HIV-1 envelope glycoprotein gp120 and gp41 are considered as two important parts in viral entry.In the process of virus entry,CD4 first binds to gp120 and causes the conformation of gp120 to change.Furthermore the conformation of gp41 has also been changed.Many peptides,macromolecular compounds and small molecule compounds which bind to gp120 or gp41 can deter the progress of virus entry.These compounds can play an important role in halting the spread of HIV-1 in this way.The structure and interaction of gp120 and gp41 are reviewed here,as well as the anti-HIV agents blocking the HIV entry by targeting the HIV-1 envelope glycoprotein.

In 2012, a new SARS-like coronavirus emerged in the Middle East, namely the Middle East respiratory syndrome coronavirus (MERS-CoV). It has caused outbreaks with high mortality. During infection of target cell, MERS-CoV S protein S1 subunit binds to the cellular receptor (DPP4), and its S2 subunit HR1 and HR2 regions intact with each other to form a stable six-helix bundle to mediate the fusion between virus and target cell membranes. Hence, blocking the process of six-helix bundle formation can effectively inhibit MERS-CoV entry into the target cells. This review focuses on the recent advance in the development of peptidic entry inhibitors targeting the MERS-CoV S2 subunit.

Aim To investigate the HIV-1 entry inhibitory activities of myriceric acid B and C isolated from Rhoiptelea chiliantha Diels et Hand-Mazz and their mechanism of action.Method The plasmids encoding envelope proteins of HIV-1 (pHXB2) and VSV (pVSV-G) were cotransfected 293T cells with pNL4-3.Luc.R-E- to produce HIV-1 Env pseudovirus and VSV-G pseudovirus,respectively,which were used for testing the antiviral activities of these compounds.ELISA and molecular docking were used to study the mechanism of action of the active compounds.Results Myriceric acid B could significantly inhibit the infection of HIV-1 Env pseudovirus with an IC_(50) of(8.3±0.2)mg·L~(-1).The carbonoxyl group at C-28 position and the hydroxyl group at the C-3 position of myriceric acid B are important for its anti-HIV-1 activity.Like other HIV-1 entry inhibitors targeting gp41 (eg,ADS-J1 and NB-64), myriceric acid B could also block the gp41 six-helix bundle formation.Molecular docking analysis suggests that myriceric acid B may bind to the hydrophobic cavity of the gp41 N-trimeric coiled coil.Conclusion Myriceric acid B is a potent HIV-1 entry inhibitor targeting gp41 and can serve as a lead compound for developing novel anti-HIV-1 drug.

Aim ADS-J1 is a low molecular HIV entry inhibitor targeting HIV transmembrane subunit gp41 through virtual screening from a compound library containing 20 000 molecules.This study is to investigate the binding sites of ADS-J1 on gp41.Methods Acid native polyacrylamide gel electrophoresis (AN-PAGE) assay was applied to test the binding ability of ADS-J1 with the peptides derived from gp41 N-terminal heptad repeat (NHR) region.Results It was reported previously that ADS-J1 could block the gp41 six-helix bundle (6-HB) formation using native polyacrylamide gel electrophoresis (N-PAGE).However,the binding sites could not be found because positive charged N-peptides derived from gp41 NHR could not show bands on the gel.In the present study,the AN-PAGE assay which could show N-peptides in the gel was established,and it was found that ADS-J1 could inhibit the gp41 6-HB formation.Moreover,ADS-J1 bound directly to the gp41 cavity region of NHR.The positively charged residue (K574) located in this region was critical for the binding of ADS-J1.Conclusions ADS-J1 inhibits HIV entry by targeting the cavity region of gp41 NHR,whereas K574 in the cavity plays a critical role for the binding.Furthermore,the AN-PAGE assay provides a simple method for studying the mechanism of action of virus entry inhibitors targeting the transmembrane protein of type I enveloped virus.

This study examined the possible role of p120ctn in the pathogenesis and development of pancreatic cancer. PANC-1 cells, a kind of human pancreatic carcinoma cell line, were cultured in this study. p120ctn was immunocytochemically detected in PANC-1 cells. The recombinant lentivirus vector was constructed to knock down the p120ctn expression of PANC-1 cells. Real-time quantitative PCR (RQ-PCR) and Western blotting were used to determine the expression of p120ctn and E-cadherin in PANC-1 cells after p120ctn knockdown. The adhesion, invasion and migration capacity of PANC-1 cells after p120ctn knockdown was detected by cell adhesion, invasion and migration assays. Cell growth was measured by the MTT method. Cell cycle and apoptosis were analyzed by fluorescence-activated cell sorting. The results showed that p120ctn knockdown led to significantly down-regulated E-cadherin and a reduced cell-to-cell adhesion ability in PANC-1 cells. shRNA-mediated knockdown of p120ctn reduced invasion and migration capacity of PANC-1 cells, inhibited cell growth, caused a significant decrease in the percentage of cells in G(1), an increase in S, and promoted apoptosis of PANC-1 cells. It was concluded that p120ctn plays a pivotal role in the proliferation and metastasis of pancreatic carcinoma, suggesting that p120ctn is a novel target for pancreatic carcinoma treatment.

