Mechanism of Qili Qiangxin Capsule for Heart Failure Based on miR133a-Endoplasmic Reticulum Stress.

OBJECTIVE: To investigate the pharmacological mechanism of Qili Qiangxin Capsule (QLQX) improvement of heart failure (HF) based on miR133a-endoplasmic reticulum stress (ERS) pathway. METHODS: A left coronary artery ligation-induced HF after myocardial infarction model was used in this study. Rats were randomly assigned to the sham group, the model group, the QLQX group [0.32 g/(kg·d)], and the captopril group [2.25 mg/(kg·d)], 15 rats per group, followed by 4 weeks of medication. Cardiac function such as left ventricular ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the maximal rate of increase of left ventricular pressure (+dp/dt max), and the maximal rate of decrease of left ventricular pressure (-dp/dt max) were monitored by echocardiography and hemodynamics. Hematoxylin and eosin (HE) and Masson stainings were used to visualize pathological changes in myocardial tissue. The mRNA expression of miR133a, glucose-regulated protein78 (GRP78), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), X-box binding protein1 (XBP1), C/EBP homologous protein (CHOP) and Caspase 12 were detected by RT-PCR. The protein expression of GRP78, p-IRE1/IRE1 ratio, cleaved-ATF6, XBP1-s (the spliced form of XBP1), CHOP and Caspase 12 were detected by Western blot. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the rate of apoptosis. RESULTS: QLQX significantly improved cardiac function as evidenced by increased EF, FS, LVSP, +dp/dt max, -dp/dt max, and decreased LVEDP (P<0.05, P<0.01). HE staining showed that QLQX ameliorated cardiac pathologic damage to some extent. Masson staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue (P<0.01). Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of miR133a and inhibited the mRNA expressions of GRP78, IRE1, ATF6 and XBP1, as well as decreased the protein expressions of GRP78, cleaved-ATF6 and XBP1-s and decreased p-IRE1/IRE1 ratio (P<0.05, P<0.01). Further studies showed that QLQX significantly reduced the expression of CHOP and Caspase12, resulting in a significant reduction in apoptosis rate (P<0.05, P<0.01). CONCLUSION: The pharmacological mechanism of QLQX in improving HF is partly attributed to its regulatory effect on the miR133a-IRE1/XBP1 pathway.

[Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota].

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1ß, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Integration of transcriptomics and proteomics to elucidate inhibitory effect and mechanism of rosmarinic acid from Perilla frutescens (L.) Britt. in treating Trichophyton mentagrophytes.

BACKGROUND: Dermatophyte caused by Trichophyton mentagrophytes is a global disease with a growing prevalence that is difficult to cure. Perilla frutescens (L.) Britt. is an edible and medicinal plant. Ancient books of Traditional Chinese Medicine and modern pharmacological studies have shown that it has potential anti-fungi activity. This is the first study to explore the inhibitory effects of compounds from P. frutescens on Trichophyton mentagrophytes and its mechanism of action coupled with the antifungal activity in vitro from network pharmacology, transcriptomics and proteomics. METHODS: Five most potential inhibitory compounds against fungi in P. frutescens was screened with network pharmacology. The antifungal activity of the candidates was detected by a broth microdilution method. Through in vitro antifungal assays screening the compound with efficacy, transcriptomics and proteomics were performed to investigate the pharmacological mechanisms of the effective compound against Trichophyton mentagrophytes. Furthermore, the real-time polymerase chain reaction (PCR) was applied to verify the expression of genes. RESULTS: The top five potential antifungal compounds in P. frutescens screened by network pharmacology are: progesterone, luteolin, apigenin, ursolic acid and rosmarinic acid. In vitro antifungal assays showed that rosmarinic acid had a favorable inhibitory effect on fungi. The transcriptomic findings exhibited that the differentially expressed genes of fungus after rosmarinic acid intervention were mainly enriched in the carbon metabolism pathway, while the proteomic findings suggested that rosmarinic acid could inhibit the average growth of Trichophyton mentagrophytes by interfering with the expression of enolase in the glycolysis pathway. Comparison of real-time PCR and transcriptomics results showed that the trends of gene expression in glycolytic, carbon metabolism and glutathione metabolic pathways were identical. The binding modes and interactions between rosmarinic acid and enolase were preliminary explored by molecular docking analysis. CONCLUSION: The key findings of the present study manifested that rosmarinic acid, a medicinal compound extracted from P. frutescens, had pharmacological activity in inhibiting the growth of Trichophyton mentagrophytes by affecting its enolase expression to reduce metabolism. Rosmarinic acid is expected to be an efficacious product for prevention and treatment of dermatophytes.

