AIM:To investigate the role of S100 calcium-binding protein A8(S100A8)in a canine model of atrial fibrillation(AF)induced by obstructive sleep apnea(OSA).METHODS:Ten adult Beagle dogs were randomly as-signed to OSA(n=5)and control(n=5)groups.The OSA model was established by daily tracheal intubation with alternat-ing airway obstruction and ventilation recovery for 4 h per day,sustained over 12 weeks.Model validation was conducted through arterial blood gas analysis,airway pressure monitoring,and esophageal pressure measurements.Open-chest elec-trophysiological studies were performed to assess atrial effective refractory period(ERP),dispersion of ERP(dERP),and AF inducibility.Tandem mass tag-based quantitative proteomics was used to identify differentially expressed proteins in atrial tissue.Key protein expression and localization were verified using immunohistochemistry and immunofluorescence.RESULTS:Compared with the control group,the OSA group exhibited significantly lower arterial blood pH and partial pressure of oxygen,and higher partial pressure of carbon dioxide in arterial blood,confirming successful model establish-ment.Histopathological analysis revealed disorganized cardiomyocyte architecture,fatty degeneration,inflammatory cell infiltration,and a significant increase in myocardial fibrosis in the OSA group(P<0.05).Electrophysiological data showed increased AF inducibility and dERP,and decreased ERP(P<0.05).Proteomic analysis identified 267 differen-tially expressed proteins,including 128 up-regulated and 139 down-regulated proteins.Immunohistochemical analysis showed significant upregulation of S100A8,S100A9,myeloperoxidase,and nuclear factor-κB p65(P<0.05),while im-munofluorescence demonstrated increased expression of matrix metalloproteinase-9 and transforming growth factor-β1 in the OSA group(P<0.01).CONCLUSION:The OSA promotes upregulation of S100A8 in myocardial tissue,enhances atrial electrical remodeling and fibrosis,and increases susceptibility to AF.These findings suggest that S100A8 may play a key role in the pathogenesis and progression of OSA-related AF.

AIM:To investigate the role of S100 calcium-binding protein A8(S100A8)in a canine model of atrial fibrillation(AF)induced by obstructive sleep apnea(OSA).METHODS:Ten adult Beagle dogs were randomly as-signed to OSA(n=5)and control(n=5)groups.The OSA model was established by daily tracheal intubation with alternat-ing airway obstruction and ventilation recovery for 4 h per day,sustained over 12 weeks.Model validation was conducted through arterial blood gas analysis,airway pressure monitoring,and esophageal pressure measurements.Open-chest elec-trophysiological studies were performed to assess atrial effective refractory period(ERP),dispersion of ERP(dERP),and AF inducibility.Tandem mass tag-based quantitative proteomics was used to identify differentially expressed proteins in atrial tissue.Key protein expression and localization were verified using immunohistochemistry and immunofluorescence.RESULTS:Compared with the control group,the OSA group exhibited significantly lower arterial blood pH and partial pressure of oxygen,and higher partial pressure of carbon dioxide in arterial blood,confirming successful model establish-ment.Histopathological analysis revealed disorganized cardiomyocyte architecture,fatty degeneration,inflammatory cell infiltration,and a significant increase in myocardial fibrosis in the OSA group(P<0.05).Electrophysiological data showed increased AF inducibility and dERP,and decreased ERP(P<0.05).Proteomic analysis identified 267 differen-tially expressed proteins,including 128 up-regulated and 139 down-regulated proteins.Immunohistochemical analysis showed significant upregulation of S100A8,S100A9,myeloperoxidase,and nuclear factor-κB p65(P<0.05),while im-munofluorescence demonstrated increased expression of matrix metalloproteinase-9 and transforming growth factor-β1 in the OSA group(P<0.01).CONCLUSION:The OSA promotes upregulation of S100A8 in myocardial tissue,enhances atrial electrical remodeling and fibrosis,and increases susceptibility to AF.These findings suggest that S100A8 may play a key role in the pathogenesis and progression of OSA-related AF.

