Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase （FAH） in the progression of glioblastoma （GBM）. MethodsDifferential expression analysis was performed on the TCGA-GBM， GSE4290， and GSE116520 datasets. Weighted gene co-expression network analysis （WGCNA） was used to identify key modules， and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments， and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets （P<0.05）. WGCNA revealed that the turquoise module was most strongly associated with tumor purity， stromal score， immune score， and ESTIMATE score （P<0.001）. Compared with normal tissues， three prognostic genes （CTSD， FAH， and THBD） were upregulated in GBM and correlated with immune infiltration （P<0.05）. FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues， and its expression was significantly associated with age stratification and TP53 mutation （P<0.05）. CCK-8 assay results showed that， compared with the shNC group， the proliferative activity of GBM cells in the shFAH group was reduced （P<0.001）. Transwell migration and invasion assays demonstrated that， relative to the shNC group， the numbers of migrated and invaded cells in the shFAH group decreased （P<0.05）. Western blot analysis revealed that the protein expression levels of PI3K， p-AKT， and p-mTOR in the shFAH group decreased compared with those in the shNC group （P<0.05）. In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group （P<0.001）. ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.

[Objective] To compare the clinical efficacy of super pulse thulium laser enucleation of the prostate (SPThuLEP) with "open tunnel" and transurethral holmium laser enucleation of the prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH), in order to provide reference for the treatment options of BPH. [Methods] The clinical data of 112 BPH patients treated in our hospital during Jan.2023 and Jul.2023 were retrospectively analyzed, including 65 treated with SPThuLEP with "open tunnel" and 57 with HoLEP.The operation time, postoperative hemoglobin decrease, postoperative bladder irrigation, catheter indwelling time, hospitalization time and complications were compared between the two groups.The changes of maximum urine flow rate (Qmax), international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) and prostate-specific antigen (PSA) were compared between the two groups before operation and one month after operation. [Results] All operations were successful without conversion to open or transurethral plasmakinetic resection.The postoperative decrease of hemoglobin in SPThuLEP group was lower than that in HoLEP group [(13.12±6.72) g/L vs. (21.02±6.51) g/L], with statistical difference (P<0.05). There were no significant differences in the operation time [(63.35±15.73) min vs.(61.02±17.55) min], postoperative bladder irrigation time [(1.07±0.45) d vs. (1.06±0.36) d], catheter indwelling time [(2.98±0.56) d vs. (3.01±0.63) d] and hospitalization time [(3.63±0.61) d vs.(3.79±0.76) d] between the two groups (P>0.05). No blood transfusion, secondary bleeding or unplanned hospitalization occurred, and there were no serious complications such as transurethral electroresection syndrome (TURS), urethral stricture and urinary incontinence.One month after operation, the Qmax, IPSS, QoL, PVR and PSA of the two groups were significantly improved compared with those before operation (P<0.05), but with no statistical difference between the two groups (P>0.05). [Conclusion] SPThuLEP with "open tunnel" has comparable efficacy as HoLEP in the treatment of BPH.With advantages of small amount of bleeding and high safety, this minimally invasive technique can be widely popularized in clinical practice.

[Objective] To evaluate the efficacy and safety of sacral neuromodulation (SNM) in the treatment of patients with benign prostatic hyperplasia (BPH) complicated with underactive bladder (UAB) who respond poorly to transurethral resection of the prostate (TURP). [Methods] A retrospective analysis was performed on 10 patients with BPH and UAB treated with TURP by the same surgeon in Zhongda Hospital Southeast University during Jan.2018 and Jan.2023.The residual urine volume was not significantly relieved after operation, and the maximum urine flow rate and urine volume per discharge were not significantly improved.All patients underwent phase I SNM, and urinary diaries were recorded before and after surgery to observe the average daily frequency of urination, volume per urination, maximum urine flow rate, and residual urine volume. [Results] The operation time was (97.6±11.2) min.During the postoperative test of 2-4 weeks, if the residual urine volume reduction by more than 50% was deemed as effective, SNM was effective in 6 patients (60.0%). Compared with preoperative results, the daily frequency of urination [(20.2±3.8) times vs. (13.2±3.2) times], volume per urination [(119.2±56.7) mL vs. (246.5±59.2) mL], maximum urine flow rate [(8.7±1.5) mL/s vs. (16.5±2.6) mL/s], and residual urine volume [(222.5±55.0) mL vs. (80.8±16.0) mL] were significantly improved, with statistical significance (P<0.05). There were no complications such as bleeding, infection, fever or pain.The 6 patients who had effective outcomes successfully completed phase II surgery, and the fistula was removed.During the follow-up of 1 year, the curative effect was stable, and there were no complications such as electrode displacement, incision infection, or pain in the irritation sites.The residual urine volume of the other 4 unsuccessful patients did not improve significantly, and the electrodes were removed and the vesicostomy tube was retained. [Conclusion] SNM is safe and effective in the treatment of BPH with UAB patients with poor curative effects after TURP.

