OBJECTIVE:To develop a method for concentration determination of voriconazole in human plasma and apply it in the clinic. METHODS:UPLC-MS/MS method was adopted. Using ketoconazole as internal standard,the determination was per-formed on Shim-pack VP-ODS column with mobile phase consisted of water(containing 1‰ formic acid and 2 mmol/L ammonium acetate)-acetonitrile(gradient elution)at flow rate of 0.3 ml/min and column temperature of 40℃.The electrospray ion source,pos-itive ionizing pattern and multiple reaction monitoring were used;the mass transition ion-pairs of voriconazole and internal standard were m/z 351.2→282.2 and m/z 532.1→490.2. RESULTS:The linear range of voriconazole were 1-10 000 ng/ml (r=0.999 5,n=5),and the limit of quantitation was 1 ng/ml;RSDs of inter-day and intra-day were all lower than 10%;method recovery was higher than 90%(RSD<8%),and extraction recovery was higher than 70%(RSD<8%). The plasma concentrations of voriconazole in 10 patients with invasive fungal infection determined by this method were 507.33-7 011.24 ng/ml,and those of 3 patients were outside the recommended treatment concentration range. CONCLUSIONS:The established method is fast,accurate and sensitive,and can be applied for the therapeutic drug monitoring of voriconazole.

Objective To explore the change of the total level of lgE and specific allergen for acute exacerbation of bronchial asthma and to offer evidence for the prevention and cure of acute exacerbation of bronchial asthma.Methods The usual inhalant and ingested antigens were chosen in asthma patients,and the allergens were detected by ELISA in sera of acute exacerbation of bronchial asthma patients.Results Total positive rate of lgE was 92％ (48/52),dust mites 61.2％ (25/52),house dust 17％ (9/52),shrimp and crab 15％ (8/52),mould 9％ (5/52).Conclusion The main allergen of acute asthma exacerbation is dust mites.House dust,shrimp and crab,and mould folloo.The rats of pollen or weed are very low.

Objective To explore the clinical characteristics of Chronic obstructive pulmonary diseases(COPD)(≥65 years old,acute episode)with active pulmonary tuberculosis.Methods62 of COPD(≥65 years old,acute episode)with active pulmonary tuberculosis from 2002 to 2007 in hospital were reviewed and analyzed.ResultsThe attack rate of active pulmonary tuberculosis is 7.3% in COPD(≥65 years old,acute episode).By Clinical analysis showed clinical manifestation and chest X-ray or CT were not typical,but positive morbility of acid-fast bacilli sputum smear and bronchoalveolar lavage fluid was higher.ConclusionThe result suggests that COPD(≥65 years old,acute episode)patients are high-risk group of active pulmonary tuberculosis and need to be diagnosed early as soon as possible.

A variety of opportunistic infections can occur in the late-stage of HIV-1 infection,Mycobacterium avium complex (MAC) infection is a common cause of disseminated bacterial infection. Since the advent of highly active antiretroviral therapy (HAART),the rate of MAC infection has declined substantially,but there is risk in individuals with low CD4 cell counts. This article describes the epidemiological,clinical,therapeutic and preventive aspects of MAC infection in HIV-sero-positive individuals.

Transforming growth factor-β(TGF-β), a member of the TGF-β superfamily, plays a role in multiple biological processes, including cell proliferation, differentiation, migration and tissue fibrosis, etc. Normally, TGF-βs widely express in normal tissues and most cell lines, such as macrophages and dendritic cells, But in pathological conditions, Cancer cells and cancer-associated fibroblasts also produce and secrete TGF-β. Scirrhous gastric cancer (SGC) is a special subtype of gastric cancer with rapid development, frequent peritoneal implantation, and accompanied by significant interstitial fibrosis deposition. these biological behavior characteristics all suggest that its occurrence and development are closely related to TGF-β expression, and TGF-β is considered to be associated with poor prognosis of the SGC. The use of antibodies and inhibitors of TGF-β and its signaling pathways can reduce the invasiveness of cancer cells and improve the prognosis of SGC patients. This paper reviews the expression and significance of TGF-β in SGC.