[Terpinen-4-ol inhibits proliferation of VSMCs exposed to high glucose via regulating KLF4/NF-κB signaling pathway].

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1ß, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1ß, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.

Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota / 中国中药杂志

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1β, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Research progress in TCM treatment of Helicobacter pylori positive functional dyspepsia / 国际中医中药杂志

The incidence rate of functional dyspepsia (FD) is high. Helicobacter pylori (Hp) infection is one of the main causes of FD. Eradication of Hp is the current first-line treatment. However, the actual efficacy of eradicating Hp with the triple/quadruple therapy of Western medicine alone is not satisfactory for Hp-positive FD patients. TCM-assisted triple/quadruple therapy for Hp positive FD has a good efficacy, which has the effects of anti-Hp, regulating gastrointestinal hormones and gastric electrical parameters, and improving gastrointestinal motility. It can improve the eradication rate of Hp, effectively alleviate the clinical symptoms of patients, and improve the pathological conditions such as abnormal gastrointestinal secretion, abnormal motility, and abnormal sensation. The diagnostic and treatment idea of integrated TCM and Western medicine is worthy of summary and promotion.

Effect of WenXin KeLi on Improvement of Arrhythmia after Myocardial Infarction by Intervening PI3K-AKT-mTOR Autophagy Pathway.

Background: Myocardial infarction (MI) is an acute and serious cardiovascular disease. Arrhythmia after MI can lead to sudden cardiac death, which seriously affects the survival outcome of patients. WenXin KeLi is a Chinese patent medicine for the treatment of arrhythmia in a clinic, which can significantly improve symptoms of palpitation and play an important role in reducing the risk of arrhythmia after MI. In this study, we aimed to explore the pharmacological mechanism of WenXin KeLi in protecting the heart. Methods: The MI model was established by ligating the left coronary artery and the ventricular fibrillation threshold (VFT) was measured by electrical stimulation. The expression of connexin43 (CX43) and autophagy-related protein were measured by Western Blot, and correlation analysis was conducted to study the relationship between cardiac autophagy, CX43, and arrhythmia in rats after MI. The effects of WenXin KeLi on arrhythmia, cardiac structure, and function in MI rats were respectively observed by electrical stimulation, cardiac gross section, Masson staining, and cardiac ultrasound. The effects of WenXin KeLi on the expression of phosphoinositide 3 kinase-protein kinase B-mammalian targets of rapamycin (PI3K-AKT-mTOR) autophagy pathway and CX43 were observed by Western Blot. Results: After 4 weeks of MI, the VFT in the model group was significantly reduced, the expression levels of yeast ATG6 homolog (Beclin1), microtubule-associated protein 1A/1B-light chain 3 (LC3II/LC3I), and p-CX43 (S368) significantly increased, the expression of sequestosome-1(P62) and CX43 significantly decreased. LC3II/LC3I and Beclin1 expression were significantly negatively correlated with the VFT, and the expression of P62 and CX43 were significantly positively correlated with the VFT. LC3II/LC3I and Beclin1 expression were negatively correlated with CX43 expression, while P62 expression was positively correlated with CX43 expression. WenXin KeLi could significantly increase the VFT, reduce the deposition of collagen fibers, and increase the index levels of the left ventricular end-diastolic anterior wall (LVEDAW), interventricular septum end-diastolic (IVSED), left ventricular end-systolic anterior wall (LVESAW), interventricular septum end-systolic (IVSES), left ventricular end-diastolic posterior wall (LVEDPW), left ventricular end-systolic posterior wall (LVESPW), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and reduce the index levels of the left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). WenXin KeLi could increase the expression of CX43, P62, AKT, p-PI3K, p-AKT (308), p-AKT (473), and p-mTOR and decrease the expression of LC3II/LC3I and Beclin1. Conclusion: WenXin KeLi can activate the PI3K-AKT-mTOR signaling pathway, improve cardiac autophagy and Cx43 expression in rats after MI, reduce the risk of arrhythmia after MI, and play a cardioprotective role.

Retrospective study on Jinghua Weikang capsule combined with Bifidobacterium in the treatment of spleen-somach damp-heat syndrome featured by helicobacter pylori infection with low count / 国际中医中药杂志

Objective:To investigate the clinical efficacy of Jinghua Weikang capsule combined with Bifidobacterium for curing patients featured by spleen-stomach damp-heat syndrome and Helicobacter pylori (Hp) infection with low DOB values.Methods:To enroll 130 cases who were admitted to the Digestion Center of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from March 2019 to March 2020. According to the treaatment protocols, the quadruple therapy group and dual therapy group, each had 65 patients. The quadruple therapy group had two different treatment protocols, 34 cases with Rabeprazole sodium enteric-coated tablet, Bismuth potassium citrate capsule, Amoxicillin capsule, and Clarithromycin, the other one had 31 cases with Rabeprazole sodium enteric-coated tablet, Bismuth potassium citrate capsule, Amoxicillin capsule, and Levofloxacin tablets. The Dual therapy group was treated with Jinghua Weikang capsule combined with Bifidobacterium. As for quadruple therapy group, 14 days was a course of treatment, while28 days was a course of treatment for dual therapy group. The two groups were treated for one course, respectively. The TCM syndromes were scored before and after treatment. After 4-weeks long drug withdrawal, all cases were reexamined via 13C-UBT. The Hp eradication rate, efficacy evaluation and adverse reactions were compared between both groups.Results:The eradication rate was 90.8% (59/65) in quadruple therapy group and 78.5% (51/65) in dual therapy group. There was no statistical difference between two groups ( χ２=3.78, P=0.052). As for quadruple therapy group, the eradication rate was 91.2% (31/34) in Protocol One and 90.3% (28/31) in Protocol Two. There was no statistical difference between two protocols ( χ２=0.01, P=0.906). After treatment, the TCM syndrome score of quadruple therapy group [(7.02±0.89) vs. (6.51±0.85), Z=-3.01], was significantly higher than that of dual therapy group ( P<0.01). The total effective rate was 93.9% (61/65) in dual therapy group and 78.5% (51/65) in quadruple therapy group. There was statistically significantly difference between two groups ( χ２=6.45, P=0.011). The adverse reactions was 24.6% (16/65) in quadruple therapy group and 6.2% (4/65) in dual therapy group. There was statistically significantly difference in two groups ( χ２=8.51, P=0.004). Conclusions:The Jinghua Weikang capsule combined with Bifidobacterium had curative effects on Hp infected patients with low DOB values. It could improve TCM Syndromes with little adverse reactions.

Evaluation of the treatment of functional dyspepsia of deficiency cold of spleen and stomach by He Style fire acupuncture / 国际中医中药杂志

Objective:To observe the curative effect of He Style fire acupuncture on functional dyspepsia of deficiency cold of spleen and stomach syndrome.Methods:Sixty patients who met the inclusion criteria from March 2017 to March 2019 in Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University were divided into 2 groups according to the random number table method, with 30 in each group. The control group was given mosapride tablets, one tablet (5 mg) each time half an hour before meals. On the basis of the control group, the treatment group was given fire acupuncture on Zusanli(ST36), Zhongwan(CV12), Pishu(BL20), Weishu(BL21), Guanyuan(CV4) and Qihai (CV6) twice a week. The course of treatment for both groups of patients was 4 weeks. A follow-up was visited at 1 month after the treatment. The total Symptom Scores and Health-Related Quality of Life Scale (SF-36) scores were performed before and after treatment, and the total scores of syndromes of patients with Deficiency cold of spleen and stomach before and after treatment were used for clinical efficacy evaluation, and adverse events during treatment were recorded.Results:The total efficiency of the treatment group was 93.3% (28/30), and 76.7% (23/30) in the control group, and the 2 groups were statistically significant ( χ2=4.78, P<0.05). After treatment, the upper abdominal pain, upper abdominal burning, postprandial fullness and discomfort, early satiety, and total scores in the treatment group were significantly lower than those in the control group ( t values were 4.27, 5.16, 3.93, 4.69, 4.28, respectively, all Ps<0.05); during follow-up, the upper abdominal pain, upper abdominal burning, postprandial fullness and discomfort and the total scores in the treatment group were significantly lower than those in the control group ( t values were 3.63, 3.22, 4.03, 3.04, respectively, all Ps<0.05). In terms of SF-36, after treatment, the treatment group showed significantly higher scores in the control group of physical function, physiology, mental health, and health changes compared with the control group ( t values were 2.97, 4.05, 4.22, 3.05, respectively, all Ps<0.05). During follow-up, the treatment group with physiological function, physical function, physical pain, overall health, life vitality, mental health, health changes scores were significantly higher than those in the control group ( t values were 3.27, 4.23 3.85, 3.15, 3.25, 6.15, 3.85, respectively, all Ps<0.05). Conclusion:He Style fire acupuncture combined with western medicine treatment can improve the symptoms of upper abdominal pain and upper abdominal burning, and the quality of lifein the patients with functional dyspepsia.

