OBJECTIVETo investigate the progressive motility, (PR), total motility (progressive + non-progressive motility, PR + NP), and acrosin activity of sperm from normal and infertile men at different time points after sperm activation.

METHODSBased on the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen and the results of modified Papanicolaou staining, we divided the semen samples into groups A (normal, n = 28), B (oligoasthenoteratospermia, n = 30), and C (asthenoteratospermia, n = 32). At 1, 24, and 48 hours after sperm activation, we detected sperm PR and PR + NP by CASA and chemical colorimetry, and determined sperm acrosin activity using the modified Kennedy method.

RESULTSSperm PR and PR + NP were significantly decreased in all the three groups at 1-24 hours and even more significantly at 24-48 hours after sperm activation as compared with the baseline (P < 0.05). Sperm acrosin activity showed remarkable reduction in group A (P = 0. 013) , even more significant at 1-24 hours than at 24-48 hours after sperm activation, but not in groups B and C (P = 0.519 and 0.979).

CONCLUSIONSperm PR, PR + NP, and acrosin activity are all decreased with the extension of time after sperm activation, each in a specific manner. Examination of sperm acrosin activity should be applied as a routine tool in the assessment of male fertility.

Acrosin ; metabolism ; Asthenozoospermia ; metabolism ; physiopathology ; Biomarkers ; metabolism ; Humans ; Infertility, Male ; metabolism ; physiopathology ; Male ; Semen ; Sperm Motility ; physiology ; Spermatozoa ; metabolism ; physiology ; Time Factors

Adult ; Embolism, Amniotic Fluid ; etiology ; therapy ; Female ; Humans ; Pregnancy

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

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

Objective:To analyze the correlation between 21-gene recurrence score (RS) and clinicopathological characteristics of patients with Lumina type breast cancer, and to explore its significance in individualized treatment.Methods:The clinicopathological data of 59 patients with surgical resection and pathological diagnosis of Lumina type breast cancer in Shanxi Provincial Cancer Hospital from May 2018 to May 2019 were retrospectively analyzed. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of 21 gene and RS was calculated. According to the 21-gene RS, the patients were divided into low recurrence risk group (RS < 18 points), intermediate recurrence risk group (RS 18-31 points) and high recurrence risk group (RS > 31 points). Univariate and multivariate logistic regression analyses were made to evaluate the correlations between different recurrence risk and clinicopathological characteristics of patients and their influence on the choice of adjuvant chemotherapy.Results:Based on the 21-gene RS, 29 patients were in low recurrence risk group, 22 cases were in intermediate recurrence risk group, and 8 cases were in high recurrence risk group. Single-factor analysis showed that age ( P = 0.012), maximum mass diameter ( P = 0.031), histological grade ( P = 0.036), progesterone receptor (PR) level ( P = 0.015), Ki-67 positive index ( P = 0.049) and molecular typing ( P = 0.010) were influencing factors of 21-gene RS recurrence risk. Multivariate logistic regression analysis showed that the age and Ki-67 positive index were negatively correlated with 21-gene RS recurrence risk (both P < 0.05). After grouping according to the 21-gene RS, 17 patients in the intermediate recurrence risk group (according to the traditional postoperative recurrence risk grouping method for breast cancer) were classified as low recurrence risk group, and 4 patients in the low recurrence risk group were classified as intermediate recurrence risk group ( χ2 = 4.535, P = 0.033). After grouping based on 21-gene RS, the number of patients who needed chemotherapy in individualized treatment decreased. Of the 17 cases, 11 cases did not undergo postoperative chemotherapy, and the remaining patients received chemotherapy. The postoperative follow-up period was 11-22 months. As of March 2020, there was no recurrence or disease progress. Conclusion:The 21-gene RS can provide objective basis for the individualized precise treatment and prognosis prediction for patients with early-stage Lumina type breast cancer.

As a model terpenoid,the ginsenoside is one of Panax ginseng’s main effective components.An overview of biosynthetic pathway of terpenoids and the HMG-CoA reductases was presented.The massive research materials indicated that the HMG-CoA reductases is the first key enzyme of the regulation of the mevalonic acid way,which has some reference value to promote the research on the biosynthetic pathway and the regulation of ginsenoside.

Adult ; Female ; Humans ; Pregnancy ; Pregnancy Complications, Infectious ; diagnosis ; Tuberculosis ; diagnosis

BACKGROUNDMany cytokines have been found to increase the insulin resistance during pregnancy complicated by glucose metabolism disorder. This study aimed to investigate which comes first, the changes of some cytokines or the abnormal glucose metabolism.

METHODSThis nested case-control study was undertaken from January 2004 to March 2005. Twenty-two women with gestational diabetes mellitus (GDM), 10 with gestational impaired glucose tolerance (GIGT), and 20 healthy pregnant women were chosen from the women who had visited the antenatal clinics and had blood samples prospectively taken and kept during their visit. The levels of tumor necrosis factor-alpha (TNF-alpha), leptin and adiponectin were determined. One-way ANOVA analysis and bivariate correlation analysis were used to assess the laboratory results and their relationship with body mass index (BMI).

RESULTSWomen with GDM have the highest values of TNF-alpha and leptin and the lowest value of adiponectin compared with those with GIGT and the healthy controls (P < 0.01) at 14-20 weeks of gestation. This was also found when these women progressed to 24-32 weeks. The significantly increased levels of TNF-alpha and leptin and the decreased level of adiponectin were found at the different periods of gestation within the same group. Positive correlation was shown between the levels of TNF-alpha and leptin at the two periods of gestation with the BMI at 14-20 weeks, while adiponectin was negatively correlated (P < 0.05).

