Hepatitis C virus (HCV) genome is of high variation,which results in persistent infection of HCV and increases the incidence of liver cirrhosis and hepatocellular carcinoma.Following the successful paradigm established for HIV protease inhibitors,HCV NS3-4A serine protease has been selected as the main target for the development of small molecule antiviral agents.In this article,we review recent progress in the discovery and development of HCV NS3-4A protease inhibitors,and discuss their antiviral activities,pharmacokinetic properties,side effects and resistance profiles.

Cyclic peptide drugs have gradually become an emerging research direction due to their some favorable properties such as high-efficiency binding affinity, high selectivity, lower toxicity, and stable metabolism. In recent years, the number of cyclic peptide drugs under clinical research has continued to increase. Unlike the previous cyclic peptide drugs, which were mostly derived from natural products and their derivatives, these cyclic peptide drugs are designed by genetically encoded display technologies which are based on rational design and in vitro evolution (such as BT1718, PTG-300, POL6326, etc). Among them, phage display technology has some advantages such as mature research system, low cost, and simpler operation that make it well recognized and praised by the majority of researchers in this field. Here, we reviewed the recent progress of applying phage display technology to explore diverse cyclic peptide libraries, which, we believe, will contribute more valuable candidate cyclic peptide drugs in clinical research.

Objective Research showed that angiotensin converting enzyme inhibitor and angiotensinⅡ(AngⅡ)receptor antagonist has good role of lowing-intraocular pressure.This study was to explore whether cultured human trabecular meshwork cells express AngⅡin vitro.MethodsThe human trabecular meshwork cells strains were cultured in DMEM+F12 medium containing 25% fetal bovine serum in vitro and passaged at the climbing sheet was prepared.The expression of AngⅡ in human trabecular meshwork cells was examined by immunohistochemistry,and AngⅡ protein was localized by Western blot.ResultsSubcultured cells showed spindle shape.AngⅡwas positively expressed in human trabecular meshwork cells by immunochemistry,showing the yellow-brown granule in cellular membrane and cytoplasm.A absence of response for AngⅡwas found in negative control sample.The band of AngⅡ protein was found at the relative molecular weight of 64 000 by Western blot.ConclusionThe result implies that human trabecular meshwork cells have the ability of synthesizing AngⅡ.It suggests that AngⅡ participates in the regulation of intraocular tension in glaucomous eye.

Objective To investigate the protective effect of physcione on acute liver injury in rats.Methods Acute liver injury rat model was constructed with 2ml/kg CCl_4((?)3 d)via intragastric administration.The serum concentrations of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and tumor necrosis factor (TNF)in different groups were detected.Hepatic histopathology of different groups was also observed to reflect the effect of physcione.Results The serum concentrations of ALT,AST and TNF in physcione group were significantly lower than those of model group(P

Objective To analyze the research status and hotspot of occupational methanol poisoning at home and abroad. Methods ， The China National Knowledge Resource Database Wanfang Data Knowledge Service Platform and Web of Science were used as the data sources. The relevant literatures on occupational methanol poisoning published in domestic and foreign ， Results journals up to June 30 2021 were searched. The bibliometrics was used to analyzed the literatures. A total of 255 literatures were included in analysis. There were 187 Chinese articles and 68 English articles. Most of Chinese articles were ， ， published from 2001 to 2005 with an average of 26.7 literatures per five years until June 2021. Among them 72 literatures （ ）， ， were published in core journals 38.5% and 176 authors from 27 provinces autonomous regions and municipality directly ， under the central government published relevant literatures. The research contents mainly focused on the classification ， ， poisoning mode clinical manifestations visual impairment and poisoning prevention and treatment of occupational methanol - ， poisoning. Most of the English literatures were published in 2016 2020 with an average of 4.9 articles per five years until June ， （ ）， 2021. Among them 36 were published in SCI journals 52.9% and 57 authors from 11 countries published relevant ， ， ， literatures. The research contents mainly focused on the clinical diagnosis drug treatment intoxication mechanism visual Conclusion sequelae and brain injury of occupational methanol poisoning. The research on occupational methanol poisoning ， ， ， mainly focuses on clinical diagnosis clinical manifestations treatment and prognosis and pathogenesis. The focus of relevant research at home and abroad is different.

Objective We reported the rehabilitative nursing points of patients with pectoralis minor muscle transplantation for recovery of thumb oppositional function. Methods We selected 10 patients who underwent pectoralis minor muscle transplantation for recovery of thumb oppositional function and gave them perfect preoperative examination and psychological nursing. We also implemented rigorous monitoring postoperation and auxiliary electric stimulation and functional exercises. The emphasis was put on the exercise of thumb oppositional function. Results The thumb oppositional function of all the ten patients recovered. The myodynamia reached level 4 and the shape of thenar was satisfying after 6 to 12 months of follow-up visit. Conclusions Sufficient preoperative psychological nursing and effective postoperative rehabilitative treatment had pivotal significance for the success of operation and the recovery of thumb oppositional function.

