Objective: To explore the efficacy of focal radiofrequency ablation (RFA) in the treatment of low-to-intermediate risk localized prostate cancer and its impact on postoperative urinary control and sexual function recovery，in order to explore the feasibility of minimally invasive methods for the treatment of localized prostate cancer. Methods: Clinical data of 28 patients with low-to-intermediate risk localized prostate cancer who underwent RFA in Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School during Jun.2017 and Feb.2021 were retrospectively analyzed.The 5-year failure-free survival (FFS) rate，surgery related complications，postoperative urinary control and sexual function were collected.The differences between the survival curves of patients in the low-risk and intermediate-risk subgroups were assessed with log-rank test and Breslow test. Results: All surgeries were successfully completed under local anesthesia.During the median follow-up of 43 (40-49) months，the 5-year FFS rate predicted by Kaplan-Meier method was 78.57%; 25 patients (89.29%) did not experience surgery-related complications; 27 patients (96.43%) were able to control urination; 1 patient developed new-onset sexual dysfunction.There was no significant difference in the survival curves between patients in the low-risk and intermediate-risk groups (P>0.05). Conclusion: RFA for patients with low-to-intermediate risk localized prostate cancer has good clinical efficacy，little impact on urinary control and sexual function recovery，and few postoperative complications，which can be used as one of the treatment options for these patients.

BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

Transcatheter aortic valve replacement (TAVR) has emerged as the first-line treatment for aortic valve stenosis. Coronary obstruction is a severe complication of TAVR, with mortality rates exceeding 30%. Coronary obstruction can be classified as acute or delayed based on the timing of the onset, and as direct or indirect obstruction according to the underlying mechanism. Risk factors for predicting coronary obstruction include a small sinus of Valsalva diameter, excessively long native leaflets, low coronary height, and small sinotubular junction height and diameter. Accurate preoperative assessment of these anatomical parameters using CT is crucial for selecting the appropriate valve type, size, and implantation depth. Preventive technical strategies for coronary obstruction include intraoperative interventional treatments (such as the "Chimney" stenting technique), leaflet modification (such as the BASILICA technique), and alignment of the annulus and coronaries. These techniques have demonstrated significant efficacy in reducing the incidence of coronary obstruction and associated mortality. This paper reviews the epidemiology, classification, and mechanisms of coronary obstruction, with a particular focus on the identification, prevention, and treatment of high-risk patients. The aim is to highlight the importance of recognizing and managing coronary risks during TAVR and to provide actionable recommendations for the prevention and treatment of coronary obstruction in clinical practice.
Humans ; Transcatheter Aortic Valve Replacement/methods* ; Risk Factors ; Aortic Valve Stenosis/surgery* ; Postoperative Complications/prevention & control* ; Coronary Occlusion/etiology*

BACKGROUND:Osteonecrosis is a common refractory disease in clinical practice,and observational studies have suggested that micronutrients may have a prognostic role in osteonecrosis.However,the specific causal association between micronutrients and osteonecrosis is not known. OBJECTIVE:To explore the causal association between micronutrients and osteonecrosis by Mendelian randomization using summary data from a large population-based genome-wide association study(GWAS)for clinical diagnosis and treatment. METHODS:The required exposure and outcome data(calcium,magnesium,iron,vitamin E,carotenoids,retinol&osteonecrosis)were extracted from the IEU OpenGWAS database,GWAS catalog database,and FinnGen database.Data were analyzed by bidirectional Mendelian randomization with inverse-variance weighted as the primary study method,and weighted median method,simple mode method,weighted mode method,and MR-Egger regression to complement the results.The reliability of the data was then verified through sensitivity analyses. RESULTS AND CONCLUSION:(1)The results found a positive correlation between serum iron concentration and osteonecrosis,while no correlation was found for other micronutrients.There was no reverse causality in all the data.(2)The results of sensitivity analysis showed a robust causality.(3)By Mendelian randomization method,this study provided evidence of causality between serum iron concentration and osteonecrosis,and understanding the causality of micronutrient elements on osteonecrosis can help in the clinical diagnosis and treatment of osteonecrosis,which is of great clinical significance.

