Effects of dry swallowing and swallowing tasks of varying consistencies and volumes on the hyoid muscles in healthy adults / 中国组织工程研究

BACKGROUND:Modification of food consistency and volume is a commonly used method of swallowing compensation in clinical practice.Dry swallowing is a commonly used method of evaluation.The hyoid muscles are very important in swallowing.The effects of dry swallowing and swallowing tasks of different consistencies and volumes on hyoid muscle activation levels are still unclear. OBJECTIVE:To explore the effects of simple dry swallowing and swallowing tasks of different consistencies and volumes on the hyoid muscles in healthy adults. METHODS:A total of 44 healthy adults were included from April to August 2019,including 19 males and 25 females,with an average age of(21.7±2.8)years.They randomly performed dry swallowing and swallowing tasks of different consistencies(the International Dysphagia Diet Standardisation Initiative(IDDSI)frame levels 0-4)and volumes(5,10,20 mL),and the surface electromyogram signals of the hyoid muscles during each swallowing task were recorded.After processing the raw surface electromyogram signals,the activation levels of the hyoid muscles were compared between dry swallowing and swallowing tasks of different consistency and volume. RESULTS AND CONCLUSION:The mean amplitude values of the suprahyoid muscles corresponding to swallowing tasks of 20 mL for levels 0-4,10 mL for level 3,and 5 mL for level 4 were higher than those of dry swallowing(P＜0.05).The mean amplitude values of the suprahyoid muscles corresponding to the 20-mL swallowing tasks of different consistencies were higher than those of the 5-mL swallowing tasks of the corresponding consistencies,except for level 3(P＜0.05).The mean amplitude values of the suprahyoid muscles corresponding to the 20-mL swallowing tasks of different consistencies were higher than those of the 10-mL swallowing tasks of the corresponding consistencies,except for levels 2 and 3(P＜0.05).The mean amplitude values of the infrahyoid muscles corresponding to all swallowing tasks were higher than that of dry swallowing(P＜0.05).The mean amplitude values of the infrahyoid muscles corresponding to the 20-mL swallowing tasks of different consistencies were higher than that of the 5-and 10-mL swallowing tasks of the corresponding consistencies(P＜0.05).The mean amplitude values of the infrahyoid muscles corresponding to the 10-mL swallowing tasks of different consistencies were higher than those of the 5-mL swallowing tasks of the corresponding consistencies,except for level 3(P＜0.05).To conclude,in healthy adults performing swallowing tasks of different volumes and consistencies,the level of activation of the hyoid muscles is less susceptible to IDDSI frame levels 0-4 consistency and more susceptible to volume.The higher volume indicates the higher activation level of the hyoid muscles.

Effect of vitamin B6 on vascular endothelial injury of atherosclerosis mice and its mechanism / 新乡医学院学报

