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.

Objective To understand mosquito density, species composition, and seasonal variations around the Beijing Capital International Airport(BCIA)and provide scientific evidence for mosquito-borne disease prevention and control. Methods Meteorological data were collected from 2016 to 2022, and mosquito density was monitored at seven surveillance sites around the BCIA from May to October each year using CO2-baited mosquito traps to analyze the relationship between mosquito density and meteorological factors. Results In total,68 518 female mosquitoes were captured, with a mosquito density of 10.20 per light · hour. The dominant species was Culex pipiens pallens(73.90%), followed by Aedes albopictus(9.71%)and Ae. vexans(9.29%);the mosquito density was highest in 2016(14.8 per light·hour)and lowest in 2022(4.46 per light·hour). Significant statistical differences were observed in mosquito density among different species(F=18.118, P<0.05). The density of Cx. pipiens pallens and other mosquito species showed a mutually exclusive trend; the peak of mosquito density varied based on years and habitats, with significant statistical differences in mosquito density among different habitats(F=8.504, P<0.05). The highest mosquito density was observed near the Wenyu River(21.50 per light·hour), whereas the lowest was recorded at the BCIA construction site(2.44 per light· hour). The monthly average temperature(r=0.595), monthly average highest temperature(r=0.575), and monthly average lowest temperature(r=0.624)showed moderate positive correlations, whereas the monthly average air pressure(r=-0.484)showed a moderate negative correlation. The monthly average minimum temperature was included in the regression model(F=25.575, P<0.000), and the equation Y=1.029X4-8.181 was used. The monthly average air pressure 2 months prior(b=-2.418, β=-1.619, P<0.05)and the monthly average relative humidity(b=-0.739, β=-1.201, P<0.05)significantly negatively predicted the mosquito density. Notably, the regression equation used was y=2526.170+(-2.418)X9+(-0.739)X13. The exposure-response analysis revealed that the density of mosquitoes was not linearly related to the average monthly air pressure, rainfall, and duration of sunshine. Conclusions The dominant mosquito species around the BCIA was Cx. pipiens pallens, Ae. albopictus, and Ae. vexans. During the control of Cx. pipiens pallens, the impact on other mosquito species must also be considered. Environmental management, breeding sites, and scientific use of pesticides should be prioritized based on the activity periods of mosquitoes. Further studies on mosquitoes and meteorological factors should be conducted to provide references and novel avenues for mosquito control.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

OBJECTIVE: To investigate cisplatin-induced cardiovascular toxicity and explore the protective effects and potential mechanism of curcumin co-treatment. METHODS: Forty adult male Sprague-Dawley rats were numbered and randomly divided into control group, cisplatin group (7.5 mg/kg, once a week, for 2 weeks), curcumin group (200 mg/kg per day, for 2 weeks) and cisplatin+curcumin group (cisplatin 7.5 mg/kg, once a week, and curcumin 200 mg/kg per day for 2 weeks) by a random number table method, with 10 rats in each group. Cardiac and vascular morphology and functions were assessed using hematoxylin-eosin and Masson's trichrome staining, serum indexes detection, echocardiography, electrocardiogram (ECG), blood pressure monitoring, vascular ring isometric tension measurement, and left ventricular pressure evaluation. The expressions of extracellular signal-regulated kinases (ERK) and phosphorylated-ERK (p-ERK) were analyzed by immunohistochemical staining. RESULTS: Cisplatin treatment induced notable cardiac alteration, as evidenced by changes in cardiac morphology, elevated serum enzymes (P<0.05), ECG abnormalities, and increased left ventricular end-diastolic pressure (P<0.05). Meanwhile, cisplatin significantly increased arterial pulse pressure (P<0.01), primarily due to a decrease in diastolic blood pressure. Severe fibrosis was also observed in the thoracic aorta wall. In vascular ring experiments, cisplatin treatment led to a significant reduction in phenylephrine-induced contraction (P<0.05) and acetylcholine-induced relaxation (P<0.01). Notably, Curcumin co-administration significantly alleviated cisplatin-induced cardiovascular damages, as demonstrated by improvement in these parameters. Furthermore, ERK expression in the myocardium and p-ERK expression in vascular smooth muscle cells were significantly upregulated following curcumin co-treatment. CONCLUSIONS Curcumin protects the heart and vasculature from cisplatin-induced damages, likely by upregulating ERK/p-ERK expression. These findings suggest that curcumin may serve as a promising therapeutic strategy for mitigating cisplatin-associated cardiovascular toxicity during tumor chemotherapy. In vitro cell culture experiments are needed to clarify the underlying mechanism.
Animals ; Curcumin/therapeutic use* ; Cisplatin/adverse effects* ; Rats, Sprague-Dawley ; Male ; Up-Regulation/drug effects* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Phosphorylation/drug effects* ; Electrocardiography ; Blood Pressure/drug effects* ; Rats ; MAP Kinase Signaling System/drug effects*