Objective To establish the early warning model based on the control chart method for hand,foot and mouth disease (HFMD) in Wuchang District and to determine the optimum alarming threshold to provide the data support for HFMD monitoring work.Methods The data of HFMD in Wuchang District during 2009-2014 were collected from the National Infectious Diseases Notification System for constructing the data base.The mobile percentile method was adopted to establish the early alarming model,which was evaluated by the screening test.The sensitivity,specificity,positive predictive value and negative predictive value were calculated.Then the receiver operating characteristic (ROC) curve was drawn and the optimum alarming threshold was found out.Results The early alarming threshold of HFMD in Wuchang District was P90,its sensitivity,specificity,positive predictive value and negative predictive value were 75.00％,93.88％,50.00％ and 97.87％,respectively.Conclusion Determining the early warning threshold should be optimized according to onset characteristics combining with the local epidemic situation,which pays attention to regional specificity and increases the monitoring ability of infectious diseases.

Objective To explore the effects of baicalin in the treatment of a preeclampsia (PE) rat model by detecting the expression of X-linked inhibitor of apoptosis protein (XIAP) and cysteine containing aspartate-9 (Caspase-9) and observing the ultrastructure of mitochondria in trophoblast cells.Methods Forty-eight pregnant Wistar rats were randomly divided into two groups:12 in the control group and 36 in the PE model group.The PE model was established with subcutaneous injection of l-nitro arginine methyl ester with 100 mg/kg per day from the 13th day of pregnancy.Beginning from the 16th day of pregnancy,the PE rats were injected with different doses of baicalin till cesarean section,and divided into three groups:non-intervention PE model group treated with saline (NIP group),low-dose baicalin intervention group (IDB group) at 50 mg/kg per day,and high-dose baicalin intervention group (HDB group) at 100 mg/kg per day.The rat tail artery blood pressure and 24-h urine protein level were measured at pregnant day 10,16 and 20.The levels of XIAP and Caspase-9 in placenta were measured by immunohistochemistry.The ultrastructure of mitochondria of trophoblast cells of the rat placenta was observed under electron microscope.T test,F test and LSD-t test were applied for statistical analysis.Results (1) On pregnant day 10,no significant differences were observed in rat tail artery systolic blood pressure,diastolic blood pressure and 24-h urine protein level between the control group and PE model group (all P＞0.05).On pregnant day 16 and 20,the systolic blood pressure,diastolic blood pressure and 24-h urine protein level of NIP,IDB and HDB groups were significantly higher than those of control group [pregnant day 16:systolic blood pressure:(137.74±5.21),(136.15±4.86),(138.28±4.79) and (110.57±3.79) mmHg (1 mmHg=0.133 kPa),diastolic blood pressure:(89.58 ± 5.50),(88.45 ± 8.59),(89.42 ± 6.29) and (80.28 ± 7.36) mmHg,24-h urine protein:(7.78 ± 0.45),(7.53 ± 0.54),(7.86± 0.57) and (6.45 ± 0.56) mg;pregnant day 20:systolic blood pressure:(145.26 ± 4.67),(131.28 ± 4.34),(130.93 ± 5.33) and (110.40 ± 6.92) mmHg,diastolic blood pressure:(89.87±6.55),(85.34±7.33),(84.64±7.36) and (80.19±7.34) mmHg,24-h urine protein:(11.18±0.42),(9.65±0.54),(9.06±0.56) and (6.31 ±0.45) mg] (all P＜0.01).On pregnant day 20,the systolic and diastolic blood pressure and 24-h urine protein level in IDB and HDB groups were significantly lower than in NIP group (all P＜0.05),but showed no significant differences between IDB and HDB groups (allP＞0.05).(2) Compared with NIP group,the expression of XIAP in control group,IDB and HDB groups were significantly increased(210.39±0.78,180.56±0.82,195.36±0.96 and 192.84± 1.06,all P＜0.01).There was no significant difference in the expression of XIAP between IDB and HDB groups (P=0.66).The expression of Caspase-9 in control group,IDB and HDB groups were significantly decreased compared with NIP group (210.36±0.55,195.53±0.96,198.42± 1.01 and 185.25±0.64,all P＜0.01).There was no significant difference in the expression of Caspase-9 between IDB and HDB groups (P=0.65).Ultrastructure of mitochondria in NIP group showed different degrees of damage,matrix swelling,and mitochondrial cristae bresk or disappearance.In IDB group,mitochondrial matrix swelling was not obvious,and mitochondrial cristae were visible.In HDB group,mitochondrial cristae were neat and clear.Conclusions Baicalin may play an important role in the treatment of preeclampsia by reversing the trophoblast apoptosis and improving the ultrastructure of mitochondria through its regulation of XIAP expression and downregulation of Caspase-9 expression.

