Objective To evaluate the effect of BML-111 on NF-κB pathway during acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 4 groups (n =8 each) using a random number table:sham operation group (group S),hemorrhagic shock and resuscitation group (group HSR),BML-111 group,and BML-111 + BOC-2 (lipoxin A4 receptor antagonist) group (group BOC-2).The animals were anesthetized with intraperitoneal pentobarbital sodium.Hemorrhagic shock was induced by blood letting and maintained for 30 min.The animals were then resuscitated for 30 min by infusion of the shed blood and lactated Ringer's solution.In group BOC-2,BOC-2 (50 μg/kg) was injected intraperitoneally before blood letting.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.The rats were sacrificed at 2 h after the end of resuscitation and lungs were removed for determination of pathological changes,myeloperoxidase (MPO) activity,intercellular adhesion molecule-1 (ICAM-1) expression (by immunohistochemistry),tumor necrosis factor-alpha (TNF-α) content (by ELISA),and NF-κB p65 and IκB-α expression (by Western blot).Results Compared with group S,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and IκB-α expression was down-regulated in group HSR.Compared with group.HSR,the MPO activity,ICAM-1 expression,and TNF-α content were significantly decreased,NF-κB p65 expression was down-regulated,IκB-α expression was up-regulated,and pathological changes of lung were attenuated in group BML-111.Compared with group BML-111,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and lκ:B-α expression was down-regulated,and pathological changes of lung were aggravated in group BOC-2.Conclusion BML-1 11 inhibits activation of NF-κB pathway and inflammatory responses,thus mitigating acute lung injury induced by hemorrhagic shock and resuscitation in rats.

Objective To evaluate the effect of lipoxin A4 receptor agonist BML-111 on acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 200-250 g,were randomized into 4 groups (n =8 each) using a random number table:sham operation group (S group),hemorrhagic shock/resuscitation group (HSR group),BML-111 group,and BML-111 plus BOC-2 (lipoxin A4 receptor antagonist) group (BOC-2 group).The animals were anesthetized with 2％ pentobarbital sodium 80 mg/kg,tracheostomized and mechanically ventilated.Left common carotid artery was cannulated for blood-letting and fluid infusion.Hemorrhagic shock was induced according to the method described by Kochanek et al.MAP was reduced to 35-45 mmHg and maintained at this level for 30 min.The animals were then resuscitated for 30 min with infusion of the blood withdrawn and lactated Ringer' s solution 2 times the volume of blood withdrawn.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.In BOC-2 group,BOC-2 (50 μg/kg) was injected intraperitoneally before blood-letting.The rats were sacrificed at 2 h after completion of resuscitation.Bronchoalveolar lavage fluid (BALF) was collected for determination of neutrophil count.Lungs were excised for microscopic examination of the pathological changes and for determination of wet/dry lung weight ratio (W/D ratio),contents of interleukin-1 (IL-1β) and IL-6,and phosphorylation of mitogen-activated protein kinase (MAPK).Results Compared with group S,the neutrophil count in BALF,W/D ratio,contents of IL-1β and IL-6,and phosphorylation of MAPK were significantly increased in HSR group (P ＜ 0.05).The neutrophil count in BALF,W/D ratio,contents of IL-1β and IL-6,and phosphorylation of MAPK were significantly lower in BML-111 group than in HSR group,and higher in BOC-2 group than in BML-111 group (P ＜ 0.05).Conclusion BML-111 can attenuate acute lung injury induced by hemorrhagic shock and resuscitation in rats and inhibition of activation of MAPK pathways and reduction of inflammatory responses in lung tissues are involved in the mechanism.

