0.05).?-defensin 2 was detected in the specimens of vocal cord polyp,but very little in the subjects of other two groups.Its expression level was significantly higher in the vocal cord polyp than that of the other two groups(P

Objective To establish collagen‐induced arthritis (CIA) model used of DBA/1J mouse ,a preliminary study of the expression levels of BM Ps in mononuclear cells of peripheral blood and the joints tissue of CIA mice .Methods We induced DBA/1J mice and developed arthritis pathology by using of bovine type Ⅱ ;then ,we detected mRNA and protein expression levels of BMPs by using quantitative PCR and immunohistochemical staining .Results We successfully established CIA mouse model .The expres‐sion of BMP4 and BMP9 mRNA was significantly down‐regulated in peripheral blood mononuclear cells and in the pathogenesis of joint tissues of CIA mice (P<0 .05) .It showed that BMP9 protein significantly decreased in joint tissues of CIA mice by immuno‐fluorescence technique (P=0 .002) .Conclusion At the genetic level ,the expression of BMP4 and BMP9 could be significantly down‐regulated in the CIA mouse .At the protein level ,BMP9 could be significantly down‐regulated in the CIA mouse .

OBJECTIVE: To evaluate the efficacy and safety of combined treatment with angiotensin II receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on diabetic kidney disease. METHODS: Randomized controlled trials (RCTs) were identified from CoChrane library, PubMed, EMbase, CNKI and VIP. Eleven RCTs involving 602 patients were included and analyzed with Rev Man 5.1 software. RESULTS: Compared with ACEI alone, combined treatment with ARB and ACEI was more effective on decreasing 24 h albuminuria, systolic pressure, average 24 h systolic pressure, diastolic pressure, and average 24 h diastolic pressure but with a high level of serum potassium. Compared with ARB alone, combined treatment with ARB and ACEI was more effective on decreasing systolic pressure and diastolic pressure. Compared with ACEI or ARB alone, we didn't get a definite conclusion that whether combined treatment with ARB and ACEI was more effective on decreasing 24 h proteinuria. CONCLUSION Based on this Meta analysis, combined treatment with ARB and ACEI is safer and has positive effect on diabetic kidney disease. However, small sample size and low methodological quality appeared in most of the trials included in this systematic review. Therefore, available evidence is insufficient to recommend a routine clinical application of combined treatment with ARB and ACEI on diabetic kidney disease.
Angiotensin Receptor Antagonists ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; therapeutic use ; Diabetic Nephropathies ; drug therapy ; Drug Therapy, Combination ; Humans ; Randomized Controlled Trials as Topic

Objective:To assess the efficacy and the safety of the radiofrequency catheter ablation (RFCA) for the septal accessory pathway (AP) in children.Methods:From September 2013 to March 2019, 626 patients plan to underwent RFCA for paroxysmal supraventricular tachycardia (PSVT) in Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.Among them, 74 consecutive patients with right or left septal APs were included in the study and their clinical and RFCA data were analyzed.Results:The age of these 74 children (45 males, 29 female) was (7.8±3.5) years, ranging from 10 months to 13 years.The body weight (BW) was (27.7±14.4) kg, with 3 patients BW<15 kg.A discordant ventricular wall motion (DVWM) was found in 5 patients, and the combined congenital heart diseases were discovered in 2 patients.A three dimensional mapping system was applied in 69 ablations, and 3 ablations were performed only with the fluoroscopy monitor of 5 cases.According to the AP location, the number of cases located in the anteroseptal, the midseptal, the mouth of coronary sinus, the left posteroseptal and the right posteroseptal, were 28, 18, 10, 10 and 8, respectively.The ablation operations were applied in 72 patients.The initial acute success reached in 67 (93.1%) patients.The ablation energy was (18.0±1.8) W, the fluoroscopy time during the ablations was (4.7±2.7) minutes, and the procedure duration was (151.5±58.6) minutes.One inadvertent complete atrioventricular block (AVB) was noted as the ablation-related complication.All 5 children with the pre-DVWM were recovered after ablations.During a follow-up of (23.8±10.8) months, 4 patients experienced the recurrence of preexcitation syndrome atrioventricular reentrant tachycardia.Conclusions:With the 3D-mapping system, the RFCA of septal APs can be performed safely and effectively in pediatric patients of paroxysmal supraventri-cular tachycardia.However, as the ablation-related complication, AVB should not be ignored.

