Objective:To discuss the role of changes of serum total bile acid(TBA)levels induced by long-term high-fat diet in the occurrence of supraventricular arrhythmia(SVA)in the apolipoprotein E knockout(ApoE-/-)mice,and to clarify its mechanism.Methods:Twenty ApoE-/-mice were randomly divided into normal diet group and high-fat diet(HFD)group(n=10);after 20 weeks of feeding,surface electrocardiogram was used to detect cardiac electrophysiology of the mice in various groups;echocardiography was used to detect cardiac systolic function and structure in the mice in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of blood lipids,total bile acid(TBA)and inflammatory factors in the mice in various groups;hematoxylin-eosin(HE)staining was used to detect cardiac inflammatory response in the mice in various groups;Masson staining was used to observe myocardial fibrosis degree in the mice in various groups.Results:Compared with normal diet group,4 cases of junctional premature beat(JPB)/junctional tachycardia(JT),1 case of premature atrial contraction(PAC)and 1 case of premature ventricular contraction(PVC)were found in HFD group,while only 1 case of JPB/JT and 1 case of PAC were found in normal diet group.Compared with normal diet group,the heart rate of the mice in HFD group was significantly decreased(P<0.05);the QRS and QT intervals were significantly prolonged(P<0.05);the ejection fraction(EF)and fractional shortening(FS)were significantly decreased(P<0.05);the end-diastolic volume(EDV)was increased(P<0.05),but there was no significant difference in end-systolic volume(ESV)between groups(P>0.05);the left ventricular internal diameter at end-diastole(LVIDd)and left ventricular internal diameter at end-systole(LVIDs)were significantly increased(P<0.05).There were no significant differences in plasma total cholesterol(TC),triglyceride(TG),high-density lipoprotein(HDL-c)and low-density lipoprotein(LDL-c)levels and body weight between normal diet group and HFD group(P>0.05).Compared with normal diet group,the TBA level of the mice in HFD group was significantly increased(P<0.05).There were no significant differences in interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1),and C-X-C motif chemokine ligand 1(CXCL-1)levels between HFD group and normal diet group.Compared with normal diet group,the interleukin-1β(IL-1β)level in HFD group showed an increasing trend,but there was no significant difference between groups(P>0.05).The HE staining results showed that the inflammatory cell infiltration was similar between HFD group and normal diet group.The Masson staining results showed that compared with normal diet group,the fibrosis of the mice in HFD group showed an increasing trend,but there was no significant difference in myocardial fibrosis area between groups(P>0.05).Conclusion:Long-term high-fat diet may increase serum TBA level in ApoE-/-mice,which may induce SVA.

Objective:To investigate the expression of miR-383(Micro RNA-383)in osteosarcoma cells and to verify whether upregulation of miR-383 can enhance the therapeutic efficacy of bortezomib against osteosarcoma.Methods:Fluorescence in situ hybridization (FISH) was used to detect the expression of miR-383 in osteosarcoma and normal bone tissues. Real-time quantitative polymerase chain reaction (qRT-PCR) was employed to measure the expression of miR-383 in different osteosarcoma cell lines (SaoS-2, HOS, U-2OS, and MG63)and the osteoblast cell line hFOB 1.19.The proliferative capacity of osteosarcoma cells treated with 5 nmol/L and 10 nmol/L bortezomib was assessed using the cell counting kit-8 (CCK-8) with dimethyl sulfoxide (DMSO) as a control. The activity of caspase-3 was also measured. HOS and MG63 cells were treated with DMSO, bortezomib, miR-383 mimics, or negative controls, and the proliferative capacity and apoptosis levels were re-evaluated using CCK-8 and flow cytometry, respectively.Results:FISH results showed that the level of miR-383-5p in osteosarcoma tissues was significantly lower than that in normal bone tissues ( P<0.05). qRT-PCR results indicated that miR-383 levels in osteosarcoma cells (MG63, HOS, Saos-2, U-2OS) were lower than those in osteoblasts (hFOB1.19), with significant differences among different osteosarcoma cell lines(all P<0.05).The lowest levels of miR-383 were observed in HOS and MG63 cells. CCK-8 and caspase-3 activity assays revealed that among the cells treated with DMSO and two doses of bortezomib, HOS and MG63 cells had higher baseline proliferative capacity. Compared with DMSO-treated control cells, cells treated with 5 nmol/L and 10 nmol/L bortezomib exhibited inhibited proliferation (all P<0.05) and increased caspase-3 activity (all P<0.05). The effect of 10 nmol/L bortezomib was stronger than that of 5 nmol/L (all P<0.05). Compared with negative control-transfected cells, osteosarcoma cells (MG63 and HOS) with overexpressed miR-383 showed inhibited proliferation and increased apoptosis levels (all P<0.05). After bortezomib treatment, osteosarcoma cells (MG63 and HOS)with overexpressed miR-383 exhibited reduced proliferative capacity and enhanced apoptosis levels (all P<0.05). Conclusions:miR-383 exerts anticancer effects in osteosarcoma by inhibiting cell proliferation. Its overexpression significantly enhances the therapeutic efficacy of bortezomib, offering a new direction for the treatment strategies of osteosarcoma.

