[Vaccine development based on RNA technology platforms].

mRNA vaccine technology has made significant progress in recent years, especially with the large-scale application driven by the COVID-19 pandemic. Moderna and Pfizer/BioNTech vaccines have become central tools in the global fight against the virus, demonstrating the potential of the mRNA platform for rapid design, production, and strong immune responses. These vaccines showcase the unique advantages of rapid response and effective protection. At the same time, mRNA technology still faces challenges, such as stability and targeted delivery. Future research will focus on improving the stability and safety of mRNA vaccine and expanding its application to more infectious diseases and cancer treatments. This article reviews platforms of mRNA vaccine, vaccine design, development of delivery system, and the application of mRNA vaccines, in order to enhance the understanding of professionals and accelerate the layout of this technology in vaccine research and application in China.

Discovery of differentially expressed proteins for CAR-T therapy of ovarian cancers with a bioinformatics analysis.

Target antigens are crucial for developing chimeric antigen receptor (CAR)-T cells, but their application to ovarian cancers is limited. This study aimed to identify potential genes as CAR-T-cell antigen candidates for ovarian cancers. A differential gene expression analysis was performed on ovarian cancer samples from four datasets obtained from the GEO datasets. Functional annotation, pathway analysis, protein localization, and gene expression analysis were conducted using various datasets and tools. An oncogenicity analysis and network analysis were also performed. In total, 153 differentially expressed genes were identified in ovarian cancer samples, with 60 differentially expressed genes expressing plasma membrane proteins suitable for CAR-T-cell antigens. Among them, 21 plasma membrane proteins were predicted to be oncogenes in ovarian cancers, with nine proteins playing crucial roles in the network. Key genes identified in the oncogenic pathways of ovarian cancers included MUC1, CXCR4, EPCAM, RACGAP1, UBE2C, PRAME, SORT1, JUP, and CLDN3, suggesting them as recommended antigens for CAR-T-cell therapy for ovarian cancers. This study sheds light on potential targets for immunotherapy in ovarian cancers.

[Mid-term efficacy evaluation of ABO incompatible living relative kidney transplantation based on protocol biopsy].

Objective: To evaluate the mid-term efficacy of ABO incompatible living donor kidney transplantation (ABOi-KT) based on the results of routine renal biopsy for transplantation. Methods: Retrospective collection of clinical data from 23 pairs of ABOi-KT donors and recipients at the First Affiliated Hospital of Sun Yat-sen University from July 2015 to November 2021. ABOi-KT was performed on recipients after desensitization treatment, and the results of routine kidney transplant biopsy at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were analyzed. Combined with blood type antibody levels and renal function recovery, the mid-term efficacy of ABOi-KT was evaluated. Results: Among the 23 recipients, there were 19 males and 4 females; age range from 19 to 47 years old [(29.6±6.7) years old], all underwent ABOi-KT successfully after receiving desensitization treatment. The follow-up time was (44.6±22.4) months, of which 22 cases were followed up for more than 1 year. The incidence rates of rejection reactions at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were 15.0% (3/20), 11.1% (1/9), 7.7% (1/13), 25.0% (3/12), and 12.5% (1/8), respectively. For receptors with rejection reactions, targeted anti-rejection therapy was performed based on clinical symptoms and various indicators. Borderline T cell mediated rejection (TCMR) can be converted to mild tubular inflammation after anti-rejection treatment. The positive rate of complement C4d in peritubular capillaries was 95.0% (19/20) one week after surgery, and the positive rate of complement C4d was 100% at 3 and 12 months after surgery. The cumulative survival rates at 1, 3, 5, and 7 years after surgery were all 100%. The cumulative survival rates at 1, 3, 5, and 7 years after kidney transplantation were 100%, 93.3%, 84.0%, and 84.0%, respectively. Except for 2 recipients who underwent transplantation in 2017 and experienced kidney failure at 30 and 49 months after surgery, all other transplanted kidneys survived. Conclusions: The results of routine renal transplant biopsy show that ABOi-KT has a good mid-term therapeutic effect. The pathological changes of ABOi-KT can be dynamically observed through routine renal transplant biopsy and targeted treatment for rejection reactions can be provided accordingly.

