Objective:To study the effect of electroacupuncture (EA) at the Pericardium Meridian on the heart function of volunteers with acute hypoxia, and to provide scientific evidence for the acupoints selection along the affected meridian in acupuncture-moxibustion therapy. Methods:Based on a self-control design, eighteen healthy volunteers were recruited in the study. Points from the Pericardium Meridian [Neiguan (PC 6), Ximen (PC 4), Quze (PC 3) and Tianquan (PC 2)], non-Pericardium Meridian point [Shousanli (LI 10)], non-meridian and non-acupoint points [1.0-1.5 cm lateral to Neiguan (PC 6) and Ximen (PC 4), respectively on both sides], and a blank control (only inhaling low-oxygen gas without EA stimulation) were selected to observe, once every week, 10 sessions in total, and only 1 acupoint was observed once. The volunteers inhaled low-oxygen gas mixture (10.8% O2 and 89.2% N2) for 30 min to imitate acute hypoxia. EA was conducted when the gas mixture was inhaled for 10 min and then lasted for 20 min; meanwhile, hemodynamic indexes such as cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI), left cardiac work (LCW), left cardiac work index (LCWI) and heart rate (HR) were recorded on a hemodynamic monitor. Results:EA at the acupoints of Pericardium Meridian significantly down-regulated the increased CO/CI, LCW/LCWI, and HR (P<0.05), and significantly up-regulated the decreased SVR/SVRI in hypoxia (P<0.05); EA at other meridian acupoints or at non-meridian and non-acupoint points didn't produce such effects. Conclusion: EA at the Pericardium Meridian can obviously improve the cardiac hyper-activation caused by acute hypoxia in healthy volunteers.

OBJECTIVECigarette smoke extract (CSE) can induce injuries of pulmonary II epithelial cells, activate nuclear factor-kappaB and increase tumor necrosis factor-alpha(TNF-alpha) secretion. This study aimed to investigate whether azithromycin can protect pulmonary II epithelial cells from injuries induced by CSE and relevant mechanisms.

METHODSPulmonary II epithelial cells (A549 cells) were cultured in vitro. After 48 hrs of culture the cells were randomly treated with serum-free DMEM only (blank control group), azithromycin + serum-free DMEM, CSE+ serum-free DMEM or CSE+azithromycin. Eight hours later the morphology of A549 cells, the activity of NF-kappaB and the levels of TNF-alpha were measured by inverted microscope, immunohistochemistry and ELISA.

RESULTSThe morphology and structure of A549 cells were changed, NF-kappaB activity increased (dark brown staining ) and TNF-alpha levels (0.307 +/- 0.036 pg/mL vs 0.234 +/- 0.028 pg/mL)increased in the CSE+ serum-free DMEM group compared with the blank control group (P < 0.01). CSE together with azithromycin treatment recovered partly the morphological injuries of A549 cells. It also attenuated NF-kappaB staining and decreased TNF-alpha levels from 0.307 +/- 0.036 pg/mL (CSE+serum-free DMEM group) to 0.269 +/- 0.009 pg/mL (P < 0.05).

CONCLUSIONSAzithromycin may inhibit NF-kappaB activity, decrease TNF-alpha secretion and thus lessen cytotoxicity of CSE to A549 cells.

Anti-Bacterial Agents ; pharmacology ; Azithromycin ; pharmacology ; Cells, Cultured ; Epithelial Cells ; drug effects ; Humans ; Immunohistochemistry ; Lung ; drug effects ; metabolism ; pathology ; NF-kappa B ; analysis ; Smoke ; adverse effects ; Tobacco ; adverse effects ; Tumor Necrosis Factor-alpha ; analysis

Adult ; Female ; Humans ; Middle Aged ; Myxoma ; pathology ; surgery ; Vulvar Neoplasms ; pathology ; surgery

