Age-related change in mitochondrial DNA copy number and its correlation with intrinsic capacity and body composition / 中华老年医学杂志

Objective:To investigate the correlation of peripheral blood relative mitochondrial DNA copy number(mtDNAcn)with intrinsic capacity and body composition, and to identify potential biomarkers for healthy aging.Methods:Clinical data of 416 patients admitted to our hospital from September 2019 to June 2021 were consecutively collected.MtDNA was extracted from peripheral blood of these subjects, and mtDNAcn was determined by a real-time fluoresence quantitative reverse transcription-polymerase chain reaction(qRT-PCR). Intrinsic capacity assessment included 5 aspects that were exercise[Morse Fall Scale(MFS), Physiological Frailty Phenotype(PFP), Sarcopenia Questionnaire(SARC-CALF), Short Physical Performance Battery(SPPB), Time Up and Go Test(TUG)]; vitality[Mini Nutritional Assessment(MNA), Multidimensional Prognostic Index(MPI)]; cognition[Mini-Mental State Examination(MMSE)scale]; psychology[Geriatric Depression Scale(GDS), Self-rating Anxiety Scale(SAS)]; sensory capacities[Cumulative Illness Rating Scale-the Comorbidity Index(CIRS-CI)]. To assess body composition, dual-energy X-ray absorptiometry was used to measure body fat, including trunk fat, total body fat, fat in the abdominal region, fat in the buttock region, and then to calculate fat index(FMI)and limb skeletal muscle mass index(ASMI).Results:Spearman correlation analysis showed that mtDNAcn had a negatively correlation with age( r=-0.176, P<0.05). After adjustment for gender and body mass index, partial correlation analysis showed mtDNAcn were still negatively correlated with age( r=-0.144, P<0.05). Furthermore, mtDNAcn was significantly correlated with 4 m gait speed, the scores of SARC-CalF, MFS, MNA, MMSE, MPI and its sub-scale's Activities of Daily Living(ADL)and Short Portable Mental Status Questionnaire(SPMSQ)( r=0.171, -0.207, -0.163, 0.221, 0.184, -0.210, 0.241, -0.269, all P<0.05). After adjustment for age, gender and body mass index, partial correlation analysis showed mtDNAcn still had a significant correlation with gait speed, the scores of MFS, MNA, MPI and SPMSQ( r=0.170, -0.170, 0.148, -0.242, -0.188, all P<0.05). In addition, the Spearman correlation analysis showed that mtDNAcn was positively correlated with FMI, trunk fat, total body fat, abdominal fat and fat in the buttock region( r=0.168, 0.143, 0.175, 0.116, 0.199, all P<0.05). However, after adjustment for age and gender, mtDNAcn was only correlated with FMI, total body fat, fat in the buttock region( r=0.126, 0.131, 0.127, all P<0.05). On the other hand, multiple linear regression analysis showed that mtDNAcn was significantly correlated with age, gait speed, FMI, total body fat, fat in the buttock region, the scores of MFS, PFP, MNA and MPI( β=-0.191, 0.156, 0.126, 0.131, 0.125, -0.119, -0.145, 0.151, -0.171, all P<0.05). Conclusions:MtDNAcn is correlated with physical function, frailty, nutrition, falling, cognition and body composition, and may be considered as a biomarker for the evaluation of the locomotion and vitality of human intrinsic capacity.

Mitochondrial protection effect of sirtuin2 inhibitor AGK2 on thioacetamide-induced L02 cells / 中国医师杂志