Objective:To investigate the role of miR-144-3p in cisplatin resistance of bladder cancer.Methods:Bladder cancer T24 cells were cultured in vitro and divided into blank group (untreated), mimetic control group, miR-144-3p mimetic transfection group, inhibitor control group, and miR-144-3p inhibitor transfection group. Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to verify the transfection effect, methyl thiazolyl tetrazolium (MTT) method was used to detect the survival rate of cells treated with cisplatin in each group, and Western blot was used to detect the expression of the target protein. The targeting relationship between miR-144-3p and nuclear factor E2 related factor 2 (Nrf2) was validated using dual fluorescence reporter gene experiments. Furthermore, Nrf2 was knocked out in each group of cells, and the mRNA and protein expression levels of HO-1, Bcl-2, and Caspase-3 were detected by qRT-PCR and Western blot in each group of cells.Results:Compared with the control group, bladder cancer cells in the miR-144-3p mimetic transfection group were more sensitive to cisplatin, while the miR-144-3p inhibitor transfection group had the opposite effect; The miR-144-3p simulant transfection group can effectively inhibit the mRNA and protein expression level of Nrf2 in bladder cancer cells (all P<0.05), while the miR-144-3p inhibitor transfection group can up regulate the mRNA and protein level of Nrf2 (all P<0.05). The miR-144-3p mimetic transfection group showed significant downregulation of mRNA and protein expression of HO-1 and Bcl-2, while the expression of Caspase-3 was upregulated (all P<0.05), while the miR-144-3p inhibitor transfection group showed the opposite results. The luciferase results confirmed that miR 144 3p can directly bind to the 3′- UTR region of Nrf2, reducing the mRNA level of Nrf2. When Nrf2 was knocked out, whether miR-144-3p mimetic transfection group or miR-144-3p inhibitor transfection group, the mRNA and protein expression levels of HO-1, Bcl-2 and Caspase-3 did not change significantly, and miR-144-3p lost the ability to regulate the cisplatin sensitivity of bladder cancer cells. Conclusions:miR-144-3p targets to regulate the sensitivity of Nrf2 to cisplatin in bladder cancer, and miR-144-3p is expected to become a new target for the treatment of cisplatin resistant or refractory bladder cancer.

Objective:To investigate the predictive value of preoperative blood parameters on the efficacy of microscopic varicocele ligation in the treatment of infertility patients with varicocele.Methods:The clinical data of 110 patients with varicocele admitted to Xi′an People′s Hospital and Tangdu Hospital of Air Force Military Medical University from June 2016 to January 2021 were analyzed retrospectively. Successful operation was defined as the restoration of all semen parameters (sperm concentration, forward motility, morphology, etc.) to normal values 6 months after operation. The patients were divided into effective treatment group (group A, 78 cases) and ineffective treatment group (group B, 32 cases). The blood parameters of the two groups were compared before operation. Spearman correlation analysis was used to determine the relationship between blood parameters [neutrophil/lymphocyte ratio (NLR) and mean platelet volume (MPV)] and the success of microscopic varicocele ligation. The predictive value of blood parameters (NLR and MPV) to the success of microscopic varicocele ligation was analyzed by receiver operating characteristic (ROC) curve.Results:There was no significant difference in clinical characteristics, and sex hormone levels between the two groups before operation (all P>0.05); There were statistically significant differences in NLR and MPV in blood parameters between the two groups (both P<0.05), and there was no significant differences in other blood parameters (both P>0.05). There was no significant difference in semen parameters between the two groups before operation (all P>0.05). After operation, the semen volume, semen concentration, forward movement and sperm morphology of patients in group A were significantly improved compared with those before operation (all P<0.05), while the parameters of patients in group B had no significant difference compared with those before operation (all P>0.05). There was a negative correlation between preoperative NLR and the success rate of spermatic vein ligation ( r=-0.719, P<0.01), and a positive correlation between MPV and the success rate of spermatic vein ligation ( r=0.522, P<0.01). The ROC curve was used to analyze the threshold of predictive variables for the success of spermatic vein ligation. The optimal critical value of NLR was 2.01 ( P<0.01), and the optimal critical value of MPV was 11.45 ( P<0.01). Conclusions:Low NLR (<2.01) and high MPV (>11.45) may be useful preoperative predictive tools for identifying the group of infertile varicocele patients who would benefit most from microscopic spermatic vein ligation.

