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.

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.

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.

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.

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

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.

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.

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).

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.

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.

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.

Effects of different ratios of medicine dosage for propofol and sevoflurane on postoperative cognitive function in elderly patients with mild cognitive impairment / 中华麻醉学杂志

Objective To evaluate the effects of different ratios of medicine dosage for propofol and sevoflurane on postoperative cognitive function in elderly patients with mild cognitive impairment.Methods Ninety-six patients of both sexes,aged 65-75 yr,weighing 60-80 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective lower limb fracture operation under general anesthesia,with mild cognitive impairment before surgery,were assigned into 4 groups (n =24 each) using a random number table:propofol group (group P),sevoflurane group (group S) and different ratios of medicine dosage for propofol and sevoflurane groups (group PS1 and group PS2).Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to evaluate the cognitive function of patients at 1 day before operation (T0) and 7 days after operation (T1).Venous blood samples were collected at T0 and T1 for determination of the concentrations of plasma apolipoprotein J (ApoJ) and soluble CD14 (sCD14) by enzyme-linked immunosorbent assay.Results Compared with group S,MMSE and MoCA scores were significantly increased and plasma concentrations of ApoJ and sCD14 were decreased at T1,and the incidence of postoperative cognitive dysfunction was decreased in P,PS1 and PS2 groups (P＜0.05).Compared with group PS1,MMSE and MoCA scores were significantly decreased and the plasma concentrations of ApoJ and sCD14 were increased at T1,and the incidence of postoperative cognitive dysfunction was increased in P and PS2 groups (P＜0.05).MMSE and MoCA scores were significantly lower and plasma concentrations of ApoJ and sCD14 were higher at T1 than at T0 in S,P and PS2 groups (P＜0.05),and there was no significant difference in the parameters mentioned above between T1 and T0 in group PS1 (P＞0.05).Conclusion Combination of propofol 1.2 μg/ml given by target-controlled infusion and 0.7-1.2％ sevoflurane inhalation for maintenance of anesthesia does not aggravate the postoperative cognitive dysfunction in elderly patients with mild cognitive impairment.

Effects of different ratios of medicine dosage for isoflurane and propofol on postoperative cognitive function of rats with mild cognitive impairment / 中华麻醉学杂志

Objective To evaluate the effects of different ratios of medicine dosage for isoflurane and propofol on postoperative cognitive function of rats with mild cognitive impairment (MCI).Methods Healthy male Wistar rats,aged 16-18 months,were used in the study.MCI model was established by occlusion of bilateral common carotid arteries.One hundred and fifty rats with MCI were divided into 5 groups (n=30 each) using a random number table:sham operation group (group S),isoflurane group (group I),propofol group (group P) and different ratios of medicine dosage for isoflurane and propofol groups (IP1,2 groups).The rats inhaled 1.9％ isoflurane for 3 h in group I.Propofol 40 mg · kg-1 · h-1 was infused intravenously for 3 h in group P.The rats inhaled 1.0％ isoflurane,and propofol 20 mg · kg 1 · h-1 was infused intravenously for 3 h in group IP1.The rats inhaled 1.4％ isoflurane,and propofol 10 mg· kg-1 · h-1 was infused intravenously for 3 h in group IP2.After disappearance of eyelash reflex,open reduction and internal fixation was performed after tibial fracture was induced.On 7 days after operation,contextual fear conditioning test and Y maze test were used to assess the cognitive function,and hippocampal tissues were obtained to count the viable neurons (using Nissl's staining) and CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12 positive neurons (by immunofluorescence) in hippocampal CA1 region.Results Compared with group S,the rate of time spent in N arm,the rate of time spent freezing,and the number of viable neurons were significantly decreased,and the number of CHOP and caspase-12 positive neurons were significantly increased in IP2,I and P groups (P＜0.05),and no significant change was found in the parameters mentioned above in group IP1 (P＞0.05).Compared with group IP1,the rate of time spent in N arm,the rate of time spent freezing,and the number of viable neurons were significantly decreased,and the number of CHOP and caspase-12 positive neurons was significantly increased in IP2,I and P groups (P＜0.05).Compared with group IP2,the rate of time spent in N arm,the rate of time spent freezing,and the number of viable neurons were significantly decreased,and the nunber of CHOP and caspase-12 positive neurons was significantly increased in I and P groups (P＜0.05).Conclusion Combination of 1.0％ isoflurane and propofol 20 mg · kg-1 · h-1 does not aggravate the postoperative cognitive dysfunction of the rats with MCI.