G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all mar-keted drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respi-ration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Ab-normalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alz-heimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To explore the relationship between long-term blood pressure variability and arteriosclerosis in women with a history of hypertensive disorders in pregnancy (HDP).Methods:This study was a retrospective cohort study. Data were obtained from the Kailuan Research Database. Women with a history of HDP who delivered between January 1990 and December 2020 and completed brachial-ankle pulse wave velocity (baPWV) measurement in the postpartum period were enrolled. Baseline data were obtained from the first post-delivery health examination, while the outcome measure was the baPWV recorded during the last follow-up visit, synchronized with blood pressure measurements. Based on long-term blood pressure variability, the enrolled study subjects were divided into the first, second, and third tertile groups in ascending order using the tertile method, and intergroup differences in clinical characteristics were compared. Multivariable logistic regression was performed to evaluate the impact of long-term blood pressure variability levels on arteriosclerosis risk in women with a history of HDP. Sensitivity analyses excluded individuals with multiple deliveries to validate the robustness of findings. Subgroup analyses were conducted based on delivery age (<40 vs. ≥40 years) and blood pressure measurement frequency (3 vs. >3 times) to explore the potential impact of different population characteristics on the study results.Results:A total of 421 study subjects were enrolled, aged (36.07±6.05) years, with a baPWV value of (1 376.80±238.18) cm/s. Long-term blood pressure variability was 4.66 (3.41, 6.50) mmHg (1 mmHg=0.133 kPa). The first, second and third quartile group included 140, 141 and 140 individuals, respectively. In the total population, the incidence of arteriosclerosis was 40.4% (170/421). The incidence rates in the first, second, and third tertile groups were 34.3% (48/140), 39.0% (55/141), and 47.9% (67/140), respectively. Multivariate logistic regression analysis showed that increased long-term blood pressure variability was an independent risk factor for arteriosclerosis in women with a history of HDP ( OR=1.702, 95% CI 1.018-2.844, P=0.043). The results of sensitivity analyses were consistent with that of the primary analysis ( OR=1.758, 95% CI 1.044-2.959, P=0.034). Subgroup analyses further indicated that in the subgroups with delivery age <40 years ( OR=2.116, 95% CI 1.153-3.885, P=0.016) and blood pressure measurement frequency >3 times ( OR=1.894, 95% CI 1.069-3.355, P=0.029), the association between long-term blood pressure variability and arterial stiffness risk was more significant. Conclusions:For women with a history of HDP, elevated long-term blood pressure variability may increase the risk of arteriosclerosis, and this effect is more pronounced in younger women (delivery age <40 years) and those with high-frequency blood pressure measurements (>3 times). Enhanced monitoring and management of blood pressure variability in this population are crucial to improving long-term cardiovascular health outcomes.

