ObjectiveTo investigate the risk factors for bleeding within 5 days and 2 weeks after endoscopic variceal ligation （EVL） or endoscopic cyanoacrylate injection （ECI） for the treatment of esophagogastric varices in patients with liver cirrhosis， as well as the safety of EVL/ECI in patients with thrombocytopenia. MethodsA total of 489 patients with liver cirrhosis and esophagogastric varices who underwent EVL/ECI in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2018 to December 2023 were enrolled as subjects， and according to the presence or absence of bleeding after surgery， they were divided into bleeding group and non-bleeding group. The risk factors for bleeding within 5 days and 2 weeks after surgery were analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups， and the chi-square test or the continuity-corrected chi-square test was used for comparison of categorical data between groups； the receiver operating characteristic （ROC） curve was plotted to determine the cut-off value of MELD score； a multivariate logistic regression analysis was used to identify the independent risk factors for postoperative bleeding. ResultsThere were no significant differences in the bleeding rates within 5 days and 2 weeks after EVL/ECI between the 386 patients with a platelet count of ≥50×10⁹/L and the 103 patients with a platelet count of （25 — 49）×10⁹/L （5 days： 1.94% vs 2.85%， P=0.870； 2 weeks： 2.91% vs 4.92%， P=0.544）. The overall bleeding rate was 2.66% （13/489） and 4.50% （22/489）， respectively， within 5 days and 2 weeks after EVL/ECI. The multivariate logistic regression analysis showed that MELD score was an independent risk factor for bleeding within 5 days （odds ratio ［OR］=3.726， 95% confidence interval ［CI］： 1.214 — 11.429， P=0.021） and 2 weeks （OR=5.760， 95%CI： 1.779 — 18.651， P=0.003） after EVL/ECI， while hemoglobin （Hb） was a protective factor against bleeding within 5 days （OR=0.972， 95%CI： 0.948 — 0.996， P=0.025） and 2 weeks （OR=0.976， 95%CI： 0.957 — 0.995， P=0.016） after surgery； portal vein tumor thrombus （OR=2.667， 95%CI： 1.000 — 7.117， P=0.050） was an independent risk factor for bleeding within 2 weeks after surgery， while platelet count ［（25 — 49）×10⁹/L］ was not a risk factor for postoperative bleeding （P>0.05）. ConclusionBoth EVL and ECI have good safety in patients with liver diseases and grade 3 thrombocytopenia. MELD score is an independent risk factor for bleeding within 5 days and 2 weeks after EVL/ECI， while Hb is a protective factor； portal vein tumor thrombus is an independent risk factor for bleeding within 2 weeks after surgery.

Background Long-term exposure to ambient fine particulate matter (PM_2.5) is a significant risk factor for cardiometabolic disorders. However, the mechanisms of its interaction with the endogenous circadian system remain incompletely understood. Objective To investigate whether chronic PM_2.5 exposure interferes with the rhythmic expression of the cardiac circadian clock, thereby disrupting downstream antioxidant defenses and metabolic homeostasis, and ultimately driving cardiometabolic dysfunction. Methods Seventy-two male C57BL/6 mice were randomly divided into a PM_2.5 exposure group (PM group) and a filtered air control group (FA group). Whole-body exposure was conducted for 8 weeks in a meteorological environmental animal exposure system. Samples were collected at six distinct zeitgeber time (ZT) points post-exposure. The 24 h ambulatory blood pressure and serum lipid profiles were monitored. Rhythm parameters were derived via cosinor analysis to compare differences in Midline statistic of rhythm (Mesor), amplitude, and phase between the two groups. The rhythmic expression of core circadian clock genes and antioxidant genes in the myocardium was detected by quantitative polymerase chain reaction (qPCR). Myocardial reactive oxygen species (ROS) levels and downstream pathway protein expression were analyzed by immunofluorescence and Western blot (WB), respectively. The expression changes of the clock gene retinoic acid receptor-related orphan receptor α (RORα) were assessed at both the mRNA and protein levels. Finally, Spearman