Nowadays, the 5-year survival rate of childhood cancer patients can be more than 80%, but some patients with relapse and refractory cancers have shown no good response to traditional strategies. Chimeric antigen receptor engineered T (CAR-T) cell therapy is promising for these patients. CAR-T cells recognize the tumor-associated antigens in a non-major histocompatibility complex-restricted manner, so their anti-tumor ability is enhanced. There are four generations of CAR-T cells now. The complete remission rate of pediatric patients with relapse and refractory acute lymphoblastic leukemia can be as high as 90% when treated with CD19-targeting CAR-T cells. Furthermore, CAR-T cell therapy can also be used to bridge to transplantation and donor CAR-T cell infusion can be a strategy to prevent relapse after hematopoietic stem cell transplantation. As to solid tumors, only patients with neuroblastoma present good response to the GD2-targeting CAR-T cell therapy. The toxic or side effects of CAR-T cell therapy include cytokine release syndrome, off-tumor effect, tumor lysis syndrome, and insertion mutation. Although the CD19-targeting CAR-T cell therapy for childhood cancer can result in a high remission rate, the relapse rate is high, including CD19and CD19relapse. The mechanisms for relapse merit further investigatio.
Antigens, CD19 ; immunology ; Child ; Humans ; Immunotherapy, Adoptive ; adverse effects ; methods ; Neoplasms ; therapy ; Receptors, Antigen, T-Cell ; genetics ; T-Lymphocytes ; transplantation

Objective To establish a kind of animal model and methods for neuroendoscope training. Methods With rat abdominal cavity hypothesized as cerebral ventricle, a set of programs for neuroendoscopic operative skill training were designed, including endoscopic techiniques, electronic coagulation, suction, flush, biopsy and balloon dilatation, and so on. Results Simulation operation was performed on rat abdomen under neuroendoscope. The procedure helped to practice the endoscopic manipulation, get to know well how to perform endoscope, coagulation, suction, flash instruments, be familiar with the usage of electric coagulation in the liquid condition. The emphasis was put on the basic skills of pure neuroendoscopic operation such as balloon dilatation, electric coagulation, cutting off,forcep biopsy and flush. Conclusions The rat model can provide a way to train pure neuroendoscopic operation. The trainer can get basic experience with regard to endoscopic manipulation, balloon dilatation, electric coagulation, suction, flush and biopsy under endoscope. The method can be an important part of neuroendoscopic laboratory training.

Objective To investigate the neuroprotective effects of angiotensin Ⅱ type 1 receptor (AT1R) blocker olmesartan medoxomil (OLM) on intracerebral hemorrhage (ICH) in spontaneously hypertensive rats (SHRs). Methods SHRs (male, 12 weeks old; weighing 300±20 g) were randomly assigned to normal, ICH, vehicle-treatment ICH (control), OLM-treatment ICH (OLM) groups. ICH was induced via stereotaxic right basal ganglia administration of collagenase type Ⅶ. One hour after ICH, the rats in OLM group were given a single oral dose of OLM (10 or 3 mg/kg solved in 1 mL sodium carboxymethylcellulose) via nasogastric feeding, and those in the control group received an equal volume of sodium carboxymethylcellulose only. Six hours after ICH induction, mean arterial blood pressure (MAP) was measured using the non-invasive method of tail-cuff plethysmography in conscious rats. Twenty-four hours after ICH induction, neurobehavior was detected by the modified limb placing test (MLPT); brain water content was measured by dry-wet method; the mRNA expression levels of receptor and target genes were analyzed by real-time PCR. Results MAP in the ICH group ([121.4±3.5] mm Hg) did not significantly differ from baseline pressure in the normal group ([120.2±3.8] mm Hg)(P>0.05); MAP in the OLM group with 10 mg/kg ([105.6±3.1] mm Hg) was significantly lower than that in the ICH group (P<0.05); the OLM group with 3 mg/kg ([120.8±3.1] mm Hg) and control group ([118.6±3.9] mm Hg) did not induce blood pressure reduction, and did not show significant difference as compared with the ICH group (P>0.05). In the hemorrhagic hemisphere, brain water content in the OLM group with 3 mg/kg (80.02%±0.32%) had significant difference from that in the ICH group (80.90%±0.36%, P< 0.05); brain water content of the control group (80.81%±0.32%) was slightly lower than that of the ICH group, without significant differences (P>0.05). The OLM group with 3 mg/kg (5.03±0.71) was showed significantly lower score of MLPT as compared with that in the ICH group (6.62±0.55, P<0.05). The score of MLPT in the control group (6.41 ±0.55) did not differ from that in the ICH group (P>0.05). In the hemorrhagic hemisphere, the mRNA expressions of AT1R and target genes, such as HO-1, COX-2, IL-6 and VCAM-1, in the OLM group with 3 mg/kg were significantly lower than those in the ICH group (P<0.05), but the difference between the control and ICH groups did not show statistical significance (P>0.05). Conclusion Treatment with low doses of OLM in the experimental ICH of SHRs may promote its neurological recovery and induce its neuroprotective effects, including reduction of edema, inhibition of inflammation and oxidative stress.

