Research advances in animal models of cholestatic liver disease / 临床肝胆病杂志

Cholestatic liver diseases (CLD) are a series of diseases due to impaired bile flow and accumulation of bile acid in the liver and/or systemic circulation caused by immune, genetic, and environmental factors. The pathogenesis of CLD remains unclear and CLD is difficult to treat. As a substitute for human diseases, animal models can provide a platform for exploring the etiology and pathogenesis of the disease and finding appropriate therapeutic targets. This article reviews the current research advances in the animal models of CLD.

Evaluation of the effect of Zhushui plaster application and nursing combined with Elemene injection on lung cancer patients with malignant pleural effusion / 中国实用护理杂志

Objective:To study the effect of Zhushui plaster application and nursing combined with elemene injection on the psychological state, the degree of cancer-related fatigue, and the quality of life of lung cancer patients with malignant pleural effusion.Methods:According to the clinical controlled trial, a total of 100 patients with malignant pleural effusion of lung cancer admitted to the Department of Cardiothoracic Surgery Ⅱ and Vascular Surgery of Ningbo Medical Center Lihuili Hospital from April 2019 to December 2021 were convenient selected and divided into control group and experimental group with 50 cases in each group by random number table method. The control group received intrapleural perfusion therapy with elemene injection, and the experimental group was treated with Zhushui plaster on the basis of the control group. The psychological state, cancer-induced fatigue and quality of life of the two groups before and after treatment were compared.Results:There was no significant difference in baseline data between the two groups before intervention (all P>0.05). There were no significant differences in psychological status, cancer-induced fatigue and the quality of life before intervention between the two groups (all P>0.05). After the intervention, the anxious and depressed scores of the patients in the experimental group were (64.12 ± 3.24) and (60.38 ± 3.00), respectively, which were lower than those in the control group, (66.00 ± 3.69) and (62.10 ± 3.30), and the differences were statistically significant ( t=2.72, 2.73, both P<0.05). The scores of perceived fatigue, emotional fatigue, cognitive fatigue and behavioral fatigue in the experimental group were (5.66 ± 0.59), (5.26 ± 0.75), (4.00 ± 0.93) and (5.08 ± 0.80), respectively, which were lower than those in the control group, (5.98 ± 0.74), (5.70 ± 1.09), (4.42 ± 1.07) and (5.52 ± 1.00), respectively, and the differences were statistically significant ( t values were 2.10-2.46, all P<0.05); in addition, the dimensions and total scores of the quality of life in the experimental group were (50.54 ± 5.09), (52.49 ± 4.46), (50.40 ± 4.40), (48.96 ± 3.32) and (202.38 ± 15.42), respectively, which were higher than those in the control group, (47.82 ± 6.69), (49.40 ± 6.28), (47.24 ± 4.70), (46.56 ± 4.13) and (191.00 ± 15.79) respectively, and the differences were statistically significant ( t values were -3.65--2.29, all P<0.05). Conclusions:Zhushui plaster application and nursing combined with elemene injection can not only effectively control the negative psychological state of lung cancer patients with malignant pleural effusion and reduce the degree of cancer-related fatigue, but also improve their quality of life.

Research progress of posterior seleral staphyloma in high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#High myopia complicated with fundus lesions is one of irreversible blinding eye diseases. Posterior seleral staphyloma(PSS)is one of the most basic pathologies in a series of complications of high myopia. This article reviews the pathogenesis, examination methods, classification and treatment of PSS in high myopia by sorting out domestic and foreign literature, providing a better understanding of the prevention and control of PSS.

Effect of electroacupuncture and pretreatment of electroacupuncture on pain sensitization and expression of P2X7R in spinal dorsal horn in rats with diabetic neuropathic pain / 中国针灸

