1.Structure and Function of GPR126/ADGRG6
Ting-Ting WU ; Si-Qi JIA ; Shu-Zhu CAO ; De-Xin ZHU ; Guo-Chao TANG ; Zhi-Hua SUN ; Xing-Mei DENG ; Hui ZHANG
Progress in Biochemistry and Biophysics 2025;52(2):299-309
GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.
2.Irreversible Electroporation for the Focal Treatment of Prostate Cancer: A Systematic Review
Kai ZHANG ; Jeremy TEOH ; Gang ZHU ; Chi-Fai NG ; Michel SUBERVILLE ; Pilar LAGUNA ; Jean de la ROSETTE
The World Journal of Men's Health 2025;43(2):321-332
Purpose:
Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique.
Materials and Methods:
A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality.
Results:
The in-field clinically significant prostate cancer rate was reported between 0%–15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%–96.8%. The post-operative pad-free rate ranged between 96.7%–100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare.
Conclusions
These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients’ urinary and erectile function
3.Irreversible Electroporation for the Focal Treatment of Prostate Cancer: A Systematic Review
Kai ZHANG ; Jeremy TEOH ; Gang ZHU ; Chi-Fai NG ; Michel SUBERVILLE ; Pilar LAGUNA ; Jean de la ROSETTE
The World Journal of Men's Health 2025;43(2):321-332
Purpose:
Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique.
Materials and Methods:
A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality.
Results:
The in-field clinically significant prostate cancer rate was reported between 0%–15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%–96.8%. The post-operative pad-free rate ranged between 96.7%–100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare.
Conclusions
These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients’ urinary and erectile function
4.Irreversible Electroporation for the Focal Treatment of Prostate Cancer: A Systematic Review
Kai ZHANG ; Jeremy TEOH ; Gang ZHU ; Chi-Fai NG ; Michel SUBERVILLE ; Pilar LAGUNA ; Jean de la ROSETTE
The World Journal of Men's Health 2025;43(2):321-332
Purpose:
Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique.
Materials and Methods:
A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality.
Results:
The in-field clinically significant prostate cancer rate was reported between 0%–15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%–96.8%. The post-operative pad-free rate ranged between 96.7%–100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare.
Conclusions
These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients’ urinary and erectile function
5.Irreversible Electroporation for the Focal Treatment of Prostate Cancer: A Systematic Review
Kai ZHANG ; Jeremy TEOH ; Gang ZHU ; Chi-Fai NG ; Michel SUBERVILLE ; Pilar LAGUNA ; Jean de la ROSETTE
The World Journal of Men's Health 2025;43(2):321-332
Purpose:
Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique.
Materials and Methods:
A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality.
Results:
The in-field clinically significant prostate cancer rate was reported between 0%–15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%–96.8%. The post-operative pad-free rate ranged between 96.7%–100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare.
Conclusions
These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients’ urinary and erectile function
6.Irreversible Electroporation for the Focal Treatment of Prostate Cancer: A Systematic Review
Kai ZHANG ; Jeremy TEOH ; Gang ZHU ; Chi-Fai NG ; Michel SUBERVILLE ; Pilar LAGUNA ; Jean de la ROSETTE
The World Journal of Men's Health 2025;43(2):321-332
Purpose:
Irreversible electroporation (IRE) is a promising alternative treatment for low-intermediate-risk localized prostate cancer. In this systematic review we aim to evaluate the safety profile and functional and oncological outcomes of this new technique.
Materials and Methods:
A systematic review of the literature was performed on PubMed, EMBASE, and Scopus up to 24 August 2023. Nineteen studies were analyzed, including 12 prospective studies and 7 retrospective studies. A total of 1,452 patients underwent IRE as the sole primary treatment modality.
Results:
The in-field clinically significant prostate cancer rate was reported between 0%–15.6% in the repeat biopsy. The retreatment rate was reported from 8% to 36.6%. The 3 years failure-free survival was presented between 90%–96.8%. The post-operative pad-free rate ranged between 96.7%–100%. Greater heterogeneity exists considering the change in erectile function. The most common reported complications were urinary tract infection and hematuria. Major complications were rare.
Conclusions
These results underline that IRE achieves favorable oncological control with an excellent safety profile, in the meantime preserving patients’ urinary and erectile function
7.Dorsally displaced distal radial double-column Die-punch fractures by dorsal approach external fixator combined with Kirschner wires.
Fu-de JIAO ; Jing-Wei ZHANG ; Li-Mei ZHU ; Lin AN ; Yun-Qiang ZHUANG ; Jian-Ming CHEN
China Journal of Orthopaedics and Traumatology 2025;38(1):87-91
OBJECTIVE:
Investigating the clinical efficacy of treating dorsally displaced distal radial double-column Die-punch fractures using a dorsal approach external fixator combined with Kirschner wires.