Ganhai Weikang capsule in the treatment of functional dyspepsia: a prospective randomized, double-blind, placebo-controlled parallel clinical study / 中华消化杂志

Objective:To explore the efficacy and safety of Ganhai Weikang capsule (GWC) in the treatment of functional dyspepsia (FD).Methods:A randomized, double-blind, placebo-controlled parallel, multi-center, superiority clinical trial was conducted. From March 2018 to April 2020, totally 324 patients with dyspepsia symptoms, who were diagnosed as chronic non-atrophic gastritis by endoscopy and pathology and met the Rome Ⅳ diagnostic criteria for FD from 7 top hospitals were enrolled, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Heilongjiang Hospital of Traditional Chinese Medicine, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Qilu Hospital of Shandong University, the First Affiliated Hospital of Zhejiang University, Beijing Hospital of Traditional Chinese Medicine of Capital Medical University and the Third Xiangya Hospital of Central South University. The patients were randomly divided into the GWC group and the placebo group according to the ratio of 1∶1. The patients of GWC group were given GWC and the patients of placebo group were given GWC capsule simulant. The patients of both groups orally took capsules before meals, 2.4 g each time and 3 times per day, and the course of treatment was 4 weeks. The main efficacy index was the total clinical effective rate after 4 weeks, and the secondary efficacy index was the changes of clinical symptom scores of upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety. The safety index included laboratory tests and adverse events. Chi-square test and Wilcoxon rank sum test were used for statistical analysis.Results:A total of 320 FD patients were enrolled in the full analysis set (FAS), which included 161 cases in GWC group and 159 cases in placebo group. A total of 298 cases were in the per-protocol set (PPS), 149 cases each in GWC group and placebo group. The results of FAS and PPS both showed that the total clinical effective rates of the GWC group were higher than those of the placebo group (84.5%, 136/161 vs. 44.0%, 70/159 and 83.9%, 125/149 vs. 46.3%, 69/149), and the differences were statistically significant ( χ2=57.07 and 46.32, both P<0.001). In addition, the differences of the total score of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (FAS: 10 (7, 14) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 3); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs. 1 (0, 3). PPS: 10 (7, 13) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 2); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs.1 (0, 3)), and the differences were statistically significant (FAS: Z=5.80, 5.91, 3.19, 3.72 and 3.30; PPS: Z=5.14, 5.11, 2.86, 3.21 and 2.84; all P<0.01). The results of FAS and PPS indicated that the improvement rates of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) of GWC group were all higher than those of the placebo group (FAS: 77.8% (54.6%, 91.3%) vs. 42.9% (28.6%, 61.5%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 60.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 41.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%). PPS: 77.8% (54.2%, 89.5%) vs. 44.0% (28.6%, 65.0%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 46.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%)), and the differences were statistically significant (FAS: Z=8.60, 7.72, 4.98, 4.24 and 5.61; PPS: Z=7.90, 7.03, 4.49, 3.88 and 4.83; all P<0.001). After 2 weeks of treatment, the differences of the total score of main symptoms and score of each symptom (upper abdominal pain, upper abdominal burning and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (5.0 (3.0, 8.0) vs. 4.0 (2.0, 6.0); 2.0 (1.0, 2.0) vs. 2.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0)), and the differences were statistically significant ( Z=2.95, 3.44, 2.43 and 2.79, all P<0.05). There was no significant difference in the incidence of adverse events between the GWC group and the placebo group (0.6%, 1/163 vs. 0, 0/159). Conclusion:The clinical total effective rate of GWC in the treatment of FD is superior to that of placebo and it has good safety.

Treatment for overactive bladder: A meta-analysis of transcutaneous tibial nerve stimulation versus percutaneous tibial nerve stimulation.