[Pelvic exenteration for late complications of radiation-induced pelvic injury: a preliminary study].

Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.

[Analysis of the serum bile acid profile to facilitate diagnosis and differential diagnosis of NA(+)-taurocholate cotransporting polypeptide deficiency].

Objective: This study focuses on Na(+)-taurocholate cotransporting polypeptide (NTCP) deficiency to analyze and investigate the value of the serum bile acid profile for facilitating the diagnosis and differential diagnosis. Methods: Clinical data of 66 patients with cholestatic liver diseases (CLDs) diagnosed and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University from early April 2015 to the end of December 2021 were collected, including 32 cases of NTCP deficiency (16 adults and 16 children), 16 cases of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), 8 cases of Alagille syndrome, and 10 cases of biliary atresia. At the same time, adult and pediatric healthy control groups (15 cases each) were established. The serum bile acid components of the study subjects were qualitatively and quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. The data were plotted and compared using statistical SPSS 19.0 and GraphPad Prism 5.0 software. The clinical and bile acid profiles of children with NTCP deficiency and corresponding healthy controls, as well as differences between NTCP deficiency and other CLDs, were compared using statistical methods such as t-tests, Wilcoxon rank sum tests, and Kruskal-Wallis H tests. Results: Compared with the healthy control, the levels of total conjugated bile acids, total primary bile acids, total secondary bile acids, glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were increased in NTCP deficiency patients (P < 0.05). Compared with adults with NTCP deficiency, the levels of total conjugated bile acids and total primary bile acids were significantly increased in children with NTCP deficiency (P < 0.05). The serum levels of taurochenodeoxycholic acid, glycolithocholate, taurohyocholate, and tauro-α-muricholic acid were significantly increased in children with NTCP deficiency, but the bile acid levels such as glycodeoxycholic acid, glycolithocholate, and lithocholic acid were decreased (P < 0.05). The serum levels of secondary bile acids such as lithocholic acid, deoxycholic acid, and hyodeoxycholic acid were significantly higher in children with NTCP deficiency than those in other CLD groups such as NICCD, Alagille syndrome, and biliary atresia (P < 0.05). Total primary bile acids/total secondary bile acids, total conjugated bile acids/total unconjugated bile acids, taurocholic acid, serum taurodeoxycholic acid, and glycodeoxycholic acid effectively distinguished children with NTCP deficiency from other non-NTCP deficiency CLDs. Conclusion: This study confirms that serum bile acid profile analysis has an important reference value for facilitating the diagnosis and differential diagnosis of NTCP deficiency. Furthermore, it deepens the scientific understanding of the changing characteristics of serum bile acid profiles in patients with CLDs such as NTCP deficiency, provides a metabolomic basis for in-depth understanding of its pathogenesis, and provides clues and ideas for subsequent in-depth research.

MRI-based radiomics analysis of bladder cancer: prediction of pathological grade and histological variant.

AIM: To develop magnetic resonance imaging (MRI)-based radiomics models for the prediction of the pathological grade and histological variant of bladder cancer. MATERIALS AND METHODS: A total of 227 patients who underwent bladder MRI and had histopathologically confirmed grades and variants were included retrospectively from January 2017 to March 2022. They were assigned to a training set (n=131) and a testing set (n=96) based on the MRI system. MRI-based radiomics features were extracted from manually segmented volumes of interest from high-b-value DWI images and ADC maps. The radiomics models were trained with all possible pipelines in the training set. One optimal model was selected using the fivefold cross-validation method and verified by the testing set according to the pathological results. Univariate and multivariate analyses were performed to identify the significant clinical and imaging factors for developing clinical-radiomics models. RESULTS: The radiomics model for grade prediction had area under the curve (AUC) values of 0.784, 0.786, and 0.733 in the training, cross-validation, and testing sets, respectively. The radiomics model for variant prediction had AUC values of 0.748, 0.757, and 0.789 in the training, cross-validation, and testing sets, respectively. The performance of the clinical-radiomics model was significantly improved compared with the radiomics models alone for the total dataset (AUC for grade: 0.846 versus 0.756; AUC for variant: 0.810 versus 0.757, p<0.05). CONCLUSION: MRI-based radiomics models could be used to predict the pathological grade and histological variants of bladder cancer with relatively good performance.

[Efficacy of arteriovenous argatroban versus heparin flush anticoagulation after cardiovascular surgery].

Objective: To compare the effects of arteriovenous argatroban and heparin flushes on platelet count and assess the occurrence of heparin-induced thrombocytopenia (HIT) and other complications in patients undergoing cardiovascular surgeries. Methods: A single-center, prospective randomized control study was conducted. Patients who underwent cardiovascular surgery at Fuwai Hospital, Chinese Academy of Medical Sciences from March to December 2019 were randomly divided into the argatroban group (250 ml normal saline plus 2.5 mg of argatroban) and the heparin group (250 ml normal saline plus 10 mg of heparin). Platelet count, hemorrhage, and thrombosis were assessed. The 4T scores of HIT, the incidences of HIT and other complications were also evaluated. Results: A total of 491 patients (307 males and 184 females) were included in the study, with a mean age of (52.3±13.7) years. There were 245 cases in the argatroban group and 246 cases in the heparin group, respectively. There was no statistically significant difference in the preoperative platelet count between the argatroban and heparin groups [198.0 (161.0, 248.0)×109/L vs 194.0 (157.2, 243.8)×109/L, P=0.498]. Likewise, there were no statistically significant differences in the platelet count between the argatroban and heparin groups at 12 h, 1 day, and 5 days after operation [127.0 (100.0, 154.0)×109/L vs 121.5 (90.2, 149.0)×109/L, 126.0 (97.0, 162.0)×109/L vs 123.5 (88.0, 151.0)×109/L, 168.0 (130.0, 215.0) ×109/L vs 161.0 (101.0, 210.5)×109/L] (repeated measures ANOVA between groups: F=3.327, P=0.069; time comparison: F=532.523, P<0.001; time interaction between groups: F=0.675, P=0.512). The proportion of 4T scores of medium and high scores (≥4)[9.8% (24/245) vs 10.6% (26/246), P=0.777] and incidence of HIT antibody positive [1.63% (4/245) vs 1.63% (4/246), P=0.726] were similar between argatroban group and the heparin group. Mechanical ventilation time was shorter in the argatroban group than that in the heparin group [13.0 (11.0, 21.0) vs 15.5 (12.0, 21.0) h, P=0.020]. Conclusion: Compared with heparin, routine management with argatroban for arteriovenous flush in patients undergoing cardiovascular surgery does not affect the HIT incidence.

[Comparison of intraoperative neurophysiological monitoring between patients with arthrogryposis multiplex congenita and adolescent idiopathic scoliosis].

