Acute Kidney Injury ; chemically induced ; Humans ; Paraquat ; poisoning ; Rhabdomyolysis ; chemically induced

Objective To investigate the synergistic effect of 11 β-hydroxysteriod dehydrogenase (11 β-HSD1) and S100A16 on the differentiation of3T3-L1 preadipocytes and its mechanism.Methods Lentiviral vectors PLJM1-11β-HSD1 and PLJM1-S100A16-GFP were respectively constructed and co-transfected into 3T3-L1 preadipocytes.The cell strains expressing 11 β-HSD1/S100A16 were screened with 2.5 μg/ml puromycin for two weeks.Western blot was employed to verify the lentiviral carrier transfection effects.The expressions of marker genes related to the adipocyte differentiation were detected by mean of realtime PCR.Oil red O staining was used to observe the lipid droplet accumulation and the content of triglyceride was measured after differentiation of preadipocytes.The effect of 11β-HSD1 and S100A16 on PPARγ promoter activity was detected by luciferase reporter gene.Results Compared with the empty vector group,the expressions of 11β-HSD1 and S100A16 protein in the lentivirus cotransfected 3T3-L1 cell strain were significantly higher.After 3T3-L1 cell strain co-expressing 1 1β-HSD1 and S100A16 was induced to differentiate for 8 days,the lipid droplets accumulation and triglyceride content were siginificantly increased,along with increased expressions of adipocyte differentiation marker genes such as PPARγ,CCAAT/enhancer binding protein α,lipoprotein lipase,fatty acid synthase,and adipocyte fatty acid-binding protein,in comparison with 11 β-HSD1 or S100A16 overexpression.The result of reporter gene indicated that 11 β-HSD1/ S100A16 enhanced PPARγ promoter activity.Conclusions 11β-HSD1 and S100A16 may jointly promote the differentiation of 3T3-L1 preadipocytes through a synergistic effect on PPARγexpression and play a critical role in the development of obesity.

Objective To evaluate the effect of modified Maze lines plus pulmonary vein (PV) isolation created by radiofrequency catheter ablation (RFCA) on atrial wall guided by a novel geometry mapping system in the treatment of elderly patients with paroxysmal atrial fibrillation (PAF). Methods After regular electrophysiological study, transseptal punctures were achieved twice with Swartz L1 and R1 sheaths. PV angiographies were conducted to evaluate their orifices and branches. A balloon electrode array catheter with 64 electrodes was put in the middle of the left atrium. Atrium geometry was constructed using Ensite 3000 Navx system. Two RFCA lesion loops and three lines (modified Maze) were created on left and right atrial walls. Each lesion point was ablated for 30 seconds with preset temperature 50 (ae) and energy 30W. The disappearance or 80% decrease of the amplitude of target atrial potential and 10 to 20(|), decrease of ablation impedance were used as an index of effective ablation. Results A total of 11 patients (7 male and 4 female, mean age, 68.7±5.1 years) were enrolled. PAF history was 7.9±4.5 years. PAF could not be prevented by mean 3.1±1.6 antiarrhythmic agents in 6.3±3.4 years. None of the patients had complications with structural heart disease or stroke. Left atrial diameter was 41.3±3.6 mm and LVEF was 59.2±3.7% on echocardiography. Two loops and three lines were completed with 67.8±13.1 (73-167) lesion points. Altogether 76-168 (89.4±15.3) lesion points were created in each patient. PAF could not be provoked by rapid burst pacing up to 600 beat per minute delivered from paroxysmal coronary sinus electrode pair.Complete PV electrical isolation was confirmed by three-dimensional activation mapping. Mean procedure time was 2.7±0.6 hours and fluoroscopy time was 17.8±9.4 minutes. Patients were discharged with oral aspirin and without antiarrhythmic agents. During follow up of 6.5±1.8 months, seven patients were PAF symptom free (63.6%). PAF attacks were decreased more than 70% in two patients (18.2%). PAF frequency did not change in another two patients (18.2%). Conclusions Ensite 3000 Navx guided modified Maze lines plus PV isolation on the atrial wall is safe and feasible in the elderly patients. It has the advantages of exact procedural endpoint, shorter X-ray exposure, fewer complications and satisfied long-term effect PAF control.

Objective Tostudyrecentclinicalefficacyandadversereactionsofpemetrexedincombi-nationwithcisplatininthetreatmentofadvancedbreastcancer.Methods Usingenvelopesandrandomlythe patients were dividing into treatment group and control group.The treatment group with 1 8 cases of advanced breast cancer were treated with pemetrexed and cisplatin while in the control group ,23 cases advanced breast cancer patients were treated with gemcitabine and cisplatin with 21 days as a cycle.The efficacy and adverse re-actions were determined according to the WHO on Response Evaluation Criteria in Solid Tumors therapy and chemotherapytoxicityevaluationcriteria.Results Tumorcontrolrateinthetreatmentgroupwas83.3%(1 5/1 8),while in the control group was 78.3%(1 8/23 ),and the difference was not statistically significant (χ2 =0.000 94,P>0.05);while the adverse reactions differenced between the treatment group and the con-trol group were statistically significant(bone marrow suppression χ2 =9.23;fatigue χ2 =4.96;nausea and vomi-tingχ2=4.98;diarrheaχ2=4.45;skinrashχ2=5.03,P<0.05).Conclusion Pemetrexedcombinedwith cisplatin in patients with advanced breast cancer has a good effect,and the adverse reaction is low.