OBJECTIVE@#To observe the occurrence time of neuralgia and the expression of purinergic ligand-gated ion channel 7 receptor (P2X7R) in the dorsal horn of the spinal cord after intraperitoneal injection of streptozotocin (STZ) in diabetic rats, and to explore the effect of electroacupuncture (EA) and pretreatment of EA on the heat pain threshold and expression of P2X7R in the spinal dorsal horn in rats with diabetic neuropathic pain (DNP), and to explore the possible mechanism of EA for DNP.@*METHODS@#PartⅠ: Thirty male SD rats were randomly selected from 64 male SD rats as the control group; the remaining rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model, and 30 rats were successfully modeled as the model group. The control group and the model group were divided into three subgroups respectively at 7, 14 and 21 days, with 10 rats in each subgroup. Body mass, fasting blood glucose (FBG) and thermal pain threshold were recorded at 7, 14 and 21 days after injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot. PartⅡ: Eight SD rats were randomly selected from 35 male SD rats as the blank group, and the remaining 27 rats were given intraperitoneal injection of STZ (10 mg/mL) at a dose of 65 mg/kg to establish the diabetes model. The 24 rats with successful diabetes model were randomly divided into a DNP group, an EA group and a pre-EA group, 8 rats in each group. Fifteen to 21 days after STZ injection, the EA group received EA at "Zusanli" (ST 36) and "Kunlun" (BL 60), continuous wave, frequency of 2 Hz, 30 min each time, once a day; the intervention method in the pre-EA group was the same as that in the EA group. The intervention time was 8 to 14 days after STZ injection. The body mass, FBG and thermal pain threshold were recorded before STZ injection and 7, 14 and 21 days after STZ injection; the expression of P2X7R in spinal dorsal horn was detected by Western blot 21 days after injection.@*RESULTS@#PartⅠ: Compared with the control group, in the model group, the body mass was decreased and FBG was increased 7, 14 and 21 days after STZ injection (P<0.01), and the thermal pain threshold was decreased 14 and 21 days after STZ injection (P<0.05), and the expression of P2X7R in spinal dorsal horn was increased 7, 14 and 21 days after STZ injection (P<0.05, P<0.01). PartⅡ: Compared with the blank group, in the DNP group, the body mass was decreased and fasting blood glucose were increased 7, 14 and 21 days after STZ injection (P<0.01). Compared with the DNP group, in the pre-EA group, the heat pain threshold was increased 14 and 21 days after STZ injection (P<0.05), while in the EA group, the heat pain threshold was increased 21 days after STZ injection (P<0.01), and the expression of P2X7R in the dorsal horn in the EA group and the pre-EA group was decreased (P<0.01).@*CONCLUSION@#The diabetic neuropathic pain is observed 14 days after STZ injection. EA could not only treat but also prevent the occurrence of DNP, and its mechanism may be related to down-regulation of P2X7R expression in the dorsal horn of the spinal cord.

Effects of Toluene on the Development of the Inner Ear and Lateral Line Sensory System of Zebrafish / 生物医学与环境科学（英文）

Objective@#The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae.@*Methods@#Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity.@*Results@#The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml @*Conclusion@#This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.

Association of serum Apelin level, silicosis stage and pulmonary function in patients with occupational silicosis / 中国职业医学

OBJECTIVE: To explore the association of serum Apelin level, silicosis stage and lung function in patients with occupational silicosis(hereinafter referred to as silicosis). METHODS: A case-control study was conducted. A total of 85 patients with silicosis were selected as the silicosis group(44, 28 and 13 patients with stage Ⅰ, Ⅱ and Ⅲ silicosis, respectively), and 120 healthy individuals without occupational hazard exposure were selected as the control group. Serum samples were collected from the cases of the two groups and the level of Apelin was determined by enzyme-linked immunosorbent assay. The pulmonary function of the silicosis group was examined. RESULTS: The median and the 25 th and 75 th percentiles \[M(P_(25),P_(75))\] of serum Apelin levels in the control group and silicosis group were 1.29(0.92, 1.77) and 0.80(0.62, 1.04) mg/L, respectively. The level of serum Apelin M(P_(25),P_(75)) in stage Ⅰ, Ⅱ and Ⅲ silicosis patients was 1.03(0.82, 1.31), 0.66(0.60, 0.80) and 0.50(0.30, 0.65) mg/L, respectively. The results of multiple linear regression analysis showed that the level of serum Apelin in the silicosis group was higher than that in the control group after excluding the influence of age and smoking(P<0.01). The level of serum Apelin decreased with the increase of silicosis stage in the silicosis group(P<0.001). Serum Apelin level in silicosis group was positively correlated with lung vital capacity, forced vital capacity, forced expiratory volume in the first second, and forced expiratory flow between 25% and 75%(all P<0.05). CONCLUSION: The lower level of serum Apein in silicosis patients, the more serious the disease and the more serious the damage to lung function. Apelin is of significance in the diagnosis, staging, treatment appraisal and prognostic evaluation of silicosis, and it can be use as a potential therapeutic target for silicosis.

