Hepatic fibrosis(HF)is a common pathological repair response occurring after liver injury and is a critical stage in the progression of chronic liver diseases towards cirrhosis.The molecular mechanisms of HF occurrence are complex.Liver injury triggers the release of various cytokines by multiple cell types,and initiates the downstream signaling pathways to activate the hepatic stellate cells(HSCs)and transform them into myofibroblasts(MFBs).MFBs can release large quantities of extracellular matrix(ECM),thereby disrupt the normal liver architecture and lead to the occurrence and development of HF.The potential therapeutic targets for HF are still in the experimental animal phase,and there are no clinical applications yet.This review summarizes the signaling pathways and related factors involving HSCs and ECM in HF,such as the transforming growth factor-β(TGF-β)/Smad signaling pathway,platelet-derived growth factor(PDGF),matrix metalloproteinases(MMPs),tissue inhibitors of metalloproteinases(TIMPs),and connective tissue growth factor(CTGF).It also discusses the related therapeutic targets,and provids the theoretical basis for the development of new drugs for HF.

Liver cancer is a common tumor that seriously threatens human life and health. Given that the early onset of liver cancer is insidious and lacks specific symptoms, hence it is difficult to screen through routine examination. Thus, clinical diagnosis of liver cancer is mostly in the advanced stage. However, advanced liver cancer has few treatment options, poor prognosis and high relapse rate, thereby causing a high mortality rate. Therefore, early diagnosis of liver cancer is particularly important. Currently, non-invasive screening of liver cancer widely used in clinical setups lacks sufficient sensitivity and specificity, hence, a more reliable diagnostic method needs to be found urgently. This article reviews the research progress of noninvasive early diagnosis of liver cancer to provide a reference for raising the early diagnosis rate of liver cancer.

With the prevalence of nonalcoholic fatty liver disease (NAFLD) in the non-obese population, more and more studies have explored the significance of NAFLD in such population. Compared with the patients with obese NAFLD, the patients with non-obese NAFLD lack the phenotype of obesity, but they still have metabolic disorders and higher risk of metabolic and cardiovascular diseases. At present, there are no effective drugs for the treatment of non-obese NAFLD, and the existing treatment methods have their own advantages and limitations in clinical practice. This article reviews the advances in the etiology and treatment of non-obese NAFLD, in order to provide a reference for guiding the clinical treatment of non-obese NAFLD.

Objective:To determine the prevalence, epidemiological characteristics, and related factors of syphilis infection among rural childbearing age people to promote medical interventions on pre-pregnancy aristogenesis and syphilis infection in Yunnan province.Methods:The subjects in this study were 18-49-year-old rural couples of childbearing age from the National Free Preconception Health Examination Project in Yunnan province during 2013-2017. The descriptive study was carried out to determine the positive rate of Treponema pallidum specific antibody (TPsAb) and related sociodemographic characteristics. Results:The overall positive rate of TPsAb was 0.38% (8 204/2 160 455) in 2 160 455 rural childbearing age people in Yunnan. The positive rate of TPsAb was 0.39% (4 019/1 040 981) in men,higher than that in women (0.37%,4 185/1 119 474). The positive rate of TPsAb was highest in the age group 45-49 years (0.70%,158/22 511). The positive rate of TP antibody in the minority ethnic groups and Han ethnic groups appeared the same (0.38%). However,the highest positive rate of TPsAb was 0.77% (461/60 153) in Hani ethnic group among all the 17 minority ethnic groups. People with education level of primary education had the highest anti-TP positive rate (0.54%,2 327/431 275). The positive rate of TPsAb appeared the highest in Zhaotong (0.73%, 2 049/281 614) area among all the 16 prefectures of the province. The positive rate of TPsAb in the population from the impoverished regions (0.50%,2 963/590 039) was higher than in other disadvantaged areas (0.34%, 3 115/929 368) or areas with average income (0.33%,2 126/641 048). Significant differences appeared in the positive rate of TPsAb among populations of different ages, ethnic, education level, and economic level groups (trend χ2 test, P<0.001). Conclusions:The positive rate of TP antibody in rural childbearing age people in Yunnan was related to multi factors,including sex,age,ethnic group,education level,area, residence, and local economic situation. The positive rate of TPsAb was higher in men than in women. And people with elder age, lower education level, being Hani or Lahu ethnic group, and Zhaotong areas had higher TPsAb positive rates and higher syphilis infection risk.

