Voltage-gated sodium channels (VGSCs), which are widely distributed in the excitable cells, are the primary mediators of electrical signal amplification and propagation. They play important roles in the excitative conduction of the neurons and cardiac muscle cells. The abnormalities of the structures and functions of VGSCs can change the excitability of the cells, resulting in a variety of diseases such as neuropathic pain, epilepsy and arrhythmia. At present, some voltage-gated sodium channel blockers are used for treating those diseases. In the recent years, several neurotoxins have been purified from the venom of the animals, which could inhibit the current of the voltage-gated sodium channels. Usually, these neurotoxins are compounds or small peptides that have been further designed and modified for targeted drugs of sodium channelopathies in the clinical treatment. In addition, a novel cysteine-rich secretory protein (CRBGP) has been isolated and purified from the buccal gland of the lampreys (Lampetra japonica), and it could inhibit the Na+ current of the hippocampus and dorsal root neurons for the first time. In the present study, the progress of the sodium channelopathies and the biological functions of voltage-gated sodium channel blockers are analyzed and summarized.
Animals ; Channelopathies ; physiopathology ; Hippocampus ; drug effects ; Neurons ; drug effects ; Neurotoxins ; pharmacology ; Venoms ; chemistry ; Voltage-Gated Sodium Channel Blockers ; pharmacology

Objective To investigate the alterations of peripheral blood T lymphocyte subsets in patients with sepsis and septic acute kidney injury, and explore the clinical significance.Methods Fifty-five patients with sepsis and forty-three patients with septic acute kidney injury were enrolled in this study. At the same period, thirty healthy subjects were enrolled as the control group.T lymphocyte subsets inclu-ding CD3 +T, CD4 +T, CD8 +T cells, and CD4 +T/CD8 +T in peripheral blood were detected by flow cy-tometry, and acute physiology and chronic health evaluation Ⅱ( APACHE Ⅱ) were graded within twenty-four hours after admission.Then, correlation of the APACHEⅡscores and T lymphocyte subsets was ana-lyzed.Results In the septic acute kidney injury group, peripheral blood CD3 +T, CD4 +T cell percenta-ges, and CD4 +T/CD8 +T ratio were significantly lower than those in the control group and the sepsis group (all P <0.05).In the septic acute kidney injury group with stage 3, CD3+T, CD4 +T cell percentages, and CD4 +T/CD8 +T ratio in the patients were significantly lower than those in stage 1 and stage 2 ( all P <0.05).In the septic acute kidney injury group,CD3 +T, CD4 +T cell percentages, and CD4 +T/CD8 +T ra-tio were significantly lower in dead group than those in survival group (all P <0.05).APACHEⅡscores in patients with sepsis were significantly negatively correlated with peripheral blood CD4 +T cell percentages and CD4 +T/CD8 +T ratio ( r =-0.645,-0.492, allP <0.05).Conclusions There are varying de-grees of cellular immune imbalance in patients with sepsis and septic acute kidney injury, characterized by decline of circulating CD3 +T, CD4 +T cell percentages, and CD4 +T/CD8 +T ratio.CD4 +T cell percenta-ges and CD4 +T/CD8 +T ratio are closely related to the severity and prognosis of septic acute kidney injury.

Objective To detect the expressions of CD70 mRNA and protein and to determine the methylation status of CD70 gene promoter in T cells from patients with systemic lupus erythematosus (SLE).Methods Peripheral blood CD4+ and CD8+ T cells were isolated from 15 patients with active SLE,15 patients with inactive SLE and 15 healthy control subjects.Real-time quantitative reverse transcription-PCR was carried out to quantify the mRNA expression of CD70,flow cytometry to determine the frequency of CD4+CD70+ and CD8+ CD70+ T cells,and bisulfite sequencing to evaluate the methylation status of CD70 gene promoter in CD4+ and CD8+ T cells.Differences in these parameters among these groups were analyzed by one-factor analysis of variance and SNK-q test.Results Compared with the healthy controls,the patients with active SLE and inactive SLE showed a significant increase in CD70 mRNA expression in CD4+ T cells (0.82 ± 0.12 and 0.73 ± 0.11 vs.0.45 ±0.09,F =53.017,P ＜ 0.01) and in the frequency of CD70+CD4+ T cells (80.30％ ± 11.04％ and 66.80％ ± 3.98％ vs.12.48％ ± 3.45％,F =311.517,P ＜ 0.01).Also,the expression of CD70 mRNA in CD4+ T cells and the frequency of CD70+CD4+ T cells were significantly higher in patients with active SLE than in patients with inactive SLE (both P ＜ 0.05).There was a positive correlation between the frequency of peripheral CD70+CD4+ T cells and disease activity in SLE in these patients (r =0.792,P ＜ 0.01).The average methylation index of the region between-600 bp and-300 bp of CD70 gene promoter in CD4+ T cells was 0.32 ± 0.05 and 0.36 ± 0.05 respectively in the patients with active and inactive SLE,significantly lower than that in the healthy controls (0.62 ± 0.05,F =152.64,P ＜ 0.01),and the patients with active SLE showed a significantly lower methylation index than those with inactive SLE (P ＜ 0.05).Conclusions The CD70 gene promoter in CD4+ T cells is significantly hypomethylated in patients with SLE,which may directly lead to the overexpression of CD70.

