Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability.

The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1ß that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability.

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

Integrated metabolomic and transcriptomic analysis of triterpenoid accumulation in the roots of Codonopsis pilosula var. modesta (Nannf.) L.T.Shen at different altitudes.

INTRODUCTION: Codonopsis Radix is a beneficial traditional Chinese medicine, and triterpenoid are the major bioactive constituents. Codonopsis pilosula var. modesta (Nannf.) L.T.Shen (CPM) is a precious variety of Codonopsis Radix, which is distributed at high mountain areas. The environment plays an important role in the synthesis and metabolism of active ingredients in medicinal plants, but there is no report elaborating on the effect of altitude on terpenoid metabolites accumulation in CPM. OBJECTIVES: This study aims to analyse the effects of altitude on triterpenoid biosynthetic pathways and secondary metabolite accumulation in CPM. MATERIAL AND METHODS: The untargeted metabolomics based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and 10 triterpenoids based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method were analysed at the low-altitude (1480 m) and high-altitude (2300 m) CPM fresh roots. The transcriptome based on high-throughput sequencing technology were combined to analyse the different altitude CPM triterpenoid biosynthetic pathways. RESULTS: A total of 17,351 differentially expressed genes (DEGs) and 55 differentially accumulated metabolites (DAMs) were detected from the different altitude CPM, and there are significant differences in the content of the 10 triterpenoids. The results of transcriptome study showed that CPM could significantly up-regulate the gene expression levels of seven key enzymes in the triterpenoid biosynthetic pathway. CONCLUSIONS: The CPM at high altitude is more likely to accumulate triterpenes than those at low altitude, which was related to the up-regulation of the gene expression levels of seven key enzymes. These results expand our understanding of how altitude affects plant metabolite biosynthesis.

PGC-1α affects cochlear pericytes migration in noise-exposed mice.

OBJECTIVE: The study aimed to observe the effects of noise exposure on the pericytes of the cochlear stria vascularis (SV) in mice and to investigate its molecular mechanism. METHOD: Male C57BL/6J mice aged 6-8 weeks were used as the subjects. Auditory Brainstem Response (ABR) was used to assess hearing loss. Hematoxylin and Eosin (HE) staining was conducted to observe morphological alterations in the SV. Immunofluorescence combined with transmission electron microscopy (TEM) was used to scrutinize changes in pericytes following acoustic injury. Western blotting (WB) was used to assess the expression variations of the migration-related protein Osteopontin (OPN). Evans Blue assay was performed to evaluate the permeability of the blood labyrinth barrier (BLB). 4-Hydroxynonenal (4-HNE) staining, in conjunction with measurements of Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Catalase (CAT) content, was used to ascertain whether oxidative stress injury occurred in the SV. WB, combined with immunofluorescence, was used to examine alterations in the expression of proliferator-activated receptor-gamma coactivator 1α (PGC-1α) in the SV and pericytes. RESULTS: Noise exposure resulted in permanent hearing loss in C57BL/6J mice, accompanied by SV swelling, migration of pericytes from their vascular attachments, BLB leakage, elevated oxidative stress levels in the SV, and reduced expression of PGC-1α on both the SV and migrating pericytes. CONCLUSION: Noise exposure may potentially increase oxidative stress levels in the SV, downregulate the expression levels of PGC-1α, promote pericytes migration, and subsequently lead to an elevation in BLB permeability.

Ultrasound-guided quadratus lumborum block provided more effective analgesia for children undergoing lower abdominal laparoscopic surgery: a randomized clinical trial.

