Objective To explore the factors affecting the quality of psychological assistance hotline connections in Shaanxi Province, and to provide a basis for optimizing services. Methods A total of 149 calls with suicidal tendencies were included from January to March 2022, and data were collected by 31 trained assessors through standardized questionnaires (general information, suicide risk, emotional intensity, and wiring characteristics). Results The results showed that 56.38% of the callers were female, with age groups concentrated between ≤ 18 years old (29.53%) and 19-34 years old (43.62%). The call duration was mainly between 31 and 45 minutes (50.34%). Operators conducted a suicide risk assessment on the callers, with 38.9% having a comprehensive assessment, 38.9% having an incomplete assessment, and 22.1% having no assessment. The main mental disorders of the callers were depression (48.32%), anxiety (15.44%), and bipolar disorder (14.77%), with 25.50% having comorbidities of ≥ 2 disorders. Emotional scores were as follows: depression (4.11 ± 0.76), sadness (3.97 ± 1.03), and despair (3.78 ± 1.05). There were significant differences in depression, anger, despair, and sadness among the callers with different levels of danger (t=4.79, 3.35, 15.79, 4.24, all P<0.05). Women had higher levels of fear than men (t=3.10, P<0.01). The longer the call duration, the higher the level of despair (t=5.66, P<0.01). Multiple regression analysis showed that incomplete suicide risk assessment by operators (B=-2.36), general procedures for operators' connections (B=5.44), and technical factors (B=2.01) significantly affected the quality of psychological assistance hotlines (all P<0.05). Conclusion Callers with suicidal tendencies generally have serious mental and psychological problems and prominent negative emotions. Strengthening the suicide risk assessment ability of operators and standardizing processes and service attitudes are key to improving the quality of psychological assistance hotlines.

Objective:To establish a prognostic model based on endoplasmic reticulum stress-related genes for evaluating the prognosis of patients with renal cell carcinoma.Methods:This study utilized Non-negative Matrix Factorization to identify molecular subgroups based on endoplasmic reticulum stress-related genes and employed Weighted Correlation Network Analysis to determine co-expressed genes associ-ated with these subgroups.A risk prognostic model was constructed using univariate Cox regression analysis and Lasso regression analysis.Preliminary experimental validations were conducted to elucidate the biological functions of model genes in renal cell carcinoma.Results:Two molecular subgroups with distinct survival prognoses were identified,and an intersection of related genes was used to construct a nov-el endoplasmic reticulum stress-related prognostic model.Patients in the high-risk group exhibited significantly poorer overall survival in both the training and validation cohorts.In vivo experiments demonstrated that PCK1,a model gene,could inhibit the proliferation,migra-tion,and invasion of renal cell carcinoma cells.Conclusions:The risk scoring model developed in this study effectively predicts the survival probability of renal cell carcinoma patients and can serve as an independent prognostic indicator.This model offers a new direction for per-sonalized treatment strategies in renal cell carcinoma patients.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Objective:To explore the clinical manifestations and genetic characteristics of a child with Leukoencephalopathy with ataxia (LKPAT) caused by a CLCN2 gene variant. Methods:A retrospective analysis was conducted on the clinical data of a child admitted to Hunan Children′s Hospital in June 2024 due to " intermittent convulsions for 13 days" . Peripheral blood samples were collected from the child and his parents for whole exome sequencing, followed by Sanger sequencing validation and pathogenicity analysis of candidate variants. Literature searches were performed using the keywords " CLCN2 gene" "chloride channel-2" "leukoencephalopathy with ataxia/LKPAT" "leukoencephalopathy" in both Chinese and English on CNKI, Wanfang, and PubMed databases. The search time was set from the establishment of the databases to July 31, 2024. Childhood-onset LKPAT literature was screened and analyzed. This study was approved by the Medical Ethics Committee of Hunan Children′s Hospital (Ethics No. HCHLL-2024-351). Results:① The child was a 7-month-and-26-day-old male infant born to consanguineous parents, presenting with epileptic seizures and borderline development. Cranial MRI revealed symmetrical long T 2 signal shadows in the posterior limb of the internal capsule, cerebral peduncle, pons, and middle peduncle of the cerebellum. Video electroencephalogram (EEG) showed an abnormal childhood EEG with one focal seizure. ② Whole exome sequencing revealed a homozygous c. 2201dup (p.Glu735Ter) variant in the CLCN2 gene of the child. Sanger sequencing confirmed that the variant was inherited from both parents. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), this variant was classified as pathogenic (PVS1+ PM3_Supporting+ PM2_Supporting). ③ A total of 8 relevant literature were retrieved, together with the present case, 16 childhood-onset LKPAT patients were cumulatively reported, which consisted of 9 males and 7 females. Twelve CLCN2 gene variants were involved, including 2 nonsense variants, 3 missense variants, 7 frameshifting variants, 2 c. 61dup variants, and 5 c.1709G>A variants. The initial symptoms of the 16 patients included headache, ataxia, epileptic seizures, spasticity, developmental delay, lower back pain, hearing impairment, and intention tremor. Three patients had the onset of the disease before the age of one, of which two had epileptic seizures as the initial symptom. Conclusion:The homozygous variant CLCN2: c. 2201dup (p.Glu735Ter) is considered the pathogenic cause of LKPAT in this child, marking the first childhood-onset case reported in China. Genetic testing has facilitated the diagnosis of childhood-onset LKPAT and expanded the spectrum of CLCN2 gene mutations.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

