Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Melatonin alleviates alcoholic liver disease via EGFR-BRG1-TERT axis regulation

Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.

Effect of electroacupuncture at "Zusanli" (ST 36) on duodenal mast cells, NGF and NTRK1 in rats with functional dyspepsia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) on duodenal mast cells, nerve growth factor (NGF) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), and to explore the mechanism of electroacupuncture at Zusanli (ST 36) on functional dyspepsia (FD).@*METHODS@#Sixty SPF-grade 10-day-old SD rats were randomly divided into a normal group, a model group, a ketotifen group and an EA group, 15 rats in each group. The FD model was prepared by iodoacetamide combined with rat tail clamping method in the model group, the ketotifen group and the EA group. The rats in the ketotifen group were injected intraperitoneally with ketotifen (1 mg•kg-1•d-1) for 7 days; the rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), with disperse-dense wave, frequency of 2 Hz/50 Hz and intensity of 0.5 mA, 20 min each time, once a day for 14 days. The gastric emptying rate and small intestinal propulsion rate in each group were observed; the morphology of duodenal mucosa was observed by HE staining; the toluidine blue staining was used to observe the number and degranulation of mast cells in duodenal mucosa; the protein and mRNA expressions of NGF, NTRK1 in duodenum were detected by Western blot and real-time PCR; the level of interleukin-1β (IL-1β) in duodenum was measured by ELISA.@*RESULTS@#Compared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were decreased (P<0.01); compared with the model group, the gastric emptying rate and small intestinal propulsion rate in the ketotifen group and the EA group were increased (P<0.01); the small intestinal propulsion rate in the EA group was higher than that in the ketotifen group (P<0.01). In the model group, local defects in duodenal mucosa were observed with a small amount of inflammatory cell infiltration; no obvious abnormality was found in duodenal mucosa of the other groups. Compared with the normal group, the mast cells of duodenal mucosa in the model group were increased significantly with significant degranulation; compared with the model group, the mast cells of duodenal mucosa in the ketotifen group and the EA group were decreased significantly, and the degranulation was not obvious. Compared with the normal group, the protein and mRNA expressions of NGF, NTRK1 as well as the level of IL-1β in duodenum in the model group were increased (P<0.01); compared with the model group, the protein and mRNA expressions of NGF, NTRK1 as well as the levels of IL-1β in duodenum in the ketotifen group and the EA group were decreased (P<0.01, P<0.05); compared with the ketotifen group, the mRNA expression of NGF, as well as the protein and mRNA expressions of NTRK1 in duodenum in the EA group were decreased (P<0.05, P<0.01).@*CONCLUSION@#EA at "Zusanli" (ST 36) could inhibit the activation of duodenal mast cells and regulate the expressions of NGF and its receptor to improve the low-grade inflammatory response of duodenum, resulting in treatment effect on FD.

The application of blunt needle buttonhole puncture of arteriovenous fistula in maintenance hemodialysis patients / 中国实用护理杂志

Objective:To explore the application of blunt needle buttonhole puncture for arteriovenous fistula in maintenance hemodialysis patients and its effect on complications.Methods:Thirty patients with maintenance hemodialysis using blunt needle buttonhole puncture for arteriovenous fistula in the hemodialysis center of Dalian Central Hospital from September 1, 2017 to September 1,2018 were included as blunt needle group. Thirty patients with common sharp needle rope ladder puncture were matched 1∶1 according to age, gender, primary disease and dialysis age as sharp needle group. They were followed up until August 31, 2019. The incidence of pain, compression hemostasis time, infection and internal fistula occlusion after puncture were compared between the two groups, and the methods and techniques of blunt needle puncture were summarized.Results:In blunt needle group, the puncture pain score was 0 in 3 cases, 1-3 in 25 cases, 4-6 in 2 cases and 7-10 in 0 case. In sharp needle group, the puncture pain score was 0 in 0 case, 1-3 in 10 cases, 4-6 in 20 cases and 7-10 in 0 case. The puncture pain in blunt needle group was significantly lower than that in sharp needle group. The difference between the two groups was statistically significant ( χ2 value was 24.156, P<0.01). The compression hemostasis time was less than 10 min in blunt needle group and more than 10 min in sharp needle group. There were 0 case of internal fistula hemangioma in blunt needle group and 21 cases in sharp needle group. The incidence of internal fistula hemangioma in blunt needle group was significantly lower than that in sharp needle group. There were 2 cases of redness at the puncture needle eye in blunt needle group and 1 case in sharp needle group. During the follow-up period, no other serious complications such as internal fistula occlusion occurred in both groups. Conclusions:Blunt needle buttonhole puncture can effectively reduce the incidence of puncture complications, reduce the degree of puncture pain in patients, shorten the compression time from the machine, the treatment is safe, worthy of clinical promotion.

