AIM:To investigate the effect of RNA interference (RNAi)-mediated insulin-like growth factor 1 receptor ( IGF1R) gene silencing on the growth , migration, and invasion of hepatocellular carcinoma cells .METHODS:The most effective siRNA targeting IGF1R gene was designed and screened .After lentiviral expression vector pLVX-shR-NA2-IGF1R carrying the most effective siRNA sequence was constructed , it was transfected into 293T cells and packed into pLVX-shRNA2-IGF1R lentivirus.Huh7 and Hep3B cells were infected with the pLVX-shRNA2-IGF1R lentivirus to screen the positive clone Huh7 cells and Hep3B cells with the lentivirus .These Huh7 cells and Hep3B cells were cultured to ana-lyze the mRNA level of IGF1R, cell proliferation, cell cycle, cell apoptosis, cell migration/invasion, and the protein levels of IGF1R, Ki-67, p-AKT, p-ERK1, Gli1,β-catenin, cyclin D1, p21 and BCL-XL.RESULTS:The mRNA expression of IGF1R in Huh7 cells and Hep3B cells with pLVX-shRNA2-IGF1R lentivirus was significantly reduced .The proliferation of these cells was remarkably inhibited , and the number in G 1 phase was increased significantly .The percentages of apop-totic cells were increased markedly , and the number of cell migration/invasion was decreased markedly .The protein levels of IGF1R, Ki-67, p-AKT, p-ERK1, Gli1,β-catenin, cyclin D1, p21 and BCL-XL were decreased significantly compared with the blank control group and negative control group .CONCLUSION:The RNAi-mediated IGF1R gene silencing sig-nificantly suppresses the growth and the malignant biological characteristics of Huh 7 cells and Hep3B cells, which may be involved in the reduced protein levels of the above genes induced by down -regulation of IGF1R expression.

Objective To study the protein expressions of Fas-associated death domain protein (FADD) and caspase-8 in rats with intracerebral hemorrhage ,and the effects of erythropoietin tp reveal the mechanism of neu-m-protection by EPO. Methods 126 male SD rats were randomly divided into three groups: Sham-operated group, intracerebral hemorrhage group, and EPO group. Each group was divided into seven subgroups according to the differ-ent time points (3,6,12,24,48,72 h and 7 d). The model of intracerebral hemorrage was established in rats by in-tracerebral injection of autogenous blood. The protein expressions of FADD and caspas-8 in rats tissue around the hemorrhagic and the normal brain tissue were detected by immunohistochemistry. Results The protein expressions of FADD and caspase-8 were increased [(4.66±0.46 ) and ( 15.89±1.81)] at 3 h after intracerebral hemorrhage, and peaked at 48 h [ (35.88±4.24 ) and (45.04±3.99)], the expressions of FADD and caspas-8 in the region around hematoma in EPO group significantly decreased compared with model group[ (3.92±0.64) and (28.24±1.90), (13.32±2.01 ) and (35.08±2.82)] at 3 h and 48 h. Conclusion The protein expressions of FADD and easpase-8 are markedly increased after intracerebral hemorrhage. EPO can protect the neurons by signifi-cantly reducing the expressions of FADD and caspase-8.

Objective To investigate the protective effect of Ganyu capsule on the experimental hepatic injury in mice and rats.Methods Acute hepatic injury was induced by intraperitoneal injection of 0.1 %CCl4 10mL/kg and D-galactosamine 500 mg/kg in mice;Cirrhosis was induced by 40 %CCl4 adding with variousagents in rats.The biochemical parameters such as serum ALT were examined and the histopathological changes of hepatic tissue was measured.Results Ganyu capsule could obviously inhibit the increase of serum ALT and AST activity and reduce the content of collagen in liver and the deseverity of hepatic fibrosis.Conclusion Ganyu capsule has protective effects on the acute and chronic hepatic injury in mice and rats.

Objective:To study the effect of sacubitril valsartan sodium tablets on serum tenascin-C (TN-C) level and myocardial remodeling in patients of chronic left heart failure (CHF) complicated with renal failure.Methods:A total of 84 patients with chronic left heart failure complicated with renal failure admitted to Qinhuangdao Jungong Hospital from October 2020 to October 2021 were included and divided into the observation group (treated with sacubitril valsartan sodium tablets) and the control group (treated with valsartan), with 42 cases in each group according to the random number table method. The clinical efficacy of the two groups was compared after 3 months of treatment. The TN-C level and cardiac function index left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), troponin T (cTnT) and other index before the treatment and after 3 months of treatment were compared between the two groups.Results:After 3 months of treatment, the total effective rate between the two groups had no significant difference ( P>0.05). After 3 months of treatment, the TN-C level in the observation group was lower than that in the control group: (32.42 ± 4.22) μg/L vs. (37.32 ± 4.86) μg/L; and the LVEF in the observation group was higher than that in the control group: (41.21 ± 5.39)% vs. (37.76 ± 5.45)%, the differences were statistically significant ( P<0.05). The LVEDD and cTnT in the two groups had no significant differences ( P>0.05). After 3 months of treatment, neuroendocrine factors norepinephrine, aldosterone, angiotensin Ⅱlevels in the in the observation group were lower than those in the control group: (1 668.60 ± 251.19) pmol/L vs. (2 005.86 ± 280.91) pmol/L, (246.97 ± 13.99) ng/L vs. (275.41 ± 19.38) ng/L, (99.68 ± 8.57) ng/L vs. (112.20 ± 9.52) ng/L, the differences were statistically significant ( P<0.05). Conclusions:Sacubitril valsartan sodium tablets have a good effect in the treatment of CHF complicated with renal failure, which can improve the cardiac function and inhibit the over-activation of neuroendocrine hormones.