OBJECTIVETo prepare a mouse model of asthma by sensitizing and challenging with house dust mite allergen Derp and evaluate its reliability by measuring airway allergy inflammation and airway responsiveness.

METHODSTwelve C57BL/6J mice were randomly divided into two groups: control and asthma model. Mice of the asthma model group were sensitized by intraperitoneal injection of house dust mite allergen Derp on the first and tenth days of the experiment. From the 17th day, the mice were challenged by intranasal Derp, once every other day, seven times. The control group was treated with normal sodium instead of Derp. Twenty-four hours after the last challenge, airway responsiveness was evaluated. Bronchoalveolar lavage and histological examination of the lung were performed.

RESULTSAirway resistance increased and dynamic lung compliance decreased significantly in the asthma model group as compared to the control group (P<0.01). When airway resistance increased by 25% and dynamic lung compliance decreased by 15%, the required metacholine concentration in the asthma model group was significantly lower than that in the control group (P<0.01). In the bronchoalveolar lavage fluid of the asthma model group, the number of total cells, absolute number of eosinophils (EOS) and the percentage of EOS in the total cell were significantly higher than those in the control group (P<0.01). Pulmonary pathological scores in the asthma model group were significantly higher than those in the control group (P<0.01). The asthma model group showed ultrastructural changes of bronchial and pulmonary arterioles. Goblet cells, mastocyte granules, and increased mucus were observed in the lung tissues of the asthma model group.

CONCLUSIONSA mouse model of asthma was prepared by sensitizing and challenging with house dust mite allergen Derp, with the characteristics of airway allergy inflammation and airway hypersensitivity reaction.

Airway Resistance ; Animals ; Arterioles ; ultrastructure ; Asthma ; etiology ; pathology ; physiopathology ; Disease Models, Animal ; Eosinophils ; pathology ; Female ; Lung ; pathology ; ultrastructure ; Lung Compliance ; Mice ; Mice, Inbred C57BL ; Pyroglyphidae ; immunology

Argyrogramma agnata has been selected as a substitutive host insect for producing Dendrolimus punctatus Cytoplasmic Polyhedrosis Virus (DpCPV). In our experiment, it is very susceptible to DpCPV. The DpCPV produced in A. agnata is designated Aa-DpCPV. The cytoplasmic polyhedra body (CPB), the virion size and the shape of Aa-DpCPV are same as that of its original DpCPV (DpCPV-W1984). The RNA bands of Aa-DpCPV and DpCPV-W1984 all have 10 RNA segments respectively in 3% PAGE, which molecular weights ranged in size from 2.98×106 to 0.66×106 Dalton. Aa-DpCPV has the same strong toxicity as that of DpCPV-W1984 (from D. punctatus) to D. punctatus (Walker) larva. So it can be applied to the pine caterpillar control. The DpCPV yield in A.agnata is 2.5×108CPB/larva.

