1.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
2.The age, sex, and provoked factors of acute symptomatic deep vein thrombosis on the left and right lower extremities.
Chong-Li REN ; Jian-Ming SUN ; Hai-Yang WANG ; Jian FU ; Ye-Liang XU ; Jin WANG ; Meng-Lin NIE
Chinese Journal of Traumatology 2025;28(2):96-100
PURPOSE:
Deep vein thrombosis (DVT) of the left and right lower extremities was treated in the same way, but the left and right extremities received different levels of attention. This study aimed to investigate the differences between the right and left lower extremity deep vein thrombosis (LEDVT).
METHODS:
Clinical characteristics of LEDVT patients from July 2020 to June 2022 were retrospectively analyzed to compare the incidence of LEDVT on different limbs, demographics, predisposing factors, and anatomical characteristics. The exclusion criteria were bilateral LEDVT and recurrent thrombosis. Measured data was analyzed using independent samples t-test or Mann-Whitney test. Count data were analyzed by Chi-square test. A p < 0.05 was considered a statistically significant difference.
RESULTS:
There were 478 patients included in this study and the ratio of left to right LEDVT on the left and right limbs was 3.16:1 (363:115). Left LEDVT predominantly affected female, with the major aged > 50 years (50 - 60 years: 16.80%; > 60 years: 57.30%). The primary predisposing factor was iliac vein compression syndrome, with iliofemoral thrombosis being the main type. Male patients with LEDVT on the right limb were predominant and the age of onset was usually ≤ 60 years (52.17%). The main predisposing factor was recent surgery or trauma (< 30 days) and femoropopliteal thrombosis was the main type. In more detail, the left iliac vein was compressed mainly in the proximal segment, and the right iliac vein was compressed mainly in the intermediate and distal segments. Recent surgery or trauma to the locomotor system and genitourinary system often induced LEDVT.
CONCLUSION
The incidence of LEDVT on the left is significantly higher than that on the right. LEDVT on different sides has different characteristics, which is crucial for prevention and diagnosis in the relevant population so there are also differences in treatment of the affected limbs.
Humans
;
Venous Thrombosis/etiology*
;
Male
;
Female
;
Middle Aged
;
Lower Extremity/blood supply*
;
Retrospective Studies
;
Adult
;
Aged
;
Age Factors
;
Sex Factors
;
Risk Factors
;
Acute Disease
;
Incidence
;
Aged, 80 and over
;
Young Adult
;
Adolescent
3.Management strategies for vesicovaginal fistula following cervical cancer radiotherapy in women
Jiemin SI ; Weidong ZHU ; Ranxing YANG ; Lujie SONG ; Chongrui JIN ; Jianwen HUANG ; Xuxiao YE ; Zuowei LI ; Wenxiong SONG ; Qiang FU ; Yinglong SA
Chinese Journal of Urology 2025;46(8):587-592
Objective:To investigate the treatment strategies for vesicovaginal fistula(VVF)in women following cervical cancer radiotherapy.Methods:A retrospective analysis was performed on the clinical data of 33 female patients with post-radiotherapy VVF after cervical cancer treatment at Shanghai Sixth People’s Hospital between January 2020 and June 2024. The patients were categorized into three groups based on surgical approaches:Group A(11 patients):Underwent prone-position VVF repair. Mean age:(50.0±9.6)years;mean radiotherapy sessions:(22.6±2.2). All had simple VVF without concurrent intestinal or surrounding soft-tissue fistulas. Among them,1 patient previously received laparoscopic VVF repair,1 transvaginal VVF repair,and 2 gracilis muscle flap packing for VVF repair. One month prior to surgery,the average daily usage of urine pads was 16.7(12.8,25.7)pieces,and the quality of life(QOL)score stood at 4.0(4.0,5.0)points. Preoperative cystoscopy revealed that 8 cases had fistulas located in the trigonal region of the bladder,while 3 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings,measured under a microscope,was 1.2(0.8,1.6)cm. Based on the Goh classification criteria for vesicovaginal fistulas,this group included 3 cases of type 1,4 cases of type 2,2 cases of type 3,and 2 cases of type 4;7 cases of type A and 4 cases of type B;as well as 3 cases of typeⅠ,7 cases of type Ⅱ,and 1 case of type Ⅲ.Group B(20 patients):Underwent gracilis muscle flap packing for VVF repair. Mean age:(58.6±8.8)years;mean