Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Objective To investigate the diagnostic efficacy and clinical value of GNB4 and Riplet gene methylation alone and in combination in the diagnosis of primary liver cancer.Methods A total of 313 patients were selected,including 78 patients with primary liver cancer,41 patients with other digestive system tumors,17 patients with non-digestive system tumors,20 patients with postoperative liver cancer,and 157 patients with benign liver disea-ses.The levels of GNB4 and Riplet gene methylation in plasma were detected using quantitative methylation-specific PCR(qMSP).Serum alpha-fetoprotein(AFP)levels were measured by direct chemiluminescence.Results The sensitivity and specificity of AFP in diagnosis were 51.3％and 94.3％,respectively;the sensitivity and specificity of GNB4 gene methylation in diagnosis were 83.3％and 99.4％,respectively;the sensitivity and specificity of Riplet gene methylation in diagnosis were 73.1％and 99.4％,respectively.The sensitivity and specificity of GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of combined diagnosis including age and gender were 93.6％and 97.5％,respective-ly.Conclusion The sensitivity and specificity of AFP in the diagnosis of primary liver cancer are limited,while the methylation levels of GNB4 and Riplet genes are higher,and the sensitivity and specificity of their combined de-tection are higher than those of AFP.The sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis are significantly higher than those of AFP,GNB4 and Riplet gene methylation alone.

BACKGROUND:With the increasing number of tendon transplantation surgeries for tendon injuries,the demand for tendon tissue engineering scaffolds is increasing.Research has found that good pore size and porosity of implants contribute to tissue healing. OBJECTIVE:To review the types of materials currently published for tendon tissue engineering scaffolds and investigate the correlation between various tendon tissue engineering scaffold materials and pores. METHODS:Articles were retrieved on PubMed,Embase,and Web of Science databases,using keywords"tendon"or"ligament"and"tissue scaffold"as well as"porosity"or"permeability".A total of 84 articles meeting the criteria were included to summarize,discuss and anticipate future development directions. RESULTS AND CONCLUSION:The materials used in the research of tendon tissue engineering are mainly divided into two categories:natural tendon scaffold materials and artificial synthetic tendon scaffold materials.Natural scaffold materials include autologous tendons,allogeneic tendons,and xenogeneic tendons.Autogenous tendons and allogeneic tendons have been used in clinical practice for many years.During the preparation of allogeneic tendons and animal experiments,it was found that the process of acellular disinfection resulted in an increase in the pore size and porosity of both types of tendons,but the specific reasons and mechanisms have not been further studied.There are many types of artificial tendon scaffold materials currently being studied,among which artificial ligament products such as Leeds Keio and LARS(Ligament Advanced Reinforcement System)are still in use in some countries.Other materials have not been promoted in clinical practice due to immature technology and other issues.The pores and porosity of artificial tendon scaffold materials also show different trends due to their different materials and preparation techniques.

ObjectiveTo establish a dose-effect curve for semi-automatic analysis of dicentric chromosomes(DC) based on an automatic chromosome analysis system. Methods A total of three healthy volunteers were recruited as the study subjects, and their peripheral blood was collected and stimulated by X-ray at doses of 0.00, 0.10, 0.25, 0.50, 0.75, 1.00, 2.00, 3.00, 4.00, and 5.00 Gy, with the absorbed dose rate of 1.0 Gy/min. Images of DC in the mid-stage of cell division were collected using a high-throughput automatic chromosome analysis system. The DCScore software was used to automatically analyze DC aberrations, and a dose-effect curve for semi-automatic analysis of DC was fitted after manual confirmation. The fitted dose-effect curve for semi-automatic analysis of DC was validated for accuracy using three proficiency test samples from the national quality assessment of biological dose. Results The incidence of DC increased with increasing irradiation doses in the range of 0.00-5.00 Gy (P<0.01). The dose-effect curve for the fitted semi-automatic analysis of DC was ŷ =0.000 8 (±0.000 2) +0.009 2(±0.000 9) D+0.014 2(±0.000 4) D² (R²= 0.999 8). The relative deviation between the estimated dose and the actual dose of the three test samples was about 20.00%, indicating curve applicability for biological dose estimation. Moreover, excluding the time spent on manual analysis, the semi-automatic analysis method increased the analysis efficiency by 26.0 times. Conclusion The semi-automatic analysis dose-effect curve for DC stimulated by X-ray is constructed for biological dose estimation, which can reduce the manual analysis time, and holds great potential for application in nuclear emergency response to large-scale radiation accidents.

Objective To explore the risk factors for the occurrence of hypertension in middle-aged and elderly residents in China using the Cox regression analysis model and decision tree model, and compare the differences between the two methods. Methods The 2011-2015 China Health and Retirement Longitudinal Study data were used. The study investigated the risk factors for hypertension using both a multivariate Cox regression model and a decision tree model. Results The results showed that the incidence rate of hypertension between 2011-2015 was 22.79%. Both the Cox regression model and decision tree model identified age, education level, body mass index, and diabetes as risk factors for hypertension. The Cox regression model also identified drinking status as a risk factor, while the decision tree model identified gender and marital status as additional risk factors. The area under the curve (AUC) suggested that the Cox regression model and decision tree model had comparable ability to predict hypertension. Conclusions The risk factors for hypertension include gender, age, education level, marital status, alcohol consumption, body mass index, and history of diabetes. The effectiveness of the hypertension prediction model established based on Cox regression model and decision tree model results is not different.

Objective:To analyze the predictive value of serum transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) in patients with non-small cell lung cancer (NSCLC) after single-port thoracoscopic radical resection.Methods:A total of 50 patients with NSCLC who underwent single-port thoracoscopic radical resection in Affiliated Hospital of Xuzhou Medical University from May 2018 to May 2020 were selected as the observation objects. Serum TGF-β1, VEGF levels and Karnofsky functional status (KPS) scores before and after surgery were compared, and the total incidence of complications was calculated. All subjects were followed up for 3 years, and serum levels of TGF-β1, VEGF and KPS scores were compared between relapsed group and non-relapsed group, survival group and death group. Pearson correlation analysis was used to explore the correlation between TGF-β1, VEGF and KPS scores. The receiver operator characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated to evaluate the predictive value of serum TGF-β1 and VEGF alone and combined detection in patients with NSCLC after single-port thoracoscopic radical resection.Results:The serum levels of TGF-β1 and VEGF were (7.16±1.94) μg/L and (42.26±5.04) ng/L in 50 patients with NSCLC one month after single-port thoracoscopic radical resection, which were lower than those before surgery [ (13.62±3.52) μg/L and (136.52±20.66) ng/L, t=11.37, P<0.001; t=31.34, P<0.001]. The KPS score one month after surgery was 66.57±8.11, which was higher than that before surgery (53.62±5.62, t=9.28, P<0.001). Postoperative wound healing was delayed in 1 of the 50 patients, pulmonary infection in 1 patient, and no pulmonary embolism and other complications occurred. The total incidence of complications was 4.00%. The serum levels of TGF-β1 and VEGF in patients in the relapsed group ( n=6) were (12.95±4.26) μg/L and (72.46±6.05) ng/L respectively, which were higher than those in the non-relapsed group ( n=44) [ (6.37±1.25) μg/L and (38.14±5.37) ng/L; t=8.34, P<0.001; t=29.99, P<0.001]. The KPS score in the relapsed group was 52.16±8.16, which was lower than that in the non-relapsed group (67.55±12.67, t=2.88, P=0.006). Serum levels of TGF-β1 and VEGF in the death group ( n=5) were (13.99±6.82) μg/L and (75.95±9.05) ng/L, which were higher than those in the survival group ( n=45) [ (6.41±3.06) μg/L and (38.52±8.37) ng/L; t=4.56, P<0.001; t=21.47, P<0.001]. The KPS score in the death group was 1.25±0.34, which was lower than that in the survival group (65.11±12.94, t=10.93, P<0.001). Pearson correlation analysis showed that serum levels of TGF-β1 ( r=-0.45, P<0.001) and VEGF ( r=-0.48, P<0.001) were negatively correlated with KPS scores. ROC curve analysis showed that when the optimal cut-off value of TGF-β1 was 8.14 μg/L, the AUC for predicting recurrence after single-port thoracoscopic radical resection was 0.516 (95% CI: 0.446-0.676), the sensitivity was 71.85%, and the specificity was 80.69%. When the optimal cut-off value of VEGF was 142 ng/L, the AUC was 0.659 (95% CI: 0.534-0.761), the sensitivity was 76.04%, and the specificity was 82.52%. The AUC of the combined detection was 0.828 (95% CI: 0.786-0.951), the sensitivity was 91.86%, and the specificity was 87.52%. The AUC of combined detection was higher than that of serum TGF-β1 ( Z=2.63, P=0.007), VEGF ( Z=2.32, P=0.013) single detection. Conclusion:The serum levels of TGF-β1 and VEGF are significantly decreased in NSCLC patients after one month of single-port thoracoscopic radical resection, and the combined detection of the two has predictive value for recurrence after single-port thoracoscopic radical resection.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective By analyzing the prevalence pattern and drug resistance of carbapenem-resistant enterobacteriaceae(CRE)infections in our hospital,we aim to provide the basis and suggestions for infection prevention and control as well as clinical management in large general hospitals.Methods A retrospective method was used to select 609 CRE strains isolated from hospitalized patients in our hospital from 2019 to 2022,and analyze their specimen sources,distribution of pathogenic bacteria,departmental distribution and drug resistance.Results A total of 6656 strains of Enterobacteriaceae and 609 strains of CRE were detected in the four years,with Klebsiella pneumoniae predominating(354 strains,58.13％),followed by Enterobacter inguinale(82 strains,13.46％)and Escherichia coli(77 strains,12.65％),and the department with the most detected CREs was the intensive care unit(ICU)(44.50％),followed by the Department of Burn Repair(13.79％),Department of Cardiac and Major Vascular Surgery(8.87％)and Department of Oncology(6.4％),and the sources of specimens were sputum(46.96％),secretions(15.60％),urine(13.30％),and blood(8.7％)in that order.The drug sensitivity results showed that the CRE strains had resistance rates＞50％to the rest of the clinically used antimicrobial drugs,except for tigecycline,polymyxin and minocycline,which were sensitive(1.31％,0.56％and 7.22％),and amikacin,fosfomycin,as well as cotrimoxazole,which had a lower resistance rate(23.65％,35.14％and 35.96％).Conclusion The overall trend of CRE detection rate in this hospital from 2019-2022 was increasing,and most of them showed multiple resistance to clinically used antibiotics,attention should be paid to strengthen the rational use of antimicrobial drugs and increase the supervision of bacterial resistance to curb the wide spread of CRE.