Objective: To compare the intraoperative neurophysiological monitoring (IONM) results between patients with arthrogryposis multiplex congenita (AMC) and adolescent idiopathic scoliosis (AIS) and to analyze the influence of congenital spinal deformity on IONM in AMC patients, thus to evaluate the efficiency of IONM in AMC patients. Methods: A cross-sectional study. The clinical data of 19 AMC patients underwent correction surgery from July 2013 to January 2022 in Nanjing Drum Tower Hospital were retrospectively reviewed. There were 13 males and 6 females with a mean age of (15.2±5.6) years, and the average Cobb angle of main curve was 60.8°±27.7°. And 57 female AIS patients of similar age and curve type with the AMC patients during the same period were selected as the control group, with an average age of (14.6±4.4) years and a mean Cobb angle of 55.2°±14.2°. The latency and amplitude of samatosensory evoked potentials (SSEPs) and transcranial electric motor evoked potentials (TCeMEPs) were compared between the two groups. The difference in IONM data between AMC patients with and without congenital spinal deformity was also evaluated. Results: The success rates of SSEPs and TCeMEPs were 100% and 14/19 for AMC patients, 100% and 100% for AIS patients. The SSEPs-P40 latency, SSEPs-N50 latency, SSEPs-amplitude, TCeMEPs-latency, TCeMEPs-amplitude showed no significant difference between AMC patients and AIS patients (P>0.05 for all). The side-difference of TCeMEPs-amplitude showed an increasing trend in AMC patients when compared with that in AIS patients, but there was no statistical difference between the two groups [(147.0±185.6) µV vs (68.1±311.4) µV, P=0.198]. The SSEPs-amplitude value was (1.4±1.1) µV on concave side in AMC patients with congenital spinal deformity, and it was (2.6±1.2) µV on concave side in AMC patients without congenital spinal deformity (P=0.041). The SSEPs-amplitude value was (1.4±0.8) µV on convex side in AMC patients with congenital spinal deformity, and it was (2.6±1.3) µV on convex side in AMC patients without congenital spinal deformity (P=0.028). Conclusions: The values of SSEPs-P40 latency, SSEPs-N50 latency, SSEPs-amplitude, TCeMEPs-latency and TCeMEPs-amplitude are similar in AMC and AIS patients. The SSEPs-amplitude of AMC patients with congenital spinal deformity is lower than that of AMC patients without congenital spinal deformity.

[A preliminary report of laparoscopic extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis to prevent parastomal hernia].

Objective: To examine the preliminary effect of laparoscopic extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis for the prevention of parastomal hernia after abdominoperineal resection for rectal cancer. Methods: This study is a prospective case series study. From June 2021 to June 2022, patients with low rectal cancer underwent laparoscopic abdominoperineal resection combined with extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis at the First Department of General Surgery, Shaanxi Provincial People's Hospital were enrolled. The clinical data and postoperative CT images of patients were collected to analyze the incidence of surgical complication and parastomal hernia. Results: Totally 6 cases of patient were enrolled, including 3 males and 3 females, aging 72.5 (19.5) years (M(IQR)) (range: 55 to 79 years). The operation time was 250 (48) minutes (range: 190 to 275 minutes), the stoma operation time was 27.5 (10.7) minutes (range: 21 to 37 minutes), the bleeding volume was 30 (35) ml (range: 15 to 80 ml). All patients were cured and discharged without surgery-related complications. The follow-up time was 136 (105) days (range: 98 to 279 days). After physical examination and abdominal CT follow-up, no parastomal hernia occurred in the 6 patients up to this article. Conclusions: A method of laparoscopic extraperitoneal colostomy anterior to posterior sheath of rectus abdominis-transversus abdominis is established. Permanent stoma can be completed with this method safely. It may have a preventive effect on the occurrence of parastomal hernia, which is worthy of further study.

[Observational study on perioperative outcomes of pelvic exenteration].

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Clinical characteristics of immune checkpoint inhibitor-related type 1 diabetes mellitus].

The clinical data of ten patients with immune checkpoint inhibitor-related type 1 diabetes mellitus were enrolled in the Second Xiangya Hospital of Central South University from January 2020 to October 2022 including 9 males and 1 female, with an average age of (57±8) years. There were 7 cases of fulminant type 1 diabetes and 3 cases of acute type 1 diabetes. Among the 10 patients, there were 5 cases of lung cancer, 2 cases of esophageal cancer, 1 case of gastric carcinom, 1 case of renal cell carcinoma, and 1 case of nasopharyngeal cancer. The drugs used in 10 patients were all programmed cell death receptor 1 (PD-1) inhibitors, including 5 cases of pembrolizumab, 3 cases of sintilimab, 1 case of tanezumab, and 1 case of toripalimab. Among them, 8 patients had diabetic ketoacidosis (DKA), 1 patient had ketosis, and 1 case had no ketosis at onset; 9 patients were negative for diabetes-related antibodies, and 1 patient was positive. All the 10 patients were successfully treated and depended on insulin therapy. Immune checkpoint inhibitors can cause type 1 diabetes, including fulminant type 1 diabetes, which mostly begins with DKA, requiring early identification and aggressive insulin therapy.