BACKGROUND: Postoperative pain treatment for pediatrics is often inadequate and the evidence of pediatric postoperative analgesia is scarce. To our knowledge, no report regarding the comparison among caudal block, transversus abdominis plane (TAP) block and quadratus lumborum (QL) block for children undergoing lower abdominal laparoscopic surgery was found at present. Thus this trial aimed to compare the efficacies of them for children undergoing lower abdominal laparoscopic surgery. METHODS: One hundred and eighty children aged from 1 to 12 years undergoing lower abdominal laparoscopic surgery were included and randomized to receive caudal block, TAP block or QL block. The primary outcome was the Face, Legs, Activity, Cry, and Consolability (FLACC) score at 30 min, 1 h, 4 h, 8 h, 12 h, and 24 h and tramadol consumption during first 24 h postoperatively. Secondary outcomes included the number of children received tramadol, time to first tramadol request, parents' satisfaction and postoperative adverse reactions. RESULTS: The QLB group had lower postoperative FLACC scores at 8 h (median difference - 0.43, P = 0.03) than the Caudal group and at 4 h (median difference - 0.6, P = 0.001) and 8 h (median difference - 0.43, P = 0.03) than the TAPB group. The tramadol consumption was lower in the QLB group (28.43 ± 6.55) than the TAPB group (37.17 ± 6.12, P = 0.023). Although the number of children received tramadol did not differ among the three groups, the time to first tramadol request was longer in the QLB group (7.20 ± 0.79) than the caudal group (8.42 ± 0.61, P = 0.008). No statistical difference was observed concerning other secondary outcomes. CONCLUSIONS: QLB produced more effective postoperative analgesia for children undergoing laparoscopic abdominal surgery compared with the TAPB and caudal block.

Qiangli Wuhu mixture alleviates LPS-induced pneumonia by inhibiting the TLR4/NF-κB/NLRP3 pathway: a study based on network pharmacology.

CONTEXT: Qiangli Wuhu (QLWH) mixture is a concoction approved and registered by Ningxia Medical Products Administration. It has therapeutic effects on various types of pneumonia. OBJECTIVE: To clarify the mechanisms of QLWH in treating pneumonia. MATERIALS AND METHODS: The potential targets of QLWH in the treatment of pneumonia were predicted by network pharmacology. Male, Institute of Cancer Research (ICR) mice were randomly divided into five groups of 12 mice, control, vehicle, QLWH (10 and 20 mg/kg) and dexamethasone (DXM), and orally treated twice daily with normal saline, QLWH or DXM. The pneumonia model was established by tracheal instillation of lipopolysaccharide (LPS). After treatment five days, ELISA, H&E staining and Western blot were used to investigate protective effects of QLWH. RESULTS: Nine hundred and ninety-four active ingredients were found through network pharmacology, corresponding to 135 targets for the treatment of pneumonia; compared to the vehicle group, QLWH (10 and 20 mg/kg) significantly decreased the levels of TNF-α (14.3% and 28.8%), IL-1ß (23.9% and 42.8%) and IL-6 (13.2% and 16.1%), increased the levels of IL-10 (134.3% and 172.9%); in terms of mechanism, QLWH down-regulated TLR4/NF-κB/NLRP3 axis related proteins in lung tissue of pneumonia model mice (p < 0.05). DISCUSSION AND CONCLUSIONS: This study combined network pharmacology and animal experiments, providing effective evidence for the clinical promotion of QLWH. Meanwhile, it is of significance for further development.

Effect of Helicobacter Pylori on Plasma Metabolic Phenotype in Patients With Gastric Cancer.

BACKGROUND: Although Helicobacter pylori (Hp) as high risk factor for gastric cancer have been investigated from human trial, present data is inadequate to explain the effect of Hp on the changes of metabolic phenotype of gastric cancer in different stages. PURPOSE: Herein, plasma of human superficial gastritis (Hp negative and positive), early gastric cancer and advanced gastric cancer analyzed by UPLC-HDMS metabolomics can not only reveal metabolic phenotype changes in patients with gastric cancer of different degrees (30 Hp negative, 30 Hp positive, 20 early gastric cancer patients, and 10 advanced gastric cancer patients), but also auxiliarily diagnose gastric cancer. RESULTS: Combined with multivariate statistical analysis, the results represented biomarkers different from Hp negative, Hp positive, and the alterations of metabolic phenotype of gastric cancer patients. Forty-three metabolites are involved in amino acid metabolism, and lipid and fatty acid metabolism pathways in the process of cancer occurrence, especially 2 biomarkers glycerophosphocholine and neopterin, were screened in this study. Neopterin was consistently increased with gastric cancer progression and glycerophosphocholine tended to consistently decrease from Hp negative to advanced gastric cancer. CONCLUSION: This method could be used for the development of rapid targeted methods for biomarker identification and a potential diagnosis of gastric cancer.