Objective To investigate the effect of vitamin B6(VB6)on vascular endothelial injury of atherosclerosis(AS)mice and its mechanism.Methods Thirty-six ApoE-/-mice were randomly divided into control group,AS group,VB6 group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group,with 6 mice in each group.The mice in the AS group,AS+LiCl group,AS+VB6 group and AS+VB6+LiCl group were fed with high-fat diet for 12 weeks to establish the AS model;the mice in the control group and VB6 group were given regular diet and normal drinking water for 12 weeks.After 12 weeks,the mice in the control group were given conventional diet and the same volume of physiological saline as the VB6 group daily by gavage;the mice in the VB6 group were given routine diet and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+LiCl group were given high-fat diet continuously and LiCl(1 mg·kg-1)by gavage daily;the mice in the AS+VB6 group were given high-fat diet continuously and VB6(50 mg·kg-1)by gavage daily;the mice in the AS+VB6+LiCl group were given high-fat diet continuously and VB6(50 mg·kg-1),LiCl(1 mg·kg-1)by gavage daily;all mice were intervened for 4 weeks.After intervention,the serum nitric oxide(NO),malondialdehyde(MD A)levels and superoxide dismutase(SOD)activity of mice in each group were measured by enzyme linked immunosorbent assay.Hematoxylin-eosin staining was used to observe the morphology of thoracic aortic tissue of mice in each group and the percentage of AS plaque area to total vascular area was calculated.The vasodilatation rate of thoracic aorta was detected by isolated vascular ring experiment.The expression of sodium/hydrogen exchanger 1(NHE1)protein in thoracic aorta was detected by immunohistochemistry.Results Compared with the control group,the NO level and SOD activity in the serum of mice in the AS group decreased,while the MDA level increased(P＜0.05);there was no significant difference in the NO,MDA levels and SOD activity in the serum of mice between the VB6 group and the control group(P＞0.05).Compared with the AS group,the serum NO level and SOD activity of mice in the AS+VB6 group increased,while the MDA level decreased(P＜0.05);there was no significant difference in serum NO,MDA levels and SOD activity of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P＞0.05).Compared with the AS+VB6 group,the serum NO level and SOD activity of mice in the AS+VB6+LiCl group decreased,while the MDA level increased(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS group was significantly higher than that in the control group(P＜0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice among the VB6 group and the control group(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the percentage of AS plaque area to total vascular area of mice between the AS+LiCl group,AS+VB6+LiCl group and AS group(P＜0.05).The percentage of AS plaque area to total vascular area of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).In the control group,the vascular endothelium of mice was smooth with orderly arrangement of cells;in the AS group,AS+LiCl group and AS+VB6+LiCl group,the tissue structure of vascular of mice was disordered and the vascular endothelium was rough;in the VB6 group and AS+VB6 group,the vascular wall structure of mice was normal,the vascular endothelium was smooth,and the cells were arranged orderly.The vasodilatation rate of thoracic aorta of mice induced by acetylcholine(Ach)in the AS group was significantly lower than that in the control group(P＜0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between the VB6 group and the control group(P＞0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by Ach between AS+LiCl group,AS+VB6+LiCl group and AS group(P＞0.05).The vasodilatation rate of thoracic aorta of mice induced by Ach in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).There was no significant difference in the vasodilatation rate of thoracic aorta of mice induced by sodium nitroprusside among the six groups(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS group was significantly higher than that in the control group(P＜0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice between the VB6 group and the control group(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6 group was significantly lower than that in the AS group(P＜0.05);there was no significant difference in the percentage of NHE1 expression in the thoracic aorta of mice among the AS+LiCl group,AS+VB6+LiCl group and the AS group(P＞0.05).The percentage of NHE1 expression in the thoracic aorta of mice in the AS+VB6+LiCl group was significantly higher than that in the AS+VB6 group(P＜0.05).Conclusion VB6 can improve vascular endothelial injury in AS mice via inhibiting the expression of NHE1 protein.

Rubescensine A reduces podocyte damage induced by high glucose through the autophagy pathway mediated by AMPK/SIRT1 pathway / 中国糖尿病杂志

Objective To investigate the mechanism that Rubescensine A reduces the podocyte damage induced by high glucose(HG)through the autophagy pathway mediated by AMP activated protein kinase/silent information regulator 1(AMPK/SIRT1)pathway.Methods Human glomerular podocytes were cultured in vitro,and randomly divided into Control group(Con),HG group,hydroxychloroquine(HCQ)group,and Rapamycin(RAP)group.CCK-8 was used to detect cell viability.Western blotting was used to detect cell apoptosis and podocyte injury related protein expression in each group.The podocyte model induced by high glucose(HG)was treated with Rubescensine A(Rub A)at different concentrations and the optimal concentration was selected.Then,human glomerular podocytes were randomly divided into Con group,HG group,Rub A group,Compound C group,and Rub A+Compound C group.The expression of autophagy,AMPK/SIRT1 pathway related proteins were detected in each group.Results Compared with Con group,the podocyte viability and the protein expressions of Synaptopodin and Bcl-2 was significantly reduced(P<0.05),while the protein expressions of Desmin and Bax were significantly increased in HG group(P<0.05).Compared with the HG group,all indicators were relieved in RAP group.However,the levels of all indicators were worsened in HCQ group.Compared with Con group,the expression levels of Desminand Bax proteins in podocytes were significantly increased(P<0.05),and the podocyte viability,number of autophagosomes,the expression levels of Synaptopodin,Bcl-2,microtubule associated protein light chain 3(LC3)II/I,Beclin-1,p-AMPK/AMPK and SIRT1 proteins were significantly reduced in HG group(P<0.05).Compared with HG group and Rub A+Compound C group,the above indicators were improved in Rub A group.Compound C group reversed the protective effect of Rub A.Conclusion Rubescensine A can promote autophagy by activating AMPK/SIRT1 pathway,thereby reduce podocyte damage induced by high glucose.

