Family with sequence similarity 3 member A(FAM3A),a novel mitochondrial protein,plays a pivotal role in hepatic glucose and lipid metabolism by enhancing ATP synthesis and secretion and mod-ulating the ATP-P2 receptor-Akt signaling pathway.Dysregulation of FAM3A is closely associated with the pathogenesis of non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM).In this study,targeting FAM3A as a therapeutic candidate,we conducted virtual screening to identify 47 small-molecule compounds with potential binding activity.Surface plasmon resonance(SPR)analysis re-vealed three compounds exhibiting high binding affinity to FAM3 A.Further structural characterization of the FAM3A-compound complexes,combined with intermolecular interaction analysis,elucidated the binding mode of the lead compound Index 2(taxifolin)to FAM3A at atomic resolution.These findings provide critical insights into the molecular mechanisms underlying ligand-FAM3A interactions and deliver valuable chemical scaffolds for the development of therapeutics targeting NAFLD and T2DM.This work establishes a foundation for advancing drug discovery efforts focused on FAM3A-mediated metabolic disor-ders.

Objective To investigate the mechanism of hippocampal neuronal plasticity of newborn neurons in the hippocampus by which exercise improves the fear and anxiety symptoms of post-traumatic stress disorder(PTSD).Methods Totally 40 C57BL/6J male mice were randomly divided into by control group(Ctrl)and PTSD group,the PTSD group was divided into a no-exercise group(PTSD),a low-intensity exercise group(L)and a high-intensity exercise group(H).The PTSD model mice were constructed by combining conditioned plantar-foot shock(CF)and single-session sustained stress(SPS).After the exercise intervention,the fear and anxiety levels of the mice were assessed using the conditioned fear test and the elevated cross maze test;Subsequently,the densities of the newborn mature neurons in dentate gyrus(DG)of hippocampus were detected by immunofluorescent double-labelling staining,and the newborn neuron morphology was marked by injecting retrovirus pRetro-U6-EF1-EGFP-3xFLAG-WPRE in DG of hippocampus to observe its morphology.The morphology of the newborn neurons was labelled to observe their dendritic length and the number of branch points;Meanwhile,the concentration level of adiponctin(APN)in the hippocampal area was determined by ELISA.Results The result showed that both high and low-intensity exercise interventions significantly reduced the freezing time of PTSD mice in the conditioned fear test,and in the elevated cross maze experiment,the residence time and the number of entries in the open arm of the mice in the H group increased significantly compared with those in the PTSD group,while the residence time and the number of entries in the closed arm were significantly reduced.In addition,both high and low-intensity exercise interventions significantly increased the surface density and dendritic length of newborn mature neurons in the hippocampal DG region of PTSD mice,and high-intensity exercise significantly increased the number of dendritic branching points,and the density of newborn mature neurons in the H group was more significantly increased compared with that in the L group.At the same time,the hippocampal APN concentration increased significantly in both L and H groups compared with the PTSD group,and it was more significant in the H group.Conclusion Exercises have an ameliorative effect on anxiety and fear symptoms in PTSD mice,and at the same time,it can increase hippocampal neuroplasticity and adiponctin secretion in PTSD mice,suggesting that the improvement of fear and anxiety symptoms in PTSD by exercise may be related to the increase of hippocampal neuroplasticity and APN secretion,and the improvement effect is better with high-intensity exercise.

Family with sequence similarity 3 member A(FAM3A),a novel mitochondrial protein,plays a pivotal role in hepatic glucose and lipid metabolism by enhancing ATP synthesis and secretion and mod-ulating the ATP-P2 receptor-Akt signaling pathway.Dysregulation of FAM3A is closely associated with the pathogenesis of non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM).In this study,targeting FAM3A as a therapeutic candidate,we conducted virtual screening to identify 47 small-molecule compounds with potential binding activity.Surface plasmon resonance(SPR)analysis re-vealed three compounds exhibiting high binding affinity to FAM3 A.Further structural characterization of the FAM3A-compound complexes,combined with intermolecular interaction analysis,elucidated the binding mode of the lead compound Index 2(taxifolin)to FAM3A at atomic resolution.These findings provide critical insights into the molecular mechanisms underlying ligand-FAM3A interactions and deliver valuable chemical scaffolds for the development of therapeutics targeting NAFLD and T2DM.This work establishes a foundation for advancing drug discovery efforts focused on FAM3A-mediated metabolic disor-ders.

Objective To explore the construction and verification of the classification model for the five properties of traditional Chinese medicine:warm,cool,cold,hot,and neutral.Methods Urine samples of mice after taking Chinese medicine of different properties were selected as research objects,and Raman spectroscopy-related technology was used for detection.The obtained data set was classified into training set and test set,and the classification model was constructed using four machine learning methods:random forest,extreme gradient boosting,support vector machine,and logistic regression.The model performance was evaluated using precision,recall,F1 score,and accuracy.Results A total of 4 888 sets of spectra were collected in this study,of which 80%,totaling 3 910 sets of spectral data,were used to build the model,and the remaining 20%,totaling 978 sets of spectral data,were used to test model performance.The accuracy of the random forest model was 92%,the extreme gradient boosting model was 87%,the support vector machine model was 83%,and the logistic regression model was 75%.The Raman shifts with the highest classification weights were 872,1 012,1 108,1 190 and 1 668 cm-1.Conclusion Raman spectroscopy combined with machine learning algorithms can be used to classify the five medicinal properties of traditional Chinese medicine,among which the random forest model has the best effect.

