Objective To develop four novel cocrystals of felodipine aimed at improving its poor solubility.Methods Felodipine-caproamide,felodipine-2,4-dihydroxybenzoic acid,felodipine-2,5-dihydroxybenzoic acid,and felodipine-3,5-dihydroxybenzoic acid cocrystals were prepared using the slurry method.The cocrystals were characterized by powder X-ray diffraction(PXRD),differential scanning calorimetry(DSC),thermogravimetric analysis(TGA),and Fourier-transform infrared spectroscopy(FT-IR).Stability tests and in vitro dissolution studies were conducted to assess their pharmaceutical properties.Results All four cocrystals demonstrated improved solubility and dissolution rates compared to pure felodipine.Notably,the felodipine-3,5-dihydroxybenzoic acid cocrystal showed superior stability and a marked increase in solubility.Conclusion Cocrystallization technology significantly enhanced the stability and dissolution profile of felodipine,underscoring its potential for pharmaceutical formulation development.

Objective To develop four novel cocrystals of felodipine aimed at improving its poor solubility.Methods Felodipine-caproamide,felodipine-2,4-dihydroxybenzoic acid,felodipine-2,5-dihydroxybenzoic acid,and felodipine-3,5-dihydroxybenzoic acid cocrystals were prepared using the slurry method.The cocrystals were characterized by powder X-ray diffraction(PXRD),differential scanning calorimetry(DSC),thermogravimetric analysis(TGA),and Fourier-transform infrared spectroscopy(FT-IR).Stability tests and in vitro dissolution studies were conducted to assess their pharmaceutical properties.Results All four cocrystals demonstrated improved solubility and dissolution rates compared to pure felodipine.Notably,the felodipine-3,5-dihydroxybenzoic acid cocrystal showed superior stability and a marked increase in solubility.Conclusion Cocrystallization technology significantly enhanced the stability and dissolution profile of felodipine,underscoring its potential for pharmaceutical formulation development.

Objective To explore the determination method of copper content in Chinese medicinal materials and to provide a scientific basis for the quality control of Chinese medicinal materials.Methods A method for rapid determination of copper content in different varieties of Chinese medicinal materials by X-ray fluorescence spectrometry was established.Results The content of copper in the linear range of 6-40 μg·g-1 showed good linearity with the response strength,which met the quantitative analysis requirements.Conclusion This method has the advantages of being simple,fast,and highly sensitive,and it can be used for rapid quality control of copper content in Chinese medicinal materials.

BACKGROUND: Women comprise more than half of people living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) worldwide and incomplete immune recovery and metabolic abnormalities affect them deeply. Studies of HIV antiretroviral therapy (ART) have a low female representation in China. We aimed to investigate immune reconstitution and metabolic changes of female HIV-positive cohort in China longitudinally. METHODS: HIV-positive women who initiated ART from January 2005 to June 2021 and were followed up regularly at least once a year were included in this study. Immunological indicators (cluster of differentiation 4 [CD4] counts and CD8 counts), viral load (VL), and metabolic indicators were collected at follow-up. All data were collected from the China Disease Prevention and Control Information System (CDPCIS). VL was tested half a year, 1 year after receiving ART, and every other year subsequently according to local policy. CD4/CD8 ratio normalization was considered as the primary outcome and defined as a value ≥1. Incidence rate and probability of CD4/CD8 ratio normalization were estimated through per 100 person-years follow-up (PYFU) and Kaplan-Meier curve, respectively. Multivariate Cox regression was used to identify independent risk factors associated with CD4/CD8 ratio normalization. We further studied the rate of dyslipidemia, hyperuricemia, diabetes, liver injury, and renal injury after ART initiation with the chi-squared tests or Fisher's exact probability tests, and a generalized estimating equation model was used to analyze factors of dyslipidemia and hyperuricemia. RESULTS: A total of 494 female patients with HIV/AIDS started ART within 16 years from January 2005 to June 2021, out of which 301 women were enrolled with a median duration of ART for 4.1 years (interquartile range, 2.3-7.0 years). The overall incidence rate of CD4/CD8 ratio normalization was 8.9 (95% confidence interval [CI], 7.4-10.6) per 100 PYFU, and probabilities of CD4/CD8 normalization after initiating ART at 1 year, 2 years, 5 years, and 10 years follow-up were 11.7%, 23.2%, 44.0%, and 59.0%, respectively. Independent risk factors associated with CD4/CD8 normalization were baseline CD4 cell counts <200 cells/μL, CD8 counts >1000 cells/μL, and more than 6 months from the start of combined ART (cART) to first virological suppression. Longitudinally, the rate of hypercholesterolemia (total cholesterol [TC]) and high triglyceride (TG) showed an increasing trend, while the rate of low high-density lipoprotein cholesterol (HDL) showed a decreasing trend. The rate of hyperuricemia presented a downtrend at follow-up. Although liver and renal injury and diabetes persisted during ART, the rate was not statistically significant. Older age and protease inhibitors were independent risk factors for increase of TC and TG, and ART duration was an independent factor for elevation of TC and recovery of HDL-C. CONCLUSIONS This study showed that women were more likely to normalize CD4/CD8 ratio in comparison with findings reported in the literature even though immune reconstruction was incomplete.
Humans ; Female ; CD4-CD8 Ratio ; HIV ; Immune Reconstitution ; Hyperuricemia/drug therapy* ; HIV Infections/drug therapy* ; Acquired Immunodeficiency Syndrome/drug therapy* ; Anti-Retroviral Agents/therapeutic use* ; Cholesterol ; Viral Load ; CD4 Lymphocyte Count ; Anti-HIV Agents/therapeutic use*

OBJECTIVE: To assess the association of gene expression with development potential of early embryos derived from patients with polycystic ovary syndrome (PCOS). METHODS: Three pairs of infertile patients with respectively matched age, body mass index, ovarian reserve and treatment with gonadotrophin-releasing hormone (GnRH) antagonists were selected. Patients with fewer embryos were assigned as the case group (n = 3), whilst the remainders were assigned as the control group (n = 3). Ovarian granulosa cells from patients were collected for the extraction of total RNA and subjected to RNA sequencing. The results were subjected to differential gene expression and functional enrichment analyses. RESULTS: Compared with the control group, 76 genes were up-regulated and 110 genes were down-regulated in the case group. The level of estradiol (E₂) was significantly higher in the control group on the trigger day with the injection of human chorionic gonadotrophin (HCG). Compared with the control group, the KRT7 gene was most significantly up-regulated, whilst the CCNYL2 gene was most significantly down-regulated in the case group. Gene ontology (GO) entries enrichment has found those associated with chromosome segregation, cell cycle regulation, and fatty acid metabolism to be significantly enriched. The genes participating in the regulation of cell assembly, differentiation, negative regulation of cell cycle, negative regulation of development, extracellular regulated protein kinases (ERK), ERK1 and ERK2 signaling pathways to be significantly down-regulated. KEGG enrichment analysis of cell signaling pathways revealed that steroid hormone biosynthesis-related genes were enriched. CONCLUSION Among patients treated with GnRH antagonists, the significant difference in the number of oocytes fertilized in vitro and the number of available embryos are associated with the difference in the expression of genes of ovarian granulosa cells.
Female ; Humans ; Pregnancy ; Embryonic Development ; Gene Expression ; Gonadotropin-Releasing Hormone/antagonists & inhibitors* ; Granulosa Cells ; Polycystic Ovary Syndrome/genetics*

