The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional ; Quality of Life ; Randomized Controlled Trials as Topic ; Rheumatic Heart Disease/drug therapy* ; Treatment Outcome

Aim To investigate the therapeutic effects of piperine (PIP) on atherosclerosis in ApoE mice fed with high fat diet and the potential mechanisms. Methods After PIP was administered for 20 weeks, aorta was stained by oil red O with the area of aortic plaque analyzed. The levels of blood lipids and serum inflammatory factors were detected. Hepatic expressions of oxidative stress related factors were determined. Human umbilical vein endothelial cells (HUVECs) were cultured and treated with a series of concentrations of PIP after LPS induction. The levels of NO and oxidative lipids were detected and factors of PI3K/Akt/eNOS pathway were analyzed. Results Serum levels of TG, LDL-C, TNF-α and CRP were significantly reduced by PIP in ApoE

Objective:To introduce the construction of Henan Cerebral Palsy Register and Rehabilitation Management System (HCPRRMS) and to explore the construction project of regional register and surveillance of cerebral palsy. Methods:The construction process, registration content and preliminary results of HCPRRMS were systematically introduced. Results:HCPRRMS was independent developed in 2014. Since March, 2015, the system has been used to register information of patients with cerebral palsy in the Third Affiliated Hospital of Zhengzhou University. Until September, 2019, a total of 23 child rehabilitation institutions had used the registration management system. There were 1357 patients with cerebral palsy registered in this system, in which 936 cases (68.98%) were male, 501 cases (36.92%) were with gestational weeks < 37, 443 cases (32.65%) were with birth weight < 2500 g, and 430 cases (31.69%) were born with hypoxic-ischemic encephalopathy. Among them, the spastic cerebral palsy patients (1117 cases, 86.74%) accounted for the highest proportion. There was significant difference among types of cerebral palsy and the classification of GMFCS. A total of 1117 patients with cerebral palsy showed MRI-identified brain abnormalities, in which, periventricular leukomalacia accounted for the most (480 cases). For the complications, epilepsy accounted for 14.44% (196 cases), vision impairment accounted for 8.03% (109 cases), hearing impairment accounted for 11.64% (158 cases). Among 769 cases aged more than two years, language-speech dysfunction accounted for 52.66% (424 cases); and among 216 cases aged more than four years, mental retardation accounted for 37.96% (82 cases). Conclusion:HCPRRMS could help to understand the risk factors, clinical characteristics, and complications of cerebral palsy.

About 15%-20% of drug-induced liver injury (DILI) will progress to chronic manifestation (CH-DILI), which sometimes advances rapidly to liver cirrhosis (LC-DILI) within 0.5-1 year with deteriorative clinical prognosis. Therefore, it is important to find a non-invasive diagnosis for early detection of liver cirrhosis. In this study, the metabolomic profiles revealed significant differences in the metabolites from the plasma of LC-DILI versus CH-DILI. We found 35 differential metabolites through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Through pathway enrichment analysis, some up-regulated metabolic pathways reflected impaired liver functions such as bile acid, lipid synthesis and decomposition during cirrhosis. Five biomarkers were found to exhibit effective diagnosis value (AUC > 0.6), including phosphatidylcholine, lysoPC (18:1 (9Z)), creatine, taurochenodeoxycholic acid and taurocholic acid. Furthermore, we found that the relative content ratio between phosphatidylcholine and lysoPC (18:1 (9Z)) had a better distinguishing ability (AUC = 0.867). The relative content ratio also had the feature to reduce systematic errors of sample processing and instrument detection, therefore having a greater value for clinical application.

The objective of this work was to develop a bioassay to quantify the antiplatelet aggregation activity of hirudo for quality evaluation and control. Antithrombin activity of hirudo extracted by high temperature decoction was determined by thrombin titration. Antiplatelet aggregation activity of hirudo was determined through pharmacodynamic experiments in vitro and in vivo using a bioassay we developed for quantifying inhibition of platelet aggregation. Methodological investigation was carried out and the titers of 12 batches of hirudo samples were determined. During the experiment, the disposal of animals is in accordance with the ethical standards of animal experiments. The results showed that the antithrombin activity of hirudo decocted at high temperature decreased significantly and almost lost its activity. Hirudo inhibited platelet aggregation and results in vivo and in vitro were consistent. These assays were employed to test 12 batches of hirudo. The results demonstrated that the biopotency of 12 batches was 113.49, 96.13, 121.22, 127.33, 83.48, 108.72, 131.41, 127.95, 76.90, 126.27, 132.89 and 573.53 U·mg^-1. The method was reliable and reproducible and can be used to assess the quality of hirudo.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

To explore novel antifatigue agents targeting with AMPA receptor, 10 compounds were synthesized and their structures were confirmed by 1H NMR, ESI-MS and elemental analysis. 1-BCP was treated as the leading compound. The antifatigue activities were evaluated by weight-loaded forced swimming test, and the AMPA receptor binding affinities were tested with radioligand receptor binding assays. The results unveiled that 5b appeared to possess potent antifatigue activities and high affinity with AMPA receptor, which deserved further studies.
Animals ; Benzamides ; chemistry ; pharmacology ; Dioxoles ; chemistry ; pharmacology ; Fatigue ; prevention & control ; Piperidines ; chemistry ; pharmacology ; Radioligand Assay ; Receptors, AMPA ; metabolism ; Swimming

OBJECTIVETo investigate the effects of naringin on the proliferation, differention and maturaion of rat calvarial osteoblasts (ROB).

METHODSegregated neonatal SD rat skull, enzyme digestion to obtain ROB. The culture medium was replaced every three days. Serial subcultivation proceeded when cells covered with 80% culture dish. Naringin supplemented into the culture at 1 x 10(-4), 1 x 10(-5), 1 x 10(-6), 1 x 10(-7) mol x L(-1) respectively. MTT method was adopted in proliferation analysis and the activity of ALP was examined after induced 9 days. Search the best concentration and supplemented into the medium, then the osteogenic differentiation markers including the secretion amount of osteocalcin, osteopontin and bone morphogenetic protein-2 were compared between the naringin-supplemented group and the control. Total RNA was isolated and the mRNA level of bFGF, IGF-1, Runx-2, Osterix, ERa and ERbeta was investigated by Real time RT-PCR. Total protein also was isolated and the expression ERa, ERbeta and collagen I was examined by Western blot. After the addition of ICI 182.780, an inhibitor of the estrogen signal pathway, these index also was examined and the changes were compared.

RESULTThe ROB proliferation was motivated by naringin dose-dependently. And it evidently leads to osteogenic process and maturation. 1 x 10(-5) mol x L(-1) is the best concentration. Naringin improved the secretion of osteocalcin, osteopontin, bone morphogenetic protein-2 and collagen I significantly. Besides, it can also enhanced the mRNA level of bFGF, IGF-1, Runx-2, Osterix, ERalpha and ERbeta. While all these effects can be restrained by ICI 182.780.

CONCLUSIONThe naringin with final concentration of 1 x 10(-5) mol x L(-1) enhances the osteogenic differentiation and maturation of ROB significantly, while the promoting effects vanished after the addition of ICI 182.780. These results suggesting that naringin is one of the phytoestrogens and have the activity of bone formation may via estrogen signal pathway, it can be developed into a new drug for osteoporosis therapy.

Alkaline Phosphatase ; genetics ; metabolism ; Animals ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Flavanones ; pharmacology ; Insulin-Like Growth Factor I ; genetics ; metabolism ; Osteoblasts ; cytology ; drug effects ; metabolism ; Osteocalcin ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Skull ; cytology ; drug effects ; metabolism

Objective This study compares a dual-freeze protocol with a triple freeze protocol for hepatic cryoablation in the Tibetan pig model.Method Cryoablation with a dual-(10-5-10-5 min)and triple-freeze (5-5-5-5-10-5 min) protocol for the normal livers of 9 Tibet pigs was performed under exposed operation.Temperature changes of cryoprobes and diameter changes of iceballs were measured during the ablation,and seven days later the pathological changes of cryozones were reviewed and the surface and depth cryolesions were measured.Results Compared with cryoablation with two freeze-thaw cycles,there was a greater iceball diameter for cryoablation by three freeze-thaw cycles.Also,seven days after cryosurgery,there were similar surface and deep cryolesions in dual-and triple-freeze protocols.Pathologically,the triple freezing protocol was associated with a longer zone of complete necrosis.Conclusions With the same freezing time (20 min),the triple-freeze protocol may become a more powerful liver-ablation method in cryosurgical application.

OBJECTIVETo observe the effects of prenatal exposure to low level lead on the protein and mRNA expression of growth-associated protein (GAP-43) in hippocampus of rat's offspring, and to explore the molecular mechanisms of lead on learning and memory.

METHODSThe pregnant rats were randomizedly divided into 4 groups and provided with doubly evaporated water in control group and 125, 250, 500 mg/L lead acetate solution via drinking water in treatment groups respectively during pregnancy. When the rat's offspring was 1, 21, 60 days old, the lead content in hippocampus was measured by hydride generation atomic absorption spectrometry, and the GFAP protein and mRNA expression at hippocampal CA1 region were observed by immunohistochemistry and in situ hybridization.

RESULTSThe content of lead in the hippocampus was (1.64 +/- 0.32), (2.33 +/- 0.42) and (3.28 +/- 0.58) microg/L, and (0.94 +/- 0.18), (1.27 +/- 0.26) and (1.79 +/- 0.42) microg/L respectively in the low, middle and high lead dosage group when the rat's offspring was one day and 21 day old. When the rat's offspring was 1, 21 days old, the content of lead in hippocampus in treatment groups was significant higher than that of control (P < 0.05), the integral optical density of GAP-43 protein and mRNA expression (except low dosage treatment at 21 d) were significantly decreased compared with the control (P < 0.01, P < 0.05), but there was no significant difference at 60-day old offsprings for the parameters above.

CONCLUSIONExposure to low level lead during pregnancy could inhibit the GAP-43 protein and mRNA expression in hippocampus of rat's offspring, which may be one of the molecular mechanisms of lead on learning and memory.

Animals ; Environmental Exposure ; adverse effects ; Female ; GAP-43 Protein ; genetics ; metabolism ; Hippocampus ; drug effects ; metabolism ; Lead ; toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar