Objective To investigate the correlation between bone mineral density(BMD)at different hip positions with muscle parameters and physical performance in middle-aged and elderly people in Kunming area.Methods 531 middle-aged and elderly volunteers were recruited from the Radiology Department of the First People's Hospital of Yunnan Province from May 2021 to April 2022.All study subjects completed the five-times-sit-to-stand test(FTSST)and hip quantitative CT(QCT)examinations.Volunteers'total hip(TH),femoral neck(FN),and intertrochanteric(IT)BMD were measured by using QCT PRO workstation and using OsiriX software to measure the area and density of their gluteus maximus muscle,gluteus medius,and minimus muscle and midthigh muscle.Divide male and female volunteers into positive and negative groups respectively based on FTSST time≥12 seconds or<12 seconds,and analyze the differences in hip BMD between the groups;Also divide male and female volunteers into three groups(50～59 years old,60～69 years old,70 years old and above)at the age of 10,and analyze the correlation between hip BMD and muscle parameters in different age and gender stratification.Control for age and BMI,and then perform partial correlation analysis on the above indicators.Results The BMD of the hip in the female FTSST positive group was lower than that in the negative group(P<0.001),while there was no statistically significant difference between the male groups(P>0.05).After adjusting for age and BMI,among males,FN BMD was positively correlated with gluteus medius and minimus muscle density in the age groups of 50～59 and 60～69(P<0.05),while TH BMD,FN BMD,and IT BMD were strongly positively correlated with gluteus medius and minimus muscle density in the age group over 70(P<0.05).For females,the correlation between hip BMD and muscle density in the age groups of 50～59 and 60～69 was weak,while BMD in all parts of the hip was not correlated with muscle density in the age group over 70(P>0.05).There was a negative correlation between TH BMD,FN BMD,and gluteus medius and minimus muscle area in the age group of 50～59 years old for males(P<0.05),while there was a significant negative correlation between TH BMD,IT BMD,and gluteus maximus area in the age group of 70 years old and above for females(P<0.05).Conclusion The BMD of various parts of the hip in the female FTSST positive group is lower than that in the negative group.The density of the gluteus medius and minimus muscle can to some extent serve as a predictive indicator of femoral neck bone strength in middle-aged and elderly men in Kunming area.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Redox-sensitive cysteine(RSC)thiol plays an important role in many biological processes such as photosynthesis,cellular metabolism,and transcription.Therefore,it is necessary to identify red-ox-sensitive cysteine accurately.However,traditional redox-sensitive cysteine identification is very ex-pensive and time-consuming.At present,there is an urgent need for a mathematical calculation method to identify sequence information and redox-sensitive cysteines quickly and accurately.Here,we devel-oped an effective predictor called iRSC-PseAAC,which used the dimension reduction algorithm LDA combined with the support vector machine to predict redox-sensitive cysteine sites.In the cross-validation results,the specificity(Sp),sensitivity(Sn),accuracy(Acc)and Matthews correlation coefficient(MCC)were 0.841,0.868,0.859 and 0.692 respectively.In the independent dataset results,the Sp,Sn,Acc and MCC were 0.906,0.882,0.890 and 0.767 respectively.compared with existing prediction methods,iRSC-PseAAC had obvious improvement effect.The method proposed for this study can also be used for many problems in computational proteomics.

BACKGROUND: Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. METHODS: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. RESULTS: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. CONCLUSIONS ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
Adult ; Humans ; Cardiovascular Diseases/prevention & control* ; East Asian People ; Prospective Studies ; Risk Factors ; Smoking

