Objective To investigate the characteristics of a novel FANCL mutation identified in a patient with premature ovarian insufficiency(POI)and to explore its potential functional impacts in vitro.Methods A novel FANCL heterozygous mutation c.1033G>A(p.Glu345Lys)was screened in a patient with POI using whole exome sequencing(WES),which was found to be inherited from a mother who had undergone early menopause.The authenticity of the mutation was identified by Sanger sequencing and the conserved nature of the mutation site was predicted by software.Overexpressing FANCL mutant and wildtype plasmids were constructed and transiently transfected into HEK293T cell lines,and the effect of the mutation was detected by qPCR,immunofluorescence and Western blot.Results The mutation site of FANCL was located within the Ring domain of FANCL,which was highly conserved across multiple species.The mutant showed no significant change in mRNA expression level,while the protein expression level was significantly down-regulated.In vitro cellular experiments further revealed that the mutation leads to decreased expression levels by reducing protein stability.Conclusion A FANCL c.1033G>A mutation was found and it may cause disease in the POI patient due to decreased protein stability.

Objective To investigate the longitudinal clinical manifestations of acute radiation dermatitis(ARD)induced by particle therapy in nasopharyngeal carcinoma patients and to analyze associated risk factors.Methods A longitudinal study design was employed,encompassing nasopharyngeal carcinoma patients who underwent particle therapy at the Shanghai Proton and Heavy Ion Center from Mar to Sept 2023.Participants were assessed weekly(1-12 weeks)following the commencement of radiotherapy and at baseline,prior to the start of treatment.Data collection included the patient demographic questionnaire,the Radiation Therapy Oncology Group(RTOG)grading criteria for acute radiation injury,and the radiation-induced skin reaction assessment scale(RISRAS).Photographic documentation was utilized to capture changes in the irradiated skin area.The enrolled patients with nasopharyngeal carcinoma were grouped according to different particle therapy regimens.Survival data were analyzed by Log-rank and Cox regression methods,while a linear mixed-effects model was applied to repeated measures data.Results A total of 119 patients with nasopharyngeal carcinoma were enrolled.The overall incidence of ARD was 89.1%,which included 39.5%of grade 1,45.4%of grade 2 and 4.2%of grade 3.With the extension of time,the severity of ARD peaked at week 7(RISRAS=13.26±4.512),then began to decrease,ultimately reaching a lower level.Multiple Cox proportional hazards models were constructed,revealing that proton/heavy ion radiotherapy was associated with a lower risk of ARD compared to photon/proton plus heavy ion radiotherapy(HR=0.19,95%CI:0.04-0.92,P=0.039).Additionally,concurrent cisplatin/nedaplatin chemotherapy was identified as a risk factor for the development of ARD.Least squares(LS)mean differences were calculated at different time points,and the results demonstrated that the RISRAS scores of the photon/proton plus heavy ion group were consistently and significantly higher from week 5 to week 7 compared with the proton plus heavy ion group,and despite a decrease by week 8,statistical differences remained(week 5:LS mean difference 3.35,95%CI:0.94-5.76,P=0.007;week 6:LS mean difference 5.23,95%CI:2.20-8.26,P=0.001;week 7:LS mean difference 7.13,95%CI:3.67-10.59,P<0.001;week 8:LS mean difference 4.04,95%CI:0.74-7.34,P=0.017).Patients undergoing concurrent cisplatin chemotherapy had higher RISRAS scores from week 7 to week 8 of radiotherapy compared with those not receiving chemotherapy[week 7:adjusted mean difference(Adj.MD)4.20,95%CI:1.96-6.57,P=0.006;week 8:Adj.MD 2.79,95%CI 0.55-5.03,P=0.015].Similarly,patients on concurrent nedaplatin chemotherapy had higher RISRAS scores from weeks 6 to 7 compared with those not on chemotherapy(week 6:Adj.MD 3.75,95%CI:1.54-5.96,P=0.001;week 7:Adj.MD 4.41,95%CI:2.12-6.70,P<0.001).Skin care measures during treatment and accompanying symptoms such as weight loss were not statistically associated with the development of ARD.Conclusion Proton/heavy ion radiotherapy has a lower risk of ARD,while concurrent cisplatin/nedaplatin chemotherapy is a risk factor for ARD.

