Role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis / 临床肝胆病杂志

ObjectiveTo investigate the role and mechanism of action of Yinchenhao Decoction in inhibiting ferroptosis of hepatocytes in mice with autoimmune hepatitis. MethodsA total of 18 specific pathogen-free female C57BL/6 mice were selected and divided into normal group， model group， and treatment group using a random number table， with 6 mice in each group. The mice in the model group and the treatment group were injected with concanavalin A （Con A） via the caudal vein to establish a mouse model of autoimmune hepatitis， and those in the normal group were injected with normal saline. The mice in the treatment group were given prophylactic treatment with Yinchenhao Decoction （4.68 g crude drug/kg） by gavage at 14 days before modeling， and Con A was injected after the last gavage. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interferon gamma （IFN-γ）， tumor necrosis factor-α （TNF-α）， iron ion， glutathione （GSH）， reactive oxygen species （ROS）， adenosine triphosphate （ATP）， and malondialdehyde （MDA） were measured； liver index and spleen index were calculated； the expression levels of GPX4 and SLC7A11 were measured； liver histopathological changes were compared between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant reductions in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. Compared with the model group， the treatment group had significant reductions in liver index， spleen index， ALT， AST， IFN-γ， TNF-α， iron ion， ROS and MDA （all P<0.05） and significant increases in the content of GSH and ATP and the protein expression levels of GPX4 and SLC7A11 （all P<0.05）. HE staining showed that compared with the normal group， the model group showed massive hepatocyte degeneration and necrosis and inflammatory cell aggregation at the portal area， and compared with the model group， the treatment group had alleviation of liver necrosis and inflammatory infiltration. ConclusionLiver injury induced by Con A may be associated with ferroptosis. Yinchenhao Decoction can increase the protein expression levels of SLC7A11 and GPX4 protein and thus inhibit ferroptosis of hepatocytes induced by Con A.

Bibliometric and bioinformatics analysis of genetic literature on susceptibility to noise induced hearing loss / 中华劳动卫生职业病杂志

Objective: To summarize and analyse of literature on the susceptibility genes of noise induced hearing loss (NIHL) , and the key genes were screened and obtained by bioinformatics method, so as to provide reference for the prevention research of NIHL. Methods: In September 2021, Based on CNKI, NCBI Pubmed database and Web of Science database, this paper conducted bibliometric analysis and bioinformatics analysis on the genetic literature related to the susceptibility to noise-induced hearing loss from 1999 to 2020. Endnote X9 software and the WPS office software were used for bibliometric analysis, and online software STRING and Cytoscape software were used for bioinformatics analysis. Results: A total of 131 literatures were included in the study, involving 40 genes in total. Bibliometric analysis shows that 131 papers which included 36 Chinese articles and 95 English articles were published in 63 biomedical journals; the highest number of published articles was 19 in 2020. Bioinformatics analysis suggests that GAPDH、SOD2、SOD1、CAT、CASP3、IL6 and other genes play a key role in the interaction network. The involved pathways mainly include MAP2K and MAPK activations, PTEN regulation, P53-depardent G1 DNA damage response, signaoling by BRAF and RAF fusions and soon. Conclusion: The study of noise induced hearing loss involves multi gene biological information, and bioinformatics analysis is helpful to predict the occurrence and development of noise induced hearing loss.

Association of serum biomarkers with frailty in elderly hospitalized patients / 中华老年医学杂志

Objective:To evaluate the association of different biomarkers with frailty in elderly hospitalized patients.Methods:In this cross-sectional study, a total of 319 elderly patients aged 65 years or older hospitalized in Beijing Hospital between September 2018 and February 2019 were enrolled.Patients had a mean age of(75.0±6.6)years and 151(47.3%)were women.Based on the Fried phenotype, patients were divided into a non-frail group(244 cases, 76.5%)and a frail group(75 cases, 23.5%). The clinical characteristics and biomarker levels of the two groups were compared.The association of different biomarkers with frailty was evaluated by using the receiver operating characteristic(ROC)curve.The Youden index was used for the optimal cutoff values and the area under the curve(AUC)were calculated.AUCs of different biomarkers were compared to assess their correlations with frailty.Results:Hemoglobin, lipid levels(triglycerides, total cholesterol and low-density lipoprotein cholesterol), and prealbumin were significantly lower in the frail group than in the non-frail group( P<0.05), while N-terminal pro-B type natriuretic peptide(NT-proBNP)and high-sensitivity C reactive protein(hsCRP)levels were significantly higher than in the non-frail group( P<0.05). Thyrotropin(TSH)and free triiodothyronine(FT3)levels were significantly lower( P<0.05)and trans-triiodothyronine(rT3)was significantly higher( P<0.05)in the frail group.The combination of six biomarkers[hemoglobin, prealbumin, hsCRP, 25-dihydroxy vitamin D3[25(OH)D3], rT3 and NT-pro BNP]had the most powerful correlation with frailty(AUC=0.705, 95% CI: 0.652-0.755), but the correlation was not significantly different from that of the combination of 3 markers(hemoglobin, rT3 and hsCRP)(ROC=0.010, 95% CI: -0.0106-0.0306, P>0.05). Either of the two combinations was significantly better than the combination of 2 markers(hemoglobin and rT3)(ROC=0.143, 95% CI: 0.0406-0.245; ROC=0.153, 95% CI: 0.0498-0.256; all P<0.01). Conclusions:Hemoglobin, lipids, prealbumin, TSH and FT3 levels decrease while NT-proBNP and hsCRP levels increase in elderly hospitalized frail patients.The 6-biomarker combination[hemoglobin, prealbumin, hsCRP, 25(OH)D3, rT3 and NT-pro BNP]and 3-biomarker combination(hemoglobin, rT3 and hsCRP)have better correlation with frailty than the 2-biomarker combination(hemoglobin and rT3).

Comparison of frailty assessment and related tools in elderly hospitalized patients with atrial fibrillation / 中华老年医学杂志

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.

Adult stem cell transplantation combined with conventional therapy for the treatment of end-stage liver disease: a systematic review and meta-analysis.

End-stage liver disease (ESLD) is characterized by the deterioration of liver function and a subsequent high mortality rate. Studies have investigated the use of adult stem cells to treat ESLD. Here, a systematic review and meta-analysis was conducted to determine the efficacy of a combination therapy with adult stem cell transplantation and traditional medicine for treating ESLD. Four databases-including PubMed, Web of Science, Embase, and Cochrane Library-were investigated for studies published before January 31, 2021. The main outcome indicators were liver function index, model for end-stage liver disease (MELD) scores, and Child‒Turcotte‒Pugh (CTP) scores. Altogether, 1604 articles were retrieved, of which eight met the eligibility criteria; these studies included data for 579 patients with ESLD. Combination of adult stem cell transplantation with conventional medicine significantly improved its efficacy with respect to liver function index, CTP and MELD scores, but this effect gradually decreased over time. Moreover, a single injection of stem cells was more effective than two injections with respect to MELD and CTP scores and total bilirubin (TBIL) and albumin (ALB) levels, with no significant difference in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. With respect to the TBIL levels, patients receiving mononuclear cells (MNCs) experienced a significantly greater therapeutic effect-starting from twenty-four weeks after the treatment-whereas with respect to ALB levels, CD34+ autologous peripheral blood stem cells (CD34+ APBSCs) and MNCs had similar therapeutic effects. Severe complications associated with adult stem cell treatment were not observed. Although the benefits of combination therapy with respect to improving liver function were slightly better than those of the traditional treatment alone, they gradually decreased over time.Systematic review registration: PROSPERO registration number: CRD42021238576.

Therapeutic effect of secretome from TNF-α stimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency.

AIM: To explore the secretome efficacy in tumor necrosis factor (TNF)-α stimulated mouse mesenchymal stem cells (MSCs) in a murine model of corneal limbal alkali injury. METHODS: Corneal limbal stem cell deficiency (LSCD) was created in the eyes of male C57 mice. Concentrated conditioned medium from TNF-α stimulated MSCs (MSC-CMT) was applied topically for 4wk, with basal medium and conditioned medium from MSCs as controls. Corneal opacification, corneal inflammatory response, and corneal neovascularization (NV) were evaluated. Corneal epithelial cell apoptosis, corneal conjunctivation, and inflammatory cell infiltration were assessed with TUNEL staining, CK3 and Muc-5AC immunostaining, and CD11b immunofluorescence staining, respectively. The effect of TSG-6 was further evaluated by knockdown with short hairpin RNA (shRNA). RESULTS: Compared to the controls, topical administration of MSC-CMT significantly ameliorated the clinical symptoms of alkali-induced LSCD, with restrained corneal NV, reduced corneal epithelial cell apoptosis, and inhibition of corneal conjunctivation. In addition, MSC-CMT treatment significantly reduced CD11b+ inflammatory cell infiltration, and inhibited the expression of pro-inflammatory cytokines (IL-1ß, TNF-α and IL-6). Furthermore, the promotion of corneal epithelial reconstruction by MSC-CMT was largely abolished by TSG-6 knockdown. CONCLUSION: Our study provides evidence that MSC-CMT enhances the alleviation of corneal alkali injuries, partially through TSG-6-mediated anti-inflammatory protective mechanisms. MSC-CMT may serve as a potential strategy for treating corneal disorders.