Objective : To analyze the survival of patients with malignant mesothelioma, so as to provide insights into the management of malignant mesothelioma. Methods : Totally 36 patients with malignant mesothelioma admitted to Cixi Third People’s Hospital from October 2012 to January 2021 were enrolled, and the demographic features, exposure to asbestos, and diagnosis and treatment were retrospectively reviewed. The survival rate and median survival time were calculated with the life-table method, and the factors affecting the survival rate of malignant mesothelioma were identified using the Kaplan-Meier estimate and log-rank test. Results : The 36 patients with malignant mesothelioma included 6 men ( 16.67% ) and 30 women ( 83.33% ), and had a median age of 61 ( interquartile range, 14 ) years. There were 30 cases with pleural malignant mesothelioma ( 83.33% ) and 6 cases with peritoneal malignant mesothelioma ( 16.67% ), 32 cases ( 88.89% ) with a history of occupational exposure to asbestos, and 26 cases ( 72.22% ) receiving palliative treatment. The 1-, 2- and 3-year cumulative survival rates were 30%, 15% and 3%, respectively, and the median survival time was 0.71 years. In addition, there were no significant differences in the survival period among patients with malignant mesothelioma in terms of gender, age, route of asbestos exposure, duration of asbestos exposure, pathogenic site and treatment regimens ( P>0.05 ). Conclusion The 36 patients with malignant mesothelioma had a median survival period of 0.71 years, and no association was found between the survival period and asbestos exposure or pathogenic site.

Objective : To examine the diagnostic and prognostic value of long non-coding RNA (lncRNA) JPX in mesothelioma, so as to provide insights into diagnosis and prognosis of mesothelioma. Methods: Patients with clinically definitive diagnosis of mesothelioma from 2015 to 2019 that were sampled from asbestos processing plants in Zhejiang Province from 2015 to 2019 were recruited in the mesothelioma group, while healthy residents without asbestos exposure or asbestos-related diseases in the same area served as controls. Participants' demographics, pathologic diagnosis and imaging features were collected, and the expression of blood lncRNA JPX was detected using lncRNA microarrays. The diagnostic value of lncRNA JPX for mesothelioma was evaluated using the receiver operating characteristic (ROC) curve, and the correlation between lncRNA JPX expression and prognosis was examined among mesothelioma patients using survival analysis. Results: There were 17 subjects in the mesothelioma group, with a mean age of (65.71±8.36) years, and 34 subjects in the controls, with a mean age of (64.24±8.70) years. LncRNA microarray detected significantly high lncRNA JPX expression in mesothelioma patients, and higher blood lncRNA JPX expression was detected in the mesothelioma group than in the control group [median (interquartile range), 1.10 (1.31) vs. 0.89 (0.54); t'=-2.300, P=0.034]. The area under the ROC curve was 0.673 (95%CI: 0.507-0.839, P=0.046), and if the cutoff was 1.759, the sensitivity and specificity were 35.3% and 100.0%, respectively. Survival analysis showed no significant difference in the survival rate of mesothelioma patients between the high lncRNA JPX expression group and the low expression group (χ2=0.212, P=0.645). Conclusions LncRNA JPX overexpression is detected in the blood of patients with mesothelioma, and lncRNA JPX expression presents a diagnostic value for mesothelioma; however, it shows little prognostic value for mesothelioma.

This study examined the possible role of p120ctn in the pathogenesis and development of pancreatic cancer. PANC-1 cells, a kind of human pancreatic carcinoma cell line, were cultured in this study. p120ctn was immunocytochemically detected in PANC-1 cells. The recombinant lentivirus vector was constructed to knock down the p120ctn expression of PANC-1 cells. Real-time quantitative PCR (RQ-PCR) and Western blotting were used to determine the expression of p120ctn and E-cadherin in PANC-1 cells after p120ctn knockdown. The adhesion, invasion and migration capacity of PANC-1 cells after p120ctn knockdown was detected by cell adhesion, invasion and migration assays. Cell growth was measured by the MTT method. Cell cycle and apoptosis were analyzed by fluorescence-activated cell sorting. The results showed that p120ctn knockdown led to significantly down-regulated E-cadherin and a reduced cell-to-cell adhesion ability in PANC-1 cells. shRNA-mediated knockdown of p120ctn reduced invasion and migration capacity of PANC-1 cells, inhibited cell growth, caused a significant decrease in the percentage of cells in G(1), an increase in S, and promoted apoptosis of PANC-1 cells. It was concluded that p120ctn plays a pivotal role in the proliferation and metastasis of pancreatic carcinoma, suggesting that p120ctn is a novel target for pancreatic carcinoma treatment.
Catenins ; genetics ; Cell Line, Tumor ; Gene Silencing ; Humans ; Pancreatic Neoplasms ; genetics