OBJECTIVES: To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy. METHODS: Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined；with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm. RESULTS: Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039). CONCLUSIONS Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.
Humans ; Electroacupuncture ; Acupuncture Therapy ; Acupuncture Points ; Diabetes Mellitus, Type 2/therapy* ; Glycated Hemoglobin ; Cognitive Dysfunction/therapy* ; Cholesterol ; gamma-Aminobutyric Acid

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.
Male ; Adult ; Humans ; Prognosis ; Retrospective Studies ; Myeloid Differentiation Factor 88 ; China/epidemiology* ; Testicular Neoplasms/drug therapy* ; Cyclophosphamide ; Rituximab/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Prednisone/therapeutic use* ; Doxorubicin/therapeutic use* ; Vincristine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Immediate-Early Proteins/therapeutic use* ; Tumor Suppressor Proteins

Objective: To explore the relationship between obesity status and death stratified by different multi-morbidity status in older adults in China. Methods: Data for older Chinese adults aged ≥65 years were from Chinese Longitudinal Healthy Longevity Survey (CLHLS). Multi-morbidity patterns based on 13 chronic conditions were explored using exploratory factor analysis. Cox models were used to examine relationships between obesity status and death stratified by disease count and multi-morbidity patterns at baseline, respectively. Besides, obesity status was defined by baseline body mass index and waist circumference. Results: A total of 6 272 participants were included in the analyses. Multi-morbidity including cardio-metabolic, sensory perception and other patterns were identified. For those without any chronic condition, compared with those without central obesity, central obesity was associated with a higher risk for death (HR=1.66, 95%CI:1.04-2.66). For those only with one chronic condition, compared with normal weight, underweight was associated with a higher risk for death (HR=1.41, 95%CI: 1.10-1.80). For those with multi-morbidity, compared with normal weight, underweight increased the risk for death (HR=1.19, 95%CI:1.05-1.34). Compared with those without central obesity, central obesity decreased the risk for death (HR=0.88, 95%CI:0.78-0.99). Conclusions: Relationships between obesity status and death varied by multi-morbidity status in older adults in China. Underweight and non-central obesity were associated with increased risks for death in older adults with only one chronic disease or multi-morbidity. Therefore, it is necessary to pay attention to multi-morbidity status in the management of obesity in older adults and provide effective targeted body weight management plan.
Aged ; China/epidemiology* ; Humans ; Middle Aged ; Multimorbidity ; Obesity/epidemiology* ; Risk Factors ; Waist Circumference

Pyroptosis is a pro-inflammatory programmed cell death, and its role in cardiac inflammatory response has become a hot topic. The activation of nucleotide binding oligomerization domain like receptor protein 3(NLRP3) inflammasome is an important mechanism for pyroptosis induced by cysteinyl aspartate specific proteinase 1(caspase-1). The existing studies have shown that cardiomyocyte pyroptosis participates in the pathogenesis of different cardiovascular diseases and the NLRP3 inflammasome-mediated cardiomyocyte pyroptosis has been most widely studied. Also, the intervention in NLRP3 inflammasome activation and cardiomyocyte pyroptosis contributes to ameliorating myocardial injury, which may be the main mechanism of many traditional Chinese medicines in exerting the cardio-protective effects. Therefore, this paper reviewed the studies on cardiomyocyte pyroptosis mediated by NLRP3 inflammasome and put forward the importance of exploring traditional Chinese medicine intervention in the activation of NLRP3 inflammasome.
Inflammasomes ; Medicine, Chinese Traditional ; Myocytes, Cardiac ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Pyroptosis

Objective To observe effects of Heyutai Fuzhu Jiangtang Tablets combined with metformin in insulin resistance (IR); To discuss its mechanism of action. Methods 6–7 week old male ZDF (fa/fa) rats were randomly divided into model group,metformin group,Heyutai Fuzhu Jiangtang Tablets group(Jiangtang Tablets group),and metformin combined with Heyutai Fuzhu Jiangtang Tablets group.ZDF(fa/+)rats were chosen as normal group.Each medication group was given relevant medicine for gavage for 6 weeks. Body weight, FBG, TG, TC, FFA, FINS, HOMA-IR, OGTT and HE staining were tested. HE staining was used to observe the pathological changes of skeletal muscle. RT-PCR and Western blot were used to detect skeletal muscle corresponding gene and protein expression. Results Compared with Jiangtang Tablets group and metformin group, TC, FFA, FBG, and HOMA-IR in metformin combined with Heyutai Fuzhu Jiangtang Tablets group decreased significantly (P<0.05, P<0.01). Blood glucose level and AUC significantly decreased at each time point in OGTT. HE staining of skeletal muscle fibers arranged in order; nucleus increased and internal movement was not significant, without obvious infiltration of inflammatory cells. Expressions of skeletal muscle InsR, Akt, and Glut4 mRNA expression increased (P<0.05, P<0.01). Expressions of skeletal muscle p-InsR, p-Akt, and Glut4 protein expression increased (P<0.05, P<0.01). Conclusion Heyutai Fuzhu Jiangtang Tablets combined with metformin can improve IR in type 2 diabetic rats, and the effect is better than single-application.

Objective To study the pharmacokinetics of amlodipine besylate and folic acid tablet in Chinese healthy volunteers.Methods A single administration of two tests and one reference formulation was given to 24 healthy volunteers by oral according to a self -control, three periods, Latin square design study.The concentrations of amlodipine were determined by LC-MS/MS method.Results The main pharma-cokinetic parameters of amlodipine were as follows: AUC0-t were (115.30 ±28.12),(119.42 ±32.80),(113.19 ±27.08) ng · mL-1 · h;Cmax were (2.59 ±0.60), (2.59 ±0.50), (2.56 ±0.59) ng· mL-1;t1/2 were(38.90 ±9.27), (33.85 ±11.31),(40.66 ±7.05) h for two test and one reference formulation, respectively.Conclusion There is no significant difference between the main pharmacokinetic parameters of three formulations.