Objective To observe the improving effect in joint function of moderate skeletal fluorosis treated by traditional Chinese medication(main ingredient was Strychnine).MethodsFrom December 2007 to July 2009,120 moderate skeletal fluorosis patients met the inclusion criteria were divided into the treatment group(60 cases)and the control group(60 cases)in the skeletal fluorosis hospital of Xinzhou,the treatment group was given basic treatment and traditional Chinese medication,the control group wa8 given basic treatment and placebo.The treatment lasted 12 weeks,follow up 24 weeks.Before treatment,after treatment 4 weeks,8 weeks,12 weeks,36 weeks,a third party evaluate comprehensive function of both upper and lower limb and joint dysfunction.Results The main effect of both drugs was statistically significance in the scores of the upper forearm in the finger by touching the posterior contralateral ear, upper arm touched by the finger back in the opposite corner subscapularis function, lower limb function and single-joint dysfunction(F values were 4.08,14.32,35.81,13.02, all P<0.05), the main effect of time also was significant (F values were 82.63,72.82,277.33,328.16, all P<0.05),①the upper forearm in the finger by touching the posterior contralateral ear functions:At the time of 8,12 weeks,scores of the treatment group were lower than those of before treatment and control group (all P<0.05);At the time of 36 weeks,scores of the treatment group were lower than that 12 weeks(all P<0.05);At the time of 8,12,36 weeks, scores of the control group were lower than those of before treatment(all P < 0.05);②upper arm function, namely fingers touching the opposite corner subscapularis:At the time of 4,8,12 weeks, scores of the treatment group were lower than those of before treatment(all P<0.05); At the time of 36 weeks, scores of the treatment group were lower than that 12 weeks(all P<0.05); At the time of 8,12,36 weeks, scores of the treatment group were lower than those of the control group (all P<0.05);③Lower extremity functions: At the time of 8,12 weeks,scores of the treatment group were lower than those of before treatment and control group (all P<0.05);At the time of 36 weeks, scores of the treatment group were lower than that 12 weeks(all P<0.05) ; At the time of 8,12,36 weeks, scores of the control group were lower than those of before treatment (all P<0.05);④single joint functions:At the time of 4,8,12 weeks,scores of the treatment group were lower than those of before treatment(all P<0.05); At the time of 36 weeks,scores of the treatment group were lower than that 12 weeks(all P<0.05) ; At the time of 8,12,36 weeks, scores of the control group were lower than those of before treatment(all P<0.05);At the time of 4,8,12,36 weeks, scores of the treatment group were lower than those of control group(all P<0.05);⑤At the end of treatment and follow-up,the improvement rate in joint functions in the treatment group were 88.33% (53/60),93.33% (56/60); the control group were 28.07%(16/57),40.35%(23/57), (Fisher test, P<0.01,X2=56.21, P<0.01). ConclusionTraditional Chinese medication(its main ingredient is Strychnine), an effective drug for improving joint dysfunction in patients suffering from moderate skeletal fluorosis, is simple and effective.

Purpose: The purpose of this study was to investigate the prevalence and risk factors of overactive bladder (OAB) in young adults and to explore the influence of OAB on mental health. Methods: Between October 2019 and January 2020, 14,010 anonymous questionnaires were distributed to freshmen at 2 universities in Henan, China. The students came from all over the country. The questionnaire included general items and information necessary to calculate the overactive bladder symptom score, the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) score, Self-Esteem Scale (SES) score, and Self-Rating Depression Scale (SDS) score. The relationships between the prevalence of OAB and its risk factors were evaluated. Results: The overall prevalence of OAB was 6.0%, with 4.3% of participants characterized as having dry OAB and 1.7% as having wet OAB. The prevalence of mild OAB was 5.5%, and that of moderate OAB was 0.5%; no severe OAB was observed. Higher prevalence rates of OAB were found among women, respondents with constipation, and respondents with primary nocturnal enuresis (PNE) (P <0.05). Compared to healthy controls, the OAB group exhibited a higher mean SDS score (52.12±8.986 vs. 47.71±9.399, P<0.001) and mean PSQI score (5.28±2.486 vs. 4.27±2.431, P<0.001), but a lower mean SES score (27.78±3.599 vs. 29.57±4.109, P<0.001). Conclusions OAB significantly affects the mental health of young adults. Female sex, constipation, and PNE are risk factors for OAB.

Ex vivo expansion of hematopoietic progenitor cells (HPCs) is valuable for clinical application, however, traditional ex vivo culture negatively affects long-term hematopoietic reconstitution ability. In the hematopoietic system, the expression of Notch receptors and their ligands has been widely reported. Active Notch signal inhibits the differentiation of HSCs while promotes their expansion, suggesting that ex vivo expansion of hematopoietic progenitor cells could be enhanced by manipulating Notch signal pathways. In this article the Notch signal pathways, Notch signal and maintenance of hematopoietic progenitor cells, Notch signal and expansion of hematopoietic progenitor cells and molecular mechanism of Notch signal maintaining undifferentiation of hematopoietic progenitor cells were reviewed.
Animals ; Hematopoietic Stem Cells ; cytology ; metabolism ; Humans ; Receptors, Notch ; metabolism ; Signal Transduction

OBJECTIVETo study the content variation of triptolide in medicinal material of Tripterygium and provide theoretical basis for the hereditary improvement, the gathering and process, the quality evaluation and the provenance division in medicinal material of Tripterygium.

