Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
Spermatogenesis/physiology* ; Animals ; Male ; Mice ; Epigenesis, Genetic ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Histones/metabolism* ; RNA Interference ; Testis/metabolism* ; Methylation ; Mice, Knockout ; Histone Demethylases

Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.

Objective:To investigate the long-term efficacy, safety and prognostic factors of intraoperative radiotherapy (IORT) for narrow-margin (resection margin < 1 cm) hepatectomy in patients with hepatocellular carcinoma (HCC) during radical surgery.Methods:A retrospective cohort study was conducted. The data of primary HCC patients undergoing radical surgery and narrow-margin hepatectomy IORT in the Cancer Hospital of the Chinese Academy of Medical Sciences from November 2009 to February 2019 were collected. IORT applied 6 MeV or 9 MeV electron beams and a single irradiation was given to the margin. Kaplan-Meier method was used for the overall survival (OS) and disease-free survival (DFS) analysis; log-rank test was used for survival comparison among subgroups. The recurrence patterns and adverse reactions were recorded. Univariate and multivariate Cox proportional hazards models were used to analyze the factors influencing the OS and DFS.Results:A total of 64 patients were enrolled, with the median age [ M ( Q1, Q3)] of 57 years (49, 63) years. All patients included 55 males (85.9%) and 9 females (14.1%). The median dose of IORT was 15 Gy (range: 12-17 Gy). The median follow-up time was 83.3 (64.4, 91.9) months. The 1-year, 3-year, 5-year, 7-year, 10-year OS rates were 90.4%, 80.6%, 75.5%, 71.4% and 47.6%, respectively; the 1-year, 3-year, 5-year, 7-year,10-year DFS rates were 77.8%, 68.1%, 59.6%, 57.6% and 38.4%, respectively. Univariate Cox regression analysis indicated that preoperative serum alpha-fetoprotein (AFP) > 400 ng/ml was an independent risk factor for poor OS (> 400 ng/ml vs. ≤ 400 ng/ml: HR = 6.57, 95% CI: 2.16-19.96, P < 0.001), while not the independent influencing factor of poor DFS ( HR = 1.71, 95% CI: 0.65-4.52, P = 0.277). The age ≤ 60 years or not, gender, viral hepatitis or not, American Joint Committee on Cancer stage, tumor diameter (> 5 cm or not), tumor number, degree of tumor differentiation, microvascular invasion or not, microsatellite nodules or not, anatomical liver resection or not, and the dose of IORT ≤15 Gy or not were not the independent influencing factors of poor OS and DFS (all P > 0.05). Kaplan-Meier method analysis showed that patients with preoperative serum AFP ≤ 400 ng/ml (48 cases) had better OS compared with those with preoperative serum AFP>400 ng/ml (16 cases) (5-year OS rate: 84.8% vs. 44.9%; 7-year OS rate: 79.9% vs.37.4%), and the difference was statistically significant ( P = 0.002). There was no statistically significant difference in the DFS between the 2 groups ( P = 0.134). During the follow-up, 28 patients (43.8%) relapsed, including 17 cases (26.6%) of early recurrence and 11 cases (17.2%) of late recurrence. No marginal recurrence was observed. There were 22 cases (34.4%) of intrahepatic recurrence alone, 2 cases (3.1%) of extrahepatic recurrence and 4 cases (6.3%) of stimutaneous recurrence inside and outside the liver. The 1-, 3-, 5- and 7-year cumulative recurrence rates inside the liver were 19.0%, 27.2%, 37.4% and 39.3% respectively, and the cumulative recurrence rates outside the liver were 6.4%, 8.0%, 9.6% and 9.6% respectively. There were no adverse reactions above grade 3 in the entire group. There were no surgery-related deaths within 30 d after the operation, and no radiation-induced liver disease occurred. Conclusions:Narrow-margin IORT helps HCC patients receiving hepatectomy to achieve favorable long-term survival and adverse reactions are tolerable. It can be used as a safe and effective adjuvant therapy alternative.

Objective To explore the clinical effect of 3D-printed interbody fusion cage applied in anterior cervical decompression and bone graft fusion for the treatment of cervical spondylotic myelopathy.Methods A total of 100 patients with cervical spondylotic myelopathy who underwent anterior cervical fusion surgery in our hospital from June 2020 to June 2023 were selected as the research subjects,they were randomly divided into the 3D group and the control group according to the random number table method,with 50 cases in each group.Patients in the 3D group were implanted with a 3D-printed interbody fusion cage which was made of microporous metal materials,while patients in the control group were implanted with intervertebral fusion cage which was made of polyetheretherketone material.The surgery-related indicators,cervical imaging parameters,cervical spinal cord function,cervical axial function and surgical complications of patients between the two groups were compared.Results There was no statistically significant difference in the operation time,intraoperative blood loss or length of hospital stay of patients between the two groups(P>0.05).The height of the cervical fusion segments and the Cobb angle of the fusion segments of patients in both groups at each time point after the operation were significantly increased compared with those before the operation(P<0.05).The height of the cervical fusion segments and the Cobb angle of the fusion segments of patients 1 month,3 months,and 6 months after the operation in the 3D group were all greater than those in the control group(P>0.05).The subjective symptom score and the total score of the Japanese orthopaedic association(JOA)of patients 6 months after the operation in the 3D group were higher than those in the control group(P<0.05).The cervical axial function of patients 6 months after the operation in the 3D group was better than that in the control group(P<0.05).The incidence of surgical complications in the 3D group was lower than that in the control group(P<0.05).Conclusion The use of 3D-printed interbody fusion cage during the anterior cervical decompression and bone graft fusion for patients with cervical spondylotic myelopathy can significantly improve the clinical symptoms of patients,achieve better cervical axial function,and have fewer complications.