Association of carbamylated high-density lipoprotein with coronary artery disease in type 2 diabetes mellitus: carbamylated high-density lipoprotein of patients promotes monocyte adhesion.

BACKGROUND: Increasing evidence showed that carbamylated lipoprotein accelerated atherosclerosis. However, whether such modification of high-density lipoprotein (HDL) particles alters in type 2 diabetes mellitus (T2DM) patients and facilitates vascular complications remains unclear. We aimed to investigate the alteration of the carbamylation in HDL among T2DM patients and clarify its potential role in atherogenesis. METHODS: A total of 148 consecutive T2DM patients undergoning angiography and 40 age- and gender-matched control subjects were included. HDL was isolated from plasma samples, and the concentration of HDL carbamyl-lysine (HDL-CBL) was measured. Furthermore, the HDL from subjects and in-vitro carbamylated HDL (C-HDL) was incubated with endothelial cells and monocyte to endothelial cell adhesion. Adhesion molecule expression and signaling pathway were detected. RESULTS: Compared with the control group, the HDL-CBL level was remarkably increased in T2DM patients (6.13 ± 1.94 vs 12.00 ± 4.06 (ng/mg), P < 0.001). Of note, HDL-CBL demonstrated a more significant increase in T2DM patients with coronary artery disease (CAD) (n = 102) than those without CAD (n = 46) (12.75 ± 3.82 vs. 10.35 ± 4.11(ng/mg), P = 0.001). Multivariate logistic regression analysis demonstrated that higher HDL-CBL level was independently associated with a higher prevalence of CAD in diabetic patients after adjusting for established cofounders (adjusted odds ratio 1.174, 95% confidence Interval 1.045-1.319, p = 0.017). HDL from diabetic patients with CAD enhanced greater monocyte adhesion than that from the non-CAD or the control group (P < 0.001). Such pro-atherogenic capacity of diabetic HDL positively correlated with HDL-CBL level. Furthermore, in-vitro incubation of carbamylated HDL (C-HDL) with endothelial promoted monocyte to endothelial cell adhesion, induced upregulation of cell adhesion molecules expression, and activated NF-κB/p65 signaling in endothelial cells. Inhibiting carbamylation of HDL or NF-κB activation attenuated the monocyte to endothelial cell adhesion and cell surface adhesion molecules expression. CONCLUSIONS: Our study identified elevated carbamylation modification of HDL from T2DM patients, especially in those with concomitant CAD. We also evidenced that C-HDL enhanced monocyte to endothelial cell adhesion, indicating a potential pro-atherogenic role of C-HDL in atherosclerosis among T2DM patients. Trial registration https://register.clinicaltrials.gov , NCT04390711 Registered on 14 May 2020; Retrospectively registered.

Safety considerations during return to work in the context of stable COVID-19 epidemic control: an analysis of health screening results of all returned staff from a hospital.

In March 2020, China had periodically controlled the coronavirus disease-19 (COVID-19) epidemic. We reported the results of health screening for COVID-19 among returned staff of a hospital and conducted a summary analysis to provide valuable experience for curbing the COVID-19 epidemic and rebound. In total, 4729 returned staff from Zhongnan Hospital of Wuhan University, Wuhan, China were examined for COVID-19, and the basic information, radiology and laboratory test results were obtained and systematically analysed. Among the 4729 employees, medical staff (62.93%) and rear-service personnel (30.73%) were the majority. The results of the first physical examination showed that 4557 (96.36%) were normal, 172 (3.64%) had abnormal radiological or laboratory test results. After reexamination and evaluation, four were at high risk (asymptomatic infections) and were scheduled to transfer to a designated hospital, and three were at low risk (infectivity could not be determined) and were scheduled for home isolation observation. Close contacts were tracked and managed by the Center for Disease Control and Prevention (CDC) in China. Asymptomatic infections are a major risk factor for returning to work. Extensive health screening combined with multiple detection methods helps to identify asymptomatic infections early, which is an important guarantee in the process of returning to work.

Ginsenoside Rg1 Performs Anti-Aging Functions by Suppressing Mitochondrial Pathway-Mediated Apoptosis and Activating Sirtuin 3 (SIRT3)/Superoxide Dismutase 2 (SOD2) Pathway in Sca-1⁺ HSC/HPC Cells of an Aging Rat Model.

BACKGROUND Aging is characterized by progressive deterioration in metabolic and physiological process. The present research assessed the antagonistic effects and mechanisms of Ginsenoside Rg1 (Rg1) on aging of HSCs/HPCs. MATERIAL AND METHODS Fifty male Sprague-Dawley (SD) rats were treated and divided into the following groups: Control (n=10), Model (n=10, treated with D-galactose, as aging model), Rg1 Control (n=10), Rg1 treatment (n=10), and Rg1 prevention (n=10). An aging rat model was established by subcutaneous injection with D-gal. HSC/HPC cells were stained using SA-ß-Gal staining. HSC/HPC cells were examined using flow cytometry assay. CFU-mix assay, with a few modifications, was performed. Cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were examined using qRT-PCR. Sirtuin 3 (SIRT3) and superoxide dismutase 2 (SOD2) expression was determined using Western blot assay and qRT-PCR. RESULTS Rg1 (treatment and prevention group) significantly decreased SA-ß-Gal-positive staining in Sca-1⁺ HSC/HPC cells compared to that of the D-gal model (p<0.05). Rg1 significantly enhanced formation capacity of CFU-Mix compared to the D-gal model (p<0.05) in Sca-1⁺ HSC/HPC cells. Rg1 significantly reduced G0/G1 phase of Sca-1⁺ HSC/HPC cells compared to that of the D-gal model (p<0.05). Rg1 significantly decreased cleaved caspase 3 and Bax expression, and increased Bcl-2 expression compared to the D-gal model (p<0.05). Rg1 treatment remarkably upregulated expressions of SIRT3 and SOD2 compared to that of the D-gal model group (p<0.05). CONCLUSIONS Rg1 conducted functions of anti-aging in Sca-1⁺ HSC/HPC cells in the D-gal-induced aging model by inhibiting mitochondrial pathway-mediated apoptosis and activating the SIRT3/SOD2 signaling pathway.

[Rationality of Asari Radix et Rhizoma in Qingfei Paidu Decoction based on literature analysis].

Qingfei Paidu Decoction is a traditional Chinese medicine compound recommended by National Health Commission of the People's Republic of China and National Administration of Traditional Chinese Medicine for clinical therapies of coronavirus disease 2019(COVID-19). Qingfei Paidu Decoction consists of 21 traditional Chinese medicines, such as Asari Radix et Rhizoma. However, the dosage of Asari Radix et Rhizoma has been questioned by some people, because of one ancient proverb. To explore the rationality of the dosage of Asari Radix et Rhizoma in Qingfei Paidu Decoction, this study systematically examined the ancient and modern physicians' understanding of the toxicity of Asari Radix et Rhizoma, and collated the application and dosage of Asari Radix et Rhizoma in ancient prescriptions and modern clinics based on literature analysis. As a result, we found that ancient and modern physicians have different understanding on the toxicity of Asari Radix et Rhizoma and that the theory about the dosage of Asari Radix et Rhizoma is flawed. We also found that the dose of Asari Radix et Rhizoma in ancient and modern clinical applications was not constrained by ancient experience. Physicians usually increase the dosage of Asari Radix et Rhizoma in clinical therapy according to the actual conditions, and there were no adverse reactions. Additionally, according to laws and regulations concerning medical affairs, physician could increase or decrease the dosage of the drug under special circumstances. Based on the analysis of safety and effectiveness of Asari Radix et Rhizoma in Qingfei Paidu Decoction, we conclude that the dose of Asari Radix et Rhizoma in Qingfei Paidu Decoction is safe, effective and reasonable.

[Analysis of property and efficacy of traditional Chinese medicine in staging revention and treatment of coronavirus disease 2019].

