Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To analyze the distribution and epidemiological characteristics of common non-bacterial pathogens in hospitalized children with acute respiratory tract infections(ARTI)from a multi-center study covering 4 regions in Fujian Province in 2023.Methods:A retrospective cohort study was conducted using medical record analysis.A total of 22 769 hospitalized children with ARTI were enrolled from January to December 2023 across seven regional pediatric medical centers in Fujian Province (covering four major geographical divisions of Fuzhou, Nanping, Sanming and Longyan; all selected hospitals were regional children′s medical centers).Using single-tube multiplex PCR with fragment analysis on a Sanger sequencing platform, the nucleic acids of 11 common non-bacterial respiratory pathogens were tested in nasopharyngeal swabs collected from 22 769 children. These pathogens included influenza A virus(FluA), influenza B virus(FluB), parainfluenza virus(PIV), respiratory syncytial virus (RSV), adenovirus (ADV), human rhinovirus (HRV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus(HMPV), Mycoplasma pneumoniae(MP), and Chlamydia (Ch). Count data were described as [ n(%)], and the chi-square test/Fisher′s exact test was used to compare the differences in rates between groups. Epidemiological features, including positive detection rates, pathogen profiles, and correlations with region, sex, age and month, were analyzed. Results:Among 22 769 children with ARTI, pathogens were detected in 16 213 cases (71.21%), including 13 340 single infections (58.59%).The detection rates of single pathogens in descending order were human rhinovirus (HRV, 12.95%), Mycoplasma pneumoniae(MP, 12.27%), respiratory syncytial virus(RSV, 11.12%), influenza A virus (Flu-A, 7.98%), parainfluenza virus(PIV, 4.66%), human metapneumovirus(HMPV, 4.60%), adenovirus(ADV, 2.70%), human bocavirus(HBoV, 0.84%), human coronavirus(HCoV, 0.82%), influenza B virus(Flu-B, 0.47%) and Chlamydia(Ch, 0.18%).Mixed infections occurred in 2 873 cases(12.62%), primarily dual infections(2 679 cases).Regional analysis revealed significant disparities:Luoyuan County Hospital (Fuzhou) exhibited the highest total detection rate(86.59%, 1 414/1 633)and mixed infection rate(23.27%, 380/1 633)(both P<0.001), with notably elevated MP (26.39%, 431/1 633);Jian′ou City Hospital(Nanping) ranked second for Flu-A(14.21%, 409/2 879), RSV(13.20%, 380/2 879) and mixed infections(17.12%, 493/2 879);Lianjiang County Hospital(Fuzhou) showed distinct prevalence of Flu-A(10.68%, 130/1 217), PIV(6.00%, 73/1 217), and HBoV(1.73%, 21/1 217); Yong′an City Hospital (Sanming) reported high MP (26.07%, 238/913) and RSV(12.38%, 113/913);Shaowu City Hospital(Nanping) was dominated by MP (18.60%, 407/2 188) and HRV(13.39%, 293/2 188); Tingzhou Hospital(Longyan) had the highest HRV (17.88%, 407/2 276) and Flu-B (0.75%, 17/2 276); and Fuzhou Children′s Hospital showed elevated ADV(3.38%, 394/11 663) and HCoV(1.08%, 126/11 663). Except for Flu-B(0.47%, 108/22 769; P=0.054) and Ch(0.18%, 40/22769; P=0.900), all pathogens and mixed infections exhibited significant regional variations ( P<0.05).Gender analysis indicated higher detection rates of HRV, RSV, Flu-A, ADV, PIV, HBoV and mixed infections in males, while MP, HMPV, Flu-B, HCoV, and Ch were more prevalent in females, with statistically significant differences for HRV and MP (both P<0.001). Age stratification showed the highest overall detection rate in the 3-<6 years group (75.48%; P<0.001): RSV and Ch peaked in infants (<1 year), HRV, PIV, ADV and HBoV in toddlers (1-<3 years), HMPV, HCoV, and mixed infections in preschool children (3-<6 years), and MP, Flu-A and Flu-B in older children (6-<18 years).Analyzing the prevalent months, the monthly prevalence trends of pathogens in various regions are similar.Seasonal trends demonstrated year-round HRV activity (peaking in spring/autumn), MP prevalence in autumn/winter, RSV surges in spring-summer (April-June) and late summer-autumn (August-October), and Flu-A predominanced in winter-spring. Conclusion:Multiplex PCR with fragment analysis demonstrated high diagnostic efficacy. The top 4 non-bacterial pathogens in Fujian Province′s ARTI-hospitalized children in 2023 were HRV, MP, RSV and Flu-A. Pathogen distribution exhibited significant regional, age and seasonal variations, emphasizing the need for targeted prevention strategies.

Infectious bone defect,one of the complex and refractory types of bone defects,is characterized by infec-tion,inflammation and subsequent bone tissue destruction.These conditions often lead to severe consequences such as limb necrosis,dysfunction or even amputation.The previous treatment method for infectious bone defect primarily involves thorough debridement and bone grafting after infection control with antibacterial drugs.Howev-er,this method carries drawbacks,including the possibility of drug resistance and systemic toxicity due to high-dose use of antimicrobial drugs.With advancements in modern medicine and in-depth research on biomaterials,va-rious novel antibacterial materials have been increasingly applied in the treatment of infectious bone defect,demon-strating promising outcomes.This paper reviews the applications and therapeutic efficacy of novel antibacterial ma-terials in treating infectious bone defect at home and abroad,aiming to provide references for clinical management.

Background::Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to investigate the epigenetic mechanisms in IUGR.Methods::IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF) 1–4 binding sites of the Igf2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing. Results::The IUGR models were constructed successfully. Igf2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group ( P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group ( P <0.05). In addition, knocking down Igf2 reduced the protein expression levels of AKT2-phosphorylation and PGC-1α ( P <0.05). In CTCF binding sites 1-4 of the Igf2/ H19 ICR, acetylated histones H3 (AcH3) enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. Histone H3 tri-methylated lysine 4 (H3K4me3) enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups ( P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group ( P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly ( P <0.05). Conclusion::The methylation status and histone modification in the Igf2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

BACKGROUND:Early exercise treatment is the main prevention way for traumatic joint contracture and is also a research focus.Swimming may be a potential intervention for joint contracture due to the special physical properties of water. OBJECTIVE:To explore the effects of swimming on the development of joint contracture in a rat model and study its mechanisms. METHODS:Twenty-four Sprague-Dawley rats were randomly divided into a blank control group(n=8)and a joint contracture group(n=16).After the surgical operation of knee joint contracture rat models,the joint contracture group was randomly subdivided into a surgical control group(n=8)and a swimming treatment group(n=8).Swimming started in the swimming treatment group in the second week after surgery and lasted for a total of 5 weeks.At the 6th week after surgery,the body mass,knee joint range of motion,and quadriceps diameter were tested,and the diameter/body mass index was calculated.Hematoxylin-eosin staining was performed to detect the pathological changes in the knee joint capsule and quadriceps muscle,and Masson staining was used to observe fibrotic changes in the knee joint capsule.Furthermore,the protein expression of transforming growth factor β1 and type I collagen in the knee joint capsule was quantified by immunohistochemical assay and western blot was performed to detect the protein expression of MuRF1 in the quadriceps femoris. RESULTS AND CONCLUSION:Compared with the blank control group,the knee range of motion decreased in the surgical control and swimming treatment groups(P<0.01),and knee extension deficit and arthrogenic extension deficit were significantly increased(P<0.01),the diameter of the quadriceps muscle was decreased(P<0.01),the joint capsule showed significant fibrosis,the quadriceps muscle was atrophied,and the diameter/body mass index was decreased(P<0.01).Compared with the surgical control group,the swimming treatment group showed a significant increase in knee joint range of motion and quadriceps diameter(P<0.01),and significant improvement in joint capsule fibrosis and quadriceps atrophy.Compared with the blank control group,collagen fiber content and expression of transforming growth factor β1 and type I collagen were increased in the joint capsule of rats in both the surgical control group and the swimming treatment group(P<0.01).Compared with the surgical control group,collagen fiber content and expression of transforming growth factor β1 and type I collagen protein in the joint capsule were decreased in the swimming treatment group.Compared with the blank control group,the expression of MuRF1 protein in the quadriceps muscle of rats in the surgical control group and the swimming treatment group was increased(P<0.05).Compared with the surgical control group,the expression of MuRF1 protein in the quadriceps muscle of rats in the swimming treatment group was decreased(P<0.05).To conclude,early swimming intervention reduces transforming growth factor β1 and type I collagen expression in the joint capsule of traumatic joint contracture rats,decreases MuRF1 expression in the quadriceps muscle,and increases joint range of motion and quadriceps diameter,thereby inhibiting the development of joint contracture.

ObjectiveTo develop an emotion management course and evaluate its effectiveness in improving emotion regulation, coping strategies, and anxiety and depression among first-year university students, so as to provide a basis for colleges to optimize mental health education courses. MethodsUsing a multi-stage cluster random sampling method, five classes of first-year students (n=169) from a university were randomly selected as participants, with three classes assigned to the experimental group (n=102) and two classes to the control group (n=67). The experimental group attended both the standard mental health education course and the emotion management course developed in this study, while the control group only attended the standard mental health education course. Pre- and post-intervention assessments were conducted using the Emotion Regulation Questionnaire (ERQ), Simplified Coping Style Questionnaire (SCSQ), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS). ResultsBefore the intervention, there were no significant differences between the experimental group and the control group in ERQ, SCSQ, SDS, and SAS scores (P>0.05). After the intervention, the experimental group demonstrated greater improvements than the control group in the ERQ expression inhibition subscale (14.42±5.05, 16.12±5.65), SCSQ positive coping tendency (1.97±0.51, 1.80±0.49) and negative coping tendency (1.26±0.55, 1.47±0.50), as well as in SDS (50.26±11.48, 53.86±8.21) and SAS (43.96±11.97, 47.59±9.50) scores (t value: 2.039, 2.144, 2.572; Z value: -2.214, -2.486; P<0.05). Compared with pre-intervention scores, the experimental group also showed improvements in the ERQ cognitive reappraisal subscale (32.19±5.76, 30.92±6.18), SCSQ positive coping tendency (1.97±0.51, 1.83±0.48), and SDS scores (50.26±11.48, 50.75±11.59) (t value: -2.654, -3.027; Z value: -2.100, P<0.05). ConclusionThe emotion management course effectively enhances students’ use of cognitive reappraisal strategies while reducing reliance on expressive suppression. It also contributes to improvements in coping strategies for life events and alleviates symptoms of depression and anxiety. Universities should consider integrating emotion management education into their curricula to enhance the mental well-being of first-year students.

The nursing experience of buttonhole cannulation for an autogenous arteriovenous fistula with an Eluvia drug-eluting stent in a patient undergoing maintenance hemodialysis was summarized.Key nursing points included:developing a scientific and rational buttonhole cannulation plan for the autogenous arteriovenous fistula stent based on its characteristics post-stent implantation;conducting preoperative ultrasonic evaluations of the arteriovenous fistula and stent;establishing and maintaining a buttonhole tunnel at the stent site;regularly monitoring and following up on the cannulation site and the condition of the autogenous arteriovenous fistula;strengthening the observation and prevention of potential complications.Through rigorous and standardized assessments,procedures,and nursing care,the patient maintained good autogenous arteriovenous fistula function without stent-related complications such as fracture,stenosis,or infection over a 14-month follow-up period.

Osteoarticular diseases,common chronic degenerative disorders in the elderly,involve the gradual deterioration and degeneration of bones or joints.The metabolic capacity declines with age.Impaired bone metabolism dis-rupts homeostasis,leading to osteoarticular dysfunctions.Cuprotosis,a novel form of programmed cell death mediated by ferredoxin 1,matters for the pathologic process in osteoarticular diseases.Cuprotosis influences the levels of intercellular signal transduction to induce oxidative stress,inflammation,pyroptosis,and ferroptosis in joints.Those cell death and mi-tochondrial dysfunction ultimately exacerbate the progression of osteoarticular diseases.Therefore,this review summarizes the mechanism of copper homeostasis-cuprotosis in osteoarticular diseases and the potential applications targeting copper homeostasis-cuprotosis.