Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

The aim of this study was to investigate the trend in testicular volume changes after orchiopexy in children with cryptorchidism. The clinical data of 854 children with cryptorchidism who underwent orchiopexy between January 2013 and December 2016 in Shenzhen Children's Hospital (Shenzhen, China) were retrospectively analyzed. The mean (standard deviation) age of the patients was 2.8 (2.5) years, and the duration of follow-up ranged from 1 year to 5 years. Ultrasonography was conducted preoperatively and postoperatively. The variables analyzed included age at the time of surgery, type of surgical procedure, laterality, preoperative testicular position, preoperative and postoperative testicular volumes, and the testicular volume ratio of them. The average testicular volumes preoperatively and at 1 year, 2 years, 3 years, and 5 years postoperatively were 0.27 ml, 0.38 ml, 0.53 ml, 0.87 ml, and 1.00 ml, respectively ( P < 0.001). The corresponding testicular volume ratios were 0.67, 0.76, 0.80, 0.83, and 0.84 ( P < 0.001). The mean volume of the undescended testes was significantly smaller than the mean normative value ( P < 0.001, lower than the 10 th percentile). The postoperative testicular volumes in children with cryptorchidism were generally lower than those in healthy boys but were still greater than the 10 th percentile and exhibited an increasing trend. The older the child is at the time of surgery, the larger the gap in volume between the affected and normal testes. Although testicular volume tends to gradually increase after orchiopexy for cryptorchidism, it could not normalizes. Earlier surgery results in affected testicular volumes closer to those of healthy boys.
Humans ; Male ; Cryptorchidism/diagnostic imaging* ; Orchiopexy ; Child, Preschool ; Testis/surgery* ; Retrospective Studies ; Organ Size ; Ultrasonography ; Infant ; Child ; Postoperative Period ; Follow-Up Studies

Objective:To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insec-ticides(NNI).Methods:Fifteen C57BL/6 male mice were randomly divided into control group(CTRI.group),exposure group(NNI group)and Lactobacillus intervention group(NNI-L group).The mice in CTRL group were given 0.02ml/g of 0.5％carboxym-ethyl cellulose sodium solution by gavage for 14 days.The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days.The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5 × 108cfu/ml of Lactobacillus reuteri powder so-lution for 14 days.Then,the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining,immunofluores-cence staining and RNA sequencing.Results:Compared with CTRL group,the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner.And the decline in the number of spermatogenic cells and sperm was observed.And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group.The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequen-cing,with significant down-regulation being found in NPFF and IGF2.While the expression of HSD3B8 was significantly up-regulated.The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri.Conclusion:Testicular spermatogenesis and endocrine function can be damaged by NNI exposure.And oral administration of Lactoba-cillus reuteri protects testis from the adverse effects of NNI toxicity.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To identify the factors influencing the diagnostic accuracy of endoscopic ultrasonography (EUS) for colorectal submucosal tumors (SMT).Methods:A retrospective analysis was conducted on 330 colorectal SMT lesions (from 323 patients) diagnosed by EUS at Shenzhen Hospital of Southern Medical University from December 2015 to October 2023. Pathological diagnosis were confirmed through endoscopic resection, EUS-guided fine needle aspiration (EUS-FNA) or surgical resection. Diagnostic accuracy was calculated for each type of colorectal SMT. Univariate and multivariate logistic regression analysis were performed to identify factors affecting EUS diagnostic accuracy.Results:The overall diagnostic accuracy of EUS for colorectal SMT was 73.6% (243/330). Among 19 SMT subtypes enrolled, neuroendocrine neoplasms (51.2%, 169/330) and lipomas (15.5%, 51/330) were most prevalent, while 17 rare subtypes each accounted for <6%. Seven rare SMT (mucosal chronic inflammation, colorectal schwannoma, xanthogranulomatous inflammation, capillary hemangioma, colonic xanthoma, lymphadenoid complex, and angiomyolipoma) showed 0% diagnostic accuracy. Seven other subtypes (granular cell tumor, leiomyoma, rectal tonsil, intestinal schistosomiasis, fibrous tissue hyperplasia, gastrointestinal stromal tumor, and lymphangioma) showed accuracy <30%, whereas five subtypes (cyst, bowel endometriosis, neuroendocrine neoplasm, lipoma, and pneumatosis cystoides intestinalis) achieved >60% accuracy. Multivariate logistic regression analysis confirmed that the lesion location (left colon VS rectum: OR=0.06, 95% CI: 0.02-0.17, P<0.001; right colon VS rectum: OR=0.04, 95% CI: 0.01-0.13, P<0.001; ileocecal valve VS rectum: OR=0.09, 95% CI: 0.02-0.42, P=0.002); echogenicity (anechoic VS hypoechoic: OR=6.26, 95% CI: 1.31-29.97, P=0.022; hyperechoic VS hypoechoic: OR=13.39, 95% CI: 4.16-43.09, P<0.001) and ultrasonic layer (layer 4 VS layer 3: OR=0.22, 95% CI: 0.06-0.81, P=0.023) were independent influencing factors of EUS diagnostic accuracy for colorectal SMT. Conclusion:Neuroendocrine neoplasms and lipomas represent the most common colorectal SMT, whereas rare and uncommon SMT exhibit low EUS diagnostic accuracy. Lesion location, echogenicity, and ultrasonic layer significantly influence EUS diagnostic accuracy for colorectal SMT.

