Objective To investigate the clinical features of gynecological malignant tumor related multiple primary malignant neoplasms (MPMN).Methods Apply retrospective and comprehensive analysis to the clinical data of 30 patients with gynecological malignant tumor related MPMN.Results Synchronous MPMN were found in 9 patients.Their average age was 50.2 years old and their median age was 49 years old.The neoplasms were located at ovary,uterus,cervix,breast and intestine.Metachronous MPMN were found in 21 patients.Their average age was 57.7 and their median age was 57 years old.The median interval between the first and the second primary malignant neoplasm was 4.0 years.The neoplasms were located at breast,ovary,uterus,gastrointestinal tract,uterine cervix,lung etc.In 30 cases,26 of them were treated by surgical operation and further adjunctive treatment of chemotherapy and (or) radiotherapy was conducted as per the neoplasm staging and its pathological results.The rest 4 patients (first primary malignant neoplasms were excised from 3 of them and another one was not treated by surgical operation) received adjunctive treatment of chemotherapy and (or) radiotherapy.Followed ups,which varied from 6 to 60 months,were made to 29 patients and 20 out of the 29 were alive.5-year survival rate of patients with gynecological malignant tumor related MPMN was 47.8％,2-year survival rate was 73.9％,and 1-year survival rate was 88.6％.Conclusion Pay more attention to the patients with gynecological malignant tumor related MPMN,examine the high-risk patients with malignant tumor comprehensively,identify whether it is recurrence,metastasis or new growth of malignant neoplasm,and further ensure early diagnosis and proper treatment,avoiding misdiagnosis and missed diagnosis.

Objective:To investigate the effect of modified transanal approach in the repair of vesicorectal fistula after radical prostatectomy.Methods:From September 2011 to December 2019, 32 cases of vesicorectal fistula after radical prostatectomy were retrospectively analyzed. All patients underwent cystostomy before repair operation. The average diameter of the fistulas was 19 (3-40) mm. There was only one fistula in 24 cases and 8 cases with more than 2 fistulas. The operation was performed in the jack knife position, and the fistula was prepared by resection of the fistula through the anus with bipolar resectoscope. Then bladder wall and rectum wall were separated by the loop and sutured respectively. After operation, the patients were treated with antispasmodic and anti-infective treatment, and the catheter was retained. Cystography and cystoscopy were reexamined 3 months after operation. Catheter was removed in the successful cases, and the failure was repaired again.Results:All operations were completed successfully. The mean operation time was 67(55-125) min, and the median follow-up was 22 (6-30) months. Thirty-one cases (96.8%) were successfully repaired, of which 25 cases were successfully repaired at the first operation, and 6 cases were successfully repaired again (all by transanal route). One case failed to be repaired. He had received external pelvic radiotherapy before operation. After the failure of repair, cystoscopy showed large fistula and stiff surrounding tissue. Then bilateral ureteral skin stoma and cystectomy were performed.Conclusions:Modified transanal approach in the repair of vesicorectal fistula after radical prostatectomy is an effective method. This kind of operation has less trauma, fewer complications and can be operated repeatedly. It is suitable for patients with low position, small fistula and without radiotherapy.

Objective:To investigate the expression of PDLIM3 in the ectopic and orthotopic endometrium of endometriosis(EMT)patients,as well as in healthy endometrium,and to explore its relationship with clinical signifi-cance.Methods:Bioinformatics analysis based on the Gene Expression Omnibus(GEO)database was conduc-ted,and a prospective cohort study was undertaken,involving 58 EMT patients treated at West China Second Hospital of Sichuan University and 27 patients with other benign gynecological diseases as the control group from December 2019 to July 2020.Ectopic and orthotopic endometrium samples were obtained from EMT patients,and normal control samples were obtained from patients with other benign gynecological diseases.Real-time quantita-tive polymerase chain reaction(qPCR),western blot,and immunohistochemistry were utilized to investigate PD-LIM3 expression in various tissue samples.Clinical parameters were analyzed to determine the correlation be-tween PDLIM3 and clinical features.Results:Compared to orthotopic endometrial tissues of EMT patients and normal endometrial tissues of control subjects,the mRNA(F =46.05,P<0.05)and protein(F =238.6,P<0.05)expression levels of PDLIM3 in ectopic endometrial lesions were significantly upregulated.The average optical density(AOD)of PDLIM3 protein obtained through immunohistochemical experiments in ectopic endometrial le-sions showed a positive correlation with the degree of dysmenorrhea(r =0.86,P<0.05)and CA 125 level(r = 0.41,P<0.05)in EMT patients.But no obvious correlation was found between the expression level of PDLIM3 and disease stage,menstrual volume,and CA199 level(P>0.05).Conclusions:The expression level of PDLIM3 in endometriosis lesions was significantly upregulated and correlated with the degree of dysmenorrhea and serum CA125 level.These findings suggest that PDLIM3 may play a significant role in the development and progression of endometriosis and could serve as a potential therapeutic target.

Objective:To explore the establishment and application of ovarian cancer organoids.Methods:Fresh ovarian tumor tissues, obtaining from patients underwent surgery in the First Affiliated Hospital of Nanjing Medical University between October 2021 and March 2022, were collected, enzymatic degraded, digested, and embedded into matrigel to establish organoids. A total of 32 ovarian cancer samples were collected. Hematoxylin eosin (HE) staining and immunofluorescence (IF) procedure were used to verify the morphological structure of organoids and their expression of molecular markers. 3D cyto-live or dead assay was used to detecte the live or dead cells in organoids. Carboplatin with a concentration ranging from 5 to 80 μmol/L (5, 10, 20, 40, 80 μmol/L) was added to organoids to calculate the 50% inhibitory concentration (IC 50) in different organoids. Results:(1) Organoids from a total of 32 patients were established, of which 18 cases could be passaged stably in the long term in vitro, while 14 could be passaged in the short time. The average amplification time of long-term passage in vitro was over 3 months, and the longest reached 9 months. (2) In HE staining, significant nuclei atypia and local micropapillary structures were observed in organoids. IF staining revealed that ovarian cancer organoids expressed molecular markers similar to primary tumor tissues, such as Pan cytokeratin (Pan-CK), p53, paired box gene 8 (PAX8), and Wilms tumor gene 1 (WT1). (3) In 3D cyto-live or dead assay, a large number of apoptotic cells were observed inside and around the organoids after added carboplatin. The sensitivity to carboplatin varied in 18 organoids could amplify in the long term, with an average IC 50 of (29.5±15.8) μmol/L. Moreover, IC 50 values of 4 organoids derived from patients received neoadjuvant chemotherapy were much higher than the 14 organoids which did not received neoadjuvant chemotherapy [(48.7±11.3) μmol/L vs (24.0±12.1) μmol/L; t=3.429, P=0.022]. Conclusions:Organoids recapitulate ovarian cancers in vitro and could be stably passaged. Organoids derived from patients received neoadjuvant chemotherapy have higher resistance to carboplatin.

