Objective:To study the expression of Resistin protein in breast cancer and to evaluate its significance to clinicopathology.Methods:The immunohistochemical technique, EnVision method, was used to evaluate the expression of Resistinin in 42 cases of normal breast tissues and 145 cases of breast cancer, and to analyze the relationship between Resistin protein expression and clinicopathological characteristics and molecular typing of invasive breast cancer patients.Results:The positive rate and strong positive rate of Resistin protein in normal breast tissue were 23.8% (10/42) and 0.0% (0/42) , respectively, while the positive rate and strong positive rate in invasive breast cancer were 88.3% (128/145) and 24.8% (36/145) . The positive rate and strong positive rate of Resistin protein in invasive breast cancer tissues were significantly higher than those in normal breast tissues (both P=0.000) . The positive rate of Resistin protein in invasive breast cancer was significantly higher in estrogen receptor (ER) -negative patients than in ER-positive patients ( P=0.006) , and it was higher in histological grade III and progesterone receptor (PR) -negative subjects than that of I-II and PR-positive, but the difference was not statistically significant ( P=0.053 and P=0.058, respectively) . The strong positive rate of Resistin protein in histological grade III, ER negative, PR negative and human epidermal growth factor receptor 2 (HER2) positive was significantly higher than that in histological grade I-II, ER positive, PR positive and HER2 negative ( P=0.001, P=0.001, P=0.001, and P=0.015, respectively) .The positive rate and strong positive rate of Resistin protein in triple negative breast cancer (TNBC) were significantly higher than those in other breast cancer subtypes ( P=0.048 and P=0.003, respectively) . Conclusion:Resistin plays an important role in the development of breast cancer and is expected to be a potential anti-cancer therapy biologic marker.

Objective:To analyze the differences in 18F-fluorodeoxyglucose (FDG) PET/CT imaging and preoperative localization between patients with temporal lobe epilepsy (TLE) and extratemporal epilepsy (ETLE) caused by focal cortical dysplasia (FCD). Methods:From April 2015 to August 2018, a total of 71 patients (45 males, 26 females, age (24.3±9.1) years) with refractory epilepsy who underwent 18F-FDG PET/CT imaging before surgery and confirmed as FCD by pathology in Xuanwu Hospital were retrospectively analyzed. Patients were divided into TLE and ETLE groups based on pathological results. 18F-FDG PET/CT images were analyzed qualitatively and compared with the operation result, then region of interest (ROI) was used to calculate the asymmetry index (AI), and evaluated the hypometabolism of every cerebral region by |AI| semi-quantitatively. Engle classification were followed-up after surgery. Independent-sample t test and χ2 test were used to analyze data. Results:Of 71 FCD patients, 35 were TLE and 36 were ETLE. The onset age of ETLE patients were younger than TLE patients ((10.1±6.5) vs (14.9±9.7) years; t=2.48, P=0.02). In TLE group, 54.29%(19/35) were completely consistent with the operation results, and 42.86%(15/35) showed hypometabolized brain regions in extratemporal lobe. In ETLE group, 27.78%(10/36) were completely consistent with the operation results, and 47.22%(17/36) showed hypometabolized brain regions in temporal lobe. There were significant differences in the lateral accuracy and positioning accuracy of 18F-FDG PET/CT between TLE and ETLE patients (97.14%(34/35) vs 75.00%(27/36), 54.29%(19/35) vs 27.78%(10/36); χ2 values: 7.19, 6.27, both P<0.05). There was no significant difference in |AI| values between the brain regions of TLE and ETLE patients ( z values: from -1.25 to -0.06, all P>0.05). Conclusion:The lateral accuracy and positioning accuracy of 18F-FDG PET/CT in TLE patients are better than that in ETLE patients.

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.

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.

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