Central nervous system(CNS)degenerative disorders refer to a spectrum of pathological alterations triggered by struc-tural damage to cerebral neural tissues,clinically manifested as diverse neurological dysfunction syndromes,including multiple sclerosis(MS),neurodegenerative diseases(NDs),and ische-mic stroke.The hallmark pathological features of these disorders involve irreversible neuronal damage and decompensation of functional neural networks,ultimately leading to progressive neurological deficits.Notably,with the accelerating global popu-lation aging,the incidence of these diseases has surged signifi-cantly.According to WHO statistics,they now rank among the top three global causes of disability and mortality.Current re-search has confirmed that the pathogenesis of CNS degenerative disorders exhibits high heterogeneity,encompassing multifaceted pathophysiological processes such as genetic predisposition,oxi-dative stress,protein misfolding,and metabolic dysregulation.This intricate pathogenic network not only complicates clinical differential diagnosis but also poses substantial challenges to the development of precision therapeutic strategies.Importantly,re-cent studies have revealed that mitochondrial homeostasis disrup-tion-induced inflammatory cascades(termed mitochondrial in-flammation)play a pivotal regulatory role in neurodegenerative progression.Key molecular mechanisms include impaired mito-phagy,aberrant mitochondrial DNA(mtDNA)release and NL-RP3 inflammasome activation.This review systematically deci-phers the molecular regulatory network of mitochondrial inflam-mation,with a focus on its biological effects in critical pathologi-cal events such as blood-brain barrier disruption,microglial hy-peractivation and neuronal apoptosis.The overarching aim is to provide a theoretical foundation for developing innovative thera-peutic strategies targeting mitochondrial homeostasis restoration.

Objective:Based on multivariate analysis of the influencing factors of fecal pollution after radical re-section in children with congenital megacolon,a risk prediction model was constructed and evaluated.Methods:A total of 200 children with Hirschsprung's disease who underwent radical surgery at Nanyang Central Hospital of Henan Province from June 2020 to June 2023 were selected,and all children were followed up for 1 year.According to the occurrence of postoperative fecal incontinence,the children were divided into the non-occurrence group and the oc-currence group.Univariate Logistic regression analysis was performed on all possible influencing factors,and the back-ward stepwise regression method was used to screen out the relevant factors affecting postoperative fecal inconti-nence in children with Hirschsprung's disease after radical surgery.A risk prediction model was constructed based on these relevant factors,and its efficacy was verified using calibration curves,the Hosmer-Lemeshow test,and ROC curves.Results:Postoperative fecal incontinence occurred in 19.50%(39/200)of the children.A statistically signifi-cant difference was observed between the non-occurrence group and the occurrence group in terms of the following data(P＜0.05):age,preoperative nutritional support,need for auxiliary defecation before surgery,length of the dis-eased intestinal segment,educational level of caregivers,preoperative hypoproteinemia,resection range,postoperative diet compliance of the children,postoperative defecation training of the children,postoperative enterocolitis,and post-operative anal dilatation therapy.Multivariate Logistic regression analysis showed that preoperative nutritional support,need for auxiliary defecation before surgery,length of the diseased intestinal segment,educational level of caregivers,postoperative diet compliance of the children,postoperative defecation training of the children,postoperative entero-colitis,and postoperative anal dilatation therapy were all independent influencing factors for postoperative fecal inconti-nence in children with Hirschsprung's Disease after radical surgery(P＜0.05).Among these factors,the educational level of caregivers was the strongest predictor of postoperative fecal incontinence in children with Hirschsprung's dis-ease after radical surgery.Results of the calibration curve showed that the concordance index of the risk prediction model for postoperative fecal incontinence in children with Hirschsprung's Disease after radical surgery was 0.837.The Hosmer-Lemeshow test results indicated no statistically significant difference between the predicted values and the actual values of risk prediction(P＜0.05),suggesting that the model had a good fit and high prediction accuracy.Re-sults of the ROC curve showed that the area under the curve(AUC)of the risk prediction model for predicting postop-erative fecal incontinence in children with Hirschsprung's Disease after radical surgery was 0.887(95%CI:0.762～1.000,P＜0.05),with a sensitivity of 0.914,a specificity of 0.763,and a Youden index of 0.677.These findings indicate that the risk prediction model has moderate discriminative ability and good predictive performance.Conclusion:Preop-erative nutritional support,need for auxiliary defecation before surgery,length of the diseased intestinal segment,edu-cational level of caregivers,postoperative diet compliance of children,postoperative defecation training of children,postoperative enterocolitis,and postoperative anal dilatation therapy are all independent influencing factors for postop-erative fecal incontinence in children with Hirschsprung's disease after radical surgery.The risk prediction model for postoperative fecal incontinence in children with Hirschsprung's disease after radical surgery,established based on multivariate analysis,is helpful for early identification of high-risk groups and timely implementation of individualized in-tervention measures.