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

Objective:To investigate the safety of early whole body computed tomography (WBCT) combined with coronary angiography (CAG) in patients with extracorporeal cardiopulmonary resuscitation (ECPR) and its application value in the diagnosis of cardiac arrest and complications of cardiopulmonary resuscitation (CPR).Methods:This was a retrospective study. Patients who underwent ECPR in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University from January 2017 to July 2021 were enrolled in this research. Patients younger than 18 years or with incomplete clinical data were excluded. The results of WBCT and CAG examinations after ECPR were collected.Results:A total of 89 patients with ECPR, aged (47±17) years, were enrolled in the study, all underwent WBCT examination, and no adverse events such as ECMO and tracheal tube shedding occurred. WBCT found 7 cases of pulmonary embolism, 3 cases of aortic dissection and 2 cases of cerebral hemorrhage. WBCT identified CPR-related complications in 42 cases, including rib fractures ( n=20), pneumothorax ( n=5), mediastinal emphysema ( n=5), subcutaneous emphysema ( n=6), and hematoma or swelling at puncture site ( n=6). Fifty-five patients underwent CAG examination, the most common culprit vessels were the left anterior descending branch disease (58.2%) followed by the left circumflex branch disease (27.3%), the right coronary artery disease (21.8%) and left main artery disease (12.7%). Conclusions:Early WBCT and CAG examinations are of great significance and safety for the guidance of treatment in ECPR patients.

Objective:To investigate the prognostic value of early lactate in patients with extracorporeal cardiopulmonary resuscitation (ECPR).Methods:A retrospective analysis was performed on the clinical data of patients with ECPR in the Emergency Medicine Department of The First Affiliated Hospital of Nanjing Medical University from March 2015 to August 2021. The age, sex, etiology, initial rhythm, prognosis, blood lactate and pH of patients with ECPR were collected, and their difference between the deceased and survived patients was compared.Results:Totally 95 patients were enrolled, with an average age of 47 years; male accounted for 69.5%, and the survival rate was 29.5%. There was no significant difference in age and sex ratio between the deceased and survived patients. However, the deceased patients had a significant lower rate of shockable rhythms (31.3% vs. 60.8%), a higher level of lactate [16.4 (11.2, 19.1) vs. 9.2 (3.2, 15.0), mmol/L], and a lower pH [7.01 (6.88, 7.23) vs. 7.37 (7.10, 7.43)] than the survived patients. Multivariate binary logistic regression analysis showed that shockable rhythm [odds ratio ( OR) = 0.295, 95% confidence interval ( CI): 0.118-0.739), lactate ( OR=1.159, 95% CI: 1.068-1.258) and pH ( OR= 0.017, 95% CI: 0.002-0.157) were independent risk factors for poor prognosis. Furthermore, a lactate level >24 mmol/L was the best threshold to predict mortality with a specificity of 100%. Combined application, the cutoff point was lactate level>16 mmol/L and pH <6.828. Conclusions:Shockable rhythm, higher early lactate and lower pH value are independent risk factors for prognosis in patients with ECPR. Early lactate > 24 mmol/L or lactate > 16 mmol/L companied with pH < 6.828 are novel indicators of the termination of ECPR.

Objective:To investigate the predictive value of platelet dynamics on the prognosis of 28-day in patients with extracorporeal membrane oxygenation (ECMO).Methods:From January 2017 to December 2020, 60 patients from the Emergency Medicine Center of the First Affiliated Hospital of Nanjing Medical University received ECMO for life support. The baseline data of the patients were collected, the minimum value of platelets on day 1-7 of the machine was calculated, and the platelet change value and change rate were calculated. The patients were divided into the survival group and death group according to the 28-day survival status after ECMO was installed, and the receiver operating curve (ROC) was drawn based on the platelet change value and change rate to evaluate its predictive value for prognosis.Results:Among patients receiving VV-ECMO, the platelet change value and change rate on day 7 had the best prediction effect on the patient's 28-day outcome ( AUCΔPLT7=0.772, P=0.016; AUCΔPLT7%=0.764, P=0.020), when the platelet change value was 4×10 9/L as the critical value, the sensitivity was 0.857, the specificity was 0.615, and when the platelet change rate was -28.99% as the critical value, the sensitivity was 0.857, the specificity was 0.615, and when the platelet change rate was -28.99%. The sensitivity was 0.643 with a specificity of 0.846. In patients receiving VA-ECMO, the platelet change rate on day 6 predicted the best effect on the patient's 28-day outcome ( AUCΔPLT6%= 0.707, P = 0.045). When the platelet change rate was -26.19% as the critical value, the sensitivity was 0.842 and the specificity was 0.643. Conclusions:Platelet dynamic changes of platelets are correlated with the 28-day prognosis of patients receiving ECMO, and the combination of platelet change value and the critical value of change rate can better predict the poor prognosis of patients in both ECMO modes.

