ObjectiveTo investigate the effect of the nitroglycerin-controlled low central venous pressure （CLCVP） technique on brain metabolic markers and cerebral blood oxygen saturation in patients undergoing laparoscopic hepatectomy for liver cancer， and to reduce the risk of neurological complications. MethodsA total of 105 patients who underwent elective laparoscopic hepatectomy for liver cancer in Haikou Hospital Affiliated to Xiangya Hospital of Central South University from April 2020 to May 2023 were enrolled and randomly divided into CLCVP group with 54 patients and non-CLCVP group with 51 patients. The patients in the CLCVP group were treated with the nitroglycerin CLCVP technique during surgery， while those in the non-CLCVP group were given conventional surgical treatment. The two groups were compared in terms of the following indicators： perioperative indicators； hemodynamic parameters and cerebral oxygen metabolism before anesthesia induction （T0）， at 5 minutes after anesthesia induction （T1）， at 5 minutes after the beginning of liver parenchyma dissection （T2）， at 5 minutes after the end of hepatectomy （T3）， and immediately after the end of surgery （T4）； the changes in liver function parameters after surgery； the incidence rate of adverse reactions. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups； the analysis of variance with repeated measures was used for comparison between multiple time points. ResultsCompared with the non-CLCVP group， the CLCVP group had significantly lower intraoperative blood loss and intraoperative fluid infusion volume （t=5.408 and 7.220， both P<0.05）， while there were no significant differences between the two groups in time of operation， anesthesia time， extubation time， resuscitation time and intraoperative urine volume （all P>0.05）. Compared with the data at T0， both groups had significant reductions in mean arterial pressure， heart rate， and central venous pressure during surgery （all P<0.05）， and compared with the non-CLCVP group， the CLCVP group had significantly lower mean arterial pressure and central venous pressure （P<0.05） and a significantly higher heart rate （P<0.05） at T2 and T3. Compared with the data at T0， both groups had a significant reduction in Ca-jvDO₂ at T2‍ ‍—‍ ‍T4 time points （all P<0.05）， while there was no significant difference in Ca-jvDO₂ between the two groups at each time point （all P>0.05）. Compared with the data at T0， the CLCVP group had a significant reduction in rSO₂ at T2‍ ‍—‍ ‍T4 time points （all P<0.05）， and the CLCVP group had a significantly lower level of rSO₂ than the non-CLCVP group at T2‍ ‍—‍ ‍T3 time points （both P<0.05）； there were no significant changes in CERO₂ and Djv-aBL in either group at each time point （all P>0.05）. At 3 and 7 days after surgery， both groups had significant increases in the liver function parameters of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， and total bilirubin （TBil） （all P<0.05）， and the CLCVP group had significantly lower levels of AST and ALT than the non-CLCVP group （all P<0.05）； there was no significant difference in TBil between the two groups at each time point （all P>0.05）. There was no significant difference in the incidence rate of perioperative complications between the two groups （χ²=0.729， P=0.394）. ConclusionThe application of the nitroglycerin CLCVP technique in laparoscopic hepatectomy for liver cancer can reduce the amount of intraoperative blood loss in patients， but it is necessary to further enhance the monitoring of cerebral blood oxygen saturation during surgery， so as to reduce the risk of neurological complications as much as possible.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

ObjectiveAlveolar macrophages (AMs) are critical for maintaining the homeostasis of pulmonary microenvironment. They process surfactants to ensure alveoli patency, and also serve as the first line of immune defense against pathogen invasion. Available studies have shown that monocyte-derived AMs continuously release pro-inflammatory cytokines and chemokines, recruiting other immune cells to the damaged area during pulmonary fibrosis. These monocyte-derived AMs maintains and amplifies inflammation, playing a negative role in pulmonary fibrosis progression. Current researches have predominantly focused on the gene expression levels of AMs in pulmonary fibrosis microenvironment, with less emphasis on the function and regulation of proteins. This study aims to investigate the differentially expressed proteins (DEPs) of AMs under normal physiological conditions and after pulmonary fibrosis, in order to gain a more comprehensive understanding of the role of AMs in the progression of pulmonary fibrosis. MethodsFirstly, the construction of bleomycin-induced pulmonary fibrosis mouse models was evaluated through using measurements such as body mass, lung coefficient, lungwet-to-dry mass ratio, H&E staining and Masson staining. Subsequently, AMs