Objective To investigate the role and underlying mechanism of activating transcription factor 3(ATF3)in suppressing lipopolysaccharide(LPS)-induced autophagy and inflammatory responses in macrophages.Methods Firstly,the gene expression omnibus(GEO)database was used to analyze ATF3 expression in peripheral blood mononuclear cells(PBMCs)from sepsis patients,and gene set enrichment analysis(GSEA)was performed to identify enriched signaling pathways.Secondly,RAW264.7 macrophages were divided into a blank control group and an LPS-stimulated group(100 ng/mL LPS).Western blotting and immunofluorescence assay were used to detect ATF3 protein expression and observe its subcellular localization,respectively.Lentiviral transduction was used to generate ATF3 knockdown and overexpression cell lines to evaluate their effects on cytokine release and bacterial clearance.Cleavage Under Targets and Tagmentation(CUT&Tag)sequencing was employed to identify downstream target genes transcriptionally regulated by ATF3.Furthermore,the impact of ATF3 knockdown or overexpression on autophagy-related gene 5(ATG5),autophagy-related gene 16-like 1(ATG16L1),and autophagy levels was evaluated.Results GEO analysis revealed that ATF3 expression was significantly elevated in PBMCs from sepsis patients(P<0.01),and GSEA showed significant enrichment of autophagy-related and inflammation-related pathways(P<0.01).In RAW264.7 cells,100 ng/mL LPS stimulation significantly increased ATF3 expression in the nucleus than the blank control group(P<0.01).ATF3 knockdown led to increased secretions of TNF-α and IL-6 and enhanced bacterial clearance of macrophages(P<0.01),whereas ATF3 overexpression significantly suppressed TNF-α and IL-6 releases,and remained bacterial clearance at a low level when compared with the conditions in the negative control(NC)group(P<0.01).CUT&Tag results demonstrated that ATF3 was enriched at the promoter regions of key autophagy genes Atg5 and Atg16l1.Compared with the NC group,ATF3 knockdown significantly up-regulated the protein levels of LC3-II/I,ATG5,and ATG16L1 while decreased p62 expression(P<0.01).Conversely,ATF3 overexpression inhibited the expression of LC3-II/I,ATG5,and ATG16L1(P<0.01),but had no significant effect on p62 level.Conclusion Sepsis induces elevated ATF3 expression in macrophages,and suppresses autophagic activity and down-regulates pro-inflammatory cytokines TNF-α and IL-6,which probably mediated by ATF3 regulating transcription of ATG5 and ATG16L1,suggesting ATF3 as a potential therapeutic target for autophagy-inflammation imbalance.

Objective:To report the preclinical trial results of the application of a domestic high-flow percutaneous left ventricular assist device (pLVAD) in patients with low cardiac output syndrome (LCOS) following cardiac surgery.Methods:Six patients who developed LCOS after direct cardiac surgery were implanted with a domestic high-flow pLVAD. Clinical outcomes, including hemodynamic changes, complications, and survival rates were observed post-implantation.Results:Four patients underwent pLVAD implantation under digital subtraction angiography (DSA) guidance, while two patients had the procedure performed under ultrasound guidance. The implantation process was straightforward, rapid, and uneventful, with no instances of bleeding or arrhythmias. The flow rate at the initiation of pLVAD support was 3.8-5.0 (4.22±0.44)L/min, and the flow rate during pump removal was 1.0-1.3(1.18±0.15)L/min. The duration of pLVAD support was 16.5-165.0(101.3±60.65)h. Hemodynamic parameters showed immediate improvement following pLVAD support: mean arterial pressure increased from (62.67±4.46)mmHg to (80.50±18.96)mmHg (1 mmHg=0.133 kPa, P=0.049), cardiac output increased from (2.45±0.66)L/min to (4.35±1.32)L/min( P=0.01), cardiac index improved from (1.95±0.21)L·min -1·m -2 to (2.77±0.33)L·min -1·m -2( P<0.001), pulmonary artery diastolic pressure decreased from (27.50±1.87) mmHg to(18.33±4.18)mmHg( P=0.001), and left ventricular ejection fraction improved from 0.27±0.04 to 0.37±0.06 ( P=0.004). No visible hemoglobinuria was noted during the support period. No malignant arrhythmias or cerebrovascular complications occurred. One patient required transition to surgical LVAD implantation, while the other five patients had the pLVAD successfully removed and were discharged. Three months later, all six patients were alive, with functional status classified as New York Heart Association (NYHA) Class Ⅰ-Ⅱ. Conclusion:The implantation of a domestic high-flow pLVAD provides a safe and effective therapeutic option for patients with LCOS following cardiac surgery.

