Objective To observe the effect of tuina on glutamate content and synaptic ultrastructure in spinal dorsal horn of rats with chronic sciatic nerve compression injury;To explore the potential mechanism of tuina regulation of the SNAP25/VGLUT2 pathway in alleviating lumbar disc herniation.Methods A chronic sciatic nerve compression injury model was used to simulate neuropathic pain in lumbar disc herniation.24 SD rats were randomly divided into blank group,model group and tuina group,with 8 rats in each group.From the 4th day after modeling,the tuina group was intervened with the tuina method for 10 minutes once a day for 14 consecutive days.The paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)of rats in each group on the day before modeling,and the 4th,10th,14th and 17th days after modeling were detected.The spinal cord tissue of the modeling side was taken,synaptic ultrastructure of spinal dorsal horn neurons was observed using transmission electron microscopy,immunofluorescence staining was used to detect the expression of NR2A in the spinal dorsal horn,Western blot was used to detect the expression of SNAP25 protein in the spinal dorsal horn,immunohistochemistry was used to detect the expression of VGLUT2 in the spinal dorsal horn,ELISA was used to detect the content of glutamate in the spinal dorsal horn.Results Compared with the blank group,PWT and PWL of the model group were significantly reduced on the 4th,10th,14th and 17th days after modeling(P<0.001),with accumulation of vesicles in the presynaptic membrane of the dorsal horn of the spinal cord,increase in the area of the postsynaptic dense zone,and enlargement of the synaptic cleft,while the protein expressions of NR2A,SNAP25 and VGLUT2 in the spinal dorsal horn increased(P<0.05,P<0.001),and the content of glutamate increased(P<0.001).Compared with the model group,PWT and PWL of the tuina group rats significantly increased on the 10th,14th and 17th days after modeling(P<0.001),synaptic vesicles were evenly distributed,the area of the postsynaptic dense zone decreased,and the synaptic cleft decreased,while the protein expressions of NR2A,SNAP25 and VGLUT2 in the spinal dorsal horn decreased(P<0.05,P<0.001),and the content of glutamate decreased(P<0.01).Conclusion Tuina may regulate the content of glutamate through the SNAP25/VGLUT2 pathway in the spinal dorsal horn,improve the synaptic ultrastructure of neurons,and have an analgesic effect on lumbar disc herniation.

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.

Objective:To evaluate the utility of ultrasonographic monitoring of the rectus femoris muscle—specifically, the rates of change in thickness and cross-sectional area (CSA)—in assessing nutritional status and long-term functional outcomes in patients with sepsis.Methods:In this prospective observational study, sepsis patients admitted to the ICU of the Second Affiliated Hospital of Soochow University between October 2023 and October 2024 were classified by nutritional status at discharge using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Differences in serial ultrasound-measured rectus femoris thickness and CSA on days 1, 3, 5, and 7 were compared between malnourished and non-malnourished groups. The predictive value of these ultrasound parameters for malnutrition was analyzed. Functional prognosis was assessed using the Sarcopenia Assessment Scale, Short Physical Performance Battery, and Manual Muscle Testing, with correlations to muscle changes examined.Results:Of the 71 enrolled patients (median age 73.00 [ IQR: 61.00–80.00]; 47.89% female, 52.11% male), those with malnutrition showed significantly greater variation rates in rectus femoris thickness and CSA on days 3, 5, and 7 compared to the non-malnourished group ( P < 0.05). ROC analysis revealed that the day-7 CSA variation rate had the highest predictive value for malnutrition (AUC = 0.817, 95% CI: 0.713-0.930). These muscle variation rates also correlated strongly with conventional nutritional markers such as BMI, albumin, and urea. Similarly, patients with impaired functional outcomes exhibited higher variation rates in muscle parameters on days 3, 5, and 7 ( P < 0.05), with the day-7 CSA variation rate being most predictive of functional prognosis (AUC = 0.749, 95% CI: 0.632-0.867). Conclusions:Ultrasonographic assessment of rectus femoris thickness and CSA variation rates provides a valuable tool for evaluating nutritional status and predicting functional prognosis in sepsis patients, outperforming traditional biomarkers. This method shows promise for guiding individualized nutrition support and rehabilitation strategies to improve long-term outcomes.

