Acetaminophen (APAP) is one of the commonly used analgesic antipyretic anti-inflammatory drugs, which cause drug-induced liver damage and even acute liver failure due to take large amounts of drugs blindly, combination drugs-using or long-term medication. The mechanisms of APAP-induced hepatotoxicity mainly focus on the generation of toxic metabolites, mitochondrial dysfunction, inflammatory response, oxidative stress, the release of damage associated molecular patterns (DAMPs), autophagy, endoplasmic reticulum stress, and microcirculatory dysfunction. This article summarizes the toxic mechanism of drug-induced liver injury induced by APAP, and summarizes the research progress of active ingredients of traditional Chinese medicine on the protective effect of APAP-induced liver injury, including polyphenols, flavonoids, saponins, organic acids, terpenoids, phenylpropanoids compounds, sugars, alkaloids and other compounds, to provide a reference for the development of drugs to prevent and treat APAP-induced liver injury.

Paracetamol (acetaminophen, APAP)is one of the commonly used analgesic, antipyretic and anti-inflammatory drugs, but it can cause acute kidney injury(AKI)or even acute renal failure due to blind, large, combined or long-term use. The mechanism reseach on the APAP-induced nephrotoxicity is mainly focused on the formation of metabolic toxic substances, oxidative stress, inflammatory response, mitochondrial dysfunction, endoplasmic reticulum stress(ERS), and changes in glomerular hemody namics. This paper summarizes the toxicity mechanism of APAP-induced AKI(APAP-AKI), and the research progress in the protec tive effect of active ingredients of traditional Chinese materia medicas(TCMM)on APAP-AKI, including polyphenols, flavonoids, quinones, terpenoids, amino acids and other type substances, with an aim to clarify the key mechanisms and signaling pathways of APAP-AKI and to provide reference for the development of drugs for the prevention and treatment of APAP-AKI.

Objective To investigate epidemic characteristics and risk factors of hypertension among residents aged above 15 years in Pudong New Area of Shanghai. Methods We selected the subjects through a multistage stratified cluster sampling procedure; all thirty towns of Pudong New Area were stratified into three levels according to their economic status and 10 657 people selected as survey subjcets from each economic level.A questionnaire survey was conducted in conjunction with measurements of body height and weight, fasting plasma glucose, 2-hour postprandial blood glucose, blood lipid and blood pressure among 10 657 inhabitants aged above 15 years.Multivariate unconditional regression model was employed to analyze the influence factors of hypertension. Results The crude prevalence rate of hypertension in the residents was 41.3%.The prevalence rates of male was high than female (P<0.001). With the increment of age, the hypertension prevalence rate of all residents were obviously elevated.The residents with lower education had a higher hypertension prevalence rate.There was no significant difference in hypertension prevalence between rural and urban.The results of logistic regresssion showed that the risk factors of hypertension were age,gender,educational level,family history of hypertension,central obesity, body mass index, C-reactive protein, 2-hour postprandial blood glucose and urinary albumin/creatinine ratio(P<0.05). Conclusion The results indicated that hypertension was highly prevalent in Pudong New Area.Body mass index ( BMI) and central obesity were related factors for hypertension which were changeable.

Objective To evaluate different hypertension management models in communities and their impact on incidence of cardio-cerebrovascular disease in hypertensive patients. Methods A total of 1 578 hypertension patients in several communities in Pudong New Area were recruited in the study ( August 2008 to December 2012 ) according to the inclusion criteria and randomly divided into two groups.The control group was given routine hypertension management and the study group was given detailed hypertension management, while health commissioners and community physicians were in charge of the follow-up and data collection. Results The incidence of cardio-cerebrovascular disease (1.33%) in study group (1.33%) was significantly lower than that of the control group (4.22%) ( P <0.05). Multivariate logistic regression analysis showed that age, male, course-of-disease, patients with hypertension family history, increase in SCr and LDL-C increased the risk for getting ardio-cerebrovascular disease (P <0.05).The risk of study group was 0.348 times the control group ( P <0.05). Conclusion Compared with control group, detailed hypertension management model conducted in study group has the advantages that effectively reduced the rate of cardio-cerebrovascular disease.

Objective To investigate the risk factors for recurrence of cerebral infarction and to propose secondary prevention methods . Methods Data of 628 patients with cerebral infarction from Jan.2012 to Dec.2014 were collected by the community reported network into a cohort study .The prevalence of recurrence and associated risk factors of cerebral infarction were investigated . Results Recurrence rate of cerebral infarction was 9.08%.History of hypertension (OR=4.797, P=0.001), long term of tobacco use ( OR=2 .844 , P=0 .005 ) , abdominal obesity or overweight ( OR=2 .421 , P=0.041) and farming(OR=3.723, P<0.001)were the independent risk factors for recurrence of cerebral infarction. Conclusion The recurrence rate of cerebral infraction is high , which is affected by various factors.

