Objective:To investigate the effect of nuclear receptor subfamily 2 group F member 2(NR2F2)on the biological behaviors of human ovarian cancer SKOV3 cells,and to clarify its molecular mechauism and provide the new idea for treatment of ovarian cancer.Methods:Gene Expression Profiling Interactive Analysis(GEPIA)Database analyse the expression level of NR2F2 gene in ovarian tissue,and analyse its correlation with clinical prognosis of ovarian cancer patients.The human ovarian cancer SKOV3 cells were divided into control group and NR2F2 over-expression(NR2F2 OE)group,which were transfected with mCherry control virus and NR2F2 OE over-expression virus,respectively,when the cell deusity reached 70％,and the stable transfection SKOV3 cell lines were screened with puromycin(puro)48h lafter.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the transfection efficiencies of the cells;RT-qPCR method was used to detect the expression levels of NR2F2 and sex-determining region Y-box 2(SOX2)mRNA in the cells in two groups;Western blotting method was used to detect the expression levels of NR2F2,ATP-binding cassette superfamily G member 2(ABCG2),and programmed cell death 1-ligand 1(PD-L1)protcins in the cells in two groups.CCK-8 assay was used to detect the proliferation activities of the cells in two groups;Wound assay was used to detect the migration rates of the cells in two groups;Transwell chamber assay was used to detect the number of transmembrane cells;Spheroidization assay was used to detect the numbers of spheroids in the cells;peripheral blood mononuclear cells(PBMCs)-mediated tumor cell killing assay was used to detect the relative densities of surviving tumor cells;CCK-8 assay was used to detect the half maximal inhibitory concentration(IC50)of paclitaxel(PTX)and carboplatin(CBP).Results:Compared with normal ovarian tissue,the expression level of NR2F2 gene in ovarian tumor tissue was decreased(P＜0.05),and decreased with the improvement of clinical pathological grading of ovarian tumor.The patients with higher expression level of NR2F2 gene had better clincal prognosis.The SKOV3 cells with NR2F2 over-expresson were successfully constructed,and the expression levels of NR2F2 mRNA and protein in the cells in NR2F2 OE group were increased compared with control group(P＜0.001).The CCK-8 assay results showed that compared with control group,the proliferation activities of the cells in NR2F2 OE group were decreased at different time points(1,2,3,and 4 d)(P＜0.05 or P＜0.01).The cell wound assay results showed that compared with control group,the migration rate of the cells in NR2F2 OE group was decreased(P＜0.001).The Transwell assay results showed that compared with control group,the number of transmembrane cells in NR2F2 OE group was decreased(P＜0.01).Compared with control group,the number of the spheroids in NR2F2 OE group was decreased(P＜0.05),and the expression levels of SOX2 mRNA(P＜0.01)and protein(P＜0.001)were increased.Compared with control group,the relative density of surviving tumor cells in NR2F2 OE group was decreased,but the difference was not significant(P＜0.05),and the expression level of PD-L1 protein was decreased(P＜0.05).Compared with control group,the proliferation activities of cells in NR2F2 OE group were decreased(P＜0.05),and the drug sensitivities of the cells to PTX and CBP were enhanced(P＜0.05);the IC50 of PTX was significantly reduced,while the IC50of CBP could not be calculated due to excessively high drug concentration;the expression level of ABCG2 protein was decreased(P＜0.05).Conclusion:The over-expression of NR2F2 may inhibit the proliferation,migration,and invasion of the human ovarian cancer SKOV3 cells,decrease the expression levels of SOX2,PD-L1 and ABCG2 proteins,suppress the stemness and immune evasion ability of the SKOV3 cells,and enhance the sensitivities of the SKOV3 cells to PTX and CBP.

Objective:To discuss the effect of long non-coding RNA(lncRNA)LINC00973 on the migration,invasion,and distant metastasis of epithelial ovarian cancer,and to clarify its molecular mechanism.Methods:The human ovarian cancer SKOV3 and OVCAR3 cells were divided into EF1a-FH empty vector control group(control group),LINC00973 overexpression group(LINC00973 OE group),U6-shRNA empty vector control group(SHV group),and LINC00973 knockdown group(LINC00973 KD group),and were transfected with lentivirus containing nonsense sequence(pLent-EF1a-FH-CMV-copGFP-P2A-Puro),LINC00973 overexpression,nonsense sequence(pLent-U6-shRNA-CMV-copGFP-P2A-Puro)and LINC00973 shRNA,respectively,followed by puromycin screening to obtain stably transfected SKOV3 and OVCAR3 cells.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of target genes in the cells in various groups;wound healing assay was used to detect the migration rate of the cells in various groups;Transwell chamber assay was used to detect the number of transmembrane cells in various groups;The mice were divided into control group(WT group),LINC00973 OE group,and LINC00973 KD group,with 4 mice in each group.SKOV3 wild-type cells,LINC00973 OE cells,and LINC00973 KD cells were intraperitoneally injected into the mice in various groups,respectively,to establish the epithelial ovarian cancer intraperitoneal implantation and metastasis model;HE staining was used to observe the morphology of the colon and liver tissues of the mice in various groups;RNA-secquencing(RNA-seq)was used to analyze the differentially expressed genes between SHV and LINC00973 KD groups in the SKOV3 cell line;RT-qPCR method was used to detect the mRNA expression levels of LINC00973 in the normal ovarian epithelial cells IOSE-80 and epithelial ovarian cancer cells SKOV3,A2780 and OVCAR3,the mRNA expression levels of LINC00973,Vimentin,Snail family transcriptional repressor 1(Snail),Twist family basic helix-loop-helix transcription factor 1(Twist),zinc finger E-box binding homeobox 1(ZEB1),zinc finger E-box binding homeobox 2(ZEB2),CXCL8 and matrix metalloproteinase(MMP)16 in the cells in various groups,and the mRNA expression levels of LINC00973,Vimentin and Twist in liver and colon tissues of the mice in various groups.Results:Compared with normal ovarian epithelial cells IOSE-80,the expression level of LINC00973 mRNA in the epithelial ovarian cancer cells SKOV3,OVCAR3 and A2780 was significantly increased(P<0.01),with the highest expression level of LINC00973 in SKOV3 and OVCAR3 cells,which were therefore selected for subsequent experiments.In SKOV3 and OVCAR3 cells,compared with control group,the expression level of LINC00973 mRNA in the cells in LINC00973 OE group was increased(P<0.01);compared with SHV group,the expression level of LINC00973 mRNA in the cells in LINC00973 KD group was decreased(P<0.05 or P<0.01),indicating successful construction of LINC00973 overexpression and knockdown cell lines.In SKOV3 cells,compared with control group,the mRNA expression levels of Vimentin and Twist in LINC00973 OE group were increased(P<0.05 or P<0.01),while no significant difference was observed in Snail mRNA expression level(P>0.05);compared with SHV group,the mRNA expression levels of Vimentin,Snail and Twist in LINC00973 KD group were decreased(P<0.01).In OVCAR3 cells,compared with control group,the mRNA expression levels of Vimentin,Snail and Twist in LINC00973 OE group were increased(P<0.01);compared with SHV group,the expression levels of Vimentin,Snail,and mRNA Twist in LINC00973 KD group were decreased(P<0.01).The wound healing assay results showed that compared with control group,the wound healing rates of the SKOV3 and OVCAR3 cells in LINC00973 OE group were significantly increased(P<0.01);compared with SHV group,the wound healing rates of the cells in LINC00973 KD group were significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of transmembrane cells of the SKOV3 and OVCAR3 cells in LINC00973 OE group were significantly increased(P<0.01);compared with SHV group,the numbers of transmembrane cells in LINC00973 KD group were significantly decreased(P<0.01).Compared with WT group,the number of peritoneal nodules in LINC00973 OE group was increased,with rough liver surface and multiple nodules formed on mesentery and colon surface,and the expression levels of LINC00973,Vimentin,and Twist mRNA in colon tissue were increased(P<0.01);compared with WT group,no nodules were formed in the peritoneal cavity of LINC00973 KD group,with smooth liver surface,no nodules in liver tissue,and decreased expression levels of LINC00973,Vimentin,and Twist mRNA,and no nodules were observed on mesentery and colon surface.The HE staining results showed that compared with WT group,the multiple lesions were observed in liver and colon tissues in LINC00973 OE group,manifested as uneven cell size,irregular shape,unclear cell boundaries,increased nuclear division,and uneven red staining in cytoplasm,while in LINC00973 KD group,the cells in liver and colon tissues were arranged neatly with regular shape,and uniform distribution of nuclei and cytoplasm.The RNA-seq results showed that compared with SHV group,no key signaling pathways related to tumor metastasis were enriched in LINC00973 KD group,and the transcription levels of metastasis-related genes CXCL8,MMP16,ZEB1,and ZEB2 were decreased.The RT-qPCR results showed that compared with control group,the expression levels of ZEB1,ZEB2,CXCL8,and MMP16 mRNA in the cells in LINC00973 OE group were significantly increased(P<0.01);compared with SHV group,the expression levels of ZEB1,ZEB2,CXCL8,and MMP16 mRNA in the cells in LINC00973 KD group were significantly decreased(P<0.01).Conclusion:LINC00973 can up-regulate the expression of metastasis-related factors Vimentin,Snail,Twist,ZEB1,ZEB2,CXCL8,and MMP16,and promote the migration,invasion,and distant metastasis of epithelial ovarian cancer.