Objective:To explore the relationship between microRNA-4429 (miR-4429) derived from serum exosomes and prognosis of radical radiation and chemotherapy for non-small cell lung cancer (NSCLC).Methods:309 blood samples of NSCLC patients were collected [before chemotherapy (T0), after 1 cycle of chemotherapy (T1) and after 2 cycles of chemotherapy (T2), 103 cases at each time point], and the expression level of miR-4429 was detected by real-time fluorescent quantitative PCR method, and the relationship between it and the prognosis of radical radiation and chemotherapy in NSCLC was analyzed.Results:The 1-year, 2-year and 3-year survival rates of 103 NSCLC patients were 69.90%, 45.63% and 34.95%, respectively. The expression levels of T1-miR-4429 and T2-miR-4429 in the survival group were 0.66±0.14 and 0.77±0.11, respectively, which were higher than T1-miR-4429 (0.60±0.06) and T2-miR-4429 (0.62±0.11) in the death group, and the differences were statistically significant ( t=2.269, 6.997, P<0.05). Restricted cubic spline fitting COX regression analysis showed that T2-miR-4429 had a linear relationship with survival in NSCLC. COX regression analysis showed that TNM staging was an independent risk factor for the survival and prognosis in NSCLC ( P<0.05), and the degree of differentiation, targeted therapy and T2-miR-4429 were all independent protective factors for the survival and prognosis in NSCLC ( P<0.05). The calibration curve of the nomogram regression model constructed by TNM stage, degree of differentiation, targeted therapy and T2-miR-4429 coincided well with the ideal curve, and the C-index was 0.713. Conclusions:The high expression level of T2-miR-4429 indicates that NSCLC patients have a low risk of poor survival prognosis. The nomogram regression model constructed by TNM staging, degree of differentiation, targeted therapy and T2-miR-4429 has a certain degree of discrimination and accuracy, which can assist in evaluating the prognosis of NSCLC.

Objective: To explore the effects of intervention programs during primipara, using the Information-motivation-behavioral skills model (IMB) intervention model on initial exclusive breastfeeding. Method: 206 women of primiparas who were registered to the top three hospitals were selected in Shandong province, 2018. These women were hospitalized in the obstetrics/gynaecology wards during the later periods. IMB model was used to support the intervention programs at the following stages: antenatal period, 1 day postpartum, 3-4 days postpartum and 42 days postpartum. Questionnaire regarding self-efficacy energy meter, knowledge and behavior related to breastfeeding, were used before and after the intervention programs. Results: Through intervention programs, statistically significant differences in breastfeeding self-efficacy scores between the four stages (F=150.680, P=0.000) were recorded. Significant differences were also noticed in scores on knowledge of breastfeeding (F=176.556, P=0.000). Conclusion The application of IMB intervention model in women at childbearing age seemed to be helpful in improving the effect of primary breastfeeding in women at childbearing age.

Objective: To study the impact of aging on pancreatic atrophy, fibrosis and exocrine hypofunction in patients with post-ERCP pancreatitis (PEP) and its severity. Methods: A retrospective study was conducted on 786 patients who underwent ERCP at the Affiliated Zhongshan Hospital of Dalian University from June 2011 to April 2018. Patients who were aged over 75 years were grouped into the elderly group while those aged less than 75 years were grouped into the younger group. The incidences and severity of post-ERCP pancreatitis in the two groups were analyzed. Results: In the elderly group, there were 308 patients. The average age was (81.8±4.8) years. In the younger group, there were 478 patients. The average age was (57.7±12.0) years. The average operation time for the elderly group was (52.5±14.1) minutes, and that for the younger group was (50.7±14.9) minutes. There were no significant differences in operation time and in the related factors between the two groups (P>0.05). There was no significant difference in the rates of hyperamylasemia between the two groups (29.9% vs 30.1%, P>0.05). The overall rate of PEP was 11.3% (89/786). In the elderly group, the rate of PEP was 6.5% (20/308), which was significantly lower than that in the younger group (χ²=11.765, P<0.05). The rates of mild, moderate and severe PEP in the elderly group was significantly lower than those in the younger group (all P<0.05). Hyperamylasemia and pancreatitis in the 2 groups were alleviated after conservative treatment. Conclusions Aging (≥75 years) resulted in pancreatic atrophy, fibrosis, exocrine hypofunction which had a protective effect on PEP.

