AIMTo investigate the combined effect of cosolvent and cyclodextrin (CD) on solubilization of insoluble drugs.

METHODSPhase-solubility method was applied to determine solubilization of two diterpenoids in cosolvent / cyclodextrin combinations. The combined effect was evaluated and explained with an established mathematical model, and the model parameters were calculated by means of nonlinear regression analysis.

RESULTSThe strong agreement between the predicted and the observed solubility data supports the validity of the proposed model, with the determination coefficients of two regression models were 0.993 and 0.992, separately.

CONCLUSIONThe validated mathematical model can be used to explain and predict the combined solubilization of the two insoluble drugs in different cosolvent systems.

2-Hydroxypropyl-beta-cyclodextrin ; Algorithms ; Diterpenes ; chemistry ; Models, Chemical ; Solubility ; Solvents ; chemistry ; Water ; chemistry ; beta-Cyclodextrins ; chemistry

Cell Membrane Permeability ; Crystallization ; Dosage Forms ; Nephelometry and Turbidimetry ; Pharmaceutical Preparations ; chemistry ; Pharmacokinetics ; Quantitative Structure-Activity Relationship ; Solubility ; Technology, Pharmaceutical ; methods ; trends

Abstract: Objective　To analyze the serotype distribution, drug resistance rate and drug resistance gene carrying of Streptococcus pneumoniae isolates in hospitalized patients, and evaluate the coverage of the vaccine to the serotype of Streptococcus pneumoniae in this area, so as to provide reference for the rational use of antibiotics in clinic. Methods　A total of 150 strains of non-repetitive Streptococcus pneumoniae isolated from inpatients from January 2015 to December 2019 were collected for serotyping and antimicrobial sensitivity test. The carrying rates of pbp2b, ermB and tetM were detected by PCR. Results　The PCR classification rate of 150 strains of Streptococcus pneumoniae was 93.1%, and the classification rate of capsular swelling test was 100%, and a total of 19 serotypes were divided, mainly 19F and 6B. Children's serotypes were predominantly 19F, 6B, and 15A; adult serotypes were predominantly 19F, 14, and 23F. The coverage rates of the PCV7, PCV10, PCV13 and PPV23 vaccines were 36.8%, 42.1%, 57.9% and 68.4%, respectively. Strains with serotypes of 19F, 6B, 3, and 23F had higher rates of resistance to antimicrobials. The sensitivity of Streptococcus pneumoniae to penicillin was greater than 96.0%. Antimicrobials with significant differences in resistance rates between invasive and non-invasive strains were penicillin, moxifloxacin, and levofloxacin. The percentage of strains carrying both ermB and tetM resistance genes was 96.0%, and the concordance rate between pbp2b, ermB and tetM resistance genes and the resistance phenotype was >98.0%. A total of 10 multi-resistance combinations were detected, with a multi-resistance rate of 62.6%, and the multi-drug resistance pattern of Streptococcus pneumoniae was mainly concentrated in the 19F and 6B serotypes. Conclusion　There are significant age differences in the serotypes of Streptococcus pneumoniae in this area. The vaccine currently used has low coverage in this region and therefore offer limited protection to the population. The drug resistance rates of Streptococcus pneumoniae varied significantly among serotypes. Erythromycin and tetracycline are not recommended for clinical treatment of Streptococcus pneumoniae. Penicillin can still be used as the first choice for clinical treatment of Streptococcus pneumoniae infection.