Objective:To investigate the relationship between the changes in inflammatory markers levels and the onset of post-traumatic stress disorder (PTSD) in the early stage of acute trauma..Methods:From January 2018 to June 2020, patients with acute trauma who were admitted to the Affiliated Hospital of Xuzhou Medical University were selected as subjects. Peripheral venous blood was collected on admission, on the 3rd and 7th day after trauma for routine blood test, C-reactive protein (CRP) and procalcitonin (PCT). The neutrophil to lymphocyte ratio (NLR) was calculated. The PCL-5 scale was used to evaluate PTSD symptoms one month later. The patients were divided into the PTSD group and non-PTSD group with the score of 38 as the boundary. The change rule of NLR in the PTSD group and the non-PTSD group were analyzed.Results:Ninety-one trauma patients were enrolled, including 23 patients in the PTSD group and 68 patients in the non-PTSD group. Compared with the healthy control group, the NLR of 91 trauma patients on admission, on the 3rd and 7th day were significantly higher (all P< 0.01). The NLR of the PTSD group was increased on the 7th day after trauma, which was significantly higher than that of the non-PTSD group ( P= 0.025). The non-PTSD group showed a decreasing trend, of which NLR on the 7th day was significantly lower than that on admission ( P= 0.001). In addition, high level of NLR on the 7th day after trauma (β= 0.206, P= 0.01) was a risk factor for PTSD onset. Conclusions:Dynamic monitoring of the changes in NLR after acute trauma would be of great clinical value to early warning of PTSD.

OBJECTIVETo explore the methylation status in promoter region of norepinephrine transporter gene (NET, SLC6A2) in heart failure ( HF) patients and its correlation with qi deficiency/blood stasis syndrome (QDS/BSS).

METHODSThirty-six patients with heart failure (NYHA classification III to IV) were recruited in the study (as the heart failure group) and their scores of QDS/BSS were evaluated. Besides, a healthy elderly group (30 cases) and a healthy youth group (30 cases) were also set up. They were recruited from Physical Examination Center of Fujian Provincial Hospital. Pyrosequencing was applied to detect the methylation in promoter region of SLC6A2 gene, and the total methylation index (MTI) of CpG island was calculated. The correlation between the methylation status in promoter region of SLC6A2 and scores of QDS/BSS was assessed using Pearson and Partial analyses. Risk factors were screened and adjusted using Logistic regression.

RESULTSBy one-factor analysis of variance, the total MTI in the HF group (219.72% ± 54.03%) was obviously higher than that in the healthy elderly group (194.47% ± 34.92%) and the healthy youth group (161.60% ± 41.11%) (all P < 0.05). Meanwhile, the total MTI was higher in the healthy elderly group than in the healthy youth group (P < 0.01). By covariance analysis , after controlling age and BMI, the total MTI was higher in the HF group than in the healthy elderly group (P = 0.041), while it was higher in the healthy elderly group than in the healthy youth group (P = 0.016). Age was found to play an essential role in affecting MTI of SLC6A2 gene promoter region among the 3 groups (F = 16.447, P = 0.01). The total MTI was quite lower in the healthy youth group. Results of Partial correlation analysis showed MTI was positively correlated with scores of qi deficiency and blood stasis respectively (r = 0.494 and 0.419 respectively, both P < 0.05). Logistic regression analysis showed after adjusting confounding factors, the relative risk (OR value) of total MTI of SLC6A2 gene in promoter region was 1.038 (95% CI, 1.006 to 1.071, P = 0.020).

CONCLUSIONSAbnormally elevated methylation of the promoter region of SLC6A2 gene is one of risk factors for HF. In addition, the degree of methylation of the promoter region of SLC6A2 gene was positively correlated with the severity of QDS/BSS.

Adolescent ; Aged ; DNA Methylation ; Heart Failure ; genetics ; physiopathology ; Humans ; Logistic Models ; Medicine, Chinese Traditional ; Norepinephrine Plasma Membrane Transport Proteins ; genetics ; Promoter Regions, Genetic ; Qi

This experiment aimed to explore and research the process of preparing baicalein and wogonin through liquid fermentation with Bacillus natto. Active enzymes of produced by B. natto was used for the biological transformation of baclin and wogonoside, in order to increase the content of the haicalein and wogonin in the scutellaria. With the content of the baicalein and wogonin as evaluating indexes, the effects of carbon source, nitrogen source, the types and suitable concentration of inorganic salt, medium pH, granularities of medical materials, liquid volume in flask, shaking speed, liquid-to-solid ratio, fermentation time on the fermentation process were studied. The optimal process conditions for liquid fermentation of scutellaria were 1.0% of peptone, 0.05% of NaCl, pH at 6, the granularities of medical materials of the scutellaria screened through 40-mesh sifter, 33% of liquid, shaker incubator speed at 200 r x min(-1), liquid-to-solid ratio of 5:1, temperature at 37 degrees C, fermentation for 6 days, baclin's conversion rate at 97.6% and wogonoside's conversion rate at 97% in the scutellaria. According to the verification test, the process was stable and feasible, and could provide data reference for the industrial production.
Bacillus subtilis ; metabolism ; Biotransformation ; Fermentation ; Flavanones ; metabolism ; Flavonoids ; metabolism ; Glucosides ; metabolism ; Soy Foods ; microbiology

