Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective:To investigate the impact of sarcopenia on the short-term outcomes and long-term prognosis in cervical cancer patients undergoing concurrent chemoradiotherapy (CCRT).Methods:A total of 410 cervical cancer patients who received CCRT in Henan Provincial People′s Hospital between January 2017 and December 2021 were prospectively enrolled in this study. They were divided into the sarcopenia and non-sarcopenia groups based on the body muscle content measured using bioelectrical impedance analysis. Short-term outcomes were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), and acute adverse reactions were assessed based on the toxicity criteria of the Radiation Therapy Oncology Group (RTOG). CCRT termination or prolonged treatment associated with various acute adverse reactions were recorded. All patients were followed up with overall survival (OS) and progression-free survival (PFS) as endpoints. Finally, the survival rate was estimated and the association between sarcopenia and PFS was analyzed.Results:Among the patients, 152 (37.1%) had sarcopenia. Compared to the non-sarcopenia group, the sarcopenia group exhibited higher incidences of grade 2 or above acute adverse reactions in the lower gastrointestinal and hematological systems, CCRT termination, or prolonged treatment. In the non-sarcopenia group, 27 deaths were recorded, with an OS of 30 (18-36) months, a 3-year OS rate of 88.7%, and a 5-year OS rate of 85.6%. In the sarcopenia group, 23 deaths were found, with an OS of 24 (15-33) months, a 3-year OS rate of 83.8%, and a 5-year OS rate of 77.7%. There was no significant difference in survival curves between both groups ( P > 0.05). In the non-sarcopenia group, 52 cases of recurrence were recorded, with a PFS of 21 (12-33) months, a 3-year PFS rate of 77.9%, and a 5-year PFS rate of 71.0%. In the sarcopenia group, 41 cases of recurrence were found, with a PFS of 15 (10.5-24) months, a 3-year PFS rate of 69.0%, and a 5-year PFS rate of 56.5%. There was a significant difference in the PFS curves between both groups ( χ2 = 5.89, P = 0.015). Multivariate Cox regression analysis identified sarcopenia as an independent risk factor for PFS ( χ2 =4.33, P = 0.037). Conclusions:Sarcopenia increases the risks of acute adverse reactions and long-term recurrence in cervical cancer patients undergoing CCRT.

Objective:To analyze predictive risk indicators associated with the development of Kümmell's disease (KD) in patients with osteoporotic vertebral compression fractures (OVCFs).Methods:A 1∶1 frequency-matched case-control study design was employed, selecting patients who visited the Department of Spine Surgery at Liuzhou Workers' Hospital from January 2021 to June 2023. Patients were divided into case and control groups based on whether they progressed to Kümmell's disease (KD). Detailed demographic information, comorbidities, and laboratory data were collected, and baseline characteristics of the two groups were compared. Initial predictive variables significantly associated with the target variable were preliminarily screened through univariate analysis. A correlation heatmap was then constructed to assess collinearity among these variables, followed by further selection of potential predictors using the Lasso regression model. Finally, a multivariable logistic regression model was used for the prediction and analysis of KD-related risk indicators.Results:Univariate analysis identified significant predictors of Kümmell's disease, including patient age, bone mineral density, kyphotic Cobb angle, and multiple vertebral fractures. These were included in the subsequent Lasso regression analysis, which identified key predictors with non-zero coefficients: age, bone density, Cobb angle, multiple vertebral fractures, platelet count (PLT), aspartate aminotransferase/alanine aminotransferase (AST/ALT), albumin (Alb), albumin/globulin ratio (Alb/Glb), alkaline phosphatase (ALP), urea (UREA), serum uric acid (SUA), fibrinogen (Fn), blood glucose (BG), and C-reactive protein (CRP). The correlation heatmap revealed the correlation and collinearity risks between these variables, with ALT and AST/ALT showing a high correlation ( r=0.750) and PLT and Alb showing a low correlation ( r=-0.110). Multivariable logistic regression indicated that the presence of multiple vertebral fractures [ OR=2.078, 95% CI (1.072, 4.025), P=0.030], increased Cobb angle [ OR=1.033, 95% CI (1.008, 1.058), P=0.009], elevated levels of ALP [ OR=1.013, 95% CI(1.004, 1.023), P=0.006], and SUA [ OR=1.004, 95% CI (1.000, 1.007), P=0.043] were associated with an increased risk of KD in patients with OVCFs. Conversely, decreased levels of Fn [ OR=0.996, 95% CI (0.992, 0.999), P=0.008] were linked to an increased risk of KD. Conclusion:Multiple vertebral fractures, increased Cobb angle, elevated levels of ALP and SUA, along with decreased levels of Fn, can be used as early-warning indicators to predict whether patients with OVCFs will develop KD. Monitoring these indicators is crucial for the early detection and intervention in these 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

