Hypoxia inducible factors(HIFs)are core molecules that enable the body to adapt to hypoxia environments.By sensing changes in intracellular oxygen pressure,HIFs regulate gene expression related to hypoxia adaptation,thereby enhancing the body's hypoxia tolerance at cellular,tissue and organ levels.On the other hand,HIFs promote the generation of red blood cells,angiogenesis,and regulate the body's energy metabolism,thereby improving its hypoxia tolerance.The enhancement of hypoxia tolerance is of great significance for the prevention and treatment of hypoxia-related diseases,upgrading of athletes'performance,enhancement of workers'efficiency at high-altitudes,and the improvement of individu-als'quality of life.This article reviews the relationships between HIFs and hypoxia tolerance as well as related mechanisms in order to provide strategies for enhancing hypoxia tolerance in the body.

Angiopoietin-like proteins(ANGPTLs)are a family of proteins that are structurally similar to angio-poietin.So far,eight ANGPTLs have been discovered,namely ANGPTL1 to ANGPTL8.They are not only angiogenic fac-tors,but also play a pivotal role in various pathophysiological processes such as glucose and lipid metabolism,redox regu-lation,chronic inflammation and cancer,and having a close connection with the occurrence and development of metabolic diseases.This review focuses on the mechanism of action of ANGPTLs in metabolic associated fatty liver disease,in order to make a contribution to the prevention and treatment of MAFLD and concurrent diseases.

Angiopoietin-like proteins(ANGPTLs)are a family of proteins that are structurally similar to angio-poietin.So far,eight ANGPTLs have been discovered,namely ANGPTL1 to ANGPTL8.They are not only angiogenic fac-tors,but also play a pivotal role in various pathophysiological processes such as glucose and lipid metabolism,redox regu-lation,chronic inflammation and cancer,and having a close connection with the occurrence and development of metabolic diseases.This review focuses on the mechanism of action of ANGPTLs in metabolic associated fatty liver disease,in order to make a contribution to the prevention and treatment of MAFLD and concurrent diseases.

Nonalcoholic fatty liver disease(NAFLD)has become the most common liver disease in the world and is an important risk factor for the progression to hepatocellular carcinoma.However,the pathogenesis of NAFLD remains unclear,and there is still a lack of specific treatment measures.Sterol regulatory element-binding proteins(SREBP)are an important nuclear transcription factor,which mainly maintains the balance of lipid metabolism inside the body by activating the genes associated with the synthesis and uptake of cholesterol,fatty acids,and triglycerides,and therefore,SREBP are a target for the treatment of metabolic diseases.This article reviews the latest advances in SREBP in the pathogenesis of NAFLD and the latest evidence of SREBP-targeted therapy for NAFLD.It is worth noting that recent studies have shown that SREBP inhibition can cause liver injury together with autophagy damage.Therefore,excessive inhibition of lipogenesis may exert a counterproductive effect on the treatment of NAFLD.In conclusion,SREBP is a promising therapeutic target for NAFLD;the molecular mechanism of SREBP in lipid metabolism is regulated by many factors,and these factors are being deeply explored and analyzed,which has an important clinical significance for the treatment of NAFLD.

Alzheimer's disease(AD)is a common neurodegenerative disease.Neuroinflammation is one of the important pathological mechanisms of AD.The generation of AD neuroinflammation is closely associated with Aβ deposition,Tau phosphorylation,glial polarization and activation of inflammasome.Acupuncture and moxibustion have such effect on the improvement of AD neuroinflammation,which can relieve neuroinflammation by regulating the polarization of microglia and astrocytes,reducing the release of inflammatory mediators,so as to delay the pathological process of AD.This article reviews the neuroinflammatory mechanism of AD and the research progress of acupuncture and moxibustion regulating AD neuroinflammation,in order to provide a theoretical basis and idea reference for the clinical and basic research of acupuncture and moxibustion in the prevention and treatment of AD.

