Objective To investigate the efficacy of plantamajoside(PMS)on diabetic peripheral neuropathy(DPN)and to explore its mechanism of action from mitochondrial autophagy.Methods Mice(C57BL/6J)were randomly divided into 6 groups(n=10):normal group(Control),model group(Model),positive drug group(LA),and low(L-PMS),medium(M-PMS),and high(H-PMS)dosage groups.High-sugar and high-fat diet with intraperitoneal injection of streptozotocin was used to duplicate the DPN model.After successful model duplication,the intervention was administered by gavage for 4 weeks.Sciatic nerve was taken,and pathological changes were observed by HE and Nissl staining;oxidative stress indexes SOD,MDA,GSH-Px and inflammatory factors such as IL-1β,IL-6,TNF-αin sciatic nerve tissues were detected by kits,and the expression of VDAC1,TOM20,COX IV,PINK1,Parkin,and autophagy proteins of Beclin1,LC3,P62 in mouse sciatic nerves was detected by Western blotting.Results PMS dose-dependently improved the behavioral indexes of DPN mice,reduced the pathological damage of sciatic nerve,and resulted in tightly arranged sciatic nerve fibers,clearly visible myelin structure,uniform coloration,and increased number of Schwann cells as well as Nissl bodies.Compared with the model group,both the M-PMS group and the H-PMS group increased the expression levels of SOD and GSH-Px(P<0.05),while decreased the expression of MDA(P<0.05);the M-PMS group and the H-PMS groups reduced the expression of IL-1β,IL-6,and TNF-α(P<0.05);the L-PMS group,M-PMS group,and H-PMS group reduced the expression levels of VDAC1,TOM20,and COX IV proteins(P<0.05);the L-PMS group,M-PMS group,and H-PMS group could differentially increase the expression of PINK1,Beclin1,Parkin,and LC3 proteins(P<0.05),and decrease the expression of P62 proteins(P<0.05).Conclusion PMS can play a role in ameliorating neurological injury in DPN mice by promoting PINK1/Parkin pathway-mediated mitochondrial autophagy and alleviating oxidative stress-related inflammatory injury.

In the era of evidence-based medicine, it is necessary to explore the unique advantages of traditional Chinese medicine (TCM) based on standardized technical methods and operating procedures in order to achieve the modernization and internationalization of TCM and benefit all humanity. The proposal of a three-pronged evidence system combining TCM theory, human experience and experimental evidence marks an important progress in the thinking method of the TCM evaluation system. The multi-evidence body integrated through appropriate methods provides a strong support for the clinical guideline recommendations and evidence-based health decision-making in TCM. Based on the current methodological progress of international evidence synthesis and grading, this paper proposes a novel approach for integrating multi-evidence in TCM: the MERGE framework. The aim is to establish a solid foundation for the development of this methodology and provide guidance for the advancement of evidence-based medicine framework in TCM.

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

Objective:To investigate the feasibility and safety of endovascular repair for traumatic thoracic aortic pseudoaneurysm.Methods:From Oct 2015 to Oct 2018, the clinical and followup data of 7 patients diagnosed as traumatic thoracic aortic pseudoaneurysm in Fuwai Hospital of Chinese Academy of Medical Sciences were analyzed retrospectively.Results:The patients average age was (51.2±11.0) years old. All patients underwent surgery in the hybrid operating room under general anesthesia. Two did thoracic endovascular aortic repair (TEVAR), three did TEVAR combined with chimney technique to reconstruct the left subclavian artery, and 1 had TEVAR combined with fenestration to reconstruct the left subclavian artery. One did TEVAR with left common carotid artery and left subclavian artery bypass. The mean operative time was (90.1±27.4) min, the mean postoperative hospital stay was (8.9±3.7) d, and the mean postoperative follow-up time was 42.4 months. All the patients received CTA reexamination of the aorta after 1, 6, 12 months and yearly thereafter. TypeⅠendoleak was found in one patient with chimney technique to reconstruct of left subclavian artery after operation. CT showed that the type Ⅰ endoleak disappeared 6 months after operation. There was no death, paraplegia or stroke during the perioperative period and follow-up period, and there was no aortic related reintervention.Conclusion:TEVAR is a safe and effective method for the treatment of traumatic pseudoaneurysm of thoracic aorta, and the early and mid-term results were satisfactory.

