Animals ; Bone Density ; Diagnosis, Differential ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Medicine, Chinese Traditional ; Osteoporosis ; drug therapy ; etiology ; metabolism ; Ovariectomy ; Phytotherapy

Fatigue ; etiology ; therapy ; Humans ; Neoplasms ; complications

Objective To study the characteristics of pharmacokinetics and pharmacodynamics of insulin dry powder inhalation and its relative bioavailability as compared with subcutaneous injection of regular insulin. Methods In this open,single-center,randomized,two-period,cross-over,euglycemic glucose clamp study,18 healthy volunteers(14 men and 4 women),aged(24.9?1.7)years,with body mass index(20.6?1.2)kg/m~2, received the insulin dry powder inhalatin(80 U)or regular insulin(15 U)subcutaneous administration.The blood samples of this study at 0,20,30,40,50,60,70,80,90,100,110,120,135,150,165,180,195, 210,225,240,270,300,330,360,390,420,450 and 480 rain were taken for serum insulin measurement, meanwhile,glucose infusion rates(GIR)were determined per 5 minutes over a period of 8 hours.Results The C_(max)were(57.9?17.8 vs 114.5?29.7)mU/L(tested vs reference preparation),T_(max)were(46.7?45.6 vs 107.8?33.7)min,GIR_(max)were(3.35?0.98 vs 5.17?1.75)mg?kg~(-1)?min~(-1)and T_(GIRmax)were(88.3?17.0 vs 151.9?34.6)min.The relative bioavailability was(10.26?2.25)%,and the relative bioefficacy was(14.33?7.26)%.Conclusion The study shows that insulin dry powder inhalation is absorbed via lungs and its action sets in earlier than that of the regular insulin injected subcutaneously.These pharmacokinetie and pharmacodynamic data may provide a reliabe guide for further clinical trial.

Objective To investigate the effect of luxS inactivation on the oxidative stress of Streptococcus mutans and perform preliminary analysis of potential mechanism.Methods Strains were grown to mid-logarithmic phase and divided into three groups,one was used as control and inoculated into normal TPY medium,and the other two groups were experimental groups,and there were separately inoculated into TPY containing 58.8 mmol/L hydrogen peroxideor TPY containing 58.8 mmol/L hydrogen peroxide and 0.1 mmol/L 2,2'-dipyridyl.The survival rate of strain was calculated at 0.5,1,and 2 h.All the data were statistically analyzed.Results Compared with the control group,the survival rate of luxS mutation was always higher than standard strain at all pre-determined time inexperimental groups (P＜0.05),and compared with experimental group without iron chelator,the survival rate of strains was not raised with the added of iron chelator (P＞0.05).Conclusion luxS gene is involved in oxidative stress tolerance of Streptococcus mutans,and the oxidative stress tolerance is not achieved by avoiding the toxic effects of the Fenton reaction

Objective To seek for the differentially-expressed proteins in patients with kidney-yin deficiency syndrome and to screen out the specific proteins,so as to provide evidence for the establishment of objective standard of kidney deficiency syndrome of traditional Chinese medicine (TCM).Methods Five patients with typical kidney-yin deficiency syndrome and 6 normal healthy volunteers were enrolled into the study.Plasma proteins in both groups were detected by antibody chip,and then the plasma proteins profile was compared and analyzed.Results A total of 25 differentially-expressed proteins between kidney-yin deficiency group and normal control group were found,of which 2 were up-regulated and 23 were down-regulated.Conclusion The differentially-expressed proteins in patients with kidney-yin deficiency syndrome are mainly related to immune disorder,protein biosynthesis,metabolism,oxidative stress,cell apoptosis,signal transduction,and so on.

Objective To study the immediate conservative breast surgical reconstruction by trans-ferring the same lateral latissimus dorsal myocutaneous flap (LDM) for the treatment of stage Ⅱ and stage Ⅲ breast cancer, combined with neoadjuvant chemotherapy. Methods Breast cancer patients in stage Ⅱ and Ⅲ with pathological diagnosis by core needle biopsy, had undergone immediate conservative breast reconstruction surgery with transferring the latissimus dorsal myocutaneous (LDM). We scored the reconstructed breast twice at one month after operation and completion of radiation. The final score was decided using the mean value of the twice evaluating score. Kaplan-Meier survival was used to analyze the survival of 18 cases with traditional mastectomy. Results The tumor size ranged from 30 mm to 55 mm before neoadjuvant chemotherapy, and ranged from 25mm to 45 mm after neoadjuvant chemotherapy. The median weight of the tumor specimens in breast conservative operation was 140 g (90 g to 220 g). A-mong the 18 patients, 16 cases had more than 3 scores with satisfied cosmetics (93.33 % ). Dorsal subcu-taneous seroma in donation area was observed in 5 of 18 patients (27.78 %) and dorsal incision dehiscence was observed in 2 of 18 patients (11.11%). None of the patients developed recurrence except that 1 pa-tient (5.55 %) had distance metastasis (bone metastasis} in a mean 22-months follow-up. The Kaplan-Meier survival curve in breast conservation reconstruction patients had no different from that of traditional mastectomy patients at the same time. Conclusions Immediate conservative breast surgical reconstruction by using the same lateral latissimus dorsal myocutaneous flap is an effective method for stage Ⅱ and stage Ⅲ breast cancer patients combined with neoadjuvant chemotherapy, which can increase satisfactory breast so that cosmetic outcome can be reached.

Usung gatufloxacun ( GTFX) as template molecule, magnetuc surface molecularly umprunted polymers ( M-MIPs) were prepared on the surface of modufued magnetuc suluca ( Fe3 O4@SuO2 ) wuth surface molecular umpruntung technuque. The polymers were characteruzed by transmussuon electron mucroscopy ( TEM ) and vubratung sample magnetometer ( VSM ) . The statuc adsorptuon experuments and Scatchard analysus suggested that there were two types of bundung sutes un the M-MIPs. The maxumum adsorptuon capacutues of M-MIPs and magnetuc non-umprunted polymers ( M-NIPs) for GTFX were 35. 1 mg/g and 23. 1 mg/g, respectuvely. The selectuvuty coeffucuents of GTFX M-MIPs to cuprofloxacun (CPFX), norfloxacun (NFLX), melamune (MEL) and tetracyclune (TC) were 2. 43, 5. 18, 6. 61 and 12. 99, and the relatuve selectuvuty coeffucuents of M-MIPs to M-NIPs for these four drugs were 2. 09, 1. 95, 3. 15 and 2. 43, respectuvely, unducatung the good specufuc recognutuon capabuluty for GTFX. Combuned wuth hugh performance luquud chromatographuc analysus, the M-MIPs were applued to extract and enruch GTFX un mulk sample wuth the recoverues more than 91 . 5%.

ObjectiveTo explore the effect of blocking the JAK/STAT signal pathway on the activity of Caspase-3 in the synovial tissue of rheumatoid arthritis rats.MethodsFifty rat models of collageninduced arthritis,which had arthritis index more than 2 were divided into the model group,the low dosage of AG490 group,the medium dosage of AG490 group and high dosage of AG490 group.Inaddition,6 rats were treated as normal control group.Normal saline,AG490 1,5,10 mg·kg-1 ·d-1 were given by intraperitoneal injection.Then the volume claws and pathologic scores of the rat models were recorded and the activity of Caspase-3 in the synovial tissue were compared.The results were analyzed by one-way ANOVA and LSD-t or Tamhane's T2 test.ResultsThe arthritis of the CIA models progressed fast,the volume of the claws and the pathological score of them were significantly higher than those of the control group.At the same time,no Caspase-3 positive express could be detected in the control group,whilethe model group had slightly increased expression.After different dosages of AG490 were applied,the swollen of joints was significantly improved compared with the model group.The histopathological score of the medium AG490 dosage of group and high dosage group(2.7±0.8,1.8+0.9) were remarkably decreased than those of the model group(4.3+1.2),the differences were statistically significant (P＜0.01).In addition,the Caspase-3 expression in the low,medium and high AG490 dosage group ( 1.90±0.15,3.13±0.33,3.56+0.34) was significantly higher than that of the model group(1.48±0.18)(P＜0.05 or P＜0.01 ).ConclusionBlocking JAK/STAT signal pathway can increase the activity of Caspase-3,reduce the excessive proliferation of synovial tissue,and improve arthritis symptoms.