from both the saline controls and the pulmonary fibrosis models (2.5×10⁵ cells per sample) were collected using FACS sorting, and protein expression profiles of these cells were obtained through label-free proteomics approach. The quality of the proteomic data was assessed by comparing our saline control proteomic data with public proteomic data of physiological AMs. Thirdly, DEPs analysis between the saline controls and the bleomycin groups was carried out using R package Prostar. Functional enrichment analyses of significantly upregulated DEPs were performed using R package Clusterprofiler for GO and KEGG pathways. Finally, the STRING database was used to explore the protein-protein interaction networks related to phagocytosis regulation, inflammatory response regulation, andI-κB/NF-κB signaling pathway. The expression levels of Tlr2 and Pycard were detected respectively by FACS and western blotting. ResultsCompared to the saline controls, mice in the bleomycin groups exhibited a lower average body mass, extensive infiltration of inflammatory cells, and deposition of collagen in the lungs. This indicates that bleomycin successfully induced pulmonary fibrosis in mouse models. The proteomic data of AMs obtained from these models was of high quality and fulfilled the research requirements. A comprehensive analysis showed that 778 proteins were upregulated in pulmonary fibrosis groups compared with control groups. Moreover, the signal pathways enriched in up-regulated DEPs were related to the I‑κB/NF‑κB pathway, inflammatory response regulation, phagocytosis regulation, TGF-β signaling, and HIF-1 pathway, indicating that AMs in pulmonary fibrosis microenvironment exerted pro-inflammatory and pro-fibrotic functions. Protein-protein interaction network analysis of the DEPs suggested that the interactions between Tlr2 and Pycard were control nodes for the pro-inflammatory phenotype of AMs, thereby contributing to pulmonary fibrosis progression. Further validation by FACS and Western blotting respectively confirmed that the expression levels of Tlr2 and Pycard in AMs were significantly increased after pulmonary fibrosis. ConclusionThis study investigates the changes in the protein expression profile of AMs in the pulmonary fibrosis microenvironment. The results show that AMs notably enhanced the activity of various pathways associated with inflammation and fibrosis, suggesting that the interaction between Tlr2 and Pycard serves as a key control node for the highly pro-inflammatory behavior of AMs.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective·To systematically integrate relevant influencing factors of advanced cancer patients'engagement behavior in advance care planning(ACP).Methods·The systematic search of Chinese and English literature on factors influencing ACP engagement behavior in advanced cancer patients from inception to December 2022 in China National Knowledge Infrastructure(CNKI),Wanfang,China Biomedical Literature Database(Sinomed),PubMed,Cochrane Library,Embase,CINAHL,and PsycINFO was conducted.After the literature quality evaluation,content extraction and summary were conducted by two researchers,and the data of quantitative research and qualitative research were extracted and integrated respectively.The final influencing factors of ACP engagement behavior of advanced cancer patients were obtained.With the help of the theoretical domain,they were mapped to the capability,opportunity,motivation-behavior(COM-B)model step by step.Results·A total of 21 studies were included and 27 factors were summarized,including 9 theoretical domains.Mapping to the COM-B model included 9 capability factors(knowledge of ACP,education level,accurate knowledge of prognosis,knowledge of the time of disease diagnosis,prior experience,subjective life expectancy,age,cancer site,and disease symptom burden),13 opportunity factors(gender,marital status,race/ethnicity,religious belief,dependent children,family economic condition,place of living,housing type,family support,social support,doctor-patient relationship,acculturation,and whether or not to establish a hospice service center)and 5 motivational factors(ACP attitude,ACP belief,ACP motivation,anxiety and depression,and death attitude).Among them,doctor-patient relationship,religious belief,ACP attitude,educational level,marital status,family support,knowledge of ACP,accurate knowledge of prognosis,age,place of living,attitude toward death,prior experience,and race/ethnicity were more influential factors on ACP engagement behavior.Conclusion·Based on the COM-B model,the influencing factors of ACP engagement behavior in advanced cancer patients can be comprehensively summarized.Future studies can use the above factors as an entry point to design continuous,multifaceted,and comprehensive interventions based on the COM-B model to promote the practice of ACP engagement behavior in advanced cancer patients.

