Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

To examine the evolution of surgical techniques and trends in overall inpatient burden for pediatric adenoidectomy in Beijing tertiary hospitals from 2013 to 2022. A retrospective observational study was conducted using the regional health information platform of Beijing. Data from children aged ≤14 years who underwent adenoidectomy between 2013 and 2022 were extracted, including total hospitalization cost, length of stay(LOS), surgical material cost, surgical fee, operative technique, perioperative antimicrobial drugs cost, coagulation factor cost, and blood transfusion cost. The Mann-Kendall trend test was used to assess temporal changes in total hospitalization expenses and the structure of cost components. The results showed that over the 10-year period from 2013 to 2022, a total of 25 989 children underwent adenoidectomy in tertiary hospitals. The proportion of children aged ≤6 years increased from 59.83% to 76.11%, showing a significant upward trend ( Z=2.15, P=0.032). Only one case required surgical hemostasis due to postoperative bleeding. During the ten-year period, the median hospitalization cost for adenoidectomy in tertiary hospitals was ￥12 425.82 (￥11 307.43, ￥14 955.42).Overall hospitalization cost demonstrated a fluctuating downward pattern, decreasing from ￥15 229.73 in 2013 to ￥13 927.52 in 2022, this declining trend was not statistically significant( Z=-0.54, P=0.592). In contrast, the surgical costs showed an upward trend over the decade increasing from ￥1 856.22 in 2013 to ￥3 726.45 in 2022, which was statistically significant ( Z=3.22, P=0.001), while the cost of surgical materials showed no significant increase ( Z=1.79, P=0.074).Concurrently, the average LOS decreased remarkably from 10.56 days in 2013 to 3.26 days in 2022 ( Z=-3.94, P<0.001). The cost of perioperative antimicrobial drugs decreased ( Z=-3.94, P<0.001), while the cost of coagulation factors and blood transfusion remained unchanged ( Z=0.54, P=0.592; Z=0.56, P=0.578). Comparison between 2013-2017 and 2018-2022 showed a significant increase in the use of coblation from 28.9% to 42.5% ( χ2=638.7, P<0.001).Furthermore, in the coblation group, total hospitalization cost decreased by 27.73%, surgical cost increased by 94.98%, surgical material cost decreased by 10.33%, LOS shortened by 56.24%, and antimicrobial drug cost increased by 43.03%. In contrast, the non-coblation group showed a 23.94% increase in total hospitalization cost, a 57.08% increase in surgical procedure cost, a 33.88% increase in material cost, and a 30.14% reduction in LOS and a 26.0% decrease in antimicrobial drugs cost. In conclusion,from 2013 to 2022, total hospitalization cost for pediatric adenoidectomy in Beijing tertiary hospitals remained stable. Compared to non-coblation techniques, coblation was associated with a shorter LOS, lower total costs, a higher proportion of surgical fees, and a decreased proportion of material costs, without a significant increase in overall healthcare costs.

Objective:To investigate the impact of delayed ileostomy closure (>6 months) on postoperative complications in patients with ulcerative colitis (UC) undergoing ileal pouch-anal anastomosis (IPAA) .Methods:Using propensity score matching. Clinical data of UC patients who underwent IPAA and subsequent ileostomy closure at Jinling Hospital from January 2014 to December 2021 were retrospectively analyzed. Patients were categorized into a routine group (2 to ≤6 months) and a delayed group (>6 months) based on the timing of ileostomy closure. A 1∶1 propensity score matching analysis was performed to compare early (≤30 days) and late (>30 days) postoperative complications between the two groups.Results:A total of 225 UC patients who underwent IPAA and ileostomy closure were included, comprising 129 males (57.3%) and 96 females (42.7%). After propensity score matching, 88 patients were included in the analysis, with 44 patients in each group. There was no significant difference in the overall incidence of early postoperative complications (11.4% vs. 15.9%, P = 0.534) or late postoperative complications (43.2% vs. 43.2%, P = 1.000) between the delayed and routine groups. Additionally, no significant differences were observed in other postoperative complications (all P > 0.05) . Conclusion:Delayed ileostomy closure following IPAA does not significantly increase the risk of postoperative complications in UC patients.

Inflammatory bowel disease (IBD) is an intestinal disease with uncertain etiology and complex mechanism. The interaction between environment and gene is a risk factor of IBD, which includes abnormal DNA methylation. In this review, we discuss the abnormal DNA methylation in IBD patients, and illustrate the interaction between gut microbiota and host through DNA methylation and its mechanism. Finally, we look forward to the prospect of regulating the interaction between gut microbiota and host through DNA methylation in the treatment of IBD.