Coronavirus disease 2019(COVID-19) triggered a severe and complicated epidemic situation, and it is of great significance to discuss the rules and characteristics of the prescription of COVID-19 in traditional Chinese medicine. This study collected prevention and treatment approaches of traditional Chinese medicine for COVID-19 released from the National Health Committee of China, 7 provinces and municipal health committees, the Chinese Medicine Administration and Handbook of Traditional Chinese Medicine Diagnosis and Treatment of COVID-19 between January 1 and February 18, 2020, and prescriptions prepared by 3 masters of Chinese medicine and 4 well-known Chinese medicine experts. These information were selected according to the inclusion and exclusion criteria, and EpiData 3.0 software was used to establish the "Traditional Chinese Medicine Prescription Library for the Prevention and Treatment of COVID-19" and the "Common Database of Traditional Chinese Medicine for the Prevention and Treatment of COVID-19". A total of 93 effective Chinese medicine prescriptions and a total of 157 kinds of constituent medicines were collected. Data analysis was performed by SPSS 18.0 software. The results showed that: ①most of the medicines are with cold and warm properties, 69 with cold medicines, accounting for 43.95%, 57 with warm medicines, accounting for 36.31%, and less with hot medicines, taking up 1.27%; ②there are many pungent, bitter and sweet medicines, and the distribution of medicinal flavors is different at different disease stage. The pungent medicines are mostly found in the early stage, the bitter drugs are the main flavor in the middle and severe stage, and the sweet medicines are mostly used in the recovery stage; ③the meridian of the drug is more concentrated at the lung, stomach, and heart, and most of drugs are into the lung meridian, accounting for 24.55%; these medicines are mostly into the lungs and stomach in the initial and middle stages, and into the heart and kidney in severe stages; ④oral drugs are mostly non-toxic, among which only 6 kinds are toxic, namely Armeniacae Semen Amarum, Dryopteridis Crassirhizomatis Rhizoma, Paridis Rhizoma, Pinelliae Rhizoma, Aconiti Lateralis Radix Praeparaia; ⑤most of the drugs have five types of functions: treating exterior syndromes, resolving dampness, clearing heat, replenishing deficiency, resolving phlegm, cough, and asthma. In the early stage, both drugs for treating exterior syndromes and heat clearing drugs were equally used, accounting for 18.81% each. In the middle stage, drugs resolving phlegm, cough, and asthma drugs are more often used, accounting for 29.61%. In the severe stage, heat clearing drugs are mostly used, accounting for 33.33%. During the recovery period, tonic deficiency drugs are used the most, accounting for 36.47%. The medical characteristics and efficacy of Chinese medicine in preventing and treating COVID-19 are closely related to the understanding of the etiology of Chinese medicine and the location and pathogenesis of the disease. Staged medication and local conditions need attention during the identification and treatment of COVID-19 clinical syndromes.

A web-based lifestyle intervention program for Chinese college students: study protocol and baseline characteristics of a randomized placebo-controlled trial.

BACKGROUND: This study aimed to describe the design and present the baseline characteristics of a web-based lifestyle intervention program, which comprises of sequentially and simultaneously delivered intervention modules targeting physical activity (PA) and fruit and vegetable consumption (FVC) in Chinese college students. METHODS: The study adopted a randomized placebo-controlled trial, using the Health Action Process Approach (HAPA) and the Compensatory Carry-Over Action Model (CCAM) as the theoretical backdrops. 556 Chinese college students participated in the 8-week web-based lifestyle intervention program. All eligible participants were randomly assigned to one of four groups: 1) the PA-first arm which received a 4-week intervention addressing PA followed by a 4-week intervention addressing FVC; 2) the FVC-first arm which received a 4-week intervention addressing FVC followed by a 4-week intervention addressing PA; 3) the PA + FVC simultaneous arm that received an 8-week intervention addressing both PA and FVC at the same time; and 4) the placebo-control arm that received 8 weeks of general health information, which is not relevant for changing actual PA and FVC behaviors. Data collection includes four time-points: at the beginning and end of the intervention, and a 3-month and 12-month follow-up after the intervention. RESULTS: At baseline, 41.7% of participants were male and 58.3% were female. 41.0% of the participants did not meet the standard PA-recommendations, while 69.6% did not adhere to the standard FVC-recommendations. In total, only 19.6% of participants met both PA and FVC recommendations. Baseline characteristics across the four groups had no significant differences (all P = .17-.99), indicating successful randomization. CONCLUSIONS: The preliminary results indicate a high prevalence of unhealthy lifestyles in college students in China, which further supports the need for web-based health intervention programs. This is also the first study that examines the comparative effectiveness of simultaneously and sequentially delivered lifestyle interventions in the Chinese population. These findings may contribute to the creation of future web-based health behavior change interventions. TRIAL REGISTRATION: ClinicalTrails.gov: NCT03627949 , 14 August, 2018.

