Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0％,males for 68.0％,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5％,males for 60.8％,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95％CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95％CI:-0.05 to-0.01;β=-0.07,95％CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95％CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.

Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0％,males for 68.0％,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5％,males for 60.8％,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95％CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95％CI:-0.05 to-0.01;β=-0.07,95％CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95％CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.

OBJECTIVE: The medicinal mushroom Sanghuangporus vaninii produces pharmaceutically valuable hispidin polyphenols in natural habitats. However, due to the slow growth in nature, S. vaninii grown in the field (sclerotia) is not reliable for pharmaceutical purposes. Although higher biomass of fungal mycelia can be obtained in submerged cultures, the accumulation of hispidin polyphenols is rare. METHODS: In this study, the polyunsaturated fatty acids (PUFAs), linoleic acid (LA), linolenic acid (ALA), and methyl jasmonate (MeJa) were employed as the stimulant agents to coordinate the accumulation of biomass and hispidin polyphenols in its submerged cultures. RESULTS: The addition of LA and ALA promoted the mycelial accumulation, while the addition of MeJa inhibited the growth of S. vaninii concomitant with reduced total polyphenols. UPLC-Triple-TOF-MS analysis revealed an increased production of hispidin, phellinstatin, pinnilidine, and its derivatives upon the addition of LA and ALA, and hypholomine B and its isomer, 3,14'-bihispidinyl, and phelligridin E upon the addition of MeJa on day 13. Intriguingly, total polyphenols from the MeJa-supplementing cultures harbored a high capacity in scavenging free radicals. Chemical structural analysis showed that hispidin polyphenols had higher antioxidant activity due to more hispidin moieties induced by MeJa. CONCLUSION The supplement of PUFAs affects the synthesis and composition of hispidin polyphenols in S. vaninii. Our results provide a possibility to coordinate the production of hispidin polyphenols via submerged cultures of S. vaninii.

Objective:To explore the relationship between job stress, job burnout and turnover intention of operating room nurses in a tertiary hospital in Shandong Province.Methods:From January 2016 to January 2019, the operating room nurses with an average daily operation volume of more than 200 operating rooms in a tertiary hospital in Shandong Province were selected as the research objects. The work pressure, job burnout and turnover intention of nurses were investigated with the Chinese nurses' job stressor scale, job burnout table and turnover intention table. Pearson related factors were used to analyze job stress, job burnout and turnover intention Multivariate logistic regression was used to analyze the factors influencing turnover intention. A total of 98 questionnaires were distributed and 98 questionnaires were returned, with a recovery rate of 100%.Results:The average score of job stress, job burnout and turnover intention were 85.49±5.42, 36.17±3.52 and 14.99±3.32, respectively. There were differences in the scores of work stress among different age, working years, education background and establishment groups ( P<0.05) . The scores of job burnout among nurses with different working years, education background, professional title, salary and establishment were different ( P< 0.05) ; the scores of turnover intention of nurses in different age, working years, professional title, salary and establishment group were different ( P<0.05) ; salary, job burnout and occupational pressure were the influencing factors of turnover intention ( P<0.05) . Conclusion:The operating room nurses have high work pressure and job burnout is an important factor leading to high turnover intention.

Objective:To explore the relationship between job stress, job burnout and turnover intention of operating room nurses in a tertiary hospital in Shandong Province.Methods:From January 2016 to January 2019, the operating room nurses with an average daily operation volume of more than 200 operating rooms in a tertiary hospital in Shandong Province were selected as the research objects. The work pressure, job burnout and turnover intention of nurses were investigated with the Chinese nurses' job stressor scale, job burnout table and turnover intention table. Pearson related factors were used to analyze job stress, job burnout and turnover intention Multivariate logistic regression was used to analyze the factors influencing turnover intention. A total of 98 questionnaires were distributed and 98 questionnaires were returned, with a recovery rate of 100%.Results:The average score of job stress, job burnout and turnover intention were 85.49±5.42, 36.17±3.52 and 14.99±3.32, respectively. There were differences in the scores of work stress among different age, working years, education background and establishment groups ( P<0.05) . The scores of job burnout among nurses with different working years, education background, professional title, salary and establishment were different ( P< 0.05) ; the scores of turnover intention of nurses in different age, working years, professional title, salary and establishment group were different ( P<0.05) ; salary, job burnout and occupational pressure were the influencing factors of turnover intention ( P<0.05) . Conclusion:The operating room nurses have high work pressure and job burnout is an important factor leading to high turnover intention.

Objective Observation of the effects of Xinmailong injection on NGAL, hs-cTnT and RAAS in elderly patients with type 2 cardio-renal syndrome (CRS) , and EvaluatIon of the clinical efficacy and safety.Methods A total of 86 elderly patients who were collected from November 2015 to February 2017 were diagnosed as type 2 CRS in our department of geriatrics. According to the random number table method, they were randomly divided into two groups. Control group (43 cases) were treated with conventional medical therapy and xinmailong group (43 cases) were treated with xinmailong injection with a dose of 5 mg/kg twice a day for 15 days. The value of sneutrophil gelatin-associated apolipoprotein (NGAL) , hypersensitive troponin T (hs-cTnT) , brain natriuretic peptide (BNP) , plasma renin activity (PRA) , and angiotensin Ⅱ (Ang Ⅱ) , aldosterone (ALD) , left ventricular ejection fraction (LVEF) , six-minute walking test and other indicators were measured before and after treatment. Results After treatment, the value of NGAL, hs-cTnT, BNP, PRA, AngⅡ and ALD decreased in both groups, the value of LVEF and six-minute walking distance increased compared with those before treatment (P <0.05); The above indicators in the xinmailong group experienced a more significant alteration than in control group in the same period (P < 0.05); no side effect occurred in both two groups during the experiment. Conclusion Xinmailong injection can reduce the levels of NGAL, hs-cTnT and BNP in elderly patients with type 2 cardio-renal syndrome, improve heart and kidney function, and have curative positive effect and good safety. This study underlined the mechanism of Xinmailong injection may be related to the inhibition of RAAS activity.

OBJECTIVETo investigate the correlation of apolipoprotein AI (ApoAI), ApoB, ApoB/ApoAI and the severity of brain white matter lesions (WML).

METHODSA total of 648 patients with WML confirmed by brain magnetic resonance imaging (MRI) were divided into mild WML group (=386) and moderate to severe WML group (=262) according to evaluations with the Fazekas scale. The demographic data, blood biochemical parameters and the levels of ApoAI, ApoB and ApoB/AI ratio were compared between the two groups to identify the risk factors of moderate to severe WML.

RESULTSUnivariate analysis showed that age, gender, hypertension, diabetes, coronary heart disease, previous stroke, homocysteine, HDL-C, ApoAI, and ApoB/AI ratio all differed significantly between the two groups ( < 0.05), but ApoB levels were similar between them ( > 0.05). Multivariate logistic regression analysis revealed that with ApoAI and ApoB/AI ratio as the continuous variables, after adjustment for the compounding factors, ApoB/AI ratio was an independent risk factor (OR=11.456, 95% : 3.622-36.229, < 0.001) and ApoAI was an independent protective factor for moderate to severe WML (OR=0.068, 95% : 0.018-0.262, < 0.001). With the upper quartiles of ApoAI level (1.38 g/L) and ApoB/AI ratio (0.58) as their respective cutoff values, patients with a high ApoAI level and a low ApoB/AI ratio were found to have the lowest incidence of moderate to severe WML ( < 0.001).

CONCLUSIONSAn increased ApoB/AI ratio is an independent risk factor and an increased ApoAI level is an independent protective factor for moderate to severe WML.

BACKGROUND:Spine infection models are rarely reported in the literature. There are fewer reports on the imaging and histological observations of the animal model of spinal infection.
OBJECTIVE:To develop a canine model of pyogenic spinal infection.
METHODS:Twelve Chinese dogs were adopted in the study. The dogs were in the right arm recumbent. The surgery was conducted by retroperitoneal approach to expose T12/L1 intervertebral space. The intervertebral discs that exposed the intervertebral space were partial y removed, and the end plate of the adjacent two vertebrae was deliberately curetted out. Suspension with different concentrations of Staphylococcus aureus and sodium morrhuate were injected into the dog intervertebral space. The aim of removal of partial intervertebral discs and destruction of endplate was to make the vertebral body bone better in contact with the bacteria. The same operation was conducted in L5/6 clearance of the animal spine. At 14 days after surgery, animals were sacrificed. The infected intervertebral disc and adjacent vertebral bodies were taken out. Bacterial contents of specimens were quantitatively determined. During sacrificing, partial liver tissues and blood samples were col ected for bacterial culture. The occurrence of systemic infection was observed.
RESULTS AND CONCLUSION:(1) Spondylodiscitis of the lumbar spinal column was consistently produced in 90%(9/10) the sites chal enged with 102 colony-forming units (CFU) Staphylococcus aureus. Liver biopsy and blood culture did not show any signs of systematic infections. (2) Two out of four animals implanted the suspension with a concentration higher than 103 CFUs died within 3 days post-implantation. (3) These results suggested that a new canine model of pyogenic spinal infection was developed. This model could be used to test the efficacy of different anti-infection strategies.

Spillage of cyst contents during surgical operation is the major cause of recurrence after hydatid cyst surgery. Instillation of a scolicidal agent into a hepatic hydatid cyst is the most commonly employed measure to prevent this complication. SB202190 is a pyridinyl imidazole derivative and is known to be a specific inhibitor of p38 MAPK. In the present study, the scolicidal effect of SB202190 was investigated. Freshly isolated Echinococcus granulosus protoscolices were subjected to SB202190 treatment (10, 20, 40, and 80 microM), and the effects on parasite viability were monitored by trypan blue staining. Corresponding effects were visualized by scanning and transmission electron microscopy. Dose-dependent protoscolex death within a few days of SB202190 treatment was observed. Although the in vitro scolicidal effect of SB202190 was satisfactory, the in vivo efficacy of this drug and also possible side effects remain to be further investigated.
Animals ; Anthelmintics/*pharmacology ; Dose-Response Relationship, Drug ; Echinococcus granulosus/*drug effects/ultrastructure ; Imidazoles/*pharmacology ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Parasitic Sensitivity Tests ; Pyridines/*pharmacology ; Survival Analysis