[Analysis of the current status and related factors of human papillomavirus infection among community-dwelling women aged 18-24 years without a history of vaccination in Shanghai City].

Objective: To understand the status of human papillomavirus (HPV) infection among young women without a history of vaccination in Shanghai, and analyze the related factors of HPV infection in this population. Methods: A total of 2 660 women aged 18-24 years old who had made an appointment for HPV vaccine at 36 community health service centers in Shanghai from July 2022 to February 2023 were selected as the study subjects. Basic information (including demographic characteristics, previous disease history, female menstrual and reproductive history, sexual life history, etc.) was collected by a self-filling electronic questionnaire. Cervical secretions were detected by HPV nucleic acid typing. The multivariate logistic regression model was used to analyze the factors related to high-risk HPV (HR-HPV) infection in the target population. Results: The age of the subjects was (23±1) years old, and the infection rate of HPV was 14.51% (386 cases), among which the infection rates of HR-HPV and low-risk HPV were 13.53% (360 cases) and 1.84% (49 cases), respectively. The main subtypes of HR-HPV infection were HPV52, 16, 58, 39 and 66. The multivariate logistic regression model analysis showed that compared with the control group, the OR (95%CI) values for HR-HPV infection in the group of married, earned less than 2 000 yuan/month, drank alcohol occasionally, gynecological disease history, had two or more sexual partners in the past year, and did not know whether the partners had other sexual partners were 0.41 (0.25-0.66), 0.39 (0.21-0.70), 1.45 (1.13-1.86), 1.29 (1.00-1.66), 2.18-5.18 (1.02-16.05), and 1.82 (1.31-2.54), respectively. Conclusion: The infection rate of HPV among women aged 18-24 years old in Shanghai remains at a high level. The main subtypes of HR-HPV infection are HPV52, 16, 58, 39 and 66. The marital status, economic income level, drinking status, gynecological disease history and sexual life history are related to HR-HPV infection.

[Feasibility of ultrasound radiomics-based models for classification of hepatic echinococcosis].

OBJECTIVE: To investigate the feasibility of establishment of ultrasound radiomics-based models for classification of hepatic echinococcosis, so as to provide insights into precision ultrasound diagnosis of hepatic echinococcosis. METHODS: The ultrasonographic images were retrospectively collected from 200 patients with hepatic echinococcosis in Shiqu County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province in October 2014, and the regions of interest were plotted in ultrasonographic images of hepatic echinococcosis lesions. The ultrasound radiomics features of hepatic echinococcosis were extracted with 25 methods, and screened using pre-selection and the least absolute shrinkage and selection operator. Then, all ultrasonographic images were randomly assigned into the training and independent test sets according to the type of lesions at a ratio of 7:3. Machine learning models for classification of hepatic echinococcosis were created based on two classifiers, including kernel logistic regression (KLR) and medium Gaussian support vector machine (MGSVM). The receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity and areas under the curves (AUC) of the created machine learning models for classification of hepatic echinococcosis were calculated. RESULTS: A total of 5 005 ultrasound radiomics features were extracted from 200 patients with hepatic echinococcosis using 25 methods, and 36 optimal radiomics features were screened through feature selection, based on which two machine learning models were created, including KLR and MGSVM. ROC curve analysis showed that MGS-VM presented a higher efficacy for hepatic echinococcosis classification than KLR in the training set, with a sensitivity of 0.82, a specificity of 0.78 and AUC of 0.88, while KLR presented a higher efficacy for hepatic echinococcosis classification than MGSVM in the independent test set, with a sensitivity of 0.82, a specificity of 0.72 and AUC of 0.86, respectively. CONCLUSIONS: Ultrasound radiomics-based machine learning models are feasible for hepatic echinococcosis classification.

