Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. However, emergence of drug resistance limits its potential use. Plumbagin is a natural quinonoid compound isolated from plant. In this study, induced apoptosis effect of the combined treatment with plumbagin and TRAIL on human melanoma A375 cell line was examined and possible mechanism was investigated. The cells were divided into four groups: control group, plumbagin group (plumbagin, 5 or 10 mumol/L), TRAIL group (TRAIL, 30 ng/mL) and plumbagin+TRAIL group (combined treatment group). The apoptosis, and the expression of DR4 and DR5 were detected by flow cytometry. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that the apoptosis rate was 8.3% in TRAIL group, 10.35%-16.94% in plumbagin group and 52.39%-65.39% in combined treatment group, respectively, with the difference being significant between combined treatment group and plumbagin or TRAIL group (P<0.05 for each). Moreover, plumbagin alone could markedly up-regulate DR5 mRNA and protein expression, and slightly increase DR4 mRNA and protein expression. Treatment of human melanoma A375 cells with plumbagin resulted in the activation of Caspase-3, but not Caspase-8. These results suggest that plumbagin might be useful for TRAIL-based treatment for melanoma.

Objective: To study the pharmacokinetics and brain/plasma concentration ratio of nortriptyline at multiple doses in mice which were pre-treated with physiological saline, piperine and verapamil. Methods: A total of 216 male Kun Ming mice[(25±3) g] were equally divided into 4 groups randomly. Each group was intragastrically administered physiological saline (B), piperine (170 μg/kg), piperine (5 mg/kg) and verapamil (5 mg/kg) for 8 days. On the 8th day, 1 h atfer giving the above drugs, each mice was intraperitoneally injected nortriptyline (13 mg/kg). The mice were sacriifced by picking off eyeballs at the time intervals of 5, 15, 30 min, and 1, 2, 4, 6, 8 and 12 h, andthe cerebra were collected and weighted. Nortriptyline in mouse plasma and brain was determined by HPLC-MS/MS. The pharmacokinetic properties of the plasma, brain and brain/plasma were calculated. Results: hTe AUC0-12 h of brain/plasma concentration ratio in the 170 μg/kg piperine group was significantly lower than that in the other groups (P<0.05), while the AUC0-12 h of brain/plasma concentration ratios in the 5 mg/kg piperine group and the verapamil group were not signiifcantly different from those of untreated mice. Conclusion: Piperine (170 μg/kg) may induce P-glycoprotein expression in the blood-brain barrier, while piperines at 5 mg/kg has no influence on P-glycoprotein expression in the blood-brain barrier.

Objective To determine the clinicopathologic characteristics and prognostic factors that may be used to predict the poor outcome of patients with borderline ovarian tumors. Methods All cases with borderline ovarian tumors treated in the West China Second University Hospital from January 2001 to June 2007 were analyzed retrospectively for elinicopathologic features, treatment parameters and outcome of treatment. Univariate and multivariate analyses were used to assess independent prognostic factors using the logistic regression model. Results The median age of 234 patients was 40. 1 years with a range of 14 to 80 years. There were 101 (43.2%), 94 (40.2% ) , 19 (8.1% ), 12 (5.1%) , 8 (3.4%) cases of serous, mutinous, mixed, endometrioid and clear cell tumors, respectively. Out of 234 cases, 182 (77.8%) underwent laparotomy and 45 ( 19.2% ) underwent laparoscopy. Seven women underwent laparoconversion. Fertility sparing surgery was performed on 119 cases (50.9% ) and radical surgery was performed on 115 cases (49.1% ). Totally 161 (68.8% ) patients had stage Ⅰ , 19 ( 8.1% ) had stage Ⅱ, 54 ( 23.1% ) had stage Ⅲ, and none had stage Ⅳ disease. Sixty-four women received postoperative chemotherapy. The median follow-up was 40 months with a range of 8 to 78 months. Recurrence was found in 26 cases (11.1%) during follow-up, and no tumor-related death was reported. The logistic regression model showed that surgery procedure ( OR=2.304, P=0.024), cyst rupture ( OR=2.213, P=0.038 ), stage ( OR= 4.114, P<0.01 ), microinvasion ( OR=2.291, P=0.046) and peritoneal implants ( OR=2.101, P = 0.016) were the five independent prognostic factors affecting recurrence. Conclusions Although patients with borderline ovarian tumors have an excellent prognosis, the risk of recurrence remains in some patients. Emphasis should be put on these patients with high risk factors and preventive strategies should be taken to prevent their progression.

