Adult ; Aged ; Atrial Fibrillation ; etiology ; prevention & control ; Bronchoalveolar Lavage ; adverse effects ; Humans ; Male ; Middle Aged

The roles of voltage-dependent K(+) channels during activation and damage in alveolar macrophages (AMs) exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage, and were adjusted to 5x10(5)/mL. After AMs were exposed to different concentrations (0, 25, 50, 100, 200 mug/mL) of quartz particles and 100 mug/mL amorphous silica particles for 24 h, the voltage-depended K(+) current in AMs was measured by using patch clamp technique. Meanwhile the leakage of lactate dehydrogenase (LDH) and the viability of AMs were detected respectively. Patch clamp studies demonstrated that AMs possessed outward delayed and inward rectifying K(+) current. Exposure to quartz particles increased the outward delayed K(+) current but it had no effect on inward rectifier K(+) current in AMs. Neither of the two K(+) channels in AMs was affected by amorphous silica particles. Cytotoxicity test showed that both silica particles could damage AM membrane and result in significant leakage of LDH (P<0.05). MTT studies, however, showed that only quartz particles reduced viability of AMs (P<0.05). It is concluded that quartz particles can activate the outward delayed K(+) channel in AMs, which may act as an activating signal in AMs to initiate an inflammatory response during damage and necrosis in AMs induced by exposure to quartz particle. K(+) channels do not contribute to the membrane damage of AMs.

Objective To investigate the effect and underlying mechanism of radioactive 125I seed implantation on the angiogenesis of transplanted human lung adenocarcinoma in nude mice.Methods An animal model of transplantd human lung adenocarcinoma was established by subcutaneous implanting A549 cells into nude mice.Twenty four tumor-bearing nude mice were randomly divided into 4 groups with different irradiation doses of blank control (without any treatment) and 0 MBq,22.2 MBq,29.6 MBq and by embedding radioactive 125I seeds with an 18 G implant needle.Tumor volumes were measured every 4 days until all mice were terminated 30 d later and the tumor growth curve was drawn.The microvessel density (MVD) in the tumor tissue was detected by immunohistochemistry S-P assay.The mRNA and protein levels of VEGF and HIF-1α of each group were detected by RT-PCR and Western blot,respectively.Results After embedding of 125I seeds,the tumor volumes of 22.2 MBq group (886 ± 97) and 29.6 MBq group (590 ± 107) were significantly smaller than those of control group (2 297 ± 149) at 54 d after administration (q =14.117,17.075,P ＜ 0.05),but there were no significant differences among 0 MBq group and control group,22.2 MBq and 29.6 MBq groups (P ＞ 0.05).The immunohistochemical CD34-positive staining demonstrated that MVD in 22.2 MBq group (522 ± 119) and 29.6 MBq group (491 ± 121) were decreased significantly compared with control group (922 ± 260) (q =4.826,5.197,P ＜0.05),but there were no significant differences among 0 MBq and control groups,22.2 MBq and 29.6 MBq groups(P ＞0.05).The mRNA expressions of VEGF and HIF-1α in 22.2 MBq group (0.279±0.0659,0.370 ±0.0857) and 29.6 MBq group (0.215 ±0.0620,0.278 ±0.0651) were significantly lower than those in the control group (q VEGFmRNA =18.881,17.211,q HIF-1αmRNA =15.376,14.733,P ＜0.05),but there were no significant differences among 0 MBq and control groups,22.2 MBq and 29.6 MBq groups(P ＞0.05).At the same time,the expression levels of VEGF and HIF-1α protein after 125I seed implantation were also obviously decreased in 22.2 MBq and 29.6 MBq groups (qvEGr =5.848,6.263,q HIF-1α =6.560,7.576,P ＜ 0.05),and no significant difference between 0 MBq and control groups(P ＞ 0.05) and between 22.2 MBq and 29.6 MBq groups (P ＞ 0.05).Conclusions Interstitial implantation with 125I seeds may potently inhibit angiogenesis in human lung adenocarcinoma xenografts of nude mice.

Objective To explore the effects of recombinant human hormone(rhGH) on the plasma total protein,plasma albmin,healing of Wound surfaces in patients with the second degree burns wound.Methods 38 pa- tients with the second degree burns wound were divided into treatment group and control group randomly.All the patients were subject general.19 patients in the treatment group were given rhGH in a dose of 0.2U/kg for 14 days beginning from postoperative 5 days.The plasma total protein concentration,plasma albumin concentration,healing rat of wound surface and scar of patients of the two group were compared.Results The plasma total protein concen- tration plasma albumin concentration of the treatment group were significantly in creased,the scar hyperplasia of the treatment group were significantly mitigated and the healing time of wound surfaces of the treatment group were sig- nificantly shortened.Conclusion rhGH is found to promote protein anabotism and shorten the healing time of wound surfaces and mitigate the scar hyperplasia patients with the second degree burns wound.

Objective To evaluate the effects of bone morphogenetic protein 2(BMP-2)gene modified tissue engineering bone combined with vascular bundle implantation in repairing segmental bone defect.Methods The isolated rabbit hone marrow stromal cells(MSCs),after being transfected by adenovirus carrying BMP-2 gene(Ad-BMP-2),were seeded on bovine cancellous bone scaffolds(BCB) to construct gone modified tissue engineering hone.The rabbit models with radial defects(2.0 cm long) were made and repaired with four methods including gene modified tissue engineering bone with vascular bundle implantation(Group A),gene modified tissue engineering bone(Group B),nongene modified tissue engineering bone with vascular bundle implantation(Group C),and only BCB scaffolds(Group D).After 4,8,and 12 weeks of operation,X-ray,histological examination,biomechanics analysis and capillary vessel ink infusion were conducted to observe angiopoiesis and osteogenesis.Results Group A gained better effect in the volume and activity of new bones than other groups,with vascular bundle sending out new branches into the transplanted bones and productive regeneration of capillary vessel.The defect in Group A was repaired satisfactorily.Group B showed better effect in speed and quality of bone formation than Group C under induction of BMP-2 gent.Mainly fibrous tissues but not new bones were observed in Group D.Conclusion BMP-2 gene therapy with vascular bundle implantation has very strong osteoinduction ability and quite good vascularization effect and is of great value to the treatment of bone nonunion and bone defects.

From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.

BACKGROUND:Both acupuncture and moxibustion and drug ale effective methods to treat simple obesity.Whether electroacupuncture is different from sibutramine to affect adipocyte products in obese organisms?OBJECTIVE:To observe the different effects of electroacupuncture and sibutramine on adipocyte produces in obesity rats and to investigate the mechanism of weight reduction by acupuncture and moxibustion.DESIGN:Layering-randomized controlled study.SETTING:Laboratory of Acupuncture and Pharmacology.Nanjing University of Chinese Medicine.MATERIALS:12045-day-old male SD rats were provided by Shanghai Experimental Animal Center.The experiment was in accordance with animal ethics standards.Sibutramine hyrdrochloride capsule was made in Fuling Pharmaceutical Factory of Taiji Group(batch number:X20010279).Electro-acupuncture apparatus(LH402A acupoint neutoelectrical stimulation equipment)was made in Beijing Huawei Chanye Developing Company.METHODS:This study was performed at the Laboratory of Acupuncture and Pharmacology,and Expefimental Animal Center,Nanjing University of Chinese Medicine from October 2004 to November 2006.①100 male SD rats underwent high-fat diet.Fifty-four alimentary obesity rats were randomly divided into electroacupuncture group,sibutramine group and obesity group.wim 18 rats in each group.Another 18 rats were regarded as a normal group.②Rats in the electroacupuncture group were given electrical stimulation(2/15 Hz,4 mA)at lateral Housanli and Neiting acupoints,contralateral alternation every other day.Rats were fixed with self-made binding instrument,and rats maintained a consciousness but not an intense struggle.The electricai stimulation lasted for 15 minutes every day,one day was an interval every 6 days.and the electroacupuncture was given for 49 days and 42 times in total.Rats in the sibutramine group were ingragastrically administrated with 0.2 g/L sibutramine hydrochloride(2.0 mg/kg/d).Rats in the control group and obesity groups were fixed the same as electroacupuncture group but not given electrical stimulation.MAIN OUTCoME MEASURES:①Obese marker:To detect body mass,body length,weight reduction rate and body mass/body fat mass,and to measure total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and triacylglycerol (TG)with biochemical chromatometry;②insulin sensitivity index:To measure fasting blood glucose,insulin and insulin sensitivity index with enzyme-linked immunosorbent assay;③adipocyte secreting regulatory substance level:To measure serum resistin,leptin,adiponectin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and its soluble receptor level with enzyme-linked immunosorbent assay.RESULTS:Among 120 rats,54 alimentary obesity rat models and 18 normal rats were included in the final analysis.①Obesemarker:Bodymass,bodyfatmass,cholesterol and TG levels in the obesity group were significantly higher than in the normal group(P＜0.01).Body mass,body fat mass,body mass/body fat mass,cholesterol and TG levels in the electroacupuncture group were significantly lower than in the obesity group(P＜0.01).TG level in the sibutramine group was significantly lower than in the obesity group(P＜0.01).Weight reduction rate in the electroacupuncture group was significantly higher than in the sibutramine group(P＜0.01).Body mass/body fat mass in the electroacupuncture group was significantly lower than in the sibutramine group(P＜0.01).②Insulin sensitivity:Blood glucose and serum insulin levels in the obesity group were significantly higher than in the normal group,and insulin sensitivity index was significantly lower than in the normal group(P＜0.01).Blood glucose and insulin levels in the electroacupuncture and sibutramine groups were significantly lower than in the obesity group,but insulin sensitivity index was significantly higher than in the obesity group(P＜0.01).③Adipocyte secreting regulatory substance level:Adiponectin in the electroacupuncture group was significantly higher than in the obesity group (P＜0.01).Resistin and TNF-αin the electroacupuncture group was significantly lower than in the obesity grollp(P＜0.01).Resistin level in the sibutramine group was significantly lower than in the obesity group(P＜0.01).CONCLUSION:The effect of electroacupuncture on abnormally secretary products of adipose tissues in obesity rats is superior to the effect of sibutramine.This may be one of important mechanisms of weight reduction by acupuncture and moxibustion,and prevention and cure of obesity and its related diseases.

