Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

Objectives:To preliminarily investigate the safety and efficacy of same-day discharge(SDD)following radiofrequency catheter ablation for arrhythmia.Methods:A total of 50 consecutive patients who underwent radiofrequency catheter ablation for arrhythmia in the SDD strategy at Fuwai Hospital from 8 July 2024 to 18 September 2024 were included in this analysis.The study evaluated the immediate success rate of the ablation,the rate of all-cause and arrhythmia-related readmission,outpatient or emergency visits and incidence of complications within 30 days post ablation,and recurrence rate of arrhythmias over a 3-month follow-up period.Results:The average age of the 50 patients was(47.2±16.1)years old,32 patients(64.0%)were male.Radiofrequency catheter ablation was performed in 47 patients(94.0%),including 18(36.0%)atrial fibrillation(AF)ablation.Three patients(6.0%)underwent electrophysiological study only.The immediate success rate for ablation patients was 100%(47/47).None of the patients developed vascular puncture-related or ablation-related complications.The average hospital stay and postoperative observation time were(6.84±1.13)hours and(3.40±1.12)hours,respectively.The all-cause and arrhythmia-related readmission,outpatient or emergency visits rates within 30 days were 12.0%(6/50)and 2.0%(1/50),respectively.Two patients(4.0%)post ablation experienced AF recurrence during the 3-months follow-up period.Conclusions:Radiofrequency catheter ablation for arrhythmias in SDD strategy is safe,effective,and feasible.

Objectives:To preliminarily investigate the safety and efficacy of same-day discharge(SDD)following radiofrequency catheter ablation for arrhythmia.Methods:A total of 50 consecutive patients who underwent radiofrequency catheter ablation for arrhythmia in the SDD strategy at Fuwai Hospital from 8 July 2024 to 18 September 2024 were included in this analysis.The study evaluated the immediate success rate of the ablation,the rate of all-cause and arrhythmia-related readmission,outpatient or emergency visits and incidence of complications within 30 days post ablation,and recurrence rate of arrhythmias over a 3-month follow-up period.Results:The average age of the 50 patients was(47.2±16.1)years old,32 patients(64.0%)were male.Radiofrequency catheter ablation was performed in 47 patients(94.0%),including 18(36.0%)atrial fibrillation(AF)ablation.Three patients(6.0%)underwent electrophysiological study only.The immediate success rate for ablation patients was 100%(47/47).None of the patients developed vascular puncture-related or ablation-related complications.The average hospital stay and postoperative observation time were(6.84±1.13)hours and(3.40±1.12)hours,respectively.The all-cause and arrhythmia-related readmission,outpatient or emergency visits rates within 30 days were 12.0%(6/50)and 2.0%(1/50),respectively.Two patients(4.0%)post ablation experienced AF recurrence during the 3-months follow-up period.Conclusions:Radiofrequency catheter ablation for arrhythmias in SDD strategy is safe,effective,and feasible.

Objective:Surgical site infection (SSI) can markedly prolong postoperative hospital stay, aggravate the burden on patients and society, even endanger the life of patients. This study aims to investigate the national incidence of SSI following abdominal surgery and to analyze the related risk factors in order to provide reference for the control and prevention of SSI following abdominal surgery.Methods:A multicenter cross-sectional study was conducted. Clinical data of all the adult patients undergoing abdominal surgery in 68 hospitals across the country from June 1 to 30, 2020 were collected, including demographic characteristics, clinical parameters during the perioperative period, and the results of microbial culture of infected incisions. The primary outcome was the incidence of SSI within postoperative 30 days, and the secondary outcomes were ICU stay, postoperative hospital stay, cost of hospitalization and the mortality within postoperative 30-day. Multivariable logistic regression was used to analyze risk factors of SSI after abdominal surgery.Results:A total of 5560 patients undergoing abdominal surgery were included, and 163 cases (2.9%) developed SSI after surgery, including 98 cases (60.1%) with organ/space infections, 19 cases (11.7%) with deep incisional infections, and 46 cases (28.2%) with superficial incisional infections. The results from microbial culture showed that Escherichia coli was the main pathogen of SSI. Multivariate analysis revealed hypertension (OR=1.792, 95% CI: 1.194-2.687, P=0.005), small intestine as surgical site (OR=6.911, 95% CI: 1.846-25.878, P=0.004), surgical duration (OR=1.002, 95% CI: 1.001-1.003, P<0.001), and surgical incision grade (contaminated incision: OR=3.212, 95% CI: 1.495-6.903, P=0.003; Infection incision: OR=11.562, 95%CI: 3.777-35.391, P<0.001) were risk factors for SSI, while laparoscopic or robotic surgery (OR=0.564, 95%CI: 0.376-0.846, P=0.006) and increased preoperative albumin level (OR=0.920, 95%CI: 0.888-0.952, P<0.001) were protective factors for SSI. In addition, as compared to non-SSI patients, the SSI patients had significantly higher rate of ICU stay [26.4% (43/163) vs. 9.5% (514/5397), χ 2=54.999, P<0.001] and mortality within postoperative 30-day [1.84% (3/163) vs.0.01% (5/5397), χ 2=33.642, P<0.001], longer ICU stay (median: 0 vs. 0, U=518 414, P<0.001), postoperative hospital stay (median: 17 days vs. 7 days, U=656 386, P<0.001), and total duration of hospitalization (median: 25 days vs. 12 days, U=648 129, P<0.001), and higher hospitalization costs (median: 71 000 yuan vs. 39 000 yuan, U=557 966, P<0.001). Conclusions:The incidence of SSI after abdominal surgery is 2.9%. In order to reduce the incidence of postoperative SSI, hypoproteinemia should be corrected before surgery, laparoscopic or robotic surgery should be selected when feasible, and the operating time should be minimized. More attentions should be paid and nursing should be strengthened for those patients with hypertension, small bowel surgery and seriously contaminated incision during the perioperative period.

