Objective To observe the value of the ratio of cerebral hyperdensities(PCHD)/venous sinus maximum density for predicting hemorrhagic transformation(HT)after endovascular treatment(EVT)in patients with acute ischemic stroke(AIS).Methods Data of 79 AIS patients with PCHD immediately after EVT were retrospectively analyzed.The patients were divided into HT group(n=41)or non-HT group(n=38)based on the presence of HT or not.Clinical data and CT parameters were compared between groups.The value of the ratio of PCHD/venous sinus maximum density for predicting HT was evaluated.Results The maximum density of PCHD and the ratio of PCHD/venous sinus maximum density in HT group were both higher than those in non-HT group(both P＜0.001).Taken 87 HU as the best cut-off value of the maximum density of PCHD,the sensitivity,specificity and area under the curve(AUC)for predicting HT after EVT in AIS patients was 90.24%,71.05%and 0.79,respectively.Taken 0.94 as the best cut-off value of the ratio of PCHD/venous sinus maximum density,the sensitivity,specificity and AUC was 97.56%,71.05%and 0.81,respectively.No significant difference of AUC was found between the former and the latter(P＞0.05).Conclusion The ratio of PCHD/venous sinus maximum density immediately after EVT could be used to predict HT in AIS patients.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

Anoctamin 1 (ANO1) is a kind of calcium-activated chloride channel involved in nerve depolarization. ANO1 inhibitors display significant analgesic activity by the local peripheral and intrathecal administration. In this study, several thiophenecarboxylic acid and benzoic acid derivatives were identified as novel ANO1 inhibitors through the shape-based virtual screening, among which the 4-arylthiophene-3-carboxylic acid analogues with the best ANO1 inhibitory activity were designed, synthesized and compound

Flagellum is a slender and wavy protein-attached filament on the surface of certain bacterial cells. It not only plays an important role in the movement and pathogenic ability of bacteria, but also participates in a variety of host immune regulation. Flagellin is a structural protein that forms the main part of flagellar filaments and can be recognized by TLR5 and other receptors in the host cell to induce the body′s immune response. At present, flagellin is widely used in the research of new immune adjuvants due to its immune activation, and its inflammation inhibitory effect also has good prospects against immune pathological damage. In this review, we summarized and analyzed the recent progress on the basic structure and function of flagellin, the host recognition mechanism, and its role in regulating the host immune system.

Rete middle cerebral artery is an abnormal process of embryonic development, which results in the normal middle cerebral artery trunk being replaced by plexiform vascular network. The main clinical manifestations are intracranial hemorrhage or ischemic cerebrovascular events. Clinicians generally do not know enough about it. This article reviews the generative mechanism, clinical manifestations, differential diagnosis and treatment of the rete middle cerebral artery.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection(ESD) for early hypopharyngeal carcinoma and precancerous lesions.Methods:Data of 23 patients with early hypopharyngeal carcinoma and precancerous lesions who underwent ESD in Sichuan Cancer Hospital from December 2015 to May 2019 were analyzed.Results:A total of 23 patients with 30 lesions were enrolled in the study. All patients were male, with mean age of 60.3 years (ranged 47-72). Of the 23 patients, 13 had synchronous esophageal cancer, 3 had metachronous esophageal cancer, and 7 high-grade intraepithelial neoplasia(HGIN) of the esophagus. The mean procedure time was 74 minutes. The en bloc resection rate was 100%. Pathological results revealed that 21 lesions were HGIN, 8 lesions were intramucosal carcinoma and 1 lesion had tumor invasion of the submucosa. Two patients had positive horizontal margin and 1 patient had positive vertical margin. The curative resection rate was 90%. No bleeding, perforation or dyspnea occurred during or after ESD.Conclusions:ESD is safe and effective for early hypopharyngeal cancer and precancerous lesions.

Objective: To evaluate the feasibility, safety and clinical value of endonasopharyngeal ultrasound-guided transnasopharyngeal needle aspiration (ENUS-TNNA) in the diagnosis of submucosal nasopharyngeal carcinoma. Methods: Clinical data of 9 patients from Sichuan Cancer Hospital with submucosal nasopharyngeal carcinoma undergoing ENUS-TNNA between December 2013 and January 2018 were retrospectively analyzed. The feasibility and safety were analyed. All 9 patients were all males with a mean age of (49.2±10.9) years. Results: Needle puncture biopsies were successfully performed in all cases, and sufficient tissue sample for histopathological examination was obtained from each of the 9 patients. No major bleeding or persistent bleeding occurred during and after puncture procedures. There were 5 patients with undifferentiated nonkeratinizing carcinoma and 4 patients poorly differentiated carcinoma. Conclusion ENUS-TNNA is a safe, feasible and effective technique to provide a diagnosis of submucosal growth type of nasopharyngeal neoplasms, which has some clinical value.

Objective To explore the expression of Fascin-1 and EGFR in triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBC) and its correlation.Methods According to ER,PR,and HER2 status,breast cancer were categorized into 2 subtypes:70 cases of TNBC and 370 cases of non-TNBC.The immunohistochemical technique,EnVision method,was used to evaluate the expression of Fascin-1 and EGFR in breast cancer.Results Expression rate of Fascin-1 and EGFR protein in TNBC was 88.6％(62/70)and 78.6％(55/70),while it was 19.2％(71/370)and 44.3％(164/370)in non-TNBC,respectively.Fascin-1 expression rate was significantly higher in EGFR positive non-TNBC cases (34.8％,57/164) than in EGFR negative cases (6.8％,14/206)(x2=46.032,P=0.000).The positive rate of Fascin-1 protein in EGFR-positive TNBC cases (92.7％,51/55) was higher than that in EGFR negative cases (73.3％,11/15),and the difference had no statistically significance (x2=2.673,P=0.102).Conclusions EGFR signal pathway may positively regulate Fascin-1 expression in non-TNBC.The relationship between EGFR and Fascin-1 in TNBC is needed for further study.

Objective To study the expression of epidermal growth factor receptor 1 (EGFR) protein in breast cancer and its correlation to molecular subtyping and hormone receptor status.Methods 467 cases of breast cancer were included.According to ER,PR,HER2,and Ki-67 status,the cases were categorized into 4 molecular subtypes,including 185 cases of luminal A,109 cases of luminal B,76 cases of HER2-enriched,and 70 cases of triple-negative breast cancer (TNBC).According to ER and PR status,the cases were divided into 4 subtypes,including 240 cases of ER+/PR+,50 cases of ER+/PR-,4 cases of ER-/PR+,and 173 cases of ER-/PR-.Results EGFR protein expression rates in Luminal A,Luminal B,HER2-enriched and TNBC were 16.8％(31/185),54.1％(59/109),97.4％(74/76),78.6％(55/70),respectively.The EGFR expression in HER2-enriched was significantly higher than those in TNBC,Luminal B and Luminal A(P＜0.01),and EGFR expression in TNBC was significantly higher than those in Luminal B and Luminal A (P＜0.01),furthermore,EGFR expression in Luminal B was significantly higher than that in Luminal A (P＜0.01).EGFR protein expression rates in ER+/PR+ subtype,ER+/PR-subtype,ER-/PR+ subtype and ER-/PR-subtype were 25.4％ (61/240),52.0％ (26/50),75.0％ (3/4),88.4％(153/173),respectively.The EGFR expression in ER-/PR-subtype was significantly higher than in ER+/PR+ subtype and ER+/PR-subtype (P＜0.01),and EGFR expression in ER+/PR-subtype was significantly higher than that in ER+/PR+ subtype (P＜0.01).EGFR protein expression rate was higher in ER-/PR-subtype than in ER-/PR+ subtype,and EGFR protein expression rate was higher in ER-/PR+ subtype than that in ER+/PR+ subtype and ER+/PR-subtype,but all of the difference were not statistically significant (P＞0.05).Conclusion EGFR protein expression is closely related to breast cancer molecular subtyping and negative hormone receptor expression,which is a potential biomarker of anti-breast cancer therapy.