BACKGROUND:Acute exercise tends to cause skeletal muscle tissue damage and lipid metabolism disorders in vivo,but the mechanism by which acute exercise combined with electroacupuncture modulates metabolic and autophagic pathways in vivo is unclear. OBJECTIVE:To observe the changes in metabolic enzymes and autophagy levels in skeletal muscle of rats subjected to acute exercise by electroacupuncture at the acupoints of"Zusanli"and"Huantiao." METHODS:Fifty male Sprague-Dawley rats were randomly divided into three groups:quiet control group(n=10),model group(n=20),and reverse electroacupuncture group(n=20).The latter two groups were set up with two time points,i.e.immediate and 3 hours after exercise groups(n=10 per time point).The model group and the reverse electroacupuncture group underwent acute exercise training after adaptive treadmill training.The rats in the reverse electroacupuncture group underwent electroacupuncture treatment(parameters:electroacupuncture on both sides of the rats at the acupoints of"Zusanli"and"Huantiao,"continuous wave,frequency of 2 Hz,intensity of 2 mA,leaving the needle in the body for 30 minutes,once a day for 7 consecutive days)before treadmill training.Bilateral gastrocnemius muscle tissues were taken under anesthesia immediately after exercise and 3 hours after exercise,and hematoxylin-eosin staining was used to observe the histopathological changes of rat skeletal muscle.ELISA kit was used to detect the activities of hepatic lipase,fatty acid synthase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 in rat skeletal muscle tissues.Immunohistochemistry and western blot were used to detect the changes in the expression of autophagy genes. RESULTS AND CONCLUSION:After hematoxylin-eosin staining,the arrangement of gastrocnemius muscle fibers in the model group was disturbed,swollen and ruptured immediately after exercise and 3 hours after exercise.In the reverse electroacupuncture group,gastrocnemius muscle fibers were tightly arranged and the number of swollen and ruptured cells was greatly reduced immediately after exercise and 3 hours after exercise,and there was no significant difference when compared with the quiet control group.Compared with the quiet control group,the activities of hepatic lipase and fatty acid synthase were lower while the activities of lipoprotein lipase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 were higher in the model group and the reverse electroacupuncture group 3 hours after exercise(P＜0.05 or P＜0.01).Compared with the model group,the activities of lipoprotein lipase and carnitine palmitoyltransferase 1 were higher in the reverse electroacupuncture group immediately after exercise(P＜0.05),while the activity of lipoprotein lipase was higher and the activity of hormone-sensitive lipase was lower in the reverse electroacupuncture group 3 hours after exercise(P＜0.01).Immunohistochemical results showed that compared with the quiet control group,the expression of P62,autophagy-related gene 5 and autophagy-related gene 7 was higher in the model group immediately and 3 hours after exercise,as well as in the reverse electroacupuncture group immediately after exercise(P＜0.05 or P＜0.01);compared with the model group,the expression of P62 and autophagy-related gene 7 was lower in the reverse electroacupuncture group immediately and 3 hours after exercise(P＜0.05).Western blot results showed that the protein expression of P62 and autophagy-related gene 7 in the reverse electroacupuncture group was lower than that in the model group immediately after exercise(P＜0.05);the protein expression of Parkin in the model group was higher than that in the quiet control group immediately and 3 hours after exercise(P＜0.05);and the protein expression of Parkin in the reverse electroacupuncture group was lower than that in the model group immediately and 3 hours after exercise(P＜0.05).To conclude,acute exercise induces disorders,swelling and rupture of gastrocnemius muscle fibers in rats and electroacupuncture on both sides of the acupoints of"Zusanli"and"Huantiao"can improve the level of lipid metabolism and regulate autophagy cells in rat skeletal muscle,preventing the disorders of lipid metabolism and damage of gastrocnemius muscle tissues caused by acute exercise.The mechanism may be closely related to the regulation of autophagy-related factor P62,autophagy-related gene 5,autophagy-related gene 7,and Parkin protein expression to promote the occurrence of autophagy or regulate the autophagy pathway in rat skeletal muscle cells.

GBA1 gene mutation is an important genetic risk factor for Parkinson’s disease (PD). This paper reports a case of a 43-year-old male PD patient carrying a rare heterozygous Thr408Met mutation in the GBA1 gene identified through whole-exome sequencing, leading to a diagnosis of GBA1-associated PD. The patient’s motor symptoms were primarily characterized by bradykinesia and rigidity, without significant cognitive decline. Treatment with low-dose levodopa combined with a dopamine agonist resulted in significant symptomatic improvement.

Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

OBJECTIVES: To establish a prognostic model for primary liver cancer (PLC) using bioinformatics methods. METHODS: Based on the data from 404 patients in the Cancer Genome Atlas (TCGA) database, we constructed a prognostic model integrating the differentially expressed genes, anoikis, and immune-related genes (DAIs) using univariate Cox regression and the LASSO-Cox approach. The predictive ability of the model was evaluated using Kaplan-Meier method and receiver-operating characteristic curves, and a nomogram was developed to facilitate its clinical applications. Gene set enrichment analysis (GSEA) was performed to explore the associated pathways and relationship between the DAIs and the tumor immune microenvironment, and the half-maximal inhibitory concentration (IC₅₀) of liver cancer drugs was calculated using the "pRRophetic" R package. We also detected the expression of SEMA7A in paired tumor and adjacent tissues from liver cancer patients. RESULTS: We constructed and validated a prognostic model based on 7 DAIs (NR4A3, SEMA7A, IL11, AR, BIRC5, EGF, and SPP1), and obtained consistent results in both the TCGA training cohort and GEO validation cohort (GSE14520), where the patients in the low-risk group were characterized by more favorable clinical outcomes and immune status. By integrating this prognostic signature with clinical information, a composite nomogram was generated. Somatic mutation analysis showed that TTN, TP53, and CTNNB1 mutations accounted for the largest proportion of total mutations, and the patients in the low-risk-low-TMB group had higher survival rate. Drug sensitivity analysis revealed differences in sensitivity to chemotherapeutic agents between high- and low-risk groups and between TP53 mutations and non-mutations. In clinical tissue specimens, SEMA7A expression was significantly higher in liver cancer tissues than in the adjacent tissues. CONCLUSIONS We established a new prognostic model based on DAIs for predicting clinical outcomes and therapeutic response of patients with primary liver cancer.
Humans ; Liver Neoplasms/diagnosis* ; Prognosis ; Anoikis ; Nomograms ; Computational Biology ; Tumor Microenvironment ; Semaphorins/metabolism*

Objective:To perform two-step clustering analysis based on urodynamics in patients with neurogenic bladder (NB) and exploring characteristics affecting success rate of sacral neuromodulation (SNM).Methods:The data of 174 NB patients who received SNM therapy in our hospital from September 2018 to August 2023, were retrospectively analysed. There were 94 males and 80 females, with average age of (50.4±17.9)years, median duration of 2 (1, 3)years, and body mass index of 21.5 (20, 25) kg/m 2. Among them, 50 patients had chronic diseases (hypertension or diabetes). Additionally, 77 patients (44.3%) presented with voiding symptoms, 47 patients (27.0%) with storage symptoms, and 50 patients (28.7%) with mixed symptoms. The etiologies included spinal cord lesions in 110 patients (63.2%), brain lesions in 21 patients (12.1%), peripheral nerve lesions in 36 patients (20.7%), and other causes in 7 patients (4.0%). All patients underwent urodynamics and SNM phase 1 test. If patient's subjective symptoms or objective indicators improved > 50%, it is defined as treatment success and feasible to received second stage of SNM. The success rate was analyzed. Clinical indicators and urodynamic parameter were collected for exploring the difference of the above indicators between two groups (with or without conversion). The 174 patients were grouped using two-step clustering analysis, dividing them into two groups. The differences in clinical data, urodynamic parameters, and the conversion rate of SNM phase II between the two groups were compared. Results:Among these patients, 126 (72%) underwent the second stage of SNM. Compared with the non-conversion group, patients in the conversion group exhibited the following characteristics: high proportion of female[51.6% (65/126) vs. 31.2% (15/48)], younger[(48.1± 18.3)year vs. (56.4±15.4) year], lower proportion of history of chronic disease[23.9% (30/126) vs. 41.7% (20/48)], storage predominant symptoms predominant[33.3% (42/126) vs. 10.4% (5/48)], sensitive bladder sensation[50.0% (63/126) vs. 11.1% (14/48)], normal detrusor contractility [26.2% (33/126) vs. 10.4% (5/48)] and detrusor-sphincter dyssynergia [21.4% (27/126) vs. 4.2% (2/48)]and lower post-void residual [105.5(49.3, 231.3) ml vs. 197.9(114.8, 284.8) ml], ( P<0.05). After excluding multicollinearity, patients were divided into two group mainly based on coordination, detrusor stability, and detrusor contractility through two-step clustering analysis: 98 patients in Group 1 and 76 patients in Group 2. The success rate was higher in Group 2 [82.9% (63/76) vs. 64.3% (63/98), P=0.006]. Compared with Group 1, Group 2 exhibited the following characteristics: higher proportion of storage symptoms [43.4% (33/76) vs. 14.3% (14/98)], sensitive bladder sensation [67.1% (51/76) vs. 26.5% (26/98)], detrusor overactivity [46.1% (35/76) vs. 3.1% (3/98)], normal detrusor contractility [43.4% (33/76) vs. 5.1% (5/98)], and detrusor-sphincter dyssynergia [38.2% (29/76) vs. 0] ( P all<0.05). Additionally, group 2 had lower post-void residual [69.0 (23.8, 136.6) ml and 197.9 (123.2, 287.4) ml] and smaller bladder capacity [(281.9±144.9) ml vs. (430.4±176.7) ml] ( P all<0.01). Conclusions:Patients with storage symptoms, low post-void residual, sensitive bladder sensation, detrusor overactivity, normal contractility, or detrusor-sphincter dyssynergia indicate a higher conversion rate to second stage, making them more suitable for SNM testing.