Moderate drought stress has been found to promote the accumulation of active ingredients in Glycyrrhiza uralensis root and hence improve the medicinal quality. In this study, the transcriptomes of 6-month-old moderate drought stressed and control G. uralensis root (the relative water content in soil was 40%-45% and 70%-75%, respectively) were sequenced using Illumina HiSeq 2000. A total of 80,490 490 and 82 588 278 clean reads, 94,828 and 305,100 unigenes with N50 sequence of 1,007 and 1,125 nt were obtained in drought treated and control transcriptome, respectively. Differentially expressed genes analysis revealed that the genes of some cell wall enzymes such as β-xylosidase, legumain and GDP-L-fucose synthase were down-regulated indicating that moderate drought stress might inhibit the primary cell wall degradation and programmed cell death in root cells. The genes of some key enzymes involved in terpenoid and flavonoid biosynthesis were up-regulated by moderate drought stress might be the reason for the enhancement for the active ingredients accumulation in G. uralensis root. The promotion of the biosynthesis and signal transduction of auxin, ethylene and cytokinins by moderate drought stress might enhance the root formation and cell proliferation. The promotion of the biosynthesis and signal transduction of abscisic acid and jasmonic acid by moderate drought stress might enhance the drought stress tolerance in G. uralensis. The inhibition of the biosynthesis and signal transduction of gibberellin and brassinolide by moderate drought stress might retard the shoot growth in G. uralensis.
Droughts ; Gene Expression Regulation, Plant ; Glycyrrhiza uralensis ; genetics ; Plant Roots ; Sequence Analysis, DNA ; Stress, Physiological ; Transcriptome

Objective To compare the different effects of 1% diatrizoate meglumine,2.5% mannitol and water as oral contrasts in PET/CT scan in gastrointestinal tract delineation and 18F-fluorodeoxyglucose (FDG) uptake. Methods Sixty-one patients referred for PET/CT scan without gastrointestinal diseases were divided into three groups randomly ( random number method). One liter of 1% diatrizoate meglumine,2.5% mannitol,or water was orally taken by groups 1 (25 cases),2 (20 cases) and 3 ( 16 cases),respectively before scan. The scan was performed with GE Discovery LS PET/CT scanner in two-dimensional (2D) mode 50 min after 18F-FDG (5.55 MBq/kg) injection. Patients with abdominal lesions were excluded from this study. The degree of gastrointestinal filling and 18F-FDG uptake was evaluated by 3 nuclear medicine physicians using visual analysis according to a 4-grade classification method:none,mild,moderate,and high. Statistically analysis was performed by Kruskal-Wallis,Mann-Whitney and paired t tests.Results Both the differences of serum glucose and insulin levels were not significant before and after contrast taken in group 2. Group 2 had better gastrointestinal filling than that of group 1 and also better than group 3 except in rectum. The stomach,jejunum,ascending,and transverse colon were better filled in group 1 than in group 3. The degree of 18F-FDG uptake of group 3 was significantly higher than that of group 2 in stomach,jejunum and ileum (z= -3. 192,-3.290,-3.290,all P＜0.05),and was also significantly higher than that of group 1 (z = - 3. 603,P ＜ 0.05) in jejunum. The degree of 18 F-FDG uptake of group 3 was significantly lower than that of group 1 in ascending colon (z = - 2. 706,P ＜ 0. 05 ) and was significantly lower than that of group 1 and 2 in transverse and descending colon (z= - 3. 503,- 2.403,- 4.225,-4. 027,all P ＜0.05),and was also significantly lower than that of group 2 in rectum (z = -4. 128,P ＜0. 01 ). The maximum CT values in stomach,jejunum,ileum and ascending colon in group 1 were ( 132 ±23),(191 ±31),(313 ±47) and (374±53) HU,respectively,whose difference was significant (t = -7.088--1.781,all P ＜0. 01 ). Conclusion Oral iso-osmotic mannitol intake has better gastrointestinal filling and less physiological 18F-FDG uptake compared to diatrizoate meglumine and water.