Objective:To evaluate the role of YTH domain family protein 2 (YTHDF2) in myocardial ischaemia-reperfusion injury (MIRI) in diabetic rats and the relationship with the nuclear factor E2-related factor 2 (NRF2)-ferritinophagy.Methods:This experiment was performed in 2 parts. Part Ⅰ Animal experiment SPF healthy male rats, aged 6-8 weeks, weighing 200-220 g, were used. A type 1 diabetes mellitus (DM) model was established by intraperitoneal injection of 1% streptozotocin at a dose of 65 mg/kg. Thirty-six diabetic rats were divided into 3 groups ( n=12 each) using a random number table method: DM sham operation group (DS group), DM myocardial ischaemia-reperfusion group (DIR group), and YTHDF2 knockdown + DM myocardial ischaemia-reperfusion group (AAV-Y+ DIR group). Another 36 non-diabetic rats were selected and divided into 4 groups using the random number table method: sham operation group (NS group, n=12), myocardial ischaemia-reperfusion group (NIR group, n=12), adeno-associated virus control group (AAV-N group, n=6), and YTHDF2 knockdown group (AAV-Y group, n=6). The MIRI model was established by ligating the left anterior descending branch of the coronary artery for 30 min, followed by reperfusion for 2 h. Adeno-associated virus was employed to knock down YTHDF2. At the end of reperfusion, serum concentrations of creatine kinase isoenzyme MB(CK-MB) and cardiac troponin Ⅰ(cTnI) were measured using enzyme-linked immunosorbent assay. The animals were sacrificed, myocardial tissues were harvested, and the pathological changes were observed with a light microscope to assess the myocardial infarct size. The expression of YTHDF2, NRF2, and nuclear receptor coactivator 4 (NCOA4) was detected by Western blot. Part Ⅱ Cell experiment H9c2 cells were divided into 9 groups ( n=24 each) using the random number table method: control group (NC group), high-glucose group (HG group), hypoxia-reoxygenation group (HR group), high-glucose hypoxia-reoxygenation group (HHR group), transfection control group (siN group), YTHDF2 knockdown group (siY group), YTHDF2 knockdown + high-glucose hypoxia-reoxygenation group (siY + HHR group), NRF2 inhibitor ML385 + high-glucose hypoxia-reoxygenation group (M + HHR group), and YTHDF2 knockdown + NRF2 inhibitor ML385 + high-glucose hypoxia-reoxygenation group (siY + M + HHR group). The cells were transfected with siRNA to knock down YTHDF2, and a high-glucose, hypoxia and reoxygenation injury model was established by subjecting cells to 48 h of high glucose, followed by 4 h of hypoxia and 2 h of reoxygenation. The cell viability and lactic dehydrogenase(LDH) activity were determined, autophagic vesicles were counted, and the expression of YTHDF2, NRF2 and NCOA4 was detected by Western blot. Results:Part Ⅰ Animal experiment At the end of myocardial ischaemia-reperfusion, serum levels of CK-MB and cTnI and the percentage of myocardial infarct size were significantly increased, the expression of YTHDF2 and NCOA4 in myocardial tissues was up-regulated, and the expression of NRF2 was down-regulated in both diabetic and non-diabetic groups ( P<0.05). Compared with NIR group, serum levels of CK-MB and cTnI and the percentage of myocardial infarct size were significantly increased, the expression of YTHDF2 and NCOA4 in myocardial tissues was up-regulated, and the expression of NRF2 was down-regulated in DIR group ( P<0.05). Compared with DIR group, serum levels of CK-MB and cTnI and the percentage of myocardial infarct size were significantly decreased, the expression of YTHDF2 and NCOA4 in myocardial tissues was down-regulated, and the expression of NRF2 was up-regulated ( P<0.05), and the pathological damage was reduced in AAV-Y + DIR group. Part Ⅱ Cell experiment Compared with HG and HR groups, the cell viability was significantly decreased, the activity of LDH was increased, the counts of autophagic vesicle were increased, the expression of YTHDF2 and NCOA4 was up-regulated, and the expression of NRF2 was down-regulated in HHR group ( P<0.05). Compared with HHR group, the cell viability was significantly decreased, the activity of LDH was increased, the counts of autophagic vesicle were increased, the expression of YTHDF2 and NCOA4 was up-regulated, and the expression of NRF2 was down-regulated in M + HHR group, and the cell viability was significantly increased, the activity of LDH was decreased, the counts of autophagic vesicle were decreased, the expression of YTHDF2 and NCOA4 was down-regulated, and the expression of NRF2 was up-regulated in siY + HHR group ( P<0.05), and no statistically significant changes were found in the above indicators in siY + M + HHR group ( P>0.05) Conclusions:YTHDF2 can down-regulate the expression of NRF2, enhance the level of ferritinophagy, and participate in the process of MIRI in diabetic rats.

Objective:This study aims to analyze historical trends and predict future trends of disability-adjusted life years (DALYs) attributable to high BMI for osteoarthritis (OA) in China. OA is a common chronic degenerative joint disease, with high body mass index (BMI) being a significant risk factor. in China.Methods:Based on the Global Burden of Disease (GBD) 2021 database, we analyzed trends in high-BMI-attributable OA. The ASR of hogh-BMI-attributable OA DALYs increased from DALYs in China from 1990 to 2021. A Bayesian age-period-cohort (BAPC) model was used to predict trends from 2022 to 2046. Age-standardized rates (ASR) and estimated annual percentage changes (EAPC) were calculated to assess trend changes of trends. A Bayesian age-period-cohort (BAPC) model was used to predict trends from 2022 to 2046. Chi-square tests were used to compare differences in high BMI attribution proportions between regions and years.Results:From 1990 to 2021, China′s OA DALYs increased from 1.829 to 5.327 million, with the proportion attributable to high BMI rising from 13.47% to 21.86% ( χ2=60 527.25, P<0.001). The ASR of high-BMI-attributable to OA increased from 27.4 (-2.2, 81.5) per 100,000 to 53.0 (-4.7, 150.7) per 100 000, with an EAPC of 2.48% [95% (uncertainty interval, UI): 2.35, 2.62]. In 2021, females showed significantly higher ASR (69.2 per 100 000) than males (36.1 per 100 000). Knee OA (ASR: 50.5/100 000) demonstrated substantially higher burden than hip OA (ASR: 2.5/100 000). Age effect analysis showed DALYs peaked at ages 80~90; period effect indicated accelerated growth after 2005; cohort effect showed a U-shaped trend with the 1990 birth cohort having the highest relative risk (approximately 3.0). Projections indicated that up to 2046, total OA DALYs will reach approximately 2.39 million with an ASR of about 71, showing more significant growth among females (ASR reaching 100). Conclusion:High-BMI-attributable to OA DALYs in China shows a significant upward trend, and is expected to continue. This trend is more pronounced among females and elderly populations than males, highlighting the urgency of implementing preventive measures for high-risk groups, particularly in weight management.

Objective:To construct a nomogram model for predicting the incidence of hepatocellular carcinoma based on serum abnormal prothrombin and alpha-fetoprotein and evaluate the predictive effect.Methods:Retrospective analysis of data from 351 patients with liver disease who received treatment at the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023, including 285 males and 66 females, aged (52.9±11.9) years. Among the 351 patients, there were 229 cases (65.2%) of hepatocellular carcinoma, 87 cases (24.8%) of liver cirrhosis, and 35 cases (10.0%) of chronic hepatitis B. All patients were randomly divided into a training set ( n=245) and a testing set ( n=106) in a 7∶3 ratio without replacement sampling. The training set was used to construct the model, and the testing set was used to evaluate the model. At the same time, gender, age, disease type, and other indicators were compared between the two sets. The risk factors of hepatocellular carcinoma were analyzed by univariate and multivariate logistic regression based on the training set, and a nomogram was constructed to predict the incidence of hepatocellular carcinoma based on the multivariate results. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive performance of nomogram, and decision curve analysis was used to evaluate the clinical applicability of the model. Results:There was no statistically significant difference in age, gender, disease type, etc. between the training and testing sets of patients (all P>0.05). Univariate logistic regression analysis showed that age, abnormal prothrombin logarithm (LnPIVKA-Ⅱ), alpha-fetoprotein logarithm (LnAFP), and diabetes were associated with hepatocellular carcinoma (all P<0.05). Multivariate logistic regression analysis showed that older age ( OR=1.07, 95% CI: 1.03-1.12), higher LnPIVKA-Ⅱ ( OR=2.97, 95% CI: 1.97-4.46), higher LnAFP ( OR=1.43, 95% CI: 1.11-1.84) and diabetes ( OR=5.17, 95% CI: 1.02-26.17) were risk factors for hepatocellular carcinoma (all P<0.05). Based on the above variables, a nomogram model for predicting the incidence of hepatocellular carcinoma was constructed. The area under the ROC curve analysis of the nomogram for predicting the incidence of hepatocellular carcinoma was 0.920 (95% CI: 0.886-0.953) in the training set and 0.934 (95% CI: 0.891-0.977) in the testing set. The calibration curve fit well with the standard curve, and the prediction was basically consistent with the actual situation. The decision curve analysis showed that the net benefit of the model was greater than 0 under most thresholds (0.1-1.0). Conclusion:The nomogram constructed based on age, LnPIVKA-Ⅱ, LnAFP and diabetes can effectively predict the incidence of hepatocellular carcinoma and has clinical applicability.

