Constipation,a common functional gastrointestinal disorder,not only severely impairs patients'quality of life but is also highly comorbid with psychiatric conditions such as anxiety and depression.Emerging evidence indicates that gut microbiota dysbiosis is a critical link connecting these two disease states.On one hand,dysbiosis exacerbates constipation by affecting host metabolism and intestinal function;on the other,it plays a central role in the pathophysiology of mood disorders.This complex interaction is primarily mediated through the"microbiota-gut-brain axis."Therefore,elucidating the intrinsic relationship among anxiety,depression,gut microbiota,and constipation has become a frontier of interdisciplinary research.

Constipation,a common functional gastrointestinal disorder,not only severely impairs patients'quality of life but is also highly comorbid with psychiatric conditions such as anxiety and depression.Emerging evidence indicates that gut microbiota dysbiosis is a critical link connecting these two disease states.On one hand,dysbiosis exacerbates constipation by affecting host metabolism and intestinal function;on the other,it plays a central role in the pathophysiology of mood disorders.This complex interaction is primarily mediated through the"microbiota-gut-brain axis."Therefore,elucidating the intrinsic relationship among anxiety,depression,gut microbiota,and constipation has become a frontier of interdisciplinary research.

OBJECTIVE To evaluate the ameliorative effect of Juanbi Tongluo Oral Liquid on sciatic neuronal apoptosis in Type 2 diabetic model mice.METHODS The Type 2 diabetes mouse model was established by feeding with high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin(STZ).The mice were treated with metformin(200 mg·kg-1·d-1),low dose(3.9 g·kg-1·d-1)and high dose(7.8 g·kg-1·d-1)Juanbi Tongluo Oral Liquid for 35 days.The latency of response to thermal stimu-lation was detected by hot plate,and the values of blood glucose insulin and glycosylated hemoglobin were determined.Biochemical kits were used to detect the expression of serum total cholesterol(T-CHO),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and oxidation product malondialdehyde(MDA).The expression of tumor cytokine α(TNF-α),interleukin(IL)-1β,IL-6 and IL-10 in serum of mice were detected by ELISA method;the injury of sciatic nerve of model mice was detected by HE staining;the apoptosis of sciatic nerve was detected by TUNEL method;and the expression of neurofilament protein NF-L,apoptosis(cleaved Caspase-3,Caspase-3)and oxidative stress(Nrf2,HO-1)signal pathway proteins in sciatic nerve of model mice were detected by Western blot method.RESULTS High-dose Juanbi Tongluo Oral Liquid shortened the latent period of heat pain response in model mice(P<0.01);downregulated fasting blood glucose and glycated hemoglobin(P<0.01),and upregulated fasting plasma insulin in model mice(P<0.01);downregulated serum T-CHO,TG,and LDL-C levels(P<0.01),upregulated HDL-C levels(P<0.01);downregulated serum pro-inflammatory factors TNF-α,IL-1β and IL-6 levels(P<0.05),upregulated the anti-inflammatory cyto-kine IL-10 level(P<0.01);inhibited sciatic nerve structural damage and apoptosis(P<0.05);downregulated the ratio of cleaved Caspase-3 to Caspase-3 in the apoptosis pathway(P<0.01);upregulated the expression of neurofilament proteins NF-L and NF-H in sciatic nerve tissue(P<0.05,P<0.01);and upregulated the expression of antioxidant stress proteins Nrf2 and HO-1(P<0.01).CONCLUSION Juanbi Tongluo Oral Liquid can improve sciatic neuronal apoptosis of Type 2 diabetic mice,which may be related to its effect on improving oxidative stress and inflammatory stress.