Integrative Rehabilitation for Hypertrophic Olivary Degeneration after Operation of Brain Stem Cavernous Malformation: A Case Report / 中国康复理论与实践

Objective To summarize the integrative rehabilitation treatment of traditional Chinese medicine (TCM) and Western medicine in hypertrophic olivary degeneration (HOD) secondary to the operation of brain stem cavernous malformation. Methods The clinical data of medication, rehabilitation and follow-up of a patient with HOD secondary to operation on brain stem cavernous malformation was retrospectively analyzed. Results Three months after operation, limb static and motor tremor, dysarthria, palate spasm, eye movement disorder and walking difficulty appeared. The patient was diagnosed as HOD according to clinical features and brain magnetic resonance imaging (MRI). He was treated with pertinence rehabilitation training combined with TCM including acupuncture and herbs. After integrative rehabilitation, he could stand and walk independently, the tremor was alleviated, the balance function improved, the activities of daily living improved, and the dosage of oral western medicine also decreased. Conclusion After intracranial surgery, secondary neurodegeneration and movement disorder may appear, and it could be improved by integrative rehabilitation treatment of TCM and Western medicine

Integrative Rehabilitation for Hypertrophic Olivary Degeneration after Operation of Brain Stem Cavernous Malformation: A Case Report / 中国康复理论与实践

Objective To summarize the integrative rehabilitation treatment of traditional Chinese medicine (TCM) and Western medicine in hypertrophic olivary degeneration (HOD) secondary to the operation of brain stem cavernous malformation. Methods The clinical data of medication, rehabilitation and follow-up of a patient with HOD secondary to operation on brain stem cavernous malformation was retrospectively analyzed. Results Three months after operation, limb static and motor tremor, dysarthria, palate spasm, eye movement disorder and walking difficulty appeared. The patient was diagnosed as HOD according to clinical features and brain magnetic resonance imaging (MRI). He was treated with pertinence rehabilitation training combined with TCM including acupuncture and herbs. After integrative rehabilitation, he could stand and walk independently, the tremor was alleviated, the balance function improved, the activities of daily living improved, and the dosage of oral western medicine also decreased. Conclusion After intracranial surgery, secondary neurodegeneration and movement disorder may appear, and it could be improved by integrative rehabilitation treatment of TCM and Western medicine

The correlation between frailty and cardiac autonomic nervous function in elderly patients / 中华老年医学杂志

Objective:To assess the correlation between frailty and cardiac autonomic nervous system function in elderly patients.Methods:Elderly hospitalized patients aged 65 years and over were enrolled and assessed for frailty by using the clinical frailty scale.Cardiac autonomic modulation was evaluated by heart rate variability analysis through 24 h electrocardiogram recording.Results:A total of 180 elderly patients were enrolled in this study, including 66 patients with frailty and 114 patients without frailty.The mean age of the frailty group was higher than that of the non-frailty group(79.8±6.0 vs.75.0±6.3, t=5.030, P<0.001). The proportions of patients with hypertension, stroke/transient cerebral ischemia attack(TIA), heart failure and osteoarthritis were higher in the frailty group than in the non-frailty group(all P<0.05). Compared with the non-frailty group, the standard deviation of normal-to-normal intervals(SDNN)[103.0(76.0, 121.2) vs.107.5(92.0, 136.0), Z=-2.108, P=0.035], the standard deviation of the averages of NN intervals in all 5-min segments(SDANN)[86.0(67.7, 106.5) vs.97.5(78.0, 126.0), Z=-2.694, P=0.007], normalized low frequency(LFnorm)(53.1±13.0 vs.59.3±13.9, t=-3.024, P=0.003)and low frequency/high frequency(LF/HF)ratio[1.2(1.0, 1.4) vs.1.4(1.1, 1.7), Z=-3.041, P=0.002]were decreased and normalized high frequency(HFnorm)(36.8±9.2 vs.32.2±10.7, t=3.033, P=0.003)was increased in the frailty group.HFnorm in the frailty group was significantly higher than that in the non-frailty group.The incidents of SDANN<92 ms, LFnorm<50 nU, HFnorm>32 nU and LF/HF ratio<1.5 were higher in the frailty group than in the non-frailty group(59.1% or 39/66 vs.41.2% or 47/114, 42.4% or 28/66 vs.22.8% or 26/114, 72.7% or 48/66 vs.49.1% or 56/114, 84.8% or 56/66 vs.65.8% or 75/114, χ2=5.346, 7.660, 9.547, 7.664, P=0.021, 0.006, 0.002, 0.006). Logistic multivariate regression analysis showed that LFnorm, HFnorm and LF/HF ratio were correlated with frailty( OR=0.971, 1.039 and 0.333, all P<0.05), and HFnorm>32 nU and LF/HF ratio<1.5 were risk factors for frailty( OR=2.401 and 2.773, both P<0.05). Conclusions:Cardiac autonomic nerve system function is impaired in elderly frail patients, with the imbalance between the sympathetic and vagus nerves.Therefore particular attention should be paid to heart rate variability in elderly patients with frailty.