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

ObjectiveRecent studies have highlighted the critical role of NUDT19 in the initiation, progression, and prognosis of specific cancer types. However, its involvement in pan-cancer analysis has not been fully characterized. This study aims to systematically explore the expression patterns, clinical significance, and immune-related functions of NUDT19 in various cancer types through multi-omics analysis, further revealing its potential role in cancer, particularly its functional and therapeutic target value in leukemia. MethodsTo achieve this goal, various bioinformatics approaches were employed to evaluate the expression patterns, clinical significance, and immune-related functions of NUDT19 in tumors and normal tissues. Additionally, we analyzed the mutation characteristics of NUDT19 and its relationship with epigenetic modifications. Using the single-cell analysis tool SingleCellBase, we explored the distribution of NUDT19 across different cell subpopulations in tumors. To validate these findings, qRT-PCR was used to measure NUDT19 expression levels in specific tumor cell lines, and we established acute myeloid leukemia (AML) cell lines (HL-60 and THP-1) to conduct NUDT19 knockdown and overexpression experiments, assessing its effects on leukemia cell proliferation, apoptosis, and invasion. ResultsPan-cancer analysis revealed the dysregulated expression of NUDT19 across multiple cancer types, which was closely associated with poor prognosis, clinical staging, and diagnostic markers. Furthermore, NUDT19 was significantly correlated with tumor biomarkers, immune-related genes, and immune cell infiltration in different cancers. Mutation analysis showed that multiple mutations in NUDT19 were significantly associated with epigenetic changes. Single-cell analysis revealed the heterogeneity of NUDT19 expression in cancer cells, suggesting its potentially diverse functional roles in different cell subpopulations. qRT-PCR experiments confirmed the significant upregulation of NUDT19 in various tumor cell lines. In AML cell lines, NUDT19 knockdown led to reduced cell proliferation and invasion, with increased apoptosis, while NUDT19 overexpression significantly enhanced cell proliferation and invasion while reducing apoptosis. ConclusionThis study demonstrates the diverse roles of NUDT19 in various cancer types, with a particularly prominent functional role in leukemia. NUDT19 is not only associated with tumor initiation and progression but may also influence cancer progression through the regulation of immune microenvironment and epigenetic mechanisms. Our research highlights the potential of NUDT19 as a therapeutic target, particularly for targeted therapies in malignancies such as leukemia, with significant clinical application prospects.