To investigate the differences in postoperative short-term complications and long-term prognosis of pancreatic cancer(PC) patients after total pancreatectomy(TP) and pancreaticoduodenectomy(PD).

Objective To investigate the predictive value of energy spectral CT radiomics on the prognosis of patients with color-ectal adenocarcinoma.Methods The clinical data and preoperative CT enhancement images of 140 patients with pathology confirmed colorectal adenocarcinoma were analyzed retrospectively.The patients were divided into a good prognosis group(n=60)and a poor prognosis group(n=80)based on the whether they had no tumor recurrence or metastasis and died from tumors within 2 years after operation.The region of interest(ROI)was drawn on the 70 keV enhancement images in CT venous phase,and all radiomics features were further extracted.All patients were randomly divided into a training set and a test set at a ratio of 6∶4,and the least absolute shrinkage and selection operator(LASSO)method was used to screen the radiomics features.The prognosis prediction models of colorectal adenocarcinoma patients were constructed by support vector machine(SVM)and extreme gradient boosting(XGBoost),respectively.The area under the curve(AUC)of receiver operating characteristic(ROC)curve was performed to analyze the predictive effective-ness of various models comprehensively.The AUC of models were verified by DeLong test.Results The differences in the energy spectral parameters including water concentration(WC),iodine concentration(IC),and Effective-Z(Eff-Z)in the venous phase were statistically significant between the two groups(P＜0.05).The AUC of the SVM model constructed from the radiomics features and the combination features were 0.82 and 0.93,with the accuracy of 0.77 and 0.88.Meanwhile,the AUC of the XGBoost model constructed from the radiomics features and the combination features were 0.90 and 0.98,with the accuracy of 0.86 and 0.93.The AUC,accuracy,sensitivity and specificity of the XGBoost model constructed from the combination of energy spectral CT parameters and radiomics features reached the optimal level,and the differences in AUC were statistically significant by DeLong test(P＜0.05).Conclusion Both the SVM and XGBoost models show higher value in preoperative prediction of prognosis of colorectal adenocarcinoma patients,and the combination model of radiomics features and energy spectral parameters(venous phase)has superior predictive effectiveness.

With the continuous development of China's economy,the people expect for higher quality medical services,and medical humanistic care is increasingly emphasized.Under this background,the"Duplex Linkage Mode",which integrates medical social workers and volunteers,has emerged.This paper reviews the current state of applying the mode in China,ex-pounds its benefits,and details its application within hospital services.This application covers guidance for outpatient and emer-gency department,inpatient ward services,hospice care,and community residents volunteer services.In addition,this paper proposes suggestions on furth for optimizing recruitment and training programs,improving management systems,establishing intel-ligent management systems,and improving volunteer support mechanisms.These measures aim to promote the sustainable and healthy development of medical humanistic services and to support the implementation of the Healthy China Initiative.