Predictive value of N-terminal B-type natriuretic peptide on outcome of elderly hospitalized non-heart failure patients / 中华心血管病杂志

Objective: To investigate the predictive value of N-terminal type B natriuretic peptide（NT-proBNP) on the prognosis of elderly hospitalized patients without heart failure（non-heart failure). Method: Elderly patients aged 65 years or older, who were admitted to Beijing Hospital from September 2018 to February 2019, were enrolled in this study. Patients with clinical diagnosis of heart failure or left ventricular ejection fraction（LVEF)<50% were excluded. The patients were divided into 2 groups based on the serum NT-proBNP level: low NT-proBNP group （<125 ng/L) and high NT-proBNP group（≥125 ng/L). Patients were followed up at 3, 6, and 12 months after enrollment, and the major adverse events were recorded. The composite endpoint events included all-cause mortality, readmission or Emergency Department visits. Cardiovascular events include death, readmission or emergency room treatment due to cardiogenic shock, myocardial infarction, angina pectoris, arrhythmia, heart failure or stroke/transient ischemic attack. Results: A total of 600 elderly patients with non-heart failure were included in the analysis. The average age was （74.9±6.5) years, including 304（50.7%) males. The median follow-up time was 344（265, 359) days. One hundred and seventy-eight（29.7%) composite endpoint events were recorded during the follow-up, 19（3.2%) patients died, and 12（2.0%) patients were lost to follow-up. There were 286(47.7%) cases in low NT-proBNP group and 314 cases（52.3%) in high NT-proBNP group. Patients were older, prevalence of atrial fibrillation and myocardial infarction was higher; MMSE scores and ADL scores, albumin and creatinine clearance rate were lower in high NT-proBNP group than in low NT-proBNP group（all P<0.05). At 1-year follow-up, the incidence of composite endpoint events was significantly higher in high NT-proBNP group than in low NT-proBNP group（33.4%（105/314) vs. 24.8%（71/286), P = 0.02). Cardiovascular events were more common in high NT-proBNP group than in low NT-proBNP group（17.5%（55/314) vs. 8.4%（24/286), P = 0.001). Kaplan-Meier survival analysis showed both composite endpoint events（Log-rank P=0.016) and cardiovascular events（Log-rank P=0.001) were higher in high NT-proBNP group than in low NT-proBNP group. All-cause mortality was also significantly higher in highNT-proBNP group than in lowNT-proBNP group（4.8%（15/314) vs. 1.4%（4/286), P = 0.020), and Kaplan-Meier survival analysis demonstrated borderline statistical significance（Log-rank P = 0.052). Cox proportional hazard regression analysis showed that after adjusting for age, sex, creatinine clearance rate, myocardial infarction, and atrial fibrillation, NT-proBNP remained as an independent risk factor for composite endpoint events（HR=1.376，95%CI 1.049-1.806, P=0.021), and cardiovascular events（HR=1.777, 95%CI 1.185-2.664, P=0.005), but not for all-cause mortality（P=0.206). Conclusions: NT-proBNP level at admission has important predictive value on rehospitalization and cardiovascular events for hospitalized elderly non-heart failure patients. NT-proBNP examination is helpful for risk stratification in this patient cohort.

Cardiac autonomic nerve function in elderly patients with frailty / 中华全科医师杂志

Objective:To assess the cardiac autonomic nervous function in elderly patients with frailty.Methods:Patients aged ≥ 65 years old admitted in Beijing Hospital from September 2018 to August 2019 were enrolled in this study. Clinical frailty score was used to assess the frailty. The cardiac autonomic modulation was evaluated by sinus heart rate turbulence analysis through 24 h electrocardiogram recording.Results:A total of 129 elderly patients were finally enrolled in this study with a mean age of (77.5±6.4) years, 58.1% of them were male. There were 53 patients in frail group and 76 patients in non-frail group. The age of the frailty group was significantly higher than that of the non-frailty group [(80.5±5.5) vs.(75.3±6.2)]; the prevalence of hypertension [84.9%(45/53)], heart failure [32.1%(17/53)] and peripheral vascular diseases [32.1%(17/53)] in the frailty group was significantly higher than that in the non-frailty group [65.8%(50/76), 1.3%(1/76), 17.1%(13/76); t=5.001, χ 2=5.879, 24.606, 3.921; all P<0.05]. Compared with non-frailty group, turbulence onset (TO) [-0.05(-0.92, 0.82)% vs. -0.74(-1.58, 0)%; Z=2.616, P=0.009] was significantly higher in frailty group, while turbulence slope (TS) [2.34(1.30, 5.00)ms/RR vs. 4.34(2.66, 6.39)ms/RR; Z=-3.048, P=0.002] was significantly lower. The rate of TO abnormality [49.1% (26/53) vs. 26.3%(20/76), χ 2=7.038, P=0.008] and TS abnormality [34.7%(29/53) vs. 21.0%(16/76); χ 2=15.579, P<0.001] in the frailty group was significantly higher than that in the non-frailty group. Multivariate logistic regression analysis showed that TO abnormality( OR=2.970, P=0.010, 95 %CI:1.300-6.785) and TS abnormality( OR=3.618, P=0.003, 95 %CI:1.565-8.364) were correlated with frailty. Conclusion:Cardiac autonomic nerve function may be impaired in elderly frail patients, and decreased vagal nerve tension may be presented.