Adult ; Anastomosis, Surgical ; Esophagus ; surgery ; Humans ; Male ; Stents ; Stomach ; surgery ; Tracheoesophageal Fistula ; surgery

Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but most output a long list of significantly enriched terms that are often redundant, making it difficult to extract the most meaningful functions. In this paper, we present GOMA, a novel enrichment analysis method based on the new concept of enriched functional Gene Ontology (GO) modules. With this method, we systematically revealed functional GO modules, i.e., groups of functionally similar GO terms, via an optimization model and then ranked them by enrichment scores. Our new method simplifies enrichment analysis results by reducing redundancy, thereby preventing inconsistent enrichment results among functionally similar terms and providing more biologically meaningful results.
Algorithms ; Breast Neoplasms ; genetics ; Computational Biology ; methods ; Databases, Genetic ; Female ; Gene Expression Profiling ; Gene Ontology ; Gene Regulatory Networks ; Humans ; Oligonucleotide Array Sequence Analysis ; methods

BACKGROUND:Femoral neck fracture is mainly fixed by three inverted triangle cannulated screws. Scholars have proposed to add a cannulated screw to enhance the fixation strength of femoral neck fracture of Pauwels III type based on three cannulated screw fixation, but the stability is not verified. OBJECTIVE:To analyze the biomechanical stability and stress of the three and four cannulated screws for the treatment of the Pauwels III femoral neck fractures. METHODS:The CT imaging results of the fourth generation of artificial bone sawbones were imported into the Mimics software wherein a three-dimensional finite element model of the proximal femur was prepared and introduced in the 3-matic software. Models of middlesegment of femoral neck with Pauwels III fractures were established. Cannulated screw models were established with UG 8.0 software and introduced in the fractures models. Finally, finite element models of Pauwels III femoral neck fractures fixed with three and four screws were established. In the same condition, an axial load of 411 N was applied on the femoral head with Abaqus software. The displacement of two markers of the broken ends and internal fixation system Von Mises stress distribution were compared between the two models. RESULTS AND CONCLUSION:(1) The displacement was 0.42 mm in three screws model, and 0.17 mm in the four screws model. (2) Von Mises stress peak was 547 MPa and 27.8 MPa in both models. The peak value was lower in models of fourscrews than that of three screws. Stress concentration position was at the fracture site in both models. The stress range of models of four screws was more extensive and scattered. (3) Finite element analysis results demonstrated that four-screw implantation for Pauwels III femoral neck fractures had strong anti-shearing force and biomechanical stability. Clinical advantages need further clinical comparative study.