Objective:To compare the clinical efficacy between microscopic varicocelectomy and laparoscopic varicocelectomy in the treatment of varicocele(VC)with male infertility.Methods:A total of 307 patients who were diagnosed with VC complicated with male infertility and admitted to the Affiliated Hospital of Qingdao University from October 2018 to October 2022 were recruited for retrospective analysis.The patients were divided into the microscopic group(180 cases)and laparoscopic group(127 cases)according to the surgery method.The pre-and postoperative clinical data of these two groups were analyzed,including the degree of dilatation and reflux time of internal spermatic vein,hemodynamic parameters of testicular capsular artery,proportion of progressive motility spermato-zoa(PR),concentration of spermatozoa,proportion of normal morphology sperm,the pregnancy outcome of spouses and the incidence of complications related with surgery within 2 years postoperatively.Results:All the surgeries for the 307 patients in this study were successful.There was no significant difference in operation time,hospitalization time and management expenses between the microscop-ic group and the laparoscopic group(P＞0.05).Compared to the patients in laparoscopic group,the patients in the microscopic group received a better improvement in venous diameter,reflux time of spermatic veins and hemodynamic parameters of testicular capsular ar-tery(P＜0.05).Moreover,the semen analysis showed that the PR,spermatozoa concentration and proportion of normal morphology sperm in the microscopic group were also obviously increased than those in the laparoscopic group(P＜0.05).During the 2-year fol-low-up period,the conception rate of spouses in the microscopic group was 67.2％,while only 47.2％in the laparoscopic group,in which the difference was statistically significant(P＜0.05).Besides,the time-to-pregnancy(TTP)within 2 years postoperatively in the microscopic group was significantly shorter than that in the laparoscopic group(P＜0.05).Meanwhile,the incidence of adverse pregnancy outcomes in the microscopic group was also significantly lower than that in the laparoscopic group(P＜0.05).It is worth mentioned that the spontaneous conception rate of spouses with successful pregnancy in the microscopic group was also significantly higher than that in the laparoscopic group(P＜0.05).Severe complication such as testicular atrophy,bleeding and infection did not appear in both of two groups.However,the incidences of testicular hydrocele and recurrence of VC postoperatively in the laparoscopic group were significantly higher than those in the microscopic group(P＜0.05).Conclusion:Both microscopic varicocelectomy and laparoscopic varicocelectomy can be applied to the management of VC combined with male infertility.But microscopic varicocelectomy showed better clinical efficacy in improving the testicular hemodynamic parameters,semen quality,pregnancy outcome and postopera-tive complications,which is worthy of further clinical applications.