AIM:This study aims to investigate the mechanism by which LINC00973 regulates multidrug re-sistance of non-small-cell lung cancer(NSCLC).METHODS:The GEPIA database was employed to analyze the expres-sion levels of LINC00973 in NSCLC and its correlation with patient prognosis in clinical settings.RT-qPCR was utilized to assess LINC00973 expression in various NSCLC cell lines and chemoresistant cells.The migration,invasion,stemness ca-pacity,and drug sensitivity of NSCLC cells with either overexpression or knockdown of LINC00973 were evaluated using wound healing assay,Transwell assay,sphere formation assay,and CCK-8 assay.RNA sequencing was conducted on LINC00973-overexpressing and parental NSCLC cells to identify dysregulated pathways and targets.The LncBase Pre-dicted v.2 and TargetScan databases were used to predict the microRNAs(miRNAs)co-bound by LINC00973 and their target genes.Mimics and inhibitors of candidate miRNAs were synthesized and transfected into NSCLC cells subjected to LINC00973 overexpression or knockdown.Changes in the expression level of LINC00973,and the mRNA and protein ex-pression levels of its target genes were assessed using RT-qPCR and Western blot.RESULTS:Analysis of the GEPIA da-tabase revealed that LINC00973 was significantly up-regulated in lung adenocarcinoma and lung squamous cell carcino-ma,correlating with poor prognosis of NSCLC patients.The LINC00973 expression was elevated in various NSCLC and chemoresistant cell lines(A549/DDP and A549/5-FU).Overexpression of LINC00973 in A549 and H520 cells markedly enhanced their migration,invasion,and stemness capabilities,while concurrently reducing sensitivity to chemotherapy and targeted therapies.RNA sequencing,along with RT-qPCR results,indicated that ATP-binding cassette transporter G5(ABCG5)was activated in LINC00973-overexpressing A549 and H520 cells.Further database analyses and dual trans-fection experiments confirmed that LINC00973 regulated ABCG5 expression through competitive binding with hsa-miR-150-5p.CONCLUSION:LINC00973,which is aberrantly up-regulated in NSCLC specimens and associated with poor clinical prognosis,promotes the expression of ABCG5 through competitive binding with hsa-miR-150-5p.This interaction leads to en-hanced invasion,stemness,and multidrug resistance in NSCLC cells.

AIM:This study aims to investigate the mechanism by which LINC00973 regulates multidrug re-sistance of non-small-cell lung cancer(NSCLC).METHODS:The GEPIA database was employed to analyze the expres-sion levels of LINC00973 in NSCLC and its correlation with patient prognosis in clinical settings.RT-qPCR was utilized to assess LINC00973 expression in various NSCLC cell lines and chemoresistant cells.The migration,invasion,stemness ca-pacity,and drug sensitivity of NSCLC cells with either overexpression or knockdown of LINC00973 were evaluated using wound healing assay,Transwell assay,sphere formation assay,and CCK-8 assay.RNA sequencing was conducted on LINC00973-overexpressing and parental NSCLC cells to identify dysregulated pathways and targets.The LncBase Pre-dicted v.2 and TargetScan databases were used to predict the microRNAs(miRNAs)co-bound by LINC00973 and their target genes.Mimics and inhibitors of candidate miRNAs were synthesized and transfected into NSCLC cells subjected to LINC00973 overexpression or knockdown.Changes in the expression level of LINC00973,and the mRNA and protein ex-pression levels of its target genes were assessed using RT-qPCR and Western blot.RESULTS:Analysis of the GEPIA da-tabase revealed that LINC00973 was significantly up-regulated in lung adenocarcinoma and lung squamous cell carcino-ma,correlating with poor prognosis of NSCLC patients.The LINC00973 expression was elevated in various NSCLC and chemoresistant cell lines(A549/DDP and A549/5-FU).Overexpression of LINC00973 in A549 and H520 cells markedly enhanced their migration,invasion,and stemness capabilities,while concurrently reducing sensitivity to chemotherapy and targeted therapies.RNA sequencing,along with RT-qPCR results,indicated that ATP-binding cassette transporter G5(ABCG5)was activated in LINC00973-overexpressing A549 and H520 cells.Further database analyses and dual trans-fection experiments confirmed that LINC00973 regulated ABCG5 expression through competitive binding with hsa-miR-150-5p.CONCLUSION:LINC00973,which is aberrantly up-regulated in NSCLC specimens and associated with poor clinical prognosis,promotes the expression of ABCG5 through competitive binding with hsa-miR-150-5p.This interaction leads to en-hanced invasion,stemness,and multidrug resistance in NSCLC cells.

