This study aims to explore the neuroprotective effect of bilobalide(BB) and the mechanisms such as inhibiting inflammatory response in macrophage/microglia, promoting neurotrophic factor secretion, and interfering with the activation and differentiation of peripheral CD4~+ T cells. BB of different concentration(12.5, 25, 50, 100 μg·mL~(-1)) was used to treat the RAW264.7 and BV2 cells for 24 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay and cell counting kit-8(CCK-8) were employed to detect the cytotoxicity of BB and appropriate concentration was selected for further experiment. Lipopolysaccharide(LPS) was applied to elicit inflammation in RAW264.7 and BV2 cells, mouse bone marrow-derived macrophages(BMDMs), and primary microglia, respectively. The effect of BB on cell proliferation and secretion of inflammatory cytokines and neurotrophic factors was detected by enzyme-linked immunosorbent assay(ELISA). Spleen monocytes of C57BL/6 female mice(7-8 weeks old) were isolated, and CD4~+ T cells were separated by magnetic beads under sterile conditions. Th17 cells were induced by CD3/CD28 and the conditioned medium for eliciting the inflammation in BMDMs. The content of IL-17 cytokines in the supernatant was detected by ELISA to determine the effect on the activation and differentiation of CD4~+ T cells. In addition, PC12 cells were incubated with the conditioned medium for eliciting inflammation in BMDMs and primary microglia and the count and morphology of cells were observed. The cytoto-xicity was determined by lactate dehydrogenase(LDH) assay. The result showed that BB with the concentration of 12.5-100 μg·mL~(-1) had no toxicity to RAW264.7 and BV2 cells, and had no significant effect on the activity of cell model with low inflammation. The 50 μg·mL~(-1) BB was selected for further experiment, and the results indicated that BB inhibited LPS-induced secretion of inflammatory cytokines. The experiment on CD4~+ T cells showed that the conditioned medium for LPS-induced inflammation in BMDMs promoted the activation and differentiation of CD4~+ T cells, while the conditioned medium of the experimental group with BB intervention reduced the activation and differentiation of CD4~+ T cells. In addition, BB also enhanced the release of neurotrophic factors from BMDMs and primary microglia. The conditioned medium after BB intervention can significantly reduce the death of PC12 neurons, inhibit neuronal damage, and protect neurons. To sum up, BB plays a neuroprotective role by inhibiting macrophage and microglia-mediated inflammatory response and promoting neurotrophic factors.
Female ; Rats ; Mice ; Animals ; Bilobalides/pharmacology* ; Neuroprotection ; Lipopolysaccharides/toxicity* ; Culture Media, Conditioned/pharmacology* ; Mice, Inbred C57BL ; Macrophages/metabolism* ; Microglia ; Cytokines/metabolism* ; Nerve Growth Factors/pharmacology* ; Inflammation/metabolism*

Objective: To understand the epidemiological characteristics of a local clustered epidemic caused by 2019-nCoV Delta variant in Ningbo and provide reference for the improvement of COVID-19 epidemic prevention and control. Methods: Case finding was conducted based on case definitions, and field epidemiological investigation of COVID-19 cases was carried out. In which Nasal and oropharyngeal swabs of the cases were collected for pathogen testing, and the results were analyzed with descriptive epidemiological methods. Results: A total of 74 COVID-19 cases were reported in this epidemic, and the cases were mainly mild ones, accounting for 87.84% (65/74), and there were no severe or critical cases. The epidemic curve showed a human-to-human transmission mode, indicating that a transmission for at least six generations had occurred. The age of the COVID-19 patients ranged from 2 years to 80 years, and 27.03% (20/74) of the cases were older than 60 years. The cases were mainly workers (55.41%, 41/74) and housework/the unemployed (27.03%, 20/74). The COVID-19 epidemic was limited, and no further spread to other areas occurred. The transmission chain among the cases was clear, and the gene sequencing results confirmed that the current epidemic was caused by 2019-nCoV Delta variant, which was highly homologous to the strains from other province. Conclusion: The local COVID-19 epidemic in Ningbo was caused by imported cases of COVID-19 from other province, and local community spread occurred through daily contacts between cases and contacts.
COVID-19/epidemiology* ; Child, Preschool ; Data Collection ; Epidemics ; Humans ; SARS-CoV-2

Objective: Moxifloxacin (MFX) shows good activity against and can be a possible antibiotic therapy to treat infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against using zebrafish (ZF) model . Methods: A formulation of labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. Results: Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. Conclusion MFX showed limited efficacy against using ZF model. Its activity needs to be confirmed.
Animals ; Anti-Bacterial Agents ; pharmacology ; Disease Models, Animal ; Moxifloxacin ; pharmacology ; Mycobacterium Infections, Nontuberculous ; drug therapy ; Mycobacterium abscessus ; drug effects ; Zebrafish

The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5

Adult ; Aged ; Aneurysm ; diagnosis ; pathology ; Computed Tomography Angiography ; methods ; Female ; Humans ; Male ; Middle Aged ; Splenic Artery ; pathology