BACKGROUND: We aim to compare the safety and effectiveness of transcutaneous tibial nerve stimulation (TTNS) versus percutaneous tibial nerve stimulation (PTNS) in treating overactive bladder. METHODS: A systematical search on PubMed, Embase, clinicalTrial.gov, and Cochrane Library Central Register of Controlled Trials from January 1, 1999 to November 1, 2020 was performed. The primary outcomes were the changes in a 3-day voiding diary. Quality of life scores were also evaluated. Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) was applied to conduct all statistical analyses. RESULTS: A total of 4 trials (2 randomized controlled trials, 1 retrospective study, and 1 before-after study) with 142 patients were eventually enrolled. Compared with PTNS, TTNS had a similar performance in the voiding frequency in 24 hours (mean difference [MD] = -0.65, 95% confidence interval [CI]: -1.35 to 0.05, P = .07), the number of urgency episodes in 24 hours (MD = 0.13, 95% CI: -0.36 to 0.62, P = .60), the number of incontinence episodes in 24 hours (MD = 0.01, 95% CI: -0.13 to 0.14, P = .93), as well as in the nocturia frequency (MD = -0.14, 95% CI: -0.52 to 0.24, P = .47). Moreover, comparable results were observed regarding HRQL scores (P = .23) and incontinence quality of life scores (P = .10) in both groups. The total complication rate in the current study was 2.1% (3/142). No adverse events were identified in the TTNS group. CONCLUSION: Current data supported that TTNS is as effective as PTNS for the treatment of overactive bladder, moreover, with no reported adverse events. However, the evidence is low-grade and well-designed prospective studies with a large sample size are warranted to verify our findings.

Clinical characteristics of drug-induced autoimmune hepatitis / 中国实用内科杂志

OBJECTIVE: To investigate the clinical characteristics of drug-induced autoimmune hepatitis(DIAIH), in order to help clinicians learn more about DIAIH and improve its clinical diagnosis. METHODS: This was a retrospective study in the patients with DIAIH and DILI treated at Shengjing Hospital of China Medical University between January 2013 and December 2017. The population characteristic,related drugs,clinical manifestations,liver biochemical parameters, autoimmune antibodies, and liver pathological features were compared between the two groups. RESULTS: There were 49 patiens with DIAIH and 436 patiens with DILI. The majority of these patients were female. There was a significant difference in the proportion of female patients, with DIAIH(91.84%, 45/49)higher than DILI(70.41%, 307/436)(χ~2=9.111, P=0.003). The patients with DIAIH had a mean age of(50.0±7.4) years. The top three drugs inducing DIAIH were Chinese herbal medicines(53.06%, 26/49), non-steroidal anti-inflammatory drugs(10.20%, 5/49) and fluvastatin(10.20%, 5/49). DIAIH occurred after more than 8 weeks of treatment. There was a significant difference in the proportion of liver failure, with DIAIH(30.61%, 15/49) higher than DILI(14.68%, 64/436)(χ~2=8.20, P=0.004). The risks of DIAIH and DILI with liver failure caused by western medicines were significantly higher than those by Chinese herbal medicines(χ~2=9.77, P=0.002; χ~2=16.09,P<0.001). The positive rate of autoimmune antibody in DIAIH patients was 100%. The positive rate of ANA was 83.67%(41/49), and that of SMA was 16.33%(8/49). The liver pathological features of interface hepatitis, plasma cells and lymphocytes infiltration in DIAIH patients were more obvious than those in DILI patients. CONCLUSION: DIAIH is more common in the female patients and is caused frequently by Chinese herbal medicines. DIAIH caused by western medicines could easily result in liver failure.

Effect of Ding's herb enema prescription on intestinal tissue relateddifferences target in rat colitis using protein array technology / 中国药理学通报

Aim To investigate the effect of Ding''s herb enema prescription on intestinal tissue related target in rat colitis induced by dextran sulfate sodium(DSS), and to elucidate the mechanism of Ding''s herb enema prescription in improving the intestinal inflammation and intestinal fibrosis.Methods Rats were fed with 3.5％ DSS.The rats were randomly divided into positive drug group, model group, Control group, and Ding''s herb enema prescription group.The positive drug group was treated with mesalazine enema, and Ding''s herb enema prescription group was treated with Ding''s herb enema prescription.The colon mucosa was taken once a day for 6 weeks.The changes of intestinal inflammatory response and intestinal fibrosis related proteins were detected by GSR-CAA-67 antibody protein array, and the differentially expressed proteins were screened out.Results Eight proteins showed statistical differences, including IFN-γ, erythropoietin(EPO), TIMP-2, TIM-1, IL-6, TIMP-1, TNF-α, IL-22 (P0.05).Conclusions Ding''s herb enema prescription has the effect of multiple targets, which may improve the intestinal inflammatory response and intestinal fibrosis to achieve the purpose of treatment of ulcerative colitis(UC).

Meta-Analysis of the Association between Tea Intake and the Risk of Cognitive Disorders.

BACKGROUND: Alzheimer's disease is a common neurodegenerative disorder in elderly. This study was aimed to systematically evaluate the association between tea intake and the risk of cognitive disorders by meta-analysis. METHODS AND FINDINGS: PubMed, Embase and Wanfang databases were systematically searched and a total of 26 observational studies were included in this study. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated and pooled by using fixed or random effects models according to the degree of heterogeneity. RESULTS: The overall pooled analysis indicated that tea intake could significantly reduce the risk of cognitive disorders (OR = 0.65, 95%CI = 0.58-0.73). Subgroup analyses were conducted based on study design, population, frequency of tea drinking and type of cognitive disorders. The results showed that tea drinking was significantly associated with the reduced incidence of cognitive disorders in all of subgroups based on study design and frequency of tea drinking. In particular, tea drinking was inversely associated with the risk of cognitive impairment (CoI), mild cognitive impairment (MCI), cognitive decline and ungrouped cognitive disorders. Moreover, for population subgroups, the significant association was only found in Chinese people. CONCLUSION: Our study suggests that daily tea drinking is associated with decreased risk of CoI, MCI and cognitive decline in the elderly. However, the association between tea intake and Alzheimer's disease remains elusive.

Oncostatin M-dependent Mcl-1 induction mediated by JAK1/2-STAT1/3 and CREB contributes to bioenergetic improvements and protective effects against mitochondrial dysfunction in cortical neurons.

Oncostatin M (OSM), a cytokine in the interleukin-6 (IL-6) family, has been proposed to play a protective role in the central nervous system, such as attenuation of excitotoxicity induced by N-methyl-D-aspartate (NMDA) and glutamate. However, the potential neuroprotective effects of OSM against mitochondrial dysfunction have never been reported. In the present study, we tested the hypothesis that OSM may confer neuronal resistance against 3-nitropropionic acid (3-NP), a plant toxin that irreversibly inhibits the complex II of the mitochondrial electron transport chain, and characterized the underlying molecular mechanisms. We found that OSM preconditioning dose- and time-dependently protected cortical neurons against 3-NP toxicity. OSM stimulated expression of myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic Bcl-2 family member expressed in differentiating myeloid cells, that required prior phosphorylation of Janus kinase-1 (JAK1), JAK2, extracellular signal-regulated kinase-1/2 (ERK1/2), signal transducer and activator of transcription-3 (STAT3), STAT1, and cAMP-response element-binding protein (CREB). Pharmacological inhibitors of JAK1, JAK2, ERK1/2, STAT3, STAT1, and CREB as well as the siRNA targeting at STAT3 and Mcl-1 all abolished OSM-dependent 3-NP resistance. Finally, OSM-dependent Mcl-1 induction contributed to the enhancements of mitochondrial bioenergetics including increases in spare respiratory capacity and ATP production. In conclusion, our findings indicated that OSM induces Mcl-1 expression via activation of ERK1/2, JAK1/2, STAT1/3, and CREB; furthermore, OSM-mediated Mcl-1 induction contributes to bioenergetic improvements and neuroprotective effects against 3-NP toxicity in cortical neurons. OSM may thus serve as a novel neuroprotective agent against mitochondrial dysfunction commonly associated with pathogenic mechanisms underlying neurodegeneration.

Treating non-alcoholic fatty liver disease patients of Gan stagnation Pi deficiency syndrome by tiaogan lidi recipe: a randomized controlled clinical trial / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of tiaogan Lipi Recipe (TLR) in treating non-alcoholic fatty liver disease (NAFLD) patients of Gan stagnation Pi deficiency syndrome (GSP-DS).</p><p><b>METHODS</b>A randomized, double blind, placebo-controlled clinical trial was performed. Totally 99 NAFLD patients of GSPDS were randomly allocated into two groups, 66 patients in the treatment group (treated with-TLR, one dose per day) and 33 patients in the control group (treated with placebos, one dose per day). The therapeutic course for all was 12 weeks. All patients received lifestyle interventions including moderate aerobic exercise, moderate caloric restriction, and dietary changes. Clinical symptoms, CT indices, liver functions and blood lipids were observed before and after treatment.</p><p><b>RESULTS</b>After 12 weeks of treatment, the total score of clinical symptoms decreased in the two groups (P <0. 01), and it was lower in the treatment group than in the control group (P <0. 05). Liver/spleen CT ratio increased in the treatment group (P <0. 01), and it was higher in the treatment group than in the control group (P <0. 01). After treatment levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) all decreased in the treatment group (P <0. 05, P <0. 01), while levels of ALT decreased in the control group (P <0. 05). Besides, all the 3 levels mentioned above were lower in the treatment group than in the control group (P <0. 05). Levels of total cholesterol (CHO) and triglyceride (TG) decreased in the two groups (P <0. 05), and they were lower in the treatment group (P <0. 05). Total effective rates of TCM syndrome, abdominal CT, liver functions, and blood lipids were 79. 69% (51/64 cases), 54. 69% (35/64 cases), 67. 65% (23/34 cases), and 67. 39% (31/46 cases) in the treatment group, while they were 56. 25% (18/32 cases), 25. 00% (8/32 cases), 33. 33% (6/18 cases), and 55. 56% (10/18 cases) in the control group. All were superior in the treatment group (P <0.05, P <0.01, respectively).</p><p><b>CONCLUSION</b>TLR combined with lifestyle intervention could safely and effectively improve clinical symptoms of NAFLD patients of GSPDS, elevate liver/spleen CT ratios, and play a role in liver protection, anti-inflammation, and lowering blood lipids.</p>

