AIM: To evaluate the effect of inhibiting ubiquitin-specific protease 14 (USPl4) activity on oxidative stress induced by H2O2 of H9c2 cells.METHODS: The H9c2 cells were incubated with H2O2 at 25 μmol/L for 2 h to establish the oxidative stress injury model.The cells were divided into control group, H2O2 group, IU1 group (25 μmol/L or 50 μmol/L) and IU1+ H2O2 group.The H9c2 cells activity was measured by MTS assay.The level of intracellular reactive oxygen species (ROS) and cell survival rate were analyzed by flow cytometry assay.The changes of the mitogen-activated protein kinase (MAPK) family related proteins were detected by Western blot.RESULTS: Compared with control group, the cell activity and the viability rate in H2O2 group were decreased (P<0.05), while the intracellular ROS, the protein levels of Bax/Bcl-2, P53, p-ERK1/2, p-JNK and p-P38 were increased (P<0.05).Compared with H2O2 group, the cell activity and the viability rate of the H9c2 cells in IU1+H2O2 group were increased (P<0.05), while the intracellular ROS, the protein levels of Bax/Bcl-2, P53, p-ERK1/2, p-JNK and p-P38 were decreased (P<0.05).CONCLUSION: Inhibition of USPl4 activity reduces the oxidative stress injury of the H9c2 cells.The mechanism may be related to inhibition of the MAPK signaling and down-regulation of apoptosis related proteins.

Objective:To explore the accuracy of mpMRI combined with Partin table, MSKCC nomogram and CAPRA score in predicting extracapsular extension and seminal vesicle invasion of prostate cancer.Methods:From January 2016 to June 2021, a total of 178 patients who underwent laparoscopic radical prostatectomy were selected. The average age of patients was (68.3±3.5) years, the average preoperative PSA level was (24.5±7.1)ng/ml, and the average percentage of positive cores in biopsy was 44.3%. The clinical T 1c stage was determined in 67 cases (37.6%), T 2a in 69 cases (38.8%) and T 2b-2c in 42 cases(23.6%). Biopsy Gleason score of 3+ 3=6 was found in 45 cases(25.3%), 3+ 4=7 in 41 cases(23.0%), 4+ 3=7 in 26 cases(14.6%), 8 with different combinations in 36 cases(20.2%), and 9 or 10 in 30 cases(16.9%). According to preoperative PSA level, biopsy Gleason score, clinical stage, age, total biopsy cores and positive cores, the posibility of extracapsular extension and seminal vesicle invasion were predicted using 2012-version Partin table and MSKCC nomogram. CAPRA score of each patient was calculated. The prediction schemes were built as follows: ①mpMRI alone, ②mpMRI combined with Partin scale, ③mpMRI combined with MSKCC nomogram, ④mpMRI combined with CAPRA score. The results of each prediction scheme were compared with postoperative pathological reports. Logistic regression analysis was used to evaluate the relationship between predictive results and postoperative pathological outcomes. The receiver operating characteristic curve of each prediction scheme was drawn. The area under curve was used to compare the predictive accuracy of each combination scheme for the pathological results of prostate cancer. The decision analysis curve of each prediction scheme was drawn. The clinical benefits of each scheme were analyzed by comparing the net return under different risk thresholds. Results:mpMRI predicted extracapsular extension in 21 cases(11.8%) and seminal vesicle invasion in 16 cases(9.0%). The postoperative pathological results reported extracapsular extension in 27 cases(15.2%) and seminal vesicle invasion in 39 cases(21.9%). Logistic regression analysis showed that mpMRI and clinical scales were predictors related to the pathological results of prostate cancer( P<0.05). The receiver operating characteristic curve of each scheme showed that the area under curve for predicting extracapsular extension by using mpMRI, mpMRI combined with Partin table, mpMRI combined with MSKCC nomogram and mpMRI combined with CAPRA score were 0.599, 0.652, 0.763 and 0.780, respectively, and the area under curve for predicting seminal vesicle invasion were 0.607, 0.817, 0.826 and 0.820, respectively. Compared with simple application of mpMRI, except that the scheme of mpMRI combined with Partin table had no obvious advantage in predicting extracapsular extension( P=0.117), any other combined scheme had higher prediction accuracy( P<0.01). mpMRI combined with MSKCC nomogram or CAPRA score was better than mpMRI combined with Partin table in predicting extracapsular invasion ( P<0.01). There was no significant difference in predicting seminal vesicle invasion among these three combination schemes ( P>0.05). The net income of the combined prediction scheme was higher than that of using mpMRI alone under any risk threshold. The scheme of using mpMRI combined with MSKCC nomogram had the highest net income. Conclusions:mpMRI combined with clinical scales has good accuracy in predicting pathological characteristics of prostate cancer in Chinese population. Compared with other schemes in this study, the combination scheme of mpMRI combined with MSKCC nomogram has the highest prediction accuracy.