Objective:To explore the protective effect of AGK2, a selective inhibitor of sirtuin 2 (SIRT2), on the mitochondria of L02 hepatocytes induced by thioacetamide (TAA) and its related mechanism.Methods:Human-derived hepatocyte line L02 cells were cultured in vitro. Different concentrations of SIRT2 inhibitor AGK2 were used as intervention drugs. Cell counting kit-8 (CCK8) was used to detect the effects of different concentrations of AGK2 on the activity of L02 cells, and the appropriate concentration was selected as the AGK2 intervention group. The normal group was not given any drug intervention. The model group was given 90 mmol/L TAA for modeling. Low, medium and high dose AGK2 groups were added with 1, 2 and 4 μmol/L AGK2, respectively 2 h before modeling. CCK8 was used to detect cell activity in each group. Morphological changes of cells were observed under inverted light microscope. The relative protein expression levels of isocitrate dehydrogenase (IDH1), malate dehydrogenase (MDH1), SIRT2 and fission protein 1 homologue (FIS1) were detected by Western blot. The expression of SIRT2 in cells of each group was observed by confocal laser scanning microscope. The mitochondrial membrane potential of cells in each group was observed under a fluorescence microscope. Results:When AGK2 concentration was 1, 2 and 4 μmol/L, the survival rate of cells were 98.05%, 95.76% and 91.65%, respectively, with no statistical significance compared with normal group (all P>0.05). When AGK2 concentration was 8, 16, 32, 64, 128 μmol/L, the cell survival rate was significantly decreased compared with normal group (all P<0.05). Compared with the model group, the L02 cells in low, medium and high AGK2 groups had better activity and adherence, and the floating cells were significantly reduced. The higher the concentration of AGK2, the better the cell activity and adherence, and the less floating cells. Compared with the model group, the red fluorescence of L02 cells in AGK2 group was enhanced, while the green fluorescence was weakened. The higher the AGK2 concentration was, the stronger the red fluorescence was, and the weaker the green fluorescence was. Compared with the model group, the fluorescence of SIRT2 in L02 cells of low, medium and high AGK2 groups was weakened, and the higher the concentration of AGK2, the weaker the fluorescence of SIRT2. The protein expressions of IDH1 and MDH1 in L02 cells of low, medium and high AGK2 groups were significantly higher than those of model group (all P<0.05), and were positively correlated with the concentration of AGK2 ( r=0.818, P<0.05; r=0.960, P<0.05); the protein expressions of SIRT2 and FIS1 were significantly lower than those of the model group (all P<0.05), and were negatively correlated with the concentration of AGK2 ( r=-0.992, P<0.05; r=-0.998, P<0.05). Conclusions:AGK2 can reduce the mitochondrial membrane potential stimulated by TAA in L02 cells, increase the protein expression of IDH1 and MDH1, and inhibit the protein expression of SIRT2 and FIS1 in L02 cells in a dose-dependent manner.

Research progress on mitochondrial dynamics and age-related diseases / 中华老年医学杂志

Mitochondrial dynamics regulates mitochondrial morphology and functions.Imbalance in mitochondrial dynamics with aging leads to mitochondrial dysfunction, accelerates the aging process and is closely related to the occurrence and progression of age-related diseases.However, the specifics of the relationship between aging and altered mitochondrial dynamics are still not fully understood.Here, we review the link between mitochondrial dynamics and aging, and discuss mechanisms underlying age-related diseases associated with altered mitochondrial dynamics, aiming to identify novel therapeutic targets and strategies for the management of age-related diseases.

The correlation of age-related mitochondrial respiratory function of peripheral blood mononuclear cells with grip strength and appendicular skeletal muscle mass / 中华老年医学杂志