Analysis on the influencing factors of low back pain in the occupational workers of key industries in China / 中国职业医学

OBJECTIVE: To explore the influencing factors of low back pain and the relationship of the influence of bad working posture, weight load and frequency of load and the dose-response relationship among the occupational workers of key industries in China. METHODS: A total of 57 501 employees from 15 key industries in China were selected as research subjects using stratified cluster sampling method. The occurrence of low back pain in the past one year, as well as occupational factors such as job type, labor organization and work posture were investigated by using the Chinese version Musculoskeletal Disorders Questionnaire. RESULTS: The prevalence of low back pain in the occupational population of key industries in China was 16.4%(9 448/57 501). Multivariate Logistic regression analysis showed that the risk of low back pain in females was higher than that in males(P<0.01). Married, obese, occasional and frequent smokers, and a history of lower back disease were associated with increased risk of low back pain(all P<0.05). The risk of low back pain was associated with older age, higher education level, and lower frequency of physical exercise(all P<0.01). The risk of low back pain was higher with longer working time, greater back curvature, and the high frequency of long standing and sitting position work, uncomfortable working posture, repeated operation per minute, and lifting>5 kg weight(all P<0.01). CONCLUSION: The influencing factors of low back pain in the occupational population of key industries in China include bad working posture, high frequency load, weight load and other individual factors. There is a dose-response relationship with low back posture load and frequency of load.

Relationship between work-related musculoskeletal disorders and ergonomic factor load in shipyard workers / 中国职业医学

OBJECTIVE: To assess the effect of ergonomic factor load on work-related musculoskeletal disorders(WMSDs) in shipyard workers. METHODS: A total of 751 shipyard workers were selected as the research subjects using judgment sampling method. The exposure level of adverse ergonomic factors was assessed using the Quick Exposure Check method. The prevalence of WMSDs was investigated using the revised Musculoskeletal Disorders Investigating Questionnaire of our research group, and the relationship between them was analyzed. RESULTS: The proportions of high or very high level of work load exposure to the neck, back, shoulder and hand in shipyard workers from high to low were 66.4%, 63.5%, 59.8% and 43.7%(P<0.01) respectively. The proportions of occupational stress, driving, vibration and working rhythm at high or very high exposure level were 20.0%, 4.1%, 22.9% and 3.2%, respectively. The prevalence of WMSDs in four body parts of shipyard workers from high to low was the back, neck, hand and shoulder(the prevalence were 44.2%, 31.2%, 26.9% and 26.6%, respectively, P<0.01). After excluding the influence of confounding factors, multiple logistic regression analysis showed that the higher the labor load exposure level and longer of the vibration tool using, the higher the risk of shoulder WMSDs [odds ratio(OR) and 95% confidence interval(CI) were 1.25(1.04-1.51) and 1.33(1.05-1.69), respectively, P<0.05]. The higher the level of occupational stress, the higher the risk of back and neck WMSDs [OR(95%CI) was 1.29(1.05-1.58) and 1.42(1.15-1.77), respectively, P<0.05]. CONCLUSION: There was a dose-effect relationship between the exposure level of shoulder load, the time of using vibration tools and the shoulder WMSDs, and there was a dose-effect relationship between the occupational stress level and the WMSDs in the back and neck.

