Aim To observe the expressions of KLF4 in the myocardium of diabetic mice and their changes under Tongxinluo capsule intervention. Methods For-ty KK/Upj-Ay mice were randomly divided into diabet-ic model group(n=10)and diabetic model with Tongx-inluo(TXL low,middle,high) groups(n =10,respec-tively). C57BL/6 mice were selected as control group ( n=10 ) . At the end of the 3 th month the mice were sacrificed and were weighed. The fasting blood-glucose (FBG),glycosylated hemoglobin(HbA1c),triglyceride ( TG) ,total cholesterol ( TC ) and insulin ( FINS ) were measured to calculate HOMA-IR. Radioimmunoassay was used to measure serum TNF-αand IL-6 . The path-ological changes in the myocardium of mice were ob-served by HE staining. KLF4 mRNA was examined by Real-time PCR, while KLF4 and NF-κB protein were measured by Western blot. Results Compared to the control group,FBG,HbA1c,TG,TC,FINS,HOMA-IR,
TNF-α and IL-6 in model group were markedly in-creased;the expressions of myocardial KLF4 were markedly decreased and the expression of nuclear NF-κB protein were markedly increased ( P < 0. 01 ) . Tongxinluo capsule could significantly reduce myocar-dial pathological damage, FINS, TG, TC, TNF-α, IL-6 level and the expression of nuclear NF-κB protein and up-regulate the expression of KLF4 ( P <0. 05 ) , but had no effect on FBG and HbA1c(P>0. 05). Conclu-sions KLF4 may be involved in the development of myocardial injury during diabetes. Tongxinluo capsule can ameliorate the myocardial damage and improve the function of diabetic myocardium by up-regulating the expression of KLF4 and inhibiting the activation of NF-κB inflammatory signal pathway.

Objective To study the effect of candesartan (Can) on the LPS‐induced proinflammatory cytokines release in VSMCs ,and to explore the role of TLR4‐mediated signaling pathway in this process .Methods Rat VSMCs were primarily cul‐tured ,and the effect of different concentrations of Can on VSMCs activity was observed by M TT assay .The cells were divided into 5 groups :A(control) ,B(LPS intervention) ,C(LPS + 10 - 7 mol/L Can) ,D(LPS + 10 - 7 mol/L Can ) and E (LPS + Can 10 - 5 mol/L Can) .mRNA and protein levels of Toll‐like receptor‐4(TLR4) ,myeloid differentiation primary response gene 88(Myd88)and nu‐clear factor‐κB(NF‐κB) nuclear translocation were determined by real‐time PCR and Western blot ,respectively ;IL‐1β and TNF‐αconcentration were detected by ELISA .The production of intercellular reactive oxygen species(iROS) was measured by the DCFH‐DA assay .Pretreating VSMCs with the inhibitors against TLR4 ,NADPH oxidase ,and NF‐κB ,or a combination with candesartan and these inhibitors ,and then the expression of IL‐1β and TNF‐α was measured by ELISA .Results Can in the concentration range of 10 - 8 - 10 - 3 mol/L had no significant effect onVSMCs activity .Compared with th control group ,Can could effectively inhibit LPS‐induced VSMCs ,IL‐1β and TNF‐α release ,decreased the mRNA and protein expression of TLR4 ,Myd88 ,reduced the produc‐tion of iROS ,inhibited the NF‐κB(p65) nuclear translocation with a concentration‐dependent manner(P< 0 .05) .Anti‐TLR4 anti‐body ,DPI ,and PDTC all inhibited LPS‐induced inflammatory cytokines release in VSMCs ,and the combination of Can and these blockers showed stronger anti‐inflammatory effect .Conclusion Can can decrease the releaseof inflammatory cytokines IL‐1β and TNF‐α in VSMCs stimulated by LPS ,which is realized by inhibiting the signaling pathway of TLR4/Myd88‐iROS‐NF‐κB .

OBJECTIVETo study the effectiveness of pie-crusting technique in improving the stiff knee.

METHODSFrom February 2012 to December 2013, 13 patients with stiff knee were reviewed retrospectively. There were 6 males and 7 females, ranging in age from 39 to 70 years old (averaged, 55.6 years old). Of the 13 cases, 8 patients had stiffness following fracture (comminuted tibial plateau fracture in 4, femoral supracondylar fracture in 3 and patellar fracture in 1), 5 patients had TKA-related stiffness.

RESULTSA follow-up lasted 8 to 12 months (mean 10 months)in 13 cases. The mean maximum flexion increased from (37 ± 6)° preoperatively to (52 ± 7)° after arthrolysis, and (108 ± 7)° after pie-crusting. At the final follow-up, mean maximum flexion was (105 ± 6)°. According to Judet evaluation system, 10 patients got an excellent result and 3 good. No major complications, such as extensor lag, skin necrosis, deep infection, dislocation of the patella or recurrent stiffness were found.

CONCLUSIONThe percutaneous technique of pie-crusting is a simple, minimally invasive and effective treatment for knee stiffness.

Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Joint Diseases ; physiopathology ; surgery ; Knee Joint ; physiopathology ; surgery ; Male ; Middle Aged ; Range of Motion, Articular ; Treatment Outcome

Objective To investigate the effect of Akt pathway inhibitor AZD5363 on cell proliferation and invasion of QBC939 and RBE cholangiocarcinoma cells and the mechanism.Methods Western blotting was used to detect Akt and downstream protein and mTOR protein expression in two cancer cell lines after process by AZD5363.Inhibition rate and cytotoxicity was tested by CCK-8 assay,and Transwell assay was used to evaluate the invasive ability of cancer cells.Results QBC9393 cell exposed to AZD5363 LD50 drug concentration (24 ±9) was significantly different compared with control group (t =4.47,P ＜ 0.05),RBE cells LD50 drug concentration (21 ± 8) was significantly different compared with control (t =4.41,P ＜ 0.05).Tumor invasion capacity of QBC939 in drug concentrations of 20 μmol/L (63 ± 12) and 0 μmoL/L (271 ± 27),the difference was statistically significant.RBE exposed AZD5363 upon drug concentrations of 20 μmol/L (58 ± 23) and 0 μmol/L (235 ± 21),the difference was statistically significant.AZD5363 promotes phosphorylation of mTOR in QBC939.Conclusions AZD5363 inhibits the proliferation and migration,inhibiting the phosphorylation of Akt and its downstream molecules.AZD5363 promotes phosphorylation of mTOR in QBC939.

Establishment and improvement of rules and regulations will benefit to the management of research institutions.A comprehensive,fair,reasonable,and workable rules and regulations are the basic guarantee for maintaining the orderly,steady,and sustainable development of the institutions.It is also help to fully mobilize the enthusiasm and creativity of all members of the institutes.In this paper,we use an example of a construction of rules and regulations in the military medical research Institutions,to analyze current information and posted suggestions on the rules and regulations formulation principles,making procedure,overall framework and main innovation for the future improvement and implementation of rules and regulations.

Objective:To study the clinical application of laparoscopic combined with multi-video debridement in treatment of complicated infectious pancreatic necrosis (CIPN).Methods:The clinical data of 34 patients with CIPN who were treated at the Department of General Surgery, Xuanwu Hospital, Capital Medical University from August 2017 to December 2019 were retrospectively studied. Based on the different video methods used, these patients were divided into 3 groups: the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group. The number of operations, operation time, blood loss, postoperative complication rates, mortality rates and total length of hospital stay were compared.Results:There were 13 patients in the laparoscopic combined with intraoperative ultrasound group, with age of (56.4±13.4) years. There were 7 patients in the laparoscopic combined with choledochoscopy group, with age of (48.0±8.4) years. There were 14 patients in the laparoscopic group with age of (51.4±15.6) years. The number of operations of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (2.2±1.1), (1.6±0.8), (2.9±1.4), respectively. The number of operations of the laparoscopic combined with choledochoscopy group were significantly less than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). The operation time of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (70.5±22.9) min, (65.7±19.9) min, (51.5±15.4) min, respectively. The operation time of the laparoscopic combined with intraoperative ultrasound group was significantly longer than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). There were no differences in blood loss, postoperative complication rate, mortality rates and total lengths of hospital stay among the three groups ( P>0.05). Conclusion:Laparoscopic combined with multi-video debridement after making full use of the advantages of each of the video methods, can be used to improve treatment outcomes of patients with CIPN.

Objective:To analyze the efficacy and safety of radioactive 125I seed implantation in the treatment of unresectable early-stage non-small cell lung cancer (NSCLC), in order to provide data for clinical practice and relevant research. Methods:A retrospective study was conducted on the data of 39 patients with early-stage NSCLC who received CT-guided radioactive 125I seed implantation from Dec 2010 to Dec 2018 in multiple hospitals.The seed implantation process consisted of preoperative planning and design, CT-guided puncture, seed implantation, and postoperative evaluation and dose verification.The efficacy and complications of the treatment were analyzed.The clinical efficacy was evaluated by adopting the Response Evaluation Criteria in Solid Tumors (RECIST) (v1.1) and the adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Results:All the patients were 70 years old on average (51-85). The median lesion diameter was 2.7 cm (1.1-6.0 cm), the median seed activity was 0.7 mCi (0.6-0.8 mCi), while the median follow-up duration was 29 months (3-97 months). Meanwhile, the 1-, 3-, and 5-year overall local control rates were 89.5%, 79%, and 79%, respectively, and the 1-, 3-, and 5-year overall survival rates were 100%, 74.8%, and 49.9%, respectively.Local recurrence and distant metastasis were the main causes of failure, accounting for 17.9% (7 cases) each.The incidence of pneumothorax was 56.4% (22 cases), among which nine cases (23.1%) required invasive closed thoracic drainage.Only 1 case of grade-2 radiation pneumonia (2.6%) was observed, with no other adverse reactions such as dermatoses, esophagitis, or myelitis being discovered.As indicated by univariate analysis, the patients with KPS scores of 80-90, pathological type of adenocarcinoma, T stage of T 1-2, and D90>180 Gy exhibited better local control ( χ2=6.202, P<0.05). Meanwhile, high D90 was also associated with a higher survival rate ( χ2=6.907, P<0.05). Conclusions:Radioactive 125I seed implantation is a safe and effective treatment for unresectable early-stage NSCLC.In cases where external beam radiotherapy is not available, radioactive 125I seed implantation can be considered as one of the treatment options.Pneumothorax is the most common complication of radioactive 125I seed implantation, and adenocarcinoma (pathological type) and higher values of D90 are predictors of better local control.

Focal Adhesion Protein-Tyrosine Kinases ; Humans ; Liver Diseases, Alcoholic ; enzymology ; pathology

Objective To explore the inhibitory effect of curcumin on LPS-induced inflammation and the activation of Toll-like receptor 4 (TLR4 )/NADPH oxidase/reactive oxygen species (ROS)signaling pathway in vascular smooth muscle cells (VSMCs).Methods Primary VSMCs were cultured and divided into control group, LPS group,LPS + curcumin 5 μmol/L group,LPS + curcumin 10 μmol/L group and LPS + curcumin 30 μmol/L group.Cell activity was observed by MTT assay.The secretion of tumor necrosis factor-α(TNF-α)and interleukin-1 (IL-1)was measured by enzyme linked immunosorbent assay (ELISA)kits.The mRNA expressions of TLR4 and p22phox were detected by real-time PCR.Expression of intracellular ROS was measured by flow cytometry. Results The activities of VSMCs were not significantly affected by curcumin at the concentration between 0 and 80 μmol/L.Curcumin (5,10 and 30 μmol/L)significantly inhibited LPS-induced oversecretion of TNF-αand IL-1, as well as overexpression of TLR4 and p22phox at the mRNA and protein levels,and ROS production in VSMCs in a concentration-dependent manner.Conclusion Curcumin has a concentration-dependent inhibitory effect on the secretion of inflammatory cytokine,overexpressions of TLR4 and p22phox,and production of ROS in VSMCs stimulated by LPS.Furthermore,curcumin may partly depend on TLR4/NADPH oxidase/ROS signaling pathways to inhibit inflammation in LPS-induced VSMCs.

OBJECTIVE:To investigate the effects of Tongxinluo capsules on inflammatory cytokines of mice with diabetic pe-ripheral neuropathy. METHODS:40 KK/Upj-Ay mice were randomly divided into model group(pure water),and Tongxinluo low, medium and high dose groups [1,2 and 4 g (medicinial materials)/kg]. 10 C57BL/6 mice were selected into the control group (pure water). The drugs were given once a day for consecutive 12 weeks,ig. The pain perception threshold,motor nerve conduc-tion velocity(MNCV)and sensory nerve conduction velocity(SNCV)were detected for the mice 1 h after the last administration of drugs. The flow cytometry was used to detect the levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β),cyclooxy-genase 2(COX-2)and monocyte chemoattractant protein 1(MCP-1)in serum. Real-time fluorescent quantitative polymerase chain reaction(RT-PCR)and Western blot were respectively employed to detect the mRNA and protein expressions of TNF-α,IL- 1β, COX-2 and MCP-1 in the mice’s sciatic nerves. RESULTS:Compared with control group,pain perception threshold in model group was decreased;MNCV and SNCV were slowed;the levels of TNF-α,IL-1β,COX-2 and MCP-1 in serum were increased;the expressions of mRNA and protein of TNF-α,IL-1β,COX-2,MCP-1 were increased,with significant differences(P<0.01 or P<0.05). Compared with model group,pain perception threshold in Tongxinluo medium and high dose groups were increased;MNCV and SNCV were increased;the levels of TNF-α,IL-1β,COX-2 and MCP-1 in serum were decreased;the expressions of mRNA and protein of TNF-α,IL-1β,COX-2,MCP-1 in sciatic nerves were decreased;the expressions of mRNA of COX-2, MCP-1 and protein of IL-1β,COX-2,MCP-1 in sciatic nerves in Tongxinluo low dose group were decreased,there were statistical significant difference(P<0.01 or P<0.05). CONCLUSIONS:Tongxinluo capsules have certain protective effects on the mice with peripheral nerve in case of diabetes by a mechanism that may be associated with the inhibition of inflammatory cytokines.