Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Purpose/Significance To build an evaluation index system of hospital intelligence in line with China's national conditions,so as to provide references for the quantitative evaluation of the degree of hospital intelligence,and to help the orderly development of hospi-tal intelligence construction.Method/Process Based on the review of the existing evaluation standard system of hospital informatization con-struction,Delphi method and analytic hierarchy process are used to discuss the construction process of hospital intelligence evaluation index system from four processes:construction of an evaluation index system,selection of experts in letter consultation,evaluation of indicator im-portance and verification of letter consultation results,and determination of the evaluation index weight.Result/Conclusion The construc-tion of hospital intelligence evaluation index system,which includes 3 first-level indexes,8 second-level indexes and 33 third-level in-dexes,is complementary to the existing evaluation system of smart hospitals,can reflect the construction foundation and development goals of the current intelligent hospitals,and has certain applicability and guidance for the future construction of smart hospitals.

Purpose/Significance To construct the conceptual model of hospital intelligence index,so as to lay the foundation for the quantitative evaluation of hospital intelligence degree,and help the intelligent construction of hospital.Method/Process The paper intro-duces the connotation of intelligence,expounds the evaluation standard system of hospital informatization construction,and considers the application of intelligence in hospital from the perspective of structure-function-effect.Result/Conclusion The conceptual model of hospital intelligence index is built.That conceptual model includes 3 first-level indicators,8 second-level indicators and 33 third-level indicators of intelligence basis,intelligence capacity and intelligence effect.As a tool for continuous improvement of medical serv-ices,regular assessment of hospital intelligence level can promote the improvement of medical quality and patient experience,and help the high-quality development of hospitals.

Objective:To analyze the level of self-management and its influencing factors in patients with systemic lupus erythematosus (SLE).Methods:A cross-sectional study. From January to December 2021, patients with SLE in the Department of Rheumatology and Immunology in the First Affiliated Hospital of Henan University of Traditional Chinese Medicine were selected as the study objects by convenience sampling method. A total of 135 questionnaires were distributed in this study, 135 were recovered, and 128 were valid. The general data of the patients were collected, and the self-management level, self-efficacy, family care and meaning in life of the patients were evaluated with the chronic disease self-management behavior scale, general self-efficacy scale (GSES), family adaption partnership growth affection resolve index (APGAR) and the meaning in life questionnaire (MLQ). Multiple linear regression analysis was applied to explore the factors affecting the self-management of SLE patients.Results:The total score of chronic disease self-management behavior scale in the 128 SLE patients was (28.77±6.58) points. Pearson correlation analysis showed strong correlation between self-efficacy, sense of life meaning and self-management ( r=0.748, 0.717, both P<0.001), there was a moderate correlation between family care and self-management ( r=0.560, P<0.001). Multiple linear regression analysis showed that educational level ( β′=0.457), disease activity ( β′=-0.211), self-efficacy ( β′=-0.372), family care ( β′=-0.510), meaning in life ( β′=-0.386) were influencing factors of self-management level in patients with SLE (all P<0.05). Conclusions:The self-management level of SLE patients needs to be improved. Disease activity, self-efficacy, meaning in life and other factors can affect the patients′ self-management level.

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.

Objective:To explore the mechanism of Xijiao Dihuang Ddecoction (XJDHT) against sepsis-induced liver injury based on transcriptomics.Methods:Sixty C57BL/6 mice were randomly (random number) divided into the sepsis group, sepsis treatment with XJDHT and control group, with 20 mice in each group. The sepsis mouse model was established by intraperitoneal (i.p.) injection of lipopolysaccharide (LPS). The control group was intraperitoneally injected with the same amount of normal saline. The sepsis treatment with XJDHT group was injected with XJDHT (crude drug 187.5 mg) twice a day 2 days before modeling. After modeling, gastric feeding was continued twice a day, while the control group and sepsis group were gavaged with the same amount of normal saline. At 72 h after LPS intervention, 9 mice in each group were randomly selected. After anesthesia, part of the liver were taken for small RNA and RNA sequencing and analysis, and part of the liver were taken for pathological examination.Results:XJDHT could improve the histopathological changes of liver in septic mice, and alleviate some abnormally expressed microRNAs (mmu-mir-292a-5p, mmu-mir-871-3p, mmu-mir-653-5p, mmu-mir-293-5p, mmu-mir-155-3p, mmu-mir-346-5p, mmu-mir-187-5p, mmu-mir-3090-3p) and their target genes.Conclusions:XJDHT can reduce the liver histopathological changes in septic mice, and its mechanism may be related to XJDHT regulating the expression of important key genes of liver of sepsis like mmu-mir-187-5p and its target genes such as ADAM8, irak3 and PFKFB3

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO). METHODS: Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing. RESULTS: A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing. CONCLUSION The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
Codon, Nonsense ; Exons/genetics* ; Exostoses, Multiple Hereditary/genetics* ; Heterozygote ; Humans ; Pedigree

OBJECTIVETo detect potential mutation of EXT1 gene in a pedigree affected with multiple osteochondroma and explore its pathogenic mechanism.

METHODSThe coding regions and their flanking sequences of the EXT1/EXT2 genes were subjected to PCR amplification and Sanger sequencing. Suspected mutations were verified by excluding possible single nucleotide polymorphisms and bioinformatics analysis. Transcripts of the EXT1 gene in the proband were analyzed by TA clone-sequencing, with its abundance compared with that of healthy controls.

RESULTSDNA sequencing has identified in the proband a novel heterozygous point mutation (c.1164+1G to A) at the 5'splice sites of intron 3 of the EXT1 gene. The same mutation was not found in the healthy controls. Bioinformatics analysis indicated that the mutation is highly conserved and can lead to skipping of exon 3 or aberrant splicing. TA clone-sequencing indicated that the numbers of transcripts with skipping of exon 3 has significantly increased in the proband (< 0.05) compared with the controls.

CONCLUSIONThe c.1164+1G to A mutation has resulted in skipping of exon 3 in a proportion of EXT1 gene transcripts. As the result, the number of transcripts with tumor suppressing function is relatively reduced and has ultimately led to the tumors.

Adult ; Base Sequence ; Child ; Exostoses, Multiple Hereditary ; genetics ; Female ; Humans ; Male ; Molecular Sequence Data ; N-Acetylglucosaminyltransferases ; genetics ; Point Mutation ; RNA Splice Sites ; RNA Splicing

OBJECTIVE To understand the disinfection,use and management of ventilator for the sake of regulation.METHODS By interviewing and on-site survey,we understanded the method and the process of disinfection and found out the using cycle of the ventilator system and the conditions of its management.RESULTS Among 44 ventilators 7 models were found:the management of 18 ventilators was irregular;the other 26 ventilators were disinfected by 2 kind and 4 types disinfect methods.their using cycles were unsure,their processes of disinfection were irregular.The responsibilities for the disinfection were unclear,lacking of monitoring the effect of disinfection and their management was irregular.CONCLUSIONS The disinfection of ventilator using and management must be regulated.