[Toxicity-reducing effect of compatibility of Tripterygium and licorice in animals: systematic review].

The aim of this paper was to systematically evaluate the toxicity-reducing effect of Tripterygium-licorice in animal experiments,and also to provide evidence for basic research on the toxicity reduction of Tripterygium wilfordii. The PubMed,EMbase,Web of Science,CBM,CNKI and Wan Fang Databases from their establishment to August 31 th,2018 were searched. Two independent reviewers screened the papers,extracted the data,assessed the risk of bias using SYRCLE assessment tool and conducted Meta-analysis with Rev Man 5. 3 software. A total of 10 papers involving 31 studies were finally included,15 studies of which were used for Meta-analysis. Four studies were included for chronic hepatotoxicity animal model. In experimental group( 34 animals),Tripterygium was administered at dose of 0. 09-0. 1 mg·kg-1·d-1,and glycyrrhizic acid was administered at dose of 90-100 mg·kg-1,both for 2 weeks; in control group( 34 animals),glycyrrhizic acid was replaced with equal volume of normal saline. Eleven studies were included for acute hepatotoxicity animal model. In experimental group( 66 animals),glycyrrhizic acid was administered at dose of 75-480 mg·kg-1 for 7 days,then glycyrrhizic acid was stopped,and Tripterygium began to be administered at dose of 0. 6-1. 0 mg·kg-1 per 24 h or 48 h for a total of 1-2 times; in control group( 66 animals),glycyrrhizic acid was replaced with equal volume of normal saline or corresponding solvent. The results of Meta-analysis showed that in both chronic hepatotoxicity animal model and acute hepatotoxicity animal model,the transaminase levels in the experimental group were lower than those in the control group( P < 0. 05). Subgroup analysis of acute hepatotoxicity animal model showed that the transaminase levels in the experimental group were lower than those in the control group for every subgroup except " glycyrrhizic acid 75 mg·kg-1" subgroup. However,in terms of the mean difference( MD) and confidence interval( CI),there was no significant difference in transaminase decline between each subgroup. Low dose of glycyrrhizic acid( 90-100 mg·kg-1) has a toxicity-reduction effect on chronic hepatotoxicity induced by tripterygium( 0. 09-0. 10 mg·kg-1). Middle and high doses of glycyrrhizic acid( 120-480 mg·kg-1) have a toxicity-reduction effect on acute hepatotoxicity induced by tripterygium( 0. 6-1. 0 mg·kg-1),but with no significant dose-effect relationship.

The Protective Effect of Propofol Against Ischemia-Reperfusion Injury in the Interlobar Arteries: Reduction of Abnormal Cx43 Expression as a Possible Mechanism.

BACKGROUND/AIMS: This experimental study aims to observe whether the protective effect of propofol against renal ischemia-reperfusion injury (IRI) in the rat interlobar artery occurs through altered expression of the gap junction protein connexin 43 (Cx43). METHODS: This study randomly divided male Sprague Dawley (SD) rats into an untreated control group, a sham-operated control group (sham group), an ischemia-reperfusion group (IR group), a propofol group (propofol+IR group) and a fat emulsion group (Intralipid group). The ischemia/reperfusion model was prepared through resection of the right kidney and noninvasive arterial occlusion of the left kidney. Forty-five minutes after renal ischemia-reperfusion, an automatic biochemical analyzer was employed to measure blood urea nitrogen (BUN) and serum creatinine (SCr); changes in renal tissue pathology were observed using hematoxylin and eosin (HE) staining, and the vasomotor activity of the interlobar artery was detected using a pressure mechanogram technique. The protein expression of Cx43 in renal artery cross-sections was determined through western blotting. RESULTS: The experimental study confirmed that the BUN and SCr of rats markedly increased after ischemia-reperfusion injury; additionally, we observed some coagulation necrosis and shedding of cells, some solidification of nuclear chromatin, degeneration of cytoplasmic vacuoles, high renal interstitial vascular congestion and obvious inflammatory cell infiltration, characterized by focal hemorrhages. Furthermore, the contraction activity of the renal interlobar artery greatly decreased, and the tension of the arteries in the renal lobe increased remarkably. After the gap junction blocking agents 2-APB and Gap27 were applied, the systolic velocity of blood vessels and the vascular contraction rate both decreased. In addition, the expression of Cx43 in kidney tissues increased markedly. The damage was more severe after 24 h of ischemic reperfusion than after only 4 h. However, after pretreatment with propofol, regardless of whether ischemia-reperfusion was applied for 4 h or 24 h, the previously increased expression of Cx43 decreased obviously, and all forms of renal damage were reversed. CONCLUSION: Our research suggests new ways for propofol to relieve ischemia-reperfusion injury by decreasing the abnormal expression of the gap junction protein Cx43. This study reveals a novel mechanism for the action of propofol against IRI, and we hope this finding will lead to new treatments for IRI.