Objective To explore the application and prospects of artificial intelligence (AI) in metabolic associated fatty liver disease (MAFLD) based on bibliometrics. Methods Relevant literature on the application of AI technology in MAFLD was retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was conducted using CiteSpace, VOSviewer, R package "bibliometrix", and online bibliometric analysis was platformed to identify hotspots and trends in this field. Results A total of 303 eligible articles were obtained. Since 2017, the number of papers in this field had experienced explosive growth. The United States was leading the research on the application of AI in MAFLD and was the most frequent participant in international cooperation. San Diego of University of California was the institution with the highest number of publications. Rohit Loomba was the author with the highest number of publications, having published 14 articles. The co-cited keyword clustering labels revealed 10 major clusters: digital image analysis, machine learning, computer-aided diagnosis, fibrosis stage, automated quantitative analysis, metaproteomics, non-invasive diagnosis, ultrasonography, electronic health records, and knowledge representation. Current research on the application of AI in MAFLD mainly focused on the diagnosis, differential diagnosis, and staging of MAFLD. Image recognition and analysis, intelligent assisted diagnosis, AI algorithms, and monitoring disease progression will be important research directions for AI in MAFLD. Conclusion Research on the application of AI in MAFLD is experiencing exponential growth. Given enormous potential and clinical application prospects of this field, the application of AI in MAFLD-related areas will remain a research hotspot in the future.

OBJECTIVE To explore the potential mechanism of action of Gexia zhuyu decoction in the intervention of metabolic-associated fatty liver disease(MAFLD)based on ferroptosis.METHODS With the help of network pharmacology,the central targets of Gexia zhuyu decoction intervening in ferroptosis of MAFLD were screened,then gene ontology,Kyoto Encyclopedia Gene and Genomes enrichment analysis and molecular docking were performed.Juvenile zebrafish with normal development at 3 d post-fertilization were randomly divided into control group,model group(5 mmol/L thioacetamide),magnesium isoglycyrrhizinate group(positive control,5 mg/mL),and Gexia zhuyu decoction low-,medium-and high-concentration groups(20,40,80 μg/mL,calculated by crude drugs).After cultured for 72 h,the contents of alanine transaminase(ALT),aspartate transaminase(AST),total cholesterol(TC),triglyceride(TG),malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),reactive oxygen species(ROS)and Fe2+were determined;the cellular structure of the liver tissues and hepatic steatosis were observed;the protein expression of silence information regulator 1(SIRT1),nuclear factor-erythroid 2-related factor 2(Nrf2)and glutathione peroxidase 4(GPX4)were detected.RESULTS The central targets of potential active ingredients of Gexia zhuyu decoction that act on ferroptosis in MAFLD included tumor proteins p53,SIRT1,Nrf2,etc.,which were enriched in biological processes such as positive/negative regulation of RNA polymerase n promoter transcription,cellular components such as nucleus and cytoplasm,molecular functions such as protein binding,as well as signaling pathways such as ferroptosis and the cancer pathway,and they might be tightly linked to the main active ingredients.Compared with model group,the contents of ALT,AST,TC,TG,MDA,ROS and Fe2+were all decreased significantly in each administration group,while the contents of SOD and GSH were increased significantly(P＜0.05);the pathological damage of liver tissue cells had improved,and the accumulation of liver lipids had decreased.The protein expressions of SIRT1,Nrf2 and GPX4 had been significantly upregulated(P＜0.05).CONCLUSIONS Gexia zhuyu decoction can regulate lipid metabolism,improve the level of oxidative stress,maintain Fe2+homeostasis,and inhibit the process of ferroptosis in juvenile zebrafish with MAFLD,and the above effects may be related to the activation of the SIRT1/Nrf2/GPX4 axis.

