OBJECTIVETo define the effects of Astragalus membranaceus on the atrial dynamics and ANP secretion in the perfused beating rabbit atria.

METHODThe experiments have been done in isolated perfused beating rabbit atria. ANP was measured by radioimmunoassay in the atrial perfusate in real-time base.

RESULTA. membranaceus (2.0, 2.5, 3.0 g L(-1)) could increase atria stroke volume from (694.70 +/- 0.01) microL g(-1) (P<0.05) to (1,003.00 +/- 8.80) microL g(-1) (P<0.001); (1,120.00 +/- 17.71) microL g(-1) and (1,195.00 +/- 8.21) microL g(-1) (P<0.001), respectively, and its could difference increase atrial pulse pressure from (0.82 +/- 0.01) kPa to (0.86 +/- 0.01) kPa (P<0.01); (0.96 +/- 0.01) kPa (P<0.001) and (1.02 +/- 0.01) kPa (P<0.001), respectively; A. membranaceus obviously increased rabbit atrial dynamics with dose-dependent manner. Simultaneously, A. membranaceus inhibited ANP secretion. Nifedipine (1.0 micromol L(-1)), a L-type Ca2+ channel inhibitor, and KB-R 7943 (10.0 micromol L(-1)), an inhibitor of reversed Na+ -Ca2+ exchanger, blocked the effects of A. membranaceus-induced augmentation of atrial dynamics but failed to modulation the inhibition of A. membranaceus on ANP secretion.

CONCLUSIONA. membranaceus increases the atrial dynamics via Na+ -Ca2+ exchanger and L-type Ca2+ channel and negatively modulates ANP secretion in beating rabbit atria.

Animals ; Astragalus membranaceus ; chemistry ; Atrial Natriuretic Factor ; metabolism ; secretion ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Female ; Heart Atria ; drug effects ; metabolism ; secretion ; Male ; Myocardial Contraction ; drug effects ; Nifedipine ; pharmacology ; Rabbits ; Radioimmunoassay ; Thiourea ; analogs & derivatives ; pharmacology

Creatine Kinase ; Humans

BACKGROUNDAutoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor (GABA B R) in patients with limbic encephalitis (LE) was first described in 2010. We present a series of Han Chinese patients for further clinical refinement.

METHODSSerum and cerebrospinal fluid (CSF) samples from patients referred to the program of encephalitis and paraneoplastic syndrome of Peking Union Medical College Hospital were tested with indirect immunofluorescence. Clinical information of patients with anti-GABA B R antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed.

RESULTSAll eighteen anti-GABA B R antibody-positive cases had limbic syndromes, and electroencephalogram (EEG) or neuroimaging evidence fulfilled the diagnostic criteria of LE. Four patients had additional antibodies against Hu in serum and one had anti-N-methyl-d-aspartate receptor antibody in both sera and CSF. Seventeen (17/18) patients presented with new-onset refractory seizure or status epileptics. Twelve (12/18) patients had memory deficits, 11 (11/18) patients had personality change, 7 (7/18) patients had disturbance of consciousness, and 3 (3/18) patients showed cerebellar dysfunction. One patient with LE had progressive motor and sensory polyneuropathy. Lung cancer was detected in 6 (6/18) patients. Ten (10/18) patients showed abnormality in bilateral or unilateral mediotemporal region on magnetic resonance imaging. Ten (10/18) patients had temporal lobe epileptic activity with or without general slowing on EEG. Seventeen patients received immunotherapy and 15 of them showed neurological improvement. Four patients with lung cancer died within 1-12 months due to neoplastic complications.

CONCLUSIONSOur study demonstrates that most Han Chinese patients with anti-GABA B R antibody-associated LE have prominent refractory epilepsy and show neurological improvement on immunotherapy. Patients with underlying lung tumor have a relatively poor prognosis. Testing for anti-GABA B R antibodies is necessary for patients with possible LE or new-onset epilepsy with unknown etiology.

Adult ; Autoantibodies ; immunology ; China ; Electroencephalography ; Epilepsy ; immunology ; pathology ; Female ; Humans ; Limbic Encephalitis ; immunology ; pathology ; Male ; Middle Aged ; Receptors, N-Methyl-D-Aspartate ; immunology ; Retrospective Studies ; gamma-Aminobutyric Acid ; metabolism

BACKGROUNDInvasive pulmonary aspergillosis (IPA) is a severe and frequently fatal disease in patients receiving treatment with immunosuppressive agents such as cyclophosphamide. Aspergillus fumigatus (A. fumigatus) now is a leading cause of IPA. Dectin-1 and Toll-like receptor 2 (TLR2) are important pattern recognition receptors involved in immune responses to A. fumigatus in vitro. However, the expression of the two receptors during the infection of A. fumigatus in vivo is not completely understood. The effects of cyclophosphamide treatment on the expression of the receptors need to be further studied.

METHODSWe established different immune status in mice models with or without A. fumigatus infection. On days 1, 3 and 5 post inoculation, pulmonary tissues from mice of the different groups were harvested. Dectin-1 and TLR2 mRNA expression in the lungs of the mice were investigated by real-time PCR. The pulmonary fungal burden in the mice with A. fumigatus infection was also evaluated.

RESULTSIn the immunocompetent mice, three days after A. fumigatus inoculation, dectin-1 and TLR2 expression increased markedly compared with the normal control group. Cyclophosphamide inhibited the clearance of pathogens and the expression of dectin-1 with or without A. fumigatus infection in the lungs as well. There was no statistical difference in TLR2 expression between the different immune status groups.

CONCLUSIONSOur results suggest that in vivo, dectin-1 and TLR2 are activated during the experimental period which would provide a broad range of possibilities for a specific and effective inflammatory response to kill A. fumigatus. Inhibition of dectin-1 expression may be one of the mechanisms of cyclophosphamide in the development of IPA.

Animals ; Aspergillosis ; immunology ; microbiology ; Aspergillus fumigatus ; immunology ; physiology ; Cyclophosphamide ; pharmacology ; Immunosuppressive Agents ; pharmacology ; Lectins, C-Type ; Lung ; drug effects ; metabolism ; microbiology ; Male ; Membrane Proteins ; genetics ; Mice ; Mice, Inbred BALB C ; Nerve Tissue Proteins ; genetics ; Polymerase Chain Reaction ; Toll-Like Receptor 2 ; genetics

In general, the volume of a parathyroid adenoma is small and rarely causes local symptoms of compression. This case of huge parathyroid adenoma presents with dyspnea as the chief complaint and does not have a series of symptoms of hyperparathyroidism, which deserves our attention.

Objective In order to test and improve the monitoring technical level and ability of radiation environmental monitoring network in Zhejiang Province, ensure the accuracy and reliability of monitoring data and information, and obtain the cosmic ray response values of instruments and equipment in this year. Methods In September 2018，an intercomparison meeting of environmental gamma radiation air absorbed dose rate within the radiation environmental monitoring network of Zhejiang province was held in Ningbo，which was organized by Zhejiang Province Radiation Environmental Monitoring Center.A total of 33 sets of instruments from 15 member units participated in the intercomparison measurements at 5 environmental measuring points, and the comparison results were evaluated by the Z score values. Results It was found that the |Z| of all measurement results were less than or equal to 2, and the evaluation results were satisfactory and acceptable. Conclusion The measured data of scintillation counters have relatively wider dispersion，and the high pressure ionization chambers have bigger response valuetocosmic ray. The measurement results of the two kinds of instruments keep a good linearity except for the measurement points of cosmic ray response.

Food intake has a great influence on blood glucose in patients with diabetes.This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D).Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement.To test effects of Majia pomelo on PPG,19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study.The dose of insulin for each patient was adjusted on the first 3 days.A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days.Blood glucose was measured to evaluate the glycemic excursions.The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34± 1.88 and 72.15±1.95 respectively.The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo,indicting Majia pomelo as a high GI but low GL fruit.Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation.It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients.These results may mean more varieties of food choices for T2D patients.

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

BACKGROUNDAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a treatable autoimmune neurologic syndrome that occurs with or without tumor association. However, some severe cases are refractory to systemic immunotherapy. This pilot study aimed to evaluate the utility and safety of intrathecal methotrexate injection for severe patients with anti-NMDAR encephalitis who did not respond to first-line immunotherapy.

METHODSIntrathecal injections with methotrexate and dexamethasone were performed weekly in four legible patients within consecutive 4 weeks. Cerebrospinal fluid (CSF) was collected at baseline and each time of intrathecal injection for identification of anti-NMDAR antibody titers.

RESULTSSignificant clinical improvement was observed in three patients associated with a stepwise decrease of CSF anti-NMDAR antibody titers (maximum: 1/320 to minimum: 1/10). After 2 months of follow-up, they were able to follow simple commands and had appropriate interactions with people (modified Rankin scale [mRS] of 0-2). At 12 months of follow-up, they all had returned to most activities of daily life (mRS of 0), and no relapses were reported. One patient showed no clinical improvement and died of neurologic complications.

CONCLUSIONSIntrathecal treatment may be a potentially useful supplementary therapy in severely affected patients with anti-NMDAR encephalitis. Further large cohort study and animal experiment may help us elaborate the utility of intrathecal injection of methotrexate and its mechanism of action.

Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor, tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.