Objective To analyze in depth the job satisfaction and influencing factors of medical staff in tertiary public hospitals in Gansu Province,especially to explore the important factors affecting the survival and development of hospitals as core talents,in order to provide reference for promoting the stable development of medical staff in medical institutions in Gansu Prov-ince.Methods From July to October 2024,a random sampling method was used to select relevant personnel from tertiary public hospitals in Gansu Province for a questionnaire survey.Descriptive analysis were conducted on the collected data.Multivariate lo-gistic regression analysis was used to identify the main influencing factors of job satisfaction among medical staff.The difference is statistically significant with P＜0.05,and the test level is α=0.05.Results 1 890 questionnaires were distributed and 1 885 valid questionnaires were collected,with an effective rate of 99.74％.The overall job satisfaction score of medical staff in tertiary hospitals in Gansu Province is 3.06±0.86,which is at a moderate level.Hospitals can consider improving management models,establishing scientific,reasonable,and humane management systems,enhancing doctors'sense of belonging,and improving sat-isfaction;The satisfaction brought by salary to medical staff is higher than promotion opportunities and career development,indi-cating that a reasonable salary incentive system in hospitals,with excellent performance and compensation,can increase doctors'subjective well-being and improve satisfaction.Optimising the allocation of health human resources and appropriately in creasing personnel allocation based can help improve doctors'job satisfaction.Conclusion The overall job satisfaction of medical staff in tertiary hospitals in Gansu Province is generally satisfactory,and there are statistically significant differences in job satisfaction a-mong medical staff with different work experience,education level and monthly income(P＜0.05).When formulating policies and measures,the government pays attention to factors that affect the job satisfaction of medical personnel,optimizes the alloca-tion of health human resources,continuously improves incentive mechanisms,and improves hospital management models,enhan-cing the job satisfaction of medical staff and laying the foundation for promoting the developmrnt of provincial health talent team.

Objective To analyze in depth the job satisfaction and influencing factors of medical staff in tertiary public hospitals in Gansu Province,especially to explore the important factors affecting the survival and development of hospitals as core talents,in order to provide reference for promoting the stable development of medical staff in medical institutions in Gansu Prov-ince.Methods From July to October 2024,a random sampling method was used to select relevant personnel from tertiary public hospitals in Gansu Province for a questionnaire survey.Descriptive analysis were conducted on the collected data.Multivariate lo-gistic regression analysis was used to identify the main influencing factors of job satisfaction among medical staff.The difference is statistically significant with P＜0.05,and the test level is α=0.05.Results 1 890 questionnaires were distributed and 1 885 valid questionnaires were collected,with an effective rate of 99.74％.The overall job satisfaction score of medical staff in tertiary hospitals in Gansu Province is 3.06±0.86,which is at a moderate level.Hospitals can consider improving management models,establishing scientific,reasonable,and humane management systems,enhancing doctors'sense of belonging,and improving sat-isfaction;The satisfaction brought by salary to medical staff is higher than promotion opportunities and career development,indi-cating that a reasonable salary incentive system in hospitals,with excellent performance and compensation,can increase doctors'subjective well-being and improve satisfaction.Optimising the allocation of health human resources and appropriately in creasing personnel allocation based can help improve doctors'job satisfaction.Conclusion The overall job satisfaction of medical staff in tertiary hospitals in Gansu Province is generally satisfactory,and there are statistically significant differences in job satisfaction a-mong medical staff with different work experience,education level and monthly income(P＜0.05).When formulating policies and measures,the government pays attention to factors that affect the job satisfaction of medical personnel,optimizes the alloca-tion of health human resources,continuously improves incentive mechanisms,and improves hospital management models,enhan-cing the job satisfaction of medical staff and laying the foundation for promoting the developmrnt of provincial health talent team.

