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 To evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans ; Venous Thrombosis/therapy* ; Retrospective Studies ; Thrombolytic Therapy/methods* ; Male ; Female ; Middle Aged ; Fractures, Bone/complications* ; Lower Extremity/injuries* ; Anticoagulants/therapeutic use* ; Aged ; Treatment Outcome ; Adult

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.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:The study investigated the full-time Clinical Research Coordinators (CRCs) working in hospitals on their current working situation and explored affecting factors to provide suggestions for a professional and systemic clinical research workforce establishment in municipal medical institutions.Methods:A questionnaire survey was designed for CRCs in municipal hospitals in Shanghai, descriptive and one-way cross-tabulation analysis were conducted, using t-test for continuous numerical variables, rank-sum test for count variables and chi-square test for categorical variables.Results:Totaling 177 CRCs in 9 municipal hospitals in Shanghai answered the questionnaire. The average age of the respondents was 28.56±7.299 years old. Their professional background was mainly nursing and pharmacy (139/177, 87.53%), and bachelor degree (114/177, 64.41%). Averagely worked 2.50±1.632 years, the average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. The CRCs employed by hospitals mainly undertook Investigator-Initiated clinical Trial/Research projects (IITs) (26/36, 72.22%), while the CRCs employed by SMO companies mainly undertook Industry-Sponsored Clinical Trial (IST) projects (96/141, 68.09%). 85.88% (152/117) of CRCs held GCP certificates valid within three years, and the proportion of CRCs employed by hospitals held GCP certificates was lower than that of SMO companies ( P<0.05). Among the CRCs employed by hospitals, 23 (63.89%) said they had no position or were not clear about their position; The CRCs in SMO companies were mainly primary and intermediate (χ 2=84.119, P<0.05). The average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. Conclusions:With the development of clinical research, the full-time specialized CRCs in medical institutions mainly have 2 sources: from SMO/CRO companies or self-employment by medical institutions. In general, there are still problems in the CRC talent team as unclear entry standards, insufficient, lack career positioning planning, large mobility, imperfect training system, and imperfect promotion mechanism. It is suggested to unify occupational access standards and set specialty in colleges or universities. Strengthen post-service education and training system, establish multi-party collaborative training mechanism, standardize the assessment and evaluation, improve the job title promotion system, to promote the rapid development of CRC team.

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.

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.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:The study investigated the full-time Clinical Research Coordinators (CRCs) working in hospitals on their current working situation and explored affecting factors to provide suggestions for a professional and systemic clinical research workforce establishment in municipal medical institutions.Methods:A questionnaire survey was designed for CRCs in municipal hospitals in Shanghai, descriptive and one-way cross-tabulation analysis were conducted, using t-test for continuous numerical variables, rank-sum test for count variables and chi-square test for categorical variables.Results:Totaling 177 CRCs in 9 municipal hospitals in Shanghai answered the questionnaire. The average age of the respondents was 28.56±7.299 years old. Their professional background was mainly nursing and pharmacy (139/177, 87.53%), and bachelor degree (114/177, 64.41%). Averagely worked 2.50±1.632 years, the average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. The CRCs employed by hospitals mainly undertook Investigator-Initiated clinical Trial/Research projects (IITs) (26/36, 72.22%), while the CRCs employed by SMO companies mainly undertook Industry-Sponsored Clinical Trial (IST) projects (96/141, 68.09%). 85.88% (152/117) of CRCs held GCP certificates valid within three years, and the proportion of CRCs employed by hospitals held GCP certificates was lower than that of SMO companies ( P<0.05). Among the CRCs employed by hospitals, 23 (63.89%) said they had no position or were not clear about their position; The CRCs in SMO companies were mainly primary and intermediate (χ 2=84.119, P<0.05). The average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. Conclusions:With the development of clinical research, the full-time specialized CRCs in medical institutions mainly have 2 sources: from SMO/CRO companies or self-employment by medical institutions. In general, there are still problems in the CRC talent team as unclear entry standards, insufficient, lack career positioning planning, large mobility, imperfect training system, and imperfect promotion mechanism. It is suggested to unify occupational access standards and set specialty in colleges or universities. Strengthen post-service education and training system, establish multi-party collaborative training mechanism, standardize the assessment and evaluation, improve the job title promotion system, to promote the rapid development of CRC team.

OBJECTIVE To explore the effects of CD20 coding gene(MS4A1)polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin's lymphoma.METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin's lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020,with a minimum follow-up period of approximately 5 years.The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay.MS4A1 tagSNPs were selected by Haploview4.2 software,including rs1051461,rs17155034,rs4939364,and rs10501385.The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.Univariate linear regression analysis was employed to examine the correlation between various factors(demographic,clinical,and genotypic variables)in patients and the steady-state trough concentration of rituximab during the first course of treatment,followed by multivariate linear regression analysis.Kaplan-Meier curves were drawn to evaluate progression-free survival(PFS)and overall survival(OS).Using MS4A1 genotype and tumor stage as independent variables,Cox regression model was employed to evaluate the factors influencing patient prognosis.RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL,which was significantly lower than 21.95 μg/mL in AA+AC carriers(P＜0.05).The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3%of the interindividual variability in rituximab concentrations.Compared with MS4A1 rs1051461 CC carriers,CT+TT carriers had significantly prolonged PFS and OS(P＜0.05).The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype(HR=4.406,95%CI:1.743-11.137,P＜0.05)and tumor Ⅲ&Ⅳ(HR=3.233,95%CI:1.413-7.399,P＜0.05)were independent risk factors for PFS.CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab,and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin's lymphoma patients.