Objective:To understand the sleep quality and mental health status of nurses in public health emergencies, and analyze the correlation between them.Methods:A total of 128 first-line nursing staff participating in public health emergencies on February 22-23, 2020 in Tianjin Beichen Hospital, Tianjin First Central Hospital, Tianjin Fourth Central Hospital were investigated by the general data questionnaire, Pittsburgh Sleep Quality Index (PSQI), and Symptom Checklist 90 (SCL-90).Results:70.3%(90/128) of nursing staff had poor sleep quality, and the total score of PSQI was (9.71±4.01) points, which was statistically significant compared with the domestic norm ( t value was 16.479, P<0.01). The total score of SCL-90 was 1.59±0.52, which was statistically significant compared with the domestic norm ratio ( t value was 4.505, P<0.01). One-way ANOVA showed that the nursing staff's age had a significant impact on sleep quality, and the difference was statistically significant ( F value was 4.092, P<0.05). Pearson correlation analysis showed that the Pittsburgh sleep quality scale index scores and symptom self-assessment scale and somatization, force, sensitive interpersonal relationship, depression, anxiety, hostile, terrorist, paranoia, and psychosis were positively correlated( r values were 0.292-0.444, P< 0.01). Conclusions:The sleep quality and mental health status of nurses in public health emergencies are poor, and the sleep quality is correlated with mental health status.

OBJECTIVE: To explore the clinical characteristics of congenital neutropenia caused by ELANE gene mutations. METHODS: Clinical manifestations, absolute blood neutrophil count, high-throughput exome sequencing for mutation screening, suspected locus Sanger sequencing verification, processes of diagnosis and treatment of two patients with congenital neutropenia caused by ELANE gene mutation were retrospectively analyzed. RESULTS: High-throughput sequencing has found that proband 1 has carried a heterozygous c.170C>T (p.Ala57Val) missense mutation in exon 2 of the ELANE gene, which was known to be pathological, and a heterozygous c.251T>G (p.Leu84Arg) mutation in exon 3 of proband 2, which was unreported previously. Sanger sequencing confirmed that neither mutation was inherited from their parents. CONCLUSION ELANE mutation is an important cause for congenital neutropenia. Detection of new pathogenic variants has enriched the mutation spectrum of the ELANE gene.

Objective To investigate the effect of moderate treadmill exercise together with modified hydroxyapatite chitosan composite hydrogel (CS/HA-g-CS) implantation on repair of full-thickness defects of articular cartilage in rats.Methods Full-thickness cartilage defects were drilled in the patellar groove of bilateral femoral condyles in a total of 24 male SD rats before they were randomly assigned into 4 groups.The control group (BC group) was subjected to no exercise or CS/HA-g-CS implantation;the chitosan group (CHI group) to CS/HA-g-CS implantation without exercise;the moderate treadmill exercise group (MIR group) to exercise 4 weeks after modeling without CS/HA-g-CS implantation;the CHI + MIR group to moderate treadmill exercise plus CS/HA-g-CS implantation 4 weeks after modeling.Half of the animals were sacrificed at week 8 and half at week 16 after operation.Femoral condyles were harvested for gross observation and histochemical measurement by O' Driscoll scoring system.mRNA expressions of glycosaminoglycan,collagen type Ⅱ and BMP-2 were detected by RT-PCR.Results Gross observation revealed:at 8 weeks after modeling,the CHI + MIR group was significantly better than the other 3 groups,with the BC group in the poorest (P ＜ 0.05);at 16 weeks after modeling,the BC group was significantly poorer than the other 3 groups (P ＜0.05) among which there were no significant differences (P ＞ 0.05).O 'Driscoll scoring revealed:at both 8 and 16 weeks after modeling,the CHI + MIR group was significantly better than the other 2 groups and the BC group significantly poorer than the other 3 groups (P ＜ 0.05) but there was no significant difference between the MIR and CHI + MIR groups(P ＞ 0.05).The expressions of collagen type Ⅱ,glycosaminoglycan and BMP-2 were significantly higher in the CHI + MIR group than in the other 3 groups (P ＜ 0.05) and significantly lower in the BC group than in the other 3 groups (P ＜ 0.05).Conclusions Moderate treadmill exercise together with CS/HA-g-CS implantation has significant positive effects on repair of full-thickness defects of articular cartilage in rats than merely moderate treadmill exercise or CS/HA-g-CS implantation alone.The defective cartilage repaired by moderate treadmill exercise together with CS/HA-g-CS implantation contains more collagen type Ⅱ and glycosaminoglycan and shows morphology of nearly normal cartilage.