Objectives:To report the clinical experience of combined interventional procedures in the treatment of elderly patients with coexisting two or more cardiovascular diseases in our medical center, and to assess the feasibility, safety and therapeutic efficacy of this management strategy. Methods : Patients were selected to the study if: 1) age ＞65 years; 2) with coexistence of two or more cardiovascular diseases which are indications for interventional therapy; 3) patients' general condition and organ functions allow the performance of combined multiple procedures; 4) the predicted procedure time is within 150 min; 5) the predicted contrast medium dosage is within 300 ml. The criteria we analyzed included procedural type, rocedural time, fluoroscopy time, dosage of contrast medium, success rates of the procedures, complications and in-hospital mortality. All patients were followed up for 30.4 ± 9.3 months,to determine the all-cause mortality, recurrence rates and adverse cardiac events. Results : From January 2000 to December 2004,combined interventional procedures were performed on 136 patients, with 2 procedures on 134 patients and 3 procedures on 2 patients.The mean procedure time was 115.4±11.6 min, the mean fluoroscopy time was 35.7±9.3 min, and the mean dosage of contrast medium used was 183.6±19.4 ml. Procedural success rate was 100%, no procedure related death or major complications occurred.Conclusion: Performed by a competent team, combined interventional procedures in elderly patients with multiple cardiovascular diseases were feasible and relatively safe.

Objective To establish an animal model for evaluating immunogenicity of pneumococcal conjugate vaccine.Methods New Zealand rabbits were intramuscularly administrated with three doses of 13-valent pneumococcal conjugate vaccine (PCV13) with two weeks interval between each injection.Serum samples were collected at different time points before and after vaccination.Quantitative enzyme-linked immunosorbent assay (ELISA) and opsonophagocytosis assay (OPA) that were in conformity with the World Health Organization (WHO) standards were used to detect the concentrations of serotype-specific antibodies and their bactericidal activities.Results The concentrations (Geometric mean concentration, GMC) of serotype-specific antibodies in rabbit serum samples were well correlated with their bactericidal activities (Geometric mean titer, GMT) following vaccination.Moreover, the dynamic changes of GMC and GMT of the same serotype-specific antibody remained consistent as time went by.Conclusion Rabbit model can be used to analyze the immunogenicity of PCV13 vaccine with quantitative ELISA and OPA, which indicates that it is a suitable animal model for evaluating immunogenicity of pneumococcal conjugate vaccine.

To evaluate the feasibility, safety and efficacy of percutaneous stent implantation for treating left main coronary artery (LMCA) stenosis. Methods Consecutive patients with unprotected left main coronary artery disease treated by stent-based percutaneous intervention (PCI) at 6 medical centers in China were enrolled. Procedural data and clinical outcomes were obtained from all patients. Results From January 2001 to December 2004, 138 patients (79 males and 59 females; mean age: 69.7±5.8 years)underwent PCI for LMCA stenosis. Bare metal stents (BMS) were implanted in 51 patients with non-bifurcational lesions and in 5 patients with bifurcational lesions from January of 2001 to June of 2003 (BMS group);. Drug eluting stents (DES) were used unselectively to cover both bifurcational and non-bifurcational lesions in 86 patients from July of 2003 to December of 2004 (DES group). Procedural success rate of the 138 cases was 98% (135/138). One patient (0.7%) with bifurcation lesion who was treated with DES died from severe heart failure 2 weeks after the procedure. During a mean follow up period of 21.3 ± 5.6 months, one patient died from renal failure, one from sudden cardiac death, 4 underwent target lesion revascularization (TLR) in the BMS group, which all occurred in patients with bifurcational lesions; whereas in the DES group no deaths occurred and only one patient with bifurcational lesion had TLR. Conclusions (1) PCI is feasible and relatively safe to treat unprotected left main coronary artery disease in elderly patients at medical centers with experienced professionals. (2) BMS and DES have similar immediate and long-term efficacy in the treatment of ostium and shaft lesions of the LMCA. (3) DES are strongly suggested in the therapy of distal bifurcation lesion of unprotected LMCA.