OBJECTIVETo construct adenoviral vectors expressing mature miRNA-30a and miRNA-30e.

METHODSThe target mmu-miR-30a and mmu-miR-30e genes amplified from mouse genome were digested and linked to the shuttle plasmid pSES-HUS, which was then transformed into competent AdEaseier cells for recombination. The confirmed recombinant plasmids were transfected into Hek-293 cells for production of the adenoviruses pAd-mmu-miR-30a and pAd-mmu-miR-30e. The obtained adenoviruses were used to infect Mefs cells, and the cellular expressions of mmu-miR-30a and mmu-miR-30e were detected using fluorescence quantitative PCR.

RESULTSmmu-miR-30a (357 bp) and mmu-miR-30e (324 bp) containing the restriction sites were amplified and linked to the shuttle plasmid pSES-HUS, which was successfully recombined with AdEasy1. After packaging in Hek-293 cells, the adenoviral vectors were obtained, which caused an increase of mmu-miR-30a expression by 26.46∓7.46 folds and mmu-miR-30e expression by 2.76∓0.25 folds in transfected Mefs cells.

CONCLUSIONWe have successfully constructed the adenoviral vectors expressing the mature miRNAs.

Adenoviridae ; genetics ; Animals ; Base Sequence ; Genetic Vectors ; HEK293 Cells ; Humans ; Mice ; MicroRNAs ; genetics ; Plasmids

OBJECTIVE:To systematically evaluate the effects of atorvastatin on pulmonary function,pulmonary arterial pres-sure and related indexes in patients with stable chronic obstructive pulmonary disease(COPD),and to provide evidence-based refer-ence. METHODS:Retrieved from Cochrane Library,PubMed,EMBase,CJFD and VIP,randomized controlled trials(RCTs)about atorvastatin combined with conventional therapy(trial group)vs. conventional therapy alone(control group)in the treatment of sta-ble COPD were collected. Meta-analysis was performed by using Rev Man 5.3 statistical software after data extraction and quality evaluation by Cochrane Handbook Manual 5.1.0. RESULTS:Totally 7 RCTs were included,involving 371 patients. Results of Me-ta-analysis showed,FEV1 [MD=0.07,95%CI(0.04,0.09),P<0.001],FEV1%pred [MD=6.18,95%CI(2.23,10.12),P=0.002] and 6MWD [MD=55.31,95%CI(36.44,74.18),P<0.001] of trial group were significantly higher/longer than those of con-trol group;pulmonary artery systolic pressure [MD=-6.78,95%CI(-11.62,-1.94),P=0.006],mean pulmonary artery pres-sure [MD=-6.61,95%CI(-7.26,-5.96),P<0.001],St. George respiratory questionnaire [MD=-13.21,95%CI(-23.90,-2.52), P=0.02] were significantly lower than control group,with statistical significance. There was no statistical difference in FEV1/FVC [MD=3.73,95%CI(-2.08,9.55),P=0.21] or hs-CRP [MD=0.29,95%CI(-1.37,1.95),P=0.73] between 2 groups. CONCLU-SIONS:Atorvastatin can significantly improve pulmonary function and pulmonary arterial pressure in patients with stable COPD, and can improve the quality of life.

Objective To develop a nomogram model based on the clinical features and the radiomics texture analysis of multimodal magnetic resonance imaging(MRI),so as to predict the tumor response in patients with advanced hepatocellular carcinoma(HCC)3 months after receiving transcatheter arterial chemoembolization(TACE).Methods A total of 105 patients with advanced HCC,whose diagnosis was pathologically-confirmed at the Suzhou Municipal Ninth People's Hospital between January 2017 and December 2021,were enrolled in this study.The patients were randomly divided into training group(n=63)and verification group(n=42).Before chemotherapy,T1WI,T2WI,dynamic contrast-enhanced(DCE)scan,and diffusion-weighted imaging(DWI)were performed by using a 3.0T MRI scanner.A.K.software was used to extract the texture.Three months after chemotherapy,according to the modified Response Evaluation Criteria in Solid Tumors(mRECIST)the patients were divided into response group(n=63)and non-response group(n=42).Results Compared with the response group,in the non-response group the percentage of Child-Pugh grade B and BCLC stage C was obviously higher and the serum alpha fetoprotein(AFP)level was remarkably elevated(P＜0.05).A.K.software extracted 396 MRI texture features,and LASSO regression analysis screened out 6 optimal predictors.The radiation score(Rad-score)was calculated by ROC.The AUC of Rad-score for predicting tumor non-response after TACE by ROC in the training group and verification group were 0.842 and 0.803 respectively.Multivariate logistic regression model analysis showed that AFP≥50 ng/mL(OR=1.568,95%CI=1.234-1.902,P=0.003),Child-Pugh grade B(OR=1.754,95%CI=1.326-2.021,P=0.001),BCLC stage C(OR=1.847,95%CI=1.412-2.232,P=0.001)and Rad-score(OR=2.023,95%CI=1.569-2.457,P＜0.001)were the independent risk factors for tumor non-response.Clinico-radiomics combination had the highest AUC value for predicting tumor non-response.The correction curve showed that the nomogram model had a good agreement.Conclusion The quantitative score of radiomics texture analysis of multimodal MRI has a certain value in predicting tumor non-response in advanced HCC patients 3 months after TACE,and the nomogram model,which is constructed if combined with clinical factors,carries good practical potential.(J Intervent Radiol,2024,32:63-68)

Objective To establish a quantitative polymerase chain reaction(PCR)method for the analysis of human-derived SRY DNA in mouse tissues,and to study the tissue distribution of human umbilical cord mesenchymal stem cells(HUCMSCs)in immunodeficient NOG mice after a single intravenous injection.Methods We established a quantitative PCR method for the analysis of human SRY DNA in mouse tissues,and validated the standard curve,linear range,accuracy,precision,and stability.Thirty-six NOG mice(18 male,18 female)were administered 3.5×107 HUCMSCs/kg by single intravenous injection.Six mice were then anesthetized and dissected after blood collection(EDTA anticoagulation)at 6,12,24,and 72 h,and at 1 and 2 weeks,respectively.DNA was extracted from lung,kidney,heart,liver,brain,spinal cord,stomach,small intestine,fat,skin,spleen,testis,uterus,and ovary tissues,and the distribution of HUCMSCs in each tissue was determined by the validated quantitative PCR method for detecting the human-derived SRY gene in mouse tissues.In addition,18 NOG mice(9 male,9 female)were divided into control(n = 6)and treatment groups(n = 12)injected intravenously with 0.9%sodium chloride and 3.5×107 cells/kg,respectively.Acute toxic reactions were observed during the administration period,and four animals were dissected at 72 h and at 2 and 4 weeks after administration to observe the gross organs.Mitochondrial protein expression was detected in paraffin sections of lung tissues by immunohistochemistry to analyze the colonization of HUCMSCs in lung tissues.Results The established RT-qPCR method for human-derived SRY DNA in mouse tissues met the validation criteria for each index.After a single intravenous injection in NOG mice,HUCMSCs were mainly distributed in the lungs and blood within 1 week after administration,with higher concentrations in lung tissues than in blood.The concentrations of HUCMSCs in lung tissue and blood remained relatively stable within 6～24 h and 6～72 h,respectively,and then decreased over time.The distribution of HUCMSCs in other tissues was not measured at all sampling points.The colonization result showed that HUCMSCs were detected in lungs 72 h after intravenous injection,but not at 2 and 4 weeks.No obvious acute toxicity was observed in NOG mice after single intravenous administration of HUCMSCs.Conclusions The above method for analyzing the distribution of HUCMSCs in mouse tissue is reliable and feasible.HUCMSCs were mainly distributed in lung and blood in NOG mice within 1 week after a single intravenous injection,and mainly colonized lung tissue at 72 h.A single intravenous administration of HUCMSCs has a good safety profile.

Oral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Cell Proliferation ; DNA, Mitochondrial ; Energy Metabolism ; Glucose ; Mouth Neoplasms/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism* ; Phosphatidylinositol 3-Kinases ; Reactive Oxygen Species