B1 corrected T1 mapping for distinguishing pathological types and differentiation degrees of lung cancers / 中国医学影像技术

Objective To observe the value of B1 corrected T1 mapping for distinguishing pathological types and differentiation degrees of lung cancers.Methods A total of 74 lesions in 65 patients with lung cancers were prospectively enrolled,including 49 poorly differentiated lesions and 25 moderately or well differentiated ones,i.e.42 adenocarcinomas,14 squamous cell carcinomas and 18 small cell lung cancers(all poorly differentiated).B1 corrected T1 mapping was performed,ROI(ROI1 and ROI2)were delineated using 2 methods,and T1 values of different pathological types and differentiation degrees lung cancers were compared.The receiver operating characteristic(ROC)curves were drawn,and the areas under the curve(AUC)were calculated.Results Significant differences of T1 values were found among different pathological types of lung cancer(all P＜0.05),as well as between small cell lung cancer and the rest 2 types of lung cancer(both P＜0.05).There were significant differences of T1 values between poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)(both P＜0.05).Taken ROI1 T1 value=1 524.21 ms as the cut-off value,the AUC of T1 value for distinguishing poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)was 0.698,with sensitivity of 64.50％and specificity of 76.00％.Taken ROI2 T1 value=1 630.68 ms as the cut-off value,the AUC of T1 value was 0.676,with sensitivity of 54.80％and specificity of 80.00％.Conclusion B1 corrected T1 mapping was helpful for distinguishing pathological types and differentiation degrees of lung cancers.

The study on the structure of deoxyhypusine synthase in Saccharomyces cerevisiae / 安徽医科大学学报

Objective To investigate the structure of deoxyhypusine synthase(DHS)in Saccharomyces cerevisiae(Dys1)and unravel the molecular mechanism of hypusine lysine modification,providing a theoretical basis for the treatment of highly proliferative diseases such as human immunodeficiency virus type 1(HIV-1)replication.Meth-ods Using the E.coli BL21 expression system,an in vitro expression vector was constructed and used to express the protein of Dys1.Dys1 protein samples were purified using methods such as affinity chromatography and molecu-lar sieving to achieve protein purification and isolation.The crystals of Dys1 were obtained using the crystallized so-lution containing 6％Polyethylene Glycol(PEG)8000,0.1 mol/L N-2-hydroxyethylpiperazine-N-ethane-sulphoni-cacid(Hepes)pH 6.5,and 8％ethylene glycol.The crystal structure of Dys1 was resolved at a resolution of 2.8 ? using X-ray crystallography.The structural analysis was performed with CCP4i and Coot software.Results The overall structure of Dys1 was a tetramer,each monomer containing a catalytic site and a cofactor NAD+binding site.The core region of the monomer adopted a Rossmann fold.The amino acid residues involved in the substrate binding sites were highly conserved among eukaryotes.Conclusion The crystal structure of Dys1 is being resolved for the first time.It reveals the binding mode of the cofactor NAD+to the enzyme and confirms that the enzyme functions as a tetramer,with the N-terminus serving as an essential modulator for its catalytic activity.

Impact of LncRNA TUG1 on high glucose-induced cardiomyocyte apoptosis by regulating the miR-181b-5p/PDCD4 axis / 天津医药

Objective To investigate the impact of long non-coding RNA(LncRNA)taurine up-regulated gene 1(TUG1)on high glucose-induced cardiomyocyte apoptosis by regulating miR-181b-5p/programmed cell death protein 4(PDCD4)axis.Methods Diabetic cardiomyopathy(DCM)cell model was established in vitro with high glucose(HG,25 mmol/L glucose).AC16 cells were divided into the NG(5.5 mmol/L glucose)group,the HG group,the HG+sh-NC group,the HG+sh-TUG1 group,the HG+miR-NC group,the HG+miR-181b-5p group,the HG+sh-TUG1+anti-miR-NC group,the HG+sh-TUG1+anti-miR-181b-5p group,the HG+miR-181b-5p+pcDNA group and HG+miR-181b-5p+pc-PDCD4 group.The Cell Counting Kit-8(CCK-8)method was applied to detect cell viability.Lactate dehydrogenase(LDH)assay was applied to detect LDH release.Quantitative real-time polymerase chain reaction(qRT-PCR)was applied to detect expression levels of TUG1,miR-181b-5p and PDCD4 mRNA.Flow cytometry was applied to detect apoptosis.Western blot assay was applied to detect levels of B-cell lymphoma 2-associated X(Bax),activated caspase 3(cleaved caspase 3)and PDCD4 proteins.Caspase-Glo3 assay was applied to assess caspase 3 activity.Dual-luciferase reporter assay was applied to verify the targeting relationship between TUG1 or PDCD4 and miR-181b-5p.Results Compared with the NG group,the cell activity decreased in the HG group,and LDH release,apoptosis rate,Bax,cleaved caspase 3 expression and caspase 3 activity increased(P＜0.05),which could be antagonized by TUG1 knockdown or miR-181b-5p overexpression(P＜0.05).Inhibition of miR-181b-5p was able to alleviate the impact of TUG1 silencing on cardiomyocyte viability and apoptosis under high glucose treatment(P＜0.05).The overexpression of PDCD4 attenuated the promotion effect of miR-181b-5p up-regulation on the viability of cardiomyocytes treated with high glucose and the inhibitory effect on apoptosis.TUG1 was able to increase the expression of PDCD4 through adsorption of miR-181b-5p(P＜0.05).Conclusion TUG1 promotes high glucose-induced cardiomyocyte apoptosis by down-regulating miR-181b-5p and up-regulating PDCD4.