OBJECTIVE:To explore the potential correlation between clinical efficacy of pemetrexed in the treatment of ad-vanced breast cancer and TS mRNA expression. METHODS:Patients with advanced breast cancer were recruited in our study. Three cycles of pemetrexed was given to these patients,TS mRNA expression of their tumor tissues were detected. The relationship of ther-apeutic efficacies of different chemotherapy with TS mRNA expression were observed and compared during the study period. RE-SULTS:58 patients received pemetrexed chemotherapy and therapeutic efficacies of them were evaluated. One patient (1.7%) had complete response,19 patients(32.8%)had partial response,31 patients(53.4%)had stable response and 7 patients(12.1%)has progressive disease. Objective response rate was 34.5%,and disease control rate was 87.9%. TS mRNA expression level of 55 pa-tients with completed TS mRNA expression analysis varied from 0.04 to 5.11,with a median of 0.62. Mann-Whitney rank test showed that,responders had lower TS mRNA expression than nonsponders at all visits,there was statistical significance (P<0.05). Chi-square test showed that patients with low expression level of baseline(before chemotherapy)TS mRNA had significantly higher objective response rate(63.3%)than those with high expression(36.7%),there was statistical significance(P<0.05). CON-CLUSIONS:TS mRNA expression level is related to therapeutic efficacy of pemetrexed,which may be useful for predicting thera-peutic efficacy of pemetrexed therapy in patients with advanced breast cancer.

Objective To explore the clinical curative effect of hollow screw internal fixation for the treatment of distal epiphyseal teenagers tibial fracture.Methods Thirty -nine cases of epiphyseal fractures of the distal tibia were treated in Shanghai Children′s Hospital between February 2005 and September 201 4.This study included 24 boys and 1 5 girls with the average age of 1 3.1 years (ranged 1 0.5 to 1 6.2 years old).Preoperative diagnosis was confirmed by the X -ray films or CT examination.All the cases were closed fractures and manipulative reduction all failed.Surgi-cal reduction was performed when plain radiographs showed the fracture gap of epiphysis board and articular surface were greater than 2 mm or after closed reduction.Under C -arm X -ray machine,ankle axial traction was performed initially.Anatomical reduction underwent according to the bone fracture type.The fractures were fixed with cannulated screws by percutaneous or open approach.Postoperative X -ray or CT confirmed anatomical reduction at articular sur-face and growth plate.All patients had been immobilized with short -leg cast for 4 -6 weeks.The ankle joint function and growth were evaluated by means of American Orthopaedic Foot and Ankle Society(AOFAS)Ankle Hindfoot Scale. Results All patients were followed up for 5 to 91 months with an average duration of 35 months.X -ray films showed that all fractures were bone healing.No uneven articular surface was found and there was no extremity rotation and shorte-ning deformity.Results were evaluated by AOFAS scoring system:excellent in 27 cases,good in 10 cases,and general in 2 cases.All patients were able to participate in the normal physical activities.Conclusions CT with multiplanar recon-struction is a premise to make an accurate diagnosis and to choose a reasonable approach.For failed closed reduction for adolescent distal tibial epiphyseal fractures,the cannulated screws are simple and may have a satisfactory effect.

Objective:To observe therapeutic effect of lyophilized recombinant human brain natriuretic peptide (Lrh-BNP)on stress cardiomyopathy (SCM)complicated acute bump failure.Methods:A total of 23 patients with SCM complicated acute bump failure were randomly divided into routine treatment group (n=10,received routine treatment)and Lrh-BNP group (n=13,received Lrh-BNP based on routine treatment).Clinical symptoms and signs,cardiac function :left ventricular ejection fraction (LVEF),stroke volume (SV),cardiac index (CI),peak early diastolic velocity/peak late diastolic velocity (E/A)assessed by echocardiography before and after treatment, and total effective rate were compared between two group.Results:Total effective rate of Lrh-BNP group was sig- nificantly higher than that of routine treatment group (92.3% vs.80.0% ,P<0.05).There were no significant difference in cardiac function indexes between two groups before treatment (P>0.05 all);after treatment,com- pared with routine treatment group,there were significant rise in LVEF [(50.2±16.3)% vs.(59.4±14.1)%],SV [(39.5±10.4)ml vs.(48.3±12.5)ml],CI [(3.7±1.1)L min-1 m-2 vs.(4.6±1.4)L min-1 m-2 ]and E/A [(1.0±0.5)vs.(1.3±0.7)]in Lrh-BNP group,P<0.05 all.Conclusion:Lrh-BNP possesses significant thera- peutic effect on stress cardiomyopathy complicated acute left heart failure.