Objective:To investigate the effects of miR-125b on radiosensitivity of cervical cancer cells and its possible downstream mechanism.Methods:The expression of miR-125b and Foxp3 in cervical cancer tissues and cells was detected by RT-qPCR. The HeLa cells were irradiated with 0, 2, 4 and 6 Gy of X-rays. The expression of miR-125b and Foxp3 in each group was detected by RT-qPCR. After downregulation of miR-125b expression and 6 Gy X-ray irradiation, the proliferation ability of HeLa cells was detected by MTT assay, and the expression of Bax and Bcl-2 proteins were detected by Western blot. The relationship between miR-125b and Foxp3 was detected by Targetscan and Dual luciferin reporter assay. After downregulation of Foxp3 expression and 6 Gy X-ray irradiation, the proliferation ability of HeLa cells was detected by MTT assay, and the expression of Bax and Bcl-2 proteins were detected by Western blot. The effects of miR-125b on radiosensitivity of HeLa cells through Foxp3 were detected. After down-regulation of Foxp3, the contents of IL-10 and TGF-β in supernatant were detected by ELISA.Results:The expression of miR-125b in the tissues and cells of cervical cancer was significantly decreased, while the expression of Foxp3 was significantly increased. The expression of miR-125b in HeLa cells was increased after radiation in a dose dependent manner. The expression of Foxp3 in HeLa cells was decreased after radiation in a dose dependent manner. After 6 Gy X-ray irradiation of HeLa cells, down-regulation of miR-125b increased the cell proliferation capacity, significantly reduced the expression of Bax and increased the expression of Bcl-2. miR-125b targets Foxp3 and negatively regulates Foxp3 expression. After 6 Gy X-ray irradiation of HeLa cells, down-regulation of Foxp3 significantly reduced the proliferation capacity of HeLa cells, increased the expression of Bax and decreased the expression of Bcl-2. Overexpression of miR-125b can enhance radiosensitivity of HeLa cells through Foxp3.After 6 Gy X-ray irradiation, down-regulation of Foxp3 reduced the expression of IL-10 and TGF-β in cells.Conclusions:Upregulation of miR-125b enhances the radiosensitivity of cervical cancer cells by targeting and negatively regulating Foxp3, and the mechanism of that may be related to the down-regulation of Foxp3 to reduce the expression of IL-10 and TGF-β in the cells.

Objective:To explore the role and molecular mechanism of trophoblastic cell surface antigen 2 (Trop2) in the invasion and migration of ovarian cancer.Methods:Through the data mining of Cancer Cell Line Encyclopedia and TCGA database, the clinical significance of Trop2 expression was analyzed. Western blot was used to detect Trop2 protein expression in ovarian cancer cell lines including A3O, A1780 and SKOV3. SKOV3 cells were used to construct Trop2-short hairpin RNA (shRNA) cell model. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the SKOV3 mRNA expression in SKOV3-shRNA and SKOV3-NC cells. Cell counting kit-8 (CCK8) was used to detect the proliferation of SKOV3-shRNA cells and SKOV3-NC cells. Flow cytometry was used to detect cell cycle and apoptosis in two groups of cells. Transwell array was used to detecte the invasion and migration of SKOV3-shRNA cells and SKOV3-NC cells. Western blot was used to detect the protein expressions of AKT, p-AKT, β-catenin, caspase3, bcl-2, E-cadherin and vimentin.Results:Trop2 mRNA highly expressed in ovarian cancer, and was related to the tumor stage and patient survival. Compared with A3O cells, Trop2 overexpressed in A1780 and SKOV3 cells ( P<0.05). The relative expression levels of Trop2 mRNA in SKOV3-NC group and SKOV3-shRNA group were 1.18±0.24 and 0.42±0.08, with statistically significant difference ( P<0.05). The results of CCK-8 array showed that the cell viability of SKOV3-NC group was significantly higher than that of SKOV3-shRNA group ( P<0.05). The proportion of G 0/G 1 cells in SKOV3-NC and SKOV3-shRNA groups were (38.67±4.22)% and (60.24±8.17)%, respectively. G 0/G 1 arrest was observed in SKOV3-shRNA cells ( P<0.05). The apoptosis rate of SKOV3-shRNA group was (26.32±1.81)%, significantly higher than (6.54±1.32)% of SKOV3-NC group ( P<0.05). The number of migrating SKOV3 cells in the SKOV3-shRNA and SkOV3-NC groups were 1 255.83±108.44 and 1 679.71±213.92, while the number of invading cells were 242.49±52.09 and 473.54±73.11, respectively. Compared with the SKOV3-NC group, the number of migrating and invading SKOV3-shRNA group was significantly reduced (all P<0.05). The expressions of p-AKT2, Bcl-2, vimentin and β-catenin were down-regulated, and the expressions of caspase 3 and E-cadherin were up-regulated in SKOV3-shRNA cells. There was no significant change in the total protein level of AKT. Conclusions:Trop2 expression is related to ovarian cancer stage and postoperative survival. Trop2 can promote ovarian cancer cell proliferation and metastasis by activating the AKT/β-catenin signaling pathway and knockdown of Trop2 inhibits the progression of ovarian cancer.

