Objective To explore the clinical efficacy of the"S.L.O.T.S."(Separate,Loop,Observe,Tension,Sign)three-layer five-step method for preserving testicular artery in microsurgical subinguinal varicocelectomy.Methods Clinical data of 190 patients with varicocele in our hospital from March 2020 to September 2022 were retrospectively analyzed.A total of 97 cases underwent"S.L.O.T.S."three-layer five-step method with preservation of testicular artery in microsurgical subinguinal varicocelectomy(microscopic group),and 93 cases underwent laparoscopic spermatic vein bundle ligation(laparoscopic group).The semen quality and postoperative complications of the two groups were compared before and after surgery.Results The laparoscopic group had significantly shorter operation time[(32.2±7.3)min vs.(65.1±8.3)min,t=28.959,P=0.000]compared to the microscopic group.The proportion of postoperative secondary hydrocele[1.0％(1/97)vs.8.6％(8/93),x2=4.470,P=0.034].epididymitis[2.1％(2/97)vs.9.7％(9/93),x2=5.049,P=0.025].and total complications[3.1％(3/97)vs.21.5％(20/93),x2=15.128,P=0.000]in the microscopic group were significantly lower than those in the laparoscopic group.The indicators of semen quality such as total number of sperm[(53.3±5.8)× 106 vs.(50.4±4.9)× 106,t=3.676,P=0.000].sperm concentration[(19.6±2.2)× 106/ml vs.(18.1±2.4)×106/ml,t=4.418,P=0.000].rate of sperm anterior motility[(46.1±5.6)％vs.(41.5±4.1)％,t=6.476,P=0.000].total sperm motility[(55.7±4.9)％vs.(51.2±3.8)％,t=7.115,P=0.000].and percentage of normal sperm[(9.0±1.7)％vs.(7.6±1.6)％,t=5.550,P=0.000]were significantly better in the microscopic group than those in the laparoscopic group.Conclusion "S.L.O.T.S."three-layer five-step method has advantages of programmed surgical steps,and effective identification and preservation of testicular arteries and lymphatic vessels,which is beneficial for improving semen quality and reducing postoperative complications such as secondary hydrocele and epididymitis.

Objective To analyze differentially expressed proteins(DEPs)in the hippocampal tissue of an amyloid-beta 1-42(Aβ1-42)-induced Alzheimer's disease(AD)rat model using Tandem mass tag(TMT)-based quantitative proteomics,followed by bioinformatic analysis to explore potential AD mechanisms.Methods Twelve male Sprague-Dawley(SD)rats were randomly assigned to a control group(n=6)and a model group(n=6).The AD model was established by bilateral hippocampal injection of Aβ1-42 in the model group,while the control group received an equivalent volume of saline.Cognitive function was assessed using the novel object recognition test,and hippocampal Aβ deposition was detected by immunofluorescence.DEPs were identified using TMT-based proteomics and subsequently analyzed via Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interaction(PPI)network analysis.Key DEPs were validated using parallel reaction monitoring(PRM)technology.Results The model group exhibited a significantly lower novel object recognition index(P<0.01)and significantly increased hippocampal Aβ deposition(P<0.01)compared to the control group.Proteomic analysis identified 183 DEPs(87 upregulated,96 downregulated).GO analysis revealed that DEPs were primarily enriched in processes such as amyloid-beta binding and ion transmembrane transport.KEGG analysis indicated significant enrichment in 42 pathways,including dopaminergic synapse,glutamatergic synapse,cholinergic synapse,and long-term potentiation.Ten core DEPs were identified from the PPI network,and PRM validation confirmed expression trends consistent with the TMT results.Conclusion Aβ1-42-induced AD involves the synergistic action of multiple targets,biological processes,and pathways.The activation of glutamatergic and dopaminergic synaptic signaling pathways,mediated by core DEPs(e.g.,Th、D1、VGLUT2、GluN2A、GluA1、GluA3、Shank1、DARPP-32、PKC-δ、PKC-α、PKA C-β、CaMKⅡα、PTK2B),likely represents a key molecular mechanism in this AD model,providing a basis for identifying potential therapeutic targets.