Objective:To investigate the feasibility,safety and effectiveness of robot-assisted laparo-scopic buccal mucosa graft ureteroplasty in the treatment of complex long proximal ureteral stricture.Methods:The clinical data of 20 patients with proximal ureteral stricture undergoing robot-assisted lapa-roscopic buccal mucosa graft ureteroplasty admitted to the Department of Urology,Peking University First Hospital and Beijing Jiangong Hospital from July 2022 to January 2023 were prospectively collected and analyzed.Intraoperative conditions,postoperative complications and follow-up data were also recorded and analyzed.Results:The operations under robot-assisted laparoscopy were performed successfully in all the 20 patients without conversion to traditional laparoscopic surgery or open surgery.The study in-cluded 14 males and 6 females with a mean age of(41±11)years(range:19 to 60 years)and a mean body mass index of(24.3±3.6)kg/m2(range:18.2 to 31.8 kg/m2).There were 9 cases on the left side and 11 cases on the right side.The strictures of all the patients were located in the proximal segment of the ureter(including the ureteropelvic junction).The mean preoperative serum creatinine was(92.2±23.3)μmol/L(range:49.2 to 138.9 μmol/L),and the mean length of ureteral stricture was(2.8±0.9)cm(range:1.0 to 4.0 cm).Ten patients had previously undergone unsuccessful reconstructive surgery.During the operation,12 patients received posteriorly augmented anastomosis with ventral onlay.The mean length of the buccal mucosa graft harvested during the operation was(3.1±0.6)cm(range:2.0 to 4.3 cm),and the median width was 1.5 cm(range:1.0 to 2.0 cm).The omentum flap was used to wrap the reconstructed ureteral segment in all the 20 cases.The median operative time was 154 min(range:113 to 300 min),and the median estimated blood loss was 45 mL(range:0 to 100 mL).The median postoperative hospital stay was 4 d(range:4 to 14 d).The mean postoperative follow-up time was(15.0±1.7)months(range:12.5 to 17.9 months),and the surgical success rate was 100.0％in this study.After surgery,11 patients reported mild discomfort at the oral donor site,2 patients deve-loped urinary tract infection,and no postoperative complications were reported in the other 7 patients.The mean serum creatinine was(90.9±23.9)μmol/L(range:60.0 to 153.0 μmol/L)six months after surgery.Conclusion:Robot-assisted laparoscopic buccal mucosa graft ureteroplasty for the treatment of complex long proximal ureteral stricture has satisfactory efficacy without severe complications,which has shown good feasibility,safety and effectiveness.However,large sample studies and long-term follow-up are still needed to evaluate its long-term efficacy.

Objective: To investigate the effect of diabetes on the risk of stroke recurrence within 1 year after onset of ischemic stroke. Methods: Patients with ischemic stroke admitted to the Department of Neurology, the Second Hospital of Hebei Medical University from October 2016 to August 2017 were enrolled prospectively. Their baseline clinical data were collected and they were followed up for one year. The risk factors for ischemic stroke in recurrence group and non-recurrence group were compared. Cox proportional hazard regression model was used to determine the independent risk factors for ischemic stroke recurrence. Kaplan-Meier survival analysis was used to explore the impact of risk factors on the risk of stroke recurrence. Results: A total of 1 436 patients with ischemic stroke were included. During the follow-up of 1 year, a total of 183 patients had recurrence (12.74%). There were significant differences in the proportion of patients with diabetes, atrial fibrillation, hyperhomocysteinemia, oral antiplatelet drugs, and statins after discharge, and baseline fasting blood glucose level between the recurrence and the non-recurrence group (all P<0.05). Multivariate Cox proportional hazards analysis showed that diabetes mellitus (hazard ratio [HR] 1.574, 95% confidence interval [CI] 1.161-2.134; P=0.003) was an independent risk factor for stroke recurrence. Taking statins (HR 0.686, 95% CI 0.481-0.979; P=0.038) and antiplatelet agents (HR 0.678, 95% CI 0.467-0.983; P=0.041) after discharge were the independent protective factors for ischemic stroke recurrence. Kaplan-Meier survival analysis showed that the recurrence rate of ischemic stroke in patients with diabetes was significantly higher than that in those without diabetes (log-rank test, P=0.003). The recurrence rate of stroke in patients taking statins and antiplatelet drugs was significantly lower than that in patients who did not take the corresponding drugs (log-rank test, all P<0.001). Conclusions Diabetes is an independent risk factor for ischemic stroke recurrence, and taking statins and antiplatelet drugs are the independent protective factors for ischemic stroke recurrence.