Objective:To investigate the relationship between 1-hour lactate (1 h Lac) and 30-day mortality in critical care patients in intensive care unit (ICU).Methods:A retrospective, observational cohort study was performed with adult critical patients (age ≥ 16 years old) having lactate records within 1 hour after ICU admission from Medical Information Mart for Intensive Care-Ⅲ database (MIMIC-Ⅲ). According to the 1 h Lac level, the patients were divided into three groups: < 2 mmol/L, 2-4 mmol/L, and > 4 mmol/L groups. The baseline characteristics were analyzed. Multivariable Logistic regression analysis was performed to assess the association between 1 h Lac and 30-day mortality. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of 1 h Lac for 30-day mortality, and Kaplan-Meier survival curve was performed according to the best cut-off value. In addition, sensitivity analysis was carried out for each classification variable.Results:A total of 3 969 ICU patients were included, with 673 died in 30 days, and the total mortality was 16.95%. There were 1 664, 1 588, 717 patients in Lac < 2 mmol/L, 2-4 mmol/L and > 4 mmol/L group, respectively. There were significant differences in age, ICU duration, ICU type, heart rate, leukocyte count, hemoglobin, creatinine, sequential organ failure score (SOFA), ventilator application, vasoactive drug use and main diagnosis among the three groups. Multivariable Logistic regression analysis showed that a 1 mmol/L increment in Lac was associated with 0.24 times higher risk of 30-day mortality [odds ratio ( OR) = 1.24, 95% confidence interval (95% CI) was 1.19-1.29, P < 0.000 1]. ROC curve analysis showed that the area under ROC curve (AUC) of 1 h Lac for predicting 30-day mortality of severe patients was 0.694 (95% CI was 0.669-0.718). The cut-off value was 3.35 mmol/L with sensitivity of 0.499 and specificity of 0.779, whilst positive likelihood ratio was 2.260, and negative likelihood ratio was 0.643. According to the cut-off value of 1 h Lac, the patients were divided into high lactate group (≥ 3.35 mmol/L) and low lactate group (< 3.35 mmol/L). In the two subgroups, 30-day mortality was 31.58% (336/1 064) and 11.60% (337/2 905), respectively. The Kaplan-Meier survival curve showed that the 30-day cumulative survival rate of high lactate group was significantly lower than that of low lactate group (Log-rank test: χ 2 = 247.72, P < 0.000 1). Multiple Logistic regression analysis showed that the 30-day mortality rate of high lactate group was 2.34 times that the level of low lactate group ( OR = 2.34, 95% CI was 1.90-2.88, P < 0.000 1), after the adjustment of age, time of admission, type of ICU, hemoglobin, leukocyte count, use of vasopressor, use of ventilator and main diagnosis of patients. Stratified analysis showed that the relationship between 1 h Lac and 30-day mortality was stable. Conclusions:1 h Lac is associated with 30-day mortality in critical care patients. The risk of death was significantly increased in critically ill patients with 1 h Lac higher than 3.35 mmol/L.

Objective This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials(RCTs)assessing the clinical efficacy of acupuncture for chronic stable angina(CSA).Methods PubMed,The Cochrane Library,Embase,CNKI,VIP,WanFang Data,CBM databases,ClinicalTrial.gov and Chinese Clinical Trial Registry were electronically searched to collect randomized controlled trials(RCTs)of acupuncture for CSA and only RCTs that included acupuncture as the sole or combination of acupuncture in the treatment of CSA.The retrieval period was from the establishment of the database to May 19,2022.The primary outcome measure was the frequency of angina attacks,and the secondary outcome measures were angina efficacy,total effective rate of ECG improvement,nitroglycerin use after treatment,patient-perceived overall effectiveness,performance on the Six-Minute Walk Test(6-MWT),depression as measured by the anxiety as measured by the Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),adverse effects.Results Twelve studies with a total of 1605 case subjects were included and grade quality of evidence reviews had 1 outcomes as medium quality evidence,5 outcomes as low quality evidence and 4 outcomes as very low quality evidence.Acupuncture treatment resulted in significantly greater reductions in angina attacks,visual analog scale(VAS),6-minute walk test,angina efficacy,electrocardiogram improvement rate,angina efficacy,total clinical response rate.Conclusion The efficacy of acupuncture combined with western medicine in treating CSA is better than that of Western medicine alone,thanks to restricted by the number and quality of included researchs,higher quality studies are required to prove above conclusions.

Motor dysfunction is the main clinical symptom and diagnosis basis of patients with Parkinson's disease (PD). A total of 30 subjects were recruited in this study, including 15 PD patients (PD group) and 15 healthy subjects (control group). Then 5 wearable inertial sensor nodes were worn on the bilateral upper limbs, lower limbs and waist of subjects. When completing the 6 paradigm tasks, the acceleration and angular velocity signals from different parts of the body were acquired and analyzed to obtain 20 quantitative parameters which contain information about the amplitude, frequency, and fatigue degree of movements to assess the motor function. The clinical data of the two groups were statistically analyzed and compared, and then Back Propagation (BP) Neural Network was used to classify the two groups and predict the clinical score. The final results showed that most of the parameters had significant difference between the two groups, ten times of 5-fold cross validation showed that the classification accuracy of the BP Neural Network for the two groups was 90%, and the predictive accuracy of Hoehn-Yahr (H-Y) staging and unified PD rating scale (UPDRS) Ⅲ score of the patients were 72.80% and 68.64%, respectively. This study shows the feasibility of quantitative assessment of motor function in PD patients using wearable sensors, and the quantitative parameters obtained in this paper may have reference value for future related research.

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Siderophores/metabolism* ; Iron/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism* ; ATP-Binding Cassette Transporters