PXR, CAR and PPAR, widely distributed in the body, are important members of the nuclear receptors (NRs) family. The activities and gene expressions of drug-metabolizing enzymes (DMEs) and transporters can be regulated by the activation of NRs, which effect the drug disposition. Multidrug resistance (MDR) is the leading cause of failure in cancer therapy. NRs, including PXR, CAR and PPAR, were shown to regulate the expressions of DMEs and transporters involved in the drug metabolism and clearance, suggesting that the modulation of NRs can be considered as a new target to overcome MDR. This review described the research progress of NR family members PXR, CAR, PPAR and their transcriptional activation mechanism, the regulation of DMEs and transporters by NRs, which may provide a valuable reference for clinical medication and overcome of MDR.

AIM: To investigate the key molecular mechanism of inflammatory response in alveolar epithelial cells induced by nontypeable haemophilus influenzae(NTHi).METHODS: A549 cells were co-cultured with NTHi(multiplicity of infection,MOI: 10) and harvested 15 min and 30 min after stimulation.The phosphorylation of p38 mitogen activated protein kinase(p38 MAPK) in A549 cells was detected by Western blotting.The intracellular expression of nuclear factor-?B(NF-?B) p65 was examined by flow cytometry 4 h after stimulation.A549 cells were preincubated with p38 inhibitor(SB203580) or NF-?B inhibitor(PDTC) for 1 h and then stimulated with NTHi for 24 h.The level of interleukin 8(IL-8) in the supernatants was determined by enzyme-linked immunosorbent assay(ELISA).RESULTS: The phosphorylation of p38 MAPK was rapidly induced by NTHi stimulation.The expression of NF-?B p65 in A549 cells after NTHi stimulation was significantly up-regulated compared with control group(P

ObjectiveTo study the effect of low molecular weight heparin sodium (LMWHS) therapy for exertional heat stroke (EHS) patients with pre-disseminated intravascular coagulation (pre-DIC).Methods A prospective randomized controlled trial (RCT) was conducted. Thirty-six patients with EHS with pre-DIC admitted to Department of Critical Care Medicine of 180th Hospital of Chinese PLA from April 2012 to November 2014 were divided into heparin sodium group (n = 20) and LMWHS group (n = 16) in accordance with the random number table. All patients received bundle treatment after being admitted to the hospital, including rapid cooling, fluid resuscitation, organ support (mechanical ventilation, hemopurification if necessary), supplement of pro-coagulation factors, etc. The patients in heparin sodium group were treated with continuous heparin sodium 12 500 U throughout 24 hours with intravenous pump for 5 days, and the patients in LMWHS group were given LMWHS 2 500 U subcutaneously, twice a day for 5 days.The incidence of DIC, incidence of bleeding and mortality of two groups were compared.The platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimer of each patient between pre and post treatment times were compared.Results No significant difference was found in the incidence of DIC and mortality between LMWHS group and heparin sodium group (31.2% vs. 30.0%,χ2 =0.007,P = 0.936; 6.2% vs. 5.0%,χ2 = 0.026,P = 0.871). Incidence of bleeding during treatment in LMWHS group was significantly lower than that in heparin sodium group (12.5% vs. 45.0%,χ2 = 4.425,P = 0.035). After treatment,PLT in both LMWHS group and heparin sodium group was significantly increased compared with that before treatment (×109/L: 140.5±17.5 vs. 110.5±16.5, 152.6±21.5 vs. 120.0±20.0, bothP< 0.05) and D-dimer was significantly decreased (mg/L: 0.5±0.1 vs. 3.2±1.2, 0.6±0.2 vs. 4.4±1.8, bothP< 0.05). APTT after treatment in heparin sodium group was significantly prolonged compared with that before treatment (s: 75.3±10.6 vs. 44.1±8.2,P< 0.05) while no change in APTT was found in LMWHS group (s: 38.6±5.5 vs. 42.1±8.4,P> 0.05). No significant difference was found in PT and Fib between pre and post treatment in all the patients.Conclusion When LMWHS was applied in EHS patients in pre-DIC stage, it could not only prevent DIC as efficiently as heparin sodium, but also results in lower incidence of bleeding. So LMWHS is safer.