CONCLUSIONSThe concentrations of TNF-alpha, leptin and adiponectin may change before the appearance of the abnormal glucose level during pregnancy. Further studies are required to verify the mechanism of this alteration and whether the three cytokines can be predictors for GDM at an early stage of pregnancy.

Adiponectin ; blood ; Case-Control Studies ; Diabetes, Gestational ; blood ; Female ; Glucose Intolerance ; Humans ; Leptin ; blood ; Pregnancy ; Prospective Studies ; Tumor Necrosis Factor-alpha ; blood

BACKGROUND: Estradiol, as an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization embryo transfer (IVF-ET) cycles. The aim of this retrospective study was to evaluate the association between elevated serum estradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and IVF-ET pregnancy and birth outcomes. METHODS: A total of 1771 infertile patients with their first fresh IVF-ET cycles were analyzed retrospectively between January 2011 and January 2016 in Peking University First Hospital. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 205), group 2 (serum E2 levels 1001-2000 pg/mL, n = 457), group 3 (serum E2 levels 2001-3000 pg/mL, n = 425), group 4 (serum E2 levels 3001-4000 pg/mL, n = 310), group 5 (serum E2 levels 4001-5000 pg/mL, n = 237), and group 6 (serum E2 levels > 5000 pg/mL, n = 137). The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates of the groups were compared as the first objective of the study. For the 360 women with singleton births among all patients, the area under the corresponding receiver operating characteristic curve (ROC curve) was calculated to assess the predictive value of the E2 change for the probability of low birth weight (LBW) infants as the second objective. RESULTS: The retrieved oocyte and MII oocyte numbers and implantation and clinical pregnancy rates gradually increased from groups 1 to 5 but decreased in group 6. The parameters of group 1 were statistically worse than those of the other groups, from group 2 to group 6 (the number of retrieved oocytes, t = 13.096, t = 23.307, t = 23.086, t = 26.376, t = 19.636, P < 0.003; the number of retrieved MII oocytes, t = 10.856, t = 20.868, t = 21.874, t = 23.374, t = 19.092, P < 0.003; the implantation rate, χ = 12.179, χ = 22.239, χ = 23.993, χ = 23.344, χ = 16.758, P < 0.003; the clinical pregnancy rate, χ = 16.415, χ = 28.074, χ = 35.387, χ = 37.025, χ = 24.590, P < 0.003). ROC analysis revealed that when a serum peak E2 of 3148 pg/mL was used to predict LBW. CONCLUSIONS The results indicate that serum E2 levels have a concentration-dependent effect on clinical outcomes. The optimal range of the E2 level during a fresh IVF-ET cycle is 1000 to 3148 pg/mL.

Roscovitine is a specific inhibitor of cyclin-dependent kinases (cdks) cdc2/cyclin B, cdk2/cyclin A, cdk2/cyclin E and cdk5/p35. The studies on the enzyme inhibitory properties and cellular effects of roscovitine revealed that it arrests cells in G(2)/M and G(1)/S phase, inhibits the proliferation of mammalian cells and induces cell death. However, the characteristics of cell death and exact mechanism by which this cdk inhibitor kills transformed cells are unknown. We previously investigated that the roscovitine induces apoptotic death of mitotic PC12 cells. The present study was to identify whether the roscovitine-induced death is related with the specific elements of caspases in pathway of apoptosis. The morphological data of caspase-3 immunofluorocytochemistry double staining with hoechst 33342 indicated that apoptotic nuclei were identified as nuclei with chromatin condensation and nuclear fragmentation, and that caspase-3 active p17 subunit co-existed in PC12 cells treated with roscovitine 50 micromol/L for 4 h. The number of the caspase-3 positive cells increased significantly to about 42%, as compared with the normal control (P<0.001). The data of MTT assay showed that the number of viable cells treated by roscovitine (50 micromol/L) alone for 12 h was 29.03%, of the untreated controls. Both a broad-spectrum caspase inhibitor Z-VAD-FMK (50 mumol/L) and a specific caspase-3 inhibitor Z-DEVD-FMK (100 micromol/L) increased viable PC12 cells to 45.16%, (Z-DEVD-FMK) and 58.06%, (Z-VAD-FMK), respectively, in the presence of roscovitine. Non-erythroid a-spectrin is a cytoskeleted protein that is a substrate of caspase-3 cysteine proteases. To confirm the activity of caspase-3 that produced in roscovitine (50 micromol/L for 12 h)-induced PC12 cell death, activated caspase-3 specific 120 kDa spectrin breakdown products (SBDP) were detected by Western bloting using the mouse anti-non-erythroid a-spectrin monoclonal antibody. The mean relative density of bands corresponding to caspase-3 specific SBDP levels were significantly increased in the cytosolic fractions treated with roscovitine, as compared to the normal control (P<0.001). These results indicate that caspase signals, especially caspase-3 signal are necessary for the progression of proliferating PC12 cell apoptotic death evoked by roscovintine.
Animals ; Apoptosis ; drug effects ; physiology ; Caspase 3 ; physiology ; Cyclin-Dependent Kinases ; antagonists & inhibitors ; PC12 Cells ; Protein Kinase Inhibitors ; pharmacology ; Purines ; pharmacology ; Rats