Objective:To investigate the expression of miR-383(Micro RNA-383)in osteosarcoma cells and to verify whether upregulation of miR-383 can enhance the therapeutic efficacy of bortezomib against osteosarcoma.Methods:Fluorescence in situ hybridization (FISH) was used to detect the expression of miR-383 in osteosarcoma and normal bone tissues. Real-time quantitative polymerase chain reaction (qRT-PCR) was employed to measure the expression of miR-383 in different osteosarcoma cell lines (SaoS-2, HOS, U-2OS, and MG63)and the osteoblast cell line hFOB 1.19.The proliferative capacity of osteosarcoma cells treated with 5 nmol/L and 10 nmol/L bortezomib was assessed using the cell counting kit-8 (CCK-8) with dimethyl sulfoxide (DMSO) as a control. The activity of caspase-3 was also measured. HOS and MG63 cells were treated with DMSO, bortezomib, miR-383 mimics, or negative controls, and the proliferative capacity and apoptosis levels were re-evaluated using CCK-8 and flow cytometry, respectively.Results:FISH results showed that the level of miR-383-5p in osteosarcoma tissues was significantly lower than that in normal bone tissues ( P<0.05). qRT-PCR results indicated that miR-383 levels in osteosarcoma cells (MG63, HOS, Saos-2, U-2OS) were lower than those in osteoblasts (hFOB1.19), with significant differences among different osteosarcoma cell lines(all P<0.05).The lowest levels of miR-383 were observed in HOS and MG63 cells. CCK-8 and caspase-3 activity assays revealed that among the cells treated with DMSO and two doses of bortezomib, HOS and MG63 cells had higher baseline proliferative capacity. Compared with DMSO-treated control cells, cells treated with 5 nmol/L and 10 nmol/L bortezomib exhibited inhibited proliferation (all P<0.05) and increased caspase-3 activity (all P<0.05). The effect of 10 nmol/L bortezomib was stronger than that of 5 nmol/L (all P<0.05). Compared with negative control-transfected cells, osteosarcoma cells (MG63 and HOS) with overexpressed miR-383 showed inhibited proliferation and increased apoptosis levels (all P<0.05). After bortezomib treatment, osteosarcoma cells (MG63 and HOS)with overexpressed miR-383 exhibited reduced proliferative capacity and enhanced apoptosis levels (all P<0.05). Conclusions:miR-383 exerts anticancer effects in osteosarcoma by inhibiting cell proliferation. Its overexpression significantly enhances the therapeutic efficacy of bortezomib, offering a new direction for the treatment strategies of osteosarcoma.

BACKGROUND:Clinical studies have shown that aerobic exercise is an important supplement to the clinical treatment of patients with pulmonary hypertension,which can alleviate the disease condition,increase exercise tolerance and improve the quality of life.However,it is not clear whether patients at different stages of pulmonary hypertension can benefit equally from exercise training. OBJECTIVE:To compare the intervention effects of early or late aerobic training on right heart failure in rats with pulmonary hypertension and explore its possible mechanism. METHODS:Sixty male Wistar rats were randomly divided into control group,model sedentary group,model early exercise group and model late exercise group,with 15 rats in each group.The model of pulmonary hypertension was established by intraperitoneal injection of monocrotaline(60 mg/kg)in the latter three groups.The model early exercise group was given 8 weeks of treadmill aerobic exercise(60%maximum running speed,60 minutes per day,5 days a week)after modeling,while the model late exercise group was trained for 6 weeks after 2 weeks of modeling.The control and model sedentary groups were fed quietly in the rat cage for 8 weeks.After training,the exercise performance,right ventricular hemodynamics,cardiopulmonary function,cardiopulmonary histopathology,reactive oxygen species level in mitochondria,activity of mitochondrial respiratory chain complex and expressions of myocardial tissue proteins were detected. RESULTS AND CONCLUSION:Compared with the model sedentary group,exercise performance and right ventricular function improved(P<0.05),myocardial collagen content,endothelin-1,tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio decreased(P<0.05),vascular endothelial growth factor and sarcoplasmic reticulum calcium-adenosine triphosphate enzyme expression increased(P<0.05),immunofluorescence intensity of mitochondrial reactive oxygen species and the protein expression of 3-nitrotyrosine decreased(P<0.05),the activities of complex I,II,IV and V increased in the model early exercise and model late exercise groups(P<0.05),but there were no significant changes in right ventricular maximum pressure,pulmonary acceleration time and pulmonary artery wall area/total vascular area ratio(P>0.05).Compared with the model late exercise group,the model early exercise group further improved exercise performance and right ventricular function,and downregulated collagen content,brain natriuretic peptide protein expression,tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio(P<0.05).To conclude,although pulmonary vascular remodeling and right ventricular overload persist in rats with pulmonary hypertension,exercise training at different stages of the disease has a cardioprotective effect.The mechanism is related to the improvement of cardiac remodeling,neurohormone system imbalance,inflammatory response and mitochondrial oxidative stress.Greater benefit is gained from initiating exercise in the early stage of the disease.

Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive behavioral therapies (CBT) on the cognitive function and alcohol craving in patients with alcohol dependence.Methods:From March 2019 to September 2021, a total of 150 patients with alcohol dependence were enrolled and randomly divided into rTMS treatment group (rTMS+ sham CBT, n=41), CBT treatment group (CBT+ sham rTMS, n=34), rTMS+ CBT treatment group( n=36) and control group (sham rTMS+ sham CBT, n=39). At baseline (before treatment), 2nd week, 8th week, 12th week and 24th week, alcohol dependence scale (ADS) was used to evaluate the degree of alcohol dependence, the obsessive compulsive drinking scale (OCDS) was used to assess patients' drinking craving, and Montreal cognitive assessment scale (MoCA) was used to assess the overall cognitive level of patients.SPSS 23.0 statistical software was used to compare the differences of ADS, OCDS and MoCA scale scores of the four groups by repeated measure ANOVA and simple effect analysis. Results:(1)The patients in the four groups were evaluated with ADS scale at baseline, 12th week and 24th week respectively.The interaction of group×time( F=1.279, P=0.279) and the main effect of group were not significant ( F=0.882, P=0.454), and the main effect of time was significant ( F=12.925, P<0.001) .Further simple effect analysis showed that the ADS score of rTMS+ CBT group was lower than that of baseline(14.48±5.70, 10.00±6.51) ( P=0.01) at 24th week.(2)Patients in the four groups were assessed with OCDs scale at baseline, 2nd week, 8th week, 12th week and 24th week, and the interaction of group×time was significant ( F=2.015, P=0.042). Further simple effect analysis showed that the OCDs scores of rTMS group and rTMS+ CBT group at each follow-up time node were lower than those at baseline period (all P<0.05). (3)Patients in the four groups were assessed with MoCA scale at baseline, 8th week, 12th week and 24th week, and the interaction of group×time was not significant ( F=1.660, P=0.106), and the main effect of group and the main effect of time were significant ( F=2.964, P=0.038; F=14.239, P<0.001). Further simple effect analysis showed that the score of MoCA scale in CBT group at the 24th week was higher than that at baseline (21.73±5.81, 24.60±3.98)( P=0.029), the score of MoCA scale in rTMS+ CBT group at the 24th week was higher than that at the 8th week (23.50±6.01, 25.95±2.87) ( P=0.006), and the score of MoCA scale in rTMS group at the 12th week was higher than that in control group (22.08±6.64, 26.64±2.46)( P=0.009). Conclusion:rTMS combined with CBT can be effective in improving alcohol craving and cognitive function in patients with alcohol dependence, and has a good long-term effect.

Objective: To determine the most influential data features and to develop machine learning approaches that best predict hospital readmissions among patients with diabetes. Methods: In this retrospective cohort study, we surveyed patient statistics and performed feature analysis to identify the most influential data features associated with readmissions. Classification of all-cause, 30-day readmission outcomes were modeled using logistic regression, artificial neural network, and EasyEnsemble. F1 statistic, sensitivity, and positive predictive value were used to evaluate the model performance. Results: We identified 14 most influential data features (4 numeric features and 10 categorical features) and evaluated 3 machine learning models with numerous sampling methods (oversampling, undersampling, and hybrid techniques). The deep learning model offered no improvement over traditional models (logistic regression and EasyEnsemble) for predicting readmission, whereas the other two algorithms led to much smaller differences between the training and testing datasets. Conclusions: Machine learning approaches to record electronic health data offer a promising method for improving readmission prediction in patients with diabetes. But more work is needed to construct datasets with more clinical variables beyond the standard risk factors and to fine-tune and optimize machine learning models.

Objective:To explore the efficacy and safety of transurethral anatomical vapor incision technique of prostate (VIT) with six-step method high power side-emitting greenlight laser in the treatment of benign prostatic hyperplasia (BPH).Methods:A retrospective analysis of 82 patients with BPH who used high power side-out green laser in the treatment from October 2018 to June 2020 in Gongli Hospital of Naval Medical University was performed. Among them, 40 patients were treated with six-step method VIT, and 42 patients were treated with photoselective vaporization of prostate (PVP). The two groups of patients were compared in age [(71.1±8.7)years vs.(72.1±7.0)years], prostate volume [75 (68.25, 89.00) ml vs. 73 (63.25, 85.00) ml], and peak urinary flow rate (Q max) [6.20 (5.20, 8.20) ) ml/s vs. 5.9 (4.75, 7.50) ml/s], post-void residual volume (PVR) [74.00 (42.50, 103.75) ml vs. 67.00 (58.00, 84.50) ml], international prostate symptom score (IPSS) [(21.2±5.2) vs. ( 21.0±3.9)], quality of life score (QOL) [5 (4, 6) vs. 5 (4, 6) ], prostate specific antigen (PSA) [6.20 (4.12, 8.43) ng/ml vs. 5.40 (3.88, 7.13) ng/ml ]. In general, there was no statistical difference ( P>0.05). The VIT group adopts the six-step method of marking, removing film, grooving, excision, trimming and crushing. In the PVP group, the prostate tissue was uniformly vaporized layer by layer from the inside to the outside. Perioperative indexes and complications were compared between the two groups. The Q max, IPSS, QOL, PVR and PSA between the two groups before and 3 months after surgery were compared. Results:All patients in the VIT group and PVP group successfully completed the surgery, and there was no case of transfer to TURP or open surgery. The average operation time was [60.00(50.00, 73.75)min vs. 70.00(50.00, 73.75)min] ( P<0.05). There was no significant difference in the amount of postoperative hemoglobin decline[15.00(10.00, 17.75)g/L vs. 16.00(14.00, 19.25)g/L], average bladder irrigation time[1(1, 1)d vs. 1(1, 1)d], indwelling catheterization time[3(3, 3)]d vs. 3(3, 3)d] and hospitalization time in patients after operation[4(3, 4)d vs. 4(4, 4)d] ( P>0.05). All patients had no blood transfusion, second bleeding, readmission, TURS, urethral stricture and urinary incontinence.There were 2 cases (5.0%) of postoperative urinary tract infection in the VIT group and 9 cases (21.4%) of postoperative urinary tract infection in the PVP group ( P<0.05), and they were cured after anti-inflammatory treatment. Three months after operation, Q max, IPSS, QOL, PVR and PSA in the two groups were significantly improved compared with preoperatively. Among them, the differences of IPSS [(5.7±2.5) points vs. (7.5±2.8) points] and PSA [2.65(2.10, 3.90)ng/ml vs. 4.00(2.45, 4.45)ng/ml] in the VIT group and PVP group after operation were statistically significant ( P<0.05). Conclusions:Applying the six-step method high power side-emitting greenlight laser transurethral anatomical VIT to treat BPH, there is less intraoperative and postoperative bleeding, short operation time, significant decrease in PSA, and fewer complications. It is a safe and effective minimally invasive technology for the treatment of BPH.

Objective:To explore the safety and efficacy of laparoscopic non-blocking partial nephrectomy assisted by high power lateral green laser in the treatment of T 1a renal tumor. Methods:The clinical data of 10 patients with T1a stage renal tumor from February 2021 to April 2021 in department of urology, Gongli hospital affiliated to Naval Military Medical University were retrospectively analyzed. There were 7 males and 3 females, aged 47.0-74.0 years, with average of(58.8±9.7)years old. The diameter of the tumor ranged from 2.0 cm to 3.8 cm, with an average of (3.1±0.6)cm. There were 6 cases on the left side and 4 cases on the right side, locate on lumbar side in 9 cases and ventral sied in 1 case. The R. E.N.A.L score was 4.0-6.0, with an average of (5.0±0.8). The preoperative creatinine was 66.9-90.1μmol/L, with an average of (75.1±9.0)μmol/L, preoperative GFR of 44. 6- 67. 3 ml /min, with an average of(56.7±7.7)ml/min, preoperative hemoglobin level of 119.0-156.0g/L, with an average of (135.8±11.4)g/L. All patients underwent laparoscopic non-blocking partial nephrectomy assisted by 180w lateral green laser, free the surrounding area of the tumor fully and completely expose the renal tumor. The laser fiber was placed through the green laser hand piece, and the fiber was connected with normal saline to wash the strip. The initial green laser vaporization power was set at 80W, and the hemostasis power at 35W.About 3mm away from the edge of the tumor, and one optical fiber away from the renal parenchyma, the renal parenchyma was cut with 80W power. In order to reduce the interference by smoke, high-pressure flushing was used through the optical fiber while vaporizing, and an attractor was used to push and peel the tumor. In case of bleeding during operation, hemostatic power can be used to close the bleeding point and gradually advance until the tumor was completely removed. The wounds of renal inner medulla and renal outer cortex were continuously sutured in 1-3 layers with barbed suture. It involved 9 cases via retroperitoneal approach and 1 case via abdominal approach. The operation time, postoperative hemoglobin decrease, extraction time of negative pressure drainage, postoperative hospital stay, postoperative pathology and postoperative complications were recorded, and the serum creatinine level and GFR level of the affected side were followed up 1 month after operation.Results:All the operations were successfully completed, and there was no conversion to open surgery or radical nephrectomy. One case changed to scissors fast resection and sutured hemostasis due to severe intraoperative bleeding. The operation time was 90.0-120.0 min, with the average of (104.5±9.0)min. The postoperative hemoglobin level was 96.0-132.0g/L, with an average of (115.2±11.8)g/L, and the difference was statistically significant ( P<0.05). The postoperative hemoglobin decreased from 12.0g/L to 25.0g/L, with an average of (20.6±4.6)g/L. The time of vacuum drainage was 5.0-7.0 days, with an average of (5.7±0.7)d. Postoperative hospital stay was 6.0-8.0 days, with an average of (6.7±0.7)d. No bleeding, urinary leakage and other complications occurred in all patients. There were 7 cases of clear cell carcinoma, 2 cases of papillary renal cell carcinoma and 1 case of angiomyolipoma. All margins were negative. One month after operation, creatinine ranged from 66.0 to 90.4μmol/L, with an average of (76.8±8.3)μmol/L, which was not significantly different compared with that before operation ( P>0.05). One month after operation, GFR was 45.1-60.8 ml/min, and with an average of (55.5±4.7)ml/min, and there was no significant difference compared with preoperative data( P>0.05). Conclusions:For T 1aN 0M 0 stage and exophytic renal tumors, laparoscopic non-blocking partial nephrectomy assisted by lateral green laser is safe and effective.

Objective To compare the clinical efficacy and safety of wide-focus high energy lithotriptor with narrow-focus low energy lithotriptor treating renal calculi. Methods A prospective study was conducted to compare both modalities for the management of renal calculi.Stone formers were randomly enrolled into two groups. Group A was managed with wide-focus high energy lithotriptor,while group B was managed with the other. Urine samples were collected to detect neutrophil gelatinase-associated lipocalin(NGAL)and α1-microglobulin(α1-MG)levels before and after SWL. Results 60 were randomized to the group A and 60 to group B. There was no significant difference between two groups in stone free rate and complication rate.For stones more than 10 mm,re-treat rate(11.1%vs 39.1%,P=0.021)was lower and complication rate(25.9%vs 4.3%,P=0.038)was higher in group A. There had a larger increase of NGAL in group A(P < 0.001)after SWL. Conclusion SWL with both lithotriptors are effective and safe for renal stones.Wide-focus high energy lithotripsy was associated with lower re-treat rate and higher complication rate for stones more than 10 mm.NGAL may play a potential role in the evalua-tion of SWL induced early renal injury.

Objective To investigate the occurrence status quo and related factors of cerebral vasospasm after cerebral ruptured aneurysms embolization.Methods Sixty-six patients withruptured cerebral aneurysms undergoing embolization treatment were selected as the research subjects,and conducted routine aneurysm embolization treatment.The cerebral vasospasm occurrence rate during hospitalization period was statistically calculated,and the related factors of cerebral vasospasm after cerebral aneurysm rupture embolization were analyzed.Results The cerebral vasospasm occurrence rate was 22.73 ％.Age,body mass index (BMI),hypertension rate,smoking history,aneurysms number,Fisher grade,Hunt-Hess grade,operation timing and Glasgow coma index (GCS) had statistically significant difference between the patients with and without cerebral vasospasm (P＜0.05).The related factors of cerebral vasospasm after embolization of ruptured aneurysms were age,hypertension,smoking history,number of aneurysms,Fisher grade,Hunt-Hess grade,operation timing and GCS index.Conclusion The cerebral vasospasm rate after embolization of ruptured aneurysms is high,and related to age,hypertension,smoking history,number of aneurysms,Fisher grade,Hunt-Hess grade,operation timing and GCS index.