Diabetic nephropathy( DN) is one of the main manifestations of diabetic microvascular dis?ease,and it is a major factor in the death of diabetes.At present,the treatment of DN is mainly focused on the control of high blood sugar and high blood pressure.Although angiotensin converting enzyme inhibitors and angio?tensin II receptor antagonists can slow the progression of DN,there were a lot of patients deteriorate to renal fail?ure.The role of vitamin B supplementation in preventing microvascular complications of diabetes has already been a focus of research for some years.In this paper,the role of B vitamins in the pathogenesis of diabetes mellitus and DN,effect of vitamin B supplementation on treatment in DN were discussed.

Isolated freshly rat islets were transferred to 24-well plates and incubated with different concentrations of glucose or resveratrol for 1 or 24 h.The results showed that resveratrol dose-dependently inhibited glucose-stimulated insulin secretion from isolated rat islets after 1 h incubation,with 10%,35%,and 80% (P<0.05 or P<0.01) decrease at the concentrations of 1,I0,and 100 μmol/L.10 μmol/L resveratrol decreased the intracellular calcium concentration by 60% (P<0.05).After incubation for 24 h,resveratrol increased palmitatesuppressed insulin secretion to 75% (P<0.01) of control.These results suggest that resveratrol acutely inhibits insulin secretion from primary pancreatic islet via regulating intracellular calcium ion concentration,and in the long run resveratrol may protect β-cells from lipotoxicity.

Objective To investigate the effects of abdominal tuina on the expression of PI3K and N-methyl-D-aspartate receptor(NMDAR)subunit NR1 in spinal dorsal horn and the morphology of spinal dorsal horn neurons in ulcerative colitis(UC)rats;To explore its mechanism of action in treating UC.Methods Totally 36 SD rats were randomly divided into normal group,model group,abdominal tuina group,mesalazine group,PI3K stimulation group and PI3K stimulation + abdominal tuina group,with 6 rats in each group.The UC model in rats was simulated by drinking dextran sulfate solution freely.The abdominal tuina group and the PI3K stimulation + abdominal tuina group were given abdominal tuina intervention,the mesalazine group was given mesalazine solution for gavage,and the PI3K stimulation group and PI3K stimulation + abdominal tuina group were given intrathecal injection of PI3K agonist,once a day,for consecutive 15 days.Abdominal withdrawal reflex(AWR)score and acetic acid twist were used to observe the abdominal pain symptoms in rats.The expression of PI3K and NR1 in spinal dorsal horn were detected by immunofluorescence staining and Western blot,and the morphological changes of spinal dorsal horn neurons were observed by Nissl staining.Results Compared with the normal group,AWR score and twisting times of rats in model group significantly increased(P<0.01),the expression of PI3K and NR1 protein in spinal dorsal horn significantly increased(P<0.05,P<0.01),the morphology of spinal dorsal horn neurons was disordered,forming a large number of vacuolar like structures,and the Nissl body structure was fuzzy and incomplete.Compared with the model group,AWR scores and twisting times of abdominal tuina group and mesalazine group significantly decreased(P<0.05,P<0.01),and the expression of PI3K and NR1 protein significantly decreased(P<0.05,P<0.01),the edema of spinal dorsal horn neurons was milder,with fewer vacuolar changes and an increase in the number of Nissl bodies;AWR scores and twisting times of PI3K stimulation group and PI3K stimulation + abdominal tuina group significantly increased(P<0.05,P<0.01),and the expressions of PI3K and NR1 protein increased(P<0.05,P<0.01),a large number of neurons underwent pyknosis and necrosis,and the number of Nissl bodies decreased,even dissolving and disappearing.Conclusion Abdominal tuina can effectively improve the symptoms of abdominal pain in UC model rats,and its mechanism may be related to inhibiting the expression of PI3K and NR1 in spinal dorsal horn and improving the morphology of spinal dorsal horn neurons.