Objective To observe the effect of tuina on glutamate content and synaptic ultrastructure in spinal dorsal horn of rats with chronic sciatic nerve compression injury;To explore the potential mechanism of tuina regulation of the SNAP25/VGLUT2 pathway in alleviating lumbar disc herniation.Methods A chronic sciatic nerve compression injury model was used to simulate neuropathic pain in lumbar disc herniation.24 SD rats were randomly divided into blank group,model group and tuina group,with 8 rats in each group.From the 4th day after modeling,the tuina group was intervened with the tuina method for 10 minutes once a day for 14 consecutive days.The paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)of rats in each group on the day before modeling,and the 4th,10th,14th and 17th days after modeling were detected.The spinal cord tissue of the modeling side was taken,synaptic ultrastructure of spinal dorsal horn neurons was observed using transmission electron microscopy,immunofluorescence staining was used to detect the expression of NR2A in the spinal dorsal horn,Western blot was used to detect the expression of SNAP25 protein in the spinal dorsal horn,immunohistochemistry was used to detect the expression of VGLUT2 in the spinal dorsal horn,ELISA was used to detect the content of glutamate in the spinal dorsal horn.Results Compared with the blank group,PWT and PWL of the model group were significantly reduced on the 4th,10th,14th and 17th days after modeling(P<0.001),with accumulation of vesicles in the presynaptic membrane of the dorsal horn of the spinal cord,increase in the area of the postsynaptic dense zone,and enlargement of the synaptic cleft,while the protein expressions of NR2A,SNAP25 and VGLUT2 in the spinal dorsal horn increased(P<0.05,P<0.001),and the content of glutamate increased(P<0.001).Compared with the model group,PWT and PWL of the tuina group rats significantly increased on the 10th,14th and 17th days after modeling(P<0.001),synaptic vesicles were evenly distributed,the area of the postsynaptic dense zone decreased,and the synaptic cleft decreased,while the protein expressions of NR2A,SNAP25 and VGLUT2 in the spinal dorsal horn decreased(P<0.05,P<0.001),and the content of glutamate decreased(P<0.01).Conclusion Tuina may regulate the content of glutamate through the SNAP25/VGLUT2 pathway in the spinal dorsal horn,improve the synaptic ultrastructure of neurons,and have an analgesic effect on lumbar disc herniation.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.

Objective To analyze the current status,hot spots and trends of Chinese and English researches in the field of aspiration after dysphasia in the past twenty years. Methods The articles about aspiration after dysphasia were retrieved from CNKI and Web of Science(WOS)core collec-tion database,from January,2003 to June,2023,and were analyzed with CiteSpace 6.1.R6. Results A total of 3 231 articles were included.The annual articles were published more and more year by year.The most English literatures came from the United States.Hot spots mainly focused on the assessment of dysphasia,prevention of complication,nutrition and rehabilitation therapy.It would concentrate on the application of the volume-viscosity swallow test and assessment scales,rehabilitation,penetration aspiration,outcome and effect validation,quality of life,feeding and nutrition condition,and evidence-based nursing,etc.,in the future. Conclusion The researches in the field of aspiration after dysphasia have been increasing in recent years,and the themes and contents of researches have been deepening.

BackgroundThe prevalence of depressive disorder in adolescents is on the rise. There have been studies on the pairwise relations between dysfunctional attitude， negative automatic thoughts， positive coping style and depressive symptoms in the past. However， the impact of the intrinsic relations among dysfunctional attitude， negative automatic thoughts and positive coping style on depressive symptoms is still unclear. ObjectiveTo explore the influence of dysfunctional attitude on adolescent depressive symptoms and examine the action path of negative automatic thoughts and positive coping style on it， in order to provide references for intervention for adolescent patients with depressisve disorder. MethodsThis study involved 162 adolescent patients with depressive disorder， who met the diagnostic criteria for depressive episodes in the International Classification of Diseases， 10th edition （ICD-10） and received treatment in Taiyuan Psychiatric Hospital from October 1， 2022 to October 31， 2023. These patients were evaluated using Self-rating Depression Scale （SDS）， Dysfunction Attitude Scale （DAS）， Positive Coping Style Subscale in Simplified Coping Style Questionnaire（SCSQ） and Automatic Thoughts Questionnaire （ATQ）. Pearson correlation analysis was adopted to examine the correlation among scores of scales above. Model 6 in Process 3.4.1 was adopted to test the acting path of negative automatic thoughts and positive coping style between dysfunctional attitude and adolescent depression symptoms. ResultsA total of 148 adolescent patients with depressive disorder completed an effective questionnaire survey， with a response rate of 91.36%. The direct effect value of dysfunctional attitude on depressive symptoms was 0.423 and the effect size was 63.32%. Negative automatic thoughts and positive coping style affected as acting path between dysfunctional attitude and depressive symptoms， with effect values of 0.156 （accounting for 23.35% of the total effect） and 0.045 （accounting for 6.74% of the total effect） respectively. Meanwhile， negative automatic thoughts and positive coping style affected as a chain reaction pathway between dysfunctional attitude and depressive symptoms， with an effect value of 0.044， accounting for 6.59% of the total effect. ConclusionDysfunctional attitude can not only directly affect the depressive symptoms of adolescent patients with depressive disorder， but also affect the depressive symptoms of adolescent patients with depressive disorder through the independent path or chain path of negative automatic thoughts and positive coping style.