Objective:To explore the role and molecular mechanism of trophoblastic cell surface antigen 2 (Trop2) in the invasion and migration of ovarian cancer.Methods:Through the data mining of Cancer Cell Line Encyclopedia and TCGA database, the clinical significance of Trop2 expression was analyzed. Western blot was used to detect Trop2 protein expression in ovarian cancer cell lines including A3O, A1780 and SKOV3. SKOV3 cells were used to construct Trop2-short hairpin RNA (shRNA) cell model. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the SKOV3 mRNA expression in SKOV3-shRNA and SKOV3-NC cells. Cell counting kit-8 (CCK8) was used to detect the proliferation of SKOV3-shRNA cells and SKOV3-NC cells. Flow cytometry was used to detect cell cycle and apoptosis in two groups of cells. Transwell array was used to detecte the invasion and migration of SKOV3-shRNA cells and SKOV3-NC cells. Western blot was used to detect the protein expressions of AKT, p-AKT, β-catenin, caspase3, bcl-2, E-cadherin and vimentin.Results:Trop2 mRNA highly expressed in ovarian cancer, and was related to the tumor stage and patient survival. Compared with A3O cells, Trop2 overexpressed in A1780 and SKOV3 cells ( P<0.05). The relative expression levels of Trop2 mRNA in SKOV3-NC group and SKOV3-shRNA group were 1.18±0.24 and 0.42±0.08, with statistically significant difference ( P<0.05). The results of CCK-8 array showed that the cell viability of SKOV3-NC group was significantly higher than that of SKOV3-shRNA group ( P<0.05). The proportion of G 0/G 1 cells in SKOV3-NC and SKOV3-shRNA groups were (38.67±4.22)% and (60.24±8.17)%, respectively. G 0/G 1 arrest was observed in SKOV3-shRNA cells ( P<0.05). The apoptosis rate of SKOV3-shRNA group was (26.32±1.81)%, significantly higher than (6.54±1.32)% of SKOV3-NC group ( P<0.05). The number of migrating SKOV3 cells in the SKOV3-shRNA and SkOV3-NC groups were 1 255.83±108.44 and 1 679.71±213.92, while the number of invading cells were 242.49±52.09 and 473.54±73.11, respectively. Compared with the SKOV3-NC group, the number of migrating and invading SKOV3-shRNA group was significantly reduced (all P<0.05). The expressions of p-AKT2, Bcl-2, vimentin and β-catenin were down-regulated, and the expressions of caspase 3 and E-cadherin were up-regulated in SKOV3-shRNA cells. There was no significant change in the total protein level of AKT. Conclusions:Trop2 expression is related to ovarian cancer stage and postoperative survival. Trop2 can promote ovarian cancer cell proliferation and metastasis by activating the AKT/β-catenin signaling pathway and knockdown of Trop2 inhibits the progression of ovarian cancer.

Objective: The aim of the study is to compare the diagnostic value of multiparametric transrectal ultrasound(TRUS) and multiparametric magnetic resonance imaging (MRI) in prostate cancer. Methods: The clinical data of 102 patients who received multiparametric TRUS (including conventional transrectal ultrasound, shear wave sonoelastography and contrast enhanced ultrasound), multiparametric MRI(including T2 weighted diffusion weighted, and dynamic contrast enhanced MRI) and laboratory tests from April 2016 to May 2018 were retrospectively analyzed. The average age was 66.1 years old, ranging 38.0-85.0 years old. The average PSA was 30.1 ng/ml, ranging 0.4-227.0 ng/ml. The average PSAD was 0.67 ng/ml^2, ranging 0.02-4.27 ng/ml². The pathology results from TRUS guided biopsy or surgical operation were chosen as gold standard. Diagnostic performance including sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV), accuracy and area under the receiver operating characteristic curve(AUROC)of multiparametric TRUS and multiparametric MRI in prostate cancer were analyzed. Results: There were 62 prostate cancer and 40 BPH patients in our study. Parallel multiparametric TRUS diagnosed 63 prostate cancer and 39 BPH, and multiparametric MRI diagnosed 75 prostate cancer and 27 BPH. The sensitivity, specificity and accuracy of parallel multiparametric TRUS were 98.4%, 70.0% and 87.3%, respectively. And those of multiparametric MRI were 95.2%, 60.0% and 81.4%, respectively. The AUROC of parallel multiparametric TRUS and multiparametric MRI were 0.842 and 0.776, with no significant differences(P=0.208). Conclusion The diagnostic value of multiparametric TRUS was not inferior to multiparametric MRI in prostate cancer.

Objective:To estimate the incidence/mortality of ovarian cancer in 2015 and the incidence/mortality trend of ovarian cancer from 2006 to 2015 in Jiangsu province, and provide evidence for prevention and treatment of ovarian cancer in Jiangsu.Methods:The incidence and death data of cancer in Jiangsu from 2006 to 2015 collected from 35 cancer registries and verified by Jiangsu provincial CDC in 2018 were used for the extraction of ovarian cancer data. The data were stratified by urban and rural, gender and age groups. The crude rates of incidence and mortality, age-standardized incidence/mortality rates (ASIR/ASMR), cumulative incidence/mortality rates (0-74 years) and truncated incidence/mortality rates (35-64 years) of ovarian cancer were calculated. Chinese population census in 2000 and world Segi’s standard population were used for the calculations of age-standardized incidence/mortality rates. Software Joinpoint 4.7.0.0 was used to analyze the annual percentage changes (APCs) of two rates from 2006 to 2015.Results:It was estimated that 2 229 ovarian cancer cases occurred in Jiangsu in 2015, accounting for 2.23 % of all cancer cases and ranking 12 th of cancer incidence in women. The crude incidence rate was 5.91/100 000, the age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 4.01/100 000 and 3.81/100 000, respectively. The cumulative incidence rate (0-74 years) was 0.42 %. It was estimated that 1 239 deaths of ovarian cancer occurred in Jiangsu in 2015, accounting for 2.18 % of all cancer deaths and ranking 13 th of cancer mortality in women. The crude mortality rate was 3.29/100 000, the ASMRC and ASMRW were 1.99/100 000 and 1.96/100 000, respectively. The cumulative mortality rate (0-74 years) was 0.24 %. The APCs of crude incidence rate and crude mortality rate were 4.66 % (95 %CI: 2.11 %-7.29 %) and 7.45 % (95 %CI: 5.46 %-9.47 %) (all P<0.05). The APCs of ASIRC and ASIRW were 2.30 % (95 %CI: -0.32 %-4.99 %) and 2.41 % (95 %CI: -0.29 %-5.20 %) (all P>0.05), and the APCs of ASMRC and ASMRW were 4.43 % (95 %CI: 2.54 %-6.36 %) and 4.55 % (95 %CI: 2.58 %-6.57 %) (all P<0.05). Conclusions:The incidence and mortality of ovarian cancer in Jiangsu were at low levels, and were higher in urban areas than in rural areas. The crude incidence and mortality rates increased, and age-standardized incidence rate was stable, but age-standardized mortality rate increased obviously.

The cultivation of research ability can promote eight-year medical students to explore the uncharted academic fields and solve complex clinical problems. One of the firts pilot universities to provide eight-year programs, Xiangya Medical College of Central South University builds on its profound experience in medical education, and establishes a curriculum structure aiming at improving the students' research ability. In the general education stage, cross-disciplinary courses are set up. In the core medical education stage, basic medical innovation experiment extracurricular research courses are set up, and a two-year overseas exchange program is set up in the postgraduate training stage. Different evaluation methods are also designed to meet the specific needs in each stage. This program has achieved preliminary effects.