Objective:To report the preclinical trial results of the application of a domestic high-flow percutaneous left ventricular assist device (pLVAD) in patients with low cardiac output syndrome (LCOS) following cardiac surgery.Methods:Six patients who developed LCOS after direct cardiac surgery were implanted with a domestic high-flow pLVAD. Clinical outcomes, including hemodynamic changes, complications, and survival rates were observed post-implantation.Results:Four patients underwent pLVAD implantation under digital subtraction angiography (DSA) guidance, while two patients had the procedure performed under ultrasound guidance. The implantation process was straightforward, rapid, and uneventful, with no instances of bleeding or arrhythmias. The flow rate at the initiation of pLVAD support was 3.8-5.0 (4.22±0.44)L/min, and the flow rate during pump removal was 1.0-1.3(1.18±0.15)L/min. The duration of pLVAD support was 16.5-165.0(101.3±60.65)h. Hemodynamic parameters showed immediate improvement following pLVAD support: mean arterial pressure increased from (62.67±4.46)mmHg to (80.50±18.96)mmHg (1 mmHg=0.133 kPa, P=0.049), cardiac output increased from (2.45±0.66)L/min to (4.35±1.32)L/min( P=0.01), cardiac index improved from (1.95±0.21)L·min -1·m -2 to (2.77±0.33)L·min -1·m -2( P<0.001), pulmonary artery diastolic pressure decreased from (27.50±1.87) mmHg to(18.33±4.18)mmHg( P=0.001), and left ventricular ejection fraction improved from 0.27±0.04 to 0.37±0.06 ( P=0.004). No visible hemoglobinuria was noted during the support period. No malignant arrhythmias or cerebrovascular complications occurred. One patient required transition to surgical LVAD implantation, while the other five patients had the pLVAD successfully removed and were discharged. Three months later, all six patients were alive, with functional status classified as New York Heart Association (NYHA) Class Ⅰ-Ⅱ. Conclusion:The implantation of a domestic high-flow pLVAD provides a safe and effective therapeutic option for patients with LCOS following cardiac surgery.

Objective:To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province.Methods:Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden.Results:From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women.Conclusions:The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Background Prolonged awkward postures during occupational activities can lead to excessive musculoskeletal load on the wrist of workers and symptoms such as wrist pain or discomfort. Objective To survey the prevalence of wrist pain among workers in 10 key industries and analyze its correlation with wrist working postures. Methods By using stratified cluster sampling method, workers from 10 key industries, such as footwear manufacturing industry, shipbuilding manufacturing industry, and automobile manufacturing industry, were selected from seven regions in North China, East China, Central China, South China, Southwest China, Northwest China, and Northeast China. The demographic information, wrist working postures, pain in wrist of the workers were collected through a cross-sectional survey. Pearson χ² test was used to compare prevalence by selected factors, trend χ² test for between group comparison, and unconditional logistic regression models for the association of wrist working postures with wrist pain. Results There were 64052 workers enrolled in this survey, and 56286 provided valid questionnaires (the effective rate was 87.8%). According to the survey, the prevalence of wrist pain was 23.3% (13112/56286), and the industries with higher prevalences were footwear manufacturing (27.1%, 1927/7106), automobile manufacturing (24.9%, 5378/21560), and shipbuilding and related equipment manufacturing (24.4%, 850/3488) industries. Finger pinching (OR=2.09, 95%CI: 1.95-2.24), frequent wrist bending (OR=2.03, 95%CI: 1.92-2.15), fixed wrist bending (OR=1.77, 95%CI: 1.69-1.85), wrist on hard edge (OR=1.34, 95%CI: 1.28-1.40), and arms over shoulders (OR=1.11, 95%CI: 1.05-1.17) increased the risk of reporting wrist pain. Conclusion Awkward postures are related to wrist pain among workers in selected 10 key industries. The related factors are wrist on hard edge, frequent wrist bending, finger pinching, fixed wrist bending, and arms over shoulders.

Zfyve16 (a.k.a. endofin or endosome-associated FYVE-domain protein), a member of the FYVE-domain protein family, is involved in endosomal trafficking and in TGF-β, BMP, and EGFR signaling. The FYVE protein SARA regulates the TGF-β signaling pathway by recruiting Smad2/3 and accelerating their phosphorylation, thereby altering their susceptibility to TGF-β-mediated T cell suppression. Zfyve16 binds to Smad4 and their binding affects the formation of Smad2/3-Smad4 complex in TGF-β signaling. However, the in vivo function of Zfyve16 remains unknown. In this study, we generated a Zfyve16 knockout mouse strain (Zfyve16) and examined its hematopoietic phenotypes and hematopoietic reconstruction ability. The proportion of Tcells in the peripheral blood of Zfyve16 mice increases compared with that in wild-type mice. This finding is consistent with the role of Zfyve16 in facilitating TGF-β signaling. Unpredictably, B cell proliferation is inhibited in Zfyve16 mice. The proliferation potential of Zfyve16 B-lymphoid cells also significantly decreases in vitro. These results suggest that Zfyve16 inhibits the proliferation of T cells, possibly through the TGF-β signaling, but upregulates the proliferation of B-lymphoid cells.
Animals ; B-Lymphocytes ; metabolism ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Movement ; Cell Proliferation ; genetics ; Intracellular Signaling Peptides and Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Mice ; Mice, Knockout ; Serine Endopeptidases ; genetics ; metabolism ; Signal Transduction ; Smad Proteins, Receptor-Regulated ; metabolism ; Transforming Growth Factor beta ; metabolism ; Up-Regulation