Objective To observe the effect of tuina on glutamate uptake and synaptic cleft in the spinal dorsal horn of rats with neuropathic pain through astrocyte NDRG2/GLT-1 pathway,and to explore the potential analgesic mechanism of tuina on neuropathic pain.Methods A total of 54 SD rats were randomly divided into naive group,model group and tuina group(n=18).The CCI model was established in the model group,and the tuina group was treated with acupressure at"Weizhong"(BL 40)from the 4th day after CCI model was successfully established for 14 days.The changes of paw withdrawal threshold at different time points were observed to evaluate the analgesic effect of tuina.Immunofluorescence was used to observe the co-expression of NDRG2?GLT-1 and astrocytes in the spinal dorsal horn.The mRNA levels of NDRG2 and GLT-1 in astrocytes were detected by quantitative real time polymerase chain reaction.The concentrations of glutamate in synaptic cleft were measured by liquid chromatography coupled to tandem mass spectrometry.The width of the synaptic cleft was observed by transmission electron microscopy.Results Compared with the naive group,the paw withdrawal threshold in the CCI group decreased continuously(P<0.01).The number of NDRG2 and GFAP co-labeling positive cells in the spinal dorsal horn increased significantly(P<0.01),and the number of GLT-1 and GFAP co-labeled positive cells was significantly reduced(P<0.01).NDRG2 mRNA expression was up-regulated and GLT-1 mRNA expression decreased in astrocytes(P<0.01).The concentrations of glutamate increased significantly(P<0.01);The synaptic cleft was significantly narrowed(P<0.05).After tuina intervention,the above trend was significantly reversed.Compared with the model group,the paw withdrawal threshold of the tuina group increased from 11 days after CCI(P<0.01),the number of NDRG2 and GFAP co-labeling positive cells in the spinal dorsal horn was significantly reduced(P<0.01),and the number of GLT-1 and GFAP co-labeled positive cells increased significantly(P<0.01);down-regulated the expression of NDRG2 mRNA and restored GLT-1 mRNA expression in astrocytes(P<0.01);decreased glutamate concentration in synaptic cleft(P<0.05),the synaptic cleft was relatively widened(P<0.05).Conclusion Tuina alleviates pain in CCI rats at the spinal cord level possibly by promoting the uptake of glutamate by NDRG2/GLT-1 pathway in astrocytes,restoring the width of synaptic cleft and reversing synaptic plasticity.

Objective To construct the medical risk comprehensive assessment system based on big data,and to evaluate its consistency and efficiency.Methods Aiming at the current situation of risk assessment of inpatients,based on the means of big data,the medical natural language processing was used to design a medi-cal risk comprehensive assessment system.The system can automatically capture various data of patients,au-tomatically generate the scores by data mining and machine learning technology and send the risk data to med-ical staff,so as to realize the automation and intellectualization.The randomized controlled analysis was used to conduct the manual scoring and machine scoring for included the score scale.The visual risk matrix diagram was automatically generated by comparing the scoring.Results The Kappa values of the scoring system in the included study of the system were as follows:the Kappa value in Caprini scale(surgery)and Padua scale(internal medicine)was 1.00,NNIS Kappa value was 1.00,Nomogram Kappa value was 0.87,Kappa value in the Morse assessment scale/Hendrich model was 0.83,Braden Kappa value was 0.80,ASA 2023 Kappa was 1.00 and NRS 2002 Kappa value was 0.90.The taking time in the machine scoring all were shorter than those in the manual scoring,and the difference was statistically significant(P＜0.05).Conclusion The risk matrix graph constructed by this system could sharply increase the evaluation efficiency and accuracy,which not only provide the accuracy diagnosis and treatment regimen,but also shorten the hospitalization duration and reduce the medical costs.