Effect of needle-knife on chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis based on CircSERPINE2-miR-1271-5P-ERG axis / 中国针灸

OBJECTIVE@#To observe the effect of needle-knife on the chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis (KOA) based on the CircSERPINE2-miR-1271-5P-E26 specific transformation-related gene (ERG) axis, and to explore the mechanism of needle-knife for KOA.@*METHODS@#Thirty-six New Zealand white rabbits were randomly divided into a normal group, a model group, a needle-knife group and a sham needle-knife group, 9 rabbits in each group. The rabbits in the model group, the needle-knife group and the sham needle-knife group were treated with modified Videman method to prepare KOA model. After successful modeling, the rabbits in the needle-knife group were treated with needle-knife at cord adhesion and nodules near quadriceps femoris tendon and internal and external collateral ligament on the affected knee joint; the rabbits in the sham needle-knife group were treated with sham needle-knife baside the needle insertion point of the needle-knife group (needle-knife was only inserted, without any operation). The treatment was given once a week, 3 times in total. The Lequesne MG behavioral score was used to evaluate the knee joint damage in each group before and after intervention. After intervention, HE staining and transmission electron microscopy were used to observe the cartilage tissue morphology and ultrastructure of chondrocytes in the knee joint in each group; TUNEL method was used to detect the level of chondrocyte apoptosis in the knee joint; real-time fluorescence quantitative PCR was used to detect the expression of CircSERPINE2, miR-1271-5P and ERG mRNA in knee cartilage tissue in each group.@*RESULTS@#After intervention, compared with the normal group, the Lequesne MG behavioral score in the model group was increased (P<0.01). Compared with the model group and the sham needle-knife group, the Lequesne MG behavioral score in the needle-knife group was decreased (P<0.01). In the model group and the sham needle-knife group, the number of chondrocytes and organelles was decreased, the cell nucleus was shrunk, mitochondria was swelling or disappeared; in the needle-knife group, the number of chondrocytes and organelles was increased, the cell nucleus was not obviously shrunk and the mitochondria was not obviously swelling. Compared with the normal group, the level of chondrocyte apoptosis in the model group was increased (P<0.01); compared with the model group and the sham needle-knife group, the level of chondrocyte apoptosis in the needle-knife group was decreased (P<0.01, P<0.05). Compared with the normal group, the expression of CircSERPINE2 and ERG mRNA in the model group was decreased (P<0.01), and the expression of miR-1271-5P mRNA was increased (P<0.01); compared with the model group and the sham needle-knife group, the expression of CircSERPINE2 and ERG mRNA in the needle-knife group was increased (P<0.01), and the expression of miR-1271-5P mRNA was decreased (P<0.01).@*CONCLUSION@#Needle-knife could reduce the knee joint damage and chondrocyte apoptosis in KOA rabbits, which may be related to up-regulating the expression of CircSERPINE2 and ERG mRNA, and inhibiting the expression of miR-1271-5P mRNA.

A highly potent and stable pan-coronavirus fusion inhibitor as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases

The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

Prediction of mortality in patients with acute exacerbation of chronic obstructive pulmonary disease / 中国医师杂志

Objective:To evaluate the risk factors of mortality in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:A total of 97 patients with AECOPD in the emergency department of Beijing Friendship Hospital Affiliated to Capital Medical University from January 2018 to January 2019 were prospectively selected and followed up for 2.5 years. According to the prognosis, they were divided into survival group (82 cases) and death group (15 cases). Logistic regression analysis was used to screen the independent risk factors for death. The area under receiver operating characteristic curve (AUC) was used to analyze the prediction accuracy. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to analyze the predictive value of the prediction model for 2.5-year mortality in AECOPD patients.Results:Drinking history ( OR=4.975, P=0.046), past long-term β receptor blockers ( OR=5.486, P=0.029) and creatine kinase isoenzyme (CK-MB) level ( OR=2.008, P=0.049) were independent risk factors for death in patients with AECOPD. The AUC was 0.729, 0.715 and 0.710 respectively. The weight values of the three in the prediction model were 5, 5 and 1 respectively and the AUC was 0.834. Kaplan Meier survival analysis showed that 8 points of the prediction model could predict the 2.5-year survival rate in AECOPD patients (Log Rank P<0.001). The risk of death in AECOPD patients with score >8 was significantly higher than that of patients with score ≤8 ( HR=12.471, 95% CI: 3.735-41.643, P<0.001). Conclusions:Drinking history, past long-term β receptor blockers and CK-MB levels are independent risk factors for 2.5-year mortality in patients with AECOPD. The combination of these three factors has high predictive value for the prognosis of patients.

Diagnosis and treatment of dwarfism with prostate cancer without prostate biopsy: a case report / 中华泌尿外科杂志

Prostate cancer in patients with dwarfism is rarely reported. One case was reported in this article. The patient was admitted to the hospital due to the PSA elevation for more than 4 years. Due to the dwarf disease, the patient could not accommodate the transrectal ultrasound probe, and was highly suspected of prostate cancer.The prostate needle biopsy was not performed. Combined with the medical history, PSA level, preoperative MRI and PSMA-PET/CT examination, the patient was clinically diagnosed with localized prostate cancer, and radical surgical treatment was performed.

Defeating enemy outside the border-development of viral entry inhibitors / 复旦学报（医学版）

About 25 years ago,we had pioneered the research fields of developing human immunodeficiency virus (HIV) fusion/entry inhibitors and anti-HIV peptide drugs.Over the past six years,we have gained some promising results in research and development of the HIV,Middle East respiratory syndrome coronavirus (MERS-COV),the Ebola virus (EBOV),and the Zika virus (ZIKV) entry inhibitors.This article provides an overview of the research progress of viral entry inhibitors against the related highly pathogenic viruses.

Development of peptidic MERS-CoV entry inhibitors / 药学学报

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.

Development of peptidic MERS-CoV entry inhibitors / 药学学报

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.