Objective: To investigate the analgesic mechanism of Tuina (Chinese therapeutic massage) by observing the effect of the N-methyl-D-aspartate receptor subunit 2B (NR2B)/postsynaptic density-95 (PSD-95) pathway on the dendritic structure of spinal cord dorsal horn in rats with lumbar disc herniation. Methods: Fifty Sprague-Dawley rats were randomly divided into a blank group, a model group, a Tuina group, a blocker agent group, and a blocker agent + Tuina group. The sciatic nerve chronic constriction injury (CCI) model was prepared by the sciatic nerve ligation method. From the 4th day after modeling, rats in the Tuina group and the blocker agent + Tuina group were subject to daily Tuina intervention, and those in the blocker agent group and the blocker agent + Tuina group were daily intrathecally injected with NR2B blocker agent (MK-801). The spontaneous pain score was used to observe the pain behavior of all rats. The expression levels of NR2B and downstream PSD-95 were measured by immunohistochemistry, and the dendritic structure changes were observed by Golgi staining for rat spinal cord dorsal horn after 14 d of continuous intervention. Results: Compared with the blank group, the degree of rat spontaneous pain after CCI was elevated in both the model and the Tuina groups (P<0.01) and was reduced in the Tuina group after the Tuina intervention compared with the model group (P<0.05). Compared with the model group, the rat spontaneous pain level after blocking NR2B was reduced in both the blocker agent group and the blocker agent + Tuina group (P<0.05). The NR2B and PSD-95 protein levels were significantly higher in the model group compared with the blank group (P<0.01); the total number of dendritic branches was increased (P<0.01), and the total dendritic length became longer (P<0.01) in the spinal cord dorsal horn. The rat NR2B and PSD-95 protein levels were significantly decreased in the Tuina group compared with the model group (P<0.01); the total dendritic branch number was reduced (P<0.01) and the total length was shortened (P<0.01) in the spinal cord dorsal horn. After blocking NR2B, the expression levels of NR2B and downstream PSD-95 protein were significantly lower in both the blocker agent group and the blocker agent + Tuina group compared to the model group (P<0.01). The total branch number was significantly reduced (P<0.01), and the total length was significantly shortened (P<0.01) of the dendrites in the spinal cord dorsal horn. Conclusion: Tuina may exert an analgesic effect by remodeling the dendritic structure in the spinal cord dorsal horn in rats with lumbar disc herniation, and its mechanism may be related to the inhibition of NR2B/PSD-95 signaling pathway.

The effect of troglitazone on glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells and its mechanism were investigated.10 μmol/L troglitazone had no effect on basal insulin secretion,but significantly decreased GSIS and stimulated AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylations (all P<0.01).These reactions were completely reversed by AMPK inhibitor compound C,suggesting that the troglitazone acutely inhibits insulin secretion via stimulating AMPK activity in beta cells.

Objective To assess the myocardial blood flow and reserve function by rest and stress 13 N-NH3 PET myocardial perfusion imaging ( MPI) , and evaluate the diagnostic value of PET and risk fac-tors of non-obstructive coronary microvascular disease ( CMVD) type 1. Methods A total of 56 patients (28 males, 28 females;age:(52.0±7.6) years) with clinical suspected CMVD type 1 from April 2017 to December 2018 were prospectively enrolled. The coronary CT angiography, coronary angiography and other clinical data were recorded. All patients underwent one-day rest and stress 13 N-NH3 PET MPI. Images were analyzed and the absolute myocardial blood flow ( MBF) and coronary flow reserve ( CFR) were obtained. Patients were divided into CMVD type 1 ( CMVD) group and non-CMVD group. The differences between 2 groups were analyzed by two-sample t test and logistic regression. Results Among 56 patients, 20 patients were diagnosed as CMVD type 1, and 36 patients were excluded as non-CMVD group. The proportion of smoking and diabetes in the CMVD group was significantly higher than that in the non-CMVD group (χ2 val-ues:9.433 and 4.114, both P<0.05). The stress MBF ((2.37±0.61) vs (3.83±1.25) ml·min-1·g-1;t=-4.807, P<0.001) and CFR (2.67±0.60 vs 3.81±0.96;t=-4.751, P<0.001) were lower in smokers than those in non-smokers, and the stress MBF was lower in diabetes patients than that in non-diabetes patients ((2.63±0.98) vs (3.62±1.28) ml·min-1·g-1;t=-2.758, P=0.008). Smoking might be the risk factor for lower stress MBF (odd ratio (OR)=0.310, 95％ CI:0.114-0.880) and lower CFR (OR=0.278, 95％ CI:0. 080-0.894), and diabetes might be the risk factor for lower stress MBF (OR=0.254, 95％ CI:0.073-0. 887) . Conclusions PET MPI can be used for the diagnosis of CMVD type 1. Smoking and diabetes are likely to be associated with the onset of CMVD type 1.

Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism.Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin,and intracellular lipid level was detected by oil red O and ELISA;RNA sequence screen-ing and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment;The effects of silencing ROBO3 on cellular lipid metabolism were explored,and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot.Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess.Further studies showed that the expression of the axon guidance factor receptor,ROBO3,increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process.Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages.Mechanistically,ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1,resulting in cholesterol accumulation in macrophages.Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs,which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.

Objective:To investigate the relationship of plasma cholinesterase (ChE) with triglyceride (TG) levels in newly diagnosed patients with type 2 diabetes (T2DM).Methods:Clinical data and biochemical parameters of 321 patients with newly diagnosed T2DM admitted to the Department of Endocrinology of People′s Hospital of Shanghai Putuo from January 2018 to June 2020 were retrospectively collected. The patients were classified into four groups based on the plasma ChE level: Q1group ( n=81, <6 915 U/L), Q2 group ( n=80, 6 916-8 268 U/L), Q3 group ( n=80, 8 269-9 578 U/L), and Q4 group ( n=80, ≥9 579 U/L). The correlation of plasma ChE with TG level was analyzed. Results:With the increased ChE level, TG level significantly increased ( P<0.001). Correlation analysis showed that ChE was positively correlated with body weight, body mass index (BMI), TG, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), uric acid (UA), alanine aminotransferase (ALT), aspartate aminotransferase (AST)( r=0.35, 0.39, 0.35, 0.31, 0.27, 0.24, 0.25, 0.11, P<0.05, P<0.01 or P<0.001)while negatively correlated with age, systolic blood pressure, blood urea nitrogen (BUN), creatinine, and glycated albumin (GA)( r=-0.46、-0.14、-0.20、-0.14、-0.21, P<0.05 or P<0.001). Multivariate stepwise regression analysis showed that ChE was an independent risk factor for TG ( β=0.270, P<0.001). Logistic Multivariate regression analysis showed that after adjustment for sex, age, body weight, hemoglobin, leukocytes, total protein, albumin, globulin, ALT, BUN, creatinine, uric acid, smoking history, drinking history, HbA 1C, GA, TC, and LDL-C, the risk of hypertriglyceridemia in Q4 was 6.024 folds higher than Q1 group ( P=0.011). With the TG (1.70 mmol/L) as cut-off value, the optimal cut-off point of the ChE was 7 801 U/L, as calculated by receiver operating characteristic(ROC) curve analysis of ChE and hypertriglyceridemia. Conclusions:ChE level is positively correlated with TG in newly diagnosed patients with T2DM.

Objective To investigate the prognostic value of rest gated myocardial perfusion SPECT imaging (GMPI) in male patients with ST-segment elevation myocardial infarction (STEMI).Methods Seventy male patients with acute STEMI were collected from July 2014 to December 2014.General infonnation including age,history of hypertension,diabetes and serum levels of NT-proBNP,cTnⅠ,hs-CRP were recorded.CAG and rest GMPI were performed to measure the LVEDV,LVESV,LVEF,and the percentage of myocardial perfusion defect size (PMPDS) was calculated.All patients were followed at least 180 d and the major cardiac events (MACE) were recorded.According to the follow-up results,patients were assigned to MACE group and non-MACE group,the prognostic value of PMPDS and NT-proBNP for MACE was analyzed by ROC curve.According to the cut-off value of PMPDS,patients were divided into 2 groups,and KaplanMeier survival curve were drawn.The data were analyzed by two-sample t test,Mann-Whitney u test,x2 test,Pearson correlation analysis and log-rank test.Results The PMPDS in STEMI patients was not correlated with cTnⅠ,hs-CRP,LVEDV and LVESV (all P＞0.05),while positively correlated with NT-proBNP (r=0.793,P＜0.05),and negatively correlated with LVEF (r=-0.609,P＜0.05).Between MACE group and non-MACE group,there was no statistical differences in age,history of hypertension,diabetes,serum levels of HDL-C,LDL-C,hs-CRP,cTnⅠ,LVEDV,LVESV,and LVEF (x2 values:0.21 and 0.37,z values:-1.0 and-1.2,t values:from-1.6 to 1.5;all P＞0.05).The PMPDS,NT-proBNP,and number of stenotic vessels were significantly different between the two groups (t =2.4,z values:-2.1 and-3.6;all P＜ 0.05).ROC curve analysis showed that the AUC of PMPDS was 0.700 with cut-off value of 14.06％,which was better than that of NT-proBNP (z=2.1,P＜0.05).When patients were separated according to the cut-off value of 14.06％,there were significant differences in MACE incidence rates between the two groups (P＜ 0.01).Conclusion Compared with NT-proBNP,PMPDS has a better prognostic value for predicting the MACE risk within 180 d in male STEMI patients,and can be used for the risk stratification of STEMI patients.

