Aim To study the effect of Guben Yanling pills on liver aging in aging mice and the related mech-anism.Methods The mice were randomly divided in-to blank control group,model group,vitamin E group(0.1 g·kg-1)and low,medium and high dose groups(0.59,1.17,2.34 g·kg-1)of Guben Yan-ling pills.The aging mouse model was established by subcutaneous injection of D-galactose(150 mg·kg-1)into the back of neck.At the same time of mod-eling,the corresponding drugs were given by gavage once a day for six weeks.The main organ indexes were calculated.HE staining was used to observe the mor-phology of liver tissue.Colorimetry was used to detect the activity of β-galactosidase in liver.ELISA was used to detect the content of TNF-α,IL-1 β,IL-6,IL-4,IL-10.Western blot was used to detect the protein relative expression level of IKKβ,Iκ Bα,NF-κB p65.Immunofluorescence was used to detect the expression level of NF-κB p65.Results Compared with the blank control group,the organ index of the brain,liv-er,kidney,spleen,and thymus in the model group decreased(P＜0.05,P＜0.01),the activity of β-galactosidase increased(P＜0.01),liver tissue mor-phology and structure were significantly damaged,the content of TNF-α,IL-1 β and IL-6 increased(P＜0.01),the content of IL-4 and IL-10 decreased(P＜0.01),the levels of IKKβ,NF-κB p65 in-creased(P＜0.01),the levels of IKBα decreased(P＜0.01),and the levels of NF-κB p65 in nucleus increased(P＜0.01).Compared with the model group,the organ indexes of brain,liver,kidney,spleen,and thymus in each dose group of Guben Yan-ling pills increased(P＜0.05,P＜0.01),the activity of β-galactosidase decreased(P＜0.01),the morpho-logical and structural damage of liver tissue was signifi-cantly improved,the content of TNF-α,IL-1 β and IL-6 decreased(P＜0.01),the content of IL-4 and IL-10 increased(P＜0.01),the levels of IKKβ,NF-κB p65 decreased(P＜0.01),the levels of IκBα in-creased(P＜0.01),and the levels of NF-κB p65 in nucleus decreased(P＜0.01).Conclusions Guben Yanling pills can antagonize liver aging in mice,and its mechanism may be related to inhibiting the activa-tion of NF-κB signaling pathway in liver,downregulat-ing downstream pro-inflammatory factor levels,upregu-lating anti-inflammatory factor levels,and alleviating inflammation in liver.

Perihilar cholangiocarcinoma(PHC)is a common malignancy of biliary tract,for which surgery is the most effective treatment.However,its prognosis is not satisfactory even after surgical resection.In recent years,there have been some new advances in the surgical treatment of PHC.In this paper,we reviewed the existing literatures,demonstrated the current situation of preoperative biliary drainage,liver hyperplasia,hepatic resection,liver transplantation and minimally invasive surgery in the treatment of PHC,and prospected the future research direction.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective Th is aim of this review was to clarify the role of neutrophils in diabetes by summarizing the characterization studies,potential trends,and research hotspots relating to neutrophils in the diabetes research field.Methods 2998 relevant studies on neutrophils in the diabetes research field indexed in Web of Science from 2010 to 2023 were retrieved,and a visual analysis of the relevant literature was conducted using CiteSpace 6.1.R6.Results Since 2012,the number of publications on this topic has grown rapidly.Bayat Mohammad,Liu Tong,Amini Abdollah,and Zhang Rui are high-yield authors,with seven related articles published.China and Shanghai Jiao Tong University are the country and institution with the most published papers.The most influential journal in this field is"Nature Medicine".Literature co-citation analysis of topics related to diabetes showed that the greatest focus is currently on"extracellular trap"and"COVID-19 patient".Co-occurrence analysis,clustering analysis,and keyword burst analysis indicated that"lymphocyte ratio"(13.08)and"neutrophil extracellular trap"(7.2)are the most researched topics in the field of neutrophils and diabetes.Literature in this field mainly focuses on"myocardial infarction","endothelial","oxidative stress",and"apoptosis".Conclusions This article highlights the evolving trends in research into neutrophils in the diabetes field using CiteSpace,providing new insights for researchers aiming to conduct research in this area.