Objective To understand the change in distribution and antimicrobial resistance of bacteria isolated from blood specimens of Hunan Province,and provide for the initial diagnosis and treatment of clinical bloodstream infection(BSI).Methods Data reported from member units of Hunan Province Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacterial antimicrobial resistance surveillance method was imple-mented according to the technical scheme of China Antimicrobial Resistance Surveillance System(CARSS).Bacteria from blood specimens and bacterial antimicrobial susceptibility testing results were analyzed by WHONET 5.6 soft-ware and SPSS 27.0 software.Results A total of 207 054 bacterial strains were isolated from blood specimens from member units in Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021,including 107 135(51.7％)Gram-positive bacteria and 99 919(48.3％)Gram-negative bacteria.There was no change in the top 6 pathogenic bacteria from 2012 to 2021,with Escherichia coli(n=51 537,24.9％)ranking first,followed by Staphylococcus epidermidis(n=29 115,14.1％),Staphylococcus aureus(n=17 402,8.4％),Klebsiella pneu-moniae(17 325,8.4％),Pseudomonas aeruginosa(n=4 010,1.9％)and Acinetobacter baumannii(n=3 598,1.7％).The detection rate of methicillin-resistant Staphylococcus aureus(MRSA)decreased from 30.3％in 2015 to 20.7％in 2021,while the detection rate of methicillin-resistant coagulase-negative Staphylococcus(MRCNS)showed an upward trend year by year(57.9％-66.8％).No Staphylococcus was found to be resistant to vancomy-cin,linezolid,and teicoplanin.Among Gram-negative bacteria,constituent ratios of Escherichia coli and Klebsiella pneumoniae were 43.9％-53.9％and 14.2％-19.5％,respectively,both showing an upward trend(both P＜0.001).Constituent ratios of Pseudomonas aeruginosa and Acinetobacter baumannii were 3.6％-5.1％and 3.0％-4.5％,respectively,both showing a downward trend year by year(both P＜0.001).From 2012 to 2021,resistance rates of Escherichia coli to imipenem and ertapenem were 1.0％-2.0％and 0.6％-1.1％,respectively;presenting a downward trend(P＜0.001).The resistant rates of Klebsiella pneumoniae to meropenem and ertapenem were 7.4％-13.7％and 4.8％-6.4％,respectively,presenting a downward trend(both P＜0.001).The resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenem antibiotics were 7.1％-15.6％and 34.7％-45.7％,respectively.The trend of resistance to carbapenem antibiotics was relatively stable,but has de-creased compared with 2012-2016.The resistance rates of Escherichia coli to the third-generation cephalosporins from 2012 to 2021 were 41.0％-65.4％,showing a downward trend year by year.Conclusion The constituent ra-tio of Gram-negative bacillus from blood specimens in Hunan Province has been increasing year by year,while the detection rate of carbapenem-resistant Gram-negative bacillus remained relatively stable in the past 5 years,and the detection rate of coagulase-negative Staphylococcus has shown a downward trend.

Objective To investigate changes in the distribution and antimicrobial resistance of bacteria isolated from cerebrospinal fluid(CSF)specimens in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021 were collected according to China Antimicrobial Resistance Surveillance Sys-tem(CARSS)technical scheme.Data of bacteria isolated from CSF specimens and antimicrobial susceptibility tes-ting results were analyzed with WHONET 5.6 and SPSS 20.0 software.Results A total of 11 837 bacterial strains were isolated from CSF specimens from member units of Hunan Province Antimicrobial Resistance Surveillance Sys-tem from 2012 to 2021.The top 5 strains were coagulase-negative Staphylococcus(n=6 397,54.0％),Acineto-bacter baumannii(n=764,6.5％),Staphylococcus aureus(n=606,5.1％),Enterococcus faecium(n=465,3.9％),and Escherichia coli(n=447,3.8％).The detection rates of methicillin-resistant coagulase-negative Staphyloco-ccus(MRCNS)and methicillin-resistant Staphylococcus aureus(MRSA)were 58.9％-66.3％and 34.4％-62.1％,respectively.No Staphylococcus spp.were found to be resistant to vancomycin,linezolid,and teicoplanin.The de-tection rate of Enterococcus faecium was higher than that of Enterococcus faecalis,and the resistance rates of En-terococcus f aecium to penicillin,ampicillin,high concentration streptomycin and levofloxacin were all higher than those of Enterococcus faecalis(all P=0.001).Resistance rate of Streptococcus pneumoniae to penicillin was 85.0％,at a high level.Resistance rate of Escherichia coli to ceftriaxone was＞60％,while resistance rates to enzyme inhibitors and carbapenem antibiotics were low.Resistance rate of Klebsiella pneumoniae to ceftriaxone was＞60％,to en-zyme inhibitors piperacillin/tazobactam and cefoperazone/sulbactam was＞30％,to carbapenem imipenem and me-ropenem was about 30％.Resistance rates of Acinetobacter baumannii to most tested antimicrobial agents were＞60％,to imipenem and meropenem were 59.0％-79.4％,to polymyxin B was low.Conclusion Among the bac-teria isolated from CSF specimens,coagulase-negative Staphylococcus accounts for the largest proportion,and the overall resistance of pathogenic bacteria is relatively serious.Bacterial antimicrobial resistance surveillance is very important for the effective treatment of central nerve system infection.