Objective:Surgical site infection (SSI) can markedly prolong postoperative hospital stay, aggravate the burden on patients and society, even endanger the life of patients. This study aims to investigate the national incidence of SSI following abdominal surgery and to analyze the related risk factors in order to provide reference for the control and prevention of SSI following abdominal surgery.Methods:A multicenter cross-sectional study was conducted. Clinical data of all the adult patients undergoing abdominal surgery in 68 hospitals across the country from June 1 to 30, 2020 were collected, including demographic characteristics, clinical parameters during the perioperative period, and the results of microbial culture of infected incisions. The primary outcome was the incidence of SSI within postoperative 30 days, and the secondary outcomes were ICU stay, postoperative hospital stay, cost of hospitalization and the mortality within postoperative 30-day. Multivariable logistic regression was used to analyze risk factors of SSI after abdominal surgery.Results:A total of 5560 patients undergoing abdominal surgery were included, and 163 cases (2.9%) developed SSI after surgery, including 98 cases (60.1%) with organ/space infections, 19 cases (11.7%) with deep incisional infections, and 46 cases (28.2%) with superficial incisional infections. The results from microbial culture showed that Escherichia coli was the main pathogen of SSI. Multivariate analysis revealed hypertension (OR=1.792, 95% CI: 1.194-2.687, P=0.005), small intestine as surgical site (OR=6.911, 95% CI: 1.846-25.878, P=0.004), surgical duration (OR=1.002, 95% CI: 1.001-1.003, P<0.001), and surgical incision grade (contaminated incision: OR=3.212, 95% CI: 1.495-6.903, P=0.003; Infection incision: OR=11.562, 95%CI: 3.777-35.391, P<0.001) were risk factors for SSI, while laparoscopic or robotic surgery (OR=0.564, 95%CI: 0.376-0.846, P=0.006) and increased preoperative albumin level (OR=0.920, 95%CI: 0.888-0.952, P<0.001) were protective factors for SSI. In addition, as compared to non-SSI patients, the SSI patients had significantly higher rate of ICU stay [26.4% (43/163) vs. 9.5% (514/5397), χ 2=54.999, P<0.001] and mortality within postoperative 30-day [1.84% (3/163) vs.0.01% (5/5397), χ 2=33.642, P<0.001], longer ICU stay (median: 0 vs. 0, U=518 414, P<0.001), postoperative hospital stay (median: 17 days vs. 7 days, U=656 386, P<0.001), and total duration of hospitalization (median: 25 days vs. 12 days, U=648 129, P<0.001), and higher hospitalization costs (median: 71 000 yuan vs. 39 000 yuan, U=557 966, P<0.001). Conclusions:The incidence of SSI after abdominal surgery is 2.9%. In order to reduce the incidence of postoperative SSI, hypoproteinemia should be corrected before surgery, laparoscopic or robotic surgery should be selected when feasible, and the operating time should be minimized. More attentions should be paid and nursing should be strengthened for those patients with hypertension, small bowel surgery and seriously contaminated incision during the perioperative period.