Objective To explore the correlation of bilateral knee joint strength asymmetry with balance,walking ability,and motor function in hemiplegic stroke patients,providing a reference for clinical assessment of stroke patients.Methods A total of 46 hemiplegic stroke patients admitted to the Rehabilitation Medicine Department of People's Hospital of Shijiazhuang from February to December 2023 were selected.According to the Berg Balance Scale(BBS)scores,patients were divided into Group A(BBS score≤20,n=23)and Group B(BBS score>20,n=23).The peak torque and differences of bilateral knee flexors and extensors were compared between two groups.Isokinetic technology was used to assess the differences in peak torque of bilateral knee joints at 60°/s and 120°/s.BBS,Functional Ambulation Classification(FAC),and Fugl-Meyer Assessment of Lower Extremity(FMA-LE)were used to evaluate patients'balance,walking ability,and lower limb motor function.The correlation between bilateral knee joint peak torque and its difference with the scores of three functional scales was analyzed.Results The peak torque of knee flexors and extensors at 60°/s in group A was significantly lower than that in group B(P<0.05).At both 60°/s and 120°/s the differences in peak torque between the healthy and affected sides of knee flexors and extensors were greater than those in group B(P<0.05).At 60°/s,the difference in peak torque of bilateral knee extensors in hemiplegic stroke patients was negatively correlated with the scores of BBS,FAC,and FMA-LE(r=-0.569,-0.582,-0.606,P<0.01),as did the knee flexors(r=-0.534,-0.386,-0.458,P<0.05).At 120°/s,similar negative correlations were observed for both knee extensors(r=-0.304,-0.304,-0.443,P<0.05)and flexors(r=-0.337,-0.349,-0.370,P<0.05).Conclusions Bilateral knee joint strength asymmetry in hemiplegic stroke patients is negatively correlated with balance and walking ability.The difference in strength between the two sides of knee joint may be one of the clinical indicators for evaluating the motor function of stroke patients.

Objective To compare the hemodynamic effects of anesthesia induction with remimazolam tosylate and etomidate in elderly frail patients.Methods This study was a single-center,prospective,randomized,single-blind trial.From January to April 2024,96 elderly frail patients undergoing elective surgery in Fuyang People's Hospital were recruited.After excluding 6 cases(3 refused to participate,1 had tracheal intubation time＞30 s,and 2 had missing data),90 patients were finally included.They were randomly divided into remimazolam tosylate group(intravenous injection of 0.2 mg/kg remimazolam tosylate for anesthesia induction,n=45)and etomidate group(intravenous injection of 0.3 mg/kg etomidate for anesthesia induction,n=45)by the random number table method.The area under the curve for mean arterial pressure(MAP)below or above baseline values(AUCMAP-and AUCMAP+),the heart rate(HR)below or above baseline values by 10％(AUCHR-and AUCHR+)within 10 minutes of anesthesia induction,the time to loss of consciousness,the time from the start of anesthesia induction to a bispectral index(BIS)＜60,the incidence of drug-related adverse reactions,the incidence of cardiovascular adverse events,and the usage of vasoactive drug administrations were compared between the two groups.Results Compared with the etomidate group,the AUCMAP-(145.10±35.75 vs.178.52±39.78)and AUCHR-[43.20(26.58,56.35)vs.54.99(43.01,65.85)]in remimazolam tosylate group were significantly reduced(P＜0.001,P=0.001).The time to loss of consciousness and the time from the start of anesthesia induction to BIS＜60 were prolonged(P＜0.001).The incidence of drug-related adverse reactions was significantly decreased(P＜0.05),and the number of norepinephrine administrations was significantly reduced(P＜0.05)in remimazolam tosylate group.However,there were no statistically significant differences in AUCMAP+,AUCHR+,the incidence of cardiovascular adverse events,and the usages of atropine,urapidil,and esmolol between the two groups(P＞0.05).Conclusion The use of remimazolam tosylate during anesthesia induction in elderly frail patients can provide more stable hemodynamic parameters and results in fewer adverse reactions than etomidate.

