ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

ObjectiveTo investigate the differences in pregnancy outcomes between dichorionic diamniotic （DCDA） twin pregnancies conceived via assisted reproductive technology （ART） and those from spontaneous conception， in order to provide evidence for the perinatal management of ART-conceived DCDA twins. MethodsA retrospective analysis was conducted on the clinical data of 549 DCDA twin parturients. Based on the mode of conception， they were divided into ART group （423 cases） and spontaneous conception group （126 cases）. The baseline characteristics， pregnancy complications and neonatal outcomes were compared between the two groups. ResultsRegarding baseline characteristics， the ART group had higher maternal age， number of previous abortions， proportions of primiparas， proportions of advanced maternal age and greater 24-hour postpartum blood loss， but lower parity and proportion of scarred uterus compared to the spontaneous conception group （P<0.05）. For pregnancy complications， the ART group exhibited higher incidences of hypertensive disorders of pregnancy， placental adhesion， postpartum hemorrhage and a higher application rate of uterine artery ascending branch ligation （P<0.05）. There were no statistically significant differences in neonatal-related indicators between the two groups. After adjusting for confounding factors such as age， number of abortions and parities， ART remained an independent risk factor for hypertensive disorders of pregnancy， placental adhesion and postpartum hemorrhage （P<0.05）， while it did not increase the risk of adverse neonatal outcomes. Further subgroup analysis by gestational age showed that in the late preterm subgroup， the risk of ART-related pregnancy complications remained elevated （P<0.05）. Additionally， neonatal outcomes showed no significant difference between the two groups in both the late preterm and term subgroups. ConclusionART increases the risk of hypertensive disorders of pregnancy， placental adhesion and postpartum hemorrhage in DCDA twin parturients. Clinically， enhanced monitoring of blood pressure during pregnancy and blood loss during delivery and postpartum， along with targeted prevention and management of these complications， are crucial for improving pregnancy outcomes.

Momordica antiviral protein 30 kD(MAP30)is a type Ⅰ ribosome-inactivating protein(RIP)with antibacterial,anti-HIV and antitumor activities but lacks the ability to target tumor cells.To in-crease its tumor-targeting ability,the arginine-glycine-aspartic(RGD)peptide and the epidermal growth factor receptor interference(EGFRi)peptide were fused with MAP30,which was named ELRL-MAP30.The efficiency of targeted therapy for triple-negative breast cancer(TNBC)MDA-MB-231 cells,which lack the expression of estrogen receptor(ER),Progesterone receptor(PgR)and human epidermal growth factor receptor-2(HER2),is limited.In this study,we focus on exploring the effect and mecha-nism of ELRL-MAP30 on TNBC MDA-MB-231 cells.First,we discovered that ELRL-MAP30 significant-ly inhibited the migration and invasion of MDA-MB-231 cells and induced MDA-MB-231 cell apoptosis.Moreover,ELRL-MAP30 treatment resulted in a significant increase in Bax expression and a decrease in Bcl-2 expression.Furthermore,ELRL-MAP30 triggered apoptosis via the Fak/EGFR/Erk and Ilk/Akt signaling pathways.In addition,recombinant ELRL-MAP30 can inhibit chicken embryonic angiogenesis,and also inhibit the tube formation ability of human umbilical vein endothelial cells(HUVECs),indica-ting its potential therapeutic effects on tumor angiogenesis.Collectively,these results indicate that ELRL-MAP30 has significant tumor-targeting properties in MDA-MB-231 cancer cells and reveals potential ther-apeutic effects on angiogenesis.These findings indicate the potential role of ELRL-MAP30 in the targeted treatment of the TNBC cell line MDA-MB-231.

Objective:To study the relationship between urinary arsenic methylation metabolism patterns and skin keratinization and pigmentation abnormalities in population exposed to arsenic through drinking water.Methods:Using a cross-sectional study method, a survey on endemic arsenic poisoning was conducted among permanent residents of drinking water endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region in 2004 (before water improvement). In 2017 (after water improvement), 71 arsenic exposed individuals were followed up as survey subjects. According to the "Diagnosis of Endemic Arsenism" (WS/T 211-2015), the clinical grading of skin injuries (skin keratinization, pigmentation abnormalities) in the survey subjects was evaluated. Urine samples were collected for detection of arsenic methylation metabolite levels by high-performance liquid chromatography inductively coupled plasma mass spectrometry and calibrated with urinary creatinine. The changes and amplitudes of urinary arsenic methylation indicators before and after water improvement were calculated and analyzed according to the outcome of skin keratinization and pigmentation abnormalities which were divided into reduced, unchanged, and added groups.Results:(1) The changes in urinary total arsenic (TAs), inorganic arsenic (iAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) levels in different outcome groups of skin keratinization were compared, and the differences were statistically significant ( H = 9.08, 8.77, 9.28, 8.57, P < 0.05). The changes in urinary TAs, iAs, MMA, DMA levels, iAs percentage (iAs%), DMA percentage (DMA%), and primary methylation index (PMI) in different outcome groups of skin pigmentation abnormalities were compared, and the differences were statistically significant ( H = 8.04, 10.67, 8.29, 9.14, 6.30, 9.10, 7.20, P < 0.05). (2) The comparison of amplitudes in urinary TAs, iAs, MMA, and DMA levels in different outcome groups of skin keratinization showed statistically significant differences ( H = 6.92, 7.34, 6.66, 6.16, P < 0.05). The amplitudes in urinary iAs level, iAs%, DMA%, and PMI in different outcome groups of skin pigmentation abnormalities were compared, and the differences were statistically significant ( H = 7.94, 7.61, 9.95, 7.22, P < 0.05). Conclusion:The changes pattern of urinary TAs, iAs, MMA, DMA, iAs%, DMA%, and PMI in population exposed to arsenic through drinking water is related to the transformation of skin keratinization and pigmentation abnormalities.