Objective To investigate the distribution and antimicrobial susceptibility of clinically isolated bacteria from intensive care units(ICUs)in hospitals of Hunan Province Antimicrobial Resistance Surveillance System from 2012 to 2021.Methods According to China Antimicrobial Resistance Surveillance System,data of clinically isolated bacterial strains and antimicrobial susceptibility testing results of bacteria from ICUs reported by all member units of Hunan Province Antimicrobial Resistance Surveillance System were analyzed with WHONET 2022 software.Results From 2012 to 2021,the total number of bacteria isolated from ICUs of member units of the Hunan Province Antimi-crobial Resistance Surveillance System was 5 777-22 369,with Gram-negative bacteria accounting for 76.1％-78.0％annually.Staphylococcus aureus ranked first among isolated Gram-positive bacteria each year.The top 5 bacteria among Gram-negative bacteria were Acinetobacter baumannii,Klebsiella pneumoniae,Escherichia coli,Pseudo-monas aeruginosa,and Stenotrophomonas maltophilia.Detection rate of methicillin-resistant Staphylococcus aureus showed a downward trend year by year.No Staphylococcus spp.were found to be resistant to vancomycin,teico-planin and linezolid.Detection rates of vancomycin-resistant Enterococcus faecalis and vancomycin-resistant Entero-coccus faecium were 0.6-1.1％and 0.6％-2.2％,respectively.Resistance rates of Escherichia coli and Kleb-siella pneumoniae to imipenem were 3.1％-5.7％and 7.7％-20.9％,respectively.Resistance rates of Pseudo-monasaeruginosa and Acinetobacter baumannii to imipenem were 24.6％-40.1％and 76.1％-80.9％,respective-ly.Detection rates of carbapenem-resistant Pseudomonas aeruginosa declined year by year.Acinetobacter baumannii maintained high susceptibility to polymyxin B,with resistance rate＜10％.Conclusion Antimicrobial resistance of bacteria from ICUs is serious.Carbapenem-resistant Enterobacteriales has an upward trend after 2019.It is nece-ssary to strengthen the surveillance of bacterial resistance and carry out multidisciplinary collaboration.

Objective To understand the antimicrobial resistance of clinically isolated Enterococcus spp.in Hunan Province.Methods Surveillance data of Enterococcus spp.resistance from member units of Hunan Provincial Anti-microbial Resistance Surveillance System from 2012 to 2021 were collected.Data were cleaned according to a unified method,and WHONET 5.6 software was adopted for statistical analysis.Results From 2012 to 2021,a total of 110 652 non-repetitive Enterococcus spp.strains were included in the analysis,mainly Enterococcus faecalis and Enterococcus faecium,accounting for 46.9％(n=37 774)and 45.9％(n=36 968),respectively,followed by En-terococcus avium(2.5％,n=1 982),Enterococcus gallinarum(1.8％,n=1 428),and Enterococcus casseliflavus(1.5％,n=1 185).The main specimen sources of Enterococcus spp.was urine(51.8％,n=57 350),followed by secretions(9.6％,n=10 660)and bile(8.5％,n=9 377).From 2012 to 2021,the resistance rates of Enteroco-ccus faecalis to ampicillin,teicoplanin,and vancomycin were 5.5％-12.0％,1.3％-2.0％,and 0.6％-1.4％,respectively.The resistance rates of Enterococcus faecium to ampicillin,teicoplanin,and vancomycin were 69.2％-85.0％,1.5％-2.8％,and 0.7％-2.5％,respectively.Except for linezolid and minocycline,the resistance rates of Enterococcus faecium to tested antimicrobial agents were all higher than those of Enterococcus faecalis.The re-sistance rates of Enterococcus faecalis and Enterococcus faecium to vancomycin decreased from 1.4％and 2.1％in 2012 to 0.6％and 0.7％in 2021,respectively,presenting a decreased trend.Conclusion Clinically isolated En-terococcus spp.maintain high antimicrobial susceptibility to vancomycin and teicoplanin.Resistance rates of Entero-coccus faecalis and Enterococcus faecium to vancomycin present decreased trends.