With the widespread application of genomics and transcriptomics in the genetics and cell biology of different species, synonymous codon usage bias has been gradually accepted and used to study the deep connection between biological evolution and biological phenotypes. It is an important part of the life activities that mRNA is expressed into proteins with normal biological activities. The synonymous codon usage patterns, which were named as 'the second genetic codon', can express genetic information carried by themselves at the levels of transcriptional regulations, translational regulations and metabolic activities through molecular mechanisms such as fine-tune translation selection. Some studies have shown that the length of mRNA half-life has significant impacts on mRNA activity and the process of transcription and translation. This review summarized the roles of synonymous codon usage patterns in transcription, translational regulation and post-translational modification, with the aim to better understand how organisms skillfully utilize the genetic effects caused by codon usage patterns to accurately synthesize different types of proteins, so as to ensure the growth or differentiation of the specific gene expression procedures to carry out smoothly and maintain the normal life cycle.
Codon/genetics* ; Codon Usage ; Half-Life ; Protein Processing, Post-Translational ; RNA, Messenger/genetics*

BACKGROUND: Epilepsy accounts for a significant portion of the global disease burden. However, little is known about the disease burden of epilepsy in China and its provinces. METHODS: We assessed the burden of epilepsy in China and its provinces, municipalities, and autonomous regions from 1990 to 2019. Burden was measured as incidence, prevalence, deaths, years lived with disability, years of life lost, and disability-adjusted life years (DALYs), by age, sex, year, and province. We used the Socio-Demographic Index (SDI) to determine the association between the provincial development level and age-standardized DALY rates of epilepsy from 1990 to 2019. RESULTS: In 2019, epilepsy caused 1367.51 thousand (95% uncertainty interval [UI]: 979.92-1837.61 thousand) DALYs, and the age-standardized DALY rate was 99.77 (95% UI: 71.33-133.52)/100,000. The age-standardized incidence and prevalence rates for epilepsy in China were 24.65/100,000 and 219.69/100,000, increased by 45.00% (95% UI: 8.03-98.74%) and 35.72% (95% UI: 0.47-86.19%) compared with that in 1990, respectively. From 1990 to 2019, the proportion of DALY caused by epilepsy in the age group under 25 years steadily decreased. The proportion of DALYs caused by epilepsy in people aged 50 years and over increased from 9.45% and 10.22% in 1990 to 29.01% and 32.72% for male and female individuals in 2019, respectively. The highest age-standardized mortality rates were seen in Tibet (4.26 [95% UI: 1.43-5.66]/100,000), Qinghai (1.80 [95% UI: 1.15-2.36]/100,000), and Yunnan (1.30 [95% UI: 0.88-1.62]/100,000), and the lowest mortality rates were in Guangdong (0.48 [95% UI: 0.39-0.64]/100,000), Zhejiang (0.56 [95% UI: 0.44-0.70]/100,000), and Shanghai (0.57 [95% UI: 0.41-0.73]/100,000). The age-standardized DALY rates across the country and in provinces, municipalities, and autonomous regions generally decreased as their SDI increased. CONCLUSIONS The disease burden of epilepsy is still heavy in China, especially in the western provinces. The incidence and prevalence of epilepsy increased between 1990 and 2019, and the burden of epilepsy in the elderly increases gradually. This study provides evidence on epilepsy prevention and care of different regions in China.
Aged ; Humans ; Male ; Female ; Middle Aged ; Adult ; Global Burden of Disease ; China/epidemiology* ; Quality-Adjusted Life Years ; Cost of Illness ; Epilepsy/epidemiology* ; Prevalence

Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

Natural killer (NK) cells are an important part of the body's innate immune system. As the first line of defense against pathogens, they need to be transformed into a mature state under the control of various cell signaling molecules and transcription factors to play cytotoxic and immune regulatory roles. Under the interaction of activated receptors and inhibitory receptors, NK cells are activated to perform a direct cell killing effect by secreting perforin and granzyme, or indirectly eliminate pathogenic microorganisms in the body by secreting various cytokines, such as type I and type II interferons. These functions of NK cells play a very important role in antiviral and anti-autoimmune diseases, especially in anti-tumor.
Humans ; Killer Cells, Natural ; Interferon-gamma ; Apoptosis ; Autoimmune Diseases ; Cytokines