radiotherapy sessions:(29.8±3.9). Three patients had concurrent rectovaginal fistulas and received colostomy for fecal diversion. History of previous interventions:3 had laparoscopic VVF repair,4 transvaginal VVF repair,and 1 both transvaginal and laparoscopic VVF repair. One month prior to surgery,the average daily usage of urine pads was 19.7(15.8,27.7)pieces,and the QOL score stood at 5.0(5.0,6.0)points. Preoperative cystoscopy revealed that 13 cases had fistulas located in the trigonal region of the bladder,while 7 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings,measured under a microscope,was 1.8(1.0,3.2)cm. Based on the Goh classification criteria for vesicovaginal fistulas,this group included 4 cases of type 1,9 cases of type 2,3 cases of type 3,and 4 cases of type 4;6 cases of type A,11 cases of type B and 3 cases of type C;as well as 1 cases of type Ⅱ,and 19 case of type Ⅲ. Group C(2 patients):Underwent ureterocutaneous diversion. Ages:67 and 73 years;radiotherapy sessions:51 and 60,respectively. Both had concurrent rectovaginal fistulas and bladder soft-tissue fistulas. The patient presented with recurrent thigh abscesses accompanied by fever. One month prior to surgery,the daily usage of urine pads was 29 and 23 pieces,respectively,and the QOL score was 6 points. Cystoscopic examination revealed that the vesicovaginal fistulas were located in the trigone of the bladder,with diameters of 3 cm and 4 cm,respectively. Additionally,partial defects were noted in the ventral wall of the urethra,while no bladder soft tissue fistulas were detected. According to the Goh classification for vesicovaginal fistulas,both cases were categorized as type 4,type C,and type Ⅲ. For Groups A and B,urinary catheters were indwelled for 3 weeks postoperatively,then removed to assess spontaneous urination and incontinence. QOL was evaluated,with a minimum 6-month follow-up. For confirmed postoperative VVF recurrence,re-repair was performed 3?6 months later based on patient preference. For Group C,double-J stents were placed in the ureters,and stoma bags were applied 3 days postoperatively. Stents were replaced every 1?2 months,with QOL assessment. Successful fistula repair in Groups A and B was defined as the absence of vaginal leakage confirmed by cystoscopy after six months of the procedure with no vaginal leakage. For Group C,surgical success was determined by the resolution of perineal urinary leakage and improvement in QOL.Results:All 33 patients completed surgery successfully. Group A:Follow-up duration:16.3(9.6,24.6)months. Surgical repair succeeded in 7 patients,with unobstructed spontaneous urination and no vaginal incontinence. Four patients had VVF recurrence:2 refused further treatment,and 2 underwent repeat gracilis muscle flap packing. One was successfully repaired,while one recurrence case refused further treatment. Group B:Follow-up duration:17.0(9.5,24.8)months(8?32 months). Thirteen patients restored spontaneous urination without recurrence. Seven had recurrence:5 refused further surgery,and 2 underwent re-repair. One repair succeeded without incontinence,while one recurrence case refused treatment. Group C:Follow-up durations were 6 and 22 months. Perineum remained dry without incontinence(no urine pads needed),and no recurrence of thigh soft-tissue redness/infection occurred. QOL scores were 2 and 3,respectively.Conclusions:Post-radiotherapy VVF in women after cervical cancer presents complex and variable conditions. The primary goal of treatment should be to improve patients’ quality of life. Treatment approaches should be selected based on the complexity of urinary fistulas and local tissue conditions. In general,patients who are younger,have received lower doses of radiation therapy,present with smaller fistula diameters,have well-vascularized and elastic perifistular tissues,and have no concurrent tissue fistulas are candidates for prone-position VVF repair. Patients who do not meet the criteria for transvaginal repair,have a history of at least two previous repair attempts,or have concurrent vaginorectal fistulas require gracilis muscle flap packing for VVF repair. Patients with three or more types of concurrent tissue fistulas,extensive pale and inelastic perifistular tissues,and who are not amenable to repair surgery undergo ureterocutaneous diversion.