Objective:To construct and validate a clinical model combining CYP11B2 gene polymorphisms with clinical parameters to predict complete postoperative hypertension remission in primary aldosteronism patients.Methods:The clinical data of a total of 116 patients with primary aldosteronism who underwent unilateral adrenalectomy from April 2018 to August 2024 were retrospectively included. There were 63 males and 53 females，with a body mass index（BMI）of（25.50 ± 2.03）kg/m 2. Genomic DNA was extracted from venous blood leukocytes before surgery，and polymerase chain reaction-restriction fragment length polymorphisms（PCR-RFLP）were used to detect CYP11B2（rs1799998）promoter region 344（C > T）base substitution. The follow-up duration was more than 6 months，with the following parameters recorded at the last follow-up：plasma aldosterone，renin，serum potassium，and sodium levels. Blood pressure progression and antihypertensive medication usage were also assessed. The postoperative outcome was determined according to the Primary Aldosteronism Surgical Outcome score（PASO）for primary aldosteronism，and the specific criteria were as follows. ① Clinical complete remission：the patient's blood pressure returned to normal（< 140/90 mmHg，1 mmHg = 0.133 kPa）and all antihypertensive drugs were discontinued；②Partial clinical remission：blood pressure returns to normal，and the number or dose of antihypertensive drugs is reduced compared with before；③Clinical non-remission：blood pressure does not drop and antihypertensive drugs do not change or increase compared with before surgery. Patients were divided into complete and incomplete remission groups. The chi-square test was used for univariate analysis，followed by binary logistic forward conditional regression for multivariate analysis，and a variety of machine learning algorithms such as random forest，logistic regression，support vector machine and gradient lifter were integrated，and the results of multivariate analysis were included to construct a postoperative blood pressure outcome model，and the predictive performance of the model was evaluated by using receiver operating characteristic（ROC）curve，calibration curve and clinical decision curve. Results:The PCR-RFLP detection results of 116 cases showed the genotype distribution of CYP11B2（344C > T）（rs1799998）as follows：CC type in 50 cases（43.1%），CT type in 46 cases（39.7%），and TT type in 20 cases（17.3%）. There were 74 cases in the complete remission group and 42 cases in the incomplete remission group，and the rate of complete remission with hypertension at the end of the operation was 63.8%. Univariate analysis showed that the the differences between complete remission group and incomplete remission group in body mass index［（24.27 ± 2.90）kg/m 2 vs.（26.98 ± 3.17）kg/m 2， P<0.001］，preoperative hypertension grade（grade 1/2/3：29/29/16 cases vs. 9/13/20 cases， P = 0.012），preoperative antihypertensive drugs（0/1/≥ 2：25/32/17 cases vs. 7/15/20 cases， P = 0.016），and CYP11B2（344C > T）（CC/TT + CT：39/35 cases vs. 11/31 cases， P = 0.006）were statistically significant. Multivariate analysis showed that the type of preoperative antihypertensive drugs［≥ 2： OR = 5.26（95% CI 1.12?24.61， P = 0.016；1： OR = 4.55（95% CI 1.23?22.47）， P = 0.025］was the strongest independent predictor，followed by CYP11B2（344C > T）［ OR = 4.02（95% CI 1.16?13.82）， P = 0.028］and BMI［ OR = 3.96（95% CI 2.26?6.92）， P < 0.001］. Comparing the receiver operating feature（ROC）curves of the four types of machine learning models，the best model was the support vector machine model with an area under the curve（AUC）of 0.88（95% CI 0.82?0.95），followed by the gradient elevator model of 0.83（95% CI 0.76?0.91），the logistic regression model of 0.78（95% CI 0.68?0.88），and the random forest model of 0.77（95% CI 0.68?0.86）. The optimal threshold of the Yoden index of the support vector machine model was 0.588，with a sensitivity of 78.5% and a specificity of 86.5%. The clinical decision curve and calibration curve show that the support vector machine model has a higher net benefit and acceptable stability and reliability. Conclusions:The support vector machine model incorporating CYP11B2 gene polymorphisms，BMI，and types of preoperative antihypertensive medications could effectively predict postoperative hypertension remission in primary aldosteronism patients，providing new evidence for personalized treatment strategies