Objective: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. Methods: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatinresistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich premRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue. Results: PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC. Conclusion Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.

Objective: We previously elucidated that long non-coding RNA Promoter of CDKN1A Antisense DNA damage Activated RNA (PANDAR) as a p53-dependent oncogene to promote cisplatin resistance in ovarian cancer (OC). Intriguingly, high level of p53-independent PANDAR was found in cisplatin-resistant patients with p53 mutation. Here, our study probed the new roles and the underlying mechanisms of PANDAR in p53-mutant OC cisplatin-resistance. Methods: A2780 and A2780-DDP cells were served as OC cisplatin-sensitive and cisplatinresistant cells. HO-8910PM cells were subjected to construct chemotherapy-induced extracellular vesicles (Chemo-EVs). Transmission electron microscopy (TEM) and nanoparticle tracking analysis were employed to evaluate Chemo-EVs. Cell viability was assessed using cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and propidium iodide staining. The relationships between PANDAR, serine and arginine-rich premRNA splicing factor 9 (SRSF9) were verified by RNA immunoprecipitation and fluorescence in situ hybridization. Tumor xenograft experiment was employed to evaluate the effects of PANDAR-Chemo-EVs on OC cisplatin-resistance in vivo. Immunofluorescent staining and immunohistochemistry were performed in tumor tissue. Results: PANDAR level increased in OC patients with p53-mutation. PANDAR efflux enacted via exosomes under cisplatin conditions. Additionally, exosomes from OC cell lines carried PANDAR, which significantly increased cell survival and chemoresistance in vitro and tumor progression and metastasis in vivo. During cisplatin-induced stress, SRSF9 was recruited to nuclear bodies by increased PANDAR and muted apoptosis in response to cisplatin. Besides, SRSF9 significantly increased the ratio of SIRT4/SIRT6 mRNA in OC. Conclusion Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.