Objective This study uses whole-genome methylation capture sequencing technology to screen differential sites and regions of gene methylation in mouse liver and colon under simulated weightlessness conditions to reveal the specific impact of weightlessness on gene methylation.Methods Six 8-week-old male C57BL/6J mice were randomized into the tail suspension group and the control group,with 3 in each.The 3 mice in the tail suspension group recieved tail suspension for simulated weightlessness for 42 days.After the experiment,DNA was extracted from liver and colon tissue and analyzed using genome-wide methylation capture sequencing technology.Results DNA analysis of liver tissue showed that a total of 7 517 differentially methylated sites and 997 differentially methylated regions were found,involving 4 892 genes.DNA analysis of colon tissue revealed 70 340 differentially methylated sites and 12 004 differentially methylated regions,affecting 12 877 genes.GO and KEGG path analysis revealed that these differentially methylated genes were mainly involved in protein binding,cell adhesion,cell activation,and various metabolic pathways.Conclusion This study successfully identified differential methylation sites and regions in mouse liver and colon under simulated weightlessness conditions through high-throughput sequencing technology.These findings help to further understand the impact of long-term space residence on biological gene methylation.It provides new research ideas for the prevention and early treatment of space flight-related diseases.

With the increasing maturity and progress of China's space technology,astronauts can stay longer in the space station and complete more complex space experiments and tasks.In the Microgravity(MG)environment of space,the digestive system of astronauts is inevitably affected,especially the liver and colon,and there are many physiological and pathological changes.MG can affect liver metabolic function,cell proliferation and differentiation,oxidative stress response and inflammatory factor levels.MG can disrupt the intestinal barrier of the colon,intestinal flora and microecology,intestinal immunity,and the gut-liver axis.However,the existing studies on the effects of MG on liver and colon are not completely clear,and there is a lack of reliable diagnostic indicators for the pathological changes of both.Therefore,in order to explore the damage mechanism of MG on liver and colon and ensure the digestive system health of astronauts,this paper reviews the research progress on the effects of MG on liver and colon.

Objective To investigate the effect of glaucocalyxin A(GLA)on neuroinflammation and the HMGB1-RAGE signaling pathway in rats with Alzheimer disease(AD).Methods Rats were given intracerebroventricular injec-tion of Aβ1-42 solution to establish a model of AD,and then the rats were randomly divided into sham-operation group,model group,donepezil group,low-dose GLA group and high-dose GLA group,and high GLA+HMGB1 group,with 15 rats in each group.The Morris water maze test was used to assess the learning and memory abilities of rats;HE staining was used to observe the pathological and morphological changes of hippocampal tissue;ELISA was used to measure the lev-els of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in hippocampal tissue;immu-nofluorescence assay was used to measure the expression of the microglia marker protein Iba-1 and the astrocyte marker protein GFAP;Western blotting was used to measure the expression of HMGB1-RAGE pathway-related proteins in hippo-campal tissue.Results Compared with the sham-operation group,the model group had significant increases in escape la-tency,the content of TNF-α/IL-6/IL-1β,the positive expression area of Iba-1 and GFAP proteins,and the expression lev-els of HMGB1,RAGE,TLR4,and p-NF-κB p65/NF-κB p65(P<0.05),as well as significant reductions in the time spent in the target quadrant and the number of platform crossings(P<0.05).Compared with the model group,the low-and high-dose GLA groups had significant reductions in escape latency,the content of TNF-α/IL-6/IL-1β,the positive ex-pression area of Iba-1 and GFAP proteins,and the expression levels of HMGB1,RAGE,TLR4,and p-NF-κB p65/NF-κB p65(P<0.05),as well as significant increases in the time spent in the target quadrant and the number of platform crossings(P<0.05),and there were no significant differences between the high-dose GLA group and the donepezil group(P>0.05).Further supplementation experiments using HMGB1 recombinant protein showed that the inhibitory effect of GLA on neuroinflammation was reversed,with a sig-nificant increase in the level of RAGE(P<0.05).Conclusion GLA can alleviate neuroinflammation in AD rats by inhibiting the HMGB1-RAGE signaling pathway.

