Injectable lipid emulsions have been routinely used in patients since 1960s as a nutritional supplement for patients requiring parenteral nutrition. In recent years, lipid injectable emulsions have been extensively studied as a kind of novel drug carrier, also the quality problems of the lipid emulsion attract more and more attentions gradually. Large diameter tail of injectable lipid emulsions as a significant quality control indicator should pay more attention. Regarding to the defect of detecting large diameter tail of lipid injectable emulsions in our country, the purpose of this article is to summarize the techniques of detecting large diameter tail, illustrate the impacts of large lipid droplet on the quality of lipid injectable emulsions, emphasize the importance of detecting large diameter tail in lipid emulsions and provide guidance for researching and developing lipid emulsions in domestic market.

OBJECTIVE:To evaluate the stability of 12 kinds of submicro emulsion in market,and screen the test method for the stability. METHODS:12 kinds of submicro emulsion in market were selected,high pressure sterilization (121 ℃,30 min), high speed centrifugation(4000 r/min,15 min),accelerated test [placing 6 months under temperature of(40±2)℃,relative hu-midity of (75 ± 5)%] were conducted to investigate the pH,particle size and other indexes,and SPSS 22.0 was used to analyze the distribution variance and chi-square test,and investigate the correlation of 3 evaluation methods. RESULTS:In terms of stabili-ty investigation,the pH value of 12 kinds of submicro emulsion decreased to some extent after accelerated test,average particle size of 6 kinds of submicro emulsion samples were greater than 300 nm,the variance of the particle size distribution of 9 kinds ap-peared in 0.05-0.15,the chi-square test results of 8 kinds distributed below 1. The average particle size of 4 kinds of submicro emul-sions changed more than 10 nm after accelerated test. In terms of stability test method,Pearson chi-square progressive significance of high pressure sterilization and accelerated test was 0.665,which was higher than 0.05,indicating there was no correlation (no significance),the stability results of high pressure sterilization can not represent the results of accelerated test;that of high speed centrifugation and accelerated test was 0.004,which was lower than 0.05,indicating stability results between high speed centrifuga-tion and accelerated test results were significantly correlated. CONCLUSIONS:The submicro emulsion in market can meet the re-quirements of stability. To a certain extent,high speed centrifugation can replace the acceleration test.

Bicyclol with benzyl alcohol structure, is a poorly water-soluble drug, used for the treatment of chronic hepatitis B. To increase the drug solubility and oral bioavailability, a Bicyclol-phospholipid complex was studied on its preparation, formation mechanism, and the influence on drug physicochemical properties and oral absorption. The complex was prepared by a solvent evaporation method. The optimal formulation was selected by orthogonal experimental design, and a reasonable evaluating method of the complexation rate was established. Various methods, such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and 31P nuclear magnetic resonance (31P-NMR), were used to explore the phase state and formation mechanism of the complex. The solubility of drug in complex was investigated in water/n-octanol. Preliminary study of its absorption and liver tissue distribution in rats was also carried out. The results showed that Bicyclol and phosphatidylcholine can be complexed entirely in the molar ratio 1 : 2. Bicyclol was dispersed in phospholipids as amorphous state. They were combined by intermolecular hydrogen bond due to charge transfer effect which occurred between the two polarities of the double bond between phosphorus and oxygen (P=O) of phosphatidylcholine and benzalcohol group of Bicyclol. The solubility of the complex compared to the active pharmaceutical ingredient (API) was effectively enhanced 5.75 times in water and 7.72 times in n-octanol, separately. In addition, drug concentrations were also enhanced 43 times in plasma and 13 times in liver with one hour after administering the complex to rats via oral gavage. All of these indicated that Bicyclol with benzalcohol group can interact with phospholipids to form complex, improving drug's physicochemical properties, thus further increasing its absorption and target tissue distribution. This study also provided theoretical reference for the research of other benzalcohol derivatives complexed with phospholipids.

OBJECTIVE:To establish a method for the separation and detection of related substances in baicalein,identify its structure and preliminarily explore the degradation mechanism. METHODS:HPLC was adopted to detect the baicalein,related impurities and forced destruction of degradation products in synthesis process:the column was ES Industries? FluoroSep-RP Phenyl with mobile phase of 0.3%formic acid-methanol-acetonitrile(gradient elution)at a flow rate of 1.0 mL/min,the detection wavelength was 275 nm,the column temperature was 10℃,and the injection volume was 10μL. LC-MS/MS was conducted to identify the related substances and conjecture degradation mechanism:the column was ES Industries? FluoroSep-RP Phenyl with mobile phase of 0.3%formic acid- methanol (gradient elution)at a flow rate of 1.0 mL/min,the detection wavelength was 275 nm,column temperature was 10℃,and the injection volume was 10μL;ion source was electrospray ion source,positive and negative ions,nebulizer pressure was 55 psi and the drying gas flow was 11 L/min,drying gas temperature was 350℃,capillary voltage was 4.0 kV,detection modes were full-scan first-order MS and selective ion full-scan second-order MS,scan ranges were m/z 100-1000 (first-order MS) and 50-500(second-order MS),ionization voltage was 80-135 eV,and the collision energy was 10-30 eV. RESULTS:The linear range of baicalein was 2.4-480μg/mL(r=0.9999);RSDs of precision,stability and reproducibility tests were lower than 2.0%;the limit of quantitation was 7.2 ng,the limit of detection was 2.4 ng. Baicalein was well separated with related substance and 3 major degradation products,the related substance was chemical synthesis precursor wood butterfly;the degradation products were 6,7-quinone derivatives and 7,8-quinone derivatives,which were isomers;oxidative degradation products were benzoic acid phenyl ester derivatives. CONCLUSIONS:The main mechanisms of alkali degradation and oxidative degradation of baicalein include pyran, reciprocal rearrangement and oxidation reaction;the established method is specific and sensitive,and can be used for the detection of related substances in baicalein.

The surface solid dispersion of honokiol was prepared by melting method with croscarmellose sodium as carrier to improve the dissolution rate of honokiol, taking the advantage of its low melting point. The dissolution rate and stability test of surface solid dispersion of honokiol were carried out. Its physical properties were then investigated by DSC, PXRD and SEM analysis. The results indicated that the dissolution rate of honokiol from sodium solid dispersion was more than 90% at 15 min while its mean dissolution time was significantly decreased. Honokiol was distributed on the surface of croscarmellose sodium in the form of microcrystal; moreover, its dissolution behavior didn′t change significantly after six months of stability tests. Therefore, surface solid dispersion of honokionl could be prepared by simple process. The formed solid dispersion achieved high drug loading and fast in vitro dissolution rate, which could provide a novel idea for developing solid preparations of honokiol.

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b.Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases.It is involved in regulating the pathological process of myocardial infarction,myocardial ischemia/reperfusion injury,cardiac hypertrophy,atrial fibrillation,diabetic cardiomyopathy,atherosclerosis,pulmonary hyperten-sion,cerebral ischemia/reperfusion injury,Parkinson's disease,and Alzheimer's disease.Obviously,miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases.However,the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed.Therefore,in this review,we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases.Drugs targeting miR-135b for the treatment of diseases and related patents,highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases,have been discussed.

OBJECTIVETo observe the therapeutic effect of Guben Xiaoliu Capsule (GXC) in treating advanced stage non-small cell lung cancer (NSCLC).

METHODSOne hundred and ninety-eight NSCLC in-patients were divided into the integrative treated group [Group A, 54 patients treated with chemotherapy (CT) plus GXC], the TCM treated group (Group B, 96 patients treated with GXC alone) and the chemotherapeutic group (Group C, 48 patients treated with CT alone). Randomized controlled observation was applied to the Group A and C. The clinical effect, quality of life (QOL), adverse reaction and survival period in the three groups were observed.

RESULTSThe immediate effective rate (CR + PR) in the Group A, B and C was 16.7%, 3.1% and 8.3%, respectively, in the Group A, it was better than that in the other two groups (P < 0.05). The improvement of clinical symptoms and QOL in the Group A and B were superior to those in the Group C (P < 0.05). The median survival rate in the three groups was 12, 15 and 9 months, respectively, the 1-, 2- and 3-year survival rate in Group A being 57.4%, 11.1% and 3.7%, respectively, in Group B, 67.7%, 9.4% and 3.1%, and in (Group C, 39.6%, 4.2% and 0, respectively, comparison between the three groups showed that the survival rates in the former two were higher than those in Group C (P < 0.05). Moreover, the incidence rate and degree of CT toxicity were milder in Group A than those in Group C (P < 0.05).

CONCLUSIONGXC has definite effect in treating NSCLC, it could raise the QOL, prolong the survival period of patients, also reduce the toxicity and enhance the efficacy of CT.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Capsules ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; mortality ; Cisplatin ; administration & dosage ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; mortality ; Male ; Middle Aged ; Mitomycins ; administration & dosage ; Phytotherapy ; Quality of Life ; Survival Analysis ; Survival Rate ; Vinblastine ; administration & dosage

Objective To analyze the changes in lung function and inflammatory indicators such as eosino-phils(EOS),Creola bodies and exhaled nitric oxide(FeNO),and to explore their value in early diagnosing asthma. Methods One hundred and thirty-five infants with high-risk asthma were selected as an observation group who were admitted to Department of Respiratory,Childrenˊs Hospital of Soochow University from April 2016 to August 2017 due to asthmatic bronchitis and asthmatic bronchopneumonia,and a total of 200 non -asthmatic and non -allergic healthy children who were screened and followed up at the Department of Cardiology in the same period were selected as a healthy control group for the measurement of moist respiratory lung function and FeNO. In the observation group,the bronchial dilation test(BDT),EOS and Creola bodies were performed simultaneously. Classification of lung function:23%≤time to peak ratio(TPTEF/Te)<28% had mild obstruction,15%≤TPTEF/Te<23% had moderate obstruc-tion,and TPTEF/Te<15% showed severe obstruction. Results The TPTEF/Te[17. 20%(8. 10%)],volume to peak ratio(VPEF/Ve)[21. 20%(6. 20%)],tidal volume per kilogram of body weight(VT/kg)[7. 80(3. 70)]and ratio of tidal expiratory flow 25% to peak tidal expiratory flow(25/PF)[0. 54(0. 20)]in the observation group were signifi-cantly lower than those in the healthy control group[22. 30%(9. 22%),27. 15%(7. 10%),8. 90(3. 17),0. 60 (0. 18)],and the differences were statistically significant(Z＝ -6. 81,-9. 35,-3. 16,-3. 52,all P<0. 05). BDT positive rate in the mild obstruction group was 20. 00%(3/15 cases),BDT positive rate in the moderate obstruction group was 26. 56%(17/64 cases),and BDT positive rate in the severe obstruction group was 48. 72%(19/39 cases). The higher the degree of obstruction,the higher the value of BDT positive diagnosis(F＝6. 353,P<0. 05). BDT of VPEF/Ve,25/PF and TPTEF/Te were consistent and statistically significant(Kappa＝0. 78,0. 49,all P<0. 001). Ti-dal expiratory flow 50% -remaining(TEF50% -r)[(117. 86 ± 42. 16)mL/s],tidal expiratory flow 25% -remai- ning(TEF25% -r)[(82. 82 ± 35. 44)mL/s]in the second wheezing group were higher than those in the first whee-zing group[(92. 81 ± 28. 40)mL/s,(65. 22 ± 24. 93)mL/s],and the differences were statistically significant( t＝3. 34,2. 77,all P <0. 05). There was no statistically significant difference in sputum EOS,FeNO and Creola body scores among wheezing children between the first and second groups(all P>0. 05). FeNO in the observation group [3. 80(5. 43)μg/L]was significantly lower than that in the healthy control group[9. 60(11. 3)μg/L],and the diffe-rence was statistically significant(Z＝14. 56,P<0. 05). Sputum EOS had a positive correlation with blood EOS and Creola bodies(r＝0. 20,0. 21,all P<0. 05);there was no correlation between lung function parameters and inflamma-tory indices(all P>0. 05). Conclusions In the acute phase of infant asthma attack,the pulmonary function presents different degrees of obstructive ventilation dysfunction,the higher the degree of obstruction,the higher the diagnostic value of BDT. The value of single FeNO measurement is limited,and continuous dynamic monitoring may be more mea-ningful in predicting the occurrence of asthma. Detection of Creola bodies may be helpful in predicting asthma.

Objective To identify M1 macrophage-related genes in rejection after kidney transplantation and construct a risk prediction model for renal allograft survival. Methods GSE36059 and GSE21374 datasets after kidney transplantation were downloaded from Gene Expression Omnibus (GEO) database. GSE36059 dataset included the samples from the recipients with rejection and stable allografts. Using this dataset, weighted gene co-expression network analysis (WGCNA) and differential analysis were conducted to screen the M1 macrophage-related differentially expressed gene (M1-DEG). Then, GSE21374 dataset (including the follow-up data of graft loss) was divided into the training set and validation set according to a ratio of 7∶3. In the training set, a multivariate Cox's model was constructed using the variables screened by least absolute shrinkage and selection operator (LASSO), and the ability of this model to predict allograft survival was evaluated. CIBERSORT was employed to analyze the differences of infiltrated immune cells between the high-risk group and low-risk group, and the distribution of human leukocyte antigen (HLA)-related genes was analyzed between two groups. Gene set enrichment analysis (GSEA) was used to further clarify the biological process and pathway enrichment in the high-risk group. Finally, the database was employed to predict the microRNA (miRNA) interacting with the prognostic genes. Results In the GSE36059 dataset, 14 M1-DEG were screened. In the GSE21374 dataset, Toll-like receptor 8 (TLR8), Fc gamma receptor 1B (FCGR1B), BCL2 related protein A1 (BCL2A1), cathepsin S (CTSS), guanylate binding protein 2(GBP2) and caspase recruitment domain family member 16 (CARD16) were screened by LASSO-Cox regression analysis, and a multivariate Cox's model was constructed based on these 6 M1-DEG. The area under curve (AUC) of receiver operating characteristic of this model for predicting the 1- and 3-year graft survival was 0.918 and 0.877 in the training set, and 0.765 and 0.736 in the validation set, respectively. Immune cell infiltration analysis showed that the infiltration of rest and activated CD4⁺ memory T cells, γδT cells and M1 macrophages were increased in the high-risk group (all P < 0.05). The expression level of HLA I gene was up-regulated in the high-risk group. GSEA analysis suggested that immune response and graft rejection were enriched in the high-risk group. CTSS interacted with 8 miRNA, BCL2A1 and GBP2 interacted with 3 miRNA, and FCGR1B interacted with 1 miRNA. Conclusions The prognostic risk model based on 6 M1-DEG has high performance in predicting graft survival, which may provide evidence for early interventions for high-risk recipients.

Objective:To explore the temporal distribution of high level of BK virus(BKV) viruria after kidney transplantation(KT)and the association of high level of viruria with clinical factors and specific human leukocyte antigen(HLA)sites in donors and recipients.Methods:From January 1, 2017 to December 31, 2019, clinical data were retrospectively reviewed for 212 recipients of cadaveric KT.A high level of urinary BKV viruria was defined as urinary BKV-DNA quantification>10 7(copies/ml)after KT while 212 recipients with the same gender composition below the threshold during the same period were selected as low-level controls.Clinical data and HLA sites of two groups were statistically analyzed and risk factors for high level of viruria screened by univariate and multifactorial Logistic regressions. Results:The median time to initial high-level BKV infection in urine after RT was 125.5 days.Based upon univariate Logistic analysis, delayed graft function(DGF)and HLA-A24 of recipient were risk factors for high-level BKV infection in urine while HLA-DQ9 of donor acted as a protective factor.Through multivariate Logistic analysis, DGF( OR=2.18, 95% CI 1.18~4.01, P=0.012)and HLA-A24( OR=1.63, 95% CI 1.06~2.53, P=0.027)of recipient were independent risk factors for high-level BKV infection in urine.And HLA-DQ9 of donors( OR=0.58, 95% CI 0.36~0.91, P=0.019)was an independent protective factor. Conclusions:High level of BKV viruria after RT is associated with donor/recipient-specific HLA sites.Early risk factor stratification and protective factors of recipients can aid in tailoring postoperative immunosuppression and screening program and developing T cell-associated vaccines.