1.Clinical implications of morular metaplasia in fertility-preserving treatment for endometrial hyperplasia and grade 1 endometrial endometrioid carcinoma patients
Shuangshuang ZHAO ; Dongcan ZHANG ; Tian LI ; Ye YAN ; Boning WANG ; Tianqi WANG ; Huiying ZHANG ; Wenyan TIAN ; Xue ZHAO ; Danfang ZHANG ; Yingmei WANG
Chinese Journal of Obstetrics and Gynecology 2025;60(11):868-875
Objective:To evaluate the clinical significance of morular metaplasia (MM) in fertility-preserving treatment for young patients with endometrial hyperplasia and grade 1 endometrial endometrioid carcinoma.Methods:Clinical data was retrospectively collected from patients diagnosed with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma under 40 years old who underwent progestin-based fertility-sparing treatmentat in Tianjin Medical University General Hospital between January 2018 and November 2022.Patients were divided into the MM group (37 cases) and the non-MM group (63 cases) based on pathological findings. Clinical characteristics, hysteroscopic features, treatment efficacy and fertility outcomes were compared between the two groups. The MM group was further stratified into three subgroups based on the timing of MM occurrence:(1) MM-Bef group ( n=10): MM was present in the initial endometrial curettage or hysteroscopic biopsy pathology before fertility-sparing treatment and disappeared after treatment; (2) MM-Sus group ( n=14): MM persisted consistently before and after therapy;(3) MM-Aft group ( n=13): MM was absent before therapy but appeared after treatment. The risk factors which had impact on the treatment outcomes of the patients were analyzed using univariate and multivariate Cox regression analysis. Results:The rate of polycystic ovary syndrome were higher in the MM group than the non-MM group [51% (19/37) vs 27% (17/63), P=0.014]. The complete response (CR) rate was significantly lower in the MM group than in the non-MM group [73% (27/37) vs 95% (60/63), P=0.006], and the median time to CR was significantly longer in the MM group (6.0 vs 5.0 months, P=0.005).Multivariate analysis identified that MM-Sus ( HR=0.355, 95% CI:0.174-0.723; P=0.004) and MM-Aft ( HR=0.314, 95% CI:0.145-0.681; P=0.003) were independent risk factors for delayed CR in fertility-sparing treatment. The patients in the MM group and non-MM group underwent hysteroscopic biopsy for 76 and 131 times. "Gravel-like change" was a more frequent hysteroscopic manifestation in the MM group than that in the non-MM group [18% (14/76) vs 2% (2/131), P<0.001]. Conclusions:Patients in the MM group have poorer treatment outcomes than patients in the non-MM group. MM-Sus and MM-Aft are risk factors for fertility-preserving treatment in young patients with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma. "Gravel-like change" is the characteristic hysteroscopic manifestations of MM.
2.First ATG101-recruiting small molecule degrader for selective CDK9 degradation via autophagy-lysosome pathway.
Ye ZHONG ; Jing XU ; Huiying CAO ; Jie GAO ; Shaoyue DING ; Zhaohui REN ; Huali YANG ; Yili SUN ; Maosheng CHENG ; Jia LI ; Yang LIU
Acta Pharmaceutica Sinica B 2025;15(5):2612-2624
Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.
3.Clinical implications of morular metaplasia in fertility-preserving treatment for endometrial hyperplasia and grade 1 endometrial endometrioid carcinoma patients
Shuangshuang ZHAO ; Dongcan ZHANG ; Tian LI ; Ye YAN ; Boning WANG ; Tianqi WANG ; Huiying ZHANG ; Wenyan TIAN ; Xue ZHAO ; Danfang ZHANG ; Yingmei WANG
Chinese Journal of Obstetrics and Gynecology 2025;60(11):868-875
Objective:To evaluate the clinical significance of morular metaplasia (MM) in fertility-preserving treatment for young patients with endometrial hyperplasia and grade 1 endometrial endometrioid carcinoma.Methods:Clinical data was retrospectively collected from patients diagnosed with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma under 40 years old who underwent progestin-based fertility-sparing treatmentat in Tianjin Medical University General Hospital between January 2018 and November 2022.Patients were divided into the MM group (37 cases) and the non-MM group (63 cases) based on pathological findings. Clinical characteristics, hysteroscopic features, treatment efficacy and fertility outcomes were compared between the two groups. The MM group was further stratified into three subgroups based on the timing of MM occurrence:(1) MM-Bef group ( n=10): MM was present in the initial endometrial curettage or hysteroscopic biopsy pathology before fertility-sparing treatment and disappeared after treatment; (2) MM-Sus group ( n=14): MM persisted consistently before and after therapy;(3) MM-Aft group ( n=13): MM was absent before therapy but appeared after treatment. The risk factors which had impact on the treatment outcomes of the patients were analyzed using univariate and multivariate Cox regression analysis. Results:The rate of polycystic ovary syndrome were higher in the MM group than the non-MM group [51% (19/37) vs 27% (17/63), P=0.014]. The complete response (CR) rate was significantly lower in the MM group than in the non-MM group [73% (27/37) vs 95% (60/63), P=0.006], and the median time to CR was significantly longer in the MM group (6.0 vs 5.0 months, P=0.005).Multivariate analysis identified that MM-Sus ( HR=0.355, 95% CI:0.174-0.723; P=0.004) and MM-Aft ( HR=0.314, 95% CI:0.145-0.681; P=0.003) were independent risk factors for delayed CR in fertility-sparing treatment. The patients in the MM group and non-MM group underwent hysteroscopic biopsy for 76 and 131 times. "Gravel-like change" was a more frequent hysteroscopic manifestation in the MM group than that in the non-MM group [18% (14/76) vs 2% (2/131), P<0.001]. Conclusions:Patients in the MM group have poorer treatment outcomes than patients in the non-MM group. MM-Sus and MM-Aft are risk factors for fertility-preserving treatment in young patients with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma. "Gravel-like change" is the characteristic hysteroscopic manifestations of MM.
4.Partial nephrectomy for renal cell carcinoma in a transplanted kidney
Shiying TANG ; Chuxiao XU ; Jianfei YE ; Huiying HE ; Hongxian ZHANG ; Guoliang WANG ; Shudong ZHANG
Chinese Journal of Urology 2025;46(3):230-232
Renal cell carcinoma in a transplanted kidney is rare, and partial nephrectomy in transplanted kidney is even more uncommon. A patient with papillary transplanted renal cell carcinoma who underwent partial nephrectomy was reported. The patient was admitted to the hospital due to the discovery of transplanted kidney mass, and the enhanced examination of CTU found a lesion in the upper pole of the transplanted kidney in the right iliac fossa, which may be renal cancer, with a diameter of about 2 cm. After open partial nephrectomy of the transplanted kidney, the postoperative pathology showed that the tumor was papillary renal cell carcinoma. The antirejection drugs were used after surgery. During the follow-up period of 16 months, there was no recurrence of transplanted kidney tumor.
5.Partial nephrectomy for renal cell carcinoma in a transplanted kidney
Shiying TANG ; Chuxiao XU ; Jianfei YE ; Huiying HE ; Hongxian ZHANG ; Guoliang WANG ; Shudong ZHANG
Chinese Journal of Urology 2025;46(3):230-232
Renal cell carcinoma in a transplanted kidney is rare, and partial nephrectomy in transplanted kidney is even more uncommon. A patient with papillary transplanted renal cell carcinoma who underwent partial nephrectomy was reported. The patient was admitted to the hospital due to the discovery of transplanted kidney mass, and the enhanced examination of CTU found a lesion in the upper pole of the transplanted kidney in the right iliac fossa, which may be renal cancer, with a diameter of about 2 cm. After open partial nephrectomy of the transplanted kidney, the postoperative pathology showed that the tumor was papillary renal cell carcinoma. The antirejection drugs were used after surgery. During the follow-up period of 16 months, there was no recurrence of transplanted kidney tumor.