The study was purposed to analyze DNA and allele structure of the partial D phenotypes D(Va) and D(VI) of the Rhesus blood group in Chinese. Through polymerase chain reaction (PCR) and direct genomic DNA sequencing, the RHD gene was detected in three weak D individuals identified serologically. The results showed that among the three weak D individuals, one was identified as partial D phenotype D(Va) (Hus) type and genotyped DccEe; another two were testified as D(VI) III type and genotyped DCcee. Moreover, the breakpoints of the replaced region by RHCE in D(Va) (Hus) were 5' end of the exon 5 and 3' end of the intron 5, and there were 7 novel polymorphisms in intron 5: 23-25(GCA)2, 98G>A, 168-169insG, 205-206insT, 494-495insA, 1256-1257insC, 1347G>T. In conclusion the whole exon 5 and intron 5 are replaced by RHCE in D(Va) (Hus) detected in Chinese.
China ; Exons ; genetics ; Genotype ; Humans ; Introns ; genetics ; Phenotype ; Polymerase Chain Reaction ; Rh-Hr Blood-Group System ; genetics ; Sequence Analysis, DNA

UNLABELLEDOBJECTIVE To study the in vitro effect and mechanism of Ginkgo biloba Extract 50 (GBE50) for inhibiting beta-amyloid (Abeta)-induced oxidative stress in rats' hippocampal neurons.

METHODSThe primary hippocampal neurons were cultured in vitro and divided into 4 groups, i. e. the normal control group (Ctrl), the Abeta group, the propanediol control group (PDO), and the six GBE50 concentrations groups (5, 10, 25, 50, 100, and 200 microg/mL). Excepted the Ctrl group, neurons were induced to oxidative stress by 20 gmolLAbeta25-35. The MTT and fluorescent probes labeling were used to observe the effect of GBE50 with different concentrations on the cell viability and the generation of intracellular reactive oxygen species (ROS) in neurons. Furthermore, Western blot was used to detect the cytoplasmic/total cytochrome C (Cyto C) ratio and total intracytoplasmal Cyto C, and the effect of the expression of oxidative stress-related protein Cyto C and activated Caspase-3 in three GBE50 concentrations groups (25, 50, and 100 microg/mL).

RESULTSCompared with the Ctrl group, the cell vitality was obviously lowered and intracellular ROS generation significantly increased after induction of 20 micromol/L Abeta25-35 (both P < 0.05). Compared with the Abeta group, the cell vitality was evidently improved after treated with different GBE50 doses. Except for 10 microg/mL, the cell vitality could be obviously elevated along with increased drug concentrations (P < 0.05). Meanwhile, the intracellular ROS generation decreased significantly in each GBE50 dose groups (P < 0.05). Abeta could increase the cytoplasmic/total Cyto C ratio and enhance the activated Caspase-3 expression significantly (P < 0.05). Compared with the Abeta group, among the three concentrations of GBE50, the Cyto C ratio was obviously lowered in the 100 microg/mL GBE50 group (P < 0.05), and the expression of activated Caspase-3 significantly decreased in 50 microg/mL and 100 microg/mL GBE50 groups (P < 0.05).

CONCLUSIONS20 micromol/L Abeta25-35 could induce the generation of intracellular ROS in hippocampal neurons. GBE50 could inhibit Abeta induced intracellular oxidative stress of neurons through lowering the cytoplasmic/total Cyto C ratio and inhibiting the activation of apoptosis protein Caspase-3 expression.

Amyloid beta-Peptides ; toxicity ; Animals ; Cells, Cultured ; Cytochromes c ; metabolism ; Hippocampus ; metabolism ; Neurons ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Peptide Fragments ; toxicity ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo search for a simple and effective surgical approach to the management of moderate to severe pediatric concealed penis in children.

METHODSWe used Devine's technique via incision between the penis and scrotum in the treatment of 68 cases of moderate to severe pediatric concealed penis. The patients were aged 3 -13 (mean 6.5) years, 30 with moderate and 38 with severe pediatric concealed penis.

RESULTSThis strategy achieved good near- and long-term effects and satisfactory appearance of the penis, which was similar to that of circumcision. At 3 months after surgery, the penile length was 3 - 5.2 cm, averaging (2.35 +/- 0.35) cm.

CONCLUSIONDevine's technique via incision between the penis and scrotum is a simple and effective surgical option for moderate to severe pediatric concealed penis in children.

Adolescent ; Child ; Child, Preschool ; Humans ; Male ; Penis ; abnormalities ; surgery ; Scrotum ; surgery ; Urologic Surgical Procedures, Male ; methods

Objective:To explore if there is premature senescence of chondrocytes in patients with Kashin-Beck disease (KBD) and osteoarthritis.Methods:Five knee cartilage samples of KBD, osteoarthritis and control groups were collected, respectively, from the Second Affiliated Hospital of Xi'an Jiaotong University. DNA was then extracted from cartilage samples and DNA methylation was analyzed by Illumina Infinium HumanMethylation450 BeadChip. At the same time, based on genome-wide methylation data, the online DNA methylation aging clock calculator (https://dnamage.genetics.ucla.edu/home) was used to calculate the DNA methylation age (DNAm age) of samples, and the results were compared with their actual ages.Results:In the comparison between KBD group and control group, 1 212 differentially methylated CpG sites were found, including 497 hypermethylated CpG sites and 715 hypomethylated CpG sites, corresponding to 264 hypermethylated genes and 368 hypomethylated genes, respectively. In the comparison between osteoarthritis group and control group, 656 differentially methylated CpG sites were found, including 343 hypermethylated CpG sites and 313 hypomethylated CpG sites, corresponding to 177 hypermethylated genes and 174 hypomethylated genes, respectively. In the above comparison, 367 overlapped CpG sites (corresponding to 182 genes) were found, which were differentially methylated in both KBD and control groups and osteoarthritis and control groups. The results of DNA methylation aging clock showed that the average age acceleration differences between DNAm age and actual age of KBD, osteoarthritis and control groups were 2.549, 0.017, and - 5.364 years, respectively, the DNAm ages of KBD and osteoarthritis groups were greater than the actual ages.Conclusion:The chondrocytes show premature senescence in both KBD and osteoarthritis.