[Detection and analysis of intestinal flora diversity in patients with complex anal fistula].

Objective: To explore the possibility that the intestinal flora profile in complex anal fistula patients is different to that of healthy controls. This was assessed by sequencing of 16S rDNA in fecal samples from cohorts representing these populations. Methods: Fecal samples were collected from 30 complex anal fistula patients and 30 matched healthy controls. Patients were included if they met the diagnostic criteria of cryptoglandular anal fistula and had exhibited symptoms for more than 3 months. Complex anal fistula is diagnosed under the following circumstances: if the fistula in question spans 2/3 or more of the diameter of the anal sphincter; if there are more than two external orifices or fistula tracks; or if recurrence is observed after previous anal fistula surgery. Patients were excluded if there were comorbities including inflammatory bowel disease (as assessed by colonoscopy), chronic diarrhea, chronic constipation, diabetes, gastrointestinal malignancies, liver/ kidney dysfunction, or cognitive impairment. Patients whose anal fistulas were caused by Crohn's disease, trauma, special infections (such as actinomycosis and tuberculosis) were also excluded, as were those who had used antibiotics, prebiotics, or probiotics that may affect intestinal microecology in the month prior to the study. Total bacterial genomic DNA was extracted by PCR amplification of the V4 hypervariable region of the 16S rRNA sequences. High-throughput sequencing and data analysis were performed on the Illumina Miseq platform. Finally, operational taxonomic unit (OTU) clustering, alpha diversity and LEfSE data analysis were carried out. The larger the Chao or ACE index is, the higher the species abundance of the microflora is expected to be. Similarly, a smaller value for the Simpson index or a larger value for the Shannon index indicates greater microflora diversity. There was no statistically significant difference in gender, age, body mass index (BMI), drinking history, or smoking history between the two groups (P>0.05), indicating that they were comparable. Results: The α-diversity analysis including ACE, Chao, Shannon and Simpson indexes indicated a richer diversity of intestinal microflora in complex anal fistula patients than in healthy controls. In both patients and controls, OUT cluster analysis demonstrated that 93.4%±32.0% and 87.4%±41.2% of sequences were from Firmicutes and Bacteroidetes spp., respectively. On a genus level, samples from anal fistula patients showed a greater abundance of Prevotella spp. (4.9%±7.4% vs. 0.1%±1.1%, P<0.001), Megamonas (3.9%±8.2% vs. 0.5%±4.2%, P<0.05) and Lachnospira (2.6%±5.7% vs. 0.1%±3.4%, P<0.05), while showing a lesser abundance of Proteobacteria spp. (0.02%±4.2% vs. 9.3%±14.4%, P<0.01), Enterococcus (0.02%±2.3% vs. 9.3%±19.6%, P<0.05), Bacteroides (24.7%±9.9% vs. 29.8%±9.1%, P<0.05) and Klebsiella (0.4%±4.2% vs. 3.9%±7.3%, P<0.05) compared with healthy controls. Intestinal flora diversity in the complex anal fistula group was richer than in controls, as indicated by a higher ACE index (293.30±44.00 vs. 218.75±33.83, t=102.069, P<0.001), a higher Chao index (318.40±41.99 vs. 250.00±46.38, t=77.818, P=0.028), a higher Shannon index (3.36±0.29 vs. 2.43±0.34, t=9.657, P=0.001), and a lower Simpson index (0.103±0.013 vs. 0.131±0.013, t=5.551, P=0.046). LDA effect size analysis suggests that the main strains of Veillonellaceae, Selenemondales and Negativicutes, which all belong to the phylum Firmicutes, have the greatest influence on the above difference (LDA>4). Conclusions: The diversity of intestinal flora in patients with complex anal fistula is greater than in healthy controls, suggesting that these bacteria or their metabolites may be involved in the occurrence and development of anal fistulas.

