Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Objective To explore the differences in stress distribution and stability of the planta pedis in the patients with unilateral and bilateral plantar fasciitis(PF)through plantar stress and center of pressure(COP)analysis.Methods A total of 100 patients with PF visiting in this hospital were enrolled,among them 50 cases were unilateral heel pain(unilateral heel pain group)and 50 cases were bilateral heel pain(bilateral heel pain).Meanwhile,50 healthy subjects were included(healthy group).In the health group and bilateral heel pain groups,the average stress value of both planta pedis surfaces of each subject was taken and named as the J0 group and H2 group,respectively.In the unilateral heel pain group,the plantar stress in 50 healthy feet and 50 affected feet were named as the J1 group and H1 group,respectively.The plantar pedis was divided into 10 regions for analysis and comparison[the first foot toe(T1),T2-5,the first-fifth metatarsal bones(M1-M5),the mid foot(MF),heel medial side(MH),heel lateral side(LH)].The subjects in 3 groups conducted the static and dynamic tests respectively,and the differences in plantar stress distribution and COP parameters among the J1,H1,H2 and J0 groups were compared respectively.Results In the static tests,the maximum pressure of the LH regions in the group J1 was increased when compared with the group J0,the contact area of LH regions in the group H1 was reduced when compared with the group J0,the maximum pressure of the M2 and M3 regions in the H1 group was increased when compared with the group J0,the contact areas of the MH and LH regions in the H2 group were decreased when compared with the group J0,the maximum pressure of the M1 region was increased when compared with the group J0,and the differences were statistically significant(P<0.05).In the dynamic tests,the maximum pressure of the T2-5 regions in the J1 group was increased when compared with the J0 group,the maximum pressure of the M3 region in the group H1 was increased when compared with the group J0,the maximum pressure of the M3 and M4 region in the group H2 was in-creased when compared with the group J0,and the differences were statistically significant(P<0.05).The COP 95%confidence ellipse area in the health group was the smallest,followed by the bilateral heel pain group,and finally the unilateral heel pain group,and the differences among 3 groups were statistically signifi-cant(P<0.05),there was also statistically significant difference between pairwise comparisons in 3 groups(P<0.05).Conclusion In the static condition,the pressure of the healthy heel and affected forefoot in the patients with PF is increased;while in the dynamic condition,the pressure of the toes of the healthy foot and forefoot of the affected foot in the patients with PF is also increased.The distribution of plantar stress in the patients with PF has larger difference compared with the healthy population,and the stability is poor.Meas-ures can be taken to improve the abnormal force on the foot,reduce pain and reduce the risk of falling.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

Objective:To analyze the characteristics of retinal neovascularization and tube diameter and the levels of miR-126 and miR-141-3p in peripheral blood of patients with diabetic retinopathy (DR).Methods:A total of 130 patients with DR Admitted to the Xi′an First Hospital from January 2020 to December 2023 were selected as the study objects (DR group), and 139 patients with type 2 diabetes who did not develop retinopathy during the same period (non-DR group) were selected. The characteristics of retinal neovascularization and tube diameter and the levels of miR-126 and miR-141-3p in peripheral blood were compared between the two groups. The patients with DR were divided into two groups according to whether retinal neovascularization and vascular diameter abnormalities occurred. The levels of miR-126 and miR-141-3p were compared between the two groups. Logistic regression analysis was used to evaluate the relationship between miR-126 and miR-141-3p levels in peripheral blood and retinal neovascularization and vascular diameter abnormalities in DR patients. Receiver operating characteristic (ROC) curve was drawn to examine the predictive efficacy of peripheral blood miR-126 and miR-141-3p levels on retinal neovascularization and tube diameter abnormalities in patients with DR.Results:There were significant differences in retinal neovascularization and vascular diameter between DR And non-DR patients. The retinal features of DR patients were significant, showing that a large number of new blood vessels form in and around the optic disc, spread to the entire retina, and form a fragile network structure, which was easy to be damaged and adhere to the vitreous cortex, and wound not disappear by itself and might invade the vitreous. The vascular diameter varied greatly, partial dilation showed abnormal blood flow, and partial stenosis reflected vascular damage. There was no significant retinal neovascularization in the non-DR group. The levels of miR-126 and miR-141-3p in the DR group were significantly lower than those in the non-DR group (all P<0.05). Among 130 patients with DR, 62 of them had abnormal retinal neovascularization and tube diameter, accounting for 47.69%. The levels of miR-126 and miR-141-3p in peripheral blood of DR patients with retinal neovascularization and vascular diameter abnormalities were lower than those in the non-DR group (all P<0.05). Logistic regression analysis showed that the levels of miR-126 and miR-141-3p in peripheral blood were associated with abnormal retinal neovascularization and tube diameter in DR patients (all P<0.05). ROC curve analysis showed that miR-126 and miR-141-3p had good predictive value for the occurrence of retinal neovascularization and tube diameter abnormalities in patients with DR. Conclusions:Some patients with DR have abnormal characteristics of retinal neovascularization and tube diameter, and peripheral blood miR-126 and miR-141-3p are related to the neovascularization and tube diameter abnormalities in patients with DR.