Relation between microRNA-152 expression and cisplatin resistance in non-small cell lung cancer cells and its mechanism / 重庆医学

Objective To investigate the action mechanism of microRNA‐152(miRNA‐152) in the cisplatin(DDP) resistance process in non‐small cell lung cancer (NSCLC) .Methods The miRNA‐152 level in NSCLC cell line A549 and its cisplatin‐resistant cell line A549/DDP was detected by the real time quantitative PCR(qRT‐PCR) .miRNA‐152 mimic was transfected for increasing the intracellular miRNA‐152 level in A549/DDP .The MTT assay ,inverted miroscope technique and flow cytometry were adopted to observe the effect of up‐regulating miRNA‐152 on cell proliferation inhibition and apoptosis ,meanwhile ,the level changes of intra‐cellular Bcl‐2 and NF‐κB were also observed by adopting qRT‐PCR and Western blot .Results The low expression of miRNA‐152 and the high expression of Bcl‐2 and NF‐κB were found in A549/DDP cells .Up‐regulation of miRNA‐152 enhanced the inhibitory effect of DDP in A549/DDP cells .Furthermore ,after up‐regulating miRNA‐152 ,the inhibiting rate and apoptosis rate of A549/DDP cells caused by DDP were significantly higher than those in the cells without up‐regulating miRNA‐152 ,the difference was statisti‐cally significant(P<0 .05) .In addition ,miRNA‐152 mimic transfection significantly decreased the expression of Bcl‐2 and NF‐κB in A549/DDP cells .Conclusion Low expression of miRNA‐152 may induce the resistance of NSCLC to DDP ,miRNA‐152 could medi‐ate the sensitivity of NSCLC cells to DDP via regulating Bcl‐2 and NF‐κB levels .

Effect of propofol post-conditioning on oxygen-glucose deprivation and restoration-induced abnormal cell cycle activation in hippocampal neurons of rats / 中华麻醉学杂志

Objective To investigate the effect of propofol post?conditioning on oxygen?glucose deprivation and restoration ( OGD∕R)?induced abnormal cell cycle activation in hippocampal neurons of rats. Methods Primarily cultured hippocampal neurons obtained from fetal Wistar rats were cultured for 7 days and seeded in culture wells (100 μl∕well) or in culture flasks (3 ml∕flask) at a density of 5×105cells∕ml. The neurons were divided into 3 groups ( n=24 each) using a random number table: control group ( group C); group OGD∕R; propofol post?conditioning group (group PP). The neurons were subjected to oxygen?glucose deprivation for 1 h followed by restoration of oxygen?gulcose supply for 24 h. Propofol 1.2μg∕ml was added immediately after onset of oxygen?glucose restoration, and the neurons were incubated for 2 h in group PP. At 24 h of oxygen?glucose restoration, cells were collected for measurement of the cell viability by methyl thiazolyl tetrazolium assay, and the mitochondrial membrane potential ( MMP ) , intracellular Ca2+concentration ( [ Ca2+] i ) and distribution of cell cycle were determined using flow cytometry. Results Compared with group C, the cell viability and MMP were significantly decreased, [ Ca2+] i was signifi? cantly increased, the proportion of the cells in G0∕G1 phase was significantly decreased, and the proportion of the cells in S and G2∕M phases was significantly increased in OGD∕R and PP groups (P<0.05). Com?pared with group OGD∕R, the cell viability and MMP were significantly increased, [ Ca2+] i was significant?ly decreased, the proportion of the cells in G0∕G1 phase was significantly increased, and the proportion of the cells in S and G2∕M phases was significantly decreased in group PP (P<0.05). Conclusion The mechanism by which propofol post?conditioning reduces OGD∕R?induced apoptosis in hippocampal neurons of rats is associated with inhibition of abnormal cell cycle activation.