Objective:To investigate the correlation of mitochondrial respiration function and oxidative phosphorylation of peripheral blood mononuclear cells(PBMCs)with grip strength and muscle mass in the elderly, and to identify potential biomarkers for the diagnosis of sarcopenia.Methods:A total of 65 patients admitted to our hospital from June 2019 to August 2020 were enrolled in this study.PBMCs were extracted from subjects.Mitochondrial oxidative respiration function was assessed via the Seahorse XF24 analyzer.Grip strength was measured using a hydraulic dynamometer, and appendicular skeletal muscle mass(ASM)was estimated by dual-energy X-ray absorptiometry(DXA). Multivariate analysis was conducted by using partial correlation analysis and multiple linear regression, in order to evaluate the correlation of mitochondrial oxidative respiration function with grip strength and ASM.Results:After adjustment for gender and body mass index(BMI), partial correlation analysis showed that grip strength and ASM had a negative correlation with age( r=-0.537 and -0.390, both P<0.001); and basal respiration, maximal respiration, ATP production and spare respiratory capacity of mitochondria in PBMCs were negatively correlated with age( r=-0.558, -0.614, -0.526 and -0.582, all P<0.001), whereas grip strength and ASM were positively correlated with basal respiration, maximal respiration, ATP production, spare respiratory capacity and proton leak of mitochondria in PBMCs(grip strength: r=0.414, 0.451, 0.362, 0.420 and 0.425, P=0.002, 0.001, 0.008, 0.002 and 0.002; ASM: r=0.319, 0.368, 0.299, 0.352 and 0.279, P=0.019, 0.006, 0.028, 0.009 and 0.041). Multiple linear regression analysis showed that grip strength and ASM were positively correlated with basal respiration, maximal respiration, ATP production, spare respiratory capacity and proton leak of mitochondria in PBMCs(grip: β=0.503, 0.548, 0.452, 0.519 and 0.532, t=3.248, 3.604, 2.774, 3.301 and 3.350, P=0.002, 0.001, 0.008, 0.002 and 0.002; ASM: β=0.302, 0.355, 0.289, 0.346 and 0.271, t=2.427, 2.856, 2.263, 2.716 and 2.091, P=0.019, 0.006, 0.028, 0.009 and 0.041). Age was negatively correlated with basal respiration, maximal respiration, ATP production and spare respiratory capacity of mitochondria in PBMCs( β=-0.581, -0.654, -0.558 and -0.640, t=-4.285, -5.157, -3.938 and -4.863, all P<0.001). Multiple linear regression analysis showed that ASM and grip strength had no significant correlation with basal respiration, maximal respiration, ATP production, spare respiratory capacity or proton leak of mitochondria in PBMCs. Conclusions:Age-related mitochondrial oxidative respiration in PBMCs can reflect changes in muscle strength and muscle mass and, combined with grip strength and ASM, may be considered as a biomarker for the evaluation of sarcopenia in the elderly.

The reliability and validity of 10-item Connor-Davidson resilience scale in the community-dwelling ol-der adults / 中华行为医学与脑科学杂志

Objective To evaluate the reliability and validity of 10 items Connor-Davidson resili-ence scale ( CD-RISC-10 ) in the community-dwelling older adults. Methods Totally 620 community-dwelling older adults randomly chosen from 16 communities in Chengdu city were investigated by CD-RISC-10,the geriatric depression scale short form ( GDS-SF) and self-made basic condition questionnaire. Results The discrimination of the 10 items was statistically significant( t=6. 84-13. 57,P<0. 01) . Exploratory factor analysis showed two factors ( strength and hardiness) were extracted,and the cumulative variance interpreta-tion rate was 42. 32％. Confirmatory factor analysis showed that model index of two sub-factors (χ2/df=1. 518( P<0. 001) ,CFI =0. 964,TLI =0. 948,IFI =0. 965,NFI =0. 904,RMSEA=0. 042) . Cronbach's αof the total scale and the two sub-factors were 0. 737,0. 673 and 0. 585 respectively. After half a month,the retest reliability coefficients of the total scale and the two sub-factors were 0. 974,0. 932 and 0. 941(P<0. 01) . Conclusion The CD-RISC-10 scale has acceptable reliability and validity,with using easily and con-veniently. Therefore,it is an effective tool for measuring the resilience of the community-dwelling older adults.