Objective: To explore the effect and possible mechanisms of has-miR-150-5p targeting HIF1α to regulate malignant biological behaviors of glioblastoma (GBM) U-251MG cells. Methods: Real-time quantitative PCR (RT-PCR) was used to detect the expression of miR-150-5p and hypoxia inducible factor 1 (HIF1α) in U-251MG cells. Luciferase report assay was carried out to verify the biological relationship between miR-150-5p and HIF1α and their biological functions in U-251MG cells. The protein expressions of miR150-5pand HIF1α in U-251MG cells were detected by western blotting. The ability of cell migration was detected by wound healing test and cell invasion ability was detected by transwell test. Results: After miR-150-5p mimic transfection, the mRNA expression of HIF1α was significantly reduced in U-251MG cells (P<0.01). Bioinformatics prediction and luciferase reporter assay demonstrated that miR-150-5p down-regulated HIF1α through directly binding to HIF1α 3’-untranslated region (3’-UTR) (all P<0.05). In U-251MG cells, miR-150-5p over-expression significantly inhibited HIF1α expression, cell invasion and migration (all P<0.05). Conclusion: miR150-5p inhibits cell invasion and metastasis through negative regulation of HIF1α, indicating that miR-150-5p and HIF1α were both potential therapeutic targets for glioblastoma.

Objective To investigate the effect of 3S jejunal interposition anastomosis in digestive tract reconstruction after radical resection for early gastroesophageal junction adenocarcinoma. Methods One hundred and eighteen patients of early gastroesophageal junction adenocarcinoma who were planned to receive radical proximal gastrectomy from February 2011 to August 2015 were prospectively enrolled and randomly divided into two groups by table of random number, including observation group (3S jejunal interposition) and control group (esophageal remnant gastric posterior wall anastomosis), with 59 patients in each group. Postoperative complications, operative time, nutritional parameters and postoperative quality of life were compared between two groups. Results The operation time in observation group was (152.3 ± 13.1) min, in control group was (146.0 ± 12.5) min, and there was no significant difference (P>0.05). The rate of complication in observation group was 8.5%(5/59), in control group was 13.6%(8/59), and there was no significant difference (P>0.05). The levels of total protein, albumin, hemoglobin, and Vitamin B126, 12, and 18 months after operation in observation group were significantly higher than those in control group (P<0.05). The rate of reflux esophagitis 6, 12 and 18 months after operation in observation group was significantly lower than that in control group (P<0.05). The gastric emptying time 6, 12 and 18 months after operation in observation group was significantly prolonged, compared with that in control group (P<0.05). The scores of whole quality of life, emotional function, body function, pain, tired, appetite, nausea and vomiting, diarrhea and constipation 6 and 18 months after operation in observation group were significantly better than those in control group (P<0.05). Conclusions The 3S jejunal interposition anastomosis in digestive tract reconstruction after radical resection for early gastroesophageal junction adenocarcinoma is a better method. The effect of antirelux is better and can improve the nutriture and quality of live for long time.

Type 1 diabetes mellitus (T1D) is an immune-mediated disease. The autoreactive T cells in T1D patients attack and destroy their own pancreatic cells. In order to systematically investigate the potential autoreactive T cell receptors (TCRs), we used a high-throughput immune repertoire sequencing technique to profile the spectrum of TCRs in individual T1D patients and controls. We sequenced the T cell repertoire of nine T1D patients, four type 2 diabetes (T2D) patients and six nondiabetic controls. The diversity of the T cell repertoire in T1D patients was significantly decreased in comparison with T2D patients (P = 7.0E
08 for CD4+ T cells, P = 1.4E
04 for CD8+ T cells) and nondiabetic controls (P = 2.7E
09 for CD4+ T cells, P = 7.6E
06 for CD8+ T cells). Moreover, T1D patients had significantly more highly-expanded T cell clones than T2D patients (P = 5.2E
06 for CD4+ T cells, P = 1.9E
07 for CD8+ T cells) and nondiabetic controls (P =1.7E
07 for CD4+ T cells, P= 3.3E
03 for CD8+ T cells). Furthermore, we identified a group of highly-expanded T cell receptor clones that are shared by more than two T1D patients. Although further validation in larger cohorts is needed, our data suggest that T cell receptor diversity measurements may become a valuable tool in investigating diabetes, such as using the diversity as an index to distinguish different types of diabetes.

Objective To investigate the clinical and pathological features of anorectal malignant melanoma ( AMM) .Methods The clinical pathological and follow-up data of 7 cases of anorectal malignant melanoma were collected.The clinical and histopathological features and immunophenotype were analyzed .Results Among the 7 cases, 5 cases were female, 2 cases were male, aged 50-68 years, the average was 61 years.The tumors located in the lower rectum in 1 cases, 2 cases of teeth near the line , 4 cases of anal anus .The structure and morphology of the cancer cells were diverse .The organizational structures were mainly diffuse , focal and acinar .The cellular morphologies were mainly epithelioid , spindle and lymphocyte like .And the results of IHC showed the expression of the following three markers, vimentin, S-100 and HMB45, were strongly positive in cancer cells.However, the expression of CK , EMA and LCA were negative .And 2 cases of CEA expression were positive , LI Ki-67 was 20%-50%.Conclusions Anorectal malignant melanoma is one kind of rare malignant tumor and its characteristic morphology , immunophenotype could be helpful for diagnosis and differential diagnosis .