Objective:To analyze the clinical and genetic characteristics of acute myeloid leukemia,myelodysplasia-related(AML-MR)patients and evaluate their prognostic risk stratification,to guide clinical treatment decisions and improve understanding of the biological characteristics and disease progression.Methods:The study analyzed cellular and molecular genetic information of 307 AML-MR patients,diagnosed based on clinical history,bone marrow morphology,cytogenetics,and molecular genetic abnormalities.The risk stratification followed the 2022 ELN guidelines.Results:57 cases(18.6％)met the AML-MR diagnostic criteria based on morphology and clinical history,110 cases(37.2％)met the AML-MR diagnostic criteria based on cytogenetic results,and 210 cases(74.5％)met the AML-MR diagnostic criteria based on molecular testing results.Among different type of mutations,ASXL1 mutation was the most frequent,followed by SRSF2 and BCOR mutations.Except for 2 cases with incomplete data that could not be classified.263(86.2％)of the 305 patients were classified as poor prognosis,20(6.6％)were classified as good prognosis group,and 22(7.2％)were classified as intermediate prognosis group.Conclusion:Molecular genetic information plays a crucial role in diagnosing AML-MR,highlighting the importance of genetics in diagnosis and prognosis.Most AML-MR patients fall into poor prognosis categories,necessitating early intensive and targeted therapy for better survival outcomes.

There seems to be a contradiction among the symptoms of"non-thirst"and"thirst after oral use of the decoction"stated in original text 41 of Shang Han Lun(Treatise on Febrile Diseases)and the symptom of"probable thirst"stated in original text 40.In this article,the symptoms of thirst or non-thirst in the syndrome of Xiao Qinglong Decoction were expounded through the analysis of the basic theories of traditional Chinese medicine about body fluid metabolism and the pathogenic mechanism of thirst,and by synthesizing the relevant articles recorded in Jin Gui Yao Lve(Synopsis of the Golden Chamber)and the understanding of the syndrome of Xiao Qinglong Decoction by later generations of practitioners.After that,the following views are put forward:non-thirst symptom is the primary sympton of the syndrome of Xiao Qinglong Decoction,which results from the disease;thirst after oral use of the decoction is due to drug-induced thirst,which can be classified into the category of physiological thirst;probable thirst symptom is related with fluid consumption by febrile disease,indicating that the disease involves yangming.The analysis of the symptoms of thirst or non-thirst in the syndrome of Xiao Qinglong Decoction is helpful for evaluation of therapeutic efficacy,and can also be used as the indications of modified medications and differential diagnosis of the disease.The exploration will provide references for the clinical use of Xiao Qinglong Decoction and will be beneficial to improving the clinical efficacy of Xiao Qinglong Decoction.

As the country with the largest number of new cancer cases and deaths,China faces a serious situation with a large cancer population base,low relative survival rate,and low adherence to cancer screening.Neighboring Japan,which has the longest life expectancy in the world,has a much higher relative survival rate than China,despite having a similarly high cancer rate,due to its well-established system of cancer prevention and control.Being an Asian country,the major prevalent cancers in China and Japan are similar in spectrum and can be referred to more.This article introduces the construction of Japan's cancer life-cycle prevention and control system of"cancer prevention","cancer care",and"coexistence with cancer"starting from the three major goals of Japan's cancer prevention and control program,and focuses on the improvement of cancer screening in Japan and the improvement of cancer survival in China.It also highlights the means and methods used to increase the cancer screening rate in Japan,with a view to providing suggestions for cancer prevention and control in China.

mRNA gene therapy has attracted much attention due to its advantages such as scalability, modification, no need to enter the nucleus and no integration of host genes. In gene therapy, safe and effective delivery of mRNA into cells is critical for the success of gene therapy. In this study, we designed and synthesized an amphiphilic cationic lipopeptide gene vector (dendritic arginine & disulfide bond-containing cationic lipopeptide, RLS) enriched with branched arginine. We achieved a 1.5-fold higher mRNA transfection efficiency in zebrafish compared to the commercial reagent Lipofectamine 2000, and confirmed its good biosafety by in vitro cytotoxicity and in vivo biosafety. First, we characterized the chemical composition of the cationic lipid peptides by nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) and time-of-flight mass spectrometry (MS). The results of particle size and potential tested by dynamic light scattering particle size analysis showed that at a nitrogen/phosphorus (N/P) ratio of 20, the RLS/mRNA composite assemblies formed homogeneous nanoparticles with an average particle size of about 220 nm and a surface ζ potential of about +21 mV. In vitro gene transfection, the transfection experiments demonstrated that RLS exhibited 1.2-fold higher transfection efficiency in human embryonic kidney 293 cells (HEK293) and 3-fold higher transfection efficiency in rat mesenchymal stem cells (MSC) compared to Lipofectamine 2000. In addition, after microinjection of RLS into zebrafish embryos, we evaluated the survival, hatching, and teratogenicity rates, all of which confirmed its favorable in vivo safety profile. Thus, this amphiphilic cationic lipid peptide RLS, enriched with branched arginine, exhibits excellent mRNA delivery properties and safety. These findings highlight its potential as a promising gene therapy tool.