Objective To observe the value of a YOLOX target detection model for automatically identifying endovascular interventional instruments on images of digital subtract angiography(DSA).Methods DSA data of 37 patients who underwent abdominal endovascular interventional therapy were retrospectively analyzed.Totally 4 435 DSA images were captured and taken as data set,which were divided into training set(n=3 991)and verification set(n=444)at the ratio of 9∶1.Six kinds of endovascular interventional instruments were labeled.YOLOX algorithm was applied for deep learning of data in training set in order to build a target detection model,and the efficacy of the model for automatically identifying endovascular interventional instruments on DSA images was evaluated based on varification set.Results A total of 6 668 labels were put on 4 435 DSA images,aimed on Terumo 0.035in loach guide wire(n=587),Cook Lunderquist super hard guide wire(n=990),Optimed 5F with graduated pig tail catheter(n=1 680),Cordis MPA multi-functional catheter(n=667),Boston Scientific V-18 controllable guide wire(n=1 330)and Terumo 6F long sheath(n= 1 414),respectively.The training set contained 527,875,1 466,598,1 185 and 1 282,while the verification set contained 60,115,214,69,145 and 132 the above labels,respectively.The pixel accuracy of YOLOX target detection model for automatically identifying the above instruments in the verification set was 95.23%,97.32%,99.18%,98.97%,97.60%and 98.19%,respectively,with a mean pixel accuracy of 97.75%.Conclusion YOLOX target detection model could automatically identify endovascular interventional instruments on images of DSA.

BACKGROUND:Atlantoaxial dislocation is often facilitated by interlaminar bone grafting.However,there are relatively few reports on the treatment of complex atlantoaxial dislocation with posterior atlantoaxial lateral mass interarticular release and fusion. OBJECTIVE:To explore the safety and effectiveness of atlantoaxial dislocation treated by simple posterior atlantoaxial lateral block interarticular release and fusion. METHODS:We retrospectively analyzed the clinical data of 30 patients with atlantoaxial dislocation who were treated from January 2017 to July 2021,all of whom suffered from reducible atlantoaxial dislocation.Posterior atlantoaxial lateral mass interarticular release and fusion were performed in all patients.During the surgery,patented instruments were used to release the atlantoaxial lateral mass joint,and posterior screw reduction and fixation were used with bone grafting in the lateral mass joint space.The postoperative follow-up period was 6 to 24 months,mean(13.0±5.4)months.During the follow-up period,cervical MRI was reviewed to observe the decompression of the upper cervical spine.X-ray films and CT scans were reviewed to observe the reduction of the upper cervical spine,as well as the internal fixation for looseness and breakage.CT scans were reviewed to assess interlateral block implant fusion.The Japanese Orthopaedic Association score was used to evaluate the improvement of spinal cord function.The neck disability index and the quality of life scale were used to assess the improvement of daily life function.The atlanto-anterior interspace and atlanto-planar spinal effective space were used to evaluate atlantoaxial repositioning and decompression. RESULTS AND CONCLUSION:(1)The surgery of 30 patients went smoothly,and no serious complications such as spinal nerve and vertebral artery injuries occurred during the operation.Postoperative review of cervical MRI showed that the spinal cord compression was lifted.X-ray film and CT showed that the atlanto-anterior gap was significantly reduced;the effective space of atlantoaxial spinal cord was significantly increased,and neurological dysfunctional symptoms were significantly reduced.(2)During the follow-up period,X-ray film and CT showed that the internal fixation was solid;no broken nails or rods occurred,and there was no recurrence of atlantoaxial dislocation.(3)The Japanese Orthopaedic Association scores,neck disability index,and quality of life scores were significantly improved at the last follow-up compared with the preoperative period(P<0.05).The average improvement rate of Japanese Orthopaedic Association scores at the last follow-up was 73.1%.The average neck disability index was 8.80%.All of the patients had a continuous bone-scalp connection between atlantoaxial lateral block joints to achieve osseous fusion.(4)These findings indicate that the use of simple posterior atlantoaxial lateral block interarticular release and fusion for the treatment of atlantoaxial dislocation can significantly increase the fusion rate and shorten the fusion time.