Humans ; Interleukin-17 ; Liver Diseases ; immunology ; Th17 Cells ; immunology

Objective: To observe the clinical efficacy of mind-refreshing and balance-restoring needling method combined with Frenkel exercises in treating ataxia after cerebral stroke. Methods: The recruited 120 patients were randomized into an observation group and a control group, with 60 cases in each group. The control group was intervened by mind-refreshing and balance-restoring needling method, while the observation group was given additional lower-limb Frenkel exercises. Before and after treatment and at the follow-up, the ataxic lower-limb function was scored using Berg balance scale (BBS) and international cooperative ataxia rating scale (ICARS), and Barthel index (BI) was adopted to score the activities of daily living (ADL). Results: After treatment, the markedly effective rate was 70.2％ and the total effective rate was 96.5％ in the observation group, versus 39.7％ and 87.9％ in the control group, and the differences in the markedly effective rate and the total effective rate were statistically significant (P<0.01, P<0.05). The intra-group comparisons showed that the BBS, ICARS and BI scores after treatment and at the follow-up were significantly different from those before treatment in both groups (all P<0.01).There were significant differences in the BBS score between the two groups after treatment and at the follow-up (P<0.05, P<0.01); the between-group differences in the ICARS and BI scores were statistically insignificant after treatment (both P>0.05), while the between-group differences in the ICARS and BI scores were statistically significant at the follow-up (both P<0.05). The interaction effects between the scoring time of BBS and BI and the group factor were statistically significant (P<0.01, P<0.05). Conclusion: Mind-refreshing and balance-restoring needling can effectively improve the lower-limb ataxic symptoms and ADL after stroke; when combined with Fenkel exercises, this needling method can produce more significant efficacy.

Objective:To investigate the therapeutic efficacy of venetoclax combined with avapritinib in treatment of refractory/relapsed acute myeloid leukemia (AML) with KIT gene mutation.Methods:The clinical data of 2 AML patients with KIT gene mutation who received venetoclax combined with avapritinib admitted to Canglang Hospital of Suzhou in October 2022 and November 2022 were retrospectively analyzed, and the relevant literature was reviewed.Results:Both patients with high-risk relapsed/refractory AML and KIT gene mutation were females; the one was 53 years and the other was 17 years. Case 1 was diagnosed with AML-M 2, and genetic testing revealed positive mutations in ASXL1, KIT, and RUNX1. The patient relapsed after transplantation and then was treated with venetoclax combined with avapritinib achieving morphologic leukemia-free status (MLFS). Case 2 was diagnosed with AML, and RUNX1-RUNX1T1 (AML1-ETO) fusion gene and KIT and DX15 gene mutations were detected. The patient was treated with venetoclax combined with avapritinib regimen after relapse, and the treatment regimen significantly reduced the tumor load. Complete remission was achieved after bridging to allogeneic hematopoietic stem cell transplantation. Conclusions:AML with KIT gene mutation is heterogeneous and some patients are difficult to treat with very poor prognosis. Bridging (secondary) hematopoietic stem cell transplantation can be the better treatment choice for relapsed patients achieving MLFS or complete remission after venetoclax combined with avapritinib treatment regimen.

OBJECTIVETo evaluate the association between vasectomy and prostate cancer.

METHODSWe searched comprehensively the databases, CBMDisc, CMCC, CMAC, CNKI (from 1978 to January 6, 2009), and PubMed (from 1965 to January 6, 2009) using the key words "vasectomy" and "prostate cancer", screened the retrieved literature according to the inclusion and exclusion criteria, performed a Meta-analysis with the software RevMan 4.2 after identification of the relevant data, and calculated the overall pooled OR (95% CI) as well as that of the association of prostate cancer with <20 and > or =20 yr vasectomy.

RESULTSA total of 20 088 cases and 232 506 controls in 27 reports (7 cohort and 20 case-control studies) were included in this investigation. The overall pooled OR (95% CI) was 1.10 (0.97-1.24), and those of <20 and > or =20 yr vasectomy were 0.94 (0.83-1.06) and 1.05 (0.90-1.23), respectively.

CONCLUSIONNo existing literature show any positive association between vasectomy and prostate cancer.

Humans ; Male ; Prostatic Neoplasms ; epidemiology ; etiology ; Risk Factors ; Vasectomy ; adverse effects

OBJECTIVETo investigate the relationship of seminal plasma levocarnitine with sperm concentration, vitality and motility.

METHODSEnrolled in this study were 64 infertile men, who were divided according to the results of routine sperm tests into a normozoospermia (n = 12), an oligozoospermia (n = 16), an asthenozoospermia (n = 20) and an oligoasthenozoospermia group (n = 16). The level of seminal plasma levocarnitine was detected by LC-MS-MS, the concentration of seminal plasma testosterone measured by chemiluminescence immunoassay, the correlation of seminal plasma levocarnitine with sperm concentration, motility and vitality determined by bivariate correlation analysis with SPSS15.0, and so was the correlation between the carnitine and sperm concentration by partial correlation analysis with seminal plasma testosterone as a control variable to exclude the influence of testosterone.

