Chondroprotective Mechanism of Eucommia ulmoides Oliv.-Glycyrrhiza uralensis Fisch. Couplet Medicines in Knee Osteoarthritis via Experimental Study and Network Pharmacology Analysis.

Background: Knee osteoarthritis (KOA) is the primary prevalent disabling joint disorder among osteoarthritis (OA), and there is no particularly effective treatment at the clinic. Traditional Chinese medicine (TCM) herbs, such as Eucommia ulmoides Oliv. and Glycyrrhiza uralensis Fisch. (E.G.) couplet medicines, have been reported to exhibit beneficial health effects on KOA, exact mechanism of E.G. nevertheless is not fully elucidated. Purpose: We assess the therapeutic effects of E.G. on KOA and explore its underlying molecular mechanism. Methods: UPLC-Q-TOF/MS technique was used to analyze the active chemical constituents of E.G. The destabilization of the medial meniscus model (DMM) was employed to evaluate the chondroprotective action of E.G. in KOA mice using histomorphometry, µCT, behavioral testing and immunohistochemical staining. Additionally, network pharmacology and molecular docking were used to predict potential targets for anti-KOA activities of E.G., which was further verified through in vitro experiments. Results: In vivo studies have shown that E.G. could significantly ameliorate DMM-induced KOA phenotypes including subchondral bone sclerosis, cartilage degradation, gait abnormality and thermal pain reaction sensibility. E.G. treatment could also promote extracellular matrix synthesis to protect articular chondrocytes, which was indicated by Col2 and Aggrecan expressions, as well as reducing matrix degradation by inhibiting MMP13 expression. Interestingly, network pharmacologic analysis showed that PPARG might be a therapeutic center. Further study proved that E.G.-containing serum (EGS) could up-regulate PPARG mRNA level in IL-1ß-induced chondrocytes. Notably, significant effects of EGS on the increment of anabolic gene expressions (Col2, Aggrecan) and the decrement of catabolic gene expressions (MMP13, Adamts5) in KOA chondrocytes were abolished due to the silence of PPARG. Conclusion: E.G. played a chondroprotective role in anti-KOA by inhibiting extracellular matrix degradation, which might be related to PPARG.

[Effect of Dendrobii officinalis superfine powder on overeating greasy-induced metabolic hypertension in rats].

Dendrobii officinalis, with a definite effect of nourishing Yin and clearing heat, has been a folk habit for drinking after being mixed with water. Because its superfine powder has the advantages of high dissolution and convenient drinking, we observed the effect of D. officinalis superfine powder on metabolic hypertension model rats and its possible mechanism in this experiment, which can be used as a reference for its clinical application for hypertension. The overeating greasy-induced metabolic hypertension model was established with high-fat, high-sugar and high-purine diet. These rats were orally administered with 400 mg·kg~(-1) and 200 mg·kg~(-1) of D. officinalis superfine powder for 20 consecutive weeks. During this period, blood pressure, blood lipid, blood glucose, insulin and other related indexes of glucose and lipid metabolism were monitored; the levels of lipopolysaccharide(LPS), C-reactive protein(CRP), interleukin 6(IL-6) and other inflammatory mediators were measured; the levels of nitric oxide(NO) and endothelin-1(ET-1) were detected, and the histomorphological and ultrastructural changes of aorta were observed. In addition, the expression of LPS/TLR4 pathway-related molecules in aorta was determined. The results showed that long-term administration of D. officinalis superfine powder significantly reduced the levels of systolic blood pressure(SBP), diastolic blood pressure(DBP) and mean arterial pressure(MBP) in metabolic hypertension model rats, decreased the levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-c), glucose(Glu), and insulin(INS) levels in blood, increased the contents of high density lipoprotein cholesterol(HDL-c),decreased the LPS, CRP, IL-6 and ET-1 levels in blood and increased NO content. Furthermore, it improved the abnormality of aortic histomorphology and endothelial ultrastructure, and inhibited the protein expression of TLR4, myeloid differentiation factor(MyD88), IL-6, interleukin-1 ß(IL-1ß), and tumor necrosis factor-α(TNF-α) as well as mRNA expression of TNF-α and IL-1ß in aorta. In conclusion, D. officinalis superfine powder may improve the abnormal function and structure of blood vessels by inhibiting the activation of LPS/TLR4 pathway, thus playing a role against metabolic hypertension.

Effect of grelin on TRX expression in chronic heart failure tissue: A protocol of systematic review and meta-analysis.

BACKGROUND: The aim of this study is to explore the effect of grelin on TRX expression (TRXE) in chronic heart failure tissue (CHFT). METHODS: We will search electronic databases from inception to the March 1, 2020 in MEDLINE, EMBASE, Cochrane Library, CINAHL, PEDro, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. We will not apply any limitations to the language and publication status. Any randomized controlled trials (RCTs) that studied the effect of grelin on TRXE in CHFT will be included. Study quality will be checked by Cochrane risk of bias and evidence quality will be appraised by Grading of Recommendations Assessment Development and Evaluation. All extracted data will be analyzed by RevMan 5.3 Software. RESULTS: This study will summarize the present RCTs to assess the effect of grelin on TRXE in CHFT. CONCLUSION: The results of this study will provide conclusive evidence of the effect of grelin on TRXE in CHFT. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040078.

Efficacy and complications of polyethylene glycols for treatment of constipation in children: a meta-analysis.

Constipation is a common childhood complaint. In 90% to 95% of children, constipation is functional, which means that there is no objective evidence of an underlying pathological condition. Polyethylene glycol (PEG or macrogol) solution is an osmotic laxative agent that is absorbed in only trace amounts from the gastrointestinal tract and routinely used to treat chronic constipation in adults. Here, we report the results of a meta-analysis of PEG-based laxatives compared with lactulose, milk of magnesia (magnesium hydroxide), oral liquid paraffin (mineral oil), or acacia fiber, psyllium fiber, and fructose in children. This meta-analysis was conducted in accordance with PRISMA guidelines and involved searches of MEDLINE, Cochrane, EMBASE, and Google Scholar databases up to February 10, 2014, using the keywords (Constipation OR Functional Constipation OR Fecal Impaction) AND (Children) AND (Polyethylene Glycol OR Laxative). Primary efficacy outcomes included a number of stool passages/wk and percentage of patients who reported satisfactory stool consistency. Secondary safety outcomes included diarrhea, abdominal pain, nausea or vomiting, pain or straining at defecation, bloating or flatulence, hard stool consistency, poor palatability, and rectal bleeding. We identified 231 articles, 27 of which were suitable for full-text review and 10 of which were used in the meta-analysis. Patients who were treated with PEG experienced more successful disimpaction compared with those treated with non-PEG laxatives. Treatment-related adverse events were acceptable and generally well tolerated. PEG-based laxatives are effective and safe for chronic constipation and for resolving fecal impaction in children. Children's acceptance of PEG-based laxatives appears to be better than non-PEG laxatives. Optimal dosages, routes of administration, and PEG regimens should be determined in future randomized controlled studies and meta-analyses.

[Impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer patients].

OBJECTIVE: To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients. METHODS: A total of 142 EGC cases screened from database of gastric cancer of Sun Yat-sen University, from Aug. 1994 to Jan. 2010, were included in this study. According to the lymph node metastasis status, they were divided into lymph node negative (n = 116) and lymph node positive (n = 26) groups. The clinicopathological features of the two groups and the impact of extent of lymph node dissection on the prognosis were analyzed. RESULTS: There were no significant differences in age, gender, tumor size and location, Borrmann typing, WHO TNM staging, histological typing, and CEA value between the two groups (P > 0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P < 0.001). Between the cases who underwent D1 (n = 21) and D2 (n = 121) dissection, there were no significant differences in postoperative hospital days, blood transfusion volume, and operation time (P > 0.05). The median numbers of LN dissected in D1 and D2 cases were 4 (0 to 16) and 20 (12 to 30), with a significant difference (P = 0.000), but the number of positive LN without significant difference (P = 0.502). The postoperative complication rates were 9.5% in the D1 and 3.3% in the D2 dissection groups, without a significant difference (P = 0.128). The median survival time of the lymph node negative and positive groups was 156 vs. 96 months (P = 0.010). In cases who received D2 and D1 lymph node dissection, the median survival time (MST) was 156 vs. 96 months (P = 0.0022). In the lymph node positive group, D2 dissection prolonged survival time significantly than D1 dissection (96 vs. 27months) (P = 0.001). Cox regression analysis showed that the extent of lymph node dissection and LN metastasis were independent prognostic factors for EGC patients. CONCLUSIONS: It is not able to accurately assess the LN metastasis status preoperatively according to the routine clinicopathological features. For the patients with unknown LN metastasis status, D2 dissection should be the first choice. Comparing with D1 dissection, the morbidity of D2 dissection are not increased, but survival time is prolonged.