Objective:To analyze the characteristics of retinal neovascularization and tube diameter and the levels of miR-126 and miR-141-3p in peripheral blood of patients with diabetic retinopathy (DR).Methods:A total of 130 patients with DR Admitted to the Xi′an First Hospital from January 2020 to December 2023 were selected as the study objects (DR group), and 139 patients with type 2 diabetes who did not develop retinopathy during the same period (non-DR group) were selected. The characteristics of retinal neovascularization and tube diameter and the levels of miR-126 and miR-141-3p in peripheral blood were compared between the two groups. The patients with DR were divided into two groups according to whether retinal neovascularization and vascular diameter abnormalities occurred. The levels of miR-126 and miR-141-3p were compared between the two groups. Logistic regression analysis was used to evaluate the relationship between miR-126 and miR-141-3p levels in peripheral blood and retinal neovascularization and vascular diameter abnormalities in DR patients. Receiver operating characteristic (ROC) curve was drawn to examine the predictive efficacy of peripheral blood miR-126 and miR-141-3p levels on retinal neovascularization and tube diameter abnormalities in patients with DR.Results:There were significant differences in retinal neovascularization and vascular diameter between DR And non-DR patients. The retinal features of DR patients were significant, showing that a large number of new blood vessels form in and around the optic disc, spread to the entire retina, and form a fragile network structure, which was easy to be damaged and adhere to the vitreous cortex, and wound not disappear by itself and might invade the vitreous. The vascular diameter varied greatly, partial dilation showed abnormal blood flow, and partial stenosis reflected vascular damage. There was no significant retinal neovascularization in the non-DR group. The levels of miR-126 and miR-141-3p in the DR group were significantly lower than those in the non-DR group (all P<0.05). Among 130 patients with DR, 62 of them had abnormal retinal neovascularization and tube diameter, accounting for 47.69%. The levels of miR-126 and miR-141-3p in peripheral blood of DR patients with retinal neovascularization and vascular diameter abnormalities were lower than those in the non-DR group (all P<0.05). Logistic regression analysis showed that the levels of miR-126 and miR-141-3p in peripheral blood were associated with abnormal retinal neovascularization and tube diameter in DR patients (all P<0.05). ROC curve analysis showed that miR-126 and miR-141-3p had good predictive value for the occurrence of retinal neovascularization and tube diameter abnormalities in patients with DR. Conclusions:Some patients with DR have abnormal characteristics of retinal neovascularization and tube diameter, and peripheral blood miR-126 and miR-141-3p are related to the neovascularization and tube diameter abnormalities in patients with DR.

Objective:To understand the incidence of HIV infections and associated factors among men who have sex with men (MSM) in Jiangsu province.Methods:Based on national AIDS sentinel surveillance in 2019, MSM from 13 cities in Jiangsu were recruited for questionnaire interview and laboratory testing during April to July, 2019. Seropositive samples were tested with Limiting-antigen avidity enzyme immunoassay to detect recent HIV infections. The incidence of HIV infection in MSM were calculated according to the formula and parameters from China CDC. Multivariable logistic regression analysis was used to identify factors associated with recent infection of HIV.Results:A total of 4 469 MSM were subjects and the incidence of HIV infection were 4.5% (95% CI: 3.4%-5.5%).Multivariate logistic regression analysis results showed that compared with these aged ≥40 years, recruitment ways from MSM venues, awareness of AIDS knowledge, non-unprotected anal sex in the past 6 months and non-syphilis infection, those who aged 18-24 years (a OR=2.083,95% CI:1.087-3.990), recruitment ways from VCT clinics (a OR=2.125,95% CI:1.175-3.843), unawareness of AIDS knowledge (a OR=2.456,95% CI:1.109-5.437), unprotected anal sex in the past 6 months (a OR=3.553,95% CI:2.143-5.889) and syphilis infection (a OR=2.414,95% CI:1.033-5.462) were higher risk of HIV infection. Conclusion:The new infection rates of HIV were high in MSM in Jiangsu province. Health education, condom use and HIV/syphilis screening promotions should therefore be top priority in the prevention and control of HIV infection in MSM.