Objective:To investigate the effect of rapamycin in treatment of tyrosine kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML) without ABL mutation.Methods:Flow cytometry was used to detect the positive expressions of p-mTOR and p-S6 in CD33 positive cells of 2 CML patients with TKI resistance in Jiangsu Province Hospital, and the influence of rapamycin on the positive expressions of p-mTOR and p-S6 in vitro.Results:Rapamycin in vitro inhibited the positive expressions of p-mTOR and p-S6 in CD33 positive cells. After 3 months of oral administration of rapamycin, the positive expressions of p-mTOR and p-S6 in CD33 positive cells were decreased, and the copy number of BCR-ABL fusion gene was also decreased simultaneously.Conclusion:Part of the resistance of CML patients to TKI may be related to the activation of intracellular signaling pathway of mTOR.

Objective:To explore the current status of HBV infection before pregnancy among rural childbearing age people in Yunnan province, find out the population at high risk and areas with high incidence and provide evidence for promoting pre-pregnancy aristogenesis and medical interventions for prevention of HBV infection.Methods:The subjects in the study were rural childbearing age people aged 18-49 who received the national free pre pregnancy eugenic health examination in Yunnan province during 2013-2017. Descriptive analysis was conducted for HBsAg positive rate and its difference among various characteristics. The SPSS 22.0 software was used for statistical analysis.Results:A total of 2 180 841 rural childbearing age people were surveyed, the HBsAg positive rate before pregnancy was 3.13%(68 314/2 180 841) in Yunnan. And the HBsAg positive rate was 3.56% (37 694/1 057 376) in men, higher than that in women (2.73%, 30 620/1 123 465). The HBsAg positive rate was highest in age group 41-49 years (3.77%, 3 126/82 931). The HBsAg positive rate was higher in minority ethnic group (3.77%, 27 974/742 518) than in Han ethnicity group (2.81%, 40 024/1 425 870). Moreover, the highest HBsAg positive rate of was 8.20%(851/10 378) in Yao ethnic group. The people with education level of primary education had the highest HBsAg positive rate (3.97%, 17 294/435 219). The HBsAg positive rate was highest in Xishuangbanna Dai autonomous prefecture (6.65%, 3 875/58 232) in Yunnan. Moreover, the HBsAg positive population in severe poor area (3.32%, 19 755/595 665) was higher than those in less poor area (3.17%, 29 750/939 101) or normal areas (2.91%, 18 809/646 075). There was significant difference in HBsAg positive rate among populations in different age groups, ethnic groups, education level groups, areas and economic level groups ( P<0.001). Conclusions:The HBsAg positive rate in rural childbearing age people in Yunnan was related to multi factors, including sex, age, ethnic group, education level, area and economic development level. The HBsAg positive rate was higher in men, older age and lower education level, minority ethnic group (especially in Yao ethnic group), from Xishuangbanna prefecture and the poor living conditions in childbearing age population.