Objective:To identify the factors influencing the diagnostic accuracy of endoscopic ultrasonography (EUS) for colorectal submucosal tumors (SMT).Methods:A retrospective analysis was conducted on 330 colorectal SMT lesions (from 323 patients) diagnosed by EUS at Shenzhen Hospital of Southern Medical University from December 2015 to October 2023. Pathological diagnosis were confirmed through endoscopic resection, EUS-guided fine needle aspiration (EUS-FNA) or surgical resection. Diagnostic accuracy was calculated for each type of colorectal SMT. Univariate and multivariate logistic regression analysis were performed to identify factors affecting EUS diagnostic accuracy.Results:The overall diagnostic accuracy of EUS for colorectal SMT was 73.6% (243/330). Among 19 SMT subtypes enrolled, neuroendocrine neoplasms (51.2%, 169/330) and lipomas (15.5%, 51/330) were most prevalent, while 17 rare subtypes each accounted for <6%. Seven rare SMT (mucosal chronic inflammation, colorectal schwannoma, xanthogranulomatous inflammation, capillary hemangioma, colonic xanthoma, lymphadenoid complex, and angiomyolipoma) showed 0% diagnostic accuracy. Seven other subtypes (granular cell tumor, leiomyoma, rectal tonsil, intestinal schistosomiasis, fibrous tissue hyperplasia, gastrointestinal stromal tumor, and lymphangioma) showed accuracy <30%, whereas five subtypes (cyst, bowel endometriosis, neuroendocrine neoplasm, lipoma, and pneumatosis cystoides intestinalis) achieved >60% accuracy. Multivariate logistic regression analysis confirmed that the lesion location (left colon VS rectum: OR=0.06, 95% CI: 0.02-0.17, P<0.001; right colon VS rectum: OR=0.04, 95% CI: 0.01-0.13, P<0.001; ileocecal valve VS rectum: OR=0.09, 95% CI: 0.02-0.42, P=0.002); echogenicity (anechoic VS hypoechoic: OR=6.26, 95% CI: 1.31-29.97, P=0.022; hyperechoic VS hypoechoic: OR=13.39, 95% CI: 4.16-43.09, P<0.001) and ultrasonic layer (layer 4 VS layer 3: OR=0.22, 95% CI: 0.06-0.81, P=0.023) were independent influencing factors of EUS diagnostic accuracy for colorectal SMT. Conclusion:Neuroendocrine neoplasms and lipomas represent the most common colorectal SMT, whereas rare and uncommon SMT exhibit low EUS diagnostic accuracy. Lesion location, echogenicity, and ultrasonic layer significantly influence EUS diagnostic accuracy for colorectal SMT.

Objective:To analyze the epidemiological characteristics and economic burden of palmoplantar pustulosis (PPP) in China.Methods:A population-based retrospective study was conducted using the data from China′s Urban Basic Medical Insurance data from January 1, 2012, to December 31, 2016. International Classification of Diseases code and diagnoses in Chinese for PPP were used to identify cases and estimate the prevalence, incidence, and cost. Subgroup analyses were performed according to age and sex, and sensitivity analyses were conducted to evaluate the robustness of the results. Age-adjusted prevalence rates were calculated based on the 2010 national census data.Results:The crude prevalence and incidence rate of PPP in 2016 were 2.730/100 000 (95% CI: 2.218/100 000-3.242/100 000) and 1.556/100 000 (95% CI: 1.154/100 000-1.958/100 000), and the prevalence rate of females (2.910/100 000) was higher than that of males (2.490/100 000, χ2=97.48, P=0.001). The incidence rate of females (1.745/100 000) was also higher than that of males (1.418/100 000, χ2=85.02, P=0.001). The age peak of incidence and prevalence of patients with PPP was in the 30-39-year age group and a small peak existed in the 0-3-year age group among people under 20 years old. From 2012 to 2016, the average number of visits was (2.44±0.04) per patient, and the total per-capita cost per year was (982.40±39.19) yuan. Conclusion:In 2016, the prevalence and incidence rate of PPP in China were higher in females than in males, and the highest age peak was in the 30-39-year age group.