Objective:To evaluate the safety and feasibility of the in-situ needle fenestration combined with the in vitro physician modified fenestration technique to reconstruct supra-aortic branches during thoracic endovascular aortic repair (TEVAR) for aortic arch lesions requiring landing at Z0 and Z1.Methods:From Nov 2017 to Dec 2019, eighteen patients who underwent both the in-situ needle fenestration and the in vitro physician modified fenestration techniques to extend the proximal landing zone to Z0 and Z1 during TEVAR were included in our study.Results:Sixteen patients underwent in vitro physician modified fenestration ,two patients underwent in vitro physician modified fenestration to reconstruct both the left common carotid artery and the innominate artery. All eighteen patients received in-situ needle fenestration to preserve the left subclavian artery. Supra aortic branches were preserved in all patients (38/38, 100%). There was no Type Ⅰ endoleak. Type Ⅱ endoleak was found in four paitnets (4/18). Type Ⅲ endoleak occurred in one patient (1/18). Type Ⅳ endoleak in four patients (4/18). Type Ⅲ endoleak needed open aortic arch repair 6 months later. The median follow-up time was 12 months. One (1/18) died in 12 months and the other patients were doing well.Conclusions:The joint application of the in-situ needle fenestration and the in vitro physician modified fenestration to reconstruct supra-aortic branches during TEVAR for aortic arch pathologies requiring landing at Z0 and Z1 was satisfactory.

The purpose of this study was to explore the role and mechanism of transient receptor potential M₂ (TRPM₂) in antigen-induced arthritis (AIA) mice. Twelve C57BL/6 mice and 12 TRPM₂ knockout mice were divided into 4 groups, includingwild type control group, wild type AIA group, TRPM₂ knockout control group and TRPM₂ knockout AIA group, with 6 mice in each group. Methylated bovine serum albumin (mBSA) was used to establish AIA mouse model. The degree of joint swelling and inflammatory cell infiltration were recorded, as well as synovial hyperplasia of the knee joints. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression of interleukin (IL)-6, IL-8, chemokine ligand 6 (CXCL-6) and tumor necrosis factor alpha (TNFα) mRNA in synovial cells of knee joints. The results showed that compared with the wild-type AIA group, the TRPM₂ knockout AIA group had more significant synovial proliferation and inflammatory cell infiltration in the synovial tissue.The neutrophil and macrophage counts rather than monocytes in the knee joints of TRPM₂ knockout AIA group were higher than those in wild-type AIA mice. The expression of IL-6, IL-8 and CXCL-6 mRNA were significantly increased in the knock out mice. In summary, TRPM₂ may inhibit inflammatory cytokines such as IL-6 and IL-8 in knee joints of AIA mice by reducing the infiltration of neutrophils and macrophages, the refore alleviates the manifestations of knee arthritis.

AIM:To study the effect of p21-activated protein kinase 2 (PAK2) knockdown by RNA interfer-ence on the proliferation and apoptosis of human breast cancer cells .METHODS:The short hairpin RNA ( shRNA) targe-ting PAK2 gene was designed and used for packing lentivirus in 293T cells.Human breast cancer MCF-7 cells were infected by the virus particles and PAK2 knockdown stable cell line was established by puromycin selection .The knockdown effi-ciency was assessed by Western blotting .The proliferation ability of MCF-7 cells was evaluated by CellTiter 96 AQueous and anchorage-independent growth assays .The cell apoptosis induced by staurosporine was detected by flow cytometry . RESULTS:The protein level of PAK2 was significantly suppressed after silencing of PAK2 gene in MCF-7 cells ( P<0.01).Furthermore, knockdown of PAK2 caused remarkable inhibition of the cell proliferation and colony formation (P<0.01).Staurosporine induced more apoptosis in the PAK2 knockdown cells compared with the control cells (P<0.01). CONCLUSION:Knockdown of PAK2 inhibits the proliferation of MCF-7 cells and increases the sensitivity of chemothera-peutic drug-induced cell apoptosis , suggesting that PAK2 might be a new therapeutic target in breast cancer treatment .