Objective:To investigate the distribution and clinical significance of amniotic fluid karyotype results in 2 725 cases from southern Anhui.Methods:The karyotypes of amniotic fluid from 2 725 cases of second-trimester pregnant women treated in our hospital from Jan 2017 to Dec 2023 were collected.The annual abnormal detection rate and overall abnormal rate were analyzed.Meanwhile,the abnormal detection rate was compared among 8 groups of different clinical indication including adverse pregnancy history,advanced maternal age(≥35 years),high risk of Down syndrome screening,high risk of non-invasive prenatal testing(NIPT),nuchal translucency thickness(NT)≥2.5 mm,abnormal ultrasound findings,two or more concurrent positive indications,and others.The abnormal detection rate was calculated within high risk of Down syndrome screening and NIPT.Results:Significant differences in annual abnormal rates were observed from 2017 to 2023(χ2=19.705,P=0.003).Among 2 725 cases,233(8.55%)showed abnormal karyotypes.Among them,abnormal autosomal number was the most prevalent(4.41%,120/2 725),with inversion being the most common chromosome structural abnormality.Significant differences in abnormal rates were noted among the eight clinical indication groups(χ2=438.516,P＜0.01).No statistical difference was found in abnormal detection rates among the three high-risk subgroups of Down syndrome screening(χ2=0.323,P=0.851),while significant differences were observed within the high-risk subgroups of NIPT(χ2=100.901,P＜0.01).Polymorphisms were detected in 65 cases(2.38%).Conclusions:Chromosomal numerical and structural abnormalities have been detected in southern Anhui over the past seven years,with variations across subgroups.Karyotype analysis effectively detects second-trimester fetal chromosomal abnormalities,aiding in the prevention of birth defects and worthing clinical application.

Objective To investigate the effects of Ras-related protein Rab-2B(RAB2B)on the biological behaviors of pancreatic cancer cells and elucidate its underlying mechanism.Methods PANC-1 cells,which exhibit relatively high RAB2B expression,and BXPC-3 cells,which display relatively low RAB2B expression,were selected from five pancreatic cancer cell lines.RAB2B-siRNA and pcDNA3.1-RAB2B plasmids were transfected into PANC-1 and BXPC-3 cells using a cell transfection technique.The CCK-8 assay was employed to evaluate the prolif-erative capacity of pancreatic cancer cells following RAB2B intervention.Wound healing and Transwell chamber assays were utilized to assess the migratory and invasive capabilities of pancreatic cancer cells.Additionally,the mRNA and protein expression levels of RAB2B,NF-κB,and Fibronectin 1(FN1)were analyzed by qRT-PCR and Western blot(WB),respectively.Results RAB2B mRNA and protein expression levels were significantly down-regulated in PANC-1 cells following transfection(P<0.05).CCK-8 assay results demonstrated that the proliferative capacity of PANC-1 cells was markedly reduced(P<0.05),and the wound-healing ability was substantially impaired(P<0.01)upon RAB2B knockdown.Transwell assays revealed a significant decrease in cell migration(P<0.01),while Western blot analysis indicated that the expression levels of phosphorylated p65 and FN1 were notably diminished(P<0.01).Conversely,overexpression of RAB2B reversed these aforementioned alterations.Conclusions Knockdown of RAB2B in PANC-1 cells significantly suppresses cell proliferation and migration,whereas overexpression of RAB2B in BXPC-3 cells markedly promotes these processes.This effect is likely mediated through the activation of the NF-κB signaling pathway and the subsequent regulation of FN1 expression.

Objective:To identify and evaluate the important risk factor set of anxiety and depression in occupational population, establish a risk prediction model, and provide scientific basis for making targeted mental health protection plan and promoting the mental health of workers.Methods:In August 2016, a cluster random sampling method was used to investigate 807 employees who underwent physical examination in a hospital as research objects. The simplified Chinese version of the core job content questionnaire, Athens Insomnia Scale, AIS-5 and Symptom Check List-90 (SCL-90) were used for the Occupational stress, insomnai and negative emotional symptom investigation. Chi-square and Fisher exact probability method were used for data analysis, and Bayesian network was used for model construcion and analysis.Results:The score of occupational stress was 0.88±0.15, and the incidence of occupational stress was 18.09% (146/807). AIS-5 scores were (3.03±2.82), and the incidence of insomnia was 15.99% (129/807). Depression (16.89±5.73) scores, anxiety (12.36±4.11) scores. Depression (16.89±5.73) score, anxiety (12.36±4.11) score, the detection rate was 8.55% (69/755), 7.31% (59/762). Gender, illness, education, insomnia and occupational stress were correlated with depression ( P<0.01), while education, illness, insomnia and anxiety were correlated ( P<0.05). When both occupational stress and insomnia existed, the detection rate of depression was the highest (0.4006) . Conclusion:Insomnia was a valid predictor of anxiety and depression, suggesting that occupational groups should pay attention to sleep quality and managers should rationalize work tasks in order to reduce the risk of anxiety and depression.