Objective To preliminarily investigate the protective effect of chronic clonorchis sinesis(Cs) infestation against sepsis in Sprague Dawley(SD) rats in order to explore its underlying mechanism.Methods Chronic Cs infestation model of SD rats was reproduced by intra-gastric administration with Cs ova.Twenty rats were randomly(random number) divided into normal group(n=10) and Cs group(n=10).The proportion of differentiation in M1 and M2 macrophages were detected by flow cytometry.The expressions of Arg-1(arginine-1),FIZZ 1,iNOs and TNF-αmRNA were examined by reverse transcriptase polymerase chain reaction(RT-PCR).The cecal ligation and puncture(CLP) procedure was performed to reproduce sepsis model of SD rats.Sixty rats were randomly(random number) divided into control group,SHAM group,CLP group,Mφ+CLP group,Cs-Mφ+CLP group,and Cs-CLP group.The cumulative mortalities were calculated.The pathological changes of the lung tissue in different groups were demonstrated by HE staining.The serum levels of cytokines TNF-α and IL-10 were detected by ELISA at 0,24,48 and 72 h after CLP procedure.Results Compared with M1 peritoneal macrophages differentiation in control group(91.9%),rat peritoneal macrophages were activated to M2 differentiation(95.1%) in chronic Cs infection group.RT-PCR assay showed expression of Arg-1 and FIZZ 1 mRNA were higher in M2 macrophages,and on the contrary, the expression of iNOS mRNA expression was higher in M1 macrophages.The expression of TNF-α mRNA in M1 was significantly higher than that in M2, whereas the expression of IL-10 mRNA in M2 was higher than that in M1.The cumulative mortality of septic rats 72 h after CLP procedure were much lower in both chronic Cs infestation group and M2 macrophages adoptive transfer group(CLP group 70%vs.Mφ+CLP group 50%vs.Cs-Mφ+CLP group 30%vs.Cs-CLP group 0%,P<0.05).In these two groups,the pathological damages in lung tissues were significantly improved.The serum level of TNF-α was decreased and the anti-inflammatory IL-10 level was increased significantly in these two groups with Cs compared with other groups.Conclusion M2 macrophages polarization induced by chronic Cs infestation with M2 phenotype gene and expression of anti-inflammatory cytokine gene play key role in increasing anti-inflammatory cytokines and decreasing pro-inflammatory cytokines to allerviate organ damage and ameliorating the survival rate in septic rats.

Objective To screen the active tuberculosis patients among HIV infected patients,and investigate the diagnostic methods for active tuberculosis among TB/HIV co-infected patients.Methods From August 2006 to March 2007,660 HIV/AIDS patients were enrolled.The study was conducted at 4 authorized hospitals for AIDS in Nanning and Liuzhou.Chest X-ray(CXR),acid-fast stain test of sputum smear and fast culture were applied if CD+4 T cell counts were below 350 cells/mm3 or the patients at least have one suspected symptom.Result The CD<;+>4 T cell count in 76.1% (502/660) of the patients was less than 200 cells/mm3.TB/HIV coinfection was found in 22.9% (151/660) of the HIV patients.Among them,74.8% (113/151) of them were pulmonary TB patients.One third of them were extra-pulmonary TB patients,and 68.1% of them involved lymph node.In 264 patients with negative sputum smear test and CXR,20.1% (53/264) of them showed positive results in fast culture tests.In addition,the non-tuberculosis mycobacterium (NTM) infection accounted for 38.5% culture positive cases.Conclusions The TB/HIV coinfection rate is 22.8%.Liquid rapid culture of sputum plays an import role in diagnosing of active tuberculosis among HIV patients.There are considerable proportions of NTM or extra-pulmonary TB coinfection in HIV patients.

[Objectives]To investigate the protective effects of recombinant Trichinella spiralis excretory-secretory 53ku pro-tein(rTsP53)on acute lung injuries in mice.[Methods]Thirty Balb/c mice were randomly divided into normal group. ALI group and rTsP53 group(n=10,respectively). Macrophages were harvested by bronchoalveolar lavage. Mortality in 72 hours was counted and compared. Pathological damage of lung tissues was observed by HE staining and graded by Smith score. Wet/dry ratio was measured. The bronchoalveolar lavage fluid concertration of IL-6 and IL-4 was measured by ELISA. The mRNA expression of TNF-α,iNOS, IL-10 and Arg-1 in alveolar lavage macrophages was detected by RT-PCR.[Results]72 h mortality of ALI mice was 70%,which was reduced to 30% in mice received rTsP53 treatment. Compared with ALI mice,the pathological damage of in rTsP53 treated-mice was improved and Smith score was declined ,combined with descending W/D ratio. IL-6 level of alveolar lavage fluid was elevated in ALI mice compared with normal group. And alveolar lavage macrophage was polarized to M2 sub-type,appeared as higher mRNA expression of TNF-α and iNOS and lower level of IL-10 and Arg-1. Bronchoalveolar lavage fluid concentration of IL-6 was declined and IL-4 was elevated in rTsP53-treated mice compared with ALI group. The macrophages of alveolar wash had higher mRNA expression of IL-10 and Arg-1,while lower level of TNF-α and iNOS,manifesting M2 polarization characteristics.[Conclusion]Recombinant T.spiralis P53 protein could protect mice from acute lung injuries induced by LPS via modulating M2 macrophage polarization,which play a role in depression of inflammatory reaction and tissue repairment.

Among the abundant known modifications that occur within messenger RNA (mRNA), N6-methyladenine (m6A) is the most common post-transcriptional modification in eukaryotes, accounting for almost 80% of all RNA methylation modification. At molecule level, m6A, a reversible modification, participates in regulation of the shearing, nucleation, translation, and degradation of mRNA. Existing studies have also revealed that m6A modification is involved in multiple physiological and pathological processes such as DNA damage repair, stem cell self-renew and differentiation, growth and development, learning and memory, and immune regulation; this kind of modification has also become an important research direction in the field of neuroscience recently. This article mainly summarizes recent processes in the molecular mechanisms of m6A methylation and its relevance to the neurodevelopment and neurological diseases, with aim to provide a comprehensive understanding of m6A regulation in this research area.