Stroke imposes a tremendous burden on patients'families and society due to its high rates of mortality,disability,and recurrence.Advances in neuroimaging technologies have provided critical theoretical foundations for investigating the pathophysiological mechanisms of stroke,as well as enabling early clinical intervention and personalized rehabilitation.This article reviewed the application of five commonly used magnetic resonance imaging(MRI)techniques in acupuncture therapy for stroke,including functional MRI(fMRI)for cerebral blood oxygen metabolism,magnetic resonance spectroscopy(MRS),diffusion MRI(dMRI),perfusion MRI(pMRI),and structural MRI(sMRI).By examining functional,metabolic,structural,and hemodynamic aspects,these imaging modalities offer evidence to validate the multi-target effect and efficacy of acupuncture in stroke treatment.

Objective:To construct and validate a clinical model combining CYP11B2 gene polymorphisms with clinical parameters to predict complete postoperative hypertension remission in primary aldosteronism patients.Methods:The clinical data of a total of 116 patients with primary aldosteronism who underwent unilateral adrenalectomy from April 2018 to August 2024 were retrospectively included. There were 63 males and 53 females，with a body mass index（BMI）of（25.50 ± 2.03）kg/m 2. Genomic DNA was extracted from venous blood leukocytes before surgery，and polymerase chain reaction-restriction fragment length polymorphisms（PCR-RFLP）were used to detect CYP11B2（rs1799998）promoter region 344（C > T）base substitution. The follow-up duration was more than 6 months，with the following parameters recorded at the last follow-up：plasma aldosterone，renin，serum potassium，and sodium levels. Blood pressure progression and antihypertensive medication usage were also assessed. The postoperative outcome was determined according to the Primary Aldosteronism Surgical Outcome score（PASO）for primary aldosteronism，and the specific criteria were as follows. ① Clinical complete remission：the patient's blood pressure returned to normal（< 140/90 mmHg，1 mmHg = 0.133 kPa）and all antihypertensive drugs were discontinued；②Partial clinical remission：blood pressure returns to normal，and the number or dose of antihypertensive drugs is reduced compared with before；③Clinical non-remission：blood pressure does not drop and antihypertensive drugs do not change or increase compared with before surgery. Patients were divided into complete and incomplete remission groups. The chi-square test was used for univariate analysis，followed by binary logistic forward conditional regression for multivariate analysis，and a variety of machine learning algorithms such as random forest，logistic regression，support vector machine and gradient lifter were integrated，and the results of multivariate analysis were included to construct a postoperative blood pressure outcome model，and the predictive performance of the model was evaluated by using receiver operating characteristic（ROC）curve，calibration curve and clinical decision curve. Results:The PCR-RFLP detection results of 116 cases showed the genotype distribution of CYP11B2（344C > T）（rs1799998）as follows：CC type in 50 cases（43.1%），CT type in 46 cases（39.7%），and TT type in 20 cases（17.3%）. There were 74 cases in the complete remission group and 42 cases in the incomplete remission group，and the rate of complete remission with hypertension at the end of the operation was 63.8%. Univariate analysis showed that the the differences between complete remission group and incomplete remission group in body mass index［（24.27 ± 2.90）kg/m 2 vs.（26.98 ± 3.17）kg/m 2， P<0.001］，preoperative hypertension grade（grade 1/2/3：29/29/16 cases vs. 9/13/20 cases， P = 0.012），preoperative antihypertensive drugs（0/1/≥ 2：25/32/17 cases vs. 7/15/20 cases， P = 0.016），and CYP11B2（344C > T）（CC/TT + CT：39/35 cases vs. 11/31 cases， P = 0.006）were statistically significant. Multivariate analysis showed that the type of preoperative antihypertensive drugs［≥ 2： OR = 5.26（95% CI 1.12?24.61， P = 0.016；1： OR = 4.55（95% CI 1.23?22.47）， P = 0.025］was the strongest independent predictor，followed by CYP11B2（344C > T）［ OR = 4.02（95% CI 1.16?13.82）， P = 0.028］and BMI［ OR = 3.96（95% CI 2.26?6.92）， P < 0.001］. Comparing the receiver operating feature（ROC）curves of the four types of machine learning models，the best model was the support vector machine model with an area under the curve（AUC）of 0.88（95% CI 0.82?0.95），followed by the gradient elevator model of 0.83（95% CI 0.76?0.91），the logistic regression model of 0.78（95% CI 0.68?0.88），and the random forest model of 0.77（95% CI 0.68?0.86）. The optimal threshold of the Yoden index of the support vector machine model was 0.588，with a sensitivity of 78.5% and a specificity of 86.5%. The clinical decision curve and calibration curve show that the support vector machine model has a higher net benefit and acceptable stability and reliability. Conclusions:The support vector machine model incorporating CYP11B2 gene polymorphisms，BMI，and types of preoperative antihypertensive medications could effectively predict postoperative hypertension remission in primary aldosteronism patients，providing new evidence for personalized treatment strategies

