To evaluate the diagnostic value of heterologous serum antibody for tuberculosis ,we detected the serum spec-imens from 102 patients with tuberculosis (included 73 pulmonary TB and 29 extrapulmonary TB) ,223 patients with other re-spiratory diseases and 100 healthy people were enrolled into the study .Results of clinical diagnosis as the golden standard were used to evaluate sensitivity and specificity of the tuberculosis antibody .Tuberculosis antibody (IgG/IgM ) ,sputum bacterial culture and sputum smear were used to test M .tuberculosis infection parallelly .Results were compared by chi-square test .Re-sults showed that the sensitivity and specificity of IgG/IgM tuberculosis antibodies in diagnosis of tuberculosis were respectively 74 .51% and 91 .64% .The sensitivity of IgG/IgM tuberculosis antibodies in diagnosis of pulmonary and extrapulmonary tuber-culosis were respectively 82 .19% and 55 .17% ,which were significant differences between the positive detection rate of pulmo-nary tuberculosis and extrapulmonary tuberculosis (P>0 .05) .The positive rate of IgG/IgM tuberculosis antibodies was higher than those in sputum culture and sputum smear (P＜0 .05) .A total of 102 cases of tuberculosis in patients in different age groups were analyzed ,and the positive detection rate of children and elderly group were 58 .33% and 36% ,respectively ,which were far below the rate in the youth group (96 .15% ) and the middle-aged group (89 .74% ) .The chi-square value for the differences in age group in the sensitivity of IgG/IgM tuberculosis antibodies was significant difference (P＜0 .05) .Six out of 425 cases of specimens were found as M .intracellulare ,and 2 as M .abscessus .However ,the IgG/IgM tuberculosis antibodies were negative in diagnosis of non-tuberculous mycobacteria .Antibody (IgG/IgM ) is sensitive ,rapid ,convenient ,and easy to manipulate the screening of tuberculosis .

Objective:To establish an LC–MS/MS method for the determination of the active metabolite(SN-38) and secondary metabolite(SN-38G) of irinotecan in rat liver microsomes incubation system, and optimize the incubation conditions. Methods:Meth-anol was selected to precipitate protein in the samples, and then the concentrations were analyzed by LC–MS/MS. All the separation was carried out on a ZORBAX Eclipse XDB-C18 column(2. 1 mm × 50 mm, 3. 5 μm) with the mobile phase of acetonitrile – water (containing 0. 1% formic acid) (23 :77) at a flow rate of 0. 3 ml·min-1. The mass spectrometer was operated with multiple reac-tions monitoring ( MRM) using electrospray ionization ( ESI) . The incubation conditions were optimized by single factor design. Re-sults:SN-38 and SN-38G showed a good linearity ( r≥0. 9972) respectively within the range of 2. 3-920 ng·ml-1 and 2. 5-1000 ng ·ml-1. The intra-and inter-day RSD was below 14. 6%(n=6). The average recovery was within the range of 74. 1%-123. 4% with RSD below 13. 5% (n=6). The optimal incubation conditions were as follows:the concentration of liver microsomal protein was 0. 3 mg·ml-1 and the incubation time was 30 min. Conclusion:The method is rapid, sensitive and accurate in the quantification of SN-38 and SN-38G in the incubation system,which provides methodological basis for the activity determination of UGT1A1 enzyme in vitro.

OBJECTIVE:To establish physiological pharmacokinetic (PBPK) model of cefdinir in healthy volunteers,and to predict pharmacokinetic process of cefdinir in volunteers after oral administration. METHODS:Using“toubao dini”“cefdinir”“logP”“pKa”as keywords,related literatures about physico-chemical constants of cefdinir were retrieved from CNKI,ScienceDi-rect,PubMed and other databases;according to related guidelines and preliminary clinical trial plan of FDA,GastroPlusTM 8.6 soft-ware was used to establish PBPK model of oral administration of cefdinir;the effectiveness of the model was evaluated by multiple error. The model was used to simulate the absorption of cefdinir in the gastrointestinal tracts. The bioequivalence of test preparation and reference preparation were evaluated through single and population(n=500)simulation tests using cmax and AUC0-∞ of cefdinir reference preparation (capsule and granular formulation) as factors when release rate t85%=15 min (i.e. accumulatively released 85% within 15 min). RESULTS:The blood concentration-time curves of cefdinir predicted by PBPK model fitted well with mea-sured value(R2≥0.95);the pharmacokinetic parameters(cmax,tmax,AUC0-∞)were close to measured results,and the multiple er-rors were less than 2. After oral administration,cefdinir was mainly absorbed by the intestinal tract (45.6%),especially by seg-ment 1 of jejunum(14.8%);the absorption amount was significantly lower than the release amount of absorption site,and reached the maximal value(about 40%)within 4 h. The results of single simulation test showed that there was no statistical significance in cmax and AUC0-∞ between cefdinir test and reference preparations (P>0.05). The results of population simulation test showed that the relative bioavailability of cefdinir test particle and test capsule respectively were 99.01%-102.99% and 97.60%-105.90%;90%CI of cmax and AUC0-∞ values were within 80%-125% of reference preparation. CONCLUSIONS:The PBPK model is accurate and reliable in this study,can provide reference for pharmacokinetic study and bioequivalence evaluation of cefdinir preparations. Test preparation and reference preparation are equivalent.

