Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective To explore the prevalence of depressive symptoms in postoperative patients with ovarian cancer and to analyze its influencing factors from multiple dimensions, including clinical characteristics, psychological factors, and laboratory indicators. Methods A cross-sectional study was conducted, which enrolled 235 postoperative patients with ovarian cancer. Depressive status was assessed using the patient health questionnaire, and the demographic, pathological, and medical record data of the patients were collected using the generalized anxiety disorder scale, Pittsburgh sleep quality index, European organization for research and treatment of cancer quality of life questionnaire core 30, and ECOG performance status score. Peripheral blood tumor marker (CA125), routine blood test, lymphocyte subsets, and serum cytokine levels were measured. Univariate and multivariate binary logistic regression analysis were used for statistical analysis. Results The prevalence of depression in postoperative patients with ovarian cancer was 39.15% (92/235). Univariate analysis showed that ECOG score ≥ 2 points, pain, anxiety, poor sleep quality, low quality of life, low life satisfaction, tumor recurrence, six or more cycles of chemotherapy, as well as higher levels of CA125, NLR, and NAR, and lower hemoglobin levels were significantly associated with depression (all P<0.05). Multivariate binary Logistic regression analysis showed that anxiety (OR=1.975, 95%CI: 1.231-3.170), sleep efficiency (OR=4.181, 95%CI: 1.211-14.43), sleep latency (OR=34.806, 95%CI: 4.258-284.542), ECOG performance status score, cognitive function (OR=0.918, 95%CI: 0.868-0.97), and life satisfaction were independent risk factors for depression (all P<0.05). Laboratory indicators were not independent influencing factors in the multivariate Logistic regression model. Conclusion Depression in postoperative patients with ovarian cancer is influenced by physiological, psychological, and social factors. Clinical management should focus on patients with anxiety, sleep disorders, poor physical condition, and low life satisfaction, and a comprehensive prevention and treatment strategy centered on psychological intervention and taking into account symptom management and social support should be implemented.

Retinal astrocytes play pivotal roles in regulating neuronal function, maintaining retinal homeostasis, and responding to pathological stress. This review focuses on recent advances in astrocyte heterogeneity, including its spatial distribution and functional states, and discusses the dual roles of pathological processes. Evidence indicates that, during the early stages of glaucoma, age-related macular degeneration, and other degenerative retinal disorders, astrocytes exert neuroprotective effects by supporting neuronal metabolism, modulating inflammatory responses, and alleviating oxidative stress. However, persistent disruption of the retinal microenvironment can drive astrocytes toward a pro-inflammatory reactive phenotype. A clearer understanding of these pathophysiological processes and molecular mechanisms may provide a theoretical basis and potential therapeutic direction for retinal neurodegenerative diseases.

This paper summarizes the clinical experience in treating children adenoid hypertrophy using the "opening the orifices and regulating qi method". It is considered that the pathogenesis of adenoid hypertrophy in children is rooted in dysfunction of zangfu （脏腑） organs， with binding of phlegm and stasis as the branch. Obstruction of the cervical passes and rebellious， chaotic qi flow run through the entire course of the disease. The "opening the orifices and regulating qi method" is proposed， which emphasizes the regulation of the lung， spleen， liver， and stomach. By opening the cervical passes， regulating zangfu organs， and eliminating phlegm and stasis to harmonize the ascent and descent of qi， a comprehensive application of external traditional Chinese medicine （TCM） therapies， such as acupuncture， umbilical moxibustion with medicinals， collateral bloodletting， and sole therapy， is utilized. Addressing both root and branch causes， this approach provides new perspectives for treating children adenoid hypertrophy using external TCM therapies.

ObjectiveTo investigate the clinicopathological features， molecular profile， treatment response， and prognosis of SMARCA4 （BRG-1） and SMARCB1 （INI-1）-deficient undifferentiated tumors of the digestive system， aiming to enhance the understanding of this rare and highly aggressive molecular subtype. MethodsThis study is a single-center retrospective analysis. We included 9 cases of malignant digestive system tumors with loss of BRG-1 expression and 3 cases with loss of INI-1 expression， all pathologically confirmed at Sun Yat-sen University Cancer Center between April 2022 and December 2025. By reviewing clinical data， histological morphology，immunohistochemistry and next-generation sequencing （NGS） results from partial cases， we systematically summarized their clinicopathological and molecular characteristics， treatment strategies， and survival outcomes. Results​ Among the 12 patients， 6 were male and 6 were female， with a median age of 62 （44-70） years. 9 cases exhibited SMARCA4 deficiency， and 3 cases exhibited SMARCB1 deficiency. Tumors originated in the stomach （5 cases）， colon （3 cases）， pancreas （1 case）， with the primary site unknown in 3 cases. The histology predominantly showed undifferentiated carcinoma， with 1 case of poorly differentiated carcinoma. The tumor cells were epithelioid with significant atypia. Epithelial markers （e.g. CKpan） were often lost or markedly decreased， while vimentin could be positive. All 9 cases tested for MMR status were mismatch repair proficient （pMMR）， and the Ki-67 proliferation index was high ［median 80% （60%-90%）］. A discordance was observed between IHC findings and NGS results in the 6 sequenced cases. The NGS profiling revealed frequent co-occurring mutations， including TP53， KRAS， and NRAS， with no germline mutations identified.The median follow-up time was 277 （55-867） days. 9 of the 12 patients presented with stage Ⅳ disease at the time of initial diagnosis. Among 3 newly diagnosed patients without metastasis who received treatment， 2 achieved prolonged recurrence-free survival. Patients with advanced disease at initial diagnosis primarily underwent platinum-based chemotherapy or combination regimens， yet their prognosis was generally poor， with a median overall survival of 60 （45-541） days， ranging from 16 to 867 days. Notably， several patients who received chemotherapy combined with targeted therapy and immunotherapy achieved extended survival. ConclusionSMARCA4/SMARCB1-deficient undifferentiated tumor of the digestive system is a distinct molecular subtype characterized by high aggressiveness and poor prognosis， predominantly affecting middle-aged and elderly individuals. Diagnosis relies on the immunohistochemical loss of BRG-1 or INI-1 proteins. While no standard of care currently exists， treatment often refers to regimens for adenocarcinoma of the primary site. Combined immunotherapy and targeted therapy may offer potential benefits， warranting further validation in large-scale prospective studies.

Objective: To investigate the knowledge, attitude and practice of infectious disease prevention and control among primary and middle school students in Gongshu District, Hangzhou City, so as to provide the evidence for implementing health education on infectious disease prevention and control in schools. Methods: Students from 12 primary and middle schools in Gongshu District were selected using a random cluster sampling method. Basic information, knowledge, attitude and practice of infectious disease middle and control were collected through questionnaire surveys. Influencing factors of practice of primary and middle school students' infectious disease prevention and control were analyzed using multivariable logistic regression model. Results: A total of 3 439 primary and middle school students were surveyed, including 1 717 boys (49.93%) and 1 722 girls (50.07%). There were 1 237 primary school students (35.97%), 1 092 junior high school students (31.75%), and 1 110 senior high school students (32.28%). The awareness of infectious disease prevention and control knowledge, the percentage of attitude towards infectious disease prevention and control, and the percentage of practice towards infectious disease prevention and control were 73.22%, 96.83%, and 60.19%, respectively. Multivariable logistic regression analysis revealed that girls (OR=1.460, 95%CI: 1.265-1.685), those who had received health education on infectious disease prevention (OR=2.088, 95%CI: 1.656-2.632), those with adequate knowledge (OR=2.129, 95%CI: 1.816-2.496), and those with positive attitude (OR=4.320, 95%CI: 2.683-6.957) were more likely to form practice for the prevention and control of infectious disease. Conversely, senior high school students (OR=0.667, 95%CI: 0.561-0.794) and those with poor self-rated health status (OR=0.678, 95%CI: 0.495-0.930) were less likely to form practice for the prevention and control of infectious disease. Conclusions The attitude towards infectious disease prevention and control among primary and middle school students in Gongshu District is relatively high, but their awareness and practice are low. It is recommended to strengthen health education on infectious disease prevention and control knowledge in a targeted manner to promote the formation of prevention and control practice among senior high school students and primary and middle school students who self-assess their health status as poor.

Objective: To investigate the association between dietary quality and overweight / obesity among primary school students, so as to provide a basis for the prevention and control of childhood obesity. Methods: In September 2022, third-grade students from six primary schools in Ningbo City, Zhejiang Province were selected by a random cluster sampling method. Data on gender, age, height, and weight were collected through questionnaire surveys and physical examinations. Body mass index (BMI) was calculated, and overweight and obesity were determined using gender- and age-specific BMI cut-off points. The Chinese dietary quality questionnaires was administered to assess the intake of health-promoting and restricted foods over the past 24 hours, thereby evaluating overall dietary quality. A multivariate logistic regression model was used to analyze the association between dietary quality and overweight / obesity among primary school students. Results: A total of 1 375 primary school students were included, comprising 722 (52.51%) boys and 653 (47.49%) girls, with a mean age of (8.47±0.30) years. Among them, 165 (12.00%) were overweight and 171 (12.44%) were obese. The score for health-promoting foods was (4.29±2.27) points. The median score of restricted foods was 2.00 (interquartile range, 3.00) points. The total dietary quality score was (10.84±2.42) points. Multivariable logistic regression analysis indicated that the restricted food score was positively associated with overweight (OR=1.073, 95%CI: 1.002-1.148), while the total dietary quality score was negatively associated with overweight (OR=0.911, 95%CI: 0.851-0.976). However, no statistically significant associations were observed between the health-promoting food score and overweight or obesity (both P>0.05), nor between the restricted food score or total dietary quality score and obesity (both P>0.05). Conclusion A higher intake of restricted foods was associated with an increased risk of overweight, while a better dietary quality was associated with a decreased risk of overweight among primary school students.

Objective To investigate the effect of PIAS3 on glucose fluctuation-induced oxidative stress and mito-chondrial dysfunction in rat cardiomyocytes.Methods H9c2 were cultured in vitro,and divided into normal glucose control group(Control),mannitol-induced osmotic pressure control group(MG),constant high glucose group(HG),intermittent hyperglycemia group(IHG),IHG+siRNA NC group,and IHG+PIAS3 siRNA group.Cell proliferation was assessed using CCK-8 assay.LDH release,MDA and GSH levels,as well as SOD activity,were detected using corresponding kits.Mitochondrial membrane potential was evaluated via JC-1 staining combined with flow cytometry.ROS levels in cells and mitochondria were determined using DCFH-DA and MitoSOX staining,re-spectively.Protein expression of PI3K,p-PI3K,AKT,and p-AKT was analyzed by Western blot.Results Com-pared with the control group,intermittent hyperglycemia promoted oxidative stress and mitochondrial dysfunction,significantly upregulated PIAS3 expression(P＜0.001)and downregulated p-PI3K and p-AKT protein levels(P＜0.001).Knockdown of PIAS3 significantly alleviated oxidative stress and mitochondrial dysfunction induced by glucose fluctuations,and increased p-PI3K and p-AKT protein levels(P＜0.001).Conclusions Knockdown of PIAS3 may alleviate glucose fluctuation-induced oxidative stress and mitochondrial dysfunction in ratcardiomyocytes by activating the PI3K/AKT signaling pathway.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a male with a normal phenotype and SRY gene-positive 46,XX/46,XY tetrazoospermia chimerism. METHODS: A male patient with an abnormal peripheral blood chromosomal karyotype detected at the Infertility Center of Taizhou Hospital of Zhejiang Province on December 2, 2013 was selected as the study subject. Peripheral venous blood samples were collected from the proband and his family members, together with a semen sample from the proband. Chromosomal karyotype analysis, red blood cell blood group identification, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH), sex-determining region Y (SRY) gene detection, and short tandem repeat (STR) microsatellite marker analysis were performed on the peripheral venous blood sample from the proband. Routine semen analysis, sperm FISH, and STR testing were also conducted. STR verification was performed on both parents. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: k20201009). RESULTS: The proband, a 37-year-old male, had normal secondary sexual characteristics and external genitalia development. The chromosomal karyotype of his peripheral blood sample was 46,XX[94]/46,XY[6]. ABO blood group typing was positive for Rh(D) type O and negative for Rh(D) type A, indicating the presence of two red blood cell populations. CMA result was arr[GRCh37](1-22)×2,(XX)×1. Autosomal and X chromosome SNP genotypes were BB-BB, AB-AB, and AA-AA, making it impossible to identify homozygous/heterozygous chimerism. FISH detection of interphase nuclei showed nuc ish XX[92]/XY[8]. Testing of the SRY gene was positive. STR analysis showed a single X peak (no Y peak) at the AMEL locus, 10/12 at the Penta D locus, and no third allele at other loci. Routine semen analysis were normal. Sperm FISH detection showed haploid nuclei nuc ish X[53]/Y[47]. Sperm STR analysis revealed an X/Y bimodal distribution at the AMEL locus and a 9/14 distribution at the Penta D locus, with no third allele observed at other loci. Above results suggested that the proband's blood and germ cell lines had originated from a heterozygous chimera formed by the fusion of two different zygotes. CONCLUSION Combined genetic techniques confirmed that the proband's peripheral blood AMEL genotype is X/X, while the sperm is X/Y. The Penta D locus showed a bi-allelic heterozygous pattern of 10/12 in the peripheral blood sample and 9/14 in the sperm sample, suggesting that the proband is a tetrazygotic chimera resulted from the fusion of 46,XX/46,XY zygotes.
Humans ; Male ; Adult ; Chimerism ; Microsatellite Repeats ; Sex-Determining Region Y Protein/genetics* ; Phenotype ; Genes, sry ; In Situ Hybridization, Fluorescence ; Karyotyping