Effect of added halide ions and pH on the solubility of nebivolol hydrochloride and the evaluation of selected, discriminating dissolution media / 药学学报

The solubility of nebivolol hydrochloride was determined in acidic aqueous media in the absence and presence of different concentration of NaCl, NaBr, or NaI at 37 ℃ in order to facilitate proper selection of dissolution media that have adequate discriminating power for enhancing the likelihood of a generic drug product to successfully pass in-vivo bioequivalence test. In the range of pH 5.0 to pH 1.0, the solubility of nebivolol hydrochloride decreased with the decrease in the pH of aqueous solution, and the solubility of nebivolol hydrochloride further decreased with the increase in the concentration of added sodium chloride. The solubility decrease of a few weakly basic drug molecules in acidic media and in higher concentration of added chloride was published previously by other researchers, and the observed decrease in the solubility in the presence of higher chloride concentration was interpreted in terms of common-ion effect. However, the results in this paper showed that the solubility of nebivolol hydrochloride also decreased when sodium chloride was replaced with sodium bromide or iodide. The approach described in this paper (i.e. substituting sodium chloride with sodium bromide or iodide) provides an effective method to verify whether common-ion effect is the true (or at least the sole) driving force behind the observed decrease in the solubility of nebivolol hydrochloride in the presence of sodium chloride. The solubility decrease reported in this paper can be interpreted in terms of salting-out effect of sodium chloride, bromide, and iodide. For hydrochloride salt of a weakly basic drug molecule like nebivolol hydrochloride, its solubility in an acidic dissolution medium can be purposely decreased to the lower end of sink condition by adding sodium chloride to make the resulting medium more discriminating. As shown in this paper, a medium at pH 1.2 with added sodium chloride is discriminating and this medium is shown to be bio-relevant to the in-vivo data collected under fasting condition (in-vivo study protocol was approved by Institutional Review Board).

TLR4/NF-kappaB p65 signaling pathway mediates protective effect of triptolide on endothelium in rats with endotoxemia / 中国中药杂志

The aim of this paper was to observe the effect of triptolide( TP) on cardiovascular function and its possible mechanism by intraperitoneal injection of bacterial lipopolysaccharide in rats with endotoxemia. Sixty male Sprague-Dawley rats were randomly divided intonormal group( NC group),endotoxemia model group( LPS group),TP low concentration intervention group( LPS + TP-L group,25 μg·kg~(-1)),TP middle concentration intervention group( LPS+TP-M group,50 μg·kg~(-1)),TP high concentration intervention group( LPS+TP-H group,100 μg·kg~(-1)) and polymyxin B group( LPS+PMX-B group,0. 2 mg·kg~(-1)). 10 mg·kg~(-1) LPS was injected intraperitoneally for 6 h to replicate the endotoxemia rat model. The rats in TP intervention groups were pre-treated 15 min before intraperitoneal injection of LPS. Rats in each group underwent total arterial intubation to measure hemodynamic parameters: heart rate( HR),left ventricular diastolic pressure( LVDP),the maximum rate of the increase/decrease of left ventricular pressure( ±dp/dtmax). The levels of BNP,CK-MB and c Tn-Ⅰ in serum and levels of TNF-α and IL-6 in plasma were detected by ELISA. The contents of p65 protein in myocardium and contents of p65,TLR4,i NOS and e NOS protein in thoracic aorta were detected by Western blot. As compared with NC group,the hemodynamic indexes in LPS group were significantly decreased; the contents of BNP,CK-MB and c Tn-Ⅰ in serum,TNF-α and IL-6 in plasma,p65 in myocardium,i NOS,e NOS,TLR4 and p65 in vascular tissues were significantly increased. As compared with LPS group,the hemodynamic indexes were significantly improved in LPS+TP-M group,LPS+TP-H group and LPS+PMX-B group; the contents of BNP,CK-MB and c Tn-Ⅰ in serum,TNF-α and IL-6 in plasma,p65 in myocardium,i NOS,e NOS,TLR4 and p65 in vascular tissues were significantly decreased in each treatment group. Triptolide has a protective effect on cardiovascular damage in a dose-dependent manner in endotoxemia rats,probably through TLR4/NF-κB p65 signaling pathway to improve endothelial function.