Effect of Schizonepetae Herba and Saposhnikoviae Radix on expression of AQP4 and AQP8 in colonic mucosa of rats with ulcerative colitis / 中国中药杂志

The aim of this paper was to investigate the effect of Schizonepetae Herba and Saposhnikoviae Radix(wind medicine) on the expression of AQP4 and AQP8 in colonic mucosa in rats with ulcerative colitis(UC). A total of 35 healthy SD male rats were randomly divided into normal group(gavaged with normal saline), DSS model group, as well as low, middle, and high dose wind medicine groups(Schizonepeta and Saposhnikovia 1∶1, gavaged at dosages of 6, 12, and 24 g·kg~(-1)·d~(-1)), with 7 in each group. UC rat model was established by free drinking of 3% dextran sulphate sodium(DSS) solution for 10 days. At the end of the 10 th day after the treatment, mice were put to death to collect colonic mucosa. The length of colon was measured; the colonic mucosal injury index(CMDI) and pathological changes of colon were observed. ELISA method was used for measuring the content of serum IL-1, IL-8, and immunohistochemical method was used to measure AQP4, AQP8 protein expressions in colon mucosa. The expressions of AQP4, AQP8 mRNA were measured by Real-time PCR. As compared with the normal group, the length of colon tissue was significantly reduced(P<0.01), CMDI scores and pathological scores were significantly increased(P<0.01), the levels of serum IL-1 and IL-8 were significantly increased(P<0.05) in model group; the immunohistochemical results showed that the protein expressions of AQP4, AQP8 were lower; the color was light yellow or brown; AQP4, AQP8 mRNA expressions in colon mucosa were significantly decreased in model group(P<0.01). CMDI scores, pathological scores, and the levels of serum IL-1, IL-8 in high, middle, low dose wind medicine groups were obvious lower than those in the model group(P<0.01 or P<0.05); the protein expressions of AQP4, AQP8 were higher; the color was chocolate brown or dark brown; the length of colon tissue, and the expressions of AQP4, AQP8 mRNA were obvious higher in wind medicine groups(P<0.01 or P<0.05). Schizonepetae Herba and Saposhnikoviae Radix could significantly improve the symptoms and histopathology of UC model rats and accelerate the intestinal mucosal healing. The mechanism may be related with up-regulating the expression level of AQP4 and AQP8 in colonic mucosa.

Research on the P-CMM-based appraisal and improvement of recruitment practice system of a tertiary hospital / 中华医院管理杂志

Objective:To improve the recruitment management process of public hospitals and enhance the quality of recruitment.Methods:Through the introduction of the people capability maturity model(P-CMM), the recruitment practice system of a tertiary hospital was evaluated. The evaluation scoring was expressed as the average score±standard deviation( ± s), and the scorer′s reliability index was expressed as Kendall coefficient. Results:According to the P-CMM recruitment practice standards, a total of 16 level-1 indicators and 35 level-2 indicators were set up. Among them, there were 7 standard projects and 9 gap projects, with reasons for the gaps analyzed.Conclusions:It is necessary to enhance the strategic vision of the recruitment process, systematically implement hospital post management, build a recruitment platform based on multi-party participation, and scientifically analyze the recruitment process to further improve the recruitment quality of public hospitals.

Clinical effect of endoscopy assisted suction-cutter removal of apocrine sweat glands / 中华医学美学美容杂志

Objective To explore the clinical effect of endoscope assisted suction-cutter removal of apocrine sweat glands in treatment of osmidrosis.Methods This study generalized and analyzed the curative effects of 30 patients with axillary osmidrosis,treated with endoscopy assisted suction-cutter removal of apocrine sweat glands.The efficacy was evaluated according to the postoperative results and complications.Results In all the 30 patients,wound healed 7 to 10 days after operation,and they resumed almost normal life after treatment.From May 2015 to April 2017,the follow-up visits showed that none of them had relapse,infection or skin necrosis.Surgical scar was slight,and in all the patients,symptoms disappeared.Conclusions The operation of endoscopy assisted suction-cutter removal of apocrine sweat glands is a minimally invasive surgery.The advantages include direct vision,radical operation,well preserved dermal vascular network and lower risk of complications.

Research on metabolic and inflammatory biomarkers related to local muscle fatigue in workers with simulated manual lifting / 中国职业医学

OBJECTIVE: To analyze the relationship between the blood biochemical indexes and the local muscle fatigue of operators with local muscle fatigue caused by moderate-load repetitive manual lifting. METHODS: Five healthy male volunteers were selected as the research subjects. They repeatedly performed simulated manual lifting operation for four periods(T1-T4), 10 minutes per period. Each period was suspended for 3 minutes to be accessed for the rating of perceived exertion(RPE) score of local muscle. Meanwhile, their venous blood was collected to be detected for serum calcium ion, creatine kinase, cartilage oligomeric matrix protein(COMP), ammonia, lactic acid, lactate dehydrogenase(LDH), C-reactive protein(CRP), and collagen type Ⅱ C terminal telopeptide(CTX-Ⅱ). RESULTS: The RPE score and serum creatine kinase level of the subjects increased with the increasing of lifting time(P<0.05). Serum calcium ion levels in time periods T2, T3 and T4 were higher than that in T1(P<0.05). Serum COMP levels in T3 and T4 were higher than that in T1(P<0.05). The levels of ammonia,lactic acid, LDH, CRP and CTX-Ⅱ in each time period showed no statistical significance(P>0.05). Serum creatine kinase, calcium ion and LDH levels were positively correlated with RPE score(correlation coefficient were 0.840, 0.512, 0.741, respectively, P<0.01). CONCLUSION: Serum creatine kinase is a sensitive, effective and objective index reflecting muscle fatigue, which is suitable for evaluating the fatigue process of moderate-load repetitive activities. Serum calcium ion has a good correlation with muscle fatigue, and serum COMP can reflect muscle fatigue to some extent.

Enhancement of T Follicular Helper Cell-Mediated Humoral Immunity Reponses During Development of Experimental Autoimmune Myasthenia Gravis / 神经科学通报·英文版

Myasthenia gravis (MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper (Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear. Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha (AChRα) subunit (R-AChR)-induced experimental autoimmune myasthenia gravis (EAMG). This model presented mild body-weight loss 10 days after the first immunization (representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization (representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In co-cultures of Tfh cells and B cells, the number of IgG2b-secreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4/Bcl-6 T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, we hypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.

Diagnostic Value of Transient Elastography for Staging of Liver Fibrosis in Patients with Chronic Liver Disease: A Meta-analysis / 胃肠病学

Background: Early diagnosis and staging of liver fibrosis are important for the prognosis and evaluating the survival of patients.Aims: To systematically assess the diagnostic value of transient elastography (TE) for staging of liver fibrosis in patients with chronic liver disease.Methods: PubMed,Embase,Cochrane Library,CNKI,Wanfang and VIP from Jan.2001 to Dec.2015 were retrieved to collect the articles with staging of liver fibrosis in patients with chronic liver disease by TE.Data extraction was conducted.Article quality was evaluated by quality assessment of diagnostic accuracy studies 2 (QUADAS2).Meta-analysis was conducted by Stata 12.0 software.Results: Twenty articles involving 5 748 patients were included.Meta-analysis showed that the combined sensitivity,specificity and AUC of TE for diagnosing significant fibrosis (≥F2) were 0.78 (95％ CI: 0.73-0.82),0.85 (95％ CI: 0.80-0.88) and 0.88 (95％ CI: 0.85-0.91),respectively.The combined sensitivity,specificity and AUC for advanced fibrosis (≥F3) were 0.89 (95％ CI: 0.86-0.91),0.88 (95％ CI: 0.85-0.91) and 0.94 (95％ CI: 0.92-0.96),respectively.The combined sensitivity,specificity and AUC for cirrhosis (F4) were 0.91 (95％ CI: 0.86-0.95),0.89 (95％ CI: 0.87-0.92) and 0.95 (95％ CI: 0.93-0.97),respectively.Conclusions: TE technique has a good diagnostic value in assessing significant fibrosis,advanced fibrosis and cirrhosis in patients with chronic liver disease,especially for advanced fibrosis and cirrhosis.

Analysis of the Clinical Effect of Botulinumtoxin Type A(Botox-A)Combined with Electromyographic Biofeedback Therapy on the Upper Limb Muscle Spasm after Stroke / 现代生物医学进展

Objective:To investigate the clinical effect of botulinumtoxin type A (Botox-A) combined with electromyographic biofeedback therapy on the upper limb muscle spasm after stroke.Methods:86 cases of patients with upper limb muscle spasm after stroke in our hospital from January 2016 to January 2017 were selected and divided into the observation group and the control group,with 43 cases in each group.Patients in the control group were treated with electromyographic biofeedback therapy,and the observation group was treated with Botox-A based on the basis of control group.The improvement of upper limb muscle spasm,Upper limb movement function,the active range of wrist joint and life skills before and after treatment were compared between two groups.Results:After treatment,the total effective rate of improvement of upper limb muscle spasm of observation group were significantly higher than that of the control group (P＜0.05);At 2 weeks and 4 weeks after treatment,the Fugl-Meyer scores,Wrist joint activities,modified Barthel index (MBI) of two groups were significantly higher than those before treatment (P＜0.05),which were significantly higher in the observation group than those of the control group (P＜0.05).Conclusion:Botox-Acombined with electromyographic biofeedback therapy had remarkable clinical effect on the upper limb muscle spasm after stroke,which could effectively reduce the upper limb spasticity,improve the arm and wrist movement ability and the ability of daily life.

New advances in diagnosis of nonalcoholic fatty liver disease / 中华肝脏病杂志

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and the spectrum of this disease includes simple liver steatosis, nonalcoholic steatohepatitis, liver fibrosis, and liver cirrhosis. At present, liver biopsy is still the gold standard for the diagnosis of NAFLD and can determine the degree of steatosis, inflammation grade, and fibrosis stage, but its clinical application is limited by its invasiveness and static nature. New diagnostic markers and noninvasive diagnostic methods have been reportedly recently, and the constant development of magnetic resonance imaging, transient elastography, and controlled attenuation parameter provides new methods for the noninvasive diagnosis of NAFLD.

Three-dimensional finite element analysis of a newly designed onplant miniplate anchorage system / 华中科技大学学报（医学）（英德文版）

The purpose of this research was to evaluate the structural stress and deformation of a newly designed onplant miniplate anchorage system compared to a standard anchorage system. A bone block integrated with a novel miniplate and fixation screw system was simulated in a three-dimensional model and subjected to force at different directions. The stress distribution and deformation of the miniplate system and cortical bone were evaluated using the three-dimensional finite element method. The results showed that the stress on the plate system and bone was linearly proportional to the force magnitude and was higher when the force was in a vertical direction (Y-axis). Stress and deformation values of the two screws (screw 1 and 2) were asymmetric when the force was added along Y-axis and was greater in screw 1. The highest deformation value of the screws was 7.5148 μm, much smaller than the limit value. The load was decreased for each single miniscrew, and the ability of the new anchorage system to bear the load was also enhanced to some degree. It was suggested that the newly designed onplant miniplate anchorage system is effective, easily implanted and minimally invasive.

Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells

Matrine (MT), the effective component of Sophora flavescens Ait, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects of MT still need to be strengthened due to its relatively low efficacy and short half-life. In the present study, we report a more effective thio derivative of MT, MD-1, and its inhibitory effects on the activation of hepatic stellate cells (HSCs) in both cell culture and animal models. Cytological experiments showed that MD-1 can inhibit the proliferation of HSC-T6 cells with a half-maximal inhibitory concentration (IC50) of 62 μmol/L. In addition, MD-1 more strongly inhibits the migration of HSC-T6 cells compared to MT and can more effectively induce G0/G1 arrest and apoptosis. Investigating the biological mechanisms underlying anti-hepatic fibrosis in the presence of MD-1, we found that MD-1 can bind the epidermal growth factor receptor (EGFR) on the surface of HSC-T6 cells, which can further inhibit the phosphorylation of EGFR and its downstream protein kinase B (Akt), resulting in decreased expression of cyclin D1 and eventual inhibition of the activation of HSC-T6 cells. Furthermore, in rats with dimethylnitrosamine (DMN)-induced hepatic fibrosis, MD-1 slowed the development and progression of hepatic fibrosis, protecting hepatic parenchymal cells and improving hepatic functions. Therefore, MD-1 is a potential drug for anti-hepatic fibrosis.

