Hot-melt extrusion technology was used to prepare solid dispersion of posaconazole for improving its dissolution. Solubility parameter, glass transition temperature and melting method were utilized to screen polymers. Using KollidonVA64, Soluplus, Eudragit L100 and combined carrier KollidonVA64-Eudragit L100 as polymer carrier, solid dispersion was prepared by hot-melt extrusion technology and characterized by drug dissolution. The formulation and process factor affecting dissolution were studied. The state of posaconazole in solid dispersion was characterized by differential scanning calorimetry and preliminary analysis of the stability was studied by influencing factors experiments. When using KollidonVA64-Eudragit L100(2 ∶8)as the carrier, 10 % triethyl citrate as the plasticizer and extrusion temperature of 150 °C, the dissolution of posaconazole was improved significantly. Drug was molecular or amorphous form in the carrier. Proportion of Eudragit L100 and KollidonVA64, temperature, drug loading and plasticizer influenced dissolution of posaconazole. Solid dispersion was stable for high temperature and strong light but sensitive to high humidity. Solid dispersion using hot-melt extrusion technology can significantly improve the dissolution of posaconazole.

To investigate the relationship between the plasma biomarker proteins and the states of Zang-Fu organs in patients with phlegm or blood stagnation syndromes due to hyperlipidemia and atherosclerosis.

Objective:To explore the risk factors for poor prognosis in patients with tuberculous meningitis (TBM), and establish their nomogram predictive models.Methods:Three hundred and fifty-eight patients with TBM, admitted to Department of Neurology, 940 th Hospital of Chinese People's Liberation Army Joint Logistic Support Force from January 2010 to February 2022, were chosen and divided into model group ( n=287) and validation group ( n=71) according to the simple random sampling at a ratio of 8:2. Their clinical data were retrospectively analyzed. Independent risk factors for poor prognosis of TBM were analyzed by least absolute shrinkage and selection operator (LASSO) and Logistic regression, and the risk factors were visualized by nomogram. Bootstrap method was used for 1 000 repeated samples for internal verification, and data from validation group were used for external verification. The discrimination and calibration of the models were evaluated by area under receiver operating characteristic (ROC) curve, calibration curve and Hosmer-Lemeshow goodness of fit test. Results:Multivariate Logistic regression analysis showed that mental symptoms ( OR=3.593, 95% CI: 1.790-7.211, P<0.001), limb weakness ( OR=3.087, 95% CI: 1.551-6.144, P=0.001), pulmonary infection ( OR=5.162, 95% CI: 2.373-11.227, P<0.001), improved British Medical Research Council (mBMRC) staging II ( OR=4.291, 95% CI: 2.037-9.039, P<0.001), mBMRC staging III ( OR=13.073, 95% CI: 3.352-50.975, P<0.001) were independent risk factors for poor prognosis in TBM patients. Consistency indexes indicated by area under ROC curves by internal verification and external verification were 0.880 and 0.823, respectively; the calibration curve coincided with the ideal curve, enjoying good Hosmer-Lemeshow fit ( P=0.546, P=0.401). Conclusion:Based on these 4 prognostic factors (mental symptoms, limb weakness, lung infection and mBMRC stages), the nomogram is helpful in predicting the risk of poor prognosis in TBM patients.

Objective This study investigated whether gut microbiota and its metabolites are altered in myasthenia gravis(MG)patients.Methods We collected fresh stool specimens from MG patients and healthy controls.16S rRNA gene sequencing and gas chromatography-mass spectrometry were used to measure abundance of gut microbiota and metabolite levels in two groups,respectively.Clinical data of the subjects were also collected including quantitative MG score(QMGS),MG-activities of daily living(MG-ADL),MG-specific quality-of-life 15(MG-QOL15),manual muscle testing(MMT),and the acetylcholine receptor antibody(AchR-Ab)titers.The correlation between the differential microbiota and the clinical characteristics was investigated.Results A total of 50 MG patients and 15 healthy controls were recruited.Simpson's index was significantly higher in the MG group(0.936±0.041)than in the control group(0.888±0.123).Alpha diversity was significantly decreased in the MG group(t=2.349,P=0.022).There was a significant difference in microbial phenotype between the two groups(R=0.966,P=0.001,Adonis).The results of LEfSe showed that the abundance of Esherichia-Shigella,Succinivibrio,Fusobacterium,and Ruminococcus-gnavus-group were up-regulated while the abundance of Lachnospira,Roseburia,Desulfovibrio,and Coprococcus were down-regulated.The results showed that the metabolites of the MG group were significantly different from those of the control group.There were 28 metabolites up-regulated and 71 metabolites down-regulated in the MG patient group.Kyoto Encyclopedia of Genes and Genomes analyses demonstrated that the majority of metabolic pathways in which differential metabolites were involved were related to amino acid metabolism and nucleotide metabolism.61.2% (30/49)of bacterial amplicon sequence variant(ASV)were significantly associated with multiple metabolites(P<0.001).The relative abundance of Lachnospiraceae in the group with MG was negatively correlated with the QMGS(r=-0.496,P<0.001),MG-ADL(r=-0.542,P<0.001),MG-QOL15(r=-0.464,P=0.007),and the AchR-Ab(r=-0.315,P=0.026).The relative abundance of Lachnospiraceae in the group with MG was positively correlated with the MMT(r=0.374,P=0.008).Conclusion The intestinal flora of MG patients is down-regulated in the abundance of beneficial bacteria and up-regulated in the abundances of harmful bacteria.Disturbance of metabolites are also present in MG patients.Regulating gut microbiota in MG patients may be a new target for treating the disease.