engaged in sexual behavior (OR = 2.341, 95% CI: 1.102-4.970), perceived themselves to be at higher risk of HPV infection (OR = 1.631, 95% CI: 1.041-2.557), recognized the necessity of HPV vaccination for males (OR = 8.955, 95% CI: 4.705-17.044), and had been exposed to HPV vaccine promotion activities in their university (OR = 2.277, 95% CI: 1.320-3.926) showed a higher willingness to receive HPV vaccine. Conversely, those who had concerns about vaccine safety (OR = 0.510, 95% CI: 0.292-0.890), were unaware of the HPV vaccine appointment process (OR = 0.400, 95% CI: 0.232-0.690), or expressed concerns about the cost of the vaccine (OR = 0.560, 95% CI: 0.322-0.976) exhibited a lower willingness to be vaccinated. Conclusions Male university students in Zhejiang Province demonstrated a relatively low level of cognition regarding HPV and HPV vaccine, yet expressed a comparatively high willingness to receive HPV vaccine. Factors affecting vaccination willingness to receive HPV vaccine among male university students included cognition of HPV and HPV vaccine, self-perceived risk of HPV infection, concerns about vaccine safety, awareness of the vaccine appointment process, and considerations regarding vaccine cost.

OBJECTIVE: To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene. METHODS: A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01). RESULTS: Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3). CONCLUSION The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Adult ; Brain/diagnostic imaging* ; Male ; Pedigree ; DNA Copy Number Variations/genetics* ; Exome Sequencing ; Genetic Association Studies ; Magnetic Resonance Imaging

ObjectiveTo explore the effects of serine hydroxymethyltransferase 1 （SHMT1） rs1979277 polymorphisms on pharmacokinetic characteristics and clinical prognosis of methotrexate （MTX） in children with acute lymphoblastic leukemia （ALL）. MethodsMatrix-assisted laser desorption/ionization time of flight mass spectrometry was used for SHMT1 rs1979277 genotyping in children with ALL . Clinical data including serum MTX concentrations， incidences of adverse events， and ALL relapse after chemotherapy with MTX were collected. The associations of SHMT1 rs1979277 G>A genotypes with dose-adjusted serum concentrations （C/D ratios）， adverse events of MTX， and relapse were analyzed. The associations between rs1979277 genotypes and SHMT1 expression were explored based on Bioinformatics methods. ResultsAmong the 146 children with ALL included， the rs1979277 GG homozygous genotype accounted for 85.62% （125/146）， while the GA heterozygous genotype accounted for 14.38% （21/146）. The frequency of the G allele was 92.81% （271/292）， while the A allele was only 7.19% （21/292）. Children with the GG homozygous genotype had higher median C/D ratios of MTX in 24 h ［12.06 （μmol·m²）/（L·g）］ and higher relapse rates （12.80%） than those in GA heterozygous genotype carriers ［10.96 （μmol·m²）/（L·g）， and 9.52%， respectively］. However， none of the above differences were statistically significant （all P>0.05）. The incidences of respiratory （19.05%） and liver disorders （33.33%） in children with the GA heterozygous genotype were significantly higher than those in GG homozygous genotype carriers （4.00% and 12.00%， respectively， P<0.05）. There were no statistically significant differences in the incidences of other adverse events. Bioinformatics analysis showed that the rs1979277 A allele was significantly associated with higher SHMT1 expression in multiple tissues， such as the tibial artery， pancreas， and adrenal gland （P<0.05）. ConclusionSHMT1 rs1979277 GA genotype may be a risk factor for respiratory and liver disorders in ALL children treated with MTX.