OBJECTIVE: To explore the clinical manifestations and genetic characteristics of a child with Leukoencephalopathy with ataxia (LKPAT) caused by a CLCN2 gene variant. METHODS: A retrospective analysis was conducted on the clinical data of a child admitted to Hunan Children's Hospital in June 2024 due to "intermittent convulsions for 13 days". Peripheral blood samples were collected from the child and his parents for whole exome sequencing, followed by Sanger sequencing validation and pathogenicity analysis of candidate variants. Literature searches were performed using the keywords "CLCN2 gene" "chloride channel-2" "leukoencephalopathy with ataxia/LKPAT" "leukoencephalopathy" in both Chinese and English on CNKI, Wanfang, and PubMed databases. The search time was set from the establishment of the databases to July 31, 2024. Childhood-onset LKPAT literature was screened and analyzed. This study was approved by the Medical Ethics Committee of Hunan Children's Hospital (Ethics No. HCHLL-2024-351). RESULTS: The child was a 7-month-and-26-day-old male infant born to consanguineous parents, presenting with epileptic seizures and borderline development. Cranial MRI revealed symmetrical long T₂ signal shadows in the posterior limb of the internal capsule, cerebral peduncle, pons, and middle peduncle of the cerebellum. Video electroencephalogram (EEG) showed an abnormal childhood EEG with one focal seizure. Whole exome sequencing revealed a homozygous c.2201dup (p.Glu735Ter) variant in the CLCN2 gene of the child. Sanger sequencing confirmed that the variant was inherited from both parents. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), this variant was classified as pathogenic (PVS1+PM3_Supporting+PM2_Supporting). A total of 8 relevant literature were retrieved, together with the present case, 16 childhood-onset LKPAT patients were cumulatively reported, which consisted of 9 males and 7 females. Twelve CLCN2 gene variants were involved, including 2 nonsense variants, 3 missense variants, 7 frameshifting variants, 2 c.61dup variants, and 5 c.1709G>A variants. The initial symptoms of the 16 patients included headache, ataxia, epileptic seizures, spasticity, developmental delay, lower back pain, hearing impairment, and intention tremor. Three patients had onset of the disease before the age of one, of which 2 had epileptic seizures as the initial symptom. CONCLUSION The homozygous variant CLCN2: c.2201dup (p.Glu735Ter) is considered the pathogenic cause of LKPAT in this child, marking the first childhood-onset case reported in China. Genetic testing has facilitated the diagnosis of childhood-onset LKPAT and expanded the spectrum of CLCN2 gene mutations.
Humans ; Chloride Channels/genetics* ; Male ; CLC-2 Chloride Channels ; Leukoencephalopathies/genetics* ; Infant ; Ataxia/genetics* ; Homozygote ; Mutation ; Retrospective Studies ; Exome Sequencing ; Genetic Testing ; Female