Metabolites and metabolic pathways of maackiain in rats based on UPLC-Q-TOF-MS / 中国中药杂志

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to investigate the metabolites of maackiain in rats based on the prediction function of UNIFI data processing system and liver microsomal incubation in vitro. Ten metabolites of maackiain after oral absorption were reasonably deduced and characterized. It was found that the biotransformation of maackiain mainly included phase Ⅰ oxidation, dehydrogenation, phase Ⅱ sulfate conjugation, glucosylation conjugation, and glucuronic acid conjugation. Among them, the product of glucosylation conjugation, trifolirhizin, was identified by comparison with the reference for the first time. Liver microsomal incubation in vitro further confirmed the metabolites and metabolic pathways of maackiain in rats. The metabolites in the blood, urine, and feces complemented each other, which revealed the migration, metabolism, and excretion modes of maackiain in rats. This study lays a foundation for the further investigation of the metabolic mechanism of maackiain in vivo and the in-depth research on the mechanism of pharmacodynamics and toxicity.

Regulated differentiation of stem cells into an artificial3D liver as a transplantable source

End-stage liver disease is one of the leading causes of death around the world. Since insufficient sources of transplantable liver and possible immune rejection severely hinder the wide application of conventional liver transplantation therapy, artificial three-dimensional (3D) liver culture and assembly from stem cells have become a new hope for patients with end-stage liver diseases, such as cirrhosis and liver cancer. However, the induced differentiation of single-layer or 3D-structured hepatocytes from stem cells cannot physiologically support essential liver functions due to the lack of formation of blood vessels, immune regulation, storage of vitamins, and other vital hepatic activities. Thus, there is emerging evidence showing that 3D organogenesis of artificial vascularized liver tissue from combined hepatic cell types derived from differentiated stem cells is practical for the treatment of end-stage liver diseases. The optimization of novel biomaterials, such as decellularized matrices and natural macromolecules, also strongly supports the organogenesis of 3D tissue with the desired complex structure. This review summarizes new research updates on novel differentiation protocols of stem cell-derived major hepatic cell types and the application of new supportive biomaterials. Future biological and clinical challenges of this concept are also discussed.

Research progress on the relationship between air pollution and chronic kidney disease / 公共卫生与预防医学

Objective To explore the relationship between exposure to air pollutants and chronic kidney disease. Methods We searched and screened the literature on air pollutant exposure and CKD, using Pubmed, Medline, Embase, and Cochrane databases from inception to May 1, 2020. Chronic exposure to air pollutants and risk of chronic kidney disease were estimated. Results Air pollutants can cause kidney damage to varying degrees, and PM2.5 and PM10 can increase the risk of chronic kidney disease. CO, NO2(NOX) and SO2 may increase the risk of chronic kidney disease. Conclusions Exposure to air pollutants, especially particulate matter( PM2.5 and PM10) ，is associated with an increased risk of chronic kidney disease.

Effect of early mobilization on the physical function of patients in intensive care unit: a Meta-analysis / 中华危重病急救医学

Objective To systematically evaluate the effect of early mobilization on the physical function of patients in intensive care unit (ICU). Methods The randomized controlled trials (RCT) about early intervention in ICU patients were retrieved from the Cochrane Library, PubMed, Wed of Science, Medline, CBM, CNKI, VIP, and Wanfang database, all of which were published literatures from the establishment to October 2018. Early activities were carried out in the intervention group, while only routine nursing was carried out in the control group. Outcome measures included the medical research council score (MRC-Score), physical function ICU test (PFIT), independent walking ability, score of quality of life health survey short form (SF-36), incidence of ICU-acquired weakness (ICU-AW) and hospital mortality. Two researchers independently screened the literature, evaluated the quality of the literature and extracted the data. After literature selection, literature quality evaluation and date extraction was performed, and RevMan 5.3 software was used for Meta-analysis. The publication bias was analyzed by funnel plot. Results A total of 13 literatures were included, 10 in English and 3 in Chinese; of the 1 347 patients, 695 in intervention group and 652 in control group. Compared with the control group, the MRC-Score was increased in intervention group [mean difference (MD) = 4.74, 95% confidence interval (95%CI) = 2.30-7.19, P = 0.000 1], independent walking ability was improved [odds ratio (OR) = 2.04, 95%CI =1.39-2.99, P = 0.000 3], the incidence of ICU-AW was decreased (OR = 0.22, 95%CI = 0.14-0.35, P < 0.000 01), and there was no significant difference in PFIT (MD = -0.19, 95%CI = -0.69-0.31, P = 0.46), physical health (PCS) after 6 months (MD = -1.39, 95%CI = -4.18-1.39, P = 0.33) and inpatient mortality (OR = 0.77, 95%CI = 0.53-1.12, P = 0.17) between two groups. It was shown by funnel plot that the publication bias of each literature was relatively small in terms of MRC-Score, PFIT, independent walking ability and SF-36. Conclusion Early mobilization are beneficial for the physical function recovery of ICU patients, which can improve the muscle strength, improve the ability of patients to walk independently, reduce the occurrence of ICU-AW, and do not increase the mortality rate in hospital.

Anti-cancer activities of S-allylmercaptocysteine from aged garlic / 中国天然药物

While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression in the past decades. Emerging evidence supports a link between garlic consumption and decreased cancer incidence. Notably, aged garlic extract (AGE) exhibits stronger anti-cancer activities than that of fresh garlic, by virtue of enrichment of several AGE-specific organosulfur compounds, including S-allylmercaptocysteine (SAMC). In this review, we summarize the up-to-date mechanistic pathways associated with the anti-proliferative, anti-metastatic and pro-apoptotic effects of SAMC in various cancer models. Based upon the proven safety and improved understanding on its anti-neoplastic properties, SAMC has gained recognition as a promising daily food supplement for cancer prevention or management.

Current status of digestive disease research filed in China from National Natural Science Foundation of China during 2010 to 2017 / 中华医学科研管理杂志

Objective To analyze the current status and future directions of digestive disease research filed in China from previous application and funded projects under H03 code of National Natural Science Foundation of China during 2010 to 2017.Methods All kinds of application and funded projects under H03 code of National Natural Science Foundation of China during 2010 to 2017 were recorded to statistically analyze the subordinate branches,distribution of applicants/institutions,interdisciplinary projects,and cultivation projects.Results The total number of application projects was increasing during the past 8 years.The main research directions include gastrointestinal,hepatic,and pancreatic non-tumor diseases.Funded projects were mainly distributed in relatively developed areas and distinguished universities.The number of funded excellent/distinguished young scholar projects in digestive disease is small.Conclusions With the funding aid from NSFC,the fundamental research in China's digestive disease field has progressed significantly.However,the overall research capacity still need to be further improved.NSFC will continue to fund related research in this field according to its "the 13th Five-Year Plan".

Garlic-derived compound -allylmercaptocysteine inhibits hepatocarcinogenesis through targeting LRP6/Wnt pathway

Whether and how garlic-derived -allylmercaptocysteine (SAMC) inhibits hepatocellular carcinoma (HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) in HCC progression and the anti-HCC mechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human HCC cells without influencing normal hepatocytes. SAMC directly interacted with Wnt-pathway co-receptor LRP6 on the cell membrane. LRP6 was frequently over-expressed in the tumor tissue of human HCC patients (66.7% of 48 patients) and its over-expression only correlated with the over-expression of -catenin, but not with age, gender, tumor size, stage and metastasis. Deficiency or over-expression of LRP6 in hepatoma cells could partly mimic or counteract the anti-tumor properties of SAMC, respectively. administration of SAMC significantly suppressed the growth of Huh-7 xenograft/orthotopic HCC tumor without causing undesirable side effects. In addition, stable down-regulation of LRP6 in Huh-7 facilitated the anti-HCC effects of SAMC. In conclusion, LRP6 can be a potential therapeutic target of HCC. SAMC is a promising specific anti-tumor agent for treating HCC subtypes with Wnt activation at the hepatoma cell surface.