Atrial Fibrillation ; therapy ; Coronary Vessels ; Humans ; Percutaneous Coronary Intervention

Purpose: The aim of this study was to compare the effectiveness and outcomes of percutaneous ablation guided by ultrasonography (US) and computed tomography (CT) in colorectal liver oligometastases (CLOM). Methods: This study included patients with CLOM treated with percutaneous ablation from January 2008 to January 2021 in this observational study. Only lesions visualized on both CT and US images were further analyzed according to whether patients’ initial ablation treatments utilized US guidance or CT guidance. The Kaplan-Meier method was used to estimate local tumor progression (LTP)–free survival after propensity score matching (PSM). The LTP-free survival and treatment-related outcomes were compared between these two groups. Results: PSM identified 116 patients from each group, with 269 and 238 lesions in the USguided and CT-guided groups, respectively. US-guided ablation had a shorter average procedure time and lower cost than CT-guided ablation (27.54±12.06 minutes vs. 32.70±13.88 minutes, P=0.003; $2,175.13±618.17 vs. $2,455.49±710.25, P=0.002). For patients >60 years of age, the cumulative LTP rate at 1 year was lower in the US-guided group than in the CT-guided group (17.8% vs. 25.1%, P=0.038). For patients with perivascular liver lesions, the cumulative LTP rate at 1 year was lower in the US-guided group (14.4% vs. 28.2%, P=0.040). Conclusion For patients whose age is >60 years or who have perivascular liver lesions, USguided ablation is better than CT-guided ablation, with a shorter treatment time and lower costs when both ablation methods are feasible for patients.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent.However,emergence of drug resistance limits its potential use.Plumbagin is a natural quinonoid compound isolated from plant.In this study,induced apoptosis effect of the combined treatment with plumbagin and TRAIL on human melanoma A375 cell line was examined and possible mechanism was investigated.The cells were divided into four groups:control group,plumbagin group (plumbagin,5 or 10 μmol/L),TRAIL group (TRAIL,30 ng/mL) and plumbagin+TRAIL group (combined treatment group).The apoptosis,and the expression of DR4 and DR5 were detected by flow cytometry.The activities of caspase-8 and caspase-3 were determined by colorimetric assay.The results showed that the apoptosis rate was 8.3% in TRAIL group,10.35%-16.94% in plumbagin group and 52.39%-55.39% in combined treatment group,respectively,with the difference being significant between combined treatment group and plumbagin or TRAIL group (P＜0.05 for each).Moreover,plumbagin alone could markedly up-regulate DR5 mRNA and protein expression,and slightly increase DR4 mRNA and protein expression.Treatment of human melanoma A375 cells with plumbagin resulted in the activation of Caspase-3,but not Caspase-8.These results suggest that plumbagin might be useful for TRAIL-based treatment for melanoma.

Objective:To investigate the safety and efficacy of sacral neuromodulation(SNM)therapy for the treatment of lower urinary tract dysfunction(LUTD)in elderly patients.Methods:Clinical data of 91 elderly patients with LUTD from multiple medical institutions who received SNM during the period from January 2012 to December 2016 were retrospectively analyzed.Patients were divided into four groups: the interstitial cystitis(IC)group(n=28), the neurogenic bladder(NB)group(n=36), the overactive bladder syndrome(OAB)group(n=13)and the idiopathic dysuria(ID)group(n=14). Different sets of evaluation parameters were used for different diseases.Patients’ baseline data and data in stage I(test phase)and stage Ⅱ(permanent SNM)were recorded, statistically analyzed and compared.Results:Ninety-one people underwent SNM treatment.Of them, 53 patients received permanent implants(stage Ⅱ), and the total conversion rate of stage I to stage Ⅱ was 58.2%(53/91). Patients receiving permanent implants(stage Ⅱ)had a preoperative period ranging from 3 months to 30 years, and were followed up for 2 to 58 months after treatment, with an average follow-up of 19.6 months.The improvement rates in stage I for urinary urgency, daily urination frequency, daily nocturnal urination frequency, maximum urine volume, daily average urine volume, daily urine leakage frequency, and quality of life score were 35.4%, 31.6%, 33.7%, 32.6%, 49.2%, 43.2% and 13.2%, respectively.The improvement rates in stage Ⅱ for urinary urgency, daily urination frequency, daily nocturnal urination frequency, maximum urine volume, daily average urine volume, daily urine leakage frequency, and quality of life score were 43.2%, 40.0%, 37.8%, 50.5%, 70.5%, 70.4% and 43.2%, respectively.Three adverse events occurred, including 1 case of recurrent symptoms, 1 case of moderate infection, and 1 case of electrical lead dislocation.Conclusions:Sacral nerve stimulation has definitive and consistent curative effects on LUTD in elderly people.The follow-up time should be extended to further study the safety of sacral nerve stimulation.

