This investigation was made on 30 adult female rats weighing approximately 150～200g. during estrus as judged from vaginal smear examination. Ovaries which investigated with electron microscope, were fixed in 3％ glutaraldehyde. Other ovaries were embeded in paraffin and examined under light microscope.Theca folliculi of large antral follicles were examined with electron microscope. Three kinds of theca cells were distinguished. They were secretory cell, fibroblast and smooth muscle cell. The secretory cell showed the characterastics of the steroidproducing cell, having smooth endoplasmic reticulum, mitochondria and lipid droplets. The fibroblast contained rough endoplasmic reticulum, free ribosomes and mitochondria in the cytoplasm. The smooth muscle cell was located in the outer layer of theca folliculi, and its structural features were typical according to the criteria of Somlyo and Somlyo: (1) pinocytotic vesicles of the cytoplasmic membranes; (2) myofilaments in the cytoplasm; (3) dense bodies intimately related to the myofilaments; and (4) location of mitochondria and endoplasmic reticulum at the nuclear poles.The ultrastructure of smooth muscle cell, its differentiation and other problems were discussed.

The report of ultrastructure of dog ovarian follicle wall has not been seen yet. This investigation was made on 5 adult dogs in the estrus stage of the cycle and examined with electron microscope. There are granular cells, fibroblasts and secretory cells in the ovarian follicle wall, The typical smooth muscle cell is absent.

Objective: To evaluate the predictive value for baseline levels of high sensitivity C-reactive protein (hs-CRP) in morbidity of pulmonary embolism (PE). Methods: We conducted a prospective cohort study of 101510 subjects in Kailuan Group by regular physical examination from 2006-07 to 2007-10, and 94314 subjects were enrolled by relevant criteria including 75252 male and 19062 female. The baseline levels of hs-CRP were divided by quartile levels as①hs-CRP<0.3l mg/L,n=25592,②hs-CRP (0.3l-0.77) mg/L,n=21746,③hs-CRP (0.78-1.9) mg/L,n=23504 and④hs-CRP≥2.0 mg/L,n=23472. The subjects were followed-up for (81.5 ± 4.76) months, the morbidity of PE was collected and the predictive value of baseline levels of hs-CRP for PE occurrence was evaluate by multivariable Cox proportional hazard regression analysis. Results: The total PE morbidity was 0.15%, the female subjects were similar with male subjects,P>0.05. As the increased baseline level of hs-CRP, PE occurrence was elevated accordingly,P<0.05. Multivariable Cox proportional hazard regression analysis presented that with adjusted age, gender, smoking, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), fasting blood glucose (FBG), neutrophile granulocyte (NEU), white blood cells (WBC) and heart rate (HR), the subjects in the highest quartile group had 2.84 times higher risk for PE occurrence than the subjects in the lowest quartile group. With the elevated baseline level of hs-CRP, the subjects’ mean age, BMI, SBP, FBG and NEU levels increased accordingly, allP<0.05; while DBP, TG and HR were similar between quartile③ and quartile④ groups, allP>0.05. WBC counts had the increasing trend in quartile①,②,③ groups and had the decreasing trend in quartile④ group, while it was similar between quartile③ and quartile④ groups,P>0.05. Conclusion: Baseline hs-CRP level may predict the risk of PE morbidity; the increased hs-CRP level could be used as one of the predictors for PE occurrence.

Ten novel podophyllotoxin derivatives (IIIa-IIIi and IV) were synthesized by three-step reactions using podophyllotoxin and N-benzyloxycarbonyl glycine-L-proline as raw material. The structures of the target compounds were confirmed by 1H NMR, 13C NMR and MS. MTT method was used to test anti-tumor activity of the target compounds on HepG2, THP-1, HeLa and MCF-7 cells. The results showed that all the target compounds had inhibitory activity against HepG2, THP-1, HeLa and MCF-7 cells, and the inhibitory activity of IIIa on HepG2 cells was the most prominent with an IC50 value of 0.58 nmol/L. The binding mode of compound IIIa and FAPα was studied by molecular docking. Compound IIIa could bind to multiple sites of FAPα enzyme.