Objective To explore the role of dehydroepiandrosterone ( DHEA) in fatty acid metabolism in the liver of obese rats induced by high fat diet. Methods Twenty-seven SD rats were divided into control group, high-fat diet group ( HF group ) , and high-fat diet combined with DHEA treatment group ( DHEA group ) . The serum glucose and insulin levels were determined, while the free fatty acids ( FFA ) level was measured by liquid chromatography-tandem mass spectrometry (LC-MS). The mRNA expressions of hormone-sensitive lipase (HSL), lipoprotein lipase ( LPL ) , acetyl-CoA carboxylase ( ACC ) , fatty acid synthase ( FAS ) , carnitine acyl-CoA transferase (CPT), and stearoyl-CoA desaturase 1 ( SCD1) were measured by real-time PCR. Finally, oil red O staining was also used to observe the changes in hepatic lipid deposition. Results ( 1) The content of hepatic FFA in HF group was significantly higher than that in control group ( P<0.05) , but decreased in DHEA group compared with that in HF group (P<0.05). (2) Compared with HF group, the mRNA expressions of HSL, LPL, ACC, FAS in DHEA group were significantly lower while the mRNA expressions of CPT1, CPT2, and SCD1 were significantly higher ( all P<0.05). (3) Oil-red O staining showed that the liver lipid content in high fat diet-fed rats were significantly increased compared with that in the chow diet group( P<0.05) , but there was no difference between HF and DHEA groups. However, the structural damage of HF group was more evident compared with DHEA group. Conclusion DHEA may reduce the content of hepatic FFA in high-fat diet-induced obese rats via inhibiting the production of FFA and promoting theβ-oxidation of FFA.

Objective To evaluate the effect of labor analgesia on maternal and neonatal outcomes. Methods The medical records of mature puerperas with singleton pregnancy from October 2018 to April 2019 at the General Hospital of Ningxia Medical University were retrospectively reviewed. Puerperas were divided into non-labor analgesia group ( NLA) and labor analgesia group ( LA) according to whether or not puerperas received labor analgesia. Maternal and neonatal outcomes were analyzed. Maternal outcomes in-cluded delivery mode, complications, intrapartum hemorrhage and blood loss at 24 h after birth, duration of the second stage of labor and prolongation, episiotomy and length of hospital stay after birth. Neonatal outcomes included Apgar score at 1, 5 and 10 min after birth, cases of Apgar score＜7 at 5 min after birth, and the proportion and reason of transfer to pediatrics unit. Results A total of 839 puerperas were includ-ed, with 551 cases in NLA group and 288 cases in LA group. Compared with NLA group, the second stage of labor was significantly prolonged ( P＜0. 01) , and no significant change was found in the other maternal or neonatal outcomes in LA group ( P＞0. 05) . Conclusion Labor analgesia can prolong the second stage of labor and exerts no effect on the neonatal outcomes.

Objective:To investigate the effect of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer (MBC) patients with different expression levels of human epidermal growth factor receptor 2 (HER2) and the influencing factors of prognosis.Methods:The retrospective case series analysis and cohort study were conducted. Clinical data of 20 MBC patients with different expression levels of HER2 treated with T-DXd at Xi'an International Medical Center Hospital from August 2021 to August 2023 were retrospectively collected to analyze the efficacy and safety of T-DXd. The Cox proportional hazards model was used for multivariate analysis of prognostic factors.Results:All 20 patients were female, with a median age [ M ( Q1, Q3)] of 49 years old (40 years old, 58 years old). Of the 20 cases, 12 had low expression of HER2 [immunohistochemistry HER2+, or immunohistochemistry ++ and fluorescence in situ hybridization (FISH)-negative], and 8 had overexpression of HER2 (immunohistochemistry HER2+++, or immunohistochemistry ++ and FISH-positive); median number of lines of treatment with T-DXd was 6 lines (3 lines, 7 lines); 14 patients had partial remission, 3 patients had stable disease, and 3 patients had disease progression, with an objective remission rate (ORR) of 70% (14/20) and a disease control rate of 85% (17/20). Eight patients with overexpression of HER2 had objective remission in 6 cases, and 12 patients with low expression of HER2 had objective remission in 8 cases, and the ORR difference between the two groups was not statistically significant ( P = 1.000). The main adverse reactions of the patients were nausea (14 cases), vomiting (12 cases), leukopenia (10 cases), elevated aspartate aminotransferase (10 cases), elevated alanine aminotransferase (9 cases), anemia (8 cases), fatigue (8 cases), alopecia (8 cases), neutropenia (6 cases), and thrombocytopenia (5 cases); ≥ grade 3 adverse reactions were bone marrow suppression and gastrointestinal reactions, all with an incidence of ≤10%. The median follow-up time was 7.1 months (1.9 months, 11.5 months). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.9-9.1 months), and the median PFS time of patients with overexpression of HER2 was longer than that of patients with low expression of HER2 [7.0 months (95% CI: 6.4- 7.6 months) vs. 4.0 months (95% CI: 1.7-6.3 months)], and the difference in PFS between the two groups was statistically significant ( P = 0.025). Multivariate Cox regression analysis showed that overexpression of HER2 was an independent protective factor for PFS in MBC patients treated with T-DXd ( HR = 0.265, 95% CI: 0.075-0.945, P = 0.041). Conclusions:MBC patients with overexpression or low expression of HER2 have a good therapeutic effect and safety profile when treated with T-DXd. The overexpression of HER2 may predict good PFS in MBC patients treated with T-DXd, and may serve as a biomarker for predicting PFS in such patients, but it may not affect the ORR.