Background::Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.Methods::In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.Results::In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). Conclusions::COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

Objective:To establish and validate an LC-MS/MS method for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in cerebrospinal fluid. Additionally, the consistency between this method and three mainstream detection methods was evaluated.Methods:This study involved method establishment, validation, and consistency evaluation. The N15 labeled β-amyloid protein was used as the internal standard. Extraction was performed using Waters MCX 96-wells solid phase extraction plate, and the eluent was collected to QuanRecovery MaxPeak 700 μl plate. At the positive ion mode, the multi-reaction ion monitoring mode based on electric spray ionization is chosen for the determination of CSF Aβ 1-42, Aβ 1-40, and Aβ 1-38. Referring to the CLSI C62-A and EP-15A3 guidelines, the method is evaluated and verified, including quantitation of limit (LOQ), linearity, recovery, precision, and accuracy. In addition, a total of 57 clinical residual CSF samples were collected and the concentrations of Aβ 1-42 and Aβ 1-40 were determined based on manual INNOTEST ELISA assay and Lumipulse G and Roche Elecsys fully automated biochemical analyzers. The comparison analysis and deviation evaluation were conducted by passing-bablok and Bland Altman methods.Results:The analysis time of this method is 8 min, and the LOQ of Aβ 1-42, Aβ1-40 and Aβ1-38 is 0.1 ng/ml, 0.5 ng/ml, and 0.1 ng/ml, respectively, and the linear range can meet the needs of clinical detection. Respectively, the recovery is 86.2%-93.8%, 100.9%-103.9% and 103.3%-107.1%; the total imprecision is 4.7%-7.4%, 3.5%-4.6% and 5.2%-10.9%. The measured values of Aβ 1-42 certified reference materials are all within the allowable uncertainty requirements. Moreover, the carryover rate of three analytes was all≤0.11%. In addition, the correlations of Aβ 1-42 and Aβ1-40 in CSF between this LC-MS/MS method and the INNOTEST ELISA method, Lumipulse G and Roche Elecsys fully automated biochemical analyzers were all deemed good, with correlation coefficient (r) ranging from 0.920 to 0.970. However, the measured values between the four methods were remarkably different.Conclusion:We established and validated a robust method based on LC-MS/MS technology for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in CSF. The method is accurate, simple, and suitable for clinical measurements. However, despite good correlations, there were substantial differences in the measurement results of Aβ 1-42 and Aβ 1-40 among different analytical platforms, indicating the need for further promotion of harmonization and standardization processes for AD classic biomarkers.

Objective:To investigate the application value of high-resolution CT in the diagnosis of early lung adenocarcinoma.Methods:The clinical data of 90 patients with early lung adenocarcinoma who received treatment from January to December 2021 in Quzhou People's Hospital were retrospectively analyzed. These patients were divided into a non-invasive group ( n = 27) and an invasive group ( n = 63) according to whether they had invasive lung adenocarcinoma or not. In the non-invasive group, there were 10 patients with atypical adenomatous hyperplasia and 17 patients with in situ adenocarcinoma. In the invasive group, there were 38 patients with minimally invasive adenocarcinoma and 25 patients with invasive adenocarcinoma. A pathological diagnosis was performed in all patients. All patients underwent a high-resolution CT examination. The incidence of lung adenocarcinoma was compared between different loci. CT signs were compared between the non-invasive group and the invasive group. The receiver operating characteristic curve was used to determine the sensitivity and specificity of high-resolution CT in the differential diagnosis of lung adenocarcinoma prior to invasion. Results:There was no significant difference in the incidence of lung adenocarcinoma among the left upper lobe, right upper lobe, left lower lobe, and right lower lobe of the lung in each group (all P > 0.05). The detection rates of pleural indentation sign, spicule sign, and vascular bundle sign in the invasive group were 28.6% (18/63), 31.57% (20/63), and 27.0% (17/63), respectively, which were significantly higher than 7.41% (2/27), 11.11% (3/27), and 7.41% (2/27) in the non-invasive group ( χ2 = 4.90, 4.23, 4.35, all P < 0.05). There were no significant differences in detection rates in the lobar sign and air bronchogram sign between the two groups (both P > 0.05). The receiver operating characteristic curve analysis results showed that the sensitivity and specificity of high-resolution CT in differentiating pre-invasive lesions were 100.0% and 64.7%, respectively. Conclusion:High-resolution CT has a good diagnostic value for early lung adenocarcinoma. It can clearly display various signs of early lung adenocarcinoma, which is worthy of clinical reference.

