Objective: The impact of prophylactic salpingectomy on the prevention of epithelial ovarian cancer (EOC) remains unclear, particularly in Asian populations where data is lacking. In this systematic review and meta-analysis study, we sought to assess whether prophylactic salpingectomy could reduce the incidence of ovarian cancer in the general population of multiple ethnicities. Methods: A systematic review and meta-analysis were conducted using PubMed/MEDLINE, EMBASE, the Cochrane Library, and Web of Science to assess the effectiveness of salpingectomy, bilateral salpingectomy (BS), and unilateral salpingectomy (US) in reducing the risk of EOC and evaluating postoperative outcomes. Results: The final analyses included 6 eligible trials (5,747,056 patients), including 1 cohort study and 5 case-control studies. The analyses of these studies demonstrated that women who underwent salpingectomy had a significantly reduced risk of EOC compared to those who did not receive salpingectomy (odds ratio [OR]=0.63; 95% confidence interval [CI]=0.45–0.89; p=0.007). Five studies (5,746,469 patients) indicated a significant reduction in EOC risk among patients who underwent BS (OR=0.48; 95% CI=0.33–0.69; p<0.001).On the other hand, in the analysis of 4 studies (5,745,887 patients) that examined US, the association with EOC risk was not significant despite the protective trend (OR=0.82; 95% CI=0.64–1.06; p=0.12). Conclusion Our results indicate BS is an effective strategy for reducing the risk of sporadic EOC, but the results did not lead to the same conclusion for patients who underwent US. When a candidate or patient is undergoing a hysterectomy or has other benign diseases, prophylactic BS may be a safe surgical procedure that carries future benefits in terms of EOC risk.

Objective: The impact of prophylactic salpingectomy on the prevention of epithelial ovarian cancer (EOC) remains unclear, particularly in Asian populations where data is lacking. In this systematic review and meta-analysis study, we sought to assess whether prophylactic salpingectomy could reduce the incidence of ovarian cancer in the general population of multiple ethnicities. Methods: A systematic review and meta-analysis were conducted using PubMed/MEDLINE, EMBASE, the Cochrane Library, and Web of Science to assess the effectiveness of salpingectomy, bilateral salpingectomy (BS), and unilateral salpingectomy (US) in reducing the risk of EOC and evaluating postoperative outcomes. Results: The final analyses included 6 eligible trials (5,747,056 patients), including 1 cohort study and 5 case-control studies. The analyses of these studies demonstrated that women who underwent salpingectomy had a significantly reduced risk of EOC compared to those who did not receive salpingectomy (odds ratio [OR]=0.63; 95% confidence interval [CI]=0.45–0.89; p=0.007). Five studies (5,746,469 patients) indicated a significant reduction in EOC risk among patients who underwent BS (OR=0.48; 95% CI=0.33–0.69; p<0.001).On the other hand, in the analysis of 4 studies (5,745,887 patients) that examined US, the association with EOC risk was not significant despite the protective trend (OR=0.82; 95% CI=0.64–1.06; p=0.12). Conclusion Our results indicate BS is an effective strategy for reducing the risk of sporadic EOC, but the results did not lead to the same conclusion for patients who underwent US. When a candidate or patient is undergoing a hysterectomy or has other benign diseases, prophylactic BS may be a safe surgical procedure that carries future benefits in terms of EOC risk.

Objective: The impact of prophylactic salpingectomy on the prevention of epithelial ovarian cancer (EOC) remains unclear, particularly in Asian populations where data is lacking. In this systematic review and meta-analysis study, we sought to assess whether prophylactic salpingectomy could reduce the incidence of ovarian cancer in the general population of multiple ethnicities. Methods: A systematic review and meta-analysis were conducted using PubMed/MEDLINE, EMBASE, the Cochrane Library, and Web of Science to assess the effectiveness of salpingectomy, bilateral salpingectomy (BS), and unilateral salpingectomy (US) in reducing the risk of EOC and evaluating postoperative outcomes. Results: The final analyses included 6 eligible trials (5,747,056 patients), including 1 cohort study and 5 case-control studies. The analyses of these studies demonstrated that women who underwent salpingectomy had a significantly reduced risk of EOC compared to those who did not receive salpingectomy (odds ratio [OR]=0.63; 95% confidence interval [CI]=0.45–0.89; p=0.007). Five studies (5,746,469 patients) indicated a significant reduction in EOC risk among patients who underwent BS (OR=0.48; 95% CI=0.33–0.69; p<0.001).On the other hand, in the analysis of 4 studies (5,745,887 patients) that examined US, the association with EOC risk was not significant despite the protective trend (OR=0.82; 95% CI=0.64–1.06; p=0.12). Conclusion Our results indicate BS is an effective strategy for reducing the risk of sporadic EOC, but the results did not lead to the same conclusion for patients who underwent US. When a candidate or patient is undergoing a hysterectomy or has other benign diseases, prophylactic BS may be a safe surgical procedure that carries future benefits in terms of EOC risk.