6.Construction and effectiveness evaluation of surgical complication monitoring mode based on medical record homepage data
Guanrong ZHANG ; Huiying LIANG ; Dan LI ; Yunlian XUE ; Jinqi YE ; Xiaohong YANG
Chinese Journal of Hospital Administration 2023;39(2):113-118
Objective:To explore the establishment of a surgical complication monitoring mode based on data on the medical record homepage, and analyze its impact on the trend of changes in surgical complication incidence.Methods:A monitoring mode of surgical complication was developed based on the " structure-process-results" framework by using surgical complication rates derived from performance appraisal for a tertiary general hospital in Guangzhou. The number of surgical complications and the number of discharged surgical patients was collected from the hospital from January 2019 to June 2022 through the home page collection system for performance appraisal of national tertiary public hospitals. Descriptive analysis was used to analyze the incidence of surgical complications, and Joinpoint regression was used to analyze the trend of changes in the incidence of surgical complications. Monthly percentage change ( MPC) and average monthly percentage change ( AMPC) were calculated. Results:Since the hospital began implementing the surgical complication monitoring mode in May 2021, the incidence of surgical complications had decreased from 2.55% in June 2021 to 0.82% in June 2022, with an MPC of -5.58% ( P=0.024), which was better than the changes from January 2019 to May 2021 ( MPC=0.18%, P=0.755). Conclusions:The surgical complication monitoring mode constructed by the hospital can effectively reduce the incidence of surgical complications, providing reference for optimizing hospital′s medical quality management process and decision-making mode.
7.A case of nephrosialidosis caused by mutation of neuraminidase 1 gene
Xiaoyi CAI ; Huiying DENG ; Ye CHEN ; Mei TAN ; Xia GAO
Chinese Journal of Nephrology 2023;39(9):712-715
The child was a 9-year-old girl, and sought medical advice due to "proteinuria for over a month". Renal biopsy result showed focal segmental glomerulosclerosis with diffuse vacuolization of glomerular podocytes and tubular epithelial cells. The child was diagnosed as type Ⅱ sialidosis with a compound heterozygote mutation in neuraminidase 1 gene for c.239C>T(p.Pro80Leu), c.220G>C(p.Val74Leu) and c.205A>G(p.Arg69Gly). Her father was proved to carry the first mutation, and her mother carried the other two, respectively. The report aims to improve the clinician's understanding of the rare disease. Early diagnosis can help avoid overuse of immunosuppressants, guide treatment reasonably and improve prognosis.
8.Analysis of the polymorphisms and haplotypes of cyclin-dependent kinase inhibitor 2B antisense RNA 1 gene in patients with ulcerative colitis
Yuan XU ; Xiaoxiao SHAO ; Dingyuan HU ; Shunyu RAO ; Huiying XIAO ; Ye FANG ; Yi JIANG
Chinese Journal of Digestion 2022;42(9):627-633
Objective:To investigate the relationship between polymorphisms and haplotypes of cyclin-dependent kinase inhibitor 2B antisense RNA 1 ( CDKN2 B- AS1) gene and the risk of ulcerative colitis (UC). Methods:From January 2012 to January 2021, a total of 534 UC patients diagnosed at the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University (Yuying Children′s Hospital) and during the same period 560 gender- and age-matched healthy controls were selected. Genotypes of CDKN2 B- AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) in venous blood were determined by matrix assisted laser desorption ionization time-of-flight mass spectrometry technique. Unconditional logistic regression was used to analyze the difference in the distribution of CDKN2 B- AS1 gene polymorphisms between UC patients and healthy controls, as well as the influence on the clinicopathologic characteristics of UC patients. Software Haploview 4.2 was used to analyze the linkage disequilibrium and haplotype. Chi-square test was used for statistical analysis. Results:The frequencies of variant genotype (AG+ GG) and variant allele (G) of rs1063192 in UC patients were higher than those in healthy controls (32.4%, 173/534 vs. 24.8%, 139/560; 18.1%, 193/1 068 vs. 13.7%, 153/1 120), and the differences were statistically significant ( OR=1.45 and 1.40, 95% confidence interval(95% CI) 1.12 to 1.89 and 1.11 to 1.77, P=0.006 and 0.004, corrected P=0.030 and 0.020). The frequency of variant allele (G) of rs10757274 in UC patients was lower than that in healthy controls (34.7%, 371/1 068 vs. 39.5%, 442/1 120), and the difference was statistically significant ( OR=0.82, 95% CI 0.69 to 0.98, P=0.025). However, the difference was not significant after Bonferroni correction (corrected P>0.05). According to the Montreal classification, the frequency of homozygous variant genotype (GG) of rs1063192 in the patients with extensive colitis was higher than that in patients with proctitis plus left-sided colitis (6.6%, 14/211 vs. 1.9%, 6/323), and the difference was statistically significant ( OR=3.92, 95% CI 1.47 to 10.42, P=0.006, corrected P=0.030). There was linkage disequilibrium among rs10757274, rs2383207, rs10757278 and rs1333048 of CDKN2 B- AS1 gene. The frequency of haplotype GGGC in UC patients was lower than that in healthy controls (33.3%, 355.5/1 068 vs. 37.8%, 423.4/1 120), and the frequency of haplotype AGGC in UC patients was higher than that in healthy controls (6.7%, 71.7/1 068 vs. 3.6%, 40.3/1 120), and the differences were statistically significant ( χ2=4.81 and 11.16, P=0.028 and<0.001). Conclusions:The variation of rs1063192 in CDKN2 B- AS1 gene may increase the risk of UC. The risk of extensive colitis in patients carrying homozygous variant genotype (GG) of rs1063192 may rise. Among the haplotypes composed of rs10757274, rs2383207, rs10757278 and rs1333048, the risk of UC may decrease in the individuals carrying haplotype GGGC. However, the risk of UC may increase in the individuals carrying haplotype AGGC. The correlation between the variation of 10757274 and the risk of UC still needs to be further verified by expanding the sample size.