Objective:To investigate the prognostic value of cardiac ultrasound left ventricular ejection fraction (LVEF) on admission in patients with septic cardiomyopathy.Methods:A retrospective cohort study was conducted. The patients with septic cardiomyopathy hospitalized in the intensive care unit of Zhoupu Hospital Affiliated to Shanghai Health College from January 2019 to March 2023 were enrolled. The general information including gender and age, LVEF on admission, severity of illness scores within 24 hours after admission [acute physiology and chronic health evaluationⅡ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score], procalcitonin (PCT), cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), and MB isoenzyme of creatine kinase (CK-MB)], mitochondria related indicators [aspartate aminotransferase (AST), AST/alanine aminotransferase (ALT) ratio], blood lactate (Lac), the usage of vasoactive drugs and mechanical ventilation, and the prognosis during hospitalization were collected. The differences in above clinical data between the two groups were compared. The variables with statistically significant differences in univariate analysis were incorporated into multivariate Logistic regression analysis to analyze the independent risk factors for death during hospitalization in patients with septic cardiomyopathy. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the prognostic value of LVEF by echocardiography on admission in patients with septic cardiomyopathy during hospitalization.Results:A total of 62 patients were enrolled, including 36 males and 26 females. Thirty-nine cases died and 23 cases survived during hospitalization, and the mortality was 62.90%. Compared with the survival group, the LVEF of patients on admission was lower in the death group [0.51 (0.40, 0.57) vs. 0.56 (0.51, 0.63), P < 0.01], APACHEⅡ score, SOFA score, Lac, NT-proBNP, CK-MB within 24 hours after admission were higher [APACHEⅡ score: 22.18±8.38 vs. 17.39±8.22, SOFA score: 9.90±3.87 vs. 7.09±3.27, Lac (mmol/L): 5.10 (2.63, 11.50) vs. 2.00 (1.40, 5.00), NT-proBNP (μg/L): 5.24 (2.84, 11.29) vs. 2.53 (0.35, 6.63), CK-MB (U/L): 1.88 (0.21, 5.33) vs. 0.17 (0.02, 1.62), all P < 0.05], and the proportion of vasoactive drug application was higher (82.05% vs. 47.83%, P < 0.01). Multivariate Logistic regression analysis showed that LVEF on admission was an independent risk factor for predicting the prognosis of patients with septic cardiomyopathy during hospitalization [odds ratio ( OR) = 0.920, 95% confidence interval (95% CI) was 0.855-0.990, P = 0.025]. ROC curve analysis showed that the area under the ROC curve (AUC) of LVEF on admission for predicting the death of patients with septic cardiomyopathy was 0.715 (95% CI was 0.585-0.845, P = 0.005). When LVEF ≤ 0.52, the sensitivity was 73.9%, and the specificity was 61.5%. Conclusions:The lower cardiac ultrasound LVEF on admission, the worse the prognosis of patients with septic cardiomyopathy. The cardiac ultrasound LVEF on admission can be used as a clinical index to evaluate the severity of the condition and predict the prognosis of patients with septic cardiomyopathy.

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.
Humans ; Apoptosis Inducing Factor/metabolism* ; NAD/metabolism* ; Dimerization ; Apoptosis

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15％ of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.T260A, p.R422W, and p.R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5％?49.7％ of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3％?17.9％, which was significantly higher than that (6.9％?7.4％) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Objective To explore the application and method of World Health Organization Rehabilitation Competency Framework (RCF) in rehabilitation human resource management, and provide theoretical and practical reference for rehabilitation human resource management.Methods Based on the International Standard Classification of Occupations issued by the International Labour Organization, the application scope of RCF was systematically analyzed. The theoretical framework of rehabilitation human resource management based on RCF was constructed in combination with competency-based human resource management framework. On this basis, taking rehabilitation nurses as an example, the corresponding management methods and paths are proposed from four aspects of human resource management, including career management, recruitment and selection, training and development, and performance appraisal and salary management.Results Based on RCF, the theoretical framework of human resource management for rehabilitation nursing positions was constructed, and the main contents and processes of human resource management based on RCF were clarified from four aspects: recruitment and selection, training and development, performance appraisal and salary management, and career management. Occupational competency of rehabilitation professionals in International Standard Classification of Occupations was analyzed by RCF.Conclusion The rehabilitation competency framework constructed by WHO can be used to supplement the responsibilities of rehabilitation-related professionals in the International Standard Classification of Occupations issued by the International Labour Organization. RCF serves as a tool for practice managers and rehabilitation professionals in identifying selection criteria, learning objectives, and professional title assessment criteria. It can also be used in recruitment and selection, training and development, performance appraisal, salary management and career management in the field of rehabilitation human resource management.