METHODHPLC method was used to determine the content of triptolide.

RESULTThe relations between triptolide and germplasm, growth year, gathering season were found out basically.

CONCLUSIONThe triptolide contents in xylem are affected by hereditary factors remarkably. While the triptolide contents in phloem are not affected obviously. The accumulation of triptolide needs the certain growth years. However when growth is beyond certain years, the triptolide content decreases with the disintegration of secondary metabolism in xylem. The triptolide in xylem is highest in winter and decreasing in growing season. The triptolide in phloem is less affected by the season.

Chromatography, High Pressure Liquid ; Diterpenes ; analysis ; metabolism ; Ecosystem ; Epoxy Compounds ; analysis ; metabolism ; Phenanthrenes ; analysis ; metabolism ; Plant Roots ; anatomy & histology ; chemistry ; Plants, Medicinal ; anatomy & histology ; chemistry ; growth & development ; Seasons ; Species Specificity ; Time Factors ; Tripterygium ; anatomy & histology ; chemistry ; growth & development ; Xylem ; chemistry

AIMTo investigate the impact of CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam.

METHODSCYP2C9 * 3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9 * 1/* 3 genotype and 11 with * 1/* 1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately.

RESULTSAfter a single oral dose of 2.5 mg glibenclamide, C(max) was (70.0 +/- 11.5) microg x L(-1) in CYP2C9 * 1/ * 3 subjects and (51.9 +/- 12.3) microg x L(-1) in * 1/ *1 subjects. AUC(0-infinity) were (435 +/- 47) vs (287 +/- 95) microg x h x L(-1) (in * 1/ * 3 vs * 1/ *1 subjects), and CL/F were (96 +/- 9.3) vs (160 +/- 51) mL x min(-1), respectively. Statistic analysis results indicated that glibenclamide AUC(0-infinity) was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.01). After a single oral dose of 8 mg lornoxicam, C(max) was (1.54 +/- 0.24) mg x L(-1) in CYP2C9 * 1/ * 3 subjects and (1.19 +/- 0.37) mg x L(-1) in * 1/ * 1 subjects. AUC(o-infinity were (14.9 +/- 2.2) vs (6.92 +/- 1.48) mg x h x L(-1) (in * 1/ *3 vs * 1/ * 1 subjects), and CL/F were (9.1 +/- 1.2) vs (20.1 +/- 4.6) mL x min(-1), respectively. Statistic analysis results indicated that lornoxicam AUC(0-infinity) was significantly higher (2. 2-fold) and subsequently CL/F was significantly lower (55% ) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.001).

CONCLUSIONCYP2C9 * 3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9 * 1/ * 3 genotype, especially lornoxicam.

Adult ; Alleles ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacokinetics ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; China ; Cytochrome P-450 CYP2C9 ; Genotype ; Glyburide ; pharmacokinetics ; Humans ; Hypoglycemic Agents ; pharmacokinetics ; Male ; Piroxicam ; analogs & derivatives ; pharmacokinetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

Administration of the immunosuppressive drug cyclosporine (CSA) after autologous peripheral blood stem cell transplantation (APBSCT) induces a systemic auto-immune syndrome resembling graft-versus-host disease (GVHD), this syndrome termed autologous GVHD has significant antitumor activity, it can reduce the incidence of tumor relapse after APBSCT. The antitumor effect of this auto-aggression syndrome can be enhanced by the administration of gamma-interferon (gamma-IFN). Five consecutive patients who received APBSCT received therapy inducing autologous GVHD. Intravenous administration of CSA [1 mg/(kg.d) for 28 days] was begin on the day of transplantation. gamma-interferon (0.025 mg/m(2) qod) was administered sub-cutaneously from days 7 throngh 28 after transplatation. Results showed that four of five occured autologous GVHD-skin demage, five in control didn't occur autologous GVHD. The relapse rate of the treated cases was 20% (1/5) versus 60% (3/5) of the control, and the median survival time of the treated cases was 20 (4 - 30) months versus 10 (2 - 20) months of the control. The data indicates that autologous GVHD results in low relapse rate of the patients rececving APBSCT.

