High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors

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 (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro 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.

Comparison of short-term effects of arthroscopic and open reduction and internal fixation with Herbert screws in treatment of radial head fractures / 中华创伤杂志

Objective:To compare the short-term clinical effect of arthroscopic and open reduction and internal fixation with Herbert screws in treatment of Mason type II radial head fractures.Methods:A retrospective case-control study was conducted to analyze the clinical data of 38 patients with unilateral radial head fractures (Mason type II) admitted to Shanghai Zhongye Hospital from January 2017 to December 2018, including 22 males and 16 females, aged from 20 to 65 years [(37.4±12.6)years]. Twenty patients were treated by arthroscopic reduction and internal fixation with Herbert screw (Group A), and eighteen by open reduction and internal fixation with Herbert screw (Group B). The operation time and fracture healing time were recorded. The visual analogue scale (VAS), elbow flexion and extension range, forearm rotation range and Mayo elbow function score were compared between the two groups before and at 1, 3, 6, and 12 months after operation. The results of Mayo elbow performance score (MEPS) and upper limb function assessment using the disabilites of the arm, shoulder, and hand (DASH) score were compared between the two groups. Complications including screw breakage or fracture displacement were also evaluated.Results:All patients were followed up for 12-14 months [(12.3±2.3)months]. There was no significant difference in operation time between the two groups ( P>0.05). The fracture healing time was (8.9±0.6)weeks in Group A and (8.7±0.6)weeks in Group B ( P>0.05). There was no significant difference in VAS between the two groups before operation ( P>0.05). The VAS was (4.8±0.5)points at 1 month after operation in Group A, lower than (6.0±0.7)points in Group B ( P<0.05). There was no significant difference in VAS between Group A and Group B at 3, 6, and 12 months after operation ( P>0.05). There was no significant difference in elbow flexion and extension range between the two groups before operation ( P>0.05). The elbow flexion and extension range in Group A was (110.4±3.8)° and (137.1±4.0)° at 1, 3 months after operation, which was significant greater than (90.6±4.7)° and (125.1±3.5)° in Group B ( P<0.05). There was no significant difference in elbow flexion and extension range between the two groups at 6 and 12 months after operation ( P>0.05). There was no significant difference in the range of forearm rotation between the two groups before operation ( P>0.05). The range of forearm rotation in Group A was (107.1±2.8)° and (138.1±2.9)° at 1, 3 months after operation, significantly greater than (95.5±3.9)°, (121.5±3.0)° in Group B ( P<0.05). There was no significant difference in forearm rotation range between the two groups at 6 and 12 months after surgery ( P>0.05). There was no significant difference in MEPS between the two groups before operation ( P>0.05). The MEPS in Group A was (50.4±3.8)points at 1 month after operation, higher than (40.6±4.7)points in Group B ( P<0.05). There was no significant difference in MEPS between the two groups at 3, 6, and 12 months after operation ( P>0.05). There was no significant difference in DASH score between the two groups before operation ( P>0.05). The DASH score was (57.1±2.8)points at 1 month after surgery in Group A, higher than (42.5±3.9)points in Group B ( P<0.05). The DASH score was not significantly different between the two groups at 3, 6, and 12 months after operation ( P>0.05). There was no screw loosening or fracture after operation, and one patient in each group had fracture displacement ( P>0.05). Conclusion:For Mason type II radial head fractures, arthroscopic Herbert screw fixation has the advantages of less trauma, less pain and faster functional recovery of the affected limb compared with open reduction and Herbert screw fixation.