Objective:To evaluate the availability and safety of laparoscopic pyeloplasty with extracorporeal ureteral tailor.Methods:Clinical data of 26 patients with ureteropelvic junction obstruction (UPJO)who were treated by laparoscopic combined with extracorporeal ureteral tailor pyeloplasty in our hospital from March 2016 to August 2019 were retrospectively analyzed. There were 19 males and 7 females. 22 cases had unilateral lesion, including 6 cases on the right side and 16 cases on the left; 2 cases were bilateral. The average age was 22.3 years old (6-54 years). 19 cases felt discomfort in the renal region and 7 cases were asymptomatic. The mean body mass index was 21.7 kg/m 2 (17.2- 26.4 kg/m 2). 5 cases had mild hydronephrosis, 17 cases had moderate hydronephrosis and 4 cases had severe hydronephrosis. 6 cases combined with cross vessels. In all the 26 cases, the ureter was pulled out of the abdomen through a laparoscopic incision, cut lengthways in vitro, sutured at the lowest point, and then returned it to the abdomen. Then, double J tube implantation and ureteropelvic anastomosis were performed under the laparoscopy. Results:26 cases were completed successfully without conversion, with the average operation time of 99 minutes (50-158 minutes), the average blood loss of 19.4 ml (10-50 ml), the average hospital stay of 6.5 days (5-11 days), and the average drainage indwelling time of 5.3 days (4-10 days). For complications, urine leakage occurred on the 3rd day after the operation in 1 case, and the daily drainage fluid was more than 500 ml, which decreased suddenly after 4 days. Postoperative average follow-up was 10.8 months (6-24 months). Renal region pain disappeared in all patients. CT reexamination 3 months after the operation showed that hydronephrosis was alleviated or disappeared in 24 cases, and there was no significant change in 2 cases compared with the preoperative images, but no progress was found in the subsequent reexamination, so we didn't deal with the hydronephrosis again.Conclusions:Laparoscopic pyeloplasty combined with extracorporeal ureteral tailor is minimally invasive and flexible, which greatly reduces the difficulty and time of operation, and has a high success rate.

Objective To study the ages at natural menopause of the women in Jilin Province, and to illustrate its influencing factors among the women in Jilin Province.Methods Through multistage stratified cluster random sampling method,23 050 people aged from 18 to 79 years were drew from nine states(a total of 32 areas)of Jilin province.The data of these residents were collected with the questionnaire and physical examinations by face-to-face interview.The number of selected female sample was 11 098. Finally, 4 881 postmenopausal women were selected.Complex weighted computation was used to estimate the ages at natural menopause.One-way ANOVA was used to compare the ages at natural menopause of the women with different birth years. Multiple linear regression analysis were used to examine the influencing factors of the ages at natural menopause. Results The mean and median ages at natural menopause were (49.11±4.19)years and 50.00 years,respectively.There were 4 881 cases of postmenopausal women,among them the women with age at natural menopause<40 years,40 year≤age at natural menopause≤45 years,46 years≤ age at natural menopause≤53 years,age at natural menopause≥54 years and age at natural menopause missing accounted for 2.27%(111 cases),13.17%(643 cases),71.97%(3 513 cases),11.74% (573 cases),and 0.85%(41 cases),respectively.Converted to birth years by age,70-79 years old was 1933-1942 birth years,60-69 years old was 1943-1952 birth years and 57-59 years old was 1953-1955 birth years.The age at natural menopause in Jilin province was statistically significant among the women with different birth years(F=21.178,P<0.001).By SNK-q test among three different birth year groups, the age at natural menopause was different between any two groups among three different birth year groups and the ages at natural menopause of 1953-1955 birth year group,1943-1952 birth year group and 1943-1952 birth year group were 50.38 years,49.51 years and 48.81 years.The age at natural menopause in urban of Jilin province was statistically significant among the women with different birth years(F=16.633,P<0.001).By SNK-q test among three different birth year groups,the age at natural menopause was different between any two groups among three different birth year groups and the ages at natural menopause of 1953-1955 birth year group,1943-1952 birth year group and 1943-1952 birth year group were 50.77 years,49.73 years,and 48.85 years,respectively.The age at natural menopause in rural of Jilin province was statistically significant among the women with different birth years(F=7.400,P=0.001 ). By SNK-q test among three different birth year groups, the age at natural menopause was different between 1953-1955 birth year group and the other two groups and the ages at natural menopause of 1953-1955 birth year group,1943-1952 birth year group and 1943-1952 birth year group were 50.09 years,49.33 years,and 48.74 years,respectively.The multiple linear regression results indicated that BMI and exercise were positively correlated with the age at natural menopause,but smoking and mental health evaluation were negatively.Consumption frequency of vegetables,fruits,bean products,and meat was no correlated with the age at natural menopause.Conclusion The differences of the ages at natural menopause between the women with different birth years are statistically significant in Jilin Province;BMI, smoking, exercise,and mental health are the influencing factors of the age at natural menopause.