Objective To investigate the dynamic expression and significance of B cell lymphoma (Bcl) 6 in fibroblast-like synoviocytes (FLS) induced osteoclast differentiation and activation in rheumatoid arthritis (RA) patients.Methods RA-FLS were co-cultured with peripheral blood monocytes (PBMCs) from healthy volunteers in the medium containing M-CSF.Bcl6 protein and mRNA in osteoclasts and their precursors were determined by immunofluorescence and Real-time PCR at day 0,7,14 and 21,respectively.Osteoclasts were identified by tartrate-resistant acid phosphatase (TRAP) staining.Bone resorption activity of osteoclasts was determined by bone slices stained with toluidine blue.Kruskal-Wallis H and Bonferroni were used for statistical analysis.Results ① Immunofluorescence staining and TRAP staining showed that Bcl6 protein was mainly expressed in the nuclei of PBMCs.After co-cultured with RA-FLS for 7 days,some PBMCs differentiated into macrophages and a few differentiated to TRAP-positive multinucleated osteoclasts,and the total Bcl6 protein expression in osteoclasts and their precursors were increased.At day 14,the total Bcl6 protein expression was increased further.At day 21,the Bcl6 protein expression in nuclei of osteoclasts was decreased while PBMCs were differentiated into osteoclasts,and total Bcl6 protein expression was decreased.②Real-time PCR showed that Bcl6 mRNA expression in osteoclasts and their precursors at day 7 tended to increase than that at day 0 (x2=3.429,P＞0.05).At day 14 after co-cultured with RA-FLS,Bcl6 mRNA expression in osteoclasts and their precursors was significantly higher than that at day 0 (x2=5.333,P=0.045).At day 21,the expression of Bcl6 mRNA was significantly lower than that at day 14 (x2=6.023,P=0.038).Conclusion Bcl6 may be involved in osteoclast differentiation and activation,and may play a role in the inflammatory status in the process of differentiation from PBMCs to macrophages.Further studies are needed to establish the mechanisms.

OBJECTIVETo observe the changes in the expressions of somatomedins in the prostate epithelial cells in anoxic condition.

METHODSWe cultured prostate epithelial cell line RWPE-1 in vitro. At 4, 8, 12, 24, 48 hours after seeding of the cells, we determined the gene and protein expressions of the epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in the prostate epithelial cells by RT-PCR and ELISA, respectively.

RESULTSWith the increase of time, the expressions of the EGF, bFGF, TGF-beta, IGF-1 and VEGF genes were obviously up-regulated, more significantly in the anoxic than in the normoxic prostate epithelial cells. Take FGF mRNA, its expression level was 0.14 +/- 0.01 in the anoxic and 0. 12 +/- 0.01 in the normoxic prostate epithelial cells at 8 hours (P = 0.01), but increased to 0.29 +/- 0.01 and 0.14 +/- 0.01, respectively, at 48 hours (P < 0.001). The expression of the TGF-beta protein was also more significantly increased in the anoxic than in the normoxic prostate epithelial cells, 0.32 +/- 0.01 versus 0.26 +/- 0.01 at 4 hours (P = 0.017) and 1.56 +/- 0.13 versus 0.87 +/- 0.06 at 48 hours (P < 0.001). The other 4 somatomedins showed no significant differences in their protein expressions between anoxic and normoxic conditions.

CONCLUSIONAnoxia can up-regulate the gene expressions of somatomedins and increase the secretion of TGF-beta in prostate epithelial cells.

Cell Hypoxia ; Cell Line ; Epithelial Cells ; metabolism ; Gene Expression Regulation ; Humans ; Male ; Prostate ; cytology ; Somatomedins ; metabolism ; Transforming Growth Factor beta ; metabolism ; Up-Regulation

Objective To explore the feasibility of team-based learning (TBL) for practice teaching of internal medicine.Methods TBL was carried out in 40 interns from clinical medical students of eight-year program.Every team included 4 ～ 5 members.The course of rheumatoid arthritis was chosen according to the course syllabus.Results The students discussed enthusiastically in the team test and in-class application exercises.More than 80％ of the students expressed that TBL was helpful to understand the course content better,to learn the disease better,to elevate personal study ability and to know others' thought processes.76％ of the students supported to carrry out TBL again.Conclusions TBL is helpful for senior medical students to elevate their ability of applying course concepts to solve practical problems through a series of team activities.Improvement of teaching idea and skill is the key to perform TBL successfully.

Aged ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Carcinoma, Large Cell ; metabolism ; pathology ; Diagnosis, Differential ; Histiocytic Sarcoma ; metabolism ; pathology ; surgery ; Hodgkin Disease ; metabolism ; pathology ; Humans ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Male ; Melanoma ; metabolism ; pathology ; Receptors, Cell Surface ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; surgery