9.Research hotspots and frontier trends in standardized residency training based on CiteSpace visual analysis software
Lifeng WEI ; Huiying FANG ; Ye LI ; Di LIU ; Libo LIANG ; Zheng KANG ; Mingli JIAO
Chinese Journal of Medical Education Research 2022;21(1):54-59
Objective:By analyzing visually field of standardized residency training from 2008 to 2018, and exploring the field research hotspots and the frontier trend, to provide direction and reference for the field of standardized residency training in our country.Methods:Using CiteSpace visualized analysis software as a research tool, a statistical analysis was conducted on 1 120 pieces of literature in the field of standardized residency training retrieved from the core database of Web of Science.Results:The research strength of standardized residency training was mainly concentrated in the United States, with a total output of 697 papers, accounting for 62.23% of the total number of articles published in the past decade. High yield author Gillespie C published 8 papers, and highly cited author Aggarwal R's paper was cited 54 times. Acad Med, a highly cited journal, was cited the most frequently, with 470 citations in past 10 years. High frequency key words were "resident", "education", "performance", etc. Mutators included "system", "older adult", "operating room", and so on.Conclusion:The research hotspots in the field of standardized residency training in recent ten years include the teaching of residents, the assessment of clinical ability of residents, the standardized patients, etc. Frontier trends focus on resident self-assessment system, surgical training, resident professional core competences, etc.
10.Clinical features and treatment efficiency of 6 children with Dent disease
Xiaoyi CAI ; Yingjie LI ; Ye CHEN ; Huiying DENG ; Mei TAN
Chinese Journal of Applied Clinical Pediatrics 2021;36(5):374-376
Objective:To summarize the clinical features, genetic testing and treatment efficacy of 6 children with Dent disease.Methods:Six children diagnosed with Dent disease in Guangzhou Women and Children′s Medical Center from January 2014 to March 2019 were enrolled.Their medical history, clinical manifestations, laboratory results, genetic test results, and proteinuria level, calciuria level and renal function after medication were measured.Results:All patients were male, with the onset age ranged from 1 to 9 years old.They were followed up for 6 months to 4 years.All the children had low molecular weight proteinuria.Urine protein electrophoresis showed that the ratio of low molecular weight proteinuria in only 2 cases was more than 50%.Renal biopsy suggested that all cases were combined with glomerular lesions.Five cases had hypercalciuria.Under the microscope, there were 5 cases of hematuria.Two case had rickets, and there was no renal calcium deposition and hypophosphatemia.Five cases were detected with CLCN5 mutations, of which p. C160Yfs*49 and p. G523D were first reported.One case had an OCRL1 mutation.Patients were treated with Hydrochlorothiazide and angiotensin converting enzyme inhibitor (ACEI). The 24 h urinary calcium level after treatment was lower than that before treatment [0.40 (0.24, 0.43) mmol/kg vs.0.12 (0.11, 0.14) mmol/kg, U=2.00, P<0.01]. However, there was no significant decrease in the 24 h-urinary protein level before and after treatment [77.09 (62.41, 88.01) mg/kg vs.80.33 (66.03, 92.52) mg/kg, U=12.00, P>0.05]. Conclusions:Dent disease is mainly characterized by low molecular weight proteinuria, and some patients may not be associated with hypercalciuria.Gene tests help to identify the disease type.ACEI and Hydrochlorothiazide can reduce the urinary calcium level, but cannot improve the level of urinary protein.

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