RESULTSThe concentrations of total seminal plasma levocarnitine, free seminal plasma levocarnitine and seminal plasma acetolevocarnitine were (91.33 +/- 40.49) mg/L, (40.89 +/- 24.13) mg/L and (50.44 +/- 21.90) mg/L; the Pearson coefficients of correlation of the levocarnitine level with sperm motility, vitality and concentration were 0.161 (P = 0.235), 0.114 (P = 0.370) and 0.637 (P < 0.001), those of free seminal carnitine with sperm motility and vitality were 0.325 (P = 0.024) and 0.316 (P = 0.029), respectively, with the oligozoospermia group excluded, and that of partial correlation between the concentrations of seminal levocarnitine and sperm was 0.641 (P < 0.001).

CONCLUSIONThe level of seminal plasma levocarnitine is positively correlated with sperm motility and vitality, and more significantly with sperm concentration.

Adult ; Carnitine ; analysis ; Humans ; Infertility, Male ; physiopathology ; Male ; Semen ; chemistry ; cytology ; Sperm Count ; Sperm Motility ; physiology ; Spermatozoa ; cytology ; physiology ; Young Adult

Objective To explore the risk factors for sudden cardiac death(SCD)after revascularization in patients with coronary heart disease and heart failure.Methods This study was a retrospective analysis of 1683 patients with coronary heart disease whose left veatricalar ejection fraction(LVEF)≤40％within 30 days before revascularization.Patients were categorized into 2 groups according their clinical outcome as with or without SCD.Their clinical,angiographic and echocardiographic characteristics were reviewed and compared.The average follow-up time was 1803 days.Results There were total 59 SCD cases.The Cox regression analysis revealed that tricuspid regurgitation(HR 2.217,95％CI 1.285-3.827,P=0.004),lef t main with triple-vessel disease(HR 3.089,95％CI 1.310-7.283,P=0.010),uric acid levels(HR 1.003,95％CI 1.001-1.005,P=0.006)were independent risk factors of SCD.Conclusions The risk of sudden cardiac death after revascularization in coronary artery disease patients with heart failure were significantly higher in patients with tricuspid regurgitation,left main with triple-vessel disease and high uric acid levels.

Objectives: To evaluate the clinical characteristics and prognosis of high risk cytogenetic abnormalities (HRCA) and various combinations of cytogenetic abnormality in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: This retrospective study collected 182 NDMM patients in the First Affiliated Hospital of Jilin University between Nov. 2009 and May 2018. HRCA included 1q+, del (17p) , t (4;14) , and t (14;16) detected by FISH, and non-HRCA included del (13q) , t (11;14) detected by FISH. The clinical characteristics among three groups, including cases who carrying a single HRCA, 1 HRCA in combination with non-HRCA and cases carrying two or more HRCAs (double/triple-hit) were observed. Kaplan-Meier curve was used to analyze both progression-free survival (PFS) and overall survival (OS) for the three groups. Results: The survivals of patients with 1 HRCA in combination with non-HRCA were similar to those with two or more HRCAs (double/triple-hit) , the median PFS (mPFS) was 19.1 m vs 12.1 m (P=0.248) and median OS (mOS) was 29.6 m vs 29.3 m (P=0.774) . Furthermore, the prognosis of these two groups were both inferior to patients with a single HRCA, respectively. (mPFS: 32.2 m, P=0.040, P=0.001; mOS: 42.3 m, P=0.021, P=0.041) . Strikingly, both the mPFS and the mOS of patients with 1 HRCA in combination with non-HRCA (regardless of high risk or not) were significantly shorter than that of cases with a single HRCA (mPFS: 15.1 m vs 32.2 m, HR=2.126, 95%CI 1.176-3.843, P=0.005; mOS: 29.3 m vs 42.3 m, HR=1.442, 95%CI 0.705-2.950, P=0.011) . Conclusion: It is of prognostic significance value for detecting double/triple-hit based on FISH cytogenetics in NDMM.
Chromosome Aberrations ; Chromosome Disorders ; Cytogenetic Analysis ; Humans ; Multiple Myeloma ; Prognosis ; Retrospective Studies