[Effects of selective inhibition of reverse mode of Na(+)/Ca(2+) exchanger on rats with contrast-induced acute kidney injury].

OBJECTIVE: Intracellular Ca(2+) overload is a key factor in contrast-induced renal tubular toxicity. Na(+)/Ca(2+) exchanger (NCX) system is one of main pathways of intracellular Ca(2+) overload. We explore the effects of KB-R7943, an inhibitor of reverse mode of NCX, on contrast-induced acute kidney injury (CI-AKI). METHODS: Rats were divided into control, CI-AKI and pre-treatment groups with KB-R7943 (5, 10 mg/kg). CI-AKI was induced by diatrizoate administration in rats with cholesterol-supplemented diet for 8 weeks. Renal function and hemodynamics were determined at Day 1 post-administration. Renal histopathology was observed under light microscope. Renal tubular apoptosis was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Renal endothelin-1 (ET-1) was measured by radioimmunoassay. The oxidative markers of renal malondialdehyde (MDA) and catalase (CAT) were measured. The expression of NCX was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Levels of serum creatinine (Scr, µmol/L ) in CI-AKI rats ((149 ± 35) µmol/L) were significantly higher than those of normal rats ((55 ± 4) µmol/L, P < 0.01). Renal ET-1, MDA and CAT, resistance index (RI) of renal blood vessels increased significantly in CI-AKI rats. The contrast-induced increases in Scr and RI of renal blood vessels were suppressed significantly and dose-dependently by pretreatment with KB-R7943. Histopathological and TUNEL results showed that contrast-induced severe renal tubular necrosis and apoptosis were significantly and dose-dependently attenuated by KB-R7943. KB-R7943 significantly suppressed the contrast-induced increments of ET-1, MDA and CAT. No significant changes in NCX1 mRNA expression were observed following contrast administration. CONCLUSION: Renal oxidative stress and ET-1 overproduction via the activation of reverse mode of NCX play an important role in the pathogenesis of CI-AKI. And inhibition of reverse mode of NCX expressed in renal tubular epithelial cell has protective effects on CI-AKI.

Do probiotics improve eradication response to Helicobacter pylori on standard triple or sequential therapy?

BACKGROUND: The standard triple therapy for the eradication of Helicobacter pylori consists of a combination of a proton pump inhibitor at a standard dose together with two antibiotics (amoxicillin 1000 mg plus either clarithromycin 500 mg or metronidazole 400 mg) all given twice daily for a period of 7-14 days. Recent reports have shown a dramatic decline in the rate of H. pylori eradication utilizing standard triple therapy from 95% down to 70-80%. AIMS: Our study was designed to evaluate the effect of adding a probiotic as an adjuvant to common regimens used for H. pylori eradication. MATERIALS AND METHODS: An open label randomized observational clinical study was designed to test three different regimens of H. pylori eradication treatment: Standard triple therapy with a concomitant probiotic added at the same time (n = 100), starting the probiotic for 2 weeks before initiating standard triple therapy along with the probiotic (n = 95), and the third regimen consists of the probiotic given concomitantly to sequential treatment (n = 76). The three arms were compared to a control group of patients treated with the traditional standard triple therapy (n = 106). RESULTS: The eradication rate for the traditional standard therapy was 68.9%, and adding the probiotic "Bifidus infantis" to triple therapy, led to a successful rate of eradication of 83% (P < 0.001). Pre-treatment with 2 weeks of B. infantis before adding it to standard triple therapy increased the success rate of eradication to 90.5%. Similar improvement in eradication rate was noted when B. infantis was added as an adjuvant to the sequential therapy leading to an eradication rate of 90.8%. CONCLUSION: Adding B. infantis as an adjuvant to several therapeutic regimens commonly used for the eradication of H. pylori infection significantly improves the cure rates.