Objective To explore the role of deep brain stimulation of subthalamic nucleus (STN-DBS) in treatment of Parkinson's disease (PD) related neuroleptic malignant syndrome (NMS).Methods The medical history,clinical features,STN-DBS programmed treatment process and treatment results of two patients admitted to our hospital in December 2014 and November 2018 were retrospectively analyzed.Results Two patients with post-operative STN-DBS were evoked by dose-reduced treatment of anti-parkinsonian drugs,and presented with high fever,disorder of consciousness,aggravation of the original parkinsonism,and increase of creatine phosphokinase,which were not correlated with outcomes of infection.After admission,anti-parkinsonian drugs and other supportive therapies were supplemented;STN-DBS modulation were given to improve the symptoms;the final parameters of patient one were the left (C+,2-,1-),pulse width 110 μs,frequency 200 Hz,and strength 3.8 V;the right side (C+,6-,5-),pulse width 110 μs,frequency 200 Hz,strength 4.4 V;and those of patient two were the left (C+,3-),pulse width 60 μs,frequency 130 Hz,strength 2.0 V;right side (C+,6-),pulse width 80 μs,frequency 160 Hz,and strength 2.8 V.Both patients were cured,but their motor function and self-care ability were severely impaired.Conclusion STN-DBS may play an important role in the treatment of PD related NMS.

BACKGROUND: Exosomes derived from breast cancer have been reported to play a role in promoting cell proliferation, migration, and angiogenesis, which has the potential to accelerate the healing process of diabetic wounds. The aim of this investigation was to examine the function of exosomes originating from 4T1 mouse breast carcinoma cells (TEXs) in the process of diabetic wound healing. METHODS: The assessment of primary mouse skin fibroblasts cell proliferation and migration was conducted through the utilization of CCK-8 and wound healing assays, while the tube formation of HUVECs was evaluated by tube formation assay. High-throughput sequencing, RT-qPCR and cell experiments were used to detect the roles of miR-126a-3p in HUVECs functions in vitro. The in vivo study employed a model of full-thickness excisional wounds in diabetic subjects to explore the potential therapeutic benefits of TEXs. Immunohistochemical and immunofluorescent techniques were utilized to evaluate histological changes in skin tissues. RESULTS: The findings suggested that TEXs facilitate diabetic wound healing through the activation of cell migration, proliferation, and angiogenesis. An upregulation of miR-126a-3p has been observed in TEXs, and it has demonstrated efficient transferability from 4T1 cells to HUVEC cells. The activation of the PI3K/Akt pathway has been attributed to miR-126a-3p derived from TEXs. CONCLUSIONS The promotion of chronic wound healing can be facilitated by TEXs through the activation of cellular migration, proliferation, and angiogenesis. The activation of the PI3K/Akt pathway by miR-126a-3p originating from TEXs has been discovered, indicating a potential avenue for enhancing the regenerative capabilities of wounds treated with TEXs.

Objective:To investigate the pharmacokinetics of sugammadex in reversal of postoperative residual neuromuscular blockade in obese patients.Methods:Sixteen patients of both sexes, aged 18-65 yr, of American Society of Anesthesiologists physical statusⅠ or Ⅱ, with body mass index of ≥25 kg/m 2, scheduled for elective laparoscopic bariatric surgery, were selected.The patients were divided into 2 groups ( n=8 each) according to the degree of obesity: group O (25 kg/m 2≤BMI<40 kg/m 2) and group M (BMI≥40 kg/m 2). In group O and group M, vecuronium was administered by closed-loop muscle relaxant injection system to maintain moderate neuromuscular blockade.The administration was stopped at the end of surgery, and sugammadex 2 mg/kg was injected according to corrected body weight (CBW) of patients when the muscle relaxation monitoring T 2 recovered naturally.The recovery time of neuromuscular blockade and the occurrence of residual neuromuscular blockade within 3 h after surgery were recorded.Arterial blood samples were collected at 2, 3, 5, 10, 15, 20, 30, 60, 120, 240, 360 and 480 min after administration of sugammadex.The concentration of sugammadex in plasma was determined by ultra-performance liquid chromatography-mass spectrometry.The pharmacokinetic parameters were calculated with PKSolver software. Results:No residual neuromuscular blockade occurred, and the pharmacokinetics of sugammadex in plasma were consistent with the linear non-compartmental model in the two groups.Compared with group O, apparent clearance was increased ( P<0.05), and no significant change was found in other pharmacokinetic parameters, recovery time of neuromuscular blockade and concentrations of sugammadex in plasma at different time point ( P>0.05) in group M. Conclusion:The pharmacokinetics of sugammadex in reversal of postoperative residual neuromuscular blockade in obese patients are consistent with the linear non-compartmental model, and the clearance of sugammadex is higher in morbidly obese patients.