OBJECTIVETo investigate the methylation status of the promoter of resion death associated protein kinase (DAPK) gene in bladder cancer cell (T24), and study the effect of 5-aza-2'-deoxycytidine (5-aza-dc) on DAPK gene reactive expression in T24 and its inhibitory effect on T24.

METHODSThe bladder cancer cell T24 was treated with different doses of 5-aza-dc. The inhibitory effect and apoptosis rate were detected by MTT and flow cytometry, and the changes of DAPK mRNA and protein expression and the methylation status of DAPK promoter were assessed by RT-PCR, Western blotting, and methylation specific PCR, respectively.

RESULTSThe growth of bladder cancer cell was inhibited significantly and the maximal apoptosis rate detected by flow cytometry was (24.12-/+1.4)%. DAPK mRNA was not expressed in bladder cancer cell T24 in normal conditions. DAPK mRNA and protein re-expressed after 5-aza-dc (12.5 micromol/L) treatment in cell line T24 for 24 h, and DAPK promoter became unmethylated.

CONCLUSIONSThe promoter methylation can be an important factor for silencing the expression of DAPK in bladder cancer cell. 5-aza-dc can inhibit the growth and induce apoptosis of bladder cancer cells through reversing unmethylation status of DAPK promoter.

Apoptosis Regulatory Proteins ; genetics ; metabolism ; Azacitidine ; analogs & derivatives ; pharmacology ; Calcium-Calmodulin-Dependent Protein Kinases ; genetics ; metabolism ; Cell Line, Tumor ; DNA Methylation ; DNA Modification Methylases ; antagonists & inhibitors ; Death-Associated Protein Kinases ; Humans ; Promoter Regions, Genetic ; genetics ; RNA, Messenger ; genetics ; metabolism ; Transcriptional Activation ; drug effects ; Urinary Bladder Neoplasms ; metabolism ; pathology

OBJECTIVETo study the association of fibrinogen(Fg) B beta -854G/A, -455G/A, -249C/T, -148C/T, 448G/A and Bcl-1G/A gene polymorphisms with factors affecting obesity, and the fibrinogen function such as plasma fibrinogen concentration and molecular reactivity.

METHODSOne thousand and three hundred ninety-one subjects from Kailuan corporation were enrolled by medical examination and questionnaire survey, and were divided into normal weight, overweight and obese groups based on body mass index (BMI). Blood biochemistry, fibrinogen concentration, fibrin monomer polymerized velocity (FMPV), and FMPV/A(max) were measured. The gene polymorphisms of the six loci were detected by polymerase chain reaction-restriction fragment length polymorphism.

RESULTSThe frequencies of Bcl-1A and its mutated genotype in the overweight group were significantly higher than that in the normal weight group (P< 0.01). In all the three groups, Fg concentration, FMPV, FMPV/A(max) in individuals with B beta -854 mutated genotype were significantly higher than those with wild type genotype (P< 0.01), and in the overweight group, FMPV/A(max) in those with B beta -455 mutated genotype, FMPV in those with B beta -249 mutated genotype, were higher than those with wild type genotype (P< 0.05).