BACKGROUND: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. METHODS: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. RESULTS: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. CONCLUSION The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals ; T-Lymphocytes, Regulatory/immunology* ; Dendritic Cells/immunology* ; Mice ; Mice, Inbred BALB C ; Membrane Proteins/metabolism* ; Receptors, Notch/metabolism* ; Lymphoid Tissue/metabolism* ; Signal Transduction/physiology* ; Coculture Techniques ; Flow Cytometry

Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity* ; Animals ; Nucleotidyltransferases/antagonists & inhibitors* ; Membrane Proteins/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Mice ; Hair Cells, Auditory, Inner/pathology* ; Antineoplastic Agents/toxicity* ; Mice, Inbred C57BL ; Hearing Loss/metabolism* ; Male ; Ototoxicity/metabolism*

ObjectiveTo investigate the trends in diabetes mortality rate and the characteristics of decreased population in Fengxian District, Shanghai from 2012 to 2021. MethodsData from the death registration records of the residents in Fengxian District between 2012 and 2021, sourced from the Shanghai Death Surveillance System, were analyzed. Indicators such as the crude mortality rate due to diabetes, the standardized mortality rate, years of life lost (YLL), and the probability of premature death were estimated. Annual percentage change (APC) was used to analyze the temporal trends of mortality and the probability of premature death due to diabetes. Rate decomposition analysis was used to assess the contributions of demographic and non-demographic factors to diabetes mortality. ResultsFrom 2012 to 2021, there were 1 471 deaths due to diabetes in Fengxian District, with a crude mortality rate of 27.51/100 000 and a standardized mortality rate of 17.58/100 000. The crude mortality rate showed an overall increasing trend (APC=4.58%, Z=3.49, P<0.05). The potential years of life lost (PYLL) due to diabetes over this period amounted to 9 715 person-years, with a PYLL rate of 1.82 ‰, and the average years of life lost (AYLL) was 11.94 years. The probability of premature death was 0.41% (APC=3.36%, t=2.33, P<0.05). Both population aging and non-aging factors contributed to the increase in diabetes mortality, with overall contribution rates of 67.99% and 32.01%, respectively. Among men, the contribution rates were 60.57% and 39.43%, while among women, they were 79.43% and 20.57%, respectively. ConclusionFrom 2012 to 2021, both the crude mortality rate and the probability of premature death due to diabetes showed an upward trend among the residents in Fengxian District, with a higher YLL. Population aging was the main factor causing the increase in mortality rate, while non-demographic factors had a greater impact on the rise in diabetes mortality among men than that in women. Therefore, the management on male diabetes patients should be strengthened.

To investigate the effects of ORF9 gene of porcine circovirus type 2(PCV2)on PK-15,eu-karyotic expression plasmid was constructed and transfected into PK-15 cells,and the effects of overexpression of ORF9 on proliferation,apoptosis and immunization of PK-15 cells were exam-ined by flow cytometry and qRT-PCR.The results showed that ORF9 gene overexpression signifi-cantly up-regulated the expression levels of the ER stress marker gene GRP78,increased the num-ber of S phase cells,accelerated cell cycle progression,increased the apoptosis rate of PK-15 cells,up-regulated the expression levels of apoptosis-related genes caspase-3,caspase-8,caspase-9,p53 and Bax(P＜0.01),down-regulated the expression levels of apoptosis-related genes Bcl-2,up-reg-ulated the expression levels of immune-related genes 1L-8,IL-10,NF-κB and TNF-α(P＜0.01),and down-regulated the expression levels of immune-related genes IL-2,IFN-β and IL-12(P＜0.01).The above results indicate that ORF9 gene may promote the proliferation and apoptosis of PK-15 cells and play a role in the escape process of PK-15 cells.