Artesunate alleviates hypoxic-ischemic brain damage in neonatal rats by inhibiting NLRP3 inflammasome activation and inflammatory cytokine secretion / 细胞与分子免疫学杂志

Objective To investigate the protective effect of artesunate on hypoxic-ischemic brain damage (HIBD) and its mechanism in neonatal rats. Methods 7-day-old neonatal SD rats were randomly divided into sham operation group, model group, artesunate 5 mg/kg group, artesunate 10 mg/kg group, artesunate 20 mg/kg group and dexamethasone 6 mg/kg group, with 18 rats in each group. HIBD models were established in groups except for the sham operation group. The sham operation group only needed to separate the left common carotid artery without ligation and nitrogen-oxygen mixed gas ventilation. Each group was injected with drug intraperitoneally right after surgery and the rats in the sham operation group and the model group were injected with an equal volume of normal saline (once a day for a total of 5 times). One hour after the last injection, the rats in each group were scored for neurological defects. After the rats were sacrificed, the brain water content was measured and the pathological changes of the brain tissues of rats were observed. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) was used to detect the neuronal cell apoptosis, and ELISA was applied to detect the levels of IL-1β, IL-6 and TNF-α in brain tissues and peripheral blood of each group of rats. Western blot analysis was adopted to detect the protein expression levels of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 in the rats brain tissues of each group. Results Compared with the model group, the neurological deficit score was decreased; the pathological damage of brain tissues was relieved; the brain water content was significantly reduced; the apoptosis number of hippocampal neurons was decreased significantly; the levels of IL-1β, IL-6 and TNF-α in brain tissues and peripheral blood were significantly reduced; the protein expression levels of NLRP3, ASC and caspase-1 were significantly lowered in the middle-dose and high-dose artesunate groups and the dexamethasone group. Conclusion Artesunate can improve the neurological function, relieve the brain damage, and alleviate the brain edema in neonatal rats with HIBD. It can protect the HIBD, which may be related to the inhibition of NLRP3 inflammasome activation and reduction of inflammatory cytokine secretion.

Construction and validation of a Nomogram-based prediction model for the risk of gout in men / 中华内分泌代谢杂志

Objective:To investigate the risk factors of gout and establish a columnar graph model to predict the risk of gout development.Methods:A total of 1 032 Han Chinese men attending the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, People′s Hospital of Xinjiang Uygur Autonomous Region, and the First Affiliated Hospital of Xinjiang Medical University from 2018 to 2020 were selected as study subjects and divided into training set(722 cases)and validation set(310 cases)by simple random sampling method in the ratio of 7∶3. General information and biochemical indices of the subjects were collected. The collected information was used to assess the risk of gout prevalence. LASSO regression analysis of R Studio software was used to screen the best predictors, and was introduced to construct a column line graph model for predicting gout risk using receiver operating characteristic(ROC)curves, and the Hosmer-Lemeshow test was used to assess the discrimination and calibration of the column line graph model. Finally, decision curve analysis(DCA)was performed using the rmda program package to assess the clinical utility of the model in validation data.Results:Age, uric acid, body mass index, total cholesterol, and waist-to-hip ratio were risk factors for gout( P<0.05). The column line graph prediction model based on the above five independent risk factors had good discrimination(AUC value: 0.923 for training set validation and 0.922 for validation set validation)and accuracy(Hosmer-Lemeshow test: P>0.05 for validation set validation); decision curve analysis showed that the prediction model curve had clinical practical value. Conclusion:The nomogram model established by combining age, uric acid, body mass index, total cholesterol, and waist-to-hip ratio indicators can predict the risk of gout more accurately.

Impact of interaction between NLRP3, TLR4 gene polymorphisms and triglyceride-glucose index on gout / 中华内分泌代谢杂志

Objective:To explore the effect of triglyceride glucose(TyG) index, single nucleotide polymorphism of Toll-like receptor 4(TLR4) and NOD-like receptor thermal protein domain associated protein 3(NLRP3) genes, and its interaction on the risk of gout.Methods:A total of 315 male patients with gout and 499 men for health checkup at the same period were selected. General data were collected through questionnaires, and peripheral venous blood was collected for biochemical test. Three single nucleotide polymorphisms(SNPs) of NLRP3 and TLR4 were detected with multiplex ligase assay reaction, and logistic regression analysis was applied to compare the correlation between NLRP3 and TLR4 alleles and gout risk. The interaction of SNP and TyG index with gout was analyzed by generalized multi-factor dimensionality reduction(GMDR) model and logistic regression.Results:After adjusting for smoking, drinking, and other factors, the risk of gout increased by 61.1% for each standard deviation increase in TyG index. CC genotypes of rs10754558, rs10759932, and rs7525979 were high risk genotypes of gout in Han ethnicity. GMDR results showed significant differences in the interaction models of rs10754558-TyG index, rs7525979-TyG index, and rs10759932-TyG index between control group and gout group( P<0.05), suggesting an interaction between the three genotypes of SNPs selected and TyG index. Stratified analysis of the three selected SNPs and TyG index showed that after adjusting for age, smoking, and other factors, the high TyG index patients carrying C/C or C/G genotype at rs10754558 displayed an increased risk of gout compared with those carrying GG genotype and low TyG index( OR=2.127, P<0.05). Conclusion:The CC genotypes of rs10754558, rs10759932, and rs7525979 are high risk genotypes for gout in Han ethnicity. The interaction between rs10754558 and TyG index may increase the risk of gout development.

The value of common clinical symptoms and signs of knee joint, elbow joint and lumbar spine in the diagnosis of endemic skeletal fluorosis / 中华地方病学杂志

Objective:To investigate the value of common clinical symptoms and signs of knee joint, elbow joint and lumbar spine in clinical diagnosis of endemic skeletal fluorosis.Methods:From August to October 2020, a cross-sectional survey of skeletal fluorosis was conducted in 8 administrative villages in Gaotai County and 5 administrative villages in Gaolan County, which were serious areas of drinking-water-borne endemic fluorosis in Gansu Province. Individuals aged ≥25 years old, residing for more than 1 year, and exhibiting symptoms and signs of the motor system in the affected villages were selected as the survey subjects. According to the X-ray diagnostic criteria in the "Diagnostic Standard for Endemic Skeletal Fluorosis" (WS/T 192-2021), they were divided into skeletal fluorosis group and non skeletal fluorosis group. The basic information of the two groups was collected, and orthopedic examination and digital radiography (DR) were performed. Multivariate logistic regression model was used to fit the effects of knee joint, elbow joint and lumbar spine related symptoms and signs on the diagnosis of skeletal fluorosis. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive effectiveness of the model for skeletal fluorosis, and Kappa test was used to evaluate the consistency between the model and X-ray diagnosis (the gold standard for diagnosis of skeletal fluorosis). Results:A total of 970 subjects were included in the investigation, including 501 in the skeletal fluorosis group and 469 in the non skeletal fluorosis group. Multivariate logistic regression analysis showed that elbow joint flexion and extension range of motion (ROM) decreased by ≥45° [odds ratio ( OR) = 2.73, 95% confidence interval ( CI): 2.00 - 3.72], elbow joint rotation ROM decreased by ≥30° ( OR = 3.34, 95% CI: 1.96 - 5.68), ulnar nerve injury symptoms ( OR = 3.77, 95% CI: 3.21 - 4.42), intermittent claudication ( OR = 2.72, 95% CI: 1.48 - 4.99), and positive straight leg elevation test ( OR = 1.69, 95% CI: 1.09 - 2.61) had certain impact on the diagnosis of skeletal fluorosis. The area under the ROC curve was 0.88, and the model had a good predictive ability for the diagnosis of skeletal fluorosis. After Kappa test, the Kappa value was 0.61, which suggested that the prediction of skeletal fluorosis by this model was in good agreement with X-ray diagnosis. Conclusions:Elbow joint flexion and extension limitation, elbow joint rotation limitation, ulnar nerve injury, intermittent claudication, and positive straight leg elevation test have certain diagnostic value for skeletal fluorosis. The combined diagnosis of these signs has good predictive ability for skeletal fluorosis.