Objective To investigate the protective effect of retigabine (a M-type potassium channel opener) on brains and its mechanism in male mice after acute cerebral ischemia reperfusion(I/R)injury.Methods Seventy male C57BL/6J mice were randomly divided sham-operated group (n=10),middle cerebral artery occlusion (MCAO) group (n=10) and prevention group (n=50) according to the random number table method;mice in the prevention group were then divided into XE991 (a M-type potassium channel blocker) group,RTG-treatment 0 h group,RTG-treatment 1 h group,RTG-treatment 3 h group,and RTG-treatment 6 h group (n=10).The MCAO models were established by suture method,and reperfusion was performed 90 min after cerebral ischemia.In RTG-treatment groups,a single dose of 10.5 mg/kg RTG was injected at the designated varying time points (0,1,3 and 6 h after the reperfusion);in XE991 group,a single dose of 3.0 mg/kg XE991 was injected after the reperfusion;mice in the sham-operated group and MCAO group received the same volume of saline.Twenty-four h after model making,infarct size was measured by TTC staining.HE staining was used to observe the morphological changes of neurons in hippocampal CA1 regions.The apoptotic neurons level and membrane protein CD40L expression in the ischemic penumbra were detected by TUNEL staining and Western blotting.Results In the sham-operated group,brain tissues had no obvious change,no infarction was observed,there was no CD40L expression,and TUNEL staining positive neurons were hardly found.(1) Cerebral artery territory infarction was visible in the MCAO group and intervention group;however,the infarction volume of the RTG-treatment groups was significantly lower than that in the MCAO group (P＜0.05);the infarction volume of the RTG-treatment 6 h group was increased as compared with that of the RTG-treatment 0 h group,RTG-treatment 1 h group,and RTG-treatment 3 h group,without significant difference (P＞0.05).(2) HE staining showed that hippocampal neurons were obviously swollen and necrotic in the MCAO group and XE991 group,while the pathological damages such as brain edema and neuron necrosis were ameliorated significantly in the RTG-treatment groups.(3) As compared with those in the MCAO group,the number of TUNEL staining positive neurons in the RTG-treatment 0 h group,RTG-treatrnent 1 h group,and RTG-treatment 3 h group and CD40L number in the RTG-treatment 0 h group and RTG-treatment 3 h group were decreased significantly (P＜0.05);as compared with that in the MCAO group,the number of TUNEL staining positive neurons increased significantly in the XE991 group (P＜0.05).Conclusion RTG has protective effect on cerebral I/R,and its mechanism might relate to reducing cell excitability and inflammation,thereby inhibiting cell apoptosis;these protection would be less effective when RTG is used outside a defined critical period of time.

Objective To investigate the effects of different concentrations and adsorption methods of aluminum hydroxide adjuvant produced by different manufacturers on the immunogenicity of the diphtheria-tetanus-acellular pertussis and inactivated poliovirus combined vaccine ( DTaP-sIPV) . Methods Five anti-gens of DTaP were adsorbed onto different concentrations (0. 42 mg/ml, 0. 47 mg/ml and 0. 52 mg/ml) of aluminum hydroxide from different manufacturers through sequential and separate adsorption. Adsorbability, anti-pertussis toxin ( PT)/filamentous hemagglutinin ( FHA)/pertactin ( PRN)/diphtheria toxoid ( DT)/tet-anus toxoid ( TT) antibodies and the potency of vaccines were detected. Results The adsorbability of alu-minum hydroxide adjuvant slightly decreased with the reduction of concentration. No significant difference in potency and antibody level was observed between sequential and separate adsorption. Moreover, no signifi-cant difference in antibody level was observed between vaccines prepared with aluminum hydroxide adjuvant produced by General Chemical Corp and our institute. Conclusion Aluminum hydroxide adjuvant produced by our institute at the concentration of 0. 52 mg/ml and separate adsorption method are suitable for prepara-tion of DTaP-sIPV.