The study of plasma levels of sCD40 and sCD40L in Alzheimer’s disease and mild cognitive impairment / 中国神经精神疾病杂志

Objective To explore the plasma levels of soluble CD40 (sCD40) and soluble CD40 ligand (sCD40L) in the patients with Alzheimer’s disease (AD) and those with amnestic mild cognitive impairment (aMCI). Methods The levels of plasma sCD40 and sCD40L were measured in 20 patients with AD, 35 patients with aMCI, and 32 cognitively normal controls (NC) using commercially available ELISAs. The cognitive function of AD and aMCI patients was mea?sured by mini-mental state examination (MMSE). Results There were significant differences in plasma sCD40 among AD, aMCI and NC groups (P<0.05) as the medians (the upper and lower quartiles) of plasma levels were 123.3 (97.4, 149.5) pg/mL, 102.9 (63.6, 124.0) pg/mL and 70.66 (51.0, 90.8) pg/mL, respectively. There were significant differences in plasma sCD40L among AD, aMCI and NC groups (P<0.05) as plasma levels were 537.0 (316.0, 1134.0) pg/mL, 316.0 (190.0,546.0) pg/mL and 167.0 (107.5,478.0) pg/mL. A negative correlation between the plasma concentrations of sCD40L and the MMSE scores was found in aMCI patients (r=-0.736, P<0.001). Conclusions There are relevant chang?es of plasma sCD40 and sCD40L levels in patients with AD and aMCI. The present results suggest that plasma levels of sCD40 and sCD40L may be appropriate biomarkers for AD patients and indicate that CD40-CD40L signaling may be in?volved in AD pathophysiology.

The preliminary clinical observation of Huganjiexian decoction in the treatment of hepatic cirrhosis / 国际中医中药杂志

Objective To observe the clinical therapeutic effects and evaluate the security of Huganjiexian decoction combined with conventional therapy on hepatic cirrhosis.MethodsBy the randomized and prospective study method,34 patients with liver cirrhosis were divided into experimental group and control group.The experimental group was treated with Huganjiexian decoction combined with conventional therapy while the control group was treated with conventional therapy alone.Patients in both groups were treated six months.At the beginning and 6 months after treatment,levels of alanine transaminase (ALT),aspartate transaminase (AST),albumin (ALB),albumin/globulin (A/G),total bilirubin (TBiL),blood urea nitrogen (BUN),serum creatinine (Scr) were determined.Results Levels ofALT、AST、TBiL decreased in both groups after being treated for six months,and the differences of downward trend of the experimental group were more significant than control group (F=36.63,40.31,38.65,P＜0.05).Levels ofALT、AST、TBiL of the experimental group were lower than those of control group significantly (F=8.67,7.62,4.36,P＜0.05 ).The A/G raised in both groups after treatment,and the upward trend of the experimental group was greatly different from that of control group (F=24.10,P＜0.05),the value of A/G of the experimental group was higher than that of control group (F=4.78,P＜0.05).The ALB raised in both groups after treatment,while the upward trend of the experimental group was no different from that of control group (F=0.89,P＞ 0.05).Thevalue of ALB had no significant changes in both groups (F=3.15,P＞0.05).Conclusion Huganjiexian decoction possessed therapeutic effect on hepatic cirrhosis,it had no obvious toxicity and side

Endoscopic features and earcinoembryonic antigen expressions of colorectal serrated adenomas / 中华消化内镜杂志

Objective To explore the endoscopic features and careinoembryonic antigen (CEA) ex-pressions of colorectal serrated adenomas (SA). Methods From June 2005 to July 2008, 27 patients with colorectal polyps and 26 cases of advanced colorectal cancer (ACC) were enrolled in the study. The pit pat-tern of the suspected lesions were observed with 0. 4% indigo carmine sodium stain and classified according to Kudo classification. The polyps were removed by biopsy, high-frequency electrical excision or endoscopic mucosa resection and the samples of ACC were collected with biopsy forceps. All specimens underwent rou-tine pathological examination and CEA expression was detected by immunohistochemistry. Results There were 47 SAs and 27 other types of polyps in polyp group. Most SAs located in left-side colon and were char-acterized by the bulge semipedunculation. The diameters of 45 serrated adenomas ranged from 3 to 8ram, and the maximal diameter of other 2 were more than 10ram. The most common type of pit pattern in SA was mixed type Ⅱ and ⅢL, with type Ⅱ predominant in a certain percentage. Expression of CEA in SA glands was significantly higher than that in proliferative polyps (P < 0. O1). Candnsion SA is an unique type of colorectal adenoma, which is capable of expressing CEA, and displays malignant potential and deserves great attention.