correlation analysis was used to explore the relationships among myocardial RORα expression, lipid profiles, and oxidative stress indicators. Results Compared to the FA group, mice in the PM group exhibited a blunted circadian rhythm in blood pressure, characterized by sustained elevation throughout the day. Chronic PM_2.5 exposure showed a significant interaction with ZT on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (F-interaction=9.11, 5.70, and 6.02, respectively; P<0.05), as well as on serum triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (F-interaction=16.32, 11.12, 15.39, and 28.09, respectively; P<0.05). Cosinor analysis further revealed that the Mesor values of T-CHO, TG, and LDL-C were significantly increased (P<0.05), while that of HDL-C was significantly decreased in the PM group (P<0.05). The oscillation amplitudes of SBP, DBP, and MAP showed a decreasing trend, whereas those of TG and LDL-C were significantly increased (P<0.05). Furthermore, SBP, T-CHO, and HDL-C all exhibited a significant phase delay (P<0.05). Mechanistically, PM_2.5 exposure significantly suppressed the expression of the positive circadian regulator RORα in the myocardium, leading to disordered rhythmic expression of core clock genes (Bmal1, Clock, Per1/2, and Cry1/2). This exposure also inhibited the rhythmic expression of antioxidant genes (GPX1, SOD2, and CAT), resulting in increased ROS generation and elevated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) proteins. Correlation analysis further revealed that myocardial RORα expression level was negatively correlated with T-CHO, TG, and LDL-C (r=−0.55, −0.63, and −0.51, respectively; P<0.001), and positively correlated with HDL-C (r=0.37, P=0.010), and antioxidant genes GPX1, SOD2, and CAT expression (r=0.34, 0.35, and 0.56, respectively; P < 0.001). Conclusion Chronic PM_2.5 exposure induces cardiometabolic dysfunction by suppressing myocardial RORα expression. This suppression disrupts the cardiac circadian clock and the diurnal balance of oxidative stress, triggering oxidative damage and elevating expression of CaMKII/NADPH pathway proteins. Collectively, these alterations precipitate the loss of cardiac metabolic rhythms and subsequent functional impairment.

AIM: To investigate the causal effects of ceramides on retinal vein occlusion(RVO)and elucidate their potential mediating mechanisms using Mendelian randomization(MR)analysis.METHODS: Genome-wide association study(GWAS)data for four ceramide species were utilized as exposures, and RVO GWAS data from the FinnGen database as the outcome. Additionally, GWAS data for 1 400 intermediate metabolites were analyzed to identify potential mediators in the ceramide-RVO pathway.RESULTS: Two ceramide species exhibited significant causal associations with RVO: ceramide(d40:1)[IVW OR(95% CI): 0.750(0.604-0.930), P<0.05] and ceramide(d42:2)[IVW OR(95% CI): 0.771(0.632-0.941), P<0.05], suggesting protective effects. Mediation analysis revealed that ceramide(d40:1)influenced RVO risk through metabolites including 3-methylxanthine, branched/straight-chain/cyclopropyl 10:1 fatty acids, glutamine, and hydroxypalmitoyl sphingomyelin. Similarly, ceramide(d42:2)acted via N-methylhydroxyproline, the same fatty acid group, N1-methyladenosine, and the leucine-to-N-palmitoyl-sarcosinate ratio.CONCLUSION: Ceramides(d40:1)and(d42:2)confer protection against RVO, partially mediated by specific metabolic pathways.

Esophagogastric variceal bleeding is a common complication and the leading cause of death in advanced liver cirrhosis， and endoscopic variceal ligation （EVL） and endoscopic cyanoacrylate injection （ECI） are commonly used treatment strategies. Thrombocytopenia is one of the most common hematological complications in liver cirrhosis， and patients with severe thrombocytopenia have the potential risk of bleeding， which may affect treatment decision-making by clinicians and endoscopists. This article reviews the evolution of guidelines and clinical research advances regarding EVL/ECI in China and globally， in order to provide a basis for decision making among clinicians.

