Objective To investigate the impact of sleep modes on the risk for diseases of the body systems.Methods Based on a subset of UK Biobank dataset comprising 87 617 participants,3 sleep dimensions including 6 sleep indicators were obtained through a wrist-worn accelerometer,that is sleep duration and onset,sleep rhythm(relative amplitude and stability),and sleep quality(sleep efficiency and number of awakenings).Latent profile analysis(LPA)was applied to identify and classify distinct sleep modes.Then their longitudinal medical records were the association between different sleep modes and the risk for 467 diseases.Results LPA identified 5 subgroups of unique sleep modes in the participants.Among the 5 subgroups,the subgroup 4 had relatively optimal levels in above sleep indicators.Compared to the subgroup 4,the other 4 subgroups exhibited variations in different sleep dimensions,with at least one indicator demonstrating an unfavorable trend.These subgroups also revealed differences in racial composition,shift work and social deprivation index.Moreover,there were notable differences in the risk of various system diseases among the subgroups(P<0.05).When compared to the subgroup 4,the other 4 subgroups exhibited an elevated risk for certain diseases(comprising a total of 126 diseases),with the diseases of the circulatory system,digestive system and musculoskeletal system most common.Among the 5 subgroups,the subgroup 2(shorter sleep duration and later sleep onset)and the subgroup 5(rhythm disorder)had the highest counts of associated risks,amounting to 85 and 91 types,respectively,but there was certain difference in their systematic composition.Conclusion There are different sleep modes within the participants,and the modes are potentially associated with an increased risk for diseases of body systems.Comprehensive interventions targeting overall sleep modes rather than single sleep indicator may yield obvious health benefits.

Objective To investigate the transgenerational effects of paternal PM2.5 exposure on offspring growth and development,and to preliminarily elucidate the role of sperm DNA methylation modifications in mediating these effects.Methods Eight-week-old male C57BL/6 mice were randomly divided into filtered air(FA),unfiltered air(UA),and concentrated PM2.5(CAP)groups,with 10 animals in each group.The exposure was conducted from November 2019 to April 2020,and then,these male mice were mated with unexposed females to generate F1 offspring,which were bred successively to produce F2 and F3 generations.All the offspring were living in PM2.5-free environment.The birth body weight,birth number,and sex ratio of the offspring were recorded,body weight growth was monitored,and organ coefficients of the heart,liver,lung,and brain were calculated.Whole-genome methylation sequencing was performed on the sperm DNA of the CAP group,FA group,and their F1 generation offspring to screen for differentially methylated regions,and the genes and pathways associated with these regions were analyzed.Results When compared with the F1～F3 offspring of the FA group,the CAP group had significantly reduced birth body weight in the F1 generation(P<0.05),no statistical differences were observed in the birth body weight in the F2 and F3 generations(P>0.05),or either in the sex ratio and birth number among the F1,F2 and F3 generations.Compared with the FA group offspring,the F1～F3 offspring of CAP group exhibited delayed body weight gain,especially in the males(P<0.05),the CAP-F1 male generation had obviously elevated liver organ coefficient(P<0.01),but no statistical changes were observed in the heart,lung,or brain coefficients among the F1～F3 generations.Between the FA group and the CAP group,37 997 differentially methylated regions were detected,with a reduction of approximately 50%in the number of differentially methylated regions in the F1 generation.Differentially methylated genes in F0 and F1 sperm were potentially related to developmental processes,including imprinting genes(Gnas,Igf2)and metabolic genes(Ppard,Rps6kb1).Conclusion Paternal exposure to PM2.5 leads to reduced birth weight and intergenerational growth retardation in offspring.Its impact on phenotypic effects is gradually weakened during intergenerational transmission.Changes in the methylation of development-related genes in sperm may be one of the mechanisms mediating this intergenerational effect.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

OBJECTIVE To provide information service support for research on proteolysis targeting chimera （PROTAC） in China and provide reference for technical development and patent layout of relevant drug research and development institutions. METHODS The patent analysis method was used to search the patent applications related to PROTAC technology that had been applied to China National Intellectual Property Administration and had been issued before Feb. 2022， using the HimmPat patent database as the search platform. The patent application trend， technology life cycle， main applicants， technology source countries， technology themes， improvement routes and other patent data were analyzed. RESULTS & CONCLUSIONS A total of 133 patents were included in this study. The patent application for PROTAC technology started relatively late in China， with the number of applicants increasing from 2 in 2015 to 30 in 2020， and the number of applications increasing from 2 in 2015 to 38 in 2020. Both the annual patent application volume and the number of applicants were in a period of rapid growth， but the average annual application volume of a single applicant was still less than 2， indicating that research in this field was still in the early stage of technology development； the number of applications from Arvinas， Hisco， and Hinova Pharmaceutical Inc. ranked among the top. Although the number of domestic applications led that of foreign applications in China， the average number of simple peer applications and the average number of simple peer countries in domestic patent applications was only 1.5， which was far lower than that of foreign applications in China， reflecting that there was still room for improvement in the “quality” level of domestic applications. The initial improvements in PROTAC technology mainly focused on the selection of E3 ligands， targets and ligands， and then new improvements such as new PROTAC development， linker design and matching methods emerged， indicating that the patent applicant had started a multi-track layout in the early stages of the development of PROTAC technology. It is suggested that the research and development of PROTAC drugs in China should focus on improving the oral bioavailability and biosafety of PROTAC drugs， overcoming potential drug resistance， and exploring rational design and evaluation methods.

500?mol/L) of propofol was needed; In biological system near the range of anaesthetic concentration, propofol effectively scavenged oxygen free radical produced by respiratory burst of PMN. Conclusion: Propofol scavenging hydroxyl radical generated in biological and nonbiological system,may be one of the main mechanisms of its antioxidation,the intralipid component of Diprivan may affect its antioxidation.

Objective: To investigate the cytotoxicity of ICE gene transfection in Combination with Antitumor Chemicals killing Hepatocellular Carcinoma Cells in vitro.Methods: The recombinant plasmid pLXSN-hICE was transferred to virus packing cell PA317 by electroporation method. And then the retrovirus containing human ICE cDNA generated by these PA317 cells were used to transfect human hepatocellular carcinoma cell line HepG2. The apoptosis of transferred cells were examined by gel electrophoresis. The influence of chemotherapeutic drug Carbo-platin to the proliferation of hepatocellular carcinoma cell line SMMC7721 and its derivative cells(SMMC7721-hICE,SMMC7721-antisence hICE,SMMC7721-neo)was observed by incorporation of 3H-TDR. Results: Electrophoresis of DNA displayed the apoptosis ladder of HepG2 transfected by ICE gene. The proliferation of SMMC7721-hICE was significantly suppressed in vitro induced by Carbo-alatin compared to the other three cell lines. Conclusion: ICE gene transfection could greatly increase the susceptibility of SMMC7721 cells to apoptotic cell death following chemotherapy. These findings suggest that combining ICE gene transfection with utilizing antitumor drugs would represent a novel approach for the effective treatment of hepatocellular carcinoma.