【Objective】 To investigate the effects of formononetin (FMN) on cardiomyocyte apoptosis and HSP90/AKT in rats with dilated cardiomyopathy-mediated heart failure. 【Methods】 Echocardiography, ELISA, histological staining, and TUNEL staining were used to observe the protective effect of different doses of FMN on dilated cardiomyopathy-mediated heart failure in rats and the apoptosis of cardiomyocytes. The potential targets of formononetin on dilated cardiomyopathy-mediated heart failure were obtained from TCMSP, DisGeNet, GeneCards, and other databases, the key targets were obtained according to the protein-protein interaction (PPI) network, and the key targets were verified by molecular docking. Western blotting was used to further verify the regulatory role of key targets in the treatment of dilated cardiomyopathy-mediated heart failure with formononetin. 【Results】 Formononetin could reduce the levels of LVIDS, LVIDD, NT-pro BNP, cTn-T, CK, CK-MB, and LDH in rats with dilated cardiomyopathy-mediated heart failure, increase the levels of EF and FS, and reduce the apoptosis of cardiomyocytes. FMN had a strong binding effect on 10 key targets (AKT1, HSP90AA1, CASP3, MAPK1, MMP9, SRC, ALB, HRAS, IGF1, and EGFR) screened by network pharmacology, with HSP90AA1 and AKT1 having the strongest binding effect. Formononetin decreased the expression of HSP90, AKT and downstream CASP3 protein, but increased the expression of p-AKT in myocardial tissue. 【Conclusion】 Formononetin may inhibit the expression of HSP90, promote phosphorylation of AKT to p-AKT, and inhibit the expression of CASP3, thereby reducing the apoptosis of cardiomyocytes and improving myocardial tissue damage, so as to achieve the purpose of treating dilated cardiomyopathy-mediated heart failure.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Aim To study the electrophysiological mechanism of dopamine inhibiting insulin secretion hv voltage-dependent potassium ( Kv) channels.Methods Islets and (3 cells were isolated from male SD rats.D,-like receptor agonist ( SKP38393), D2-like receptor agonist (Quinpirole) and antagonist (Epiclopride) were used according to the experiment.Insulin secretion was detected by insulin radioimmunoassay.Whole-cell j J patch-clamp technique was applied to detect Kv channel currents and action potential duration of p cells.Di- BAC4(3) staining was used to observe membrane potential.Results SKF38393 did not affect insulin secretion and the Kv channel currents.Quinpirole signifi cantly inhibited insulin secretion and increased Kv channel currents.Dopamine significantly inhibited insulin secretion, increased Kv channel currents and shortened action potential duration of p cells, which could be reversed by epiclopride.In addition, dopamine de-creased membrane potential of INS-1 cells.Conclusions Dopamine inhibits insulin secretion by acting on D2-like receptors, resulting in actived Kv channels, shortened action potential duration and decreased cell membrane potential.

OBJECTIVE: To observe the clinical effect of platelet rich plasma (PRP) combined with β tricalcium phosphate bioceramic bone in the treatment of non traumatic necrosis of the femoral head in ARCO stageⅡ. METHODS: From January 2017 to December 2018, 100 patients (160 hips) with ARCO stageⅡnon traumatic necrosis of the femoral head were divided into PRP group and control group. In PRP group, 50 patients (80 hips), 22 males and 28 females, aged from 18 to 65 (43.47± 7.23) years, with a course of 4 to 18 (15.8±2.9) months, underwent core decompression and bone grafting combined with PRP implantation. There were 50 cases (80 hips) in the control group, including 27 males and 23 females, aged 20 to 63 (45.72± 7.43) years, and the course of disease was 6 to 19 (14.9±3.8) months. Hip X-ay film was followed up after operation. Harris score and VAS score were used to evaluate the curative effect, and the survival rate of hip joint was recorded. RESULTS: All patients had good wound healing, no infection, thrombosis and other complications. All patients were followed up for 12 to 14 (12.0±0.4) months. Twelve months after operation, the image expression of PRP group was better than that of control group( CONCLUSION Platelet-rich plasma(PRP) combined with artificialbone for core decompression and bone grafting can change the situation of simple artificial bone implantation and uncertain curative effect, improve the success rate of this operation, effectively reduce the collapse rate of femoral head necrosis in the early and middle stage, delay or even avoid hip replacement.
Adolescent ; Adult ; Aged ; Artemisinins ; Bone Transplantation ; Decompression, Surgical ; Female ; Femur Head/surgery* ; Femur Head Necrosis/surgery* ; Humans ; Male ; Middle Aged ; Naphthoquinones ; Platelet-Rich Plasma ; Treatment Outcome ; Young Adult