ObjectiveTo investigate the effect of icariin （ICA）-mediated vitamin D system on peripheral blood dendritic cells （DCs） and helper T cells 17 （Th17）/regulatory T cells （Treg） balance in myocardial remodeling model of Dahl salt-sensitive rats. MethodFifty SPF Dahl salt-sensitive rats were divided into model group， vitamin D group （3×10^-5 mg·kg^-1·d^-1）， and high-， medium-， and low-dose ICA groups （120， 60， 30 mg·kg^-1·d^-1）， and 10 Dahl salt-resistant rats were used as normal group. The myocardial remodeling model was established by feeding rats with a high-salt diet containing 8% NaCl. After six weeks of modeling， the normal group and the model group were given an equal volume of ultrapure water by gavage， and other groups were continuously administrated for six weeks. Cardiac echocardiography， hematoxylin-eosin （HE） staining， and Masson staining were used to observe the pathological changes in cardiac structure and fibrosis. The levels of serum 25（OH）D₃， B-type N-terminal pro-brain natriuretic peptide （NT-ProBNP）， interleukin （IL）-17， transforming growth factor （TGF）-β₁， IL-12， and IL-10 were detected by enzyme-linked immunosorbent assay （ELISA）. The phenotype of peripheral blood DCs and the ratio of Th17/Treg cells of rats were detected by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expressions of vitamin D receptor （VDR），1α-hydroxylase （CYP27B1）， and 24-hydroxylase （CYP24A1） in peripheral blood DCs of rats. ResultCompared with the control group， the rats in the model group had pathological changes such as disordered arrangement of myocardial cells and cytoplasmic hypertrophy and swelling. Myocardial collagen fibers proliferated significantly， and the arrangement of myocardial fibers was disordered. The levels of serum 25（OH）D₃ and IL-10 were significantly decreased， and the levels of serum IL-17， TGF-β₁， IL-6， IL-12， and NT-ProBNP were significantly increased （P<0.05）. The costimulatory molecules CD40， CD80， CD86， and MHC-Ⅱ were highly expressed in the peripheral blood DCs， and the expression of CD11 and CD11b was lower （P<0.05）. The proportion of Th17 cells in the peripheral blood was significantly increased， and the proportion of Treg cells was decreased. The ratio of Th17/Treg was increased （P<0.05）. The mRNA and protein expressions of CYP24A1 in peripheral blood DCs increased， and the mRNA and protein expressions of CYP27B1 and VDR decreased （P<0.05）. Compared with the model group， the arrangement of myocardial fibers in each drug administration group was relatively regular， and the swelling of myocardial cells was significantly reduced. The pathological morphology of myocardial tissue was improved to varying degrees. The pathological changes in myocardial tissue were improved and alleviated to varying degrees. The drug could reduce the serum levels of NT-ProBNP， IL-17， TGF-β₁， IL-6， and IL-12 and increase the level of serum 25（OH）D₃ and IL-10 （P<0.05）. The expression of costimulatory molecules CD40， CD80， CD86， and MHC-Ⅱ in the peripheral blood DCs of rats was decreased， and the expression of CD11 and CD11b molecules was increased （P<0.05）. The drug could reduce the proportion of Th17 cells in peripheral blood and the ratio of Th17/Treg cells and increase the proportion of Treg cells （P<0.05）. It could decrease the mRNA and protein expressions of CYP24A1 in peripheral blood DCs of rats and elevate the mRNA and protein expression of VDR and CYP27B1 （P<0.05）. ConclusionICA can regulate the phenotype of peripheral blood DCs and the ratio of Th17/Treg cells by regulating the vitamin D system and play a role in improving myocardial remodeling from the perspective of immune balance.