OBJECTIVE: To explore the genetic basis for a neonate with Pierre-Robin sequence. METHODS: The child was subjected to chromosomal karyotyping, single nucleotide polymorphism array (SNP-array)-based comparative genomic hybridization and fluorescence in situ hybridization (FISH) analysis. RESULTS: The child has featured microgthnia, glossoptosis, upper airway obstruction, mandible dehiscence and short neck. He was found to have a karyotype of 46,XY,der(4)add(4)(q34). Her mother's karyotype was determined as 46,XX,t(1;4)(q43;q34), while his father was 46,XY. SNP-array analysis suggested the child to be arr [hg19] 1q42.2q44 (232 527 958-249 202 755)× 3; 4q34.3q35.2 (168 236 901-190 880 409)× 1. The result of SNP-array for both parents was normal. FISH analysis confirmed that his mother has carried a balanced t(1;4)(q42;34) translocation. The aberrant chromosome 4 in the child has derived from his mother's translocation, which gave rise to partial 1q trisomy and 4q monosomy. CONCLUSION The 1q42.2q44 duplication and 4q34.3q35.2 deletion of the child probably underlay his abnormal phenotype of Pierre-Robin sequence.
Child ; Comparative Genomic Hybridization ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant, Newborn ; Male ; Monosomy ; Pierre Robin Syndrome/genetics* ; Translocation, Genetic ; Trisomy/genetics*

Objective: The goal of this research was to understand the demographic distribution and related factors of non-marital and non-commercial heterosexual transmission (non-commercial transmission) for HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome). Methods: Data related to HIV/AIDS infected by non-marital heterosexual transmission and whose present address was in Qian Dongnan, were collected from Information System on the HIV/AIDS Prevention and Control. Information included demographic characteristics, the members of non-marital sex partners, transmission path, detection source, CD4⁺T lymphocyte level, et al. cases belong to homosexual history, injective drug use or non-classified non-marital heterosexuality transmission were excluded, totally collect HIV/AIDS 919 cases. Multivariate logistic regressions were used to analyze potential factors associated with non-marital and non-commercial heterosexual transmission. In addition, in March and June 2017, using a convenience sampling, we conducted one-to-one interviews among 10 HIV/AIDS who were infected by non-marital heterosexuality and had non-marital and non-commercial heterosexual experience in Kaili Center for Disease Control and Prevention. The content of the interview included basic information, sexual orientation, the main place of making friends and sexual behavior, attitude to commercial heterosexuality and non-martial and non-commercial heterosexuality and so on. Results: Out of the 919 cases, 645 (70.2%) were male, the proportion of non-commercial transmission was 55.06% (506). The proportion of female HIV/AIDS with non-commercial transmission was 84.7% (232), which was higher than male (42.5%(274)) (χ²=138.35, P<0.001). The proportion of Han HIV/AIDS with non-commercial transmission was 61.5% (275), which was higher than other religion (52.2%(412)) (χ²=6.32, P=0.012). The proportion of HIV/AIDS with non-commercial transmission who had 0-5 non-marital sexual partners was 58.8% (498), which was higher than who had>5 non-marital sexual partners (11.1%(8)) (χ²=61.10, P<0.001). The proportion of HIV/AIDS with non-commercial transmission who lived mobile was 72.9% (94), which was higher than who lived fixedly (52.2%(412)) (χ²=19.34, P<0.001). Qualitative interviews results revealed that the age of the respondents were 22-69. Respondents whose ages are in 22-34 were more likely to use mobile phone (4/10) and respondents whose ages are in 35-69 were less likely to look partners through party and the context of working. Conclusion The proportion of cases being infected by non-marital and non-commercial heterosexual transmission in Qian dongnan was higher than general national levels. The characteristics of sex, marriage status, migration, vocation, the members of non-marital sex partners were significant differed between commercial heterosexual transmission and non-marital and non-commercial heterosexual transmission.

Objective To explore the risk factors of hemorrhagic transformation and prognosis of acute ischemic stroke (AIS) after intravenous thrombolysis. Methods From June 2017 to June 2019,211 patients with AIS undergoing intravenous thrombolysis were selected as the research object. Among them,34 patients with hemorrhagic tromsformation (HT) were recorded as HT group,and 177 patients without hemorrhagic transformation The patient was recorded as a non-HT group,with a bleeding conversion rate of 16.11%. The relationship between intensive blood pressure reduction and bleeding conversion and prognosis in patients with AIS intravenous thrombolysis was analyzed during intravenous thrombolysis. Results Univariate analysis revealed gender,age,time interval between onset to start of treatment (OTT),blood glucose at admission,baseline blood pressure,and baseline from the onset to start of treatment (reombinant tissue plasminogen activator,rt-PA) The National Institute of Health stroke scale (NIHSS) score,type 2 diabetes,atrial fibrillation,and venous thrombolysis have statistically significant differences (P<0.05 or P<0.01),which is a vein Risk factors related to HT after thrombolysis;binary logistic analysis showed that the baseline NIHSS score of 17.5 was divided into independent risk factors for the transformation of venous thrombolysis hemorrhage in AIS patients (OR=1.639,P=0.013). Atrial fibrillation (OR=9.129,P<0.01) is an independent risk factor for the prognosis of patients with intravenous thrombolysis. Conclusion The baseline NIHSS score of 17.5 is divided into independent risk factors for HT after intravenous thrombolysis in AIS patients,and intensive blood pressure reduction during intravenous thrombolysis is a related risk factor for HT;atrial fibrillation is an independent risk factor for the prognosis of patients with intravenous thrombolysis.

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.