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.

As a serine protease,thrombin can convert soluble fibrinogen into insoluble fibrin and plays a pivotal role in the coagulation cascade.Therefore,the accurate quantitative assay of thrombin levels is of great value in the evaluation of coagulation function,clinical screening and prognostic monitoring of coagulation-related diseases,and screening of drugs for targeted therapy.Existing methods for thrombin detection can be divided into two categories,e.g.,the assay of concentration levels using nucleic acid aptamers as the affinity elements and the assay of activity levels based on the hydrolytic cleavage of substrate peptides.In recent years,electrochemical biosensors have attracted much attention in thrombin detection due to high sensitivity,high selectivity,simple instrument,fast response,and good portability.In this review,the latest research progress in methods for electrochemical detection of thrombin was summarized,focusing on the detection principles and the applied signal amplification strategies of related electrochemical biosensors.In addition,the challenges with respect to the practical use of electrochemical thrombin biosensors and the prospects were discussed.

OBJECTIVE To investigate the result of human immunodeficiency virus(HIV)screening for the people visiting to a three-A hospital of Sichuan Province and analyze the prevalence of complications with hepatitis B virus(HBV)infection,hepatitis C virus(HCV)infection and Treponema pallidum(TP)infection in the emerging HIV infection patients.METHODS The result of HIV screening for the people who visited to Ziyang Central Hos-pital from Jan.1,2020 to Dec.31,2024 and the test results of HBV,HCV and TP for the emerging HIV infec-tion patients were collected and were summarized and statistically analyzed by SPSS.0 software.RESULTS Totally 289 891 case-times were tested for HIV,1529 cases were previously diagnosed with HIV,465 of whom were tested posi-tive for the first time,there was significant difference in the positive rate of test for the first time among the 5 years(x2=15.998,P=0.003).Totally 353 cases were confirmed positive among the 465 primary positive screening cases.Among the emerging HIV infection patients,the positive rate was higher in the male than in the female(x2=141.141,P＜0.001),and the positive rate was high among the population aged more than 40 year old(x2=11.448,P＜0.001),mi-grant workers(x2=270.110,P＜0.001)and low education level population(x2=25.911,P＜0.001).The detection rate of gp41 was up to 100.00％in strip type testing.The analysis of the ratio of relative light unit(RLU)to Cutoff val-ue(COI)in the initial screening experiment showed that when COI was greater than 50,all of the confirmed tests were positive,when COI ranged between 1 and 5,the false positive rate was 97.06％.The incidence of complica-tion with HBV infection in the emerging HIV infection patients was increased year by year(x2=20.355,P＜0.001),and the incidence of complication with HCV infection was increased in recent two years(x2=10.690,P=0.030).CONCLUSIONS There is no obvious rise of positive rate of HIV screening among the people visiting to the hospital in recent 5 years.The sensitivity of the primary screening of clinical laboratory is high without posi-tive missing test.The positive rates of HBV and HCV are increased among the emerging HIV infection patients.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To use machine learning to predict the efficacy of accelerated corneal collagen cross-linking (A-CXL) surgery, identify prognostic factors, and construct models to predict postoperative disease progression.Methods:A single-center retrospective study was conducted.A total of 82 keratoconus patients (112 eyes) who underwent A-CXL surgery at the West China Hospital of Sichuan University between March and December 2021 were enrolled.Preoperative and follow-up examinations included anterior segment evaluation by slit-lamp microscopy, corneal topography using Pentacam, and corneal biomechanical indices using Corvis ST.Disease progression was defined as an increase in maximum keratometry (Kmax) of ≥1 D from the preoperative level at the last follow-up.Various machine learning algorithms were employed to analyze corneal topography, biomechanical parameters and corneal densitometry values to identify prognostic factors and construct models for predicting postoperative disease progression.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (No.2023496).Written informed consent was obtained from each subject.Results:During follow-up, 15.1% (17/112) of the eyes showed progression after A-CXL.The preoperative astigmatism and stress-strain index (SSI) in the progression group were (-5.41±2.72)D and 1.41±0.78, respectively, which were significantly higher than (-3.30±2.54)D and 0.95±0.98 in the non-progression group ( t=2.80, 2.03; both P<0.05).Cox regression analysis identified preoperative astigmatism (hazard ratio [HR]=1.20), SSI (HR=1.10), and anterior corneal densitometry of 2-6 mm (CDA6) (HR=2.10) as significant risk factors for post-A-CXL progression.Among various machine learning models developed and validated, the area under the curve (AUC) values for logistic regression, multilayer perceptron (MLP) model, and random forest (RF) exceeded 0.700.For F1-score, the AUC values for logistic regression, MLP, and RF were 0.870, 0.880, and 0.880, respectively.The network structure of the visualized MLP was a single-layer, 24-neurons neural network with 80% accuracy in predicting whether progression occurred after A-CXL.The clinical nomogram developed in conjunction with astigmatism, SSI, and CDA6 predicted the cumulative probability of progression at 0.5, 1, and 2 years postoperatively based on the sum of the specified values for each variable, and based on the optimal cutoff value, keratoconus corneas could be classified into high-, intermediate-, and low-risk groups, respectively.The time-dependent subject operating characteristic curves of the nomogram showed AUCs of 0.734, 0.685, and 0.935 at 0.5, 1, and 2 years postoperatively, respectively, all of which performed well in predicting progression. Conclusions:Preoperative astigmatism, SSI, and CDA6 are significant risk factors for post-A-CXL progression in keratoconus.The MLP model can accurately predict postoperative disease progression, and the clinical nomogram combining preoperative astigmatism, SSI, and CDA6 can effectively differentiate between low-, medium-, and high-risk postoperative progression outcomes.