Inhibition of ginsenoside Rb 1 on the epithelial-mesenchymal transition of renal tubular epithelial cells by regulating TGF-β1/Smad3 signaling pathway / 中国药房

OBJECTIVE To study the effects of ginsenoside Rb 1（G-Rb1）on epithelial-mesenchymal transition （EMT）of renal tubular epithelial cells and its potential mechanism. METHODS The growth factor β1（TGF-β1）10 ng/mL was used to induce EMT of human renal tubular epithelial cells HK- 2. The morphological changes of HK- 2 cells were observed after treated with 10， 20，30 μmol/L G-Rb1 for 48 h. The transcriptional activities of biovector SBE in human embryonic kidney cell HEK 293 were determined after 24 h treatment with 1.0，2.5，5.0，10，20，30 μmol/L G-Rb1. Effects of above concentration of G-Rb 1 on the viability of HK- 2 cells were determined after 24 h of treatment. mRNA expressions of α-smooth muscle actin （α-SMA），collagen Ⅰ （COL-Ⅰ）and fibronectin （FN）in HK- 2 cells were detected after treated with 10，20，30 μmol/L G-Rb1 for 24 h. The expressions of α-SMA，Smad3，p-Smad3，COL-Ⅰ，FN and E-cadherin were detected after treated with 10，20，30 μmol/L G-Rb1 for 24 h. RESULTS G-Rb1 of 10-30 μmol/L significantly inhibited TGF-β1-induced EMT in HK- 2 cells and the increase of transcriptional activities of biovector SBE induced by TGF-β1（P＜0.05），but had no effects on relative activities of HK- 2 cells（P＞0.05）. The protein and mRNA expressions of α-SMA，COL-Ⅰ and FN ， the protein expressions of Smad 3 and p-Smad 3 were significantly up-regulated induced by TGF-β1（P＜0.05），while the protein expression of E-cadherin was significantly down- regulated（P＜0.05）；G-Rb1 could effectively reverse aboveprotein or mRNA expressions. CONCLUSIONS G-Rb1 can protect renal tubular epithelial cells from EMT induced byxiezhishen TGF-β1 to a certain extent ，which may be related to inhibiting the activation of TGF-β1/Smad3 signaling pathway.

Identification of anthelmintic parbendazole as a therapeutic molecule for HNSCC through connectivity map-based drug repositioning

Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.

The poly(ADP-ribosyl)ation of BRD4 mediated by PARP1 promoted pathological cardiac hypertrophy

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy.

Advances in biodegradation of macrolide antibiotics / 生物工程学报

Macrolide antibiotics are a class of broad-spectrum antibiotics with the macrolide as core nucleus. Recently, antibiotic pollution has become an important environmental problem due to the irregular production and abuse of macrolide antibiotics. Microbial degradation is one of the most effective methods to deal with antibiotic pollution. This review summarizes the current status of environmental pollution caused by macrolide antibiotics, the degradation strains, the degradation enzymes, the degradation pathways and the microbial processes for degrading macrolide antibiotics. Moreover, the critical challenges on the biodegradation of macrolide antibiotics were also discussed.

To explore the relationship between serum AHSG,AQP1,TIMP-1 and the progression and recurrence of acute cerebral infarction based on Nrf2/ARE signal pathway / 中风与神经疾病杂志

@#Objective　To investigate the relationship between serum AHSG,AQP1,TIMP-1 and the progression and recurrence of acute cerebral infarction.Methods　This study adopts a prospective study 120 elderly patients with cerebral infarction who were treated in our hospital from January 2017 to December 2019 were selected as the research group,and 120 patients who underwent physical examination during the same period were selected as the control group,and the difference between the two groups was compared.The differences in the levels of AHSG,AQP1,TIMP-1,Nrf2,and ARE in patients with different disease severity and different recurrence conditions were analyzed to determine the correlation between AHSG,AQP1,TIMP-1 and the progression and recurrence of acute cerebral infarction.Results　AHSG,AQP1,TIMP-1,Nrf2,ARE levels were significantly higher than those in the control group;AHSG,AQP1,TIMP-1,Nrf2,and ARE levels are statistically significant.through correlation analysis;the severity and recurrence of the patients withcerebral infarction were positively correlated with the levels of AHSG,AQP1,TIMP-1,Nrf2,and ARE.Conclusion　In the progression and recurrence of cerebral infarction disease,through the regulation of Nrf2/ARE signal pathway,serum AHSG,AQP1 and TIMP-1 levels show a significant upward trend.

Effects of viscosity and head position on the surface electromyography of the suprahyoid muscles during swallowing / 中华物理医学与康复杂志

Objective:To explore the effect of swallowing fluids of different viscosities in different head positions on the surface electromyography (sEMG) of the suprahyoid muscles.Methods:Twenty healthy adults were asked to swallow 5ml of liquids with 5 different viscosities in 3 different head positions. sEMG signals were recorded from their suprahyoid muscles in real time. The interactions between viscosity, head position and suprahyoid muscle activation were determined using simple effect analysis.Results:Significant head position and viscosity effects were observed. In the head-turning-right or the right head-flexion position, the net amplitude values of the left suprahyoid muscles were significantly higher than those from the right side when swallowing fluid of the same viscosity. Meanwhile, the net amplitude values of the left suprahyoid muscles increased gradually and significantly from the neutral position to the head-turning-right and the right head-flexion positions. When swallowing fluid with a viscosity of 0 to 3, the net amplitude values of the right suprahyoid muscles in the right head-flexion position were significantly lower than in the neutral and right head-flexion positions. With a viscosity of 4 the values of the former were significantly higher than the latter. The net amplitude of the left superhyoid muscle group when swallowing zero-viscosity food in a head-turning-right position was significantly lower than that when swallowing food of viscosity 1 to 4. In the right head-flexion position, the net amplitude of the left superhyoid muscle group when swallowing zero-viscosity food was significantly lower than that when swallowing food of viscosity 2 to 4. When swallowing fluid of viscosity 1 it was also significantly lower than that when swallowing food of viscosity 3 to 4. In the same position, the net amplitude of the right suprhyoid muscle group when swallowing fluid of viscosity 4 was significantly higher than that with a viscosity of 0 to 1. At viscosity 3 it was significantly higher than with a viscosity of 1.Conclusion:Swallowing fluids of different viscosities in different head positions can affect the contraction of the suprahyoid muscles to different degrees.

Study on Improvement Effect of Salvianolate on Renal Interstitial Fibrosis Model Rats and Its Mechanism / 中国药房

OBJECTIVE：To study the improve ment effect of salvianolate on renal interstitial fibrosis （RIF）model rats and its possible mechanism. METHODS ：Totally 50 male SD rats were randomly divided into normal group ，model group ，losartan group （positive control group ，9 mg/kg）and salvianolate low-dose and high-dose groups （18，36 mg/kg）according to body weight ，with 10 rats in each group. Except for normal group ，other groups were given adenine 250 mg/kg intragastrically to establish RIF model. After modeling ，administration groups were given relevant medicine intragastrically ，and normal group and model group were given constant volume of normal saline intragastrically ，the volume was 10 mL/kg，once a day ，for consecutive 30 days. After last medication，the serum levels of creatinine （Scr），urea nitrogen （BUN）and 24 h proteinuria （24 h UPro ）were detected by ELISA. HE staining and Masson staining were used to observe the histopathological characteristics and fibrosis of the kidney. The degree of renal tubular injury and glomerulosclerosis were scored ，and the percentage of positive staining area of renal tissue was calculated ； immunohistochemistry and Western blot assay were used to determine the protein expression of Wnt 5a，Wnt5b，and β-catenin. RESULTS：Compared with normal group ，Scr，BUN and 24 h UPro levels ，renal tubular injury score ， glomerulosclerosis score ， the percentage of positive staining area in renal tissue ，the protein expression of Wnt 5a and β-catenin were increased significantly in model group （P＜0.05），while the expression of Wnt 5b protein was decreased significantly （P＜0.05）. Pathological changes such as mesangial hyperplasia ，fibrous tissue increase and inflammatory cell infiltration were observed under microscope. Compared with model group ，above indexes of rats were improved significantly in losartan group ，salvianolate low-dose and high-dose groups （P＜ 0.05），and the effect of salvianolate had dose-dependent trend. CONCLUSIONS ：Salvianolate has the improvement effect on RIF model rats induced by adenine ，and its mechanism may be related to inhibition of Wnt/ β-catenin signal pathway.

Case report of congenital complete heart block in premature twins and literatures review / 中华实用儿科临床杂志

Objective:To investigate the pathogenesis, precaution and treatment of neonatal congenital complete heart block (CCHB) in twins.Methods:The clinical data of a case of premature twins with neonatal CCHB from the Department of Neonatology, the First Affiliated Hospital of Xinxiang Medical University were retrospectively analyzed and related literature was reviewed.Results:(1)Case review: the 37-year-old gravida had no symptoms.Fetal ultrasound cardiogram(fUCG)at 23 weeks of gestation indicated bradycardia and CCHB.Then, the mother was diagnosed with undifferentiated connective tissue disease.After treatment with human immunoglobulin, dexamethasone and hydroxychloroquine, fUCG at 31 weeks of gestation still suggested CCHB.An emergency cesarean section was performed on the diagnosis of threatened preterm labor.With weakly positive neonatal antinuclear antibody (ANA), and positive Ro60 and Ro52 autoantibodies, twins were diagnosed with CCHB by 24 hour-Holter monitors.One of the twins was discharged with CCHB (ventricular rate of 80-90 times/min) after systemic therapy, but the weight increased to 2 200 g. The other one of the twins suffered from the sudden decrease of heart rate and blood pressure and finally died of sudden cardiac arrest.(2) Literature search: two cases in Chinese and 9 cases in English were reviewed.Among them, 9 cases were sjogren syndrome type A (SSA)/Ro and sjogren syndrome type B(SSB)/La related CCHB, and 2 cases were idiopathic CCHB.Conclusions:The placental transfer of anti-SSA or anti-SSB is an important mechanism of neonatal CCHB in twins, and other factors may also be involved.Current treatments are unsatisfactory.Most patients need pacemaker implantation.Early diagnosis and prenatal management can improve the prognosis.

Effect of Wenxin granule combined with sotalol in the treatment of arrhythmia and its influence on the levels of Ang Ⅱ, CRP and NT-proBNP / 中国基层医药

Objective:To investigate the therapeutic effect of Wenxin granule combined with sotalol on patients with arrhythmia and its influence on the levels of plasma angiotensin Ⅱ(Ang Ⅱ), C-reactive protein (CRP) and NT-proBNP.Methods:From January 2018 to October 2019, 162 patients with arrhythmia admitted to Taizhou Central Hospital were divided into observation group (81 cases) and control group (81 cases) according to the random digital table method.The control group was treated with sotalol, and the observation group was treated with Wenxin granule on the basis of the control group.The course of treatment in both two groups was 2 months.The changes of cardiac function, Ang Ⅱ, CRP and NT-proBNP levels, as well as adverse reactions were compared before and after treatment.Results:The total effective rate of the observation group (92.59%, 75/81) was higher than that of the control group (77.78%, 63/81) (χ 2=7.044, P<0.05). After treatment, the LVEDD [(53.18±3.09)mm] and LVESD [(52.19±2.35)mm] in the observation group were lower than those in the control group [(58.97±2.73)mm and (57.79±2.65)mm], while the SV [(76.93±3.67)mL] and LVEF [(53.90±2.64)%] in the observation group were higher than those in the control group [(71.35±2.87)mL and (46.75±2.18)%], the differences were statistically significant ( t=12.638, 14.230, 10.779, 18.795, all P<0.05). The plasma AngⅡ [(96.52±12.16)ng/L], CRP [(4.30±0.69)mg/L] and NT-proBNP [(394.25±47.15)ng/L] in the observation group were lower than those in the control group [(135.42±23.15)ng/L, (6.27±0.78)mg/L and (565.29±56.72)ng/L] ( t=13.389, 17.025, 20.870, all P<0.05). The incidence of adverse reactions in the observation group (11.11%) was lower than that in the control group (30.86%) (χ 2=9.529, P<0.05). Conclusion:Wenxin granule combined with sotalol is effective in the treatment of arrhythmia, which can reduce the plasma levels of Ang Ⅱ, CRP and NT-proBNP, improve the heart function and has no obvious adverse reactions.

Evaluation of comprehensive sexuality education course on sexual knowledge and attitude of college students / 中国学校卫生

Objective@#To provide empirical evidence on the effectiveness of comprehensive sexuality education (CSE) on sexual knowledge and sexual attitudes improvement among college students.@*Methods@#Sexual knowledge and attitudes questionnaire survey was implemented among college students in Beijing, who later received the CSE for a full semester. Sexual knowledge and attitude were evaluated after intervention and were compared with control students.@*Results@#The average score of sexual knowledge was low among college students in Beijing. Most students held neutral attitudes towards "AIDS community" and "masturbation behavior" and positive attitudes towards "LGBT"(58.85%, 68.75%, 61.98%). Compared with the control group, after one semester of CSE curriculum intervention, the average scores of the five dimensions on sexual knowledge in the intervention group was significantly improved(11.79±1.16, 9.36±1.23, 4.84±0.88, 4.91±1.00, 5.35±1.03)(t=11.25, 15.74, 10.37, 5.59, 8.17, P<0.01), and the attitudes towards "sexual minorities", "AIDS communities" and "masturbation behavior" were also significantly improved(30.59±3.91, 17.70±3.41, 10.12±2.17)(t=5.16, 5.83, 2.97, P<0.01).@*Conclusion@#College students’ knowledge of sexuality is not optimistic. The attention to proper sexual attitudes is in great need. Systematic and comprehensive sexuality education curriculum could improve college students’ sexual knowledge and attitudes.