BACKGROUND: Knee osteoarthritis (OA) is a major cause of disability among the older adults. Few treatments are safe and effective. Moxibustion is commonly used in treating knee OA in Chinese medicine (CM). CO Laser moxibustion device is a substitute for traditional moxibustion, which mimics the effects of traditional moxibustion. More data are needed to support its application in knee OA. OBJECTIVE: ObjectiveThe trial aims to assess the effect and safety of CO laser moxibustion in patients with knee osteoarthritis compared with a sham control. METHODS: This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers.This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers. DISCUSSION CO laser moxibustion device, designed as a substitute for CM moxibustion, is easy to use and control with no choking smoke and smell, and is a plausible method for double-blind research. This study would provide rigorous evidence for the effect and safety of CO laser moxibustion in treating knee OA (Trial registration No.: ISRCTN15030019).

The polarity of ameloblasts and odontoblasts is crucial for their differentiation and function. Polarity-related molecules play an important role in this process. This review summarizes the process of polarity formation of ameloblasts and odontoblasts and their related regulators.
Ameloblasts ; Cell Differentiation ; Odontoblasts

OBJECTIVETo investigate expression features and correlation of genes expression on MyD88-dependent signaling pathway in synovial membrane (SM) of progression of knee osteoarthritis (OA).

METHODSSixty Wistar rats were randomly divided into 6 groups, including blank group (N), false surgical group, model groups[2 weeks (2W), 4 weeks (4W), 8 weeks (8W) and 12 weeks (12W)], with 10 rats in each group. The models were established by using Hulth method. Control group was experienced no surgery, while false surgical group was only opened joint cavity and sutured. The SM samples was collected according to the time designed above. The relative expression quantity of MyD88, TLR4 and NF-κB was detected by Real-time PCR after the extraction of the total RNA and reverse transcription. The correlation analysis was obtained by SPSS.

RESULTSThere was no significant difference in each gene mRNA expression between false surgical and blank group(> 0.05), while enhanced expression was found in the model groups(<0.05). The correlation index among MyD88, TLR4 and NF-κB was 0.91 and 0.86 respectively, and had significant difference among them.

CONCLUSIONSPositively relative among MyD88, TLR4 and NF-κB played main role in TLR4/NF-κB signal passway, and could predicate the expression of other genes in the passway. It also could further provide the basis for clarify the pathologic mechanism of knee OA.

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage

This study was designed to explore the antidepressant mechanism of Bupleuri radix through establishing the active components-targets network and protein interactions network and analyzing the functions and pathways of targets. The main active ingredients of Bupleuri radix were obtained by TCMSP, literature study and the results of our own work. Based on the DRAR-CPI, GeneCards and OMIM were used to predict and screen the active components of Bupleuri radix. The Cytoscape software was used to construct the active components-targets network of Bupleuri radix. The protein interactions network was constructed using the String database and Cytoscape software. The relation of the main active ingredients and targets were validated by Systems Dock Web Site. The GO and KEGG pathways involved in the targets were analyzed by DAVID. Using DisGeNET database to attribute the type of targets. The results showed that 15 active components and 50 targets of Bupleuri radix were involved. The network results showed that the process of metabolism, regulation and response to stress were mainly involved, by adjusting the PI3K-AKT, MAPK, Rap1, Ras, FoxO, neurotrophin and other signaling pathways to play its antidepressant effect. This study reflects the characteristics of multicomponents-multi-targets and multi-pathways of Bupleuri radix, which provides new ideas and clues for further research on the mechanism of anti-depressive effects of Bupleuri radix.

The bone morphogenetic protein (BMP) family is an important factor in the regulation of cell ular life activities and in the development of almost all tissues. BMP-mediated signaling plays an important role in tooth root development, which is a part of tooth development. Epithelial and mesenchymal interactions are involved in tooth root development, but the BMP signaling pathway has a different effect on tooth root development in epithelial and mesenchymal. This review summarizes the advances of BMP signaling in tooth root development.
Bone Morphogenetic Protein 2 ; Bone Morphogenetic Protein 7 ; Bone Morphogenetic Proteins ; physiology ; Odontogenesis ; Signal Transduction ; Tooth ; Tooth Root ; growth & development