In order to understand the genomic characteristics and genetic variation and strain type of infectious bursal disease virus(IBDV)isolate GZGY2022,which caused the death of chickens in Guizhou farm,primers were designed to amplify the whole genome of the isolate,and genetic evo-lution and strain type analysis were performed after cloning and sequencing.The results showed that the A and B segments of IBDV genome were 3 260,2 827 bp,respectively,encoding VP2-VP5 and VP1 genes.The nucleotide sequence homology between the A and B segments of this strain and the VvIBDV were 96.2％-98.7％and 87.7％-98.9％,respectively,which is the highest with NN1172 strain,83.1％-94.7％and 90.1％-91.0％with other strains.The results of genetic evolution and strain type study showed that IBDV strains can be divided into 6 branches according to antigen and virulence,and the A and B segments of the strain were clustered in the evolutionary branch of VvIBDV,and the strain was A3B3 genotype according to the new genotype classification method.The results of amino acid sequence analysis showed that there were 3 and 7 unique amino acid site variations in the A and B segments of the strain,respectively,and 13 unique characteristic amino acid sites in the coding region of the full-length genome were consistent with VvIBDV.The VP2 sequence of segment A has 19 characteristic amino acid identical with VvIBDV,among which hyper variable regions 222A,242I,253Q,256I,279D,284A,294I and 299S were characteristic ami-no acid sites of the VvIBDV,and the heptapeptide region sequence SWSASGS was consistent with the virulent strain.The VP1 sequence of segment B has 10 characteristic amino acid identical with VvIBDV,among which 61I,145T and 287A were the characteristic amino acid sites of the VvIB-DV.In addition,the nucleotide sequence GGTGCC of 777-782 did not form the restriction endo-nuclease site of Kpn Ⅰ,and combined with the triplet site 145/146/147(TEG),the segment B was consistent with the NN1172 strain,showed that its virulence was slightly weaker than that of the B2 strain of VvIBDV.The results of recombination analysis showed that there were no breaks and recombination sites in the sequence of the strain,and no recombination event occurred.In summa-ry,this study found that GZGY2022 strain belonged to the A3B3 genotype non-recombinant VvIB-DV strain,and its special amino acid sites were consistent with the molecular characteristics of VvIBDV.This study lays the foundation for further exploring the genomic characteristics and path-ogenicity of VvIBDV.

Objective To investigate the effect of acacetin on oxidative stress injury in diabetic cataract(DC)rats and its regulation of sirtuin 1(Sirt1)/adenosine monophosphate-activated protein kinase(AMPK)/nuclear factor-erythroid 2-related factor 2(Nrf2)signaling pathway.Methods Sixty SD rats were randomly divided into the control group,model group,low-dose acacetin group,high-dose acacetin group,and acacetin+Sirt1 inhibitor(EX527)group.DC rat models were constructed except for the control group.Rats in the low-dose and high-dose acacetin groups were injected with 10 mg·kg-1 and 20 mg·kg-1 acacetin subcutaneously through the neck,twice a day,respectively.Rats in the acacetin+EX527 group were injected with 20 mg·kg-1 acacetin subcutaneously through the neck,twice a day;additionally,3.5 mg·kg-1 EX527 was administered subcutaneously through the osmotic micro-pump for 4 weeks.The same amount of nor-mal saline was pumped into rats in the rest groups for 4 weeks.After administration,blood pressure and fasting blood glu-cose(FBG)were measured.The lens opacity was observed under the slit lamp irradiation,and the histopathological chan-ges in the lens were observed after hematoxylin-eosin staining.Enzyme-linked immunosorbent assay was performed to de-termine the serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),in-terleukin(IL)-6,and IL-1 β.Western blot was applied to detect the expression levels of Sirt1,phosphorylated AMPK(p-AMPK),AMPK,and Nrf2 proteins.Results Compared with the control group,the lens epithelial cells(LECs)of rats in the model group showed patchy and striped shapes,and migration and aggregation occurred;the systolic blood pres-sure(SBP),FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β increased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins decreased(all P＜0.05).Compared with the model group,the migration and aggregation of LECs improved in the low-dose and high-dose acacetin groups,the SBP,FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β decreased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins increased(all P＜0.05).Compared with the high-dose acacetin group,the morphological chan-ges and aggregation of LECs in the acacetin+EX527 group were more significant,the SBP,FBG,lens opacity score,and the levels of MDA,IL-6 and IL-1 β increased,while the expression levels of SOD,GSH-Px,Sirt1,p-AMPK/AMPK,and Nrf2 proteins decreased(all P＜0.05).Conclusion Acacetin may protect DC rats from oxidative stress injury by activating the Sirt1/AMPK/Nrf2 pathway.