Objective To analyze differentially expressed proteins(DEPs)in the hippocampal tissue of an amyloid-beta 1-42(Aβ1-42)-induced Alzheimer's disease(AD)rat model using Tandem mass tag(TMT)-based quantitative proteomics,followed by bioinformatic analysis to explore potential AD mechanisms.Methods Twelve male Sprague-Dawley(SD)rats were randomly assigned to a control group(n=6)and a model group(n=6).The AD model was established by bilateral hippocampal injection of Aβ1-42 in the model group,while the control group received an equivalent volume of saline.Cognitive function was assessed using the novel object recognition test,and hippocampal Aβ deposition was detected by immunofluorescence.DEPs were identified using TMT-based proteomics and subsequently analyzed via Gene Ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interaction(PPI)network analysis.Key DEPs were validated using parallel reaction monitoring(PRM)technology.Results The model group exhibited a significantly lower novel object recognition index(P<0.01)and significantly increased hippocampal Aβ deposition(P<0.01)compared to the control group.Proteomic analysis identified 183 DEPs(87 upregulated,96 downregulated).GO analysis revealed that DEPs were primarily enriched in processes such as amyloid-beta binding and ion transmembrane transport.KEGG analysis indicated significant enrichment in 42 pathways,including dopaminergic synapse,glutamatergic synapse,cholinergic synapse,and long-term potentiation.Ten core DEPs were identified from the PPI network,and PRM validation confirmed expression trends consistent with the TMT results.Conclusion Aβ1-42-induced AD involves the synergistic action of multiple targets,biological processes,and pathways.The activation of glutamatergic and dopaminergic synaptic signaling pathways,mediated by core DEPs(e.g.,Th、D1、VGLUT2、GluN2A、GluA1、GluA3、Shank1、DARPP-32、PKC-δ、PKC-α、PKA C-β、CaMKⅡα、PTK2B),likely represents a key molecular mechanism in this AD model,providing a basis for identifying potential therapeutic targets.

Stroke imposes a tremendous burden on patients'families and society due to its high rates of mortality,disability,and recurrence.Advances in neuroimaging technologies have provided critical theoretical foundations for investigating the pathophysiological mechanisms of stroke,as well as enabling early clinical intervention and personalized rehabilitation.This article reviewed the application of five commonly used magnetic resonance imaging(MRI)techniques in acupuncture therapy for stroke,including functional MRI(fMRI)for cerebral blood oxygen metabolism,magnetic resonance spectroscopy(MRS),diffusion MRI(dMRI),perfusion MRI(pMRI),and structural MRI(sMRI).By examining functional,metabolic,structural,and hemodynamic aspects,these imaging modalities offer evidence to validate the multi-target effect and efficacy of acupuncture in stroke treatment.