Objective To observe the effects of exercise combined with probiotic intervention on glycolipid metabolism,oxidative stress,and skeletal muscle satellite cell expression in type 2 diabetic rats.Methods From 60 8-week-old SPF-grade SD male rats,10 rats were randomly selected as the normal control group(NC),and the rest were injected intraperitoneally with streptozotocin,establishing a rat model of type 2 diabetes mellitus.The diabetic rats were randomly divided into model(TN),exercise+diabetes(YTN),probiotic+diabetes(GTN),and exercise+probiotics+diabetes(YGTN)groups.The exercise groups were subjected to 6 weeks of incremental load aerobic treadmill exercise(speed of 15 m/min for 30 min in week 1,15 m/min for 60 min in week 2,and 19.3 m/min for 60 min in weeks 3～6,with continuous training until week 6,5 days/week).The GTN and YGTN groups were administered 10.0 mL/(kg·d)of Lactibiane Iki probiotic solution(concentration of 107 CFU/mL)one hour before training.Glycolipid metabolism indexes,oxidative stress indexes,and expression of skeletal muscle satellite cell proteins were measured in rats.Results(1)The levels of fasting plasma glucose(FBG),fasting serum insulin(FINS),hemoglobin Alc(HBA1C)and(homeostasis model assessment-insulin resistance index(HOMA-1R)were higher in the TN,YTN,GTN,and YGTN groups than in the NC group(P＜0.01).The levels of FBG in the YGTN group were lower than those in the TN,YTN,GTN,and YGTN groups(P＜0.05).Serum FINS levels in YTN,GTN and YGTN groups were all decreased compared with those in the TN group(P＜0.01).Serum HBA1C levels were lower in the YGTN group than the TN,YTN,and GTN groups(P＜0.01).The HOMA-IR indices of rats in the YGTN group decreased more significantly compared with those in the TN,YTN,and GTN groups(P＜0.01).The result showed that FBG,FINS,HBA1C,and HOMA-IR decreased more significantly in rats in the aerobic exercise combined with probiotic intervention group than the other intervention groups.(2)Serum total cholesterol(T-CHO),triglyceride(TG),low density lipoprotein cholesterol(LDL)and free fatty acid(FFA)levels in the TN group were higher than those in the NC group(P＜0.05),and those of the YGTN group were lower than those of the TN group(P＜0.05)and basically restored to the level of the NC group.Serum high density lipoprotein cholesterol(HDL)levels were lower in the TN group than the NC group(P＜0.05),Serum HDL levels of rats in TN group were lower than those of the NC group(P＜0.05),and those in the YGTN group were higher than those of TN group(P＜0.05),which were basically restored to the level of NC group.The result showed that aerobic exercise combined with probiotic intervention reduced serum T-CHO,TG,LDL,FFA levels and increased HDL levels more significantly than other interventions in diabetic rats.(3)Serum malondialdehyde(MDA)and 8-iso-prostaglandin F2α(8-isoPGF2α)levels of rats in the TN group were higher than those in the NC group(P＜0.05 or P＜0.01),and those of rats in the YGTN group were lower than those in the TN group(P＜0.05 or P＜0.01).Serum catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)in the TN group were lower than those in the NC group(P＜0.01),and those of rats in the YGTN group were higher than those of the NC group(P＜0.01)and were basically restored to the levels of NC group.(4)The protein expression levels of paired box gene 7(Pax7),myogenic determination gene(MyoD),myogenin(MyoG)and myogenic factor 5(Myf5)in the skeletal muscle of rats in the TN group were lower than those in the NC group(P＜0.05 or P＜0.01),and these levels were higher in the YGTN group than the TN group(P＜0.05 or P＜0.01);basically,the levels were restored to those of the NC group.In the TN group,myostatin(MSTN)protein expression was higher in the TN group than the NC group(P＜0.05),and that in the YGTN group was lower than that in the TN group(P＜0.05)and basically restored to the level of the NC group.Conclusions The result showed that probiotics and aerobic exercise had a synergistic effect in improving blood glucose and insulin levels,attenuating insulin resistance,improving lipids and oxidative radicals,and preventing the phenomenon of disturbed glucose metabolism,thus achieving dynamic equilibrium regulation in type 2 diabetic rats.Aerobic exercise combined with probiotics also promoted myoblast differentiation,which played a role in preventing T2DM-induced loss of muscle mass and strength as well as muscle tissue complications.

Objective To understand the testing performance of drug manufacturers and testing institute in Yunnan province by organizing proficiency testing of microbiological examination of non-sterile drugs,and to improve the testing performance and quality management level of participants by interpretation of unsatisfactory results.Methods According to the requirements of relevant China National Accreditation Service for Conformity Assessment (CNAS),preparation values of positive or negative was determined as assigned values for qualitative items,and the median value was as assigned value for enumeration items.Using robust statistical methods and Z-score for assessment,if all the 4 items were satisfactory,it would be assessed as overall satisfactory performance,and contrariwise,it would be assessed as unsatisfactory performance.If partial item were satisfactory,it would be assessed as partially satisfactory performance.Results 152 laboratories participated in this proficiency testing program,116 laboratories obtained satisfactory performance and the satisfactory rate was 76.31％;33 laboratories obtained partially satisfactory performance,and the partially satisfactory rate was 21.71％;3 laboratories obtained unsatisfactory performance and the unsatisfactory rate was 1.97％.To classify the participants with type,the satisfactory rate for drug control institute was 88.23％ and the satisfactory rate of drug manufacturers was 74.81％.Conclusion The testing performance of participating laboratories in microbiological examination of non-sterile drugs is generally good,which can ensure the smooth implementation of the program and the accuracy and effectiveness of the results.The testing capacity and quality management level of a few laboratories need to be improved.