Objective To investigate the effect of total flavone of Cydonia oblonga on oxidative damage of human lens epithelial cells induced by high glucose and its mechanism.Methods A cell injury model was established by inducing human lens epithelial cells with high glucose.Human lens epithelial cells were cultured in the medium containing 30 mmol·L-1 glucose for 24 h,which was recorded as the high glucose group.Cells in the control group were cultured in a medium con-tainning 5.5 mmol·L-1 glucose for 24 h.Human lens epithelial cells were inoculated into 96-well plates with 5 × 103 cells per well,and treated with mediums containing 10 mmol·L-1,20 mmol·L-1,and 40 mmol·L-1 total flavone of Cydonia ob-longa combined with 30 mmol·L-1 glucose for 24 h.They were recorded as high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblonga group,and high glucose+high total flavone of Cydonia oblonga group.Human lens epithelial cells were transfected with anti-miR-NC and anti-miR-370 with Lipo-fectamine2000 transfection reagent,and treated with 30 mmol·L-1 glucose for 24 h,which were recorded as high glucose+anti-miR-NC group and high glucose+anti-miR-370 group.Human lens epithelial cells were transfected with miR-NC and miR-370 mimics,and treated with medium containing 30 mmol·L-1 glucose and 40 mmol·L-1 total flavone of Cydonia oblonga for 24 h,which were labeled as high glucose+total flavone of Cydonia oblonga+miR-NC group and high glucose+total flavone of Cydonia oblonga+miR-370 group.The activities of superoxide dismutase(SOD)and cata-lase(CAT),and the content of malondialdehyde(MDA)were measured by Enzyme-linked immunosorbent assay;flow cy-tometry was applied to detect apoptosis rate;quantitative reverse transcription polymerase chain reaction was applied to detect the expression level of miR-370;Western blot was applied to detect the expression of apoptosis-related proteins.Results Compared with the control group,the activities of SOD and CAT decreased and the content of MDA increased in the human lens epithelial cells of the high glucose group,and the differences were statistically significant(all P＜0.05);compared with the high glucose group,the activities of SOD and CAT significantly increased and the content of MDA signifi-cantly decreased in the high glucose+low total flavone of Cydonia oblonga group,the high glucose+medium total fla-vone of Cydonia oblonga group and the high glucose+high total flavone of Cydonia oblonga group(all P＜0.05).Com-pared with the control group,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 of human lens epithelial cells in the high glucose group significantly increased(all P＜0.05);compared with the high glucose group,the apoptosis rate,Caspase-3 and Caspase-9 protein expressions of human lens epithelial cells in the high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblonga group,and high glucose+high total fla-vone of Cydonia oblonga group significantly decreased(all P＜0.05).The expression levels of miR-370 in human lens epi-thelial cells were 1.00±0.00,4.04±0.36,3.22±0.24,2.42±0.23 and 1.62±0.14 in the control group,high glucose group,high glucose+low total flavone of Cydonia oblonga group,high glucose+medium total flavone of Cydonia oblon-ga group,and high glucose+high total flavone of Cydonia oblonga group,respectively.There was a statistically different significance among the five groups(F=256.138,P＜0.05).Compared with the high glucose+anti-miR-NC group,the ex-pression of miR-370 significantly decreased,the activities of SOD and CAT significantly increased,and the content of MDA significantly decreased in human lens epithelial cells of the high glucose+anti-miR-370 group(all P＜0.001).Compared with the high glucose+anti-miR-NC group,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 of the hu-man lens epithelial cells in the high glucose+anti-miR-370 group significantly decreased(all P＜0.001).Compared with the high glucose+total flavone of Cydonia oblonga+miR-NC group,the activities of SOD and CAT significantly de-creased,and the content of MDA,apoptosis rate,and protein expressions of Caspase-3 and Caspase-9 significantly in-creased in the human lens epithelial cells of high glucose+total flavone of Cydonia oblonga+miR-370 group(all P＜0.001).Conclusion The expression of miR-370 increases in high glucose-induced human lens epithelial cells.Total fla-vone of Cydonia oblonga can inhibit the oxidative stress and apoptosis of high glucose-induced human lens epithelial cells,and the mechanism may be related to the decreased expression of miR-370.