Objective:Based on multivariate analysis of the influencing factors of fecal pollution after radical re-section in children with congenital megacolon,a risk prediction model was constructed and evaluated.Methods:A total of 200 children with Hirschsprung's disease who underwent radical surgery at Nanyang Central Hospital of Henan Province from June 2020 to June 2023 were selected,and all children were followed up for 1 year.According to the occurrence of postoperative fecal incontinence,the children were divided into the non-occurrence group and the oc-currence group.Univariate Logistic regression analysis was performed on all possible influencing factors,and the back-ward stepwise regression method was used to screen out the relevant factors affecting postoperative fecal inconti-nence in children with Hirschsprung's disease after radical surgery.A risk prediction model was constructed based on these relevant factors,and its efficacy was verified using calibration curves,the Hosmer-Lemeshow test,and ROC curves.Results:Postoperative fecal incontinence occurred in 19.50%(39/200)of the children.A statistically signifi-cant difference was observed between the non-occurrence group and the occurrence group in terms of the following data(P＜0.05):age,preoperative nutritional support,need for auxiliary defecation before surgery,length of the dis-eased intestinal segment,educational level of caregivers,preoperative hypoproteinemia,resection range,postoperative diet compliance of the children,postoperative defecation training of the children,postoperative enterocolitis,and post-operative anal dilatation therapy.Multivariate Logistic regression analysis showed that preoperative nutritional support,need for auxiliary defecation before surgery,length of the diseased intestinal segment,educational level of caregivers,postoperative diet compliance of the children,postoperative defecation training of the children,postoperative entero-colitis,and postoperative anal dilatation therapy were all independent influencing factors for postoperative fecal inconti-nence in children with Hirschsprung's Disease after radical surgery(P＜0.05).Among these factors,the educational level of caregivers was the strongest predictor of postoperative fecal incontinence in children with Hirschsprung's dis-ease after radical surgery.Results of the calibration curve showed that the concordance index of the risk prediction model for postoperative fecal incontinence in children with Hirschsprung's Disease after radical surgery was 0.837.The Hosmer-Lemeshow test results indicated no statistically significant difference between the predicted values and the actual values of risk prediction(P＜0.05),suggesting that the model had a good fit and high prediction accuracy.Re-sults of the ROC curve showed that the area under the curve(AUC)of the risk prediction model for predicting postop-erative fecal incontinence in children with Hirschsprung's Disease after radical surgery was 0.887(95%CI:0.762～1.000,P＜0.05),with a sensitivity of 0.914,a specificity of 0.763,and a Youden index of 0.677.These findings indicate that the risk prediction model has moderate discriminative ability and good predictive performance.Conclusion:Preop-erative nutritional support,need for auxiliary defecation before surgery,length of the diseased intestinal segment,edu-cational level of caregivers,postoperative diet compliance of children,postoperative defecation training of children,postoperative enterocolitis,and postoperative anal dilatation therapy are all independent influencing factors for postop-erative fecal incontinence in children with Hirschsprung's disease after radical surgery.The risk prediction model for postoperative fecal incontinence in children with Hirschsprung's disease after radical surgery,established based on multivariate analysis,is helpful for early identification of high-risk groups and timely implementation of individualized in-tervention measures.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective:To explore the current status and influencing factors of intrinsic capacity in elderly patients with Parkinson's disease.Methods:Convenience sampling was used to select 306 elderly patients with Parkinson's disease who attended Xuanwu Hospital of Capital Medical University from March to September 2024 for the study. Influencing factors were screened based on the health ecology model. Elderly patients with Parkinson's disease were surveyed using the General Information Questionnaire, Connor-Davidson Resilience Scale, Family APGAR Scale, Social Support Rating Scale, and Intrinsic Capacity Assessment Tool. Multiple linear regression was used to analyze the factors influencing the total score and the scores of each dimension of intrinsic capacity in elderly patients with Parkinson's disease.Results:A total of 306 questionnaires were distributed and 301 valid questionnaires were recovered, with a valid recovery rate of 98.37% (301/306). The total intrinsic capacity score of 301 elderly patients with Parkinson's disease was (67.21±11.47), of which 297 elderly patients with Parkinson's disease had impaired intrinsic capacity, and the rate of impaired intrinsic capacity was 98.7% (297/301). The dimensions in descending order of impairment were motor [89.7% (270/301) ], mental [76.1% (229/301) ], sensory [70.4% (212/301) ], vitality [38.2% (115/301) ], and cognitive [25.6% (77/301) ]. Multiple linear regression analysis showed that age, Hoehn-Yahr staging, levodopa equivalent dosage, activity of daily living, history of falls, regular exercise, psychological resilience, social support, and monthly income were the factors influencing the total intrinsic capacity score of elderly patients with Parkinson's disease ( P<0.05) and heterogeneity of influencing factors in each dimension. Conclusions:Elderly patients with Parkinson's disease have a high rate of impaired intrinsic capacity, with the motor dimension being the most severely impaired. Healthcare professionals should pay attention to the assessment of the intrinsic capacity of elderly patients with Parkinson's disease, and customize interventions according to the influencing factors to promote the functioning of elderly patients so as to reduce the burden of care on families and society.

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

From the perspective of competitive endogenous RNA(ceRNA) constructed by metastasy-associated lung adenocarcinoma transcript 1(Malat1) and microRNA 16-5p(miR-16-5p), the improvement mechanism of Tonggu Xiaotong Capsules(TGXTC) on the imbalance and disorder of "cholesterol-iron" metabolism in chondrocytes of osteoarthritis(OA) was explored. In vivo experiments, 60 8-week-old C57BL/6 mice were acclimatized and fed for 1 week and then randomly divided into two groups: blank group(12 mice) and modeling group(48 mice). The animals in modeling group were anesthetized by 5% isoflurane inhalation, which was followed by the construction of OA model. They were then randomly divided into model group, TGXTC group, Malat1 overexpression group, and TGXTC+Malat1 overexpression(TGXTC+Malat1-OE) group, with 12 mice in each group. The structural changes of mouse cartilage tissues were observed by Masson staining after the intervention in each group. RT-PCR was employed to detect the mRNA levels of Malat1 and miR-16-5p in cartilage tissues. Western blot was used to analyze the protein expression of ATP-binding cassette transporter A1(ABCA1), sterol regulatory element-binding protein(SREBP), cytochrome P450 family 7 subfamily B member 1(CYP7B1), CCAAT/enhancer-binding protein homologous protein(CHOP), acyl-CoA synthetase long-chain family member 4(ACSL4), and glutathione peroxidase 4(GPX4) in cartilage tissues. In vitro experiments, mouse chondrocytes were induced by thapsigargin(TG), and the combination of Malat1 and miR-16-5p was detected by double luciferase assay. The fluorescence intensity of Malat1 in chondrocytes was determined by fluorescence in situ hybridization. The miR-16-5p inhibitory chondrocyte model was constructed. RT-PCR was used to analyze the levels of Malat1 and miR-16-5p in chondrocytes under the inhibition of miR-16-5p. Western blot was adopted to analyze the regulation of TG-induced chondrocyte proteins ABCA1, SREBP, CYP7B1, CHOP, ACSL4, and GPX4 by TGXTC under the inhibition of miR-16-5p. The results of in vivo experiments showed that,(1) compared with model group, TGXTC group exhibited a relatively complete cartilage layer structure. Compared with Malat1-OE group, TGXTC+Malat1-OE group showed alleviated cartilage surface damage.(2) Compared with model group, TGXTC group had a significantly decreased Malat1 mRNA level and an increased miR-16-5p mRNA level in mouse cartilage tissues(P<0.01).(3) Compared with the model group, the protein levels of ABCA1 and GPX4 in the cartilage tissue of mice in the TGXTC group increased, while the protein levels of SREBP, CYP7B1, CHOP and ACSL4 decreased(P<0.01). The results of in vitro experiments show that,(1) dual-luciferase was used to evaluate that miR-16-5p has a targeting effect on the Malat1 gene.(2)Compared with TG+miR-16-5p inhibition group, TG+miR-16-5p inhibition+TGXTC group had an increased mRNA level of miR-16-5p and an decreased mRNA level of Malat1(P<0.01).(3) Compared with TG+miR-16-5p inhibition group, TG+miR-16-5p inhibition+TGXTC group exhibited increased expression of ABCA1 and GPX4 proteins and decreased expression of SREBP, CYP7B1, CHOP, and ACSL4 proteins(P<0.01). The reasults showed that TGXTC can regulate the ceRNA of Malat1 and miR-16-5p to alleviate the "cholesterol-iron" metabolism disorder of osteoarthritis chondrocytes.
Animals ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Chondrocytes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred C57BL ; Mice ; Osteoarthritis/drug therapy* ; Iron/metabolism* ; Male ; Cholesterol/metabolism* ; Humans ; Capsules ; RNA, Competitive Endogenous

Objective: Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits. Methods: We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase. Results: HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters. Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.