Health hazards of hexavalent chromium in drinking water / 中华地方病学杂志

Objective To learn the exposure levels and health hazards of long-term exposure to hexavalent chromium (Cr6+) through drinking water in a west county,and to provide a scientific basis for making preventive measures.Methods Five water points were selected to test the Cr6+ concentration of drinking water in the county in 2015,data of 3 water points with water Cr6+ concentrations exceeded the standard (Cr6+ ＞ 0.05 mg/L) were selected from 12 drinking water points in some west counties in the recent six years (2009-2014) as the exposed group,2water points that drinking water Cr6+ concentrations not exceeded the standard (Cr6+ ≤0.05 mg/L) in the county and adjacent to the exposed group were selected as the control group.Sixty villagers were selected as the investigation objects in each water point to conduct internal medicine,ears,nose,throat (ENT),dermatology and health examination,urinary chromium content,routine blood and urine test were done.Determination of hexavalent chromium concentration in drinking water was done according to The Drinking Water Standard Examination Method 1,5-diphenylcarbazide Spectrophotometry (GB/T 5750-2006);routine urine was tested using the 10 urine analyzer test;urinary chromium was tested using graphite furnace atomic absorption spectrometer;routine blood five classification was tested using automatic blood analyzer;determination of drinking water hexavalent chromium concentration was done according to The Hygienic Standard for Drinking Water (GB 5749-2006).Higher than 0.05 mg/L was judged as exceeded the standard;physical examination was done according to The Diagnostic Criteria of Occupational Chromium Nasal Disease (GB Z12-2002) and The Diagnostic Standard of Occupational Contact Dermatitis (GB Z20-2002).Results There were 184 and 109 people in the exposed group and the control group,respectively.The average concentration of Cr6+ exceeding the standard ratio was 2.82-3.22 in drinking water,the nasal septum nucosa perforation,skin erythema edema,skin ulcers were 4.9％ (9/184),4.3％ (8/184) and 4.3％ (8/184) in the exposed group,and the urinary chromium level (0.31 μg/L) in the exposed group was significantly higher than that of the control group (0.27 μg/L,Z =-4.078,P ＜ 0.05).Routine blood test result of mean corpuscular haemaglobin (MCH) was (29.56 ± 2.07) pg,platelet counts (PLT) was (222.38 ± 47.53) × 109/L and plateletcrit (PCT) was (0.25 ± 0.05)％ in the exposed group,it was all higher than those of the control group [(29.03 ±2.95) pg,(211.74 ±75.27)× 109/L,(0.24 ± 0.08)％,t =1,940,2.318,2.079,all P ＜ 0.05];standard difference coefficient of variation of red blood cell distribution width (RDW-CV) was (13.14 ± 1.05)％,lymphocyte number (LYMPH) was (2.01 ± 0.64) × 109/L in the exposed group,it was all lower than those of the control group [(13.38 ±1.54)％,(2.21 ± 1.02) × 109/L,t =-1.989,-1.956,all P ＜ 0.05].The positive rate of glycosuria,uric bravery red,and urine nitrite in routine urine test of exposed group was 17.39％ (32/184),23.36％ (43/184),7.61％ (14/184);it was all higher than those of the control group [(8.25％ (9/109),11.93％ (13/109),0.91％ (1/109),x2 =4.746,5.798,6.309,all P ＜ 0.05].Conclusions Urine chromium accumulation has been found in populations long-term exposed to 2.82-3.22 times excessive Cr6+ through drinking water,which has affected the population's health to some extent.Therefore,it is necessary to speed up the local drinking water improvement project.

Influence of Electro-acupuncture on E-Selectin and Resistin Protein Expression in Hippocampus of Rats with Chronic Stress Depression / 中国中医药信息杂志

Objective To observe the effects of electro-acupuncture on the E-selectin and resistin protein expression in the hippocampus of rats of chronic stress depression;To explore the role and mechanism of electro-acupuncture in the micro-environment of brain with depression. Methods 40 Fourty rats were randomly divided into four groups:blank group, model group, model+EA group, and model+fluoxetine group by using chronic stress combined with solitary raising methods, 10 rats in each group. Electro-acupuncture intervention was used 1 hour before the modeling. Electro-acupuncture was given at points Baihui (Du 20) and Yintang (Extra) for twenty minutes (2 Hz, 0.6 mA) every day. Fluoxetine was given at the volume of 5 mL/kg, dosage of 10 mg/kg. E-selectin and resistin protein expression in hippocampus were determined by biotin label-based antibody array. Results Compared with the blank group, the protein expression of E-selectin and resistin in the model group increased (fold change=1.23, 1.22). Compared with the model group, E-selectin and resistin expression decreased (fold change=0.65, 0.62;fold change=0.76, 0.65). Conclusion Electro-acupuncture intervention could down-regulate E-selectin and resistin expression in the hippocampus of chronic stress depression model.

Clinical reaserch on DCTAA and CIK from stem in treating patients of moderate and advanced stage lung cancer / 肿瘤研究与临床

ObjectiveTo observe the treatment effects in 48 cases of advanced lung cancer patients,with the immune therapy of the dendritic cells loading of tumor autologous antigen (DCTAA) combining with the cells induced factor of the killer cells(CIK)from the matched umbilical cord blood cells.MethodsThe peripheral blood mononuclear cell(PBMC)from the matched umbilical cord blood cells was seperated,and induced to CIK and DC with some cytokines in vitro, such as CD3McAb, IL-2, IFN-γ IL-1α, etc. After 12 to 15 days, the amplified CIK cells obtained were obtained, with the strict quality control, infused the CIK cells to the patients body back in six times,about(5-8)×109 CIK cells in each time.In the fifth day of the cultivation,DETAA cells were loaded and DCTAA cells were collected in the eighth day,and then hypodermic injection was done. The patient' s general situation after the immune treatment was observed, such as the size of the tumors, clinical symptom score, the quality of life and immune indexes. Karnofsky score, weight, toxic side effects and the patient's survival were also studied.ResultsIn the 48 cases with the DCTAA-CIK treatment, complete remission (CR), partial remission (PR)was 37 cases, the overall remission rate was 77.1％. The improvement rate of clinical symptom scores was from 78.9 ％ to 84.7 ％, the increasing rate of Karnofsky score was 89.6 ％ (43/48). 1-year survival reached to 80.6 ％. There were significant difference in little toxic side effects(P ＜ 0.01). The proportion of CD3, CD4 and NK cells in peripheral blood cells increased significantly (P ＜ 0.01) after DCTAA-CIK cells treatment[(42.21±6.12)％, (24.42±3.01)％, 0.99±0.34, (24.98±3.02) ％; (71.58±7.64) ％, (37.25±2.13) ％, 1.62±0.45, (35.23±4.11) ％](t = 6.34, 5.67, 0.25, 4.43, P ＜0.01).ConclusionThe DCTAA-CIK immune therapy is benefit for advanced lung cancer,not only improve the immune function but also ameliorate the clinical symptoms.

Aminoglycosides Modifying Enzyme Genes and intⅠ gene in Stenotrophomonas maltoplilia / 中华医院感染学杂志

OBJECTIVE To study the aminoglycosides modifying enzyme genes and intⅠ gene in Stenotrophomonas maltophilia in Chinese Armed Police Forces General Hospital.METHODS The samples of 27 multi-resistant S.maltophilia were collected from inpatiens from Jan 2006 to Oct 2007 in this Hospital.The sensitivity of the isolates to 14 antibacterial agents was determined using a broth induction method.The aminoglycosides modifying enzyme genes and intⅠ 1 gene were detected by PCR.RESULTS The multi-drug resistance of S.maltophilia was a serious problem.In 27 strains of S.maltophilia,the positive ant(2″)-Ⅰ were in 5 strains(18.5%),aac(3)-Ⅱ in 3 strains(11.1%)and aac(6')-Ⅱ in 1 strain(3.7%).The positive intⅠ gene was found in 11 strains(29.6%).CONCLUSIONS Multi-resistant S.maltophilia resistant to aminoglycosides mainly due to the presence of aminoglycoside modifying enzymes ant(2″)-Ⅰ,aac(3)-Ⅱ and aac(6')-Ⅱ.The aminoglycoside modifying enzymes ant(3″)-Ⅰ and aac(6)-ⅠZ were not detected carrying IntⅠ would be the reason of S.maltophilia resistant to aminoglycosides.

The detection of serum levels of sIL-2R and TNF-? and its significance in patients with chronic cor pulmonale / 中国综合临床

Objective To evaluate the significance of sIL 2R and TNF ? in chronic cor pulmonale.Methods The sIL 2R and TNF ? were detected by means of ELISA.The correlation with PaO 2 and PaCO 2 was analyzed using linear correlation.Results The levels of sIL 2R and TNF ? in patients at exacerbation stage were higher than that of remission stage and normal controls (P

Medicine and Human Care / 中国医学伦理学

The medical progress provides the care in medicine both to psychological factors and social factors.So,it's necessary to advocate human care in medicine.It is also an important condition form technique supremacy transforming into human care in practice,the medical care not only to human being but to technique,psychology health,and life care.