OBJECTIVETo explore the mechanism of natural moxibustion on regulating immune imbalance in asthma rats.

METHODSSeventy SD male rats were divided into a normal group, a placebo group, a dexamethasone group, a big-cake for long-course moxibustion group, a big-cake for short-course moxibustion group, a small-cake for long-course moxibustion group and a small-cake for short-course moxibustion group, ten rats in each one. The rat model of asthma was established by egg albumen sensitization and stimulation in all the groups except the normal group. The natural moxibustion was used in all moxibustion groups, in which big cake of 1 cmX 1 cm size was used in the big-cake groups and small cake of 0.5 cmX 0. 5 cm size was used in the small cake groups. According to relevant acupoints, the natural moxibustion was performed, 5 h per time, once a day. Four times of treatment was considered one course, and three courses were required in the long-course groups and one course was required in the short-course groups. Intraperitoneal injection of dexamethasone was applied in the dexamethasone group, which had the same course as long-course moxibustion group. After the treatment, changes of EOS in peripheral blood of asthma rats were observed; enzyme linked immunosorbent assay (ELISA) was applied to test the contents of IgE, IL-4 and IFN-gamma in the lung tissue; real-time Q-PCR method was adopted to measure the expression level of transcription factor T-bet and GATA binding protein 3 (GATA-3) in the lung tissue.

RESULTSCompared with the normal group, the EOS in whole blood as well as IL-4 and IgE in plasma were all increased in the placebo group (all P< 0. 01), IFN-gamma in plasma was obviously decreased (P<0. 01); while the levels of EOS, IgE and IL-4 were significantly reduced (all P<0. 01), the content of IFN-gamma was increased (P<0. 01) in all moxibustion groups and dexametnasone group. Compared with the normal group, the expression of T-bet mRNA in the placebo group was significantly reduced (P<0. 01). Each treatment group could significantly increase the expression of T-bet mRNA and reduce that of GATA-3 mRNA (P<0. 01). Compared with the short-course moxibustion groups, the expression of T-bet mRNA was obviously increased in the long-course moxibustion group and dexamethasone group (both P<0.01), and that of GATA-3 mRNA was reduced (P<0.01). There was no significant difference between long-course moxibustion group and dexamethasone group (P> 0. 05), and also no significant difference could be seen between big-cake moxibustion group and small-cake moxibustion group (P>0. 05).

CONCLUSIONThe natural moxibustion could obviously reduce airway inflammation in asthma rats. With time passing, the efficacy is enhanced, indicating evident timeliness, which has no apparent relationship with the size of moxibustion cake.

Animals ; Asthma ; genetics ; metabolism ; therapy ; Cytokines ; genetics ; metabolism ; Humans ; Male ; Moxibustion ; Rats ; Rats, Sprague-Dawley ; Transcription Factors ; genetics ; metabolism

Objective To elucidate the biocompatibility differences of 4 dialyzers with different membranes in maintenance hemodialysis (MHD)patients. Methods A total of 60 MHD patients were enrolled in the prospective,randomized,control,cohort study.In baseline,synthetic polysulfone(PS)membrane dialyzer was used in all the patients for at least 3 months.Then the patients were randomly divided into three groups:ployethersulfone(PES)membrane group,cellulose triacetate (CTA)membrane group,and synthetic polymethylmethacrylate(PMMA)membrane group.Study duration was 6 months.No dialyzer was reused.The biocompatibility markers were detected repeatedly at different time points and compared with each other in different dialyzer groups. Results The blood levels of high sensitive C reactive protein,interleukin-1β and interleukin-13 were not significantly different among different groups on every time point.However,the blood complements levels and WBC count were significantly different among four kinds of dialyzer.When the dialyzers changed from PS to PMMA membrane,C3a levels and WBC count changed significantly(P＜0.05).Moreover,the change of C5a level was significantly different between PES group and PMMA group on month 3(P＜0.05). Conclusion There are some differences of biocompatibiliy among different dialyzer membranes.