To explore the protective effect of Angelica sinensis polysaccharides(ASP) on subacute renal damages induced by D-galactose in mice and its mechanism. Male C57BL/6J mice were randomly divided into 3 groups, with 10 mice in each group. The D-galactose model group was subcutaneously injected with D-galactose (120 mg x kg(-1)), qd x 42; the ASP + D-galactose model group was intraperitoneally injected with ASP since the 8th day of the replication of the D-galactose model, qd x 35; and the normal control group was subcutaneously injected with saline at the same dose and time. On the 2nd day of after the injection, the peripheral blood was collected to measure the content of BUN, Crea, UA, Cys-C; paraffin sections were made to observe the renal histomorphology by HE staining; senescence-associated β-g-alactosidase (SA-β-Gal) stain was used to observe the relative optical density (ROD) in renal tissues; transmission electron microscopy was assayed to observe the renal ultrastructure; the renal tissue homogenate was prepared to measure the content of SOD, GSH-PX, MDA; the content of AGEs and 8-OH-dG were measured by ELISA. According to the result, compared with the D-galactose model group, the ASP + D-galactose model group showed obviously decreases in the content of BUN, Crea, UA, Cysc, AGES, 8-OH-dG, the number of hardening renal corpuscle, renal capsular space and renal tubular lumen, ROD of SA-β-Gal staining positive kidney cells, mesangial cells, basement membrane thickness, podocyte secondary processes fusion and MDA and increases in the number of normal renal corpuscle, ribosome and rough endoplasmic reticulum in podocytes, the activity of SOD and GSH-PX. In Conclusion, A. sinensis polysaccharides can antagonize kidney subacute damages induced by D-galactose in mice. Its protective mechanism may be correlated with the inhibition of the oxidative stress injury.
Angelica sinensis ; chemistry ; Animals ; Deoxyguanosine ; analogs & derivatives ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Galactose ; adverse effects ; Humans ; Kidney ; anatomy & histology ; drug effects ; injuries ; Kidney Diseases ; chemically induced ; drug therapy ; metabolism ; prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; drug effects ; Polysaccharides ; administration & dosage ; Protective Agents ; administration & dosage

BACKGROUNDMitochondrial dysfunction plays a pivotal role in the progression of left ventricular (LV) remodeling and heart failure (HF). Recombinant human neuregulin-1 (rhNRG-1) improves cardiac function in models of experimental HF and in clinical trials; however, its impact on mitochondrial function during chronic HF remains largely unknown. The purpose of this study was to investigate whether rhNRG-1 could attenuate the functional and structural changes that occur in cardiac mitochondria in a rat model of HF induced by myocardial infarction.

METHODSSixty adult rats underwent sham or coronary ligation to induce HF. Four weeks after ligation, 29 animals with LV ejective fraction ≤ 50% were randomized to receive either vehicle or rhNRG-1 (10 µg×kg(-1)×d(-1), I.V.) for 10 days, another 12 sham-operated animals were given no treatment. Echocardiography was used to determine physiological changes. Mitochondrial membrane potential (MMP), respiratory function and tissue adenosine triphosphate (ATP) production were analyzed. Cytochrome c expression and cardiomyocyte apoptosis were determined. Oxidative stress was evaluated by reactive oxygen species production using fluorescence assays and gene expression of glutathione peroxidase measured by real-time quantitative PCR.

RESULTSCompared with sham-operated animals, vehicle treated HF rats exhibited severe LV remodeling and dysfunction, significant mitochondrial dysfunction, increased mitochondrial cytochrome c release, increased myocyte apoptosis and enhanced oxidative stress. Short-term treatment with rhNRG-1 significantly attenuated LV remodeling and cardiac function. Concomitant with this change, mitochondrial dysfunction was significantly attenuated; with ATP production, MMP and respiratory function restored, cytochrome c release and apoptosis inhibited, and oxidative stress reduced.

CONCLUSIONThe present study demonstrated that rhNRG-1 can significantly improve LV remodeling and cardiac function in the failing heart, this beneficial effect is related to reducing mitochondrial dysfunction, myocyte apoptosis and oxidative stress.

Animals ; Apoptosis ; drug effects ; Blotting, Western ; Echocardiography ; Heart Failure ; Mitochondria ; drug effects ; metabolism ; Myocardial Infarction ; drug therapy ; metabolism ; pathology ; Neuregulin-1 ; therapeutic use ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Real-Time Polymerase Chain Reaction