Reversal of liver fibrosis through AG490 inhibitor-mediated inhibition of the TGFbeta1-STAT3 pathway / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the role of TGF-beta1 and STAT3 signaling in liver fibrosis using a rat model system and to determine the therapeutic mechanism of AG490 in relation to this signaling pathway.</p><p><b>METHODS</b>Rats were randomly divided into a control group and DENA-induced liver fibrosis model group, and then subdivided into AG490 treatment groups. During fibrosis development, liver tissue samples were collected at different time points (0, 4 and 8 weeks) and evaluated according to the Scheuer scoring system. Expression of STAT3, TGFbeta1, alpha-SMA, E-cadherin, MMP2 and TIMP1 was measured by PCR (mRNA) and immunohistochemistry and western blotting (protein).</p><p><b>RESULTS</b>Increasing degrees of inflammation and fibrosis were observed in liver tissues of DENA-treated rats throughout model establishment. The mRNA expression of TGFbeta1 and STAT3 was significantly increased in DENA-induced rats with advanced fibrosis (AF) compared to those with early fibrosis (EF) (P = 0.034 and P = 0.012 respectively). The protein expression of TGF-beta1, phospho-Smad2, alpha-SMA, E-cadherin, STAT3 and phospho-STAT3 was significantly increased in DENA-induced rats with AF compared to the unmodeled control group (P = 0.048, P = 0.003, P = 0.002, P = 0.028, P = 0.009 and P = 0.039). The protein expression of E-cadherin was lower in the DENA-induced rats with AF than in those with EF (P = 0.026). STAT3 and TGF-beta1 co-expression was detected in AF tissues. DENA-induced AG490-treated rats with AF showed substantially lower protein expression of STAT3, TGF-beta1, MMP2 and TIMP1 compared to DENA-induced untreated rats with AF (P = 0.006, P = 0.018, P = 0.010 and P = 0.005); in addition, the degrees of fibrosis and inflammation were also greatly reduced in the DENA-induced AG490-treated rats with AF compared to DENA-induced untreated rats with AF (P = 0.042 and P = 0.021). Conclusions STAT3 signal transduction may regulate the TGF-beta1 pathway and affect liver fibrosis, especially in the advanced phase. AG490 can inhibit TGFbeta1-STAT3 signaling, resulting in reversal of liver fibrosis.</p>

Cholestasis morbidity rate in first-hospitalized patients with chronic liver disease in Shanghai / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the epidemiological status of cholestasis in first-hospitalized patients with chronic liver disease in Shanghai, and to provide a scientific basis for developing prevention and treatment measures.</p><p><b>METHODS</b>From April 2005 to September 2014, 5,146 first-hospitalized patients in Shanghai with a diagnosis of chronic liver disease were enrolled in this study. Clinical data of the 4,660 patients who fit the study criteria for participation were collected for retrospective analysis.Diagnosis of cholestasis was made according to serum alkaline phosphatase (ALP) levels higher than 1.5 times the upper limit normal (ULN) and gamma-glutamyltransferase (GGT) levels higher than 3 times the ULN. The incidence rate of cholestasis was assessed for relation to age, sex, etiology, and type of liver disease, and statistically compared to the general clinical data and specific biochemical indicators with potential sex-related differences. T-test and chi-square test were performed for the statistical analyses.</p><p><b>RESULTS</b>Of the 4,660 study participants, 10.26% had cholestasis; the prevalence of cholestasis increased with increasing age in male patients. The distribution of the cholestasis incidence according to the type of chronic liver disease was: 75.00%, primary sclerosing cholangitis; 42.86%, primary biliary cirrhosis; 35.97%, hepatic tumor; 30.77%, autoimmune hepatitis; 28.31%, drug-induced liver disease; 16.46%, alcoholic hepatitis; 13.98%, cryptogenic cirrhosis; 12.99%, schistosomal cirrhosis; 7.53%, alcoholic cirrhosis; 7.32%, mixed cirrhosis; 5.94%, viral liver cirrhosis; 2.70%, nonalcoholic fatty liver disease. There was no significant difference in the prevalence of cholestasis between the two sexes. In the patients with cholestasis, the levels of GGT and total bilirubin were significantly different between the two sexes.</p><p><b>CONCLUSION</b>The incidence rate of cholestasis in first-hospitalized patients with chronic liver disease was 10.26%, and the rate increased with increased age. Patients with primary sclerosing cholangitis or primary biliary cirrhosis had higher incidence rates of cholestasis. Incidence rates of cholestasis of the various chronic liver diseases were not related to sex.</p>