Protective effect of epigallocatechin-3-gallate on hypoxia/reoxygenation injury in cardiac myocytes and its mechanism / 中国药理学通报

Aim To observe the protective effect of epigallocatechin-3-gallate (EGCG) on hypoxia/reoxygenation (H/R) injury of cardiac myocytes and its mechanisms.Methods H9c2 cardiac myocytes were cultured in vitro and randomly divided into five groups:normal group(N group),H/R group,EGCG low dose group (L group),EGCG medium dose group (M group),and EGCG high dose group(H group).The cardiomyocyte H/R injury model was established and EGCG was pretreated.Cell survival rate was tested by CCK-8 method.The cell apoptotic rate was detected using Annexin V-FITC/PI double staining.The contents of total antioxidant capacity(T-AOC) and tumor necrosis factor α(TNF-α) in cell culture medium were tested according to the kit instructions.The protein expression of Akt and p-Akt was observed using Western blot,while the gene expressions of PI3K,Akt,caspase3 were detected by using fluorescence quantitative PCR method.Results Compared with model group,EGCG increased cell survival rate and reduced the apoptosis after H/R injury.Meanwhile,pretreatment EGCG improved the activity of T-AOC,reduced the level of TNF-α,up-regulated the expression of PI3K,Akt and p-Akt,and down-regulated the expression of caspase3.Conclusion EGCG reduces apoptosis and protects cardiac myocytes by influencing PI3K/Akt signal path

Risk factors for periprosthetic joint infection after hip or knee arthroplasty in Mainland of China: a meta-analysis / 中国组织工程研究

BACKGROUND: Periprosthetic joint infection (PJI) is a serious and catastrophic complication after hip or knee arthroplasty. With aging population increasing, more patients will undergo hip or knee arthroplasty. Studies have shown that the risk for PJI following arthroplasty is different in different populations. OBJECTIVE: To evaluate the risk factors for PJI after hip or knee arthroplasty in Mainland of China through a meta-analysis, thereby providing reference for the prevention and control of postoperative PJI. METHODS: A computer-based search of WanFang, CNKI, VIP, CBM, PubMed, Cochrane, Embase and Medline databases was performed and the literatures concerning the risk factors for PJI after hip or knee arthroplasty in Mainland of China published before September 2016 were collected by manual retrieval and retrospective approach. All the literatures were screened based on the inclusion and exclusion criteria, followed by data extraction and analyzed on RESULTS AND CONLUSION: (1) Finally 14 literatures were included, including 417 patients with PJI. (2) The results of the meta-analysis showed that the risk factors for PJI after hip or knee arthroplasty including the complication of diabetic mellitus, long-term use of steroids, long operation time (> 90 minutes), age (> 65 years), and history of hip or knee Stata 12.0 software. surgery. (3) To conclude, PJI after hip or knee arthroplasty is related to multiple factors, so physicians should pay attention to these factors to reduce the incidence of PJI.

Clinical Observation of Acupuncture plus Hyperbaric Oxygen for Depression After Cerebral Stroke / 上海针灸杂志

Objective To observe the clinical efficacy of acupuncture plus hyperbaric oxygen in treating depression after cerebral stroke.Method A total of 120 patients with depression after cerebral stroke were randomized into a treatment group of 60 cases and a control group of 60 cases. The treatment group was intervened by acupuncture plus hyperbaric oxygen, while the control group was intervened by Fluoxetine. Before the treatment, and respectively after 14-d and 28-d treatments, the patients were evaluated by Hamilton Depression Scale (HAMD) and National Institute of Health Stroke Scale (NIHSS), and the therapeutic efficacies were compared between the two groups. Result The treatment group was significantly superior to the control group in comparing therapeutic efficacy (P<0.01). After 1 course of treatment, the HAMD and NIHSS scores dropped significantly in the treatment group (P<0.01); the scores in the control group showed a declining tendency but without statistical significances (P>0.05). After 2 treatment courses, the HAMD and NIHSS scores were significantly different from those before the treatment in both groups (P<0.01), and the differences were more significant in the treatment group (P<0.01).Conclusion Acupuncture plus hyperbaric oxygen is effective in treating depression after cerebral stroke, and it can obviously improve the neural function.