Objective To explore the clinical efficacy of the"S.L.O.T.S."(Separate,Loop,Observe,Tension,Sign)three-layer five-step method for preserving testicular artery in microsurgical subinguinal varicocelectomy.Methods Clinical data of 190 patients with varicocele in our hospital from March 2020 to September 2022 were retrospectively analyzed.A total of 97 cases underwent"S.L.O.T.S."three-layer five-step method with preservation of testicular artery in microsurgical subinguinal varicocelectomy(microscopic group),and 93 cases underwent laparoscopic spermatic vein bundle ligation(laparoscopic group).The semen quality and postoperative complications of the two groups were compared before and after surgery.Results The laparoscopic group had significantly shorter operation time[(32.2±7.3)min vs.(65.1±8.3)min,t=28.959,P=0.000]compared to the microscopic group.The proportion of postoperative secondary hydrocele[1.0％(1/97)vs.8.6％(8/93),x2=4.470,P=0.034].epididymitis[2.1％(2/97)vs.9.7％(9/93),x2=5.049,P=0.025].and total complications[3.1％(3/97)vs.21.5％(20/93),x2=15.128,P=0.000]in the microscopic group were significantly lower than those in the laparoscopic group.The indicators of semen quality such as total number of sperm[(53.3±5.8)× 106 vs.(50.4±4.9)× 106,t=3.676,P=0.000].sperm concentration[(19.6±2.2)× 106/ml vs.(18.1±2.4)×106/ml,t=4.418,P=0.000].rate of sperm anterior motility[(46.1±5.6)％vs.(41.5±4.1)％,t=6.476,P=0.000].total sperm motility[(55.7±4.9)％vs.(51.2±3.8)％,t=7.115,P=0.000].and percentage of normal sperm[(9.0±1.7)％vs.(7.6±1.6)％,t=5.550,P=0.000]were significantly better in the microscopic group than those in the laparoscopic group.Conclusion "S.L.O.T.S."three-layer five-step method has advantages of programmed surgical steps,and effective identification and preservation of testicular arteries and lymphatic vessels,which is beneficial for improving semen quality and reducing postoperative complications such as secondary hydrocele and epididymitis.

Humans ; Early Detection of Cancer ; Endoscopy ; Esophageal Neoplasms/epidemiology* ; Risk Factors ; Mass Screening

Objective To establish a human α-synuclein nuclear localization signal transgenic mouse model and investigate the effects of α-synuclein nuclear localization on the behavior of mice.Methods Human α-synuclein nuclear localization signal and EGFP lentiviral vectors were constructed.Transgenic mice were created with the microinjection method.Using PCR and Western Blot method to identify the genotypes and protein expression of the transgenic founder mice and their offsprings.The immunofluorescence was used to examine the localization of human α-synuclein in the mouse brain tissue.The behavioral changes of the transgenic mice were evaluated by the open field test,rotarod test,and O maze test.Results The h SNCA-NLS gene was successfully inserted into the mouse genome,the human α-syn was successfully expressed,and the human α-syn has localized with the nuclear.Further studies found that human α-synuclein nuclear localization signal transgenic mice had significant motor dysfunction,astrocyte proliferation and inflammatory response at 2 months of age and exhibited significant anxiety-like symptoms and reduced expression of the γ-aminobutyric acid(GABA)gene at 9 months of age,which persisted until 12 months of age.Conclusions A human α-synuclein nuclear localization signal transgenic mouse model has been successfully established.The mice exhibit significant motor dysfunction and anxiety-like symptoms.The successful establishment of this model provides a foundation for studying the role of α-syn nuclear localization in Parkinson's disease.