Influences of combined traffic noise on the ability of learning and memory in mice.

OBJECTIVE: The present study aimed to evaluate the influences of combined traffic noise (CTN) on the ability of learning and memory in mice. MATERIALS AND METHODS: The Institute of Cancer Research (ICR) mice were exposed to CTN from highways and high-speed railways for 42 days, whose day-night equivalent continuous A-weighted sound pressure level (Ldn) was 70 dB(A). On the basis of behavioral reactions in Morris water maze (MWM) and the concentrations of amino acid neurotransmitters in the hippocampus, the impacts of CTN on learning and memory in mice were examined. RESULTS: The MWM test showed that the ability of learning and memory in mice was improved after short-term exposure (6-10 days, the first batch) to 70 dB(A) CTN, which showed the excitatory effect of stimuli. Long-term exposure (26-30 days, the third batch; 36-40 days, the fourth batch) led to the decline of learning and memory ability, which indicated the inhibitory effect of stimuli. Assays testing amino acid neurotransmitters showed that the glutamate level of the experimental group was higher than that of the control group in the first batch. However, the former was lower than the latter in the third and fourth batches. Both, behavioral reactions and the concentrations of amino acid neurotransmitters, testified that short-term exposure and long-term exposure resulted in excitatory effect and inhibitory effect on the ability of learning and memory, respectively. CONCLUSION: The effects of 70 dB(A) CTN on the ability of learning and memory were closely related to the exposure duration. Furthermore, those effects were regulated and controlled by the level of glutamate in the hippocampus.

New Mutation of Coenzyme Q Monooxygenase 6 Causing Podocyte Injury in a Focal Segmental Glomerulosclerosis Patient / 中华医学杂志(英文版)

Background@#Focal segmental glomerulosclerosis (FSGS) is a kidney disease that is commonly associated with proteinuria and the progressive loss of renal function, which is characterized by podocyte injury and the depletion and collapse of glomerular capillary segments. The pathogenesis of FSGS has not been completely elucidated; however, recent advances in molecular genetics have provided increasing evidence that podocyte structural and functional disruption is central to FSGS pathogenesis. Here, we identified a patient with FSGS and aimed to characterize the pathogenic gene and verify its mechanism.@*Methods@#Using next-generation sequencing and Sanger sequencing, we screened the causative gene that was linked to FSGS in this study. The patient's total blood RNA was extracted to validate the messenger RNA (mRNA) expression of coenzyme Q monooxygenase 6 (COQ6) and validated it by immunohistochemistry. COQ6 knockdown in podocytes was performed in vitro with small interfering RNA, and then, F-actin was determined using immunofluorescence staining. Cell apoptosis was evaluated by flow cytometry, the expression of active caspase-3 was determined by Western blot, and mitochondrial function was detected by MitoSOX.@*Results@#Using whole-exome sequencing and Sanger sequencing, we screened a new causative gene, COQ6, NM_182480: exon1: c.G41A: p.W14X. The mRNA expression of COQ6 in the proband showed decreased. Moreover, the expression of COQ6, which was validated by immunohistochemistry, also had the same change in the proband. Finally, we focused on the COQ6 gene to clarify the mechanism of podocyte injury. Flow cytometry showed significantly increased in apoptotic podocytes, and Western blotting showed increases in active caspase-3 in si-COQ6 podocytes. Meanwhile, reactive oxygen species (ROS) levels were increased and F-actin immunofluorescence was irregularly distributed in the si-COQ6 group.@*Conclusions@#This study reported a possible mechanism for FSGS and suggested that a new mutation in COQ6, which could cause respiratory chain defect, increase the generation of ROS, destroy the podocyte cytoskeleton, and induce apoptosis. It provides basic theoretical basis for the screening of FSGS in the future.