Objective: Through screening the serum TSH in rural pregestational women, fo find out the high incidence area and high risk population of thyroid disease in Yunnan province, to reduce the probability of infertility and abnormal pregnancy and provide important reference basis for prenatal aristogenesis. Methods: The serum TSH level of 30 163 rural pregestational women(20-49 yeas old) which from 16 different areas and 16 different ethnicities of Yunnan province was detected by using TSH3-Ultra (TSH3-UL) reagent on a Siemens centar-XP automatic chemiluminescence apparatus. Results: 1 797 women were found with abnormal serum TSH level, the abnormal rate was 5.96%. Among them, the proportion of women with decreased TSH was 3.09% and increased TSH was 2.87%, compared with the normal reference range. And there was a significant difference of abnormal serum TSH rate between pregestational women from different areas and ethnicities. Moreover, in the 16 tested areas, the highest abnormal serum TSH rate was 8.90% from Ximeng county, the lowest was 3.60% from Diqing state. However in the 16 tested ethnicities, the highest abnormal serum TSH rate was 9.73% from Lisu ethnic minority and the lowest was 3.60% from Tibetan ethnic minority. Conclusions The results inferred that ethnic and regional factors both to some extent affect the prevalence of thyroid disease in pregestational women and it is a small probability event that high occurrence of TSH decreased or increased situation simultaneously happened in one area or one ethnicity.

Objective To investigate the mechanism of improvement of gait behavior in PD rat models by low frequency electrical stimulation of pedunculopontine tegmental nucleus (PPTN) by optogenetics method. Methods (1) Twenty-four healthy adult male SD rats were randomly divided into a sham-operated group 1, a lesion group 1 and a photoactivation group (n=8); normal saline was injected into the right medial frontal tract (MFB) of the sham-operated group 1; 6-hydroxydopamine (6-OHDA) was injected into the lesion group 1 and photoactivation group to induce PD models; two weeks after modeling, injection of adeno-associated virus hsynapsin-ChR2-mcherry into the right PPTN of the three groups was performed, and the photoactivation group received blue-ray stimulation by implanting optical fibers into the PPTN at the same time. (2) Twenty-four healthy adult male SD rats were randomly divided into a sham-operated group 2, a lesion group 2 and a photoinhibition group (n=8);normal saline was injected into right MFB of the sham-operated group 2; 6-OHDA was injected into the lesion group 2 and photoinhibition group to induce PD models; two weeks after modeling, injection of adeno-associated virus hsynapsin-NpHR-mcherry into the right PPTN of the three groups was performed, and the photoinhibition group received yellow-ray stimulation by implanting optical fibers into the PPTN at the same time. (3) Three weeks after injection of adeno-associated virus, Catwalk gait analysis was used to assess the behavioral ability of rats in each group. Results (1) As compared with the sham-operated group 1, lesion group 1 had significantly increased front claw spacing and back front claw spacing, and significantly decreased stride length and pressure of damaged lateral and contralateral limbs, and significantly decreased swing speed of contralateral limb (P<0.05); as compared with those in the lesion group 1, the front claw spacing and back claw spacing were significantly shortened, and stride length and pressure of damaged lateral and contralateral limbs were statistically increased in the photoactivation group (P<0.05). (2) As compared with the sham-operated group 2, lesion group 2 had significantly increased front claw spacing and back front claw spacing, significantly decreased stride length of damaged lateral limb, and significantly decreased pressure and swing speed of damaged lateral and contralateral limbs (P<0.05); no significant differences were noted on the front claw spacing and back front claw spacing, pressure and swing speed of damaged lateral and contralateral limbs between lesion group 2 and photoinhibition group (P>0.05). Conclusion The mechanism of low frequency electrical stimulation of PPTN improving gait behavior of PD rat models is related to activation of PPTN neurons.