Hepatocellular carcinoma （HCC） with biliary duct tumor thrombus （BDTT） is currently not common in clinical practice and is easily misdiagnosed， and previously， it was often considered an advanced stage of the disease with a poor prognosis， making its treatment challenging. However， in-depth studies in recent years have gradually deepened our understanding of this disease， leading to significant changes in diagnostic and treatment concepts. Currently， comprehensive treatment， mainly surgery， is used for treatment， but there is still controversy over the selection of clinical treatment strategies. This article provides a detailed discussion on surgical methods and prognosis， in order to provide a reference for clinical treatment options.

BACKGROUND:Differentially expressed RNA-binding proteins in the intervertebral disc plays a key role in intervertebral disc degeneration,and decreased levels of the RNA-binding protein KRT18 are associated with degenerative disc disease,but its specific role in the nucleus pulposus cells has not yet been fully determined. OBJECTIVE:To investigate the interaction of KRT18 with mRNA and long non-coding RNA on nucleus pulposus cells of the intervertebral disc and its mechanism. METHODS:Normal and degenerated nucleus pulposus cells were obtained from nucleus pulposus samples of patients undergoing interbody fusion for lumbar fracture or intervertebral disc degeneration.iRIP-seq,functional enrichment analysis,and DNA microarray analysis were performed to identify the mRNA and long non-coding RNA binding with KRT18.Subsequently,KRT18 was knocked down in nucleus pulposus cells based on the analysis results,and the expression levels of related genes were detected at the protein and RNA levels through protein immunoblotting and qRT-PCR,respectively. RESULTS AND CONCLUSION:Through iRIP-seq analysis,we identified abundant KRT18 binding sites within the GUAAUC and AGCCUC sequences,indicating that KRT18 may be involved in regulating RNA transcription,translation,stability or play a role in cell signaling pathways.It can stably bind to mature mRNA,among which highly expressed genes include CRLF1,IGFBP4,etc.At the same time,the peak genes of long non-coding RNA binding with it include SNHG25,SNHG12,NEAT1,USP32,EIF4A2 and CDH4.Most of these genes are involved in various biological processes such as apoptosis and inflammation,and can mediate related pathways of extracellular matrix metabolism.KRT18 can regulate their stability,transport,translation,splicing and other functions,thus affecting gene expression and cell function.We further verified through experiments the knockdown of KRT18 in nucleus pulposus cells,and found that the level of extracellular matrix metabolism was inhibited and unbalanced,resulting in intervertebral disc degeneration in vitro.This study investigated the regulatory mechanism of KRT18 from the perspective of its binding with mRNA and long non-coding RNA for the first time,and speculated the potential function of KRT18 in the pathogenesis of intervertebral disc degeneration,laying a foundation for future research on the key functions of KRT18.

The da Vinci Surgical System provides surgeons with a three-dimensional image view with greater clarity, which improves surgical precision, particularly in confined surgical spaces. Compared to laparoscopic surgery, robotic surgery has a shorter learning curve and may be a better choice for surgeons. However, some surgeons are susceptible to laparoscopic experience when performing robotic surgery, which can diminish the advantages of the robotic system. We discussed some key issues such as indications, use of energy instruments, surgical approach, lymph node dissection, and digestive tract reconstruction, from the habit of laparoscopic surgery, in light of our team's experience with robotic radical gastric cancer surgery and the latest literature, in order to help beginners better understand the robotic surgical system.