Influence of smoking on insulin resistance in male patients with obstructive sleep apnea-hypopnea synddrome / 医学研究生学报

Objective Smoking can induce and aggravate obstructive sleep apnea-hypopnea synddrome (OSAHS), but there are few reports on its influence on insulin resistance of OSAHS patients. The article aimed to discuss the influence of smoking on insulin resistance in male patients with OSAHS.Methods A total of 141 OSAHS patients were divided into smoking group (n=104) and non-smoking group (n=37) according to smoking history. The smoking group were subdivided into two subgroups: ≥600 cigarettes/year and < 600 cigarettes/year according to smoking index. General clinical data of all patients were collected,while night sleeping data were gained by PSG overnight sleep monitoring. Fasting insulin(FINS), fasting blood glucose (FBG), concentration of serum C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interletkin-6 (IL-6), lipidperoxide (LPO) and activity of superoxide dismutase (SOD), glutathione peroxides (GSH-PX) were detected on all patients. Insulin resistance was evaluated by measuring HOMA-IR and FINS.Results Compared with non-smoking group, the patients in smoking group had a longer lack of oxygen time, lower oxygen saturation, higher CRP, TNF-alpha, IL-6 , LPO levels and lower SOD, GSH-PX activity. Significant differences were found in FBG, FINS, HOMA-IR and IR incidence between 2 subgroups(P<0.05), and the indexes of these 2 subgroups were both higher than those of non-smoking gorup, representing statistical significance(P<0.05).Conclusion Smoking is likely to be one of the important factors that lead to insulin resistance in male OSAHS patients. Oxidative stress, inflammation, hypoxia may be its influencing factors.

Juncus inhibits osteoclast formation induced by RANKL / 天津医药

Objective To observe the effect of Juncus effuses on osteoclasts differentiation from bone marrow macrophages (BMMs) induced by receptor activator for nuclear factor-κ B ligand (RANKL), and its mechanism thereof. Methods BMMs were isolated from whole bone marrow of 8-week-old C57/BL6 mice, and CCK-8 was used to detect the effect of Juncus on BMMs cell proliferation. Tartrate resistant acid phosphatase (TRAP) staining was used to show that 50 μg/L RANKL and 30 μg/L macrophage colony stimulating factor (M-CSF) stimulated the BMMs differentiation into osteoclasts, but the process was inhibited by Juncus (0, 6.25, 12.5 and 25 μmol/L). RT-PCR was used to detect the expressions of osteoclast-specific genes including calcitonin receptor (CTR), vacuolated H+triphosphate transporter -d2 (V-ATPase-d2) and -a3 (V-ATPase-a3), activated T nuclear factor 1 (NFATC1) and C-FOS. Results There was no inhibition in the proliferation of BMMs cells treated with Juncus less than 12.5 μmol/L detected by CCK-8. The 50 μg/L RANKL can induce BMMs differentiated into positive multinuclear giant cells detected by TRAP staining, but Juncus significantly inhibited osteoclast formation with a concentration dependence. The results of RT-PCR experiment showed that Juncus inhibited the expression of specific genes in osteoclast differentiation in concentration-dependent manner. Conclusion Juncus can inhibit osteoclast formation in concentration-dependent manner, resulting from the inhibitory effect on osteoclast specific gene expression.

A low rank Hankel matrix reconstruction method for ultrafast magnetic resonance spectroscopy.

Magnetic resonance spectroscopy has many important applications in bio-engineering while acquiring high dimensional spectroscopy is usually time consuming. Non-uniformly sampling can speed up the data acquisition but the missing data points have to be restored with proper signal models. In this work, a specific two dimensional (2D) magnetic resonance signal, in which the first dimension lies in frequency domain while the second dimension lies in time domain, is reconstructed with a proposed low rank Hankel-matrix method. This method explores two general properties: 1) the rank of a structured matrix, converted from a 2D exponential signal, is equal to the number of 2D spectral peaks; 2) this rank is small if the spectrum is sparse. Results on real magnetic resonance spectroscopy show that proposed method outperforms the state-of-compressed sensing method on recovering low-intensity spectral peaks.

Effects of different ratios of medicine dosage for isoflurane and propofol on GABAAreceptor α1sub-unit proteostasis during hypoxia injury to hippocampal neurons of rats / 中华麻醉学杂志