Objective Hydroquinone(HQ),one of the phenolic metabolites of benzene,is widely recognized as an important participant in benzene-induced hematotoxicity.However,there are few relevant proteomics in HQ-induced hematotoxicity and the mechanism hasn't been fully understood yet. Methods In this study,we treated K562 cells with 40 μmol/L HQ for 72 h,examined and validated protein expression changes by Label-free proteomic analysis and Parallel reaction monitoring(PRM),and performed bioinformatics analysis to identify interaction networks. Results One hundred and eighty-seven upregulated differentially expressed proteins(DEPs)and 279 downregulated DEPs were identified in HQ-exposed K562 cells,which were involved in neutrophil-mediated immunity,blood microparticle,and other GO terms,as well as the lysosome,metabolic,cell cycle,and cellular senescence-related pathways.Focusing on the 23 DEGs and 5 DEPs in erythroid differentiation-related pathways,we constructed the network of protein interactions and determined 6 DEPs(STAT1,STAT3,CASP3,KIT,STAT5B,and VEGFA)as main hub proteins with the most interactions,among which STATs made a central impact and may be potential biomarkers of HQ-induced hematotoxicity. Conclusion Our work reinforced the use of proteomics and bioinformatic approaches to advance knowledge on molecular mechanisms of HQ-induced hematotoxicity at the protein level and provide a valuable basis for further clarification.

A new method was developed for simultaneous detection of total 19 kinds of organophosphate esters(OPEs)and their diester metabolites(di-OPEs)in human serum(1.0 mL)and urine(1.5 mL)with low volume of samples.The target compounds were determined using ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)after acetonitrile liquid-liquid extraction combined with purification using an ENVI-18 solid-phase extraction(SPE)column.OPEs and di-OPEs were separated using a Shim-pack GIST C18 column(100 mm×2.1 mm,2 μm)with a Shim-pack GIST-HP(G)C18 guard column.An electrospray ionization source(ESI)was employed in mass spectrometry analysis,with positive/negative ion mode using the multiple reaction monitoring(MRM).All target compounds were separated within 15 min,and exhibited good linear relationships in the concentration range of 2-100 ng/mL,with correlation coefficients(R2)above 0.994.The method detection limits(MDL)in serum ranged from 0.001 to 0.178 ng/mL and the MDL in urine ranged from 0.001 to 0.119 ng/mL.The recoveries of the analytes spiked in serum and urine matrices at two concentration levels were 30.5%-126.8%,with the relative standard deviations(RSDs)ranged from 1%to 23%.In addition,paired serum and urine samples from 11 patients were analyzed.For all samples tested,the internal standards of OPEs exhibited recoveries between 61%and 114%,whereas the internal standards for di-OPEs had recoveries ranging from 43%to 103%.OPEs and di-OPEs exhibited high detection frequencies in 22 serum and urine samples.Triethyl phosphate(TEP),tributyl phosphate(TBP),tris(2-ethylhexyl)phosphate(TEHP),tris(2-butoxyethyl)phosphate(TBEP),tris(1-chloro-2-propyl)phosphate(TCIPP),triphenyl phosphate(TPHP),tri-m-tolyl-phosphate(TMTP)and 2-ethylhexyl diphenyl phosphate(EHDPP)were universally detected in all serum samples.TCIPP was identified at the highest concentrations(median 0.548 ng/mL)in serum samples.In urine samples,the detection frequency for 12 kinds of target compounds reached 100%.Notably,TBP emerged as the predominant OPE in urine,demonstrating a median concentration of 0.506 ng/mL.Regarding di-OPEs,bis(2-chloroethyl)phosphate(BCEP)and bis(2-butoxyethyl)hydrogen phosphate(BBOEP)were the most abundant in urine,with median concentrations of 6.404 and 2.136 ng/mL,respectively.The total concentrations of OPEs and di-OPEs in serum and urine were 1.580-3.843 ng/mL and 5.149-17.537 ng/mL,respectively.These results not only confirmed the effectiveness of the method in detection of OPEs and di-OPEs in biological matrices,but also revealed the widespread presence of OPE compounds in human body and pointed to potential exposure risks.