Objective To explore the validity and feasibility of the left transthoracic and esophageal hiatal approach for Siewert type Ⅱ adenocarcinoma of the esophagogastric junction under a single position.Methods The clinical data of 64 patients with Siewert type Ⅱ AEG(single position transthoracic approach group)treated with the left transthoracic and esophageal hiatal approach under a single position and 56 patients with the laparoscopic transesophageal slit approach(transabdominal approach group)in the Department of Thoracic Surgery,Huaihe Hospital of Henan University,from January 2017 to December 2018 were retrospectively analyzed.The clinical and pathological data,perioperative indicators(operation time,intraoperative blood loss,postoperative first ambulation time,postoperative first peristalsis time,postoperative drainage volume at 3 d,incidence of postoperative complications,postoperative hospital stay),postoperative complications(positive surgical margin,proximal esophageal resection margin,tumor diameter,total number of dissected lymph nodes,positive lymph node dissection rate,postoperative histopathology,and TNM staging of tumor pathology),and survival indicators(tumor recurrence and metastasis rate and survival at 1 month,3 months,6 months,1 year,3 years,5 years after surgery)were compared between the two groups.Kaplan-Meier method was used to analyze the postoperative survival rate of the two groups.Univariate analysis using χ2 test was employed to analyze factors influencing 5-year postoperative survival rate in Siewert type Ⅱ AEG patients.Results No significant difference was observed in clinical and pathological data,such as gender,age,American Society of Anesthesiologists(ASA)grade,tumor differentiation,pTNM stage,and tumor diameter between the two groups(P>0.05).No significant differences were noted in intraoperative blood loss,incidence of postoperative complications,and survival rates at 1 month,3 months,6 months,1 year,and 3 years after surgery between the two groups(P>0.05).The single position transthoracic approach group exhibited a higher postoperative drainage volume at 3 d compared to the transabdominal approach group(P<0.001),a shorter surgical time(P<0.001),a longer time to first mobilization,first intestinal peristalsis,and hospital stay after surgery(P<0.01),a longer proximal esophageal margin(P<0.001),a higher total number of lymph node dissections(P<0.001),and a higher positive lymph node dissection rate(P<0.05)than the transabdominal approach group.The 5-year recurrence-free survival rate of the single position transthoracic approach group was higher than that of the transabdominal approach group,with a statistically significant difference(P=0.013).The Kaplan-Meier survival curve showed no statistically significant difference in the 5-year overall survival rate between the two groups of patients after surgery(P=0.456).The results of univariate analysis indicated that there are significant relationships between tumor differentiation degree,pTNM stage,tumor diameter,and lymph node positivity rate with the 5-year postoperative survival rate in Siewert type Ⅱ AEG patients(P<0.05).Conclusion Siewert type Ⅱ AEG patients can be treated with the left transthoracic and esophageal hiatal approach under a single position,achieving the same effect as laparoscopic transesophageal slit approach,and it can be actively promoted as a complementary choice of operation in the clinic.

Objective To observe the difference of bone micro-structure in different regions of proximal femur,micro-CT scanning was performed on 30 proximal femur specimens to explain the mechanism of proximal femur fracture and to provide anatomical basis for prosthesis design.Methods Totally 30 intact proximal femur specimens were obtained from 60-80 year-old cadavers.Micro-CT scanning was used to measure the trabecular thickness(Tb.Th),trabecular number(Tb.N),trabecular space(Tb.Sp),connectivity(Conn)and bone mineral density(BMD)and other parameters in 7 regions of proximal femur,including proximal pressure trabecular(PPT),distal pressure trabecular(DPT),femoral head-neck junction(FHNJ),head and neck of femoral neck(HNFN),the base of femoral neck(BPFN),intertrochanteric line(IL)and greater trochanter(GT).Results The bone mineral density of IL and GT were higher than those of BPFN,FHNJ,DPT and PPT.The trabecular thickness of GT was the largest,followed by IL,BPFN and HNFN,and the smallest was FHNJ,DPT and PPT.The trabecular space of IL was larger than that of GT,and the data of both were larger than those of other parts,among which DPT and PPT were the smallest.The trabecular number of IL and GT were the smallest,BPFN,HNFN and FHNJ were larger,and DPT was the largest.The volume fraction of IL was the smallest,BPFN and HNFN were larger,DPT and PPT were the largest.Conclusion The bone density,trabecular thickness,bone volume,and total volume of GT and IL in the proximal femur of elderly patients are all relatively large,so the reason for the high incidence of fractures is not due to weak internal bone microstructure;The bone density,trabecular thickness,and trabecular gap at the proximal and distal ends of the vertical trabecular bone are relatively small.If it is necessary to perform core decompression for prosthesis filling at this location,the design should be conducive to the mechanical conduction of the prosthesis and the regeneration of surrounding bone tissue.