Objective To evaluate the effects of different ratios of medicine dosage for isoflurane and propofol on GABAAreceptor(GABAAR)α1subunit proteostasis during hypoxia injury to hippocampal neurons of rats. Methods The hippocampal neurons isolated from fetal rats obtained from Wistar rats were primarily cultured and divided into 6 groups(n=60 each)using a random number table: control group (group C), hypoxia group(group H), isoflurane group(group I), propofol group(group P)and dif-ferent ratios of medicine dosage for isoflurane and propofol groups(group IP1and group IP2). The cells were subjected to hypoxia for 6 h in group H. Cells were incubated for 3 h with 1.9 % isoflurane and with 22.4 μmol∕L propofol after being subjected to hypoxia for 6 h in I and P groups, respectively. Cells were incubated for 3 h with 1.0% isoflurane and 6.7 μmol∕L propofol and with 1.4% isoflurane and 3.4 μmol∕L propofol after being subjected to hypoxia for 6 h in IP1and IP2groups, respectively. Then the culture medi-um was replaced with plain culture medium. At 24 h of incubation, the cells were collected for measure-ment of cell viability by CCK-8 assay, GABAAR α1mRNA expression(by quantitative polymerase chain reaction), GABAAR α1expression in the cytomembrane(by Western blot), level of GABAAR α1subunit endoplasmic reticulum-associated degradation(ERAD)(by immunoprecipitation and Western blot)and CCAAT∕enhancer-binding protein homologous protein(CHOP)expression(by immunofluorescence). Re-sults Compared with group C, the cell viability was significantly decreased, the expression of GABAAR α1mRNA and GABAAR α1in cytomembrane was down-regulated, the expression of CHOP was up-regula-ted, and the level of GABAAR α1subunit ERAD was increased in the other five groups(P<0.05). Com-pared with group H, the cell viability was significantly decreased, the expression of GABAAR α1mRNA and GABAAR α1in cytomembrane was down-regulated, the expression of CHOP was up-regulated, and the level of GABAAR α1subunit ERAD was increased in I, P and IP2groups(P <0.05), and no significant change was found in the parameters mentioned above in group IP1(P<0.05). Compared with group I or group P, the cell viability was significantly increased, the expression of GABAAR α1mRNA and GABAAR α1 in cytomembrane was up-regulated, the expression of CHOP was down-regulated, and the level of GABAAR α1subunit ERAD was decreased in IP1and IP2groups(P<0.05). Compared with group IP1, the cell viability was significantly decreased, the expression of GABAAR α1mRNA and GABAAR α1in cy-tomembrane was down-regulated, the expression of CHOP was up-regulated, and the level of GABAAR α1 subunit ERAD was increased in group IP2(P<0.05). Conclusion Combination of 1.0% isoflurane and 6.7 μmol∕L propofol does not aggravate hypoxia-induced destruction of GABAAR α1subunit proteostasis in hippocampal neurons of rats.

Appropriate compatibility of propofol and sevoflurane for posterior lumbar interbody fusion of patients with mild cognitive impairment / 临床麻醉学杂志

Objective To investigate the appropriate compatibility of appropriate compatibility of sevoflurane and propofol for patients with mild cognitive impairment (MCI) undergoing posterior lumbar interbody fusion in order to protect their cognitive function.Methods Eighty patients, 41 males, 39 females, aged 65-75 years, BMI 17-26 kg/m2, ASA physical status Ⅰ or Ⅱ, scheduled to undergo elective posterior lumbar interbody fusion, were to be scored according to Montreal cognitive assessment (MoCA), mini mental state examination (MMSE), dementia scale (CDR) and daily living ability scale (ADL) to identify patients with MCI before the surgery.They were randomly assigned to 4 groups (n=20 each) using a random number table: TCI propofol 2.0-2.5 μg/ml group (group P), TCI propofol 1.2 μg/ml+sevoflurane 0.6 MAC group (group PS1), TCI propofol 0.6 μg/ml+sevoflurane 0.9 MAC group (group PS2), 1.0-1.5 MAC sevoflurane group (group S).MoCA and MMSE were used to evaluate the cognitive function of patients 1 d before the operation (T0), after patients become wide-awake (T1), 3 d and 7 d after operation (T2 and T3).Apolipoprotein J (ApoJ) concentration related to cognitive function in blood samples, which were drawn at T0-T3 would be measured with ELISA method.Results Compared with T0, the scores of MMSE and MoCA in four groups decreased significantly (P＜0.05) at T1, the scores of MMSE and MoCA in group S decreased significantly (P＜0.05) at T2;compared with T1, the score of MMSE in the four groups increased significantly at T2, T3 (P＜0.05).The scores of MMSE at T1, T3 in group S decreased significantly compared with groups P, PS1 and PS2 (P＜0.05).The scores of MoCA at T2, T3 in group S decreased significantly compared with groups P, PS1 and PS2 (P＜0.05).Compared with T0, the concentration of plasma ApoJ in the four groups increased significantly at T1 (P＜0.05).Compared with T1, the concentration of plasma ApoJ in the four groups decreased significantly at T2 and T3 (P＜0.05).Compared with group PS1, the concentration of plasma ApoJ at T1, T3 increased significantly in groups S and group PS2 (P＜0.05).Conclusion TCI propofol 1.2 μg/ml combined with 0.6 MAC sevoflurane group is the appropriate compatibility of sevoflurane and propofol for patients with MCI undergoing posterior lumbar interbody fusion,because it has less negative influence on cognitive function and lower concentration of plasma ApoJ.