Objective To investigate the relationship between the rat depression behaviors induced by chronically unpredicted stress (CUS) with interleukin-1β (IL-1β),interleukin-6 (IL-6) protein expression and indole-2,3-dioxygenase (IDO) mRNA and protein expression.Methods Thirty male Sprague Dawley (SD)rats were divided into the control group (CG) and model group (MG).The solitary raise combined with CUS 28 d continued stimulus was used to establish the rat depression model.The open field test (OFT) and the force swimming test (FST) were used to evaluate the rat depression behaviors;qRT-PCR was used to determine the mRNA expression of IDO in hippocampus and cortex;Western blot was used to determine the protein expressions of IL-1β,IL-6 and IDO in hippocampus and cortex.Results Compared with the CG group,the OFT score in the rats of the MG group was significantly decreased(P＜0.01),the immobility time in FST was significantly extended (P＜0.00),the expression of IDO mRNA in hippocampus and cortex was significantly increased (P＜0.01) and the protein expression of IL-1β,IL-6 and IDO in hippocampus and cortex was significantly increased (P＜0.05).Conclusion The rat depression behaviors induced by CUS may be associated with the increase of intracerebral inflammatory cytokine expression and inducing IDO over-expression.

Aim To study the role of histone acetyla-tion and its involvement in the depression-like behav-iors of rats induced by chronic unpredictable stress (CUS ). Methods Thirty male Sprague Dawley (SD ) rats were randomly divided into control group and model group.The method of solitary condition with CUS for consecutive 28 days was used to establish the rat depression model.The open-field test (OFT)and the forced swimming test (FST)were used to evaluate the depressive behaviors of rats;the real time PCR was used to detect the change of HDAC2 mRNA, and Western blot was used to determine the protein expres-sions of H3,H4,acH3 and acH4 in the prefrontal cor-tex and hippocampus of rats.Results Model group showed obvious depression-like behaviors with decrea-sing locomotive activity in OFT (P <0.01 )and in-creasing immobility time in FST (P<0.01),up-regu-lating the mRNA and protein expression of HDAC2 (P<0.0 1 ),and down-regulating the protein expression of acH3 and acH4 (P<0.01)in the prefrontal cortex and hippocampus significantly,compared with control group.Conclusion The mechanism of depressive be-haviors of rats induced by CUS may be associated with down-regulating the level of histone acetylation modifi-cation.

Objective: To investigate the clinical status of lymphoid tissue neoplasms patients with bacteria bloodstream infections, bacteriology and drug susceptibility results, and provide the basis for rational clinical anti-infection option. Methods: A retrospectively analysis of clinical data and bacterial susceptibility test results of patients with bacteria bloodstream infections from September 2010 to December 2014 was conducted. Results: A total of 134 cases including 107 patients with bloodstream infections were enrolled. 84 cases were male, 50 cases were female, the median age was 31 (12-71) years old. 112 cases were agranulocytosis, and 106 cases were severe agranulocytosis (ANC<0.1×10⁹/L) . 27 cases underwent hematopoietic stem cell transplantation, 100 cases received chemotherapy[33 cases with VD (I) CP±L (vincristine+daunorubicin/idarubicin + cyclophosphamide + prednison±asparaginasum) induction chemotherapy, 41 cases with intensive chemotherapy of Hyper-CVAD/MA or MA (mitoxantrone+cytarabine) , 26 cases with other chemotherapy regimens], and 7 cases were infected without chemotherapy. 10 patients discharged from hospital owing to treatment abandoning, 120 cases were cured through anti-infective therapy, 2 patients died of bacteria bloodstream infections, 1 patient died of sudden cardiac, and 1 patient died of GVHD after allogenic hematopoietic stem cell transplantation. A total of 144 strains were isolated, including 108 strains (75.0%) of Gram-negative bacteria and 36 strains (25.0%) of Gram-positive cocci. The susceptibility of Gram-negative bacteria to the carbapenems was 98.00%, and the adjustment treatment rate of carbapenems was 3.0%. The susceptibility of Gram-negative bacteria to the other antibiotics was 60.30%, and the adjustment treatment rate was 90.5%. The susceptibility of Grampositive cocci to the carbapenems was 49.3%, and to glycopeptides and linezolid was 100.0%. Comparing all patients’empirical use of antimicrobial agents with the drugs susceptibility results of blood cultures, 80.1% of the patients’initial drug selection was sensitive. Conclusion The lymphoid neoplasms patients experienced bacteria bloodstream infections most often after receiving the chemotherapy regimens of treating acute lymphoblastic leukemia. The majority type of bacteria was Gram-negative bacteria. Drug susceptibility test showed that susceptibility of Gram-negative bacteria to the carbapenems was the highest, and the treatment adjustment rate was obviously lower. The susceptibility of Gram-positive cocci to glycopeptides and linezolid was high, and which could be applied to the patients with Gram-positive cocci sepsis on basis of susceptibility results in general.