Objective:Kawasaki disease shock syndrome（KDSS）and macrophage activation syndrome（MAS）are both severe forms of Kawasaki disease. The coexistence of these two critical illnesses is extremely rare，which can be life-threatening in severe cases. The purpose of this study is to summarize the clinical features of children with KDSS complicated with MAS，and provide a basis for precise diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical manifestations，laboratory tests，imaging characteristics，treatment，and prognosis of 10 children with KDSS and MAS admitted to Beijing Children's Hospital，Capital Medical University from January 2021 to June 2024.Results:Among the 10 children，six were male and four were female，and the age of onset was three months to eleven years old. Acute kidney injury was observed in five patients. Laboratory tests revealed significant increases in serum ferritin，C-reactive protein，B-type natriuretic peptide，aspartate aminotransferase，alanine aminotransferase，creatinine，triglycerides，and interferon-γ，while platelet count and albumin were significantly decreased. Six patients had cardiac enlargement，three had reduced ejection fraction，seven had pericardial effusion，and seven had coronary artery damage. All children were treated with immunoglobulin and methylprednisolone pulse therapy，as well as vasoactive drug infusion to improve circulation and maintain blood pressure. All children were discharged after clinical improvement，and most had a good prognosis.Conclusion:Children with KDSS may develop MAS，which present a complex and rapidly progressing condition often accompanied by a significant increase in ferritin levels. Early diagnosis and treatment can lead to a favorable prognosis.

Objective:To conduct a scoping review on the critical values for lifestyle risk factors in young and middle-aged patients with prediabetes progressing to diabetes, so as to provide a reference for clinical screening, prevention, intervention, and patient self-management.Methods:Guided by the scoping review methodology and framework developed by Arksey et al., research questions were identified. Through systematic searches of Chinese and English literature databases, studies on risk factors in young and middle-aged patients with prediabetes progressing to diabetes published from the establishment of the database to August 11, 2024 were screened. Studies examining critical values for lifestyle risk factors were selected for data extraction, summary of findings, and qualitative analysis.Results:A total of 19 articles were ultimately included. Lifestyle risk factors encompassed diet, exercise, smoking, drinking, and step count. Specific indicators included daily sugar intake >25 grams, weekly exercise time <150 min, daily exercise time <30 min, weekly drinking ≥3 times with ≥180 ml of clear liquor per session, and daily step count <5 000 steps.Conclusions:There are different characteristics and critical values of the influence of various factors on the progress of diabetes. Future research should further standardize criteria and conduct large-scale, multicenter, long-term follow-up studies to establish optimal critical values for lifestyle factors, thereby providing evidence for diabetes screening, prevention, and intervention.

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

Objective:To conduct a scoping review on the critical values for lifestyle risk factors in young and middle-aged patients with prediabetes progressing to diabetes, so as to provide a reference for clinical screening, prevention, intervention, and patient self-management.Methods:Guided by the scoping review methodology and framework developed by Arksey et al., research questions were identified. Through systematic searches of Chinese and English literature databases, studies on risk factors in young and middle-aged patients with prediabetes progressing to diabetes published from the establishment of the database to August 11, 2024 were screened. Studies examining critical values for lifestyle risk factors were selected for data extraction, summary of findings, and qualitative analysis.Results:A total of 19 articles were ultimately included. Lifestyle risk factors encompassed diet, exercise, smoking, drinking, and step count. Specific indicators included daily sugar intake >25 grams, weekly exercise time <150 min, daily exercise time <30 min, weekly drinking ≥3 times with ≥180 ml of clear liquor per session, and daily step count <5 000 steps.Conclusions:There are different characteristics and critical values of the influence of various factors on the progress of diabetes. Future research should further standardize criteria and conduct large-scale, multicenter, long-term follow-up studies to establish optimal critical values for lifestyle factors, thereby providing evidence for diabetes screening, prevention, and intervention.

Monkeypox(MPX)is a viral zoonotic disease caused by monkeypox virus(MPV)infection.For many years it has been confined to the African region,with only a handful of cases in other parts of the world.But in recent years,monkeypox out-breaks have slowly spread to other regions.MPV is the cause of the human monkeypox disease,which is similar in clinical pres-entation to smallpox,although the fatality rate of MPV infection is lower than that of smallpox,but more and more confirmed ca-ses are reported,which raises various concerns.This article mainly reviews the biological characteristics,epidemiological characteristics,clinical treatment,prevention and conclusions of MPV,which helps to improve people's understanding of MPV transmission,symptoms,prevention and protection measures,and also provides a theoretical basis for further research on MPV.

PARP7 is a mono-ADP ribotransferase belonging to the PARP family that acts as a specific amino acid to catalyze the transfer of ADP ribose from NAD+to itself and other sub-strate proteins.PARP7 is overactive in many tumors and can in-terfere with interferon signaling pathways to enable cancer cells to achieve immune escape.Inhibition of PARP7 can restore IFN-β expression in tumor cells,thereby activating T cell-mediated anti-tumor immunity in vivo,so PARP7 is considered as a new immunomodulatory target for cancer therapy.At present,only one selective inhibitor of PARP7,RBN-2397,has entered phaseⅠ clinical studies.This article focuses on the structure and bio-logical function of PARP7,the correlation between PARP7 and cancer occurrence,and the research progress of PARP7-related inhibitors,in order to provide theoretical basis and new ideas for the research and development of new PARP7 inhibitors and the structural optimization of RBN-2397.