4.Expert consensus on infection prevention and control of Creutzfeldt-Jakob disease in medical institutions
Tianxiang GE ; Yangyang JIA ; Chunhui LI ; Jianrong HUANG ; Xiujuan MENG ; Xiaodong GAO ; Jingping ZHANG ; Fu QIAO ; Lijuan XIONG ; Hui LIANG ; Wei LI ; Haiyan LOU ; Wenjuan WU ; Tianxin XIANG ; Jiansen CHEN ; Biao ZHU ; Kaijin XU ; Zhihui ZHOU ; Hongliu CAI ; Meihong YU ; Yan ZHANG ; Yanwan SHANGGUAN ; Haiting FENG ; Hangping YAO ; Lei GUO ; Tieer GAN ; Weihong ZHANG ; Jimin SUN ; Ye LU ; Qun LU ; Meng CAI ; Jin SHEN ; Yunsong YU ; Anhua WU ; Liu-yi LI ; Tingting QU
Chinese Journal of Infection Control 2025;24(4):437-450
Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.
5.Expert consensus on infection prevention and control of Creutzfeldt-Jakob disease in medical institutions
Tianxiang GE ; Yangyang JIA ; Chunhui LI ; Jianrong HUANG ; Xiujuan MENG ; Xiaodong GAO ; Jingping ZHANG ; Fu QIAO ; Lijuan XIONG ; Hui LIANG ; Wei LI ; Haiyan LOU ; Wenjuan WU ; Tianxin XIANG ; Jiansen CHEN ; Biao ZHU ; Kaijin XU ; Zhihui ZHOU ; Hongliu CAI ; Meihong YU ; Yan ZHANG ; Yanwan SHANGGUAN ; Haiting FENG ; Hangping YAO ; Lei GUO ; Tieer GAN ; Weihong ZHANG ; Jimin SUN ; Ye LU ; Qun LU ; Meng CAI ; Jin SHEN ; Yunsong YU ; Anhua WU ; Liu-yi LI ; Tingting QU
Chinese Journal of Infection Control 2025;24(4):437-450
Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.
6.Efficacy of the transpubic access in the treatment of female urogenital tract injury
Weidong ZHU ; Jiemin SI ; Chongrui JIN ; Wenxiong SONG ; Xuxiao YE ; Lujie SONG ; Qiang FU ; Yinglong SA
Chinese Journal of Urology 2025;46(10):774-777
Objective:To explore the application value of transpubic access on female urogenital tract injury.Methods:A retrospective analysis was conducted on 15 female patients with urogenital tract injury caused by trauma admitted to our department from May 2020 to October 2024,all of whom were complicated urethral stricture or atresia,accompanied by urethrovaginal fistula or vaginorectal fistula. All patients underwent suprapubic vesicostomy before surgery,and 1 case underwent sigmoidostomy simultaneously. The mean age of the patients was(29.6 ± 3.2)years old,and the course of disease was 6-24 months. Preoperative urethrography and urethroscope showed the location of urethral stenosis,with proximal urethra stricture in 7 cases and distal urethra stricture in 8 cases. The average length of strictures was(2.8±0.2)cm. The urethral ultrasonography,magnetic resonance and CTU examination showed 8 patients were complicated with urethrovaginal fistula,and 1 patient was complicated with vaginorectal fistula. All patients underwent transpubic access and resection of symphysis pubis. According to the specific conditions of urethral stricture,7 of them underwent end-to-end urethral anastomosis,5 cases underwent bladder wall flap urethroplasty,3 cases underwent vulva flap urethroplasty,8 cases underwent urethral vaginal fistula repair,1 case underwent vagino-rectal fistula repair,and 7 cases underwent vaginoplasty during the operation.Results:All the 15 patients underwent successful operation without complication. After the catheter being removed 4 weeks after surgery,2 patients had urgent urinary incontinence and 3 patients had stress urinary incontinence. The bladder neck was reconstructed 3 months after surgery,the symptoms of urinary incontinence improved in 1 case,urinary incontinence remained in 2 cases,and pharmaceutical or physical therapy were continued. Two patients could not urinate normally after the catheter was removed and still carried the vesicostomy tube,waiting for further treatment. The other 8 patients had unobtrusive voiding after extubating,and were followed up for an average of(22.5±3.2)months. There was no recurrence of urinary fistula,and the average maximum urinary flow rate was(22.8±3.2)ml/s.Conclusions:The transpubic approach is a safe and effective way to treat female genital tract injury by different surgical methods according to specific conditions,especially for patients with severe trauma,poor local tissue conditions,complicated urethrovaginal fistula or vagino-rectal fistula.