Objective To explore the influence of quality of life for schizophrenic patients who exercise yoga and manual therapy. Methods Totally 105 schizophrenic patients were divided into 3 groups: yoga group of 38 patients, manual group of 24 patients, and control group of 42 patients. All patients were surveyed by GQOLI-74 before and after treatment and treated with the antipsychotic drugs. 38 patients in Yoga group practical Yoga exercise for 8 weeks. 24 patients in manual group practiced manual. After 8 weeks, all patients were measured by GQOLI-74 again. Results The results showed the scores of 18 of 20 factors ( except factor 1 and factor 4) , four dimensions and full score in yoga group and manual therapy group were significantly higher than that in control group (P ＜0. 05). The scores of 11 factors ( sleep and energy, malaise of physical, function of sport and feeling,stress state of spiritual, negative affect, positive affect, cognition, self pride, negative affect, spare recreation time, marriage and family ) and 3 dimensions ( physical function, psychological function, social function) and full score in Yoga group were significantly higher than those in manual group. Conclusions Yoga exercise and manual therapy were benefit for the quality of life of schizophrenic patients. Yoga exercise was better than manual therapy.

OBJECTIVETo analyze the clinical and laboratory features of patients with congenital dyserythropoietic anemia type I (CDA-I), and improve the clinical diagnostic accuracy.

METHODSThe clinical and hematological features of 5 patients diagnosed as CDA-I in our hospital between July 2002 and July 2007 were analyzed retrospectively, and the related literatures was reviewed.

RESULTSFive CDA-I patients, 1 male and 4 females, all had a long history of varied degree of chronic anemia. One patient had congenital malformations, 3 jaundice and 4 hepatosplenomegaly. Bone marrow specimens invariably showed hypercellularity due to erythroid hyperplasia with megaloblastic changes, irregularly shaped nuclear, and chromatin bridges in 0.2% to 0.6% of all erythroblasts. All the 5 patients' bone marrow erythroblasts showed spongy heterochromatin appearances (swiss-cheese) with electron microscopy examination. There was no morphologic abnormality in the granulocytes and megakaryocytes. Serum ferritin levels were increased in 3/4 patients. One patient had been misdiagnosed as hereditary spherocytosis and performed splenectomy in the local hospital with no improvement in Hb level.

CONCLUSIONSCDA-I is a rare congenital anemia characterized by ineffective erythropoiesis, jaundice, hepatosplenomegaly and iron overload, and may be misdiagnosed. Keeping these manifestations in mind should avoid misdiagnosis.

Adolescent ; Adult ; Anemia, Dyserythropoietic, Congenital ; blood ; diagnosis ; Female ; Humans ; Male ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the mechanism of hyperlipidemia- and imflammation-induced functional impairment of the endothelium.

METHODSThe experiment was conducted using 3 groups of rats fed for 20 weeks with standard chow (control group), high-fat diet and high-fat diet with daily fenofibrate treatment (10 mg/kg, starting since the fifth week), respectively. After 4 and 20 weeks of feeding, respectively, serum lipid level and NO concentration were measured in the rats, and the epithelial vascular cell adhesion molecule-1 (VCAM-1) expression and cell adhesiveness to the aortic endothelium were observed.

RESULTSCompared with the control group, the rats with hyperlipidemia induced by long-term high-fat diet feeding showed lower NO concentration and increased leukocyte accumulation on the endothelial surface, exhibiting also stronger and more extensive endothelial expression of VCAM-1. In contrast, the hyperlipidemic rats with fenofibrate treatment shoed significantly decreased VCAM-1 expression and leukocyte adhesion with recovery of the NO level.

CONCLUSIONNO deficiency and activation of inflammation are involved in vascular impairment in rats with high-fat diet-induced hyperlipidemia, and fenofibrate can effectively prevent atherosclerosis by restoring NO concentration and down-regulating VCAM-1 expression in these rats.

Animals ; Atherosclerosis ; prevention & control ; Cell Adhesion ; Endothelium, Vascular ; drug effects ; metabolism ; Fenofibrate ; pharmacology ; Hyperlipidemias ; drug therapy ; metabolism ; Inflammation ; Leukocytes ; cytology ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vascular Cell Adhesion Molecule-1 ; metabolism

Animals ; Chemokine CCL2 ; analysis ; genetics ; Diabetes Mellitus, Experimental ; drug therapy ; physiopathology ; Drug Therapy, Combination ; Fatty Acids, Monounsaturated ; administration & dosage ; Indoles ; administration & dosage ; Kidney ; drug effects ; physiopathology ; Male ; NF-kappa B ; analysis ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Tetrazoles ; administration & dosage ; Transcription Factor RelA ; Valine ; administration & dosage ; analogs & derivatives ; Valsartan

OBJECTIVETo build 3D-pharmacophore model of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors using distance comparisons method and design novel EGFR inhibitors.

METHODSThirteen typical EGFR inhibitors were selected, and their biologically active conformations were obtained by using DOCK5.0 program, then 3D-pharmacophore model of EGFR inhibitors was built using distance comparisons method.

RESULTSValidation of the 3D-pharmacophore model was carried out and novel structures with potential inhibitory activity were selected by means of 3D-searching and docking method.

CONCLUSIONThis method can improve hit rate of lead compounds discovery and can be used to design novel EGFR inhibitors.

Drug Design ; Enzyme Inhibitors ; Epidermal Growth Factor ; metabolism ; Models, Chemical ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; chemistry ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; chemistry ; Structure-Activity Relationship