Clinical Observation of Acupuncture plus Hyperbaric Oxygen for Depression After Cerebral Stroke / 上海针灸杂志

Objective To observe the clinical efficacy of acupuncture plus hyperbaric oxygen in treating depression after cerebral stroke.Method A total of 120 patients with depression after cerebral stroke were randomized into a treatment group of 60 cases and a control group of 60 cases. The treatment group was intervened by acupuncture plus hyperbaric oxygen, while the control group was intervened by Fluoxetine. Before the treatment, and respectively after 14-d and 28-d treatments, the patients were evaluated by Hamilton Depression Scale (HAMD) and National Institute of Health Stroke Scale (NIHSS), and the therapeutic efficacies were compared between the two groups. Result The treatment group was significantly superior to the control group in comparing therapeutic efficacy (P<0.01). After 1 course of treatment, the HAMD and NIHSS scores dropped significantly in the treatment group (P<0.01); the scores in the control group showed a declining tendency but without statistical significances (P>0.05). After 2 treatment courses, the HAMD and NIHSS scores were significantly different from those before the treatment in both groups (P<0.01), and the differences were more significant in the treatment group (P<0.01).Conclusion Acupuncture plus hyperbaric oxygen is effective in treating depression after cerebral stroke, and it can obviously improve the neural function.

Development of Tianma HPLC fingerprint and discriminant analysis / 中国中药杂志

Tianma(the tuber of Gastrodia eleta) is a widely used and pricy Chinese herb. Its counterfeits are often found in herbal markets, which are the plant materials with similar macroscopic characteristics of Tianma. Moreover, the prices of Winter Tianma(cultivated Tianma) and Spring Tianma(mostly wild Tianma) have significant difference. However, it is difficult to identify the true or false, good or bad quality of Tianma samples. Thus, a total of 48 Tianma samples with different characteristics(including Winter Tianma, Spring Tianma, slice, powder, etc.) and 9 plant species 10 samples of Tianma counterfeits were collected and analyzed by HPLC-DAD-MS techniques. After optimizing the procedure of sample preparation, chromatographic and mass-spectral conditions, the HPLC chromatograms of all those samples were collected and compared. The similarities and Fisher discriminant analysis were further conducted between the HPLC chromatograms of Tianma and counterfeit, Winter Tianma and Spring Tianma. The results showed the HPLC chromatograms of 48 Tianma samples were similar at the correlation coefficient more than 0.848(n=48). Their mean chromatogram was simulated and used as Tianma HPLC fingerprint. There were 11 common peaks on the HPLC chromatograms of Tianma, in which 6 main peaks were chosen as characteristic peaks and identified as gastrodin, p-hydroxybenzyl alcohol, parishin A, parishin B, parishin C, parishin E, respectively by comparison of the retention time, UV and MS data with those of standard chemical compounds. All the six chemical compounds are bioactive in Tianma. However, the HPLC chromatograms of the 10 counterfeit samples were significantly different from Tianma fingerprint. The correlation coefficients between HPLC fingerprints of Tianma with the HPLC chromatograms of counterfeits were less than 0.042 and the characteristic peaks were not observed on the HPLC chromatograms of these counterfeit samples. It indicated the true or false Tianma can be identified by either the similarity or characteristic peaks on HPLC fingerprint. Comparing the Winter Tianma with Spring Tianma showed that the HPLC chromatograms of 15 winter Tianma samples and 11 spring Tianma samples were similar at the mean correlation coefficient of 0.908. But the intensity of the characteristic peaks were different between the two groups of Tianma samples, i.e. the intensity of gastrodin, paishin A and C in winter Tianma was lower than those in spring Tianma. The Winter Tianma and Spring Tianma could be discriminated by either the Fisher unstandardized discrimination function or Linear discriminant function, based on the peak areas of 11 common peaks on HPLC chromatograms as variate.

Oxidative stress and stem cell transplantation / 中国组织工程研究

BACKGROUND:Stem cel s with wide variety of sources have the potential of differentiation and self-renewal. In additional, autologous stem cel s can avoid immune rejection after transplantation, and thus it has become one of the most promising alternative strategies for tissue/organ transplantation. However, due to the adverse environments at injured sites, such as oxidative stress and inflammation, current stem cel transplantation efficacy is relatively low. OBJECTIVE:To review the effects of oxidative stress on stem cel s and on their transplantation efficiency as wel as relevant mechanisms. METHODS:PubMed database was searched by the first author for relevant articles about stem cel s published from 1990 to 2015. The keywords were“stem cel transplantation, stem cel , oxidative stress, molecular mechanism”. After eliminating literatures which had poor authority or similar content, 97 articles were involved in result analysis. RESULTS AND CONCLUSION:Different types of stem cel s have different basal endogenous antioxidant stress levels. Oxidative stress through multiple molecular pathways causes cel aging, apoptosis and cancer, which also can result in apoptosis of cancer cel s. Stem cel s can adjust endogenous antioxidant levels through multiple paths. To improve the endogenous antioxidant stress level using a variety of methods can increase stem cel transplantation efficiency and prevent stem cel cancerization due to oxidative stress, which makes the clinical application of stem cel transplantation therapy safer and more popular.

Currently Clinical Views on Genetics of Wilson's Disease / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>The objective of this study was to review the research on clinical genetics of Wilson's disease (WD).</p><p><b>DATA SOURCES</b>We searched documents from PubMed and Wanfang databases both in English and Chinese up to 2014 using the keywords WD in combination with genetic, ATP7B gene, gene mutation, genotype, phenotype.</p><p><b>STUDY SELECTION</b>Publications about the ATP7B gene and protein function associated with clinical features were selected.</p><p><b>RESULTS</b>Wilson's disease, also named hepatolenticular degeneration, is an autosomal recessive genetic disorder characterized by abnormal copper metabolism caused by mutations to the copper-transporting gene ATP7B. Decreased biliary copper excretion and reduced incorporation of copper into apoceruloplasmin caused by defunctionalization of ATP7B protein lead to accumulation of copper in many tissues and organs, including liver, brain, and cornea, finally resulting in liver disease and extrapyramidal symptoms. It is the most common genetic neurological disorder in the onset of adolescents, second to muscular dystrophy in China. Early diagnosis and medical therapy are of great significance for improving the prognosis of WD patients. However, diagnosis of this disease is usually difficult because of its complicated phenotypes. In the last 10 years, an increasing number of clinical studies have used molecular genetics techniques. Improved diagnosis and prediction of the progression of this disease at the molecular level will aid in the development of more individualized and effective interventions, which is a key to transition from molecular genetic research to the clinical study.</p><p><b>CONCLUSIONS</b>Clinical genetics studies are necessary to understand the mechanism underlying WD at the molecular level from the genotype to the phenotype. Clinical genetics research benefits newly emerging medical treatments including stem cell transplantation and gene therapy for WD patients.</p>

Preliminary application of Back-Propagation artificial neural network model on the prediction of infectious diarrhea incidence in Shanghai / 中华流行病学杂志