AIM:To observe the effect of folic acid(FA)on C2C12 myoblast proliferation and differentia-tion,and to explore its mechanism.METHODS:During the proliferation stage,C2C12 myoblasts were treated with vari-ous concentrations of FA(0,2.5,5,10 and 20 μmol/L).The cell status was observed under a microscope,cell viability was detected using the MTT method,and cell proliferation was assessed using the EdU method.In the differentiation stage,C2C12 cells were divided into control(Ctrl)group(0 μmol/L FA)and FA group(10 μmol/L FA).On day 2 or 4 of differentiation,immunofluorescence staining and Western blot were employed to detect the expression of myoblast differen-tiation-related proteins,myoblast determination protein 1(MyoD),myogenin(MyoG)and myosin heavy chain(MyHC).The myotubule formation in each group was analyzed.On day 4 of differentiation,C2C12 cells were treated with FA for 0,1,3 and 6 h,and the protein levels of p-JNK,JNK,p-p38 MAPK and p38 MAPK at each time point were detected by Western blot.Additionally,C2C12 cells after 4-day differentiation were divided into Ctrl group,FA group,FA+ SP600125(specific inhibitor of JNK)group,and FA+SB203580(specific inhibitor of p38)group.The cells in FA+ SP600125 and FA+SB203580 groups were treated with 10 μmol/L SP600125 or SB203580 for 1 h,followed by treatment with 10 μmol/L FA for 24 h.The cells in FA group were treated with 10 μmol/L FA for 24 h,while the cells in Ctrl group were left untreated.The protein levels of p-JNK,JNK,p-p38 MAPK,p38 MAPK and MyHC were detected by Western blot.RESULTS:(1)Compared with 0 μmol/L FA group,the number of the cells in other concentration groups in-creased,cell viability was raised(P＜0.05 or P＜0.01),and the rate of EdU positive cells increased(P＜0.05).(2)Com-pared with Ctrl group,the expression levels of MyoD,MyoG and MyHC in FA group were increased(P＜0.05),and the myotube fusion index was raised(P＜0.05 or P＜0.01).(3)Compared with 0 h group,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK were elevated after FA treatment for 1,3 and 6 h(P＜0.05 or P＜0.01),and showed a trend of gradual increase with the extension of treatment time.(4)After FA treatment,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK,and the expression of MyHC were elevated(P＜0.01).Treatment with SP600125 decreased the ratio of p-JNK/JNK and the expression of MyHC(P＜0.05),while SB203580 intervention cut down the ratio of p-p38 MAPK/p38 MAPK and the expression of MyHC(P＜0.05 or P＜0.01).CONCLUSION:Folic acid can promote the differentiation of C2C12 myoblasts by activating the JNK/p38 MAPK signaling pathway.

Objective:To investigate the expression of nuclear matrix protein 4 (NMP4) in hepatocellular carcinoma (HCC), and its relationship with clinicopathological features and survival prognosis of patients.Methods:The clinical data of 100 HCC patients who were treated with radical resection of liver cancer in the Department of Hepatobiliary Surgery of the Third Affiliated Hospital of Wenzhou Medical University from July 1, 2014 to July 1, 2019 were retrospectively analyzed. There were 63 males and 37 females, aged (58.5±10.4) years old. Immunohistochemical method was used to detect the expression of NMP4 protein in HCC cancer tissue and the corresponding adjacent normal tissue. According to the expression of NMP4 in HCC tissues, 100 patients were divided into two groups: the NMP4-positive expression group ( n=62) and the NMP4-negative expression group ( n=32). Univariate analysis was performed on the relationship between NMP4 expression and clinical pathological features as well as overall survival of HCC patients. Cox multivariate analysis was performed on the factors influencing postoperative prognosis of HCC patients. Results:Immunohistochemistry results showed that NMP4 was primarily expressed in the nucleus, the positive expression rate of NMP4 in HCC tissues was higher than that in adjacent non-cancerous tissues [62.0% (62/100) vs. 8.0%(8/100)], and the difference was statistically significant ( χ2=2.12, P=0.003). Univariate analysis revealed that the overall survival of HCC patients was correlated with the degree of tumor differentiation, tumor length, BCLC stage, number of tumor foci, vascular tumor thrombus and expression of NMP4 (all P<0.05). Cox multivariate analysis revealed that low differentiation, high BCLC stage (stage C), number of tumor foci (≥3), and positive expression of NMP4 were independent risk factors affecting postoperative survival and recurrence-free survival of HCC patients. The median overall survival and median recurrence-free survival of HCC patients in the NMP4-positive expression group were 22.3 months and 11.5 months, respectively. In contrast, that in the NMP4-negative expression group were 40.6 months and 19.4 months, respectively. The cumulative survival rate and recurrence-free survival rate of HCC patients in the NMP4-positive expression group were lower than those in the NMP4-negative expression group, and the differences were statistically significant (both P<0.05). Conclusion:Positive NMP4 expression was closely correlated with malignant biological progression and poor prognosis of HCC patients.