Objective To evaluate the effectiveness of perioperative fasting abbreviation in traumatic patients undergoing selective surgeries.Methods The traumatic patients undergoing selective surgeries from November 2016 to January 2017 at our department were selected for this prospective cohort study.They were divided into an intervention group (69 patients) and a control group (121 patients) according to the wards where they stayed.The intervention group was fasted for solids 6 hours prior to surgery and received oral solution with maltodextrin 2 hours prior to surgery.After surgery,they were allowed to drink liquids as soon as they were awakened.Normal food was allowed 2 hours later.The control group was fasted for either liquids or solids the night before surgery.After surgery,the patients who had received brachial plexus block only were allowed liquids with no limitation while the other patients were allowed liquids 6 hours after surgery and then were free for solids and liquids if no discomfort was observed.The time periods for preoperative liquids and solids fasting and for postoperative intake of liquids and solids were recorded and compared between the 2 groups.The perioperative well-beings (including anxiety,thirst,hunger,nausea,fatigue,dizziness,sweating and stomach discomfort) and serum glucose levels were compared between the 2 groups.Adverse reactions were observed.Results The preoperative fasting time for liquids for the intervention group (4.5 ± 2.9 hours) was significantly shorter than that for the control group (14.3 ±3.9 hours) (P ＜ 0.05).The preoperative fasting time for solids for the intervention group (17.6 ± 3.0 hours) were significantly longer than that for the control group (16.1 ±3.8 hours) (P ＜ 0.05).The postoperative fasting time periods for both liquids [1 (0,3) h] and solids [2 (1,4) h] for the intervention group were significantly shorter than those for the control group [6(6,6) h] hours and [6(6,6) h] (P ＜ 0.05).Compared with the control group,the perioperative anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort were significantly improved in the intervention group (P ＜ 0.05).The average serum glucose level was similar in both groups upon admission (P ＜ 0.05);it was significantly higher in the intervention group immediately before surgery (P ＜ 0.05) but was gradually decreased after surgery until there was no significant difference between the 2 groups (P ＞ 0.05).No major adverse reaction was observed in either group.Conclusion The protocol of perioperative fasting abbreviation may be safe and feasible in traumatic patients for selective surgeries,showing benefits of decreased anxiety,thirst,hunger,nausea,fatigue,dizziness and stomach discomfort.

Objective To compare the perioperative characteristics and long term outcomes between extracorporeal membrane oxygenation (ECMO)-conventional cardiopulmonary switch (experimental group,26 cases) and off-pump high-risk coronary artery bypass grafting (OPCABG group,24cases).Methods Perioperative characteristics and survival rate were retrospectively analyzed between experimental group and OPCABG group.Long term survival rates without major cardiovascular adverse events (MACE) were comparatively analyzed via Kaplan-Meier curves.Results The average Euroscore value were 11.7 ± 2.4 and 10.9 ± 2.0,respectively(P =0.208).The experimental group had a higher complete revascularization rate (96.2％ vs.66.7％,P =0.009),a shorter length of postoperative ECMO support [(33.1±23.6)h vs.(80.8±18.5)h],an intensive care unit stay[(4.8±1.1)d vs.(10.2±9.0)d]and a hospital stay [(17.7±6.3)d vs.(28.2±17.5)d] (all P＜0.05) as compared with OPCABG group.Preoperative New York Heart Association (NYHA) grading of cardiac function (r =0.511,P =0.008) and intraoperative ultrafiltration volume (r =-0.442,P =0.024) were significantly correlated with postoperative ECMO continuation in the experimental group.The follow-up period was (45.4 ± 15.2) months.The experimental group had a higher survival rate without MACE than had the OPCABG group (Log-rank test:x2=4.828,P=0.028).Conclusions The ECMO-conventional cardiopulmonary switch mode might facilitate a higher complete revascularization,a lower incidence of postoperative morbidities and improve the longterm survival rate without MACE for patients with high risks.