Objective:To summarize the experience and effect of extracorporeal cardiopulmonary resuscitation (ECPR) in the treatment of out-of-hospital cardiac arrest (OHCA) in adults.Methods:The data of 40 adults with OHCA-ECPR in Emergency Department of the First Affiliated Hospital of Nanjing Medical University from April 2015 to April 2022 were retrospectively analyzed. The patients were grouped by discharge survival/in-hospital death, with/without bystander resuscitation, and with/without interhospital transport. Age, sex, Charlson comorbidity index, initial rhythm, no-flow time, time from cardiac arrest to extracorporeal membrane oxygenation (ECMO) initiation (CA-Pump On time), ECMO evacuation success rate, survival rate, ECMO treatment time, time-to-death, and length of hospital stay were analyzed.Results:①Among the 40 patients with OHCA-ECPR, 9 patients (22.5%) survived upon discharge, 7 (77.8%) of whom had good neurological outcomes.②The no-flow time in the survival group was significantly shorter than that in the death group, and the proportion of shockable initial rhythm was higher.③Bystander resuscitation greatly shortened the no-flow time.④The regional OHCA-ECPR interhospital transport extended the CA-Pump On time, without affecting patients’ prognosis.Conclusions:ECPR improves the prognosis of patients with OHCA. Bystander resuscitation greatly shortens the no-flow time. ECPR is significantly effective in patients with short no-flow time and shockable initial rhythm. Regional interhospital transport ECPR is recommended to benefit more patients with OHCA.

Objective:To analyze whether lower anticoagulation intensity can reduce the incidence of complications in patients with extracorporeal membrane oxygenation (ECMO).Methods:Clinical data of 88 non-cardiac surgery patients who received ECMO support for more than 72 h were collected in the Extracorpical Life support Center of Jiangsu Province Hospital from March 2015 to March 2021. According to the average activated partial thromboplastin time (APTT) level on the third day of ECMO, the patients were divided into the APTT < 50 s group ( n=53) and APTT ≥50 s group ( n=35). The venovenous ECMO (VV-ECMO) subgroup was divided into the APTT <50 s group ( n=23) and APTT ≥50 s group ( n=10). The venoarterial ECMO (VA-ECMO) subgroup was divided into the APTT <50 s group ( n=30) and APTT≥50 s group ( n=25). The average daily transfusion volume of red blood cells during ECMO, the incidence of bleeding, the incidence of thrombosis and all-cause mortality were compared between the two groups. Results:There were no significant differences in the incidence of thrombosis and all-cause mortality in the APTT <50 s group compared with the APTT ≥50 s group ( P>0.05), but the incidence of bleeding and the daily transfusion volume of red blood cells were significantly decreased (7.5% vs. 35.7%; 0.50 U vs. 0.88 U) ( P < 0.05). In 33 VV-ECMO patients, the all-cause mortality, incidence of bleeding, average daily transfusion volume of red blood cells in the APTT <50 s group were lower than those in the APTT ≥50 s group, and the incidence of thrombosis was higher, but there was no statistical difference between the two groups ( P>0.05). In the 55 VA-ECMO patients, there were no significant differences in all-cause mortality, incidence of bleeding, thrombosis and average daily transfusion volume of red blood cells between the two groups ( P > 0.05). Conclusions:The lower anticoagulation intensity in patients without anticoagulation can reduce the occurrence of bleeding in ECMO patients. It is reasonable for such patients to have a lower anticoagulation intensity and studies with larger sample size need to be carried out.