Novel compound heterozygous mutations in ZAP70 in a Chinese patient with leaky severe combined immunodeficiency disorder.

In humans, the complete lack of tyrosine kinase ZAP70 function results in combined immunodeficiency (CID), with abnormal thymic development and defective T cell receptor (TCR) signaling of peripheral T cells, characterized by the selective absence of CD8+ T cells. So far, 15 unique ZAP70 mutations have been identified in approximately 20 patients with CID, with variable clinical presentations. Herein, we report the first case from China of novel compound heterozygous mutations in ZAP70 (c.598-599delCT, p.L200fsX28; c.847 C>T, R283H). The patient suffered from early-onset and recurrent infections, but showed normal growth and development without signs of failure to thrive, thus presenting as leaky SCID. The patient also had clinical manifestations of autoimmunity, such as eczematous skin lesion, inflammatory bowel disease (IBD), and intractable diarrhea, suggesting compromised T cell tolerogenic functions. Residual ZAP70 expression was identified. Immunological analysis revealed the selective absence of CD8+ T cells in the periphery and the presence of CD4+ T cells that failed to respond to phytohemagglutinin. Stimulation with lectin from pokeweed mitogen also failed to stimulate B cell proliferation in the patient. The frequency of Tfhs and Tregs in the patient was lower compared with the normal reference. Compared with the age-matched healthy control, the level of IL-17 was higher and the levels of IFN-γ, IL-4, and IL-21 were lower. Infants with selected CD8 deficiency and severe autoimmune disorders or exaggerated inflammation should be screened for ZAP70 deficiency.

Evaluating Efficacy and Safety of Combination Medication of Atorvastatin and a Herbal Formula Containing Salvia miltiorrhiza and Pueraria lobata on Hyperlipidemia.

Despite being a potent hypolipidemic drug, atorvastatin (AS) possesses certain adverse effects. Using AS and an herbal formula (Danshen and Gegen, DG) in combination may achieve potentiated hypolipidemic effects and also reduce its adverse effects. Hence, this study aimed to investigate the efficacy and safety of an AS and DG combination on high-fat diet-induced hyperlipidemia. Treatment outcomes were assessed by measuring parameters including body weight, adipose tissue, liver, total cholesterol, triglyceride, and low-density and high-density lipoprotein cholesterol. Measurements of adverse effects were achieved by determining aspartate aminotransferase (AST), alanine transaminase (ALT), and creatine kinase (CK). Danshen and Gegen, as well as AS alone, reduced body weight, adipose tissue, liver weight, liver fat vacuoles, total liver lipids, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in high-fat diet-fed mice but increased AST, ALT, and CK. A combination of AS and DG was able to enhance reduced effects on the aforementioned parameters in relation to hyperlipidemia over AS or DG alone. It also reduced the elevation of AST, ALT, and CK induced than by AS or DG alone. Results demonstrated that an AS and DG combination resulted in stronger hypolipidemic effects than with AS or DG alone. Additionally, DG might attenuate adverse effects of AS on the liver and skeletal muscle. Copyright © 2017 John Wiley & Sons, Ltd.

[Strategy of constructing post-market integral evaluation system of traditional Chinese medicine injection].