Objective To study the effects of nitric oxide synthase(NOS) and nitric oxide(NO) in post-asphyxial renal injury in neonatal rats.Methods Forty-eight Wistar neonatal rats were randomly divided into 4 groups:controls,2 h,24 h and 48 h post-asphyxia groups (12 in each group).The rats were decapitated in different times(2 h,24 h and 48 h) after asphyxia for 30 minutes.The renals were dissected to determined the concentrations of NO and NOS.And the scores of renal tubules were measured under light microscope.Results Compared with control group,the levels of NO and NOS significantly increased at 2 h and 24 h after asphyxia.The scores of renal tubules were significant difference at 24 h and 48 h after asphyxia compared to controls.Conclusion These findings suggest NOS and NO may play an important role in the development of post-asphyxia renal injury.

Objective To explore the clinical manifestation, diagnosis and prognosis of Leigh syndrome in children. Method Clinical data from 4 cases of Leigh syndrome conifrmed by genetic testing were retrospectively analyzed. The related literature were reviewed. Results In 4 cases, 3 were boys and one was a girl, 3 cases were onset in infant and one case was in school age. The main manifestations were mental retardation, low muscle tone, convulsions, feeding dififculties, drooping eyelids, extraocular muscle paralysis and nystagmus, irritation, activity intolerance etc. The brain magnetic resonance imaging (MRI) revealed symmetry long T1, T2 abnormal signal in brainstem, bilateral globus pallidus, thalamus, cerebellar dentate nuclei, and periaqueductal, 3 cases involved midbrain, one case involved thalamus, and one case involved cerebellar dentate nuclei;2 cases had encephalatrophy. Electromyography was normal in all cases. The levels of lactate in blood and cerebrospinal lfuid were increased. Mitochondrial DNA (mtDNA) detection found the mutation of mtDNA 8993 T>G in one case, and the mutation of mtDNA 9176 T>C in another 3 cases. The case onset in school age died of respiratory failure one month later, and another 3 cases were still in follow up, there were mental retardation, but no signiifcant setback. Conclusion The clinical manifestations of Leigh syndrome in children are diverse. The diagnosis is based on the typical clinical manifestations and MRI, blood and/or cerebrospinal lfuid lactate levels. The genetic testing is the golden standard for diagnosis.

Objective:To explore the clinical features and prognosis of patients with primary central nervous system lymphoma(PCNSL).Methods:A retrospective analysis was performed on the relationship between clinical features,treatment regimen and prognosis in 46 newly diagnosed patients with primary central nervous system lymphoma who were diagnosed and treated in The Second Hospital of Lanzhou University from January 2015 to September 2022.Fisher's exact probability method was used to analyze the differences in clinical data of different subgroups.Kaplan-Meier survival curve was used to analyze the overall survival rate and progression-free survival rate of patients with different treatments,and the factors influencing survival were analyzed.Results:Among 46 patients with PCNSL,which pathological type were diffuse large B-cell lymphoma(DLBCL).There were 26(56.5％)cases of male and 20(43.5％)of female,with a median age of 54(17-71)years.In Hans subtypes,14 cases(30.4％)of GCB subtype,32 cases(69.6％)of non-GCB subtype.32 cases(69.6％)of Ki-67 ≥80％.Among 36 patients who completed at least 2 cycles of treatment with follow-up data,the efficacy evaluation was as follows:overall response rate(ORR)was 63.9％,complete response(CR)rate was 47.2％,17 cases of CR,6 cases of PR.The 1-year progression-free survival rate and 1-year overall survival rate was 73.6％and 84.9％,respectively.The 2-year progression-free survival rate and 2-year overall survival rate was 52.2％and 68.9％,respectively.The ORR and CR rate of 17 patients treated with RMT regimen was 76.5％and 52.9％(9 cases CR and 4 cases PR),respectively.Univariate analysis of 3 groups of patients treated with RMT regimen,RM-BTKi regimen,and RM-TT regimen as first-line treament showed that deep brain infiltration was associated with adverse PFS(P=0.032),and treatment regimen was associated with adverse OS in PCNSL patients(P=0.025).Conclusion:Different treatment modalities were independent prognosis predictors for OS,the deep brain infiltration of PCNSL is a poor predictive factor for PFS.Patients with relapse/refractory(R/R)PCNSL have a longer overall survival time because to the novel medication BTKi.They have strong toleration and therapeutic potential as a first-line therapy for high-risk patients.