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on hypertension induced by insulin resistance in rats and to provide mechanistic insights into its therapeutic effect. Male Sprague-Dawley (SD) rats were fed with high-fructose (10%) water to develop mild hypertensive models within 4 weeks, then randomized into 4 groups: model control, FGF21 0.25, 0.1 and 0.05 micromol x kg(-1) x d(-1) groups. Five age-matched normal SD rats administrated with saline were used as normal controls. The rats in each group were treated once a day for 4 weeks. Body weight was measured weekly, systolic blood pressure (SBP) was measured noninvasively using a tail-cuff method, insulin sensitivity was assessed using oral glucose tolerance test (OGTT) and HOMA-IR assay. At the end of the treatment, blood samples were collected, and blood glucose, serum cholesterol, serum triglyceride and serum insulin were measured. The results showed that blood pressure of the rats treated with different doses of FGF21 returned to normal levels [(122.2 +/- 3.5) mmHg, P < 0.01] after 4-week treatment, whereas, SBP of untreated (model control) rats maintained a high level [(142.5 +/- 4.5) mmHg] throughout the treatment. The observation of blood pressure in 24 h revealed that SBP of FGF21 treated-rats maintained at (130 +/- 4.5) mmHg vs. (143 +/- 5.5) mmHg for model control (P < 0.01). FGF21 treatment groups improved serum lipids obviously, total cholesterol (TC) and triglyceride (TG) levels decreased significantly to normal levels. The serum NO levels of three different doses FGF21 treatment group were significantly higher than that of the model control group [(7.32 +/- 0.11), (7.24 +/- 0.13), (6.94 +/- 0.08) vs. (6.56 +/- 0.19) micromol x L(-1), P < 0.01], and the degree of improvement showed obvious dose-dependent manner, indicating that FGF21 can significant increase serum NO in fructose-induced hypertension rat model and improve endothelial NO release function. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF21 significantly ameliorates blood pressure in fructose-induced hypertension model by relieving insulin resistance. This finding provides a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of essential hypertension.

Insulin is the most common medicine used for diabetic patients, unfortunately, its effective time is short, even the long-acting insulin cannot obtain a satisfactory effect. Fibroblast growth factor (FGF)-21 is a recently discovered glucose mediator and expected to be a potential anti-diabetic drug that does not rely on insulin. In this study, db/db mice were used as the type 2 diabetic model to examine whether mFGF-21 has the long-term blood lowering effect on the animal model. The results showed that mFGF-21 could stably maintain the blood glucose at normal level for a long-term in a dose-dependent manner. Administration of mFGF-21 once a day with three doses (0.125, 0.25 and 0.5 mg x kg(-1)) could maintain blood glucose of the model animals at normal level for at least 24 h. Administration of mFGF-21 every two days with the same doses could maintain blood glucose of the model animals at normal level for at least 48 h, although it took longer time for blood glucose to reach to normal level depending on doses used (twenty injections for 0.125 mg x kg(-1) and 0.25 mg x kg(-1) doses, ten injections for 0.5 mg x kg(-1) dose). Surprisingly, the blood glucose of the treated model animals still maintained at normal level for 24 h after the experiment terminated. Glycosylated hemoglobin level of the animals treated with mFGF-21, which represented long-term glucose status, decreased significantly compared to the control group and the insulin group. The results suggest that FGF-21 has potential to become a long-acting and potent anti-diabetic drug.

ObjectiveTo assess the effectiveness of tele-medicine and self-management goal(SMG) setting technique used in the diabetes management in the community setting.Methods It is a control-group study.415 type 2 diabetic residents were recruited from the Shanghai Wuliqiao community based on existing medical records.The subjects were divided into two groups,the study group was cared by general practitioners (GPs) specialists cooperation through the tele-medicine mechanism,the other was a control group.For the study group,a cooperation pathway between community health care centers and general hospitals were established.Standardized training and guidelines were provided to community health workers,regarding the setting of management goals of blood glucose and blood pressure,treatment plan,patient education,and SMG techniques.Fasting blood glucose ( FBG ) and 2 h postprandial blood glucose (2hBG) in the study group were monitored,followed by community health workers visiting monthly with seminars for diabetes education.At the baseline and the 12tb month,FBG,2hBG,HbA1C,blood pressure,triglyceride,total cholesterol,body mass index,waist-hip ratio were determined in each group.A survey was conducted to evaluate the costs of diabetes treatments,the knowledge base related to their disease,lifestyle,and the awareness of the new care model.The rates of achieving the goal of blood glucose,blood pressure,and HbA1Ccontrol were calculated.Internet case discussion between GPs-Specialists and referral to certain specialists were implemented when some patients did not reach the control goal.ResultsBy the 12 month follow up,FBG,2hBG,HbAIc,blood pressure of the study group were lower than the baseline,and as well as the control group with statical significance (P＜0.05).There are other improvcments:diabetes knowledge (29.1％ vs 5.5％ ),healthy diet (9.6％ vs -10.4％ ),blood glucose monitoring (30.3％ vs 10.8％ ),support for diabetes care in community (35.7％ vs 9.4％ ),and the preference of the new model (63.8％ vs 17.9％ ) with statistical significauce (P＜0.01 ).As for the medical costs,the study group's monthly costs were consistently lower than the control's.( -3.39Yuan vs 32.26 Yuan,P＜0.05).ConclusionsThe new diabetes care model based on GPs-Specialists tele-medicine and SMG in community opens the door to the community based care model formulation in regard to the health quality and costs control.The deployment of more technologies and management techniques could be explored further to improve the outcomes of community based chronic disease care model.