<p><b>OBJECTIVE</b>To establish BP artificial neural network predicting model regarding the daily cases of infectious diarrhea in Shanghai.</p><p><b>METHODS</b>Data regarding both the incidence of infectious diarrhea from 2005 to 2008 in Shanghai and meteorological factors including temperature, relative humidity, rainfall, atmospheric pressure, duration of sunshine and wind speed within the same periods were collected and analyzed with the MatLab R2012b software. Meteorological factors that were correlated with infectious diarrhea were screened by Spearman correlation analysis. Principal component analysis (PCA) was used to remove the multi-colinearities between meteorological factors. Back-Propagation (BP) neural network was employed to establish related prediction models regarding the daily infectious diarrhea incidence, using artificial neural networks toolbox. The established models were evaluated through the fitting, predicting and forecasting processes.</p><p><b>RESULTS</b>Data from Spearman correlation analysis indicated that the incidence of infectious diarrhea had a highly positive correlation with factors as daily maximum temperature, minimum temperature, average temperature, minimum relative humidity and average relative humidity in the previous two days (P < 0.01), and a relatively high negative correlation with the daily average air pressure in the previous two days (P < 0.01). Factors as mean absolute error, root mean square error, correlation coefficient(r), and the coefficient of determination (r(2)) of BP neural network model were established under the input of 4 meteorological principal components, extracted by PCA and used for training and prediction. Then appeared to be 4.7811, 6.8921,0.7918,0.8418 and 5.8163, 7.8062,0.7202,0.8180, respectively. The rate on mean error regarding the predictive value to actual incidence in 2008 was 5.30% and the forecasting precision reached 95.63% .</p><p><b>CONCLUSION</b>Temperature and air pressure showed important impact on the incidence of infectious diarrhea. The BP neural network model had the advantages of low simulation forecasting errors and high forecasting hit rate that could ideally predict and forecast the effects on the incidence of infectious diarrhea.</p>

Reversal effect of mifepristone on adriamycin resistance in human breast cancer cell line MCF-7/ADM in vitro and in vivo / 中南大学学报(医学版)

OBJECTIVE@#To explore the reversal effect of mifepristone(MIF) on adriamycin(ADM) resistance in human breast cell line MCF-7/ADM in vitro and in vivo.@*METHODS@#The transplantable models of MCF-7 cells resisting against adriamycin were established in nude mice by subcutaneous implantation to observe the reversal effect of MIF in vivo. The mice were randomly divided into 4 groups: a control group(treated with saline water 0.2 mL intraperitoneally and edible oil 0.5 mL orally), an MIF group (treated with mifepristone 30 mg/kg orally and saline water 0.2 mL intraperitoneally), an ADM group (treated with adriamycin 5 mg/kg intraperitoneally and edible oil 0.5 mL orally) and an ADM+MIF group (treated with ADM 5mg/kg intraperitoneally and mifepristone 30 mg/kg orally every 3 days). Tumor changes were investigated after different drug treatments. The reversal effect of 5 micromol/L MIF in vitro on the ADM resistance cell line MCF-7/ADM and non ADM resistance cell line MCF-7 was determined by 4,5-dimethylthiazol-2-yl (MTT) assay.@*RESULTS@#(1) The inhibitory rate of 5 micromol/L of MIF for both cell lines MCF-7 and MCF-7/ADM was less than 5%, and it had no statistical difference compared with the group that was not treated with MIF(P > 0.05). (2) ADM could inhibit the growth of both MCF-7 and MCF-7/ADM,but the inhibition concentration 50 (IC(50)) of MCF-7 (0.42 mg/L) was obviously less than that of MCF-7/ADM(17.21 mg/L) (P < 0.05). (3) IC(50) of MCF-7/ADM of MIF+ADM group was 1.96 mg/L in vitro, which was significantly less than that in ADM alone group(17.21 mg/L) (P < 0.05), and 5 micromol/L of MIF reversed ADM resistance with fold-reversal of 8.78. (4) MIF had some effect on the inhibition of MCF-7/ADM cell growth in vivo, the xenograft volume in the MIF+ADM group [(232.5149 +/- 309.2377) mm(3)] was significantly smaller than that in the control group[(962.2309 +/- 261.1313) mm(3) ] after the 4 week treatment(P<0.05), and also smaller than that in the MIF group [(778.2846 +/- 42.6919) mm(3)] and in the ADM group [(508.9648 +/- 16.2609) mm(3)](P < 0.05). There was significant inhibition on xenograft weight after MIF combined with ADM treatment in vivo, and the inhibitory rate was 78.0%.@*CONCLUSION@#MIF can effectively reverse ADM resistance in human breast cancer cell line MCF-7/ADM both in vitro and in vivo.