ObjectiveTo investigate the effect of rosiglitazone (RSG), a high-affinity synthetic agonist for PPAR-γ, on the expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG)in rheumatoid arthritis fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms. MethodsRAFLS were incubated with different concentrations of RSG(0, 5, 10, 15, and 20 μmol/L) for 3 days, RAFLS proliferation was detected by Cell Counting Kit-8 assay, and then the expression of RANKL and OPG was examined by real-time PCR and Western blot. The expression of phosphorylated ERK, p38 and JNK was also detected after RA-FLS was incubated with RSG(0, 15, and 20 μmol/L) for 3 days. One-way ANOVA and Bonferroni were used for statistical analysis. ResultsRSG (5, 10, 15, and 20 μmol/L) had significantly inhibited the expression of RANKL mRNA(0.503±0.005, 0.438±0.031, 0.161±0.042, 0.050±0.018) and protein (1.72±0.09, 1.58x±0.05, 1.46±0.11, 1.22x±0.14) in RA-FLS (F=200.820, F=13.602, P＜0.01 ), while the expression of OPG mRNA (2.8 ±0.5, 7.0 ±3.2, 8.4 ±2.3, 25.7 ±5.1 ) and protein ( 1.21 ±0.11, 1.52 ±0.16, 1.63±0.11, 1.91 ±0.03) increased significantly (F=26.531, F=24.872, P＜0.01), both in a dose dependent manner. The ratio of RANKL/OPG mRNA and protein significantly reduced (F=453.425, P＜0.01 ;F=4.173, P＜0.05 ). RSG (15, 20 μ mol/L) significantly inhibited the expression of p-ERK-1/2 protein (0.55±0.06, 0.45±0.06, F=6.991, P＜0.05). ConclusionRSG can inhibit RANKL expression in RA-FLS through p-ERK pathway.

Objective To evaluate the value of plasma ProGRP,CYFRA 21-1 and CEA in patiens with lung cancer.Methods The levels of plasma ProGRP,CYFRA 21-1 and CEA were detected in 85 healthy control,49 benign lung diseases and 143 lung neoplasms.The levels of ProGRP in the patients with SCLC was monitored.Results The level of plasma ProGRP in SCLC ( M 179.1 ng/ml) was significantly higher than adenocarcinoma ( M 35.3 ng/ml),squamous-cell carcinoma ( M 33.3 ng/ml),healthy control (M 35.6 ng/m)and benign lung diseases (M 33.3ng/m ),P ＜ 0.001.The sensitivity and specificity for diagnosing SCLC by ProGRP were 60.6％ and 95.0％ respectively.In the effective treatment group,ProGRP reduced 45.9％,in the progression group,ProGRP increased 103.1％,P ＜ 0.05.The level of CEA in the metastatic adenocarcinoma (M 10.22 ng/ml ) was significantly higher than non-metastatic adenocarcinoma ( M 3.85ng/ml) and squamous cell carcinoma ( M 2.56 ng/ml) ( P ＜ 0.01 ).Conclusion The plasma ProGRP is a good indicator for diagnosing and evaluating cure effect in SCLC; the high expression of CEA is related to the metastatic adenocarcinoma.

OBJECTIVETo explore the clinical value of determination of ATP levels in CD4(+) cells of patients with cytomegaloviral pneumonia after kidney transplantation.

METHODSTwenty-eight patients with cytomegaloviral pneumonia following kidney transplantation and 30 healthy volunteers were enrolled in this study. ATP-bioluminescence assay (ATP-CVA) was used to assess the immune response of CD4(+) cells to phytohemagglutinin (PHA) stimulation in the normal volunteers and the recipients (before and at 1, 2, and 4 weeks after renal transplantation, before and at 2 and 4 week after the treatment).

RESULTSATP concentration in CD4(+) cells of the recipients was 402-/+58 ng/ml before the operation, significantly lower than that in normal volunteers (458-/+196 ng/ml, P<0.05), and reached the lowest level in the first week after operation especially in the recipients with antibody-inducing therapy; ATP level increased slowly since week 2 post-operation, but still remained significantly lower than the preoperative by the fourth week (266-/+87 ng/ml, P<0.05), especially in the recipients receiving antibody-inducing therapy. In the event of cytomegaloviral pneumonia, ATP level underwent a mild reduction to 152-/+78 ng/ml in comparison with the postoperative level at the first week (P>0.05), and was significantly lower than preoperative level (P<0.01); the decrease was especially obvious during the exacerbation of the condition. ATP level then increased slowly after effective treatment, but was still lower than the preoperative level at 4 weeks after the operation (336-/+92 ng/ml, P<0.05).

CONCLUSIONThe determination of ATP level in CD4(+) cells allows more accurate assessment of the cellular immunity in the renal transplant recipients with cytomegaloviral pneumonia to help in the clinical treatment of the patients.

Adenosine Triphosphate ; blood ; Adult ; Aged ; CD4-Positive T-Lymphocytes ; metabolism ; Case-Control Studies ; Cytomegalovirus Infections ; immunology ; Female ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Pneumonia, Viral ; immunology ; metabolism ; virology ; Postoperative Complications ; immunology ; metabolism ; Young Adult