Objective To observe the expression change of HRG-1 gene between urinary bladder carcinoma and normal tissues,and to investigate the effect of HRG-1-siRNA on the proliferation and apoptosis of human bladder carcinoma cells.Methods Immunohistochemisty was used to detect the expression of HRG-1 in 85 cases of bladder carcinomas and 20 normal bladder tissues.The siRNA of HRG-1 was designed,synthesized,and transfected into bladder cancer cell line T24.Results The HRG-1 gene expression had significant differences between bladder carcinoma and normal bladder tissues (P ＜ 0.05).The positive expression of HRG-1 gene had significant differences between the pathological grades and clinical stages of bladder carcinomas (P ＜0.05).After treated with siRNA,the expression levels of HRG-1 protein and mRNA in T24 cells decreased obviously (P ＜ 0.05).The apoptosis rate of T24 cells transfected with HRG-1-siRNA was significantly different from control-siRNA group and blank group (P ＜ 0.01).Conclusions The high expression of HRG-1 gene may play an important role in bladder carcinoma,and siRNA targeting HRG-1 can suppress HRG-1 protein expression markedly and enhance apoptosis of T24 cells.

Objective To investigate the antitumor activities of adenovirus-mediated NDRG2 gene (Ad-NDRG2) and docetaxel on human prostate cancer DU145 cells.Methods The protein expressions of cyclin D1,cycliu E,and NDRG2 in the cells were determined by Western blot.MTT and flow cytometry were used to observe the effects of docetaxel (10-6 mol/L,10-7 mol/L,and 10-s mol/L) and Ad-NDRG2 on prostate cancer cell line DU145 in single or synergistic administration ways for 24 and 48 hours in vitro.Male BALB/C-nu mice with DU145 prostate cancer cell lines were treated by docetaxel and Ad-NDRG2 singly or synergistically in vivo.Results After infected by adenovirus,the protein expression of NDRG2 increased,but cyclin D1 and cyclin E decreased in DU145 cells.Ad-NDRG2 inhibited the cell growth (inhibition ratio =41.8％,t =4.18,P ＜0.01),promoted apoptosis (apoptosis ratio =32.4％,x2 =11.66,P ＜0.05),changed the ratio of G2/M phase from 50.2％ to 23.6％,and reversed partially the G2/M arrest,of DU145 cells induced by 10-7 mol/L docetaxel.In vivo experiment showed that docetaxel,Ad-NDRG2,and combination of docetaxel and Ad-NDRG2 inhibited tumor growth with a inhibition rate of 30.7％,28.2％,and 55.8％,respectively.The coefficient of drug interaction (CDI) of docetaxel and Ad-NDRG2 was 0.89.Conclusions Ad-NDRG2 can enhance the growth suppression and apoptosis induced by docetaxel in synergistic way in vitro and in vivo.It demonstrated the great potential of Ad-NDRG2 in the treatment of androgen-independent prostate carcinoma.