Objective:To establish an HPLC-MS/MS method for the determination of vinblastine in rat plasma. Methods:Aceto-nitrile was used to precipitate protein in the samples after the addition of internal standard, and then the concentration was analyzed by HPLC/MS/MS. All the separations were carried out on an Ultimate C18 column (150 mm × 2. 1 mm, 5. 0 μm). The mobile phase was composed of acetonitrile and 10 mmol·L-1 ammoniumacetate (containing 0. 1% formic acid) (49 ∶51) and was pumped at a flow rate of 0. 3 ml·min-1 under 40 °C. The detection was performed with multiple reactions monitoring (MRM) using electrospray ioniza-tion (ESI). The precursor/product ion transitions were monitored at m/z 811. 4→m/z 224. 2 (positive ion mode) for vinblastine and m/z 825. 4→m/z 807. 4(positive ion mode) for internal standard vincristine. Results:Good linearity of vinblastine was obtained with-in the range of 0. 457-950 ng·ml-1(r=0. 997 1). The lower limit of quantification was 0. 457 ng·ml-1. The extraction recoveries were within the range of 89. 15%-95. 28%. The precision of intra-and inter-day was not more than 7. 95%. T1/2 of vinblastine in rats was (5. 86 ± 2. 37) h, and AUC(0-t) and AUC(0-∞) was (68. 45 ± 14. 51) and (95. 03 ± 33. 09)μg·L-1 ·h, respectively. Conclu-sion:The method is fast, sensitive and accurate, which provides research basis for the development of vinblastine and transporters re-search in medicine. The concentration of vinblastine in rats is low, and the half-life is long.

Objective To evaluate postprandial pharmacokinetics and bioequivalence of two preparations of cefdinir capsules in Chinese healthy volunteers. Methods In a two-way cross-over study, 24 healthy male volunteers were divided into two groups randomly and a single dose of cefdinir capsules of test and reference preparation were administered orally, respectively.The concentration in plasma was determined by LC-MS/MS. Pharmacokinetic parameters and bioequivalence were calculated and evaluated by DAS. Results The main pharmacokinetic parameters of test and reference were as follows: AUCt (4.35±1.09) μg??h??mL-1 and (4.12±1.22) μg??h??mL-1, AUC0-∞(4.53±1.12) and (4.53±1.73) μg??h??mL-1, t1/2 (1.74±0.29) h and (2.13±1.65) h, tmax(4.44±0.86) h and (4.54 ±1.16) h, Cmax(900±250) ng??mL-1 and (876±269) ng??mL-1 . Conclusion The test and reference preparation of cefdinir capsules are bioequivalent.

Little is known about the effects of chronic alcohol intake on the outcome of acute kidney injury (AKI). Hence, we examined the effects of chronic alcohol intake on the development of renal fibrosis following AKI in an animal model of bilateral renal ischemia–reperfusion (IR) injury. We first found that chronic alcohol exposure exacerbated bilateral IR-induced renal fibrosis and renal function impairment. This phenomenon was associated with increased bilateral IR-induced extracellular matrix deposition and an increased myofibroblast population as well as increased bilateral IR-induced expression of fibrosis-related genes in the kidneys. To explore the mechanisms underlying this phenomenon, we showed that chronic alcohol exposure enhanced β-arrestin 2 (Arrb2) expression and Akt and glycogen synthase kinase-3 (GSK3)β activation in the kidneys. Importantly, pharmacological GSK3 inhibition alleviated bilateral IR-induced renal fibrosis and renal function impairment. Furthermore, we demonstrated that Arrb2(−/−) mice exhibited resistance to IR-induced renal fibrosis and renal function impairment following chronic alcohol exposure, and these effects were associated with attenuated GSK3β activation in the kidneys. Taken together, our results suggest that chronic alcohol exposure may potentiate AKI via β-arrestin 2/Akt/GSK3β-mediated signaling in the kidney.
Acute Kidney Injury* ; Animals ; Extracellular Matrix ; Fibrosis ; Glycogen Synthase Kinase 3* ; Glycogen Synthase Kinases* ; Glycogen Synthase* ; Glycogen* ; Kidney ; Mice* ; Models, Animal ; Myofibroblasts