[Rethinking of surgical indications for pancreatic cystic tumors].

With the progress of imaging technology and the popularization of healthy examination, the detection rate of pancreatic cystic neoplasm(PCN) has increased significantly. PCN has complex disease spectrum, strong heterogeneity, and diverse surgical treatment strategies. Surgical timing and methods directly affect patients' prognosis. Therefore, how to identify malignant tumors and formulate reasonable treatment strategies are the keys to treat PCN. Many guidelines for clinical diagnosis and treatment of PCN have been released, but there are still many disputes about its surgical indications. Hence, fully assessing the surgical indications is of great significance to improve the PCN patients' prognosis. This paper deeply discusses on the surgical indications of PCN by reviewing the current clinical diagnosis, treatment and research progress of PCN, in order to standardize the diagnosis and treatment of PCN.

Comparison of Survival Outcomes between Minimally Invasive Surgery and Open Radical Hysterectomy in Early-Stage Cervical Cancer.

OBJECTIVES: To compare the survival outcomes between minimally invasive surgery (MIS) and laparotomy radical hysterectomy in patients with early-stage cervical cancer. METHODS: We conducted a retrospective study involving women who received a radical hysterectomy for cervical cancer, stage IA1 with lymphovascular invasion, IA2, IB1, IB2, or IIA from 2008 to 2016. Clinicopathologic and perioperative outcomes were compared using appropriate statistical methodologies. RESULTS: Oncologic survival outcomes were analyzed using the Kaplan-Meier method. Among the 105 cases identified, 58 (55.2%) and 47 (44.8%) women underwent MIS and open radical hysterectomy, respectively. Over a median follow-up period of 62 months, women who underwent MIS and open radical hysterectomy had a 5-year overall survival rate of 87.9% and 89.4% (p = 0.845) and a 5-year disease-free survival rate of 82.5% and 86.7% (p = 0.624), respectively. CONCLUSIONS: For early-stage cervical cancer, patients who underwent MIS radical hysterectomy had survival outcomes that were comparable to those who underwent open surgery at our institute.

[Effects of Toxoplasma gondii infection on mouse and human uterine natural killer cells].