OBJECTIVE: To investigate the effects of Niaoduqing granule on the urine metabolic profile in chronic renal failure (CRF) rats. METHODS: Thirty six male SD rats were divided into the normal control group, the model group, and the Niaoduqing group with 12 rats in each group. The CRF was induced by gavage of 250 mg·kg·d adenine for 21 d. UPLC-Q-TOF-MS/MS technique was used in combination with principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to analyze the urine metabolic profiles in three groups. The endogenous substances with the variable importance projection (VIP)>1 and <0.05 were screened as the potential biomarkers for CRF, and enrichment analysis of metabolic pathways was carried out. RESULTS: Compared with the normal control group, the model group had lower body weight, higher kidney coefficient, higher serum creatinine and urea nitrogen levels (all <0.01), while the above indexes in the Niaoduqing group were ameliorated compared with the model group (all <0.01). Fifteen potential biomarkers were found in the urine of the model group, which were involved in 9 metabolic pathways including phenylalanine, tyrosine and tryptophan biosynthesis, glyoxylate and dicarboxylate metabolism, valine, leucine and isoleucine biosynthesis, arachidonic acid metabolism, cysteine and methionine metabolism, tricarboxylic acid cycle, glycerophosphatide metabolism, tryptophan metabolism and tyrosine metabolism. CONCLUSIONS Niaoduqing granules has therapeutic effect on rats with CRF, which may be related to the regulation of amino acid metabolism, lipid metabolism and energy metabolism.
Animals ; Biomarkers ; urine ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Kidney Failure, Chronic ; drug therapy ; urine ; Male ; Metabolome ; drug effects ; Metabolomics ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

Recently, liposomes have been widely used in cancer therapeutics, but their anti-tumor effects are suboptimal due to limited tumor penetration. To solve this problem, researchers have made significant efforts to optimize liposomal diameters and potentials, but little attention has been paid to liposomal membrane rigidity. Herein, we sought to demonstrate the effects of cholesterol-tuned liposomal membrane rigidity on tumor penetration and anti-tumor effects. In this study, liposomes composed of hydrogenated soybean phospholipids (HSPC), 1,2-distearoyl--glycero-3-phosphoethanolamine--[methoxy(polyethylene glycol)-2000] (DSPE-PEG) and different concentrations of cholesterol were prepared. It was revealed that liposomal membrane rigidity decreased with the addition of cholesterol. Moderate cholesterol content conferred excellent diffusivity to liposomes in simulated diffusion medium, while excessive cholesterol limited the diffusion process. We concluded that the differences of the diffusion rates likely stemmed from the alterations in liposomal membrane rigidity, with moderate rigidity leading to improved diffusion. Next, the tumor penetration and the anti-tumor effects were analyzed. The results showed that liposomes with moderate rigidity gained excellent tumor penetration and enhanced anti-tumor effects. These findings illustrate a feasible and effective way to improve tumor penetration and therapeutic efficacy of liposomes by changing the cholesterol content, and highlight the importance of liposomal membrane rigidity.

Objective: To evaluate the efficacy and safety of low dose sublingual nifedipine dripping pills (5 mg) in treating moderate and severe hypertension in comparison with normal dose (10 mg) of sublingual nifedipine dripping pills. Methods: This study was designed as a randomized, double-blind, positive drug parallel controlled, multi-center, non-inferiority clinical trial. Patients with moderate and severe hypertension were enrolled by 14 clinical trial centers, randomly divided into the trial group (sublingual 5 mg nifedipine dripping pills) and the control group (sublingual 10 mg nifedipine dripping pills). The changes in blood pressure were monitored continuously within 2 hours after the initial administration, repeated the dose in 20 minutes interval after the initial administration for up to additional 3 doses (maximum 4 doses) if the antihypertensive efficacy was not satisfactory. The efficacy of antihypertensive therapy between the two groups was evaluated by repeated administration rates and blood pressure changes at 60 minutes post the initial administration, and the safety of treatment was evaluated by recording adverse event rate of the two groups. Results: The anti-hypertensive effective rates at 60 minutes after sublingual administration were 83.5% (202/242) and 86.7% (208/240) respectively between the trial group and control group (χ²=1.307, P=0.253) . On the aspect of antihypertensive effectiveness at 60 minutes after single dose of sublingual administration, the anti-hypertension effective rates of the trial group and the control group were 85.6% (154/180) and 87.2% (164/188) respectively (χ²=0.221, P=0.639). Prevalence of the repeated administration was also similar between the two groups (25.6%(62/242) in the trial group and 21.7% (52/240) in the control group, χ²=1.043, P=0.307). On the safety aspect, there was no adverse events/reactions in the trial group, but there were 15 cases of adverse events/reactions occurred in control group (6.25%, χ²=15.611, P<0.001). Conclusions In the treatment of moderate to severe hypertension, the antihypertensive efficacy of low dose nifedipine dripping pills is similar to that of conventional dosage, and the safety profile of low dose nifedipine dripping pills is better than that of the conventional dose.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment