Icodextrin peritoneal dialysis solution may produce cytotoxic α-dicarbonyl degradation products during heat sterilization, which must be monitored and controlled. The study established an o-phenylenediamine (OPD) derivatization HPLC-MS/MS method for the detection of these degradation products, enabling qualitative and quantitative analysis of α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution. The results indicated that the main α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution are 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 4-deoxyglucosone (4-DG), and 3,4-dideoxyglucosone-3-ene (3,4-DGE), along with two monocarbonyl degradation products, furfural and 5-hydroxymethylfurfural. The quantitative method for 3-DG, 3-DGal, 3,4-DGE and their structural analog, glucosone, was validated. 3-DG, 3-DGal, and glucosone exhibited good linear relationships within the range of 5-150 ng/mL, while 3,4-DGE showed good linearity in the range of 1-150 ng/mL. The spiked recovery rates for all compounds were between 86.8% and 100.0%. The detection limits for glucosone, 3-DG, and 3-DGal were approximately 2.4 ng/mL, and approximately 0.5 ng/mL for 3,4-DGE. The method established in this study can accurately determine α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution, providing an important basis for the quality control.

ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia （AML） and its correlation with clinical indicators and prognosis， and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia （AML） patients. Clinical samples from non-M3 AML patients were collected， with TRIM28 expression levels measured using real-time quantitative PCR （qPCR）. The analysis focused on correlations between TRIM28 expression and various clinical indicators， treatment efficacy， and patient prognosis. Furthermore， small interfering RNA （siRNA） technology was employed to downregulate TRIM28 expression in human primary AML cells （HL60 cell line）. The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry， respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples （P<0.000 1）， TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group （P<0.01）， and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group， and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation， positively correlated with age， bone marrow blast， peripheral blood blast and white blood cell， negatively correlated with hemoglobin. In addition， interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis， and plays a key role in the proliferation and apoptosis of AML cells， suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.

Copper is an essential trace element in the human body, extensively involved in key physiological and biochemical processes such as antioxidant defense, energy metabolism, neural signaling, and immune regulation. In recent years, increasing research has focused on the potential role of copper dyshomeostasis in the development of chronic diseases. Studies indicate that abnormal copper levels, particularly elevated free copper, may increase the risk of cardiovascular disease, neurodegenerative disorders, diabetes, and cancer by inducing oxidative stress, impairing mitochondrial function, and disrupting immune regulation. Concurrently, copper homeostasis abnormalities have been demonstrated to be closely associated with increased all-cause mortality and accelerated aging. This systematic review comprehensively examined physiological functions, metabolic pathways, and environmental exposure characteristics of copper. It emphasized the epidemiological and mechanistic links between copper metabolism disorders and multiple chronic diseases, while exploring the potential applications of copper ion transporters and chelating agents in disease intervention. This work provides scientific evidence for the prevention, control, and precision treatment of copper-related chronic diseases.

Hepatocellular carcinoma (HCC) is a lethal cancer with high morbidity rates worldwide. It is a major threat to public health in China, due to the combination of known and new risk factors, such as endemic hepatitis B virus (HBV), dietary aflatoxin exposure, and the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although many methods for surveillance and multimodal therapies, such as surgery, local ablation, transarterial therapy, and new systemic agents, have been available, the survival rates of HCC remains poor. They have very limited durable responses, long post-treatment recurrence rates, and high resistance to treatment. This reflects an imperfect picture of the biological cause of the disease and a need for new mechanistic or targeted techniques. A significant characteristic of HCC, in common with other aggressive cancers, is the presence of reprogrammed, hyperactive cell metabolism. Tumor cells hijack metabolic pathways to promote their uncontrolled growth, stress survival, invasion and metastasis. While classical mechanisms such as the Warburg effect, lipid metabolism and glutamine utilization have been understood, the lysosome, which was once viewed as a static “waste disposal unit” to remove old organelles and proteins, is instead a dynamic signaling and metabolic core. The lysosomes incorporate nutrients, energy and stress signals by master regulators such as mTORC1 (activated on its surface) that balance anabolic growth and catabolic recycling to the cellular demands. In HCC, lysosomes are not passive, but are highly active and dysregulated. HCC cells upregulate lysosomes, which scavenge intracellular components via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.

ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×10⁷/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.

Cirrhotic portal hypertension is a clinical syndrome caused by persistently elevated portal venous pressure due to liver cirrhosis and can lead to a series of complications， among which esophagogastric variceal bleeding has become one of the most severe complications due to sudden onset and a high mortality rate. Since the release of Expert consensus on diagnosis and treatment of esophagogastric variceal bleeding in cirrhotic portal hypertension （2019 edition）， significant advances have been achieved in this field in China and globally. In order to formulate an expert consensus aligned with the situation of China， Chinese Society of Surgery， Chinese Medical Association organized and compiled Expert Consensus on diagnosis and treatment of esophagogastric variceal bleeding in cirrhotic portal hypertension （2025 edition）. This article elaborates on the key updates in the new edition and explores the major differences between the old and new editions， in order to enhance the understanding of the new edition among clinicians and provide a reference for clinicians in clinical work.

ObjectiveTo investigate the feasibility， safety， and efficacy of surgery-assisted transjugular intrahepatic portosystemic shunt （SA-TIPS） in the treatment of portal hypertension comorbid with complex portal vein thrombosis， including cavernous transformation of the portal vein （CTPV）. MethodsAn analysis was performed for the data of 36 patients with portal hypertension and complex portal vein thrombosis who underwent SA-TIPS in Beijing Shijitan Hospital， Capital Medical University， from November 2023 to January 2025， including general status， technical data of the surgical process （surgical success rate， puncture times， time of operation， the number of stents used， and the length of shunt）， perioperative complications， and surgical recovery. The change in portal pressure gradient （PPG） after shunt was compared， and the rate of reaching the standard for PPG reduction was calculated， as well as stent patency rate within 1 week after surgery. The paired samples t-test was used for comparison of continuous data between two groups. ResultsAmong the 36 patients， 34 （94.4%） underwent SA-TIPS successfully. The incidence rate of perioperative complications was 16.7% （6/36）， including 3 cases of thoraco-abdominal hemorrhage， 2 cases of intraoperative arrhythmia， and 1 case of incision infection. There was a significant reduction in PPG after SA-TIPS （t=19.85， P<0.01）， and the patients achieving a ≥50% reduction in PPG accounted for 76.5% （26/34）. Imaging reexamination within 1 week showed a shunt patency rate of 100%. ConclusionSA-TIPS has a high technical success rate， a favorable safety profile， and good efficacy in the treatment of portal hypertension comorbid with complex portal vein thrombosis （including CTPV）， and therefore， it holds promise for clinical application.

Objective To analyze the main causes and risk factors of unplanned reoperation after liver transplantation. Methods The clinical data of 242 liver transplant recipients in the First Affiliated Hospital of Anhui Medical University from January 2015 to December 2024 were retrospectively analyzed. According to whether unplanned reoperation was performed during the same hospitalization after surgery, the recipients were divided into the reoperation group (n=36) and the non-reoperation group (n=206). The preoperative, intraoperative and postoperative data of the two groups, as well as donor and graft-related data, were compared to analyze the risk factors of unplanned reoperation after liver transplantation and the survival status of the two groups. Results Among the 242 liver transplant recipients, 36 underwent unplanned reoperations, with a total of 54 procedures including various laparotomies, endoscopic and interventional surgeries, among which there were 20 laparotomies, 18 endoscopic surgeries and 16 interventional surgeries. The most common cause of unplanned reoperation was biliary complications (20 times), followed by vascular complications (17 times). Compared with the non-reoperation group, the reoperation group had longer graft cold ischemia time, higher postoperative fatality rate of recipients, longer length of stay in the intensive care unit and postoperative hospital stay, and higher total hospitalization costs (all P<0.05). The incidence of unplanned reoperation was higher in recipients who underwent split liver transplantation (P<0.05). Multivariate analysis showed that intraoperative blood loss ≥1 000 mL, positive culture of graft perfusate and split liver transplantation were independent risk factors for unplanned reoperation (all P<0.05). The postoperative 7-day, 1-month, 3-month and 6-month survival rates of recipients in the reoperation group and the non-reoperation group were 100% vs. 98.1%, 88.9% vs. 94.2%, 69.4% vs. 90.8% and 66.7% vs. 90.8%, respectively, and the postoperative survival rate of recipients in the reoperation group was lower than that in the non-reoperation group (P<0.05). Conclusions The main causes of unplanned reoperation after liver transplantation are biliary complications, vascular complications, abdominal incision infection and intra-abdominal hemorrhage. Intraoperative massive blood loss, positive culture of graft perfusate and split liver transplantation are the risk factors associated with unplanned reoperation after liver transplantation.

Objective:To investigate the diagnostic consistency of extrauterine growth restriction (EUGR) assessed by the Fenton 2013 preterm growth charts (Fenton 2013) and the growth charts by International Fetal and Newborn Growth Consortium for the 21st Century (IG-21).Methods:This multicenter retrospective cohort study included 5 591 preterm infants with a gestational age (GA) at birth of less than 32 weeks admitted to 19 member hospitals of the Neonatal Perinatal Collaborative Network of Suxinyun from January 1 st, 2019, to December 31 st, 2024. Clinical data including baseline characteristics, complications, feeding practices and anthropometrics were processed and analyzed. EUGR was assessed using both the Fenton 2013 and the IG-21. A decrease in weight Z-score at discharge compared to admission by more than 1 was defined as longitudinal EUGR, and discharge weight below the P10 for the corresponding corrected GA was defined as cross-sectional EUGR. Diagnostic consistency was assessed using the Kappa coefficient between the 2 standards, and diagnostic performance of the 2 standards was compared using the McNemar test. Risk factors for EUGR under different definitions were analyzed using univariate analysis and multivariate Logistic regression analysis. Results:A total of 5 591 preterm infants were included, with a GA at birth of (29.7±1.6) weeks and a birth weight of (1 360±315) g and at discharge with a corrected GA of (36.3±2.0) weeks and weight of (2 246±370) g. Detection rates of cross-sectional and longitudinal EUGR diagnosed by Fenton 2013 were both higher than those by IG-21 (37.0% (2 214/5 991) vs. 23.7% (1 324/5 591), 61.1% (3 662/5 991) vs. 30.7% (1 714/5 591), χ2=326.77 and 1 358.05, both P<0.001). Using Fenton 2013 as a reference, IG-21 demonstrated superior diagnostic value and consistency in identifying cross-sectional EUGR compared with longitudinal EUGR (sensitivity of 100.0% (3 377/3 377) vs. 99.6% (1 922/1 929), specificity of 59.8% (1 324/2 214) vs. 46.6% (1 707/3 662), positive predictive value of 79.1% (3 377/4 267) vs. 49.6% (1 922/3 877), negative predictive value of 100.0% (1 324/1 324) vs. 99.6% (1 707/1 714), accuracy of 84.1% (4 701/5 591) vs. 64.9% (3 629/5 591), and Kappa 0.64 vs. 0.37, all P<0.001). In multivariate Logistic regression models, risk factors common to EUGR across both standards included smaller GA at birth, lower birth weight, boy, early-onset sepsis, late-onset sepsis and the elder age at full enteral feeding (all P<0.05). Hemodynamically significant patent ductus arteriosus remained an independent risk factor for longitudinal EUGR regardless of whether by the Fenton 2013 or IG-21 standard (adjust odds ratio ( aOR) =1.25 and 1.27, 95% CI 1.09-1.42 and 1.11-1.45). In addition, under the IG-21 standard, severe bronchopulmonary dysplasia was an independent risk factor for cross-sectional EUGR ( aOR=1.54, 95% CI 1.00-2.38), while severe necrotizing enterocolitis was an independent risk factor for longitudinal EUGR ( aOR=2.18, 95% CI 1.01-4.73). Conclusions:IG-21 showed lower detection rates of both cross-sectional and longitudinal EUGR than Fenton 2013, suggesting greater clinical applicability of IG-21 by reducing overdiagnosis while maintaining sensitivity for predicting complications. Across both standards, cross-sectional EUGR facilitates early identification of growth restriction, whereas longitudinal EUGR better tracks dynamic growth patterns and complications of preterm infants.

BACKGROUND:Bone remodeling is the biological basis of orthodontic tooth movement.Type 2 diabetes mellitus leads to metabolic changes in the jaw and alveolar bone,so it is hypothesized that tooth mobility characteristics may be altered in a high-sugar environment.OBJECTIVE:To explore the impact of type 2 diabetes mellitus on orthodontic tooth movement in rats within one tooth movement cycle.METHODS:Seventy-two Sprague-Dawley rats were selected.Forty rats were randomly chosen and fed with a high-fat diet to construct a type 2 diabetes mellitus model.Thirty-two rats that were successfully modeled were randomly divided into a type 2 diabetes mellitus group(n=16)and a diabetic orthodontic group(n=16).The remaining 32 rats were randomly divided into a control group(n=16)and an orthodontic group(n=16).The rats in the orthodontic group and the diabetic orthodontic group were equipped with nickel-titanium coil spring orthodontic force application devices to move the unilateral maxillary first molars mesially with a force of 50 g.The rats were anesthetized and sacrificed on the 3rd,7th,14th,and 21st days after orthodontic treatment,and Micro-CT was used to measure the mesial displacement of the first molars and detect the changes in the bone microstructure parameters on the tension side.RESULTS AND CONCLUSION:There were significant differences in the tooth movement distances among the four groups of rats on the 3rd,7th,14th,and 21st days of orthodontic treatment(P＜0.05).There were significant differences in bone mineral density,bone volume fraction and trabecular bone separation on the tension side among the four groups on the 7th,14th,and 21st days of orthodontic treatment(P＜0.05).There were differences in the trabecular thickness among the four groups on the 3rd and 14th days of orthodontic treatment(P＜0.05).The diabetic orthodontic group had the smallest tension-side alveolar bone mineral density,bone volume fraction,and trabecular thickness,and the largest tooth movement distance and trabecular separation on the 21st day of orthodontic treatment.The above results indicate that type 2 diabetes mellitus adversely affects bone microstructural parameters on the tension side in orthodontic tooth movement in rats,suggesting the occurrence of an osteoporotic state.