A randomized trial of Chinese medicine Lirukang Granule combined with psychological intervention for cyclomastopathy and menoxenia.

OBJECTIVE: To observe the influence of therapy with Chinese medicine Lirukang Granule (, LRKG) combined with psychological intervention on anxiety states and sex hormones in patients with cyclomastopathy and menoxenia. METHODS: A total of 470 subjects were randomly assigned to three groups by the net-central randomization system, the treatment group (161 patients, treated with LRKG and psychological intervention), the Chinese medicine group (157 patients, treated with LRKG), and the psychological intervention group (152 patients, treated with psychological intervention). The dose of LRKG was 12 g three times per day; psychological intervention included establishing relations, cognitive intervention and psychological persuasion, 30-40 min per session, once a week. The therapy duration for all groups was three months. The efficacy was compared and anxiety state/State-Trait Anxiety Invertory (STAI) scoring was measured before and after treatment. The serum estradiol (E2), progesterone (P), prolactin (PRL) and follicle stimulating hormone (FSH) levels of 60 patients selected randomly from each group during the luteal phase were measured before and after treatment, and a group of 20 healthy women were evaluated for comparison. A follow-up was arranged for one year after treatment. RESULTS: Thirty subjects were lost to follow-up. (1) Comparison of efficacy: the markedly effective rate and the total effective rate of the treatment group were 86.67% (131/150) and 98.00% (147/150), respectively; of the Chinese medicine group, 64.58% (93/144) and 90.27% (130/144), respectively; and of the psychological intervention group, 0% (0/146) and 3.42% (5/146), respectively. The markedly effective rate and the total effective rate in the treatment group were significantly higher than those in the Chinese medicine and psychological intervention groups (P < 0.05). (2) Comparison of STAI scoring: STAI scoring was decreased dramatically in the treatment group after treatment compared with that of the Chinese medicine group (P < 0.01), but there was no significant difference compared with the psychological intervention group. (3) Comparison of levels of sex hormones: E2, P, PRL and FSH of the three patient groups were disordered before treatment, and significantly different from healthy women (P < 0.01). After treatment, the levels of P and FSH of the treatment group were significantly increased (P < 0.01), E2 and PRL were significantly reduced, which were also significantly decreased compared with the psychological intervention groups (P < 0.01). (4) FOLLOW-UP: the markedly effective rate and the total effective rate of the treatment group remained higher than those of the other two groups after one year of treatment (P < 0.05). (5) Adverse reactions: no obvious adverse reactions were found among the three groups. CONCLUSIONS: Therapy with Chinese medicine combined with psychological intervention was effective for short-term and long-term treatment of cyclomastopathy and menoxenia. The mechanism might be related to the regulation of sex hormones.

A randomized controlled trial comparing total glucosides of paeony capsule and compound glycyrrhizin tablet for alopecia areata.

OBJECTIVE: To observe the efficacy and safety of total glucosides of paeony capsule (TGPC) in patients with mild and moderate alopecia areata. METHODS: A total of 86 outpatients were randomly allocated into two groups of TGPC (treatment, 44 cases) and compound glycyrrhizin tablet (control, 42 cases). The treatment group was given oral TGPC, three times daily and 600 mg per time; the control group was given oral compound glycyrrhizin tablets, three times daily and 50 mg per time. In addition, both groups were given 10 mg of vitamin B(2) and tapped the bold patches with massage. The treatment course was three months for both groups. Peripheral blood T-cell subsets (CD3(+)CD4(+), CD3(+)CD8(+), Th, Ts, Th/Ts) of 10 patients randomly selected from each group respectively were tested before and after three months of treatment. The effectiveness and adverse reaction of all cases were observed each month. The safety was evaluated according to the incidence rate of adverse reaction. RESULTS: In the treatment group, the cured and markedly effective rate was 36.36% (16/44), 50.00% (22/44) and 68.18% (30/44) at the end of first, second and third month of treatment, respectively, and the incidence rate of adverse reaction was 13.64% (6/44). In the control group, the cured and markedly effective rate was 38.10% (16/42), 57.14% (24/42) and 71.43% (30/42), respectively, and the incidence rate of adverse reaction was 16.67% (7/42). The cured and markedly effective rate and the incidence rate of adverse reaction were similar in both groups (P>0.05). TGPC and compound glycyrrhizin tablet can inhibit CD3(+)CD4(+) and CD3(+)CD8(+), and decrease the ratio of Th/Ts (P<0.05). CONCLUSION: TGPC is effective and safe in the treatment of alopecia areata.