Objective To investigate AXIN2 mRNA expression level in hepatocellular carcinoma (HCC) , and to analyze the effect of AXIN2 gene methylation status on its mRNA expression and HCC genesis and development. Methods Fifty-three surgical excised HCC specimens and paired adjacent non-cancerous specimens, seven normal liver specimens and five HCC cell lines were collected. The expression of AXIN2 at mRNA level and the methylation status of AXIN2 gene promoter were determined by quantitative PCR. Results The expression of AXIN2 mRNA was lower in HCC tissues (0.1629 + 0.0679) than that in adjacent non-cancerous tissues (0. 4155 + 0. 2330), and there was significant difference (Z= -2. 567, P = 0. 010). The methylation level of AXIN2 gene in HCC and adjacent non-cancerous tissues (39. 77% ±3. 89%, and 36. 92% ±2. 81%) was significantly higher than that in normal liver tissues (7. 38% ±2. 40% , t=-3. 663 ,P = 0. 009;t= -4. 591 ,P = 0. 007).AXIN2 gene was hypermethylated in all five HCC cell lines. There was a negative correlation between AXIN2 mRNA expression level and the degree of methylation ( r = -0. 458, P = 0. 032). The methylation level was higher in TNM Ⅲ patients of HCC than that in TNM Ⅰ and Ⅱ patients (P =0.008). Conclusion The down-regulation of AXIN2 gene mRNA expression is correlated with its hypermethylation status. The low expression of AXIN2 mRNA and the abnormal methylation of promoter may be one of the important mechanism of HCC genesis and development.

AIMTo prepare the sustained-release nitrendipine microspheres with a solid dispersed structure in liquid system.

METHODSThe sustained-release nitrendipine microspheres with a solid dispersed structure was prepared in liquid system by combining spherical crystallization technique and solvent deposition method in one step. The resultant microspheres were evaluated for the recovery, micromeritc properties, incorporation efficiency. The factors of effect on the formation and the release rate of microspheres were also investigated.

RESULTSThe recovery of microspheres (280-900 microns) was more than 70% and the bulk density was around 0.7 kg.L-1. The incorporation efficiency always exceeded 95%. The formation of microspheres was mainly affected by the amount of bridging liquid and the emulsifying agents in poor solvent. The release rate of nitrendipine from the microspheres could be controlled as desired by adjusting the ratio of talc to Eudragit RS PO in the formulation.

CONCLUSIONThe presented method was suitable for preparing sustained-release microspheres of a water insoluble drug.

Delayed-Action Preparations ; Drug Carriers ; Microspheres ; Nitrendipine ; administration & dosage ; Particle Size ; Technology, Pharmaceutical ; methods

OBJECTIVESTo measure continuously the urine beta-FSH excretion in the patients with male hypogonadism, and to evaluate the significance of urine beta-FSH when used in the clinical practice and pathophysiological study on male hypogonadism.

METHODSFour health male volunteers (aged 19, 22, 27 and 33 years), four patients with the hypogonadotropic hypogonadism (aged 17, 17, 19 and 24 years) and five patients with idiopathy hypogonadism (hypergonadotropic, aged 16, 16, 17, 20 and 22 years) were asked to collect their morning-first urine samples for 30 to 32 days. One normal men collected his urine samples for 63 days. The urine beta-FSH was assayed with the method of EIA, then corrected by creatinine (Cr) concentration.