Objective To evaluate the effect of high flow nasal catheter oxygen (HFNCO) therapy on extubation failure rate,reintubation rate,and incidence of related complications within 48 h after extubation in mechanically ventilation patients.Methods A prospective,single-center,randomized controlled trial was conducted in the ICU of a teaching hospital affiliated to a medical university.A total of 77 patients with mechanical ventilation duration of ≥ 48 h and met the condition of spontaneous breathing test (SBT) were selected.The patients whose LUS ≥ 14 at 30 min of SBT were enrolled,and were randomly (random number) divided into 3 groups according to different oxygen therapies:the traditional oxygen therapy group,the noninvasive ventilation (NIV) group,and the HFNCO group.The effect of oxygen therapy and outcomes after extubation were compared among the three groups.The measurement data were presented as the mean±standard deviation (SD),and the numeration data were expressed as ratio or constituent ratio.The independent sample t test and LSD-t test were used for the comparisons between the two groups and the one-way ANOVA for differences between multiple groups.The differences between enumeration data were assessed by chi-square test.A P＜0.05 was considered statistically significant.Results There was no significant difference in gender,age and other general conditions between the two groups (P＞0.05).The NIV group and HFNCO group had lower extubation failure rate (14.29％,15.38％ vs 34.87％) and reintubation rate (10.7％,11.54％ vs 21.74％) than the convertional oxygen therapy group (P＜0.05).In addition,the traditional oxygen therapy group had longer mechanical ventilation duration [(24.33±4.42) d vs (8.58±1.09) d,(8.37±2.43) d],antibiotic use time [(19.21±4.37) d vs (8.34±2.54) d,(7.41±1.06) d],and ICU hospitalization time [(27.27±4.24) d vs (10.38±2.07) d,(9.44±0.79) d],all P＜0.05.Conclusions Treatment with HFNCO or NIV after extubation can effectively reduce the rates of extubation failure and reintubation,and improve the outcome of the mechanical ventilation.There is no difference in clinical efficiency between the NIV group and HFNCO group.However,compared with NIV,HFNCO can effectively reduce respiratory rate and avoid the retention of CO2,which has a wider application prospect in clinical practice.

Objective To investigate the feasibility and safety of microwave coagulo-necrotic therapy (MCN) combined with laparoscopic splenectomy (LS) in the treatment of primary hepatocellular carcinoma (PHC) complicated by hypersplenism. Methods A retrospective analysis was performed for the clinical data of 22 PHC patients with hypersplenism who were admitted to Baoji Municipal People' s Hospital from January 2008 to December 2012 and underwent MCN combined with LS. Their clinical data were collected, and postoperative complications and survival were observed. The t-test was used for comparison of continuous data, and the Kaplan-Meier method was used to plot cumulative survival curves. Results In MCN therapy, 5 patients underwent thoracotomy, 15 underwent laparotomy, and 2 underwent laparoscopic surgery; in LS treatment, 17 underwent hand-assisted LS and 5 underwent simple LS. The mean time of operation was (303. 24 ±56. 02) min, the mean blood loss volume was (146. 92 ± 60. 72) ml, and the mean weight of the resected spleen was (670. 42 ± 204. 54) g. Of all patients, 6 (27. 27％ ) experienced postoperative recurrence, 5 (22. 73％ ) experienced portal vein thrombosis, and 2 (9. 09％ ) experienced pleural effusion. There was a significant increase in platelet count at 1 month after surgery [ (15. 72 ± 5. 47) ×104/μl vs (4. 43 ±1. 03) ×104/μl, t = 6. 83, P ＜ 0. 001]. The 1-, 3-, and 5-year overall survival rates after surgery were 90. 91％, 68. 18％, and 59. 09％, respectively, and the 1-, 3-, and 5-year disease-free survival rates were 59. 09％, 13. 64％, and 13. 64％, respectively.Conclusion MCN combined with LS is safe, effective, and feasible in the treatment of PHC complicated by hypersplenism.