Objective To evaluate the effect of propofol postconditioning on necroptosis during hy-poxia-reoxygenation (H∕R) injury in diabetic cardiomyocytes. Methods Normally cultured H9C2 cardio-myocytes were divided into 5 groups (n= 19 each) using a random number table: control group (group C), high glucose group (group HG), H∕R group, propofol postconditioning (group P) and solvent dimethyl sulfoxide (DMSO) control group (group DMSO). H9C2 cells were incubated for 48 h in DMEM culture medium containing 5. 5 and 25 mmol∕L glucose in group C and group HG, respectively. In group H∕R, H9C2 cells were incubated for 48 h in DMEM culture medium containing 25 mmol∕L glucose and then un-derwent H∕R. H9C2 cells were incubated for 48 h in DMEM culture medium containing 25 mmol∕L glucose and then underwent H∕R, and propofol at the final concentration of 50 μmol∕L was added at the onset of reoxygenation in group P. In group DMSO, H9C2 cells were incubated for 48 h in DMEM culture medium containing 25 mmol∕L glucose and then underwent H∕R, and DMSO at the final concentration of 150μmol∕L was added at the onset of reoxygenation. The model of cardiomyocyte H∕R injury was established by subjecting cardiomyocytes to 6 h of hypoxia followed by 12 h of reoxygenation. At 12 h of reoxygenation, the cell viability was measured by CCK8 assay, the product of lactate dehydrogenase (LDH) in culture medium was measured, the level of reactive oxygen species (ROS) was determined by flow cytometry, cardiomyo-cyte apoptosis was detected by TUNEL, and the expression of receptor-interacting protein 1 ( RIP1), RIP3, Bax, Bcl-2, activated caspase-3 and caspase-3 was determined by Western blot. The apoptotic rate and ratio of activated caspase-3∕caspase-3 were calculated. Results Compared with group C, the cell via-bility was significantly decreased, the product of LDH was increased, the level of ROS and apoptotic rate were increased, the expression of RIP1, RIP3 and Bax was up-regulated, the expression of Bcl-2 was down-regulated, and the ratio of activated caspase-3∕caspase-3 was increased in group HG ( P < 0. 05). Compared with group HG, the cell viability was significantly decreased, the product of LDH was increased, the level of ROS and apoptotic rate were increased, the expression of RIP1, RIP3 and Bax was up-regula-ted, the expression of Bcl-2 was down-regulated, and the ratio of activated caspase-3∕caspase-3 was in-creased in group H∕R (P<0. 05). Compared with group H∕R, the cell viability was significantly increased, the product of LDH was decreased, the level of ROS and apoptotic rate were decreased, the expression of RIP1, RIP3 and Bax was down-regulated, the expression of Bcl-2 was up-regulated, and the ratio of acti-vated caspase-3∕caspase-3 was decreased in group P (P<0. 05), and no significant change was found in the indexes mentioned above in group DMSO (P>0. 05). Conclusion The mechanism by which propofol post-conditioning ameliorates H∕R injury in diabetic cardiomyocytes may be related to inhibiting necroptosis.

Objective:To investigate the protein expression of GTPBP4 in human hepatocelluar carcinoma (HCC) tissues and the influ-ence of GTPBP4 silencing by siRNA on the proliferation and cell cycle of HCC cell line Hep G2. Methods:Western blot analysis was per-formed to observe the protein expression of GTPBP4 in 24 cases of HCC tissues compared with their adjacent noncancerous liver tis-sues. Lentivirus-mediated RNA interference (RNAi) was used to silence GTPBP4 expression in Hep G2, and the infection efficiency was observed under a fluorescence microscope. The silencing effect was tested by Western blot and real-time PCR. After silencing the GT-PBP4 gene, cell proliferation was detected using CCK-8 assay, and the cell cycle was observed using flow cytometry. Results:(1) GT-PBP4 was overexpressed in 21 cases (87.5%) of HCC tissues (P<0.000 1). (2) After the lentivirus with GFP reporter infected the Hep G2 cells, 90%of the cells showed green fluorescence. LV-GTPBP4-RNAi effectively inhibited the expression of GTPBP4 at both mRNA (70%) and protein (67%) levels. (3) The proliferation ability of the LV-GTPBP4-RNAi group significantly decreased after 96 h (inhibition rate:54.51%). Flow cytometry showed that the LV-GTPBP4-RNAi group significantly increased at the G0/G1 phase, whereas the S phase de-creased and arrested at the G0/G1 phase. Conclusion:GTPBP4 overexpression in HCC tissues was associated with hepatocarcinogenesis and promoted tumor cell proliferation, but the specific molecular mechanisms remain to be investigated.