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca²⁺-interfering therapeutic effect. Based on these characteristics, amorphous calcium carbonate (ACC), as a brunch of calcium-based biomaterials, has the potential to become a widely used biomaterial. Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However, the standalone presence of ACC is unstable in vivo. Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination. ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo, such as Ca²⁺ with an immune-regulating ability and CO₂ with an imaging-enhancing ability. Owing to these characteristics, ACC has been studied for self-sacrificing templates of carrier construction, targeted delivery of oncology drugs, immunomodulation, tumor imaging, tissue engineering, and calcium supplementation. Emphasis in this paper has been placed on the origin, structural features, and multiple applications of ACC. Meanwhile, ACC faces many challenges in clinical translation, and long-term basic research is required to overcome these challenges. We hope that this study will contribute to future innovative research on ACC.

Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and tox-icokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

Objective:To analyze the value of the Padua prediction score and the bleeding risk score in the risk assessment of venous thromboembolism(VTE)and hemorrhage in elderly patients with choledocholithiasis during endoscopic retrograde cholangiopancreatography(ERCP).Methods:Clinical data of 171 elderly patients with choledocholithiasis treated with ERCP at the Affiliated Hospital of Xinjiang Medical University from September 2017 to September 2019 were retrospectively analyzed.The Padua prediction score and bleeding risk score were used to evaluate the occurrence of VTE and hemorrhage risk stratification.Results:Of all patients treated with the procedure, 18 of them had complications after surgery, including postoperative pancreatitis(9 cases), biliary infections(4 cases), hemorrhage(3 cases)and VTE events(2 cases). In addition, complications occurred in elderly patients in different age groups, with no significant difference in incidence(all P>0.05). Evaluation models showed that 32.7%(56/171)were at high risk for VTE, and 15.2%(26/171)were at high risk for hemorrhage.Furthermore, 2 VTE events occurred in the high-risk group and, of 3 hemorrhage events, 2 were occurred in the low-risk group and 1 in the high-risk group.There was no significant difference in the incidence of complications between the high-risk group and the low-risk group( χ2=0.000, 2.867, P=1.000, 0.090). Logistic regression analysis results showed that scores of the two assessment models were not influencing factors for VTE/hemorrhage(Padua prediction score: OR=8.383, 95% CI: 0.926-75.869, P=0.059; bleeding risk score: OR=2.860, 95% CI: 0.250-32.740, P=0.398). Conclusions:For elderly choledocholithiasis patients treated with ERCP, the Padua prediction score and the bleeding risk score have limited ability for risk assessment.More attention needs to be paid to the two VTE risk factors, i.e., malignant tumors and previous VTE history, in addition to previous bleeding risk for antithrombotic therapy.

Background: The prevalence rate of ulcerative colitis (UC) in China has increased significantly in recent years, and Toll-like receptor 2 (TLR2), TLR4 and NOD2/CARD15 may be closely related to the development of UC. Aims: To explore the influence of TLR2, TLR4 and NOD2/CARD15 gene polymorphisms on the pathogenesis of UC. Methods: Studies on correlation of TLR2, TLR4 and NOD2/CARD15 gene polymorphisms with UC were retrieved from PubMed, CBM, CNKI, Wanfang, VIP databases. Literatures were enrolled according to the inclusion and exclusion criteria, and the quality was evaluated and data were extracted. RevMan 5.3 software was used to conducted meta-analysis. Results: Fifteen eligible articles were included. Meta-analysis showed that TLR2 Arg753Gln gene polymorphism was not associated with risk of UC (P>0.05). Except the recessive model, TLR4 Asp299Gly gene polymorphism could increase the risk of UC (P<0.05). The overdominant model of TLR4 Thr399Ile gene could increase the risk of UC (P<0.05), but not the dominant model and recessive model (P>0.05). No significant association between NOD2/CARD15 (Arg702Trp, Gly908Arg and Leu1007fsinsC) gene polymorphism and UC was found (P>0.05). Conclusions: Existing evidence shows that TLR4 (Asp299Gly, Thr399Ile) gene polymorphisms are associated with an increased risk of UC, however, NOD2/CARD15 (Arg702Trp, Gly908Arg and Leu1007fsinsC) and TLR2 (Arg753Gln) gene polymorphisms are not associated with UC.