Objective To analyze trend changes of disease burden of hypertensive nephropathy (HTN) between 2012 and 2023 in Chongqing, and to provide the suggestion for HTN prevention and treatment. Methods Death cases of HTN from Chongqing death registration data between 2012 and 2023 were analyzed to calculate indicators such as mortality, age standardization mortality rate (ASMR), rate of years of life lost (YLL) and Average years of life lost. The mortality of HTN between male and female, urban and rural were compared by Chi-square test. The trend change was explained by average annual percent of change (AAPC). Results The mortality and standardized mortality of HTN in Chongqing decreased from 5.44/100 000 and 3.13/100 000 in 2012 to 2.76/100 000 and 1.07/100,000 in 2023 respectively. The average annual percent change (AAPC) was -5.41% and -8.35% respectively, and the differences in the change trends were statistically significant (P<0.01). The mortality and standardized mortality of HTN in males and females decreased with AAPC of 5.50%, 8.07%, 5.27% and 8.69% respectively, and the differences in the change trends were all statistically significant (all P< 0.05). From 2012 to 2014, 2019 and 2021, the mortality rate of HTN in rural areas was higher than that in urban areas (all P < 0.05). The mortality and standardized mortality of HTN in rural areas decreased with AAPC of 6.58% and 9.46% respectively, and the differences in the change trends were all statistically significant (all P<0.05). The rate of YLL and standardized YLL of HTN in Chongqing decreased from 96.02/100 000 and 60.42/100 000 in 2012 to 44.98/100 000 and 21.49/100 000 in 2023 respectively. The AAPC was -5.83% and -7.80% respectively, and the differences in the change trends were statistically significant (both P < 0.05). AYLL of HTN were 17.88 years in 2012, and it was 17.08 years in 2023. There were no statistically significant differences in the changes (both P > 0.05). The standardized AYLL of HTN in rural areas increased at an average annual rate of 1.14%, and the difference was statistically significant (P < 0.05). Conclusion The mortality and YLL rate of HNT in Chongqing was lower than it in China. Moreover, its trend was decreased. It should be strengthened early screening and healthy management of HNT.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Mitophagy,a special form of selective autophagy,plays a significant role in the pathogenesis of atherosclerosis by regulating cellular lipid metabolism,inflammation,and oxidative stress.However,its regulatory mech-anism is complex and has not been fully elucidated.Notably,many drugs and herbal ingredients exhibit anti-atherosclerot-ic effects by modulating mitophagy in macrophages,vascular endothelial cells,and vascular smooth muscle cells,offering potential new avenues for the prevention and treatment of atherosclerosis.In this article,we review the role of mitophagy in regulating cellular functions and the progression of atherosclerosis,as well as summarize potential therapeutic drugs that may contribute to anti-atherosclerosis by modulating mitophagy.Our aim is to provide a new literature basis for further ex-ploration of the role of mitophagy in atherosclerosis.

Objective To explore the advantages of high-frequency ultrasound-guided"cross-shaped"positioning method in accurate positioning and surgical effect in open reduction and internal fixation of rib fractures.Methods Retrospective analysis of 97 cases of multiple rib fractures treated surgically in our department from october 2019 to october 2024.Patients were divided into three groups based on different localization methods.The control group designed the surgical incision according to the results of chest three-dimensional reconstruction,the ultrasound group determined the incision based on the control group combined with high-frequency ultrasound,and Based on the method used in the ultrasound group,the"cross-localization"technique was combined to determine the incision in the cross-shaped group.The comparison of surgical-related data included fracture positioning accuracy,incision length of per singer rib,postoperative drainage volume,duration of drainage tube retention,postoperative pain score,operative time,intraoperative blood loss,length of hospital stay and incision infection rate.Additionally,commonly used inflammatory markers(white blood cell count,neutrophil percentage,CRP,IL-6,NF-κB)and pain-related biomarkers(PGE2,5-HT)were also included in the comparative analysis.Results In the control group,ultrasound group,and crossover group,aside from wound infections,the respective accuracies of fracture localization were 68.97％vs 87.50％vs 97.22％,the length of single rib incision was(3.50±1.23)cm vs(2.70±0.62)cm vs(2.45±0.58)cm,the volume of drainage on the day of surgery was(170.55±27.85)ml vs(150.69±24.67)ml vs(120.34±18.45)ml,the duration of drainage tube retention was(4.17±1.12)days vs(3.67±0.95)days vs(3.12±0.65)days,the postoperative pain scores were(6.86±2.15)vs(5.54±1.15)vs(4.89±1.53),the operation times were(75.84±15.62)minutes vs(67.74±11.85)minutes vs(57.35±9.36)minutes,the intraoperative blood loss was(85.78±11.78)ml vs(72.65±8.92)ml vs(62.23±9.63)ml,and the length of hospital stay was(8.42±1.47)days vs(7.12±1.14)days vs(6.56±1.32)days.The crossover group showed superior results in all metrics compared to the other two groups,with statistically significant differences(P＜0.05).The inflammatory and pain stress indicators for the control,ultrasound,and crossover groups were as follows:white blood cell counts[(16.39±4.15)× 109/Lvs(13.25±2.45)× 109/L vs(12.02±2.77)× 109/L],neutrophil percentages[(80.14±12.21)vs(72.36±10.34)vs(65.73±8.83)],CRP[(31.86±6.87)mg/L vs(27.72±5.65)mg/L vs(24.69±4.11)mg/L],IL-6[(46.35±11.42)pg/L vs(41.42±8.75)pg/L vs(35.53±9.51)pg/L],NF-B[(22.55±4.98)pg/L vs(17.34±3.62)pg/L vs(15.91±3.84)pg/L],PGE2[(240.37±21.65)ng/L vs(209.45±23.24)ng/L vs(180.21±18.72)ng/L],and 5-HT[(290.62±34.37)ng/L vs(270.85±26.98)ng/L vs(210.62±19.64)ng/L].The crossover group demonstrated statistically significant differences compared to both the control and ultrasound groups(P＜0.05).There was no statistically significant difference in incision infection among the three groups(P＞0.05).Conclusion The ultrasound-guided"cross"positioning method for rib fracture open reduction and internal fixation can more accurately locate the incision,shorten the incision length and hospitalization time,reduce postoperative inflammatory response and patient pain,and facilitate rapid recovery after surgery.

Objective To evaluate the prognostic value of serum tissue factor pathway inhibitor-1(TFPI-1)combined with nuclear factor-κB(NF-κB)in severe traumatic brain injury(STBI).Methods The medical re-cords of 127 patients with STBI admitted to the hospital from July 2022 to August 2024 were retrospectively ana-lyzed and followed up for 6 months.They were divided into poor prognosis group(n=53)and good prognosis group(n=74)according to the prognosis of STBI patients.The serum NF-κB level,clinical data and serum TFPI-1 level of the two groups were compared.The factors affecting the adverse prognosis of STBI patients was screened,and the value of serum NF-κB and serum TFPI-1 in predicting the adverse prognosis of STBI patients were ana-lyzed.Results The serum NF-κB level in the poor prognosis group was higher than good prognosis group,and the serum TFPI-1 level was lower than good prognosis group(P<0.05).The proportion of patients aged>60 years old was higher than good prognosis group(P<0.05).Serum TFPI-1 level(OR=0.328,95%CI:0.156～0.689)was a protective factor for poor prognosis in STBI patients(P<0.05),serum NF-κB level(OR=3.773,95%CI:1.797～7.924)and age>60 years(OR=3.543,95%CI:1.687～7.441)were independent risk factors for poor prognosis in STBI patients(P<0.05).The area under the curve(AUC)of serum TFPI-1 and NF-κB levels and their combined prediction of poor prognosis in STBI patients were 0.784,0.847 and 0.931,respectively(P<0.05),and the AUC value of the combined TFPI-1 and NF-κB levels was higher(P<0.05).Conclusion Serum NF-κB combined with serum TFPI-1 has higher prognostic value in STBI patients.