METHODS:
Retrospectively analyzed the clinical data of 15 patients with distal radial double-column Die-punch fractures treated with an external fixator combined with Kirschner wire between July 2020 and January 2023. There were 10 males and 5 females;6 cases on the left side and 9 on the right;age ranged from 22 to 76 years old. Recorded the preoperative and the final follow-up Cooney wrist function scores for the patients. The fracture healing time, and occurrence of complications were recorded.
RESULTS:
All 15 patients were followed up ranged from 12 to 16 months post-operation. All fractures achieved bony union, healing time ranging form 8 to 16 weeks. Not a single patient exhibited complications such as surgical site infection, fracture redislocation, or tendon injury. All individuals had their Kirschner wires and external fixation devices removed six weeks post-operatively and commenced rehabilitative therapy for wrist articulation. The Cooney wrist function scores at preoperative and ranged from 5 to 45 scores, at the latest follow-up ranged from 65 to 100 scores. At the final follow-up, the results were assessed as excellent in 10 patients, good in 4 patients, and fair in 1 patient.
CONCLUSION
The clinical efficacy of treating distal radial double-column Die-punch fractures using a dorsal approach external fixator combined with Kirschner wires is satisfactory.
Humans
;
Male
;
Female
;
Middle Aged
;
Adult
;
External Fixators
;
Bone Wires
;
Aged
;
Retrospective Studies
;
Radius Fractures/physiopathology*
;
Young Adult
;
Fracture Fixation/methods*
8.Prediction of testicular histology in azoospermia patients through deep learning-enabled two-dimensional grayscale ultrasound.
Jia-Ying HU ; Zhen-Zhe LIN ; Li DING ; Zhi-Xing ZHANG ; Wan-Ling HUANG ; Sha-Sha HUANG ; Bin LI ; Xiao-Yan XIE ; Ming-De LU ; Chun-Hua DENG ; Hao-Tian LIN ; Yong GAO ; Zhu WANG
Asian Journal of Andrology 2025;27(2):254-260
Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans
;
Male
;
Azoospermia/diagnostic imaging*
;
Deep Learning
;
Testis/pathology*
;
Retrospective Studies
;
Adult
;
Ultrasonography/methods*
;
Sperm Retrieval
;
Sertoli Cell-Only Syndrome/diagnostic imaging*
9.Correlation between pathological features at the positive margin and biochemical recurrence after radical prostatectomy in patients with organ-confined prostate cancer.
Xin-Huan FAN ; Yan ZHANG ; Lin-Lin ZHU ; Cheng-Yi LIU ; De-Gang CHEN ; Shi-Fang SANG ; Peng-Cheng XU
National Journal of Andrology 2025;31(3):202-207
Objective: To investigate the correlation between pathological features at the positive margins and biochemical recurrence after radical prostatectomy for prostate cancer. Methods: From June 2014 to December 2019, a total of 200 patients with organ-confined prostate cancer who underwent radical prostatectomy were included in this study by the method of case matching (1∶1). One hundred patients with positive surgical margin and 100 with negative surgical margin were enrolled in this study. All patients did not receive any adjuvant treatment after surgery with a clinical stage of T2/N0. BCR-free survival was estimated using the Kaplan-Meier method. An optimal cutoff for the PSM length which differentiated risk for BCR was identified by Classification and Regression Tree analysis (CART). Cox proportional hazards regression model was used to assess the association between variables and BCR-free survival. Results: A total of 200 patients were included in this study, and 177 patients with pT2 stage were pathological after operation. The median follow-up time of this group of patients was 32.8 months ranged from 5.6 to 80.5 months. A total of 28 cases of biochemical recurrence were found through PSA follow-up after surgery, including 6 cases (6.0%) in the negative margin group and 22 cases (22.0%) in the positive margin group. The result of Kaplan Meier survival curve analysis showed that the non biochemical recurrence survival time of the negative margin group was longer than that of the positive margin group (log rank χ2=9.336, P=0.003). It was found that the length of positive margin ≥1 mm in the positive margin group was positively correlated with postoperative biochemical recurrence. Multivariate Cox proportional hazards regression was used to identify that the highest Gleason score ≥8 and the length of positive ≥1 mm were independent factors of postoperative biochemical recurrence in both the overall patients and the patients with positive margin. Conclusion: The patients with highest Gleason score ≥8 and the length of positive ≥1mm are at elevated risk for BCR.
Humans
;
Male
;
Prostatectomy
;
Prostatic Neoplasms/pathology*
;
Neoplasm Recurrence, Local
;
Margins of Excision
;
Prostate-Specific Antigen/blood*
;
Proportional Hazards Models
;
Middle Aged
;
Aged
;
Neoplasm Staging
;
Kaplan-Meier Estimate
10.Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer:A Single-Institution Study
Qing Zi KONG ; Qun Li LIU ; Qin De HUANG ; Tong Yu WANG ; Jie Jing LI ; Zheng ZHANG ; Xi Xi WANG ; Ling Chuan LIU ; Di Ya ZHANG ; Kang Jia SHAO ; Min Yi ZHU ; Meng Yi CHEN ; Mei LIU ; Hong Wei ZHAO
Biomedical and Environmental Sciences 2024;37(5):457-470
Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

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