OBJECTIVE: To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics. METHODS: Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis. RESULTS: Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway. CONCLUSION Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.
Female ; Rats ; Animals ; Glucocorticoids/adverse effects* ; AMP-Activated Protein Kinases ; Proteomics ; Rats, Sprague-Dawley ; Osteoporosis/genetics* ; Nuclear Proteins/adverse effects*

OBJECTIVE: To observe the effect of moxibustion on the regulation of nuclear factor-kappa B (NF-κB) and inflammatory factors by multiple microRNAs (miRNAs) in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), and to explore the anti-inflammatory mechanism of moxibustion on IBS-D. METHODS: Twelve of 52 newborn rats were randomly selected into a normal group. The remaining rats were made into IBS-D model. A total of 36 rats with successful model were randomly divided into a model group, a medication group and a moxibustion group, 12 rats in each group. The rats in the medication group were intraperitoneally injected with pyrrolidine dithiocarbamate (PDTC). The rats in the moxibustion group were treated with moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for 20 min each time. All the intervention was given once a day for 7 days. Before and after modeling as well as after intervention, the body mass, loose stool rate and the minimum volume threshold of abdominal withdrawal reflex (AWR) were measured. After intervention, the contents of serum tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-8 were detected by ELISA method; the morphology of colon tissues was observed by HE staining, and the expressions of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues were detected by real-time PCR. The expressions of NF-κB p65, TNF-α, IL-1β and IL-8 protein in colon tissues were detected by immunofluorescence. RESULTS: After modeling, the body mass and the minimum volume threshold of AWR in the model group were lower than those in the normal group (P<0.01); the rates of loose stool in the model group were higher than those in the normal group (P<0.01); after intervention, in the model group, the inflammatory infiltration of colon tissues was obvious, and the serum levels of TNF-α, IL-1 β, IL-8 were higher than those in the normal group (P<0.05); the expression of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues was higher than that in the normal group (P<0.05); the protein expression of NF-κB p65, TNF-α, IL-1β, IL-8 was also higher than that in the normal group (P<0.01). After intervention, the body mass and the minimum volume threshold of AWR in the medication group and the moxibustion group were both higher than those in the model group (P<0.05); the loose stool rate in the medication group and the moxibustion group were lower than those in model group (P<0.05); the inflammatory cells infiltration in the colon tissues was less, the serum levels of TNF-α, IL-1β and IL-8 as well as the protein expression of NF-κB p65, TNF-α, IL-1β and IL-8 in the colon tissues in the medication group and the moxibustion group were lower than those in the model group (P<0.05, P<0.01). The expression of miR-125b, miR-31, miR-18a and NF-κB p65 mRNA in the medication group were lower than those in the model group (P<0.05). The expression of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in the moxibustion group were lower than those in the model group (P<0.05). The miR-155, miR-125b, miR-29b, miR-31, miR-18a were positively correlated with NF-κB p65 mRNA (0<r<1, P<0.01). CONCLUSION The anti-inflammatory mechanism of moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for IBS-D rats may be related to regulating multiple miRNAs to inhibit NF-κB signal pathway and reduce the expression of inflammatory factors.
Animals ; Diarrhea/therapy* ; Interleukin-8/genetics* ; Irritable Bowel Syndrome/therapy* ; MicroRNAs/genetics* ; Moxibustion ; NF-kappa B/metabolism* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Tumor Necrosis Factor-alpha/genetics*

Cinnabaris is a traditional Chinese medicine(TCM) commonly used for sedation and tranquilization in clinics, and its safety has always been a concern. This study intends to investigate the species and tissue distribution of mercury in rats after continuous administration of Cinnabaris. In the experiment, 30 rats were randomly divided into the control group(equivalent to 0.5% carboxy-methyl cellulose sodium), low-dose Cinnabaris group(0.2 g·kg~(-1)), high-dose Cinnabaris group(2 g·kg~(-1)), pseudogerm-free control group(equivalent to 0.5% sodium carboxymethyl cellulose), and pseudogerm-free Cinnabaris group(2 g·kg~(-1)). They were orally administered for 30 consecutive days. Ultrasound-assisted acid extraction method combined with high performance liquid chromatography and inductively coupled plasma-mass spectrometry(HPLC-ICP-MS) was adopted to determine inorganic mercury [Hg(Ⅱ)], methylmercury(MeHg), and ethylmercury(EtHg) in different tissue, plasma, urine, and feces of rats. The optimal detection conditions and extraction methods were optimized, and the linearity(R~2>0.999 3), precision(RSD<7.0%), and accuracy(spike recoveries ranged from 73.05% to 109.5%) of all the mercury species were satisfied, meeting the requirements of analysis. The results of mercury species detection showed that Hg(Ⅱ) was detected in all the tissue of the five experimental groups, and the main accumulating organs were the intestinal tract, stomach, and kidney. MeHg existed at a low concentration in most tissue, and EtHg was not detected in all groups. In addition, pathological examination results showed that hepatocyte vacuolar degeneration, loose cytoplasm, light staining, and mononuclear cell infiltration were observed in the high-dose Cinnabaris group, low-dose Cinnabaris group, and pseudogerm-free Cinnabaris group, with slightly milder lesions in the low-dose Cinnabaris group. Hydrous degeneration of renal tubular epithelium could be seen in the high-dose Cinnabaris group and pseudogerm-free Cinnabaris group, but there was no significant difference between the other groups and the control group. No abnormal changes were found in the brain tissue of rats in each group. This paper studied the different mercury species and tissue distribution in normal and pseudogerm-free rats after continuous administration of Cinnabaris for 30 days and clarified its effects on the tissue structure of the liver, kidney, and brain, which provided supporting evidence for the safety evaluation of Cinnabaris.
Rats ; Animals ; Mercury/analysis* ; Tissue Distribution ; Methylmercury Compounds/analysis* ; Chromatography, High Pressure Liquid/methods* ; Sodium