Objective To analyse MMACHC mutations for 45 pedigrees with combined methylmalonic aciduria and homocyctinuria by Sanger sequencing, and to discuss the utility of prenatal genetic diagnosis for these pedigrees.Method Peripheral blood was collected from 45 probands and their parents from 2012-2015 in Genetic Counselling Clinic of the First Affiliated Hospital of Zhengzhou University, and the DNA were extracted from the blood.Then the coding sequence of MMACHC gene was amplified by PCR, and the PCR products were further sequenced to detect mutations for each pedigree.For 12 families, chorionic villus sampling was performed on the pregnant women to make prenatal genetic diagnosis.Result There were 14 distinct mutations detected in the 45 pedigrees, and the most frequent mutations are c.609G>A(W203X),c.658-660delAAG(K220del)and c.80A>G (Q27A).Two of those mutations have not been reported before:one is a splicing site mutation c.81+1G>A;while the other is a missense mutation c.665A>G,p.Y222C.Most mutations were found in exon 4.Among the 12 pedigrees who received prenatal diagnosis, 2 fetuses were normal, 7 fetuses were carriers of heterozygous mutation, and the other 3 fetuses were patients with compound heterozygous mutation or homozygous mutation.The couples whose fetuses were normal or carriers continued the gestation, while the couples whose fetuses were patients decided to terminate the pregnancy.After delivery, the outcome of the fetuses was the same as the prenatal diagnose results.Conclusion Two novel mutations of MMACHC were identified and prenatal genetic diagnosis helps to avoid the delivery of combined methylmalonic aciduria and homocyctinuria patients.

Objective: To observe the impact of vareniline tartrate on vascular endothelial function and inlfammatory factor releasing in acute coronary syndrome (ACS) patients with nicotine dependence after smoking withdrawal treatment.
Methods: We recruited the in-hospital ACS patients who were smoking ≥10 cigarettes/day for more than 10 years with at least moderate nicotine dependence, and randomly divided them into 2 groups: Varenicline group, the patients received oral medication for 2 weeks and Self withdrawal group, the patients without medication assistance.n=52 in each group. All patients received (10-30) min daily mission and consulting for quit smoking for 2 weeks. The basic information was recorded and blood levels of NO, IL-6 and ET-1 were compared before and after withdrawal treatment.
Results: Compared with they were before, after 2 weeks withdrawal treatment, in Varenicline group, blood levels of ET-1 decreased as (33.950 ± 1.439) ng/L vs (170.198 ± 12.602) ng/L and IL-6 decreased as (0.103 ± 0.020) ng/L vs (0.307 ± 0.051) ng/L; in Self withdrawal group, ET-1 decreased as (60.795 ±7 .036) ng/L vs (170.511 ± 12.374) ng/L, all P<0.05; while NO levels were similar,P>0.05. After treatment, ET-1 level in Varenicline group (33.950 ± 1.439) ng/L was lower than Self withdrawal group (60.795 ± 7.036) ng/L and IL-6 level in Varenicline group (0.103 ± 0.020) ng/L was also lower than Self withdrawal group (0.258 ± 0.042) ng/L, allP<0.05; while NO levels were similar between 2 groups,P>0.05.
Conclusion: Compared with self withdrawal, varenicline tartrate may effectively inhibit inlfammatory factor releasing in ACS patients with nicotine dependence, and therefore improve the vascular endothelial function.