OBJECTIVE: To examine the effects of Toxoplasma gondii infection on the proportion, quantity, differentiation and function of mouse and human uterine natural killer cells (uNK cells), so as to explore the role of uNK cells in abortion of early pregnancy caused by T. gondii infection. METHODS: Pregnant mice were injected intraperitoneally with T. gondii tachyzoites on day 6.5 of pregnancy, and the abortion mouse model caused by T. gondii infections was constructed. Mouse uterine lymphocytes were isolated on day 9.5 of pregnancy. Human uterine lymphocytes were isolated from fresh human decidual specimens after abortion in normal early pregnancy and co-cultured with tachyzoites of the T. gondii RH strain for 48 h at T. gondii/uterine lymphocytes ratios of 0.5:1, 1:1 and 2:1. The phenotypes of mouse uNK cells (CD122, NK1.1, DX5) and human uNK cells (CD3, CD56, CD11b, CD27) and the expression of intracellular cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by flow cytometry. Mouse and human uNK cells were sorted by magnetic beads, and the cytotoxicity of uNK cells was tested using the lactate dehydrogenase (LDH) release assay at effector/target cell ratios of 1:1, 5:1, 10:1 and 20:1 with mouse or human uNK cells as effector cells and mouse YAC-1 cells or human K562 cells as target cells. RESULTS: On day 9.5 of pregnancy, the mouse abortion rate was significantly higher in the infected group than that in the control group (83.02% vs. 3.51%; χ2 = 71.359, P < 0.001). Significantly lower absolute number of uNK cells [(4 547 ± 1 610) cells/mouse vs. (8 978 ± 3 339) cells/mouse; U = 2.000, P < 0.05], lower NK1.1 expression on uNK cell surface [(74.53 ± 8.37)% vs. (93.00 ± 1.11)%; U = 0.000, P < 0.05], higher proportion of NK1.1-DX5-cells [(20.10 ± 8.03)% vs. (5.04 ± 0.68)%; U = 0.000, P < 0.05], lower proportion of NK1.1+ DX5+ cells [(21.70 ± 12.48)% vs. (45.75 ± 2.26)%; U = 0.000, P < 0.05] and higher IFN-γ expression [(16.74 ± 1.36)% vs. (8.13 ± 1.90)%; U = 0.000, P < 0.05] were detected in the infected group than in the control group, while no significant difference was seen in TNF-α expression between the two groups [(67.98 ± 9.20)% vs. (52.93 ± 10.42)%; U = 2.000, P > 0.05]. The mouse uNK cells showed a strong cytotoxicity in the infected group, and the cytotoxicity gradually increased with the effector/target cell ratio. The cytotoxicity of uNK cells against YAC-1 cells was 2.30%, 4.32%, 8.12% and 12.65% in the infected group and 1.21%, 1.63%, 2.51% and 3.22% in the control group at effector/target cell ratios of 1:1, 5:1, 10:1 and 20:1, respectively. Following co-culture of human uterine lymphocytes and tachyzoites of the T. gondii RH strain for 48 h, the proportion [TOX 2:1 group vs. control group: (6.61 ± 1.75)% vs. (17.48 ± 4.81)%; F = 7.307, P < 0.01], and absolute number of human uNK cells in uterine lymphocytes of human uNK cells in uterine lymphocytes [TOX 2:1 group vs. control group: (12 104 ± 5 726) cells/well vs. (65 285 ± 21 810) cells/well; H = 11.540, P < 0.01] were significantly lower in the infected group than in the control group. A lower proportion of CD56brightCD16- NK cells [TOX 2:1 group vs. control group: (25.25 ± 5.90)% vs. (36.03 ± 4.51)%; F = 3.213, P > 0.05] and higher proportion of CD56dimCD16+ NK cells [TOX 2:1 group vs. control group: (11.15 ± 2.15)% vs. (7.09 ± 2.24)%; F = 2.992, P > 0.05] were detected in uNK cells in the infected group than in the control group, and the ratio of CD56brightCD16- cells/CD56dimCD16+ cells was significantly lower in the infected group than in the control group [TOX2:1 group vs. control group: (2.37 ± 0.92) vs. (5.58 ± 2.39); H = 8.228, P < 0.05]. In addition, the proportion of CD11b+CD27- cells in human uNK cells was significantly higher in the infected group than in the control group [TOX 2:1 group vs. control group: (30.28 ± 6.91)% vs. (17.48 ± 4.67)%; H = 6.556, P < 0.05], while no significant differences were found between the two groups in terms of IFN-γ [TOX 2:1 group vs. control group: (14.13 ± 1.28)% vs. (15.19 ± 1.64)%; F = 1.639, P > 0.05] or TNF-α expression [TOX 2:1 group vs. control group: (54.76 ± 10.02)% vs. (50.33 ± 3.67)%; F = 0.415, P > 0.05]. Human uNK cells presented a strong cytotoxicity in the infected group, and the cytotoxicity gradually increased with the effector/target cell ratio. The cytotoxicity of human uNK cells against K562 cells was 11.90%, 28.11%, 49.91% and 73.35% in the infected group and 12.21%, 21.63%, 33.51% and 48.22% in the control group at effector/target cell ratios of 1:1, 5:1, 10:1 and 20:1, respectively. CONCLUSIONS: T. gondii infection presents diverse effects on the differentiation and secretion ability of mouse and human uNK cells. However, T. gondii infection causes a reduction in the absolute number and enhances the cytotoxicity of both mouse and human uNK cells.