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 Metabolomics combined with machine learning algorithms was used to systematically study the preoperative serum metabolites of patients with early postoperative cognitive dysfunction(POCD)after heart valve replacement,so as to screen biomarkers that may predict early POCD after heart valve replacement and explore the corresponding metabolic regulatory mechanisms.Methods A total of 60 patients underwent heart valve replacement under extracorporeal circulation were selected and divided into early-POCD group(group P)and non-POCD group(group N)according to whether POCD occurred or not.Metabolomic analysis was performed on preoperative serum samples of patients in group P and group N to screen the differential metabolites and metabolic pathways.The biomarkers related to early POCD were identified by random forest algorithm.Results A total of 532 differential metabolites were detected by metabonomics analysis,and 5 biomarkers were screened by random forest algorithm,namely quinoline,3'-sialyllactose,sphingomyelin(d18∶1/20∶0),lysophosphatidylcholine[P-18∶1(9Z)]and 25-hydroxycholesterol.Among them,the main metabolic pathways were phenylalanine metabolism,primary bile acid biosynthesis,ascorbic acid and aldonate metabolism,pentose and glucuronate interconversion,tryptophan metabolism,drug metabolism-cytochrome P450,porphyrin and chlorophyll metabolism.Conclusion Many metabolic pathways in patients with early POCD after heart valve replacement under extracorporeal circulation have changed before operation,which may lead to the occurrence of early POCD.Quinoline,3'-sialyllactose,sphingomyelin(d18∶1/20∶0),lysophosphatidylcholine[P-18∶1(9Z)]and 25-hydroxycholesterol may be biomarkers for predicting early POCD.

OBJECTIVE: To analyze the gene mutation characteristics and survival time of patients with newly diagnosed acute myeloid leukemia (AML) based on next-generation sequencing(NGS) gene detection. METHODS: A retrospective analysis was conducted on the clinical data of 92 patients with AML (non APL) admitted to our hospital from January 2018 to May 2022. AML related genes tested were using NGS, the mutation characteristics and survival time of AML patients were analyzed. RESULTS: Among the 92 patients, 41 were males and 51 were females. A total of 38 types of gene mutations were detected. Six-two patients carried at least one gere mutation, while no gene mutations were detected in 30 patients. In the group with favourable prognosis (n =14), the frequencies of higher gene mutations were NRAS, KIT (21.43%, n =3), KRAS (14.29%, n =2). In the group with intermediate prognosis (n =64), the gene mutation frequencies from high to low were DNMT3A (18.75%, n =12), NPM1 (17.19%, n =11), IDH2, FLT3-ITD, CEBPA (12.50%, n =8), TET2 (10.94%, n =7). In the poor prognosis group (n =14), ASXL1, TP53, EZH2, NRAS had higher gene mutation frequency than others(14.29 %, n =2 ). Statistical analysis revealed that KIT had a relative hotspot of mutations in the intermediate-risk group, and DNMT3A had a relative hotspot of mutations in the high-risk group (P < 0.05). The correlation analysis of genes with high mutation rates in different prognostic groups, such as NRAS, KIT, IDH2, DNMT3A, NPM1, and FLT3-ITD, with prognosis found that KIT was a factor affecting OS (P < 0.05), while no significant differences were observed for the others(P >0.05). CONCLUSION The frequency of gene mutations is high in AML patients, 67.4% of the patients carried at least one gene mutation. The mutation frequency varies among different genes in patients with different karyotypes, and there are obvious dominant mutations. KIT and DNMT3A can be used as factors for evaluating the prognosis of AML.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Mutation ; Prognosis ; Retrospective Studies ; Male ; Female ; High-Throughput Nucleotide Sequencing ; Middle Aged ; DNA Methyltransferase 3A ; Adult ; Aged ; Survival Analysis ; Proto-Oncogene Proteins c-kit/genetics*

OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

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*

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Aim To investigate the effect of KHSRP on the malignant biological behavior of gastric cardia ade-nocarcinoma by targeting JAK1/STAT3 signaling axis.Methods The expression levels of KHSRP in adeno-carcinoma tissues of gastric cardia adenocarcinoma and adjacent tissues were collected and compared.qRT-PCR experiment to detect transfection efficiency in gas-tric cardia adenocarcinoma cell lines(OE-19,TE-7,BIC-1,FLO-1,SK-GT-4,BE-3)and normal gastric mucosal epithelial cell line(GES-1).The knockdown and overexpression of KHSRP were treated by packa-ging lentiviral Vector,and the cells were divided into sh-NC group,sh-KHSRP group,vector group,and KH-SRP group.Cell counting kit-8(CCK-8)and Tran-swell assay were used to determine the effects of KH-SRP on the proliferation,migration and invasion of ade-nocarcinoma cells of gastric cardia adenocarcinoma.Xenograft tumor models were used to detect the effects of knockdown and overexpression of KHSRP in live an-imals.WB experiments confirmed that KHSRP targeted the JAK/STAT signaling pathway.Results KHSRP was overexpressed in GCA tissues and cell lines(P＜0.05).Cell function assay analysis showed that KH-SRP overexpression significantly promoted GCA cell proliferation,migration and invasion in vitro(P＜0.05).After KHSRP knockdown,the phosphorylation levels of JAK1 and STAT3 in JAK/STAT signaling pathway were significantly decreased,and the situation was opposite after KHSRP overexpression(P＜0.05).Conclusion KHSRP regulates the malignant progres-sion of metastasis of gastric cardia adenocarcinoma by activating JAK1/STAT3 signaling axis.

Objective To determine the application effect of esketamine pretreatment in laparoscopic high ligation of hernia sac in children.Methods A total of 70 children who received laparoscopic high ligation of hernia sac under general anesthesia were selected and divided into the control group and the observation group according to the random number table method,with 35 cases in each group.The control group received conventional general anesthesia,while the observation group was intravenously injected with 0.5 mg/kg of esketamine 15 minutes before the induction of general anesthesia.The preoperative anxiety score,respiratory mechanics indexes,lung injury status,anesthesia recovery,and adverse reactions during the awakening period were compared between the two groups.Results The anxiety scores of the observation group 10 minutes before anesthesia and immediately before anesthesia were significantly lower than those of the control group(P<0.05).The peak airway pressure and mean airway pressure of the observation group 30 minutes after establishing pneumoperitoneum and at the end of the operation were significantly lower than those of the control group(P<0.05).The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)at the end of the operation in the observation group were significantly lower than those in the control group(P<0.05).There was no statistically significant difference in the time of spontaneous breathing recovery,time to regain consciousness,tracheal extubation time,or post-anesthesia care unit(PACU)stay time between the two groups(P>0.05).The incidence of adverse reactions during the anesthetic awakening period in the observation group was significantly lower than that in the control group(P<0.05).Conclusion Esketamine pretreatment can significantly alleviate preoperative separation anxiety for children undergoing laparoscopic high ligation of hernia sac,reduce lung injury,and decrease airway pressure,which is beneficial to lung protection and postoperative anesthetic recovery,and has few adverse reactions.