CONCLUSIONIndividuals with Bcl-1A and its mutated genotype are susceptible to overweight. The B beta -455 and -249 mutated genotypes are accumulative genes for overweight by regulating the Fg function.

Aged ; Case-Control Studies ; Female ; Fibrinogen ; genetics ; Gene Frequency ; Genotype ; Humans ; Linkage Disequilibrium ; Male ; Obesity ; genetics ; prevention & control ; Polymorphism, Genetic ; Regression Analysis

BACKGROUNDThe sensitization and elicitation phases are involved in the immunopathogenesis of contact hypersensitivity (CHS). Langerhans cells (LCs) are believed to play pivotal roles in the sensitization stage of CHS. Local hyperthermia on skin induces the migration as well as maturation of epidermal LCs. Although fever-range whole body hyperthermia and local hyperthermia at 43°C prior to sensitization were reported to suppress CHS, the effects of different temperatures and the timing sequence of local hyperthermia on CHS have not been tackled.

METHODSLocal hyperthermia was applied to murine dorsal skin 3 days prior to, concurrent with, or 2 days post sensitization with fluorescein isothiocyanate (FITC) in BALB/c mice. Local hyperthermia temperatures at 37°C, 39°C, 41°C and 43°C were applied to mouse dorsal skin and the severity of CHS was calculated by measuring the swelling response of the challenged ears.

RESULTSLocal hyperthermia at 39°C, 41°C and 43°C prior to sensitization reduced the severity of CHS, as compared with that at 37°C. The suppression of CHS was temperature dependent in that higher temperature had a stronger effect. On the contrary, the hyperthermia treatments, either concurrent with or post-sensitization, resulted in an enhanced temperature-dependent ear swelling response.

CONCLUSIONSThe severity of murine CHS could be influenced by local hyperthermia at the sensitization stage in a temperature dependent manner. The temporal effect of local hyperthermia suggested a novel factor in interpreting the severity of allergic contact dermatitis.

Animals ; Dermatitis, Contact ; therapy ; Female ; Hyperthermia, Induced ; Langerhans Cells ; physiology ; Mice ; Mice, Inbred BALB C

OBJECTIVETo study the distribution characteristics of Beta-fibrinogen (Fg)B gene-854G/A, -455G/A, -249C/T, -148C/T, 448G/A and Bcl-1 G/A polymorphism in North China Han population, and the influence on plasma Fg concentration and molecular reactivity. Further more, to explore the role of Fg gene polymorphisms combining with multi-physiological and environmental factors in the development of cerebral infarction.

METHODSCluster sampling, health examination and questionnaires surveys of 1652 subjects from Tangshan Kailuan Group Corporation were conducted. Blood biochemistry, Fg concentration, fibrin monomer polymerized velocity (FMPV), absorbance maximum (Amax) and FMPV/Amax were measured. The six polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism.

RESULTSIn the population, the proportion of the FgB beta-249 T variation allele was 65.49%, while the proportion of the rest loci was predominantly wild type. The significant differences in Fg concentration and FMPV/Amax were found in -854 genotype groups. The Fg concentration in -854GA group was higher than those in GG and AA group. Only the distribution frequencies of FgB beta Bcl-1 A variation allele, GA and AA genotype in the cerebral infarction group were higher than those in non-infarction group, and the prevalence of cerebral infarction in AA genotype group was higher than other groups (the probability value of above-mentioned results were all P<0.01).

CONCLUSIONSFgB beta Bcl-1A allele and variation genotype were susceptible to cerebral infarction. FgB beta-455GA/448G linkage genotype may contribute to the increased plasma Fg concentration. FgB beta-854 was one of the main controlling gene loci for plasma Fg concentration and molecular reactivity.

Aged ; Asian Continental Ancestry Group ; genetics ; Cerebral Infarction ; blood ; genetics ; Female ; Fibrinogen ; genetics ; metabolism ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic