Ratio of procalcitonin/Simpson's dominance index predicted the short-term prognosis of patients with severe bacterial pneumonia.

Objective: The aim of this study was to explore the predictive value of the ratio of procalcitonin (PCT) in serum to Simpson's dominance index (SDI) in bronchoalveolar lavage fluid (BALF), in short-term prognosis of patients with severe bacterial pneumonia (SBP). Methods: This is a retrospective review of case materials of 110 patients with SBP who selected BALF metagenomic next-generation sequencing technique in the intensive care unit (ICU) of the Affiliated Hospital of Yangzhou University from January 2019 and July 2022. Based on the acute physiology and chronic health status score II, within 24 h after admission to the ICU, patients were divided into a non-critical group (n = 40) and a critical group (n = 70). Taking death caused by bacterial pneumonia as the endpoint event, the 28-day prognosis was recorded, and the patients were divided into a survival group (n = 76) and a death group (n = 34). The SDI, PCT, C-reactive protein (CRP), PCT/SDI, and CRP/SDI were compared and analyzed. Results: Compared with the non-critical group, the critical group had a higher PCT level, a greater PCT/SDI ratio, a longer ventilator-assisted ventilation time (VAVT), and more deaths in 28 days. Compared with the survivors, the death group had a higher PCT level, a lower SDI level, and a greater PCT/SDI ratio. The SDI level was significantly negatively correlated with the VAVT (r = -0.675, p < 0.05), while the PCT level, ratio of PCT/SDI, and ratio of CRP/SDI were remarkably positively correlated with VAVT (r = 0.669, 0.749, and 0.718, respectively, p < 0.05). The receiver operating characteristic (ROC) curves analysis showed that the area under ROC curves of PCT/SDI predicting patient death within 28 days was 0.851, followed by PCT + SDI, PCT, SDI, and CRP/SDI (0.845, 0.811, 0.778, and 0.720, respectively). The sensitivity and specificity of PCT/SDI for predicting death were 94.1% and 65.8%, respectively, at the optimal value (11.56). Cox regression analysis displayed that PCT/SDI (HR = 1.562; 95% CI: 1.271 to 1.920; p = 0.039) and PCT (HR = 1.148; 95% CI: 1.105 to 1.314; p = 0.015) were independent predictors of death in patients. Conclusion: The ratio of PCT/SDI was a more valuable marker in predicting the 28-day prognosis in patients with SBP.

Clinical characteristics of cognitive impairment and its related risk factors in post-stroke epilepsy

Objective: Post-stroke epilepsy (PSE) patients are prone to cognitive impairment (CI) due to multiple factors. This study aimed to assess clinical characteristics of CI and its related risk factors in newly diagnosed Chinese Han adult epilepsy patients with ischaemic stroke. Methods: Data were collected on PSE patients hospitalized in the neurology ward of the Affiliated Hospital of Yangzhou University, from January 2016 to May 2019. Newly diagnosed PSE patients were followed for six months; their cognitive functions were then assessed according to the Chinese Beijing version of the Montreal Scale (MoCA) and patients were divided into a PSE+CI group (MoCA scale score <26) (n=81) or PSE-CI group (MoCA scale score ≥26) (n=36). Data collection tools also included the Chinese versions of the Zheng Self-assessment Anxiety Scale, the Zheng Self-assessment Depression Scale, the Barthel index and the National Hospital Seizure Severity Scale. We compared the basic clinical characteristics between the two groups of patients and investigated the factors of CI in PSE patients. Results: In total, CI was present in 81 (69%) and absent in 36 (31%) PSE patients. MoCA total score in the PSE+CI group was 20.85±4.13 and 27.53±1.34 in the PSECI group. The Bonferroni corrected significance level was 0.0013. Scores for multiple cognitive domains (visuospatial/executive skills, naming, attention, language and delayed recall) were lower in the PSE+CI group than the PSE-CI group. Moreover, the PSE+CI group had a higher incidence of depression and anxiety. Univariate analysis showed that diabetes (p= 0.000) and the number of antiepileptic drugs (AEDs) (p= 0.001) were associated with CI in PSE. Binary logistic regression analysis showed that diabetes (odds ratio [OR]: 5.242, 95% confidence interval [CI]: 1.680-16.363, p= 0.004), high homocysteine levels (OR: 1.103, 95% CI: 1.008-1.207, p= 0.033) and the number of AEDs (OR: 3.354, 95% CI: 1.225-9.180, p= 0.019) were associated with CI in PSE. Significance: Diabetes, high homocysteine levels and a higher number of AEDs may be risk factors for CI in PSE.

Effects of ABCB1, UGT1A1, and UGT1A9 Genetic Polymorphisms on the Pharmacokinetics of Sitafloxacin Granules in Healthy Subjects.

Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single-dose and multidose cohorts and the effects of ABCB1, UGT1A1, and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single-dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high-fat meal. The multidose study included 1 cohort receiving 100 mg of sitafloxacin granules once daily for 5 days. PK parameters were calculated using noncompartmental parameters based on concentration-time data. The genotypes for ABCB1, UGT1A1, and UGT1A9 single-nucleotide polymorphisms were determined using Sanger sequencing. Subsequently, the association between sitafloxacin PK parameters and target single-nucleotide polymorphisms was analyzed. Sitafloxacin granules were well tolerated up to 200 and 100 mg in the single-dose and multidose studies, respectively. Sitafloxacin AUC and Cmax increased linearly within the detection range, and a steady state was reached within 3 days after the administration of multiple oral doses. Our findings showed that Cmax was lower in the ABCB1 (rs1045642) mutation group, whereas t1/2 was longer in the UGT1A1 (rs2741049) and UGT1A9 (rs3832043) mutation groups. In conclusion, sitafloxacin granules were safe at single doses and multiple doses up to 200 and 100 mg/day, respectively, with a linear plasma PK profile. However, ABCB1 (rs1045642), UGT1A1 (rs2741049), and UGT1A9 (rs3832043) genetic polymorphisms are likely to influence the Cmax or t1/2 and thereby merit further clinical evaluation.

Presence of anaplastic lymphoma kinase in inflammatory breast cancer.

Although Inflammatory Breast Cancer (IBC) is recognized as the most metastatic variant of locally advanced breast cancer, the molecular basis for the distinct clinical presentation and accelerated program of metastasis of IBC is unknown. Reverse phase protein arrays revealed activation of the receptor tyrosine kinase, anaplastic lymphoma kinase (ALK) and biochemically-linked downstream signaling molecules including JAK1/STAT3, AKT, mTor, PDK1, and AMPKß in pre-clinical models of IBC. To evaluate the clinical relevance of ALK in IBC, analysis of 25 IBC patient tumors using the FDA approved diagnostic test for ALK genetic abnormalities was performed. These studies revealed that 20/25 (80%) had either increased ALK copy number, low level ALK gene amplification, or ALK gene expression, with a prevalence of ALK alterations in basal-like IBC. One of 25 patients was identified as having an EML4-ALK translocation. The generality of gains in ALK copy number in basal-like breast tumors with IBC characteristics was demonstrated by analysis of 479 breast tumors using the TGCA data-base and our newly developed 79 IBC-like gene signature. The small molecule dual tyrosine kinase cMET/ALK inhibitor, Crizotinib (PF-02341066/Xalkori®, Pfizer Inc), induced both cytotoxicity (IC50 = 0.89 µM) and apoptosis, with abrogation of pALK signaling in IBC tumor cells and in FC-IBC01 tumor xenograft model, a new IBC model derived from pleural effusion cells isolated from an ALK(+) IBC patient. Based on these studies, IBC patients are currently being evaluated for the presence of ALK genetic abnormalities and when eligible, are being enrolled into clinical trials evaluating ALK targeted therapeutics.

[Capillary electrophoresis fingerprints of Baizi Yangxin Wan].

The capillary electrophoresis fingerprint (CEFP) of Baizi Yangxin Wan (BZYXW) was established by capillary zone electrophoresis (CZE). The chromatographic fingerprint resolution index (RF) was applied to optimize the CEFP conditions. The electrophoretic separation was performed on a 75 cm (the effective length of 57 cm) x 75 microm uncoated fused silica capillary with 50 mmol/L sodium borate-50 mmol/L Na2HPO(4)-200 mmol/L H3BO(3)-150 mmol/L NaHCO3 (7:7:1:1, v/v/v/v) containing 4% acetonitrile (pH 9.70) as the background electrolyte (BGE), and the BGE was chosen by using the triangular prism optimization method. The running voltage was set at 12 kV, and the detection wavelength at 228 nm. The sample solution was injected into the capillary by hydraulic pressure in 25 s. The CEFPs were produced by the electropherograms from 12 batches of BZYXW, and the 17 co-possessing peaks were selected as the fingerprint peaks of BZYXW's CEFP by choosing ferulic acid peak as the referential peak. According to the results of classification, the reference CEFP (RCEFP) was synthesized from 12 batches of BZYXW. Taking the RCEFP for the qualified model, the systematically quantified fingerprint method(SQFM) was applied to evaluate the quality of 17 batches of BZYXW, in which the qualities of 3 batches was evaluated as good, 1 batch as fine, 3 batches as moderate, 1 batch as common, and 4 batches as inferior. The triangular prism optimization method was suggested to be good to optimize the BGE. The results showed that the BZYXW-CEFP was established with good precision and reproducibility, which can be served as a novel reference to identify and control the quality of BZYXW.