7.Lymph node metastasis in the prostatic anterior fat pad and prognosis after robot-assisted radical prostatectomy
Zhou-jie YE ; Yong SONG ; Jin-peng SHAO ; Wen-zheng CHEN ; Guo-qiang YANG ; Qing-shan DU ; Kan LIU ; Jie ZHU ; Bao-jun WANG ; Jiang-ping GAO ; Wei-jun FU
National Journal of Andrology 2025;31(3):216-221
Objective:To investigate lymph node metastasis(LNM)in the prostatic anterior fat pad(PAFP)of PCa patients after robot-assisted radical prostatectomy(RARP),and analyze the clinicopathological features and prognosis of LNM in the PAFP.Methods:We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urolo-gy of PLA General Hospital from January 2017 to December 2022.All the patients underwent routine removal of the PAFP during RARP and pathological examination,with the results of all the specimens examined and reported by pathologists.Based on the pres-ence and locations of LNM,we grouped the patients for statistical analysis,compared the clinicopathological features between different groups using the Student's t,Mann-Whitney U and Chi-square tests,and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio.Results:Lymph nodes were detected in 77(7.7%)of the 1 003 PAFP samples,and LNM in 11(14.3%)of the 77 cases,with a positive rate of 1.1%(11/1 003).Of the 11 positive cases,9 were found in the upgraded pathological N stage,and the other 2 complicated by pelvic LNM.The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group(81.8%[9/11]vs 36.2%[359/992],P=0.005),and so did the cases with Gleason score ≥8(87.5%[7/8]vs 35.5%[279/786],P=0.009).No statisti-cally significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the pa-tients with PAFP LNM only and those with pelvic LNM only.Conclusion:The PAFP is a potential route to LNM,and patients with LNM in the PAFP are characterized by poor pathological features.There is no statistically significant difference in biochemical recur-rence-free survival between the patients with PAFP LNM only and those with pelvic LNM only.Routine removal of the PAFP and inde-pendent pathological examination of the specimen during RARP is of great clinical significance.
8.Efficacy of the transpubic access in the treatment of female urogenital tract injury
Weidong ZHU ; Jiemin SI ; Chongrui JIN ; Wenxiong SONG ; Xuxiao YE ; Lujie SONG ; Qiang FU ; Yinglong SA
Chinese Journal of Urology 2025;46(10):774-777
Objective:To explore the application value of transpubic access on female urogenital tract injury.Methods:A retrospective analysis was conducted on 15 female patients with urogenital tract injury caused by trauma admitted to our department from May 2020 to October 2024,all of whom were complicated urethral stricture or atresia,accompanied by urethrovaginal fistula or vaginorectal fistula. All patients underwent suprapubic vesicostomy before surgery,and 1 case underwent sigmoidostomy simultaneously. The mean age of the patients was(29.6 ± 3.2)years old,and the course of disease was 6-24 months. Preoperative urethrography and urethroscope showed the location of urethral stenosis,with proximal urethra stricture in 7 cases and distal urethra stricture in 8 cases. The average length of strictures was(2.8±0.2)cm. The urethral ultrasonography,magnetic resonance and CTU examination showed 8 patients were complicated with urethrovaginal fistula,and 1 patient was complicated with vaginorectal fistula. All patients underwent transpubic access and resection of symphysis pubis. According to the specific conditions of urethral stricture,7 of them underwent end-to-end urethral anastomosis,5 cases underwent bladder wall flap urethroplasty,3 cases underwent vulva flap urethroplasty,8 cases underwent urethral vaginal fistula repair,1 case underwent vagino-rectal fistula repair,and 7 cases underwent vaginoplasty during the operation.Results:All the 15 patients underwent successful operation without complication. After the catheter being removed 4 weeks after surgery,2 patients had urgent urinary incontinence and 3 patients had stress urinary incontinence. The bladder neck was reconstructed 3 months after surgery,the symptoms of urinary incontinence improved in 1 case,urinary incontinence remained in 2 cases,and pharmaceutical or physical therapy were continued. Two patients could not urinate normally after the catheter was removed and still carried the vesicostomy tube,waiting for further treatment. The other 8 patients had unobtrusive voiding after extubating,and were followed up for an average of(22.5±3.2)months. There was no recurrence of urinary fistula,and the average maximum urinary flow rate was(22.8±3.2)ml/s.Conclusions:The transpubic approach is a safe and effective way to treat female genital tract injury by different surgical methods according to specific conditions,especially for patients with severe trauma,poor local tissue conditions,complicated urethrovaginal fistula or vagino-rectal fistula.
9.Management strategies for vesicovaginal fistula following cervical cancer radiotherapy in women
Jiemin SI ; Weidong ZHU ; Ranxing YANG ; Lujie SONG ; Chongrui JIN ; Jianwen HUANG ; Xuxiao YE ; Zuowei LI ; Wenxiong SONG ; Qiang FU ; Yinglong SA
Chinese Journal of Urology 2025;46(8):587-592
Objective:To investigate the treatment strategies for vesicovaginal fistula(VVF)in women following cervical cancer radiotherapy.Methods:A retrospective analysis was performed on the clinical data of 33 female patients with post-radiotherapy VVF after cervical cancer treatment at Shanghai Sixth People’s Hospital between January 2020 and June 2024. The patients were categorized into three groups based on surgical approaches:Group A(11 patients):Underwent prone-position VVF repair. Mean age:(50.0±9.6)years;mean radiotherapy sessions:(22.6±2.2). All had simple VVF without concurrent intestinal or surrounding soft-tissue fistulas. Among them,1 patient previously received laparoscopic VVF repair,1 transvaginal VVF repair,and 2 gracilis muscle flap packing for VVF repair. One month prior to surgery,the average daily usage of urine pads was 16.7(12.8,25.7)pieces,and the quality of life(QOL)score stood at 4.0(4.0,5.0)points. Preoperative cystoscopy revealed that 8 cases had fistulas located in the trigonal region of the bladder,while 3 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings,measured under a microscope,was 1.2(0.8,1.6)cm. Based on the Goh classification criteria for vesicovaginal fistulas,this group included 3 cases of type 1,4 cases of type 2,2 cases of type 3,and 2 cases of type 4;7 cases of type A and 4 cases of type B;as well as 3 cases of typeⅠ,7 cases of type Ⅱ,and 1 case of type Ⅲ.Group B(20 patients):Underwent gracilis muscle flap packing for VVF repair. Mean age:(58.6±8.8)years;mean radiotherapy sessions:(29.8±3.9). Three patients had concurrent rectovaginal fistulas and received colostomy for fecal diversion. History of previous interventions:3 had laparoscopic VVF repair,4 transvaginal VVF repair,and 1 both transvaginal and laparoscopic VVF repair. One month prior to surgery,the average daily usage of urine pads was 19.7(15.8,27.7)pieces,and the QOL score stood at 5.0(5.0,6.0)points. Preoperative cystoscopy revealed that 13 cases had fistulas located in the trigonal region of the bladder,while 7 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings,measured under a microscope,was 1.8(1.0,3.2)cm. Based on the Goh classification criteria for vesicovaginal fistulas,this group included 4 cases of type 1,9 cases of type 2,3 cases of type 3,and 4 cases of type 4;6 cases of type A,11 cases of type B and 3 cases of type C;as well as 1 cases of type Ⅱ,and 19 case of type Ⅲ. Group C(2 patients):Underwent ureterocutaneous diversion. Ages:67 and 73 years;radiotherapy sessions:51 and 60,respectively. Both had concurrent rectovaginal fistulas and bladder soft-tissue fistulas. The patient presented with recurrent thigh abscesses accompanied by fever. One month prior to surgery,the daily usage of urine pads was 29 and 23 pieces,respectively,and the QOL score was 6 points. Cystoscopic examination revealed that the vesicovaginal fistulas were located in the trigone of the bladder,with diameters of 3 cm and 4 cm,respectively. Additionally,partial defects were noted in the ventral wall of the urethra,while no bladder soft tissue fistulas were detected. According to the Goh classification for vesicovaginal fistulas,both cases were categorized as type 4,type C,and type Ⅲ. For Groups A and B,urinary catheters were indwelled for 3 weeks postoperatively,then removed to assess spontaneous urination and incontinence. QOL was evaluated,with a minimum 6-month follow-up. For confirmed postoperative VVF recurrence,re-repair was performed 3?6 months later based on patient preference. For Group C,double-J stents were placed in the ureters,and stoma bags were applied 3 days postoperatively. Stents were replaced every 1?2 months,with QOL assessment. Successful fistula repair in Groups A and B was defined as the absence of vaginal leakage confirmed by cystoscopy after six months of the procedure with no vaginal leakage. For Group C,surgical success was determined by the resolution of perineal urinary leakage and improvement in QOL.Results:All 33 patients completed surgery successfully. Group A:Follow-up duration:16.3(9.6,24.6)months. Surgical repair succeeded in 7 patients,with unobstructed spontaneous urination and no vaginal incontinence. Four patients had VVF recurrence:2 refused further treatment,and 2 underwent repeat gracilis muscle flap packing. One was successfully repaired,while one recurrence case refused further treatment. Group B:Follow-up duration:17.0(9.5,24.8)months(8?32 months). Thirteen patients restored spontaneous urination without recurrence. Seven had recurrence:5 refused further surgery,and 2 underwent re-repair. One repair succeeded without incontinence,while one recurrence case refused treatment. Group C:Follow-up durations were 6 and 22 months. Perineum remained dry without incontinence(no urine pads needed),and no recurrence of thigh soft-tissue redness/infection occurred. QOL scores were 2 and 3,respectively.Conclusions:Post-radiotherapy VVF in women after cervical cancer presents complex and variable conditions. The primary goal of treatment should be to improve patients’ quality of life. Treatment approaches should be selected based on the complexity of urinary fistulas and local tissue conditions. In general,patients who are younger,have received lower doses of radiation therapy,present with smaller fistula diameters,have well-vascularized and elastic perifistular tissues,and have no concurrent tissue fistulas are candidates for prone-position VVF repair. Patients who do not meet the criteria for transvaginal repair,have a history of at least two previous repair attempts,or have concurrent vaginorectal fistulas require gracilis muscle flap packing for VVF repair. Patients with three or more types of concurrent tissue fistulas,extensive pale and inelastic perifistular tissues,and who are not amenable to repair surgery undergo ureterocutaneous diversion.
10.Discovery of novel small molecules targeting hepatitis B virus core protein from marine natural products with HiBiT-based high-throughput screening.
Chao HUANG ; Yang JIN ; Panpan FU ; Kongying HU ; Mengxue WANG ; Wenjing ZAI ; Ting HUA ; Xinluo SONG ; Jianyu YE ; Yiqing ZHANG ; Gan LUO ; Haiyu WANG ; Jiangxia LIU ; Jieliang CHEN ; Xuwen LI ; Zhenghong YUAN
Acta Pharmaceutica Sinica B 2024;14(11):4914-4933
Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC50 = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.


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