Objective:To explore the clinical effectiveness of high-frequency color Doppler ultrasound (HFCDU) assisted harvest of radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap to repair soft tissue defect below the elbow.Methods:A retrospective study was conducted on the clinical data of patients who underwent repair of soft tissue defects below the elbow using the radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap at the Second Hospital of Tangshan from January 2016 to June 2021. Prior to the surgery, HFCDU was utilized to identify and measure the course of the lateral forearm cutaneous nerve and the perforating branch of the radial artery surrounding the wound. Subsequently, the flap rotation point, axis, and area were meticulously designed. During the surgical procedure, the skin flap was harvested either through a subcutaneous tunnel or by direct transfer, while the nerve stump at the defect site was anastomosed end-to-end with the lateral cutaneous nerve of the forearm contained in the skin flap. After reducing the wound at the donor site, it was either directly sutured or repaired using a medium-thick skin graft harvested from the thigh. After surgery, the survival of the skin flap, wound healing at the donor site, and the survival of the skin graft were observed. At the last follow-up, the static two-point discrimination of the flap was measured, and patient satisfaction with the appearance of the flap was assessed using the Michigan hand outcomes questionnaire(MHQ). This questionnaire categorized satisfaction into five levels: very dissatisfied (1 point), dissatisfied (2 points), fair (3 points), satisfied (4 points), and very satisfied (5 points). The scar condition of the donor site was evaluated according to the Vancouver scar scale (VSS), which scored from 0 to 15 points, with higher scores indicating more severe scarring. Descriptive analysis of the data was performed using SPSS 27.0 software.Results:A total of 33 patients were included in the study, comprising 20 males and 13 females, with an average age of (41.0±11.7) years (range, 23-65 years). The defect locations included 6 forearms, 9 wrists, and 18 hands, with all patients having exposed bones and (or) tendons. The defect area ranged from 3.0 cm × 2.5 cm to 12.0 cm × 5.0 cm. The detection result of cutaneous nerves and perforating blood vessels using HFCDU were consistent with the actual findings during surgery, showing no discrepancies. The area of the skin flaps ranged from 3.5 cm × 3.0 cm to 13.0 cm × 6.0 cm. All 33 skin flaps survived postoperatively, with good blood supply and no infections reported; the wounds at the donor site healed primarily, and all grafted skin survived. The duration of postoperative follow-up was (15.6±2.9) months (range, 10-24 months), and the patients’ static two-point discrimination of the flap was measured at (12.5±3.3) mm (range, 8-20 mm). The result of the MHQ indicated that 23 patients were very satisfied with the appearance of the flap (5 points), while 10 patients were satisfied (4 points). The VSS score for the donor site was (4.3±0.9) points (range, 3-6 points), indicating that the scar at the donor site was mild.Conclusion:HFCDU can accurately identify the lateral forearm cutaneous nerve and the perforating branch of the radial artery.The radial artery perforator-pedicled lateral forearm neurocutaneous vascular flap can provide a reliable blood supply, good appearance, sense and patient satisfaction, which is suitable for repairing soft tissue defects below the elbow.

Objective:To compare the prognostic values of different classification by using transpulmonary pressure gradient (TPG), diastolic pressure gradient (DPG) and pulmonary vascular resistance (PVR) in patients with pulmonary hypertension due to left heart disease (PH-LHD), and investigated hemodynamic and clinical factors associated with mortality in patients with PH-LHD.Methods:This was a single-center prospective cohort study. In-hospital patients diagnosed with PH-LHD via right heart catheterization at the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, from September 2013 to December 2019 were enrolled. Patients were divided according to TPG (cutoff value 12 mmHg; 1 mmHg=0.133 kPa), DPG (cutoff value 7 mmHg), PVR (cutoff value 3 Wood Units), and the combination of TPG and PVR. Baseline characteristic was recorded. All patients were followed up until the occurrence of endpoint event, defined as all-cause death that occurred during the follow-up period, or until April 18, 2022. Receiver operating characteristic curves were used to compare the predictive value of 3 classification methods for all-cause death in PH-LHD patients. The optimal cutoff values were calculated using Jorden index. Survival analysis was performed using Kaplan-Meier analysis, and log-rank test was used to compare the predictive efficacy of classification methods based on optimal cutoff values or guidance-recommended thresholds for the survival of PH-LHD patients. Variables showing statistical significance in the univariate analysis were incorporated into multivariate Cox regression model to analyze the independent risk factors for all-cause mortality.Results:A total of 243 patients were enrolled, aged (54.9±12.7) years old, including 169 (69.5%) males. During a median follow-up of 57 months, there were 101 (41.6%) deaths occurred. Grouping results were as follows: (1) TPG: TPG≤12 mmHg group 115 patients, TPG>12 mmHg group 128 patients; (2) DPG: DPG<7 mmHg group 193 patients, DPG≥7 mmHg group 50 patients; (3) PVR: PVR≤3 Wood Units group 108 patients, PVR>3 Wood Units group 135 patients; (4) TPG and PVR: TPG≤12 mmHg and PVR≤3 Wood Units group 89 patients, TPG>12 mmHg and PVR>3 Wood Units group 109 patients. PVR ( AUC=0. 698,95% CI:0.631-0.766) had better predictive value for all-cause mortality than TPG ( AUC=0.596, 95% CI: 0.523-0.669) and DPG ( AUC=0.526, 95% CI: 0.452-0.601) (all P<0.05). The optimal cutoff values for TPG, DPG, and PVR were13.9 mmHg, 2.8 mmHg, and 3.8 Wood Units, respectively. Kaplan-Meier analysis based on the optimal cutoff values or guidance-recommended thresholds showed that PVR and TPG were the predictors of survival ( P<0.05), while DPG did not showed significance ( P>0.05). Multivariate Cox regression analysis showed that age, PVR and log 2N-terminal pro-B-type natriuretic peptide were independent risk factors for all-cause mortality in PH-LHD patients (all P<0.05). Conclusion:Classification according to PVR was most valuable in predicting all-cause death in PH-LHD patients, while TPG showed moderate predictive ability and DPG had no predictive value.

Objective To compare and analyze the efficacy and risks of percutaneous CT/ultrasound-guided bipolar radiofrequency ablation(RFA)under local anesthesia with robotic-assisted laparoscopic partial nephrectomy(RAPN)for the treatment of sporadic small renal mass.Methods A retrospective study was conducted on 93 consecutive patients with T1a stage small renal mass during Mar.2019 and Oct.2021.Among them,51 underwent RAPN,and 42 underwent RFA.General information,tumor characteristics,perioperative and follow-up data were collected and statistically analyzed.Results There were no significant differences in general information and tumor characteristics between the two groups(P＞0.05).The operation time[(96.0±20.0)min vs.(113.5±24.1)min,P＜0.001],hospital stay[(3.5±0.8)day vs.(6.9±1.8)day,P＜0.001],and hospital costs[(2.4±0.7)ten thousand yuan vs.(6.6±0.4)ten thousand yuan,P＜0.001]were significantly decreased in the RFA group than in the RAPN group.There were no significant differences in the incidence of perioperative complications and long-term disease-free survival rate between the two groups(P＞0.05).However,the difference between one-year postoperative estimated glomerular filtration rate(eGFR)and preoperative eGFR was significantly lower in the RFA group than in the RAPN group[-2.3(-4.7-1.3)mL/(min·1.73 m2)vs.-5.0(-9.1 2.8)mL/(min·1.73 m2),P=0.003],and the reduction of one-year postoperative creatinine and preoperative creatinine was slightly lower in the RFA group than in the RAPN group[4.0(-0.2-5.5)μmol/L vs.4.5(1.8-9.2)μmol/L,P=0.122].Conclusion RFA can achieve comparable disease-free survival rate as RAPN in the treatment of T1a renal tumor,and can effectively preserve renal function,reduce medical costs,save medical resources,and lower the incidence of perioperative complications.