RESULTSThe urine beta-FSH level of normal men was (1.16 +/- 0.20) micrograms/mg Cr, with the peak variation in their curves, peak level at 2.76 micrograms/mg Cr. The levels of urine beta-FSH of 4 patients with the hypogonadotropic hypogonadism were lower significantly than those of normal men [(0.58 +/- 0.31) (0.93 +/- 0.47) (0.47 +/- 0.33) and (0.60 +/- 0.40) micrograms/mg Cr], without fluctuation in their curves. beta-FSH levels of 5 patients with idiopathy hypogonadism were higher significantly [(3.02 +/- 0.93), (4.36 +/- 1.12), (4.79 +/- 0.78), (4.64 +/- 1.42) and (3.88 +/- 1.42) micrograms/mg Cr], with irregular fluctuation, the highest peak level at 6.83 micrograms/mg Cr. The second sexual characteristics of hypogonadal patients were poor and serum testosterone levels low.

CONCLUSIONSThe urine beta-FSH level raised with irregular fluctuation in patients with idiopathy hypogonadism, while lowed without any fluctuation in patients with the hypogonadism. These findings suggested that the urine beta-FSH excretion was useful for the clinically classified diagnoses and pathophysiological study on male hypogonadism, and for observing the treatment reaction of androgen replacement.

Adolescent ; Adult ; Follicle Stimulating Hormone, beta Subunit ; urine ; Humans ; Hypogonadism ; metabolism ; urine ; Luteinizing Hormone ; urine ; Male ; Testosterone ; urine

OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the pharmacokinetics-genetic polymorphis relationship. METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release (ER) 80 mg tablet and an immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study, ef-fects of BCRP, SLCO1B1, MDR1, CYP2C9, and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using high-performance liquid chromatography-tandem mass spectrometry. RESULTS The SLCO1B1 T521C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1B1 T521C genotype correlated with the AUC0-24of repeat doses (P=0.01). The CYP2C9*3 genotype correlated with the AUC0- 24after the first dose IR 40 mg capsule (P<0.05); however, the difference between CYP2C9*1/*1 and CYP2C9*1/*3 was not statistically significant after repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.

This study was amid to construct the pharmacophore model of L-type calcium channel antagonist in the application of screening Drugbank and TCMD. This paper repositions the approved drugs resulting from virtual screening and discusses the relocation-based drug discovery methods, screening antihypertensive drugs with L-type calcium channel function from TCMD. Qualitative hypotheses wre generated by HipHop separately on the basis of 12 compounds with antagonistic action on L-type calcium channel expressed in rabbit cardiac muscle. Datebase searching method was used to evaluate the generated hypotheses. The optimum hypothesis was used to search Drugbank and TCMD. This paper repositions the approved drugs and evaluates the antihypertensive effect of the chemical constituent of traditional Chinese medicine resulting from virtual screening by the matching score and literature. The results showed that optimum qualitative hypothesis is with six features, which were two hydrogen-bond acceptors, four hydrophobic groups, and the CAI value of 2.78. Screening Drugbank achieves 93 approved drugs. Screening TCMD achieves 285 chemical constituents of traditional Chinese medicine. It was concluded that the hypothesis is reliable and can be used to screen datebase. The approved drugs resulting from virtual screening, such as pravastatin, are potentially L-type calcium channels inhibitors. The chemical constituents of traditional Chinese medicine, such as Arctigenin III and Arctigenin are potentially antihypertensive drugs. It indicates that Drug Repositioning based on hypothesis is possible.
Animals ; Antihypertensive Agents ; chemistry ; pharmacology ; Calcium Channel Blockers ; chemistry ; pharmacology ; Calcium Channels, L-Type ; genetics ; metabolism ; Drug Repositioning ; methods ; Molecular Structure ; Myocardium ; metabolism ; Rabbits