As an important representative of modern Chinese medicine, traditional Chinese medicine (TCM) injzection has become an indispensable part of the Chinese medicine industry. However, its development is now restricted by the bottleneck of insufficient core competitiveness, low-level research and production, even injection quality and the safe use are not guaranteed. Thus, it is urgent to reevaluate post-marketing TCM injection generally and to make secondary development. Under current circumstances, taking major brands which have good clinical and market foundation, as well as research value, as the main subject of cultivation and evaluation is an important approach to innovative development of TCM injection industry. Unlike oral proprietary Chinese medicine, the cultivatation of major brands of TCM injection needs higher technical support, quality standards and more timely feedback. Therefore, a post-market integral evaluation system adaptive to TCM injection is required. This article discussed some key points on the construction of a post-market integral evaluation system of TCM injection in three levels： optimizing evaluation methods, building synergistic innovation platforms which combine the medical research institutions and pharmaceutical enterprises, and finally constructing the integral evaluation system. A "five to one" structure has been proposed to enhance TCM injection effectiveness, safety and adaptability on the whole, which are from the following aspects： mechanism research, clinical evidence validation, literature information mining, sustainable development of resources and industrialization operation.

[Clinical application evaluation of Guidelines for Diagnosis and Treatment of Common Diseases of Otolaryngology in Traditional Chinese Medicine].

This study is to assess the Guidelines for Diagnosis and Treatment of Common Diseases of Otolaryngology in Traditional Chinese Medicine in clinical application and provide evidence for further guideline revision. The assessment was divided into applicability assessment and practicability assessment. The applicability assessment based on questionnaire survey and the traditional Chinese medicine (TCM) practitioners were asked to independently fill the Questionnaire for Applicability Assessment on the Guidelines for Diagnosis and Treatment in Traditional Chinese Medicine. The practicability assessment was based on prospective case investigation and analysis method and the TCM practitioners-in-charge filled the Case Investigation Questionnaire for Practicability Assessment on the Guidelines for Diagnosis and Treatment in Traditional Chinese Medicine. The data were analyzed in descriptive statistics. 151 questionnaires were investigated for applicability assessment and 1 016 patients were included for practicability assessment. The results showed that 88.74% of them were familiar with the guidelines and 45.70% used them. The guidelines quality and related items were similar in applicability assessment and practicability assessment, and scored highly as more than 85.00% except the "recuperating and prevention". The results suggested that the quality of Guidelines for Diagnosis and Treatment of Common Diseases of Otolaryngology in Traditional Chinese Medicine was high and could better guide the clinical practice. The "recuperating and prevention" part should be improved and the evidence data should be included in future guideline revision, so that the clinical utilization rate could be increased.

[Clinical application evaluation of Guidelines for Diagnosis and Treatment of Common Diseases of Gynecology in Traditional Chinese Medicine].

To evaluate the clinical applicability and application of Guidelines for Diagnosis and Treatment of Common Diseases of Gynecology in Traditional Chinese Medicine, 11 diseases from Guidelines for Diagnosis and Treatment of Common Diseases of Gynecology in Traditional Chinese Medicine were evaluated by methods of questionnaire and prospective case study at 16 construction units for traditional Chinese medicine standards research and extension. Results showed that 361 clinical doctors accepted the applicability survey of guidelines, and 87.26% of them were more familiar to the guideline and 25.21% of them used the guideline. In syndrome differentiation and treatment related contents, rationality of prescription medication and syndrome classification was higher, accounted for 91.69% and 86.98% respectively, but the rationality of recuperation prevention was lower, accounted for 44.6%. 75.62% clinical doctors believed that the Guidelines for Diagnosis and Treatment of Common Diseases of Gynecology in Traditional Chinese Medicine was applicable. The application of the guidelines is evaluated by prospective observation of 2 935 cases. The higher compliance between the guideline and clinical practice was present in TCM (traditional Chinese medicine) disease diagnosis and WM (western medicine) disease diagnosis, accounted for 98.30% and 94.11% respectively. The lower compliance was present in recuperation prevention, accounted for 59.39%. The safety and economy of the guideline was higher, accounting for 95.64%, 94.75%, respectively. The comprehensive evaluation results showed that the rate of the overall treatment effect with technical level, satisfaction degree or applicability in clinical practice which were 7-9 points is 77.38%, 74.00%, 76.90% respectively. This guideline has a high clinical compliance and can be used as a standard for common diseases of gynecology, but there are also some conditions with poor applicability, which does not conform to the actual situation, and needs to be further revised.