Objective To explore the prevalence and clinical characteristics of food allergy in bronchial asth-matic children less than 14 years old in China. Methods A case - controlled study was designed. The questionnaires were given to children,who were diagnosed to be asthmatic during the national epidemiological survey of asthma in chil-dren in 31 cities from September 2009 to August 2010. Non - asthmatic children,matched with the cases in age and gender,were selected during the same survey as control subjects if they were matched with the cases in age and sex. In-formation regarding the food allergen and symptom of food - induced anaphylaxis was analyzed. The difference in food allergy was compared between children with or without bronchial asthma. Results As a result,9235 asthmatic children and 11391 control subjects were enrolled in the case - control study. There were 14. 66％(1354 / 9235 cases)of the asthmatic children who had food allergy,compared to 3. 99％(455 / 11391 cases)of the non - asthmatics children, and the findings showed a significant difference (χ2 = 725. 25,P < 0. 001). The most common food allergens were fish and shrimp in both groups,and the difference was not significant [44. 09％ (597 / 1354 cases)vs. 42. 20％ (192 / 455 cases),χ2 = 0. 50,P > 0. 05]. The rate of peanut allergy was 4. 58％ (62 / 1354 cases)and 1. 54％ (7 / 455 cases) (χ2 = 8. 58,P < 0. 05),respectively. And the rates of fruit allergy in the asthmatic group and the non - asthmatic group were 14. 03％(190 / 1354 cases)and 27. 69％(126 / 455 cases)(χ2 = 44. 01,P < 0. 05),respectively. Cutaneous and nasal symptoms were common clinical manifestations. The rates of rash,pruritus,and swelling sympions were 47. 27％(640 / 1354 cases)and 61. 32％(279 / 455 cases)(χ2 = 26. 90,P < 0. 001),respectively for asthmatic group and non -asthmatic group. Rates of nasal symptoms were 17. 13％(232 / 1354 cases)and 10. 55％(48 / 455 cases)(χ2 = 11. 29, P = 0. 001),respectively in the asthmatic group and the non - asthmatic groups. Respiratory symptoms,such as cough and wheezing,were 25. 33％(343 / 1354 cases)and 5. 49％(25 / 455 cases)(χ2 = 80. 72,P < 0. 001)in 2 groups. Twenty cases of 1354 asthmatic children had severe food allergy,while such severe conditions occurred only 1 child without asthma (455 cases)occurred severe condition (1. 48％ vs. 0. 22％,χ2 = 4. 96,P < 0. 05). Conclusion The-rate of food allergen sensitization is highly prevalent in the children with asthma. Compared to those without asthma, and their types of food allergen and clinical symptoms are different from the latter.

Objective To compare the application of PCR-fluorescence probe, Bactec MGIT960 and Xpert MTB／RIF in diagnosis of tuberculosis from non-respiratory specimens.Methods Non-respiratory specimens from 225 patients with suspected tuberculosis admitted in Zhejiang Hospital of Integrated Chinese Medicine and Western Medicine from October 2017 to August 2018 were collected.There were 177 cases of tuberculosis and 48 cases of non-tuberculosis confirmed by clinical diagnosis.All specimens were tested with PCR-fluorescence probe, Xpert MTB／RIF and Bactec MGIT960.The clinical diagnostic results were used as the gold standard, and the receiver operating characteristic curve ( ROC) was drawn to evaluate the diagnostic values of three methods.The consistency of PCR-fluorescence probe method with Xpert MTB／RIF assay was analyzed.Results The sensitivity of PCR-fluorescent probe, Xpert MTB／RIF and Bactec MGIT960 in diagnosis of tuberculosis was 53.67%(95／177), 58.76%(104／177) and 31.07%(55／177), respectively.The sensitivity of PCR-fluorescent probe and Xpert MTB／RIF was higher than that of Bactec MGIT 960 culture ( χ2 ＝17.60 and 27.41, P＜0.01), while there was no significant difference between the PCR-fluorescent probe and the Xpert MTB／RIF (χ2 ＝0.93, P＞0.05).The specificity of three methods were 100.00%(48／48), 100.00%(48／48) and 97.92%(47／48), respectively (F＝1.83, P＞0.05).ROC curve analysis showed that the area under the ROC curve ( AUC) of PCR-fluorescent probe, Xpert MTB／RIF, and Bactec MGIT960 was 0.768, 0.794, and 0.645, respectively.The diagnostic value of PCR-fluorescent probe and Xpert MTB／RIF for tuberculosis was significantly higher than that of Bactec MGIT960 (Z＝5.19 and 6.52, P＜0.01); while Xpert MTB／RIF was superior to PCR-fluorescence probe (Z＝2.8, P＜0.05).In various types of specimens , there was no significant difference in the detection rate of tuberculosis between PCR-fluorescent probe method and Xpert MTB／RIF (χ2 ＝0.73, P＞0.05).The PCR-fluorescent probe and Xpert MTB／RIF had a good consistency (kappa＝0.829).Conclusion Xpert MTB／RIF is superior to PCR-fluorescence probe in the detection of tuberculosis in non-respiratory specimens such as tissues and pus, but the two have good consistency.The PCR-fluorescence probe method is economical and practical , and easy to promote, which has a high clinical application prospects.

Objective:To evaluate the diagnostic effects of Xpert MTB/RIF, Fluorescence PCR melting curve and gene chip technology for rapid screening of rifampicin-resistant tuberculosis.Methods:The clinical data of 150 patients diagnosed with tuberculosis by Bactec MGIT 960 liquid culture drug susceptibility in Zhejiang Chinese Medicine and Western Medicine Integrated Hospital from September 2016 to August 2019 were collected, including Xpert MTB/RIF and gene chip results. The isolated and cultured strains from patients were subjected to fluorescence PCR melting curve detection. Using Bactec MGIT 960 drug susceptibility results as the reference, the diagnostic efficacy of Xpert MTB/RIF, Fluorescence PCR melting curve and gene chip technology for rifampicin resistance were analyzed, and the receiver operating characteristic curve (ROC) was drawn for comparative analysis.Results:Take Bactec MGIT 960 as the gold standard, the sensitivity of Xpert MTB/RIF, Fluorescence PCR melting curve and gene chip technology for rifampicin resistance were 88.89% (16/18), 94.44% (17/18), 88.89% (16/18) respectively; the specificity were 96.21% (127/132), 96.21% (127/132), 95.45% (126/132), respectively. There was no statistically significant difference in the sensitivity and specificity among the three detection methods ( P>0.05). The Kappa values of the three molecular methods for detecting rifampicin resistance were 0.794, 0.827 and 0.770, respectively. The three detection methods have good diagnostic value for rifampicin resistance ( P<0.01), but there is no statistically significant difference between the three methods ( P>0.05). There were 8 cases of inconsistent results between the three methods and Bactec MGIT 960 drug sensitivity. Conclusion:Xpert MTB/RIF, Fluorescence PCR melting curve and gene chip technology have comparable ability to detect rifampicin resistance, all of these have high sensitivity and specificity for detecting rifampicin resistance and are suitable for rapid screening.

Objective:To explore the clinical application value of MRI-PDFF on different liver segments for the evaluation of non-alcoholic fatty liver disease (NAFLD).Methods:178 volunteers from March 2019 to February 2020 were included. PDFF values ??of all nine segments of the liver were measured using CSE3.0T MRI scan. The obtained average value was used to represent the average liver fat content. PDFF values of each or combined liver segment were equally compared with the average value to observe the representativeness of fat content. Receiver operating characteristic curve was used to analyze the diagnostic performance of each liver segment, and the Youden index was used to calculate the cutoff value. Paired-sample t-test or non-parametric Kruskal-Wallis test were used to compare measurement data among groups.Results:178 volunteers average liver fat content ranged from 0.89% to 42.61% with MRI-PDFF, and 71.35% (127/178) of the volunteers had PDFF > 5%. There was no significant difference between SIII, SIVb, SV, and SVIII liver segments when compared with the average value ( P > 0.05). PDFF values ??of SI, SII, and SIV a liver segments were all lower than the average value, while the PDFF values ??of SVI and SVII liver segments were all higher than the average value ( P ??< 0.05). MRI-PDFF sensitivity value for diagnosing liver steatosis of nine liver segments was 85.8% ~ 94.5%, and the specificity was higher than 96.0%. Among them, the SV liver segment had the highest sensitivity (94.5%), and the corresponding optimal diagnostic threshold value was 5.13%. Compared with single and combined liver segment, the PDFF value of SII, SV, SVI combined liver segment had the highest diagnostic performance for fatty liver, with the sensitivity and specificity of 96.9%, and 100%, respectively, and the corresponding optimal diagnostic threshold value was 5.17%. Conclusion:Compared with single and other combined liver segments, MRI-PDFF values of SII, SV, and SVI combined liver segments have higher sensitivity and specificity for the diagnosis of NAFLD, and it can be used as the first choice for the determination of liver fat content with MRI.