Objective To explore the effects of plantamajoside on the proliferation and invasion of human gastric cancer cell line BGC823.Methods BGC823 cells were randomly separated into a control group,a plantamajoside group,an AAV-NC(transfection of empty plasmids packaged with lentivirus)group and a plantamajoside+AAV-HIF-1α(transfection of HIF-1α overexpression plasmid packaged with lentivirus)group.Cell proliferation,inva-sion,apoptosis,the numbers of vascular mimicry(VM)lumens and vascular branches,the expression of prolifera-tion,apoptosis,epithelial mesenchymal transition(EMT)related proteins,HIF-1α/VEGF pathway proteins of cells were all examined.Results Compared with control group,the BGC823 cell viability,colony formation num-ber,invasion number,VM lumen number,vascular branch number,and expression of Ki-67,PCNA,vimentin,MMP9,Snail,VEGFA,VE-cadhering,HIF-1α and VEGF protein were all lower in plantamajoside group(P＜0.05).The apoptosis rate,the cleaved Caspase-3,Bax,and E-cadherin protein expression were significantly increased(P＜0.05).Compared with plantamajoside group,the BGC823 cell viability,colony formation number,invasion number,VM lumen number,vascular branch number,and expression of Ki-67,PCNA,vimentin,MMP9,Snail,VEGFA,VE-cadherin,HIF-1α and VEGF protein were higher in the plantamajoside+AAV-HIF-1α group(P＜0.05).The apoptosis rate,the cleaved caspase-3,Bax,and E-cadherin protein expression were lower(P＜0.05).Conclusions Plantamajoside inhibits proliferation,EMT,invasion,and VM of human gastric cancer cell line and induce its apoptosis.

Objective:To summarize the clinical manifestations, genetic characteristics and diagnosis and treatment processes of ATP1A2 gene-related childhood neurological diseases presenting with hemiplegic migraine (HM) or epilepsy, and enhance the understanding of clinicians on the diseases related to this gene. Methods:A retrospective study was performed; data of 5 children with ATP1A2 gene variations admitted to Department of Neurology, Hunan Children's Hospital from April 2015 to June 2024 were collected, and their clinical characteristics were summarized. ATP1A2 gene variations were confirmed by whole exome sequencing on these 5 children's families using next-generation sequencing (NGS), and then, further validated by Sanger sequencing. A comprehensive literature search was performed through PubMed, CNKI, and Wanfang databases to summarize the disease spectrum associated with this gene. Results:Among the 5 pediatric patients, 3 exhibited HM phenotype (all presented with neurological symptoms of epilepsy/febrile seizures within the first year of life, followed by HM onset after intervals ranging from 3 years and 3 months to 7 years); 2 pediatric patients aligned with epilepsy phenotype, including one instance of drug-resistant focal-onset epileptic encephalopathy. These 5 pediatric patients carried de novo missense variants in the ATP1A2 gene, encompassing 5 distinct mutation sites. Notably, the c.1023C>G (p.Cys341Trp) and c.2458G>A (p.Ala820Thr) variants were not documented in ClinVar or HGMD databases, and were classified as likely pathogenic according to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Literature review revealed that all reported ATP1A2 mutations in Chinese pediatric patients were missense variants, with c.2143G>C (p.Gly715Arg) being the most commonly prevalent (8/29, 27.6%). The predominant clinical manifestation was HM (22/29), characterized by hemiplegia, aphasia, fever, impaired consciousness, and convulsions (early transient neurological symptoms frequently manifested as febrile seizures [12/22, 54.4%]); additionally, alternating hemiplegia of childhood was noted in 4 pediatric patients and epilepsy in 3 pediatric patients. Conclusion:ATP1A2 gene variants can lead to neurological disorders such as HM and epilepsy, with varied severity at same phenotype; the missense variants c.1023C>G and c.2458G>A in the ATP1A2 gene expand the spectrum of ATP1A2 gene variants and may serve as genetic causes of epilepsy.

Ferroptosis is a cell death pattern associated with the regulation of the Nrf2/GPX4 signaling pathway.Activating the Nrf2/GPX4 signaling pathway can regulate the expression of genes and proteins related to oxidative stress,alleviate stress damage,and inhibit cell ferroptosis.At present,research on the intervention of traditional Chinese medicine in ferroptosis has made certain progress.Through literature research,it can be found that some traditional Chinese medicine active monomers can activate the Nrf2/GPX4 signaling pathway to inhibit ferrop-tosis,play a protective role in tissues and organs,and have ther-apeutic potential in various diseases.Some traditional Chinese medicine active monomers exhibit characteristics of multi organ protective effects and bidirectional regulation.This article discus-ses the relevant research on the inhibition of ferroptosis by acti-vating the Nrf2/GPX4 signaling pathway with traditional Chinese medicine active monomers,and proposes suggestions to provide reference and ideas for further basic and applied research.