Objective:To investigate the predictive value of preoperative D-dimer level for futile recanalization (FR) after mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS).Methods:It was a nested case-control study. A total of 116 patients with large vessel occlusion (LVO) stroke, who underwent successful recanalization (modified Thrombolysis in Cerebral Infarction, mTICI≥2b) after MT at the Stroke Unit of Beijing Hospital from August 2018 to January 2022,were consecutively enrolled, including 72 males (62.1%) with the age of (72.8±13.1) years. According to the 3-month modified Rankin Scale (mRS) score after MT, patients were divided into the meaningful recanalization group (mRS 0-2, n=41) and the futile recanalization group (mRS 3-6, n=75). The baseline clinical data of enrolled patients was collected. Logistic regression analysis was used to identify the independent risk factors for FR after MT in patients with AIS. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of D-dimer for FR. Results:Multivariate logistic regression analysis showed that high baseline systolic blood pressure (SBP) ( OR=1.038, 95% CI: 1.012-1.065, P=0.004), baseline National Institutes of Health Stroke Scale (NIHSS) score≥12 ( OR=10.157, 95% CI: 3.624-28.470, P<0.001) and high preoperative D-dimer level ( OR=4.536, 95% CI: 1.379-14.922, P=0.013) were independent predictors of FR after MT in AIS patients with LVO. ROC curve analysis indicated a good predictive value of preoperative D-dimer for the occurrence of FR ( AUC=0.733, 95% CI: 0.638-0.829, P<0.05), the optimal cut-off value of D-dimer was 2.65 μg/L(Lg), with the Youden index, sensitivity, specificity and accuracy of 0.435, 53.3%, 90.2% and 66.4%, respectively. Conclusion:High preoperative D-dimer level is an independent predictor of futile recanalization after MT in AIS patients with LVO, which shows good predictive ability for futile recanalization.

ObjectiveTo investigate the correlation between the color， odor and volatile components of Paeoniae Radix Alba（PRA） and its processed products， and to examine the effects of different processing methods on the odor and color formation of PRA. MethodThe odor and chromaticity information of PRA， honey chaff-fried PRA and honey bran-fried PRA were identified by electronic nose and colorimeter， and the volatile components in the different processed products of PRA were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and analyzed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， then the differential key flavor components among the three were screened according to the principles of variable importance in the projection（VIP） value>1 and relative odor activity value（ROAV）≥1. Pearson correlation analysis was used to investigate the association between the differential flavor components and the colorimetric values and electronic nose sensors， respectively. ResultAfter being fried with honey chaff and honey bran， the lightness value（L^*） of PRA decreased， and red-green value（a^*） and yellow-blue value（b^*） increased significantly（P<0.05， P<0.01）. The odor differences were mainly reflected in the S1， S2， S4， S5， S6， S8 and S11 sensors， and the results of PCA of the electronic nose indicated that the odor differences among PRA， honey chaff-fried PRA and honey bran-fried PRA were obvious， among which the overall odor intensity of honey bran-fried PRA was higher than that of honey chaff-fried PRA. A total of 47 volatile components were identified from PRA and its processed products， including 21 for PRA， 36 for honey chaff-fried PRA， and 37 for honey bran-fried PRA. Odor analysis revealed that 12， 24 and 22 volatile components may be the key flavor components in PRA， honey chaff-fried PRA and honey bran-fried PRA， respectively. Correlation analysis showed that the L^* of the decoction pieces was negatively correlated with the content of the Maillard reaction products， the a^* and b^* were positively correlated with the content of the Maillard reaction products， the S1 and S8 sensors were negatively correlated with the content of the Maillard reaction products， and the S2， S4， S5， S6 and S11 sensors were positively correlated with the Maillard reaction products. ConclusionThe color of PRA is deepened after being stir-fried with honey chaff and honey bran， and 5-hydroxymethylfurfural， furfural and other components are generated at the same time， which is in line with the theory of burning aroma strengthens the spleen of stir-fried with honey chaff and honey bran. Honey bran-fried PRA has a stronger Maillard reaction than honey chaff-fried PRA， which makes honey bran-fried PRA with a burnt flavor and a dark yellow color， while honey chaff-fried PRA has a sweet flavor and a bright yellow color.

Objective:To collect data on urinary flow rate in the elderly female population across the country and to analyze the range of reference values.Methods:This study enrolled 333 subjects from July 2020 to June 2022.The study implementation process was divided into two steps.In the first step, subjects completed an electronic questionnaire, which included basic information about the subject, a short form for urinary incontinence, and a scoring form for the symptoms of overactive bladder syndrome.In the second step, the staff introduced the use of a mobile uroflowmetric device and distributed the instrument and materials.Uroflow rate data were automatically uploaded to a cloud database via the mobile phone.Subsequently, two or more physicians specializing in urinary control performed Uroflow rate-qualifying screenings and conducted statistical analyses.Results:A total of 333 subjects were enrolled in the study, and the researchers collected 1375 qualified urine flow rate records using a mobile urine flow rate instrument.The age of the subjects ranged from 60 to 84 years, with a mean age of 69 years.The reference ranges for urinary flow rate were found to be 24.8-26.2 s, with a mean urinary flow rate of 12.2-12.9 ml/s, a maximum urinary flow rate of 22.2-23.4 ml/s, and a time to peak of 8.5-9.7 s. The study observed a tendency for both maximal and mean urinary flow rates to decrease in older women as their age increased(Pearson correlation coefficient: -0.1, P<0.001). Conclusions:The uroflow rate of older women decreases with aging.Specifically, the average uroflow rate of women over 80 years old is lower than that of other age groups.This study aims to establish normal uroflow parameters for uroflowmetry in healthy older women in China.