Abstract To understand the relationship between cardiovascular disease (CVD) and adverse childhood experiences (ACEs), the present review aims to describe the burden and influencing factors of CVD, epidemiological characteristics and burden of ACEs, current research on the relationship between ACEs and CVD, and the mechanism of ACEs leading to CVD. It is proposed that further assessment of the relationship is warranted through identifying blood biomarkers, conducting prospective cohort studies and intervention studies. Such efforts would provide valuable scientific insights for primary prevention strategies for cardiovascular disease.

OBJECTIVE By conducting evidence evaluation research on literatures,this study aims to reveal the o-verall characteristics and research hotspots in the field of combat trauma-related infections,ultimately providing data support for the prevention and control of such infections.METHODS Relevant research in this field was sys-tematically collected from open-source databases to construct a dataset.The overall characteristics,research hotspots,prevention and control strategies,and future challenges of trauma-related infections were summarized and analyzed.RESULTS From 2004 to 2024,184 papers were published.The United States contributed the most publications,with Uniformed Services University of the Health Sciences being the most productive research insti-tution and Professor Clinton K.Murray as the author with the highest number of publications.The top five key-words with the highest frequency were combat related injury,infection,Acinetobacter baumannii,epidemiology and management.Among the publicly published literature data on war trauma-related infections,blast injuries ac-counted for the largest proportion,mainly multi-site injuries,with limb injuries being the most common.Bacteri-al infections were more common than fungal infections,with gram-negative bacteria being predominant and A.baumannii being the most common.Besides early wound management and the use of antibacterial drugs,in-creased attention should be paid to infection prevention and control in austere environments and the development of novel countermeasures.These advancements are critical to address projected changes in combat trauma,inclu-ding increasingly complex injuries and substantially elevated risks of infection and antimicrobial resistance.CONCLUSION This study systematically presents research hotspots,developmental trends,and prospects in com-bat trauma-related infections through evidence evaluation study,providing novel perspectives for researchers and facilitating further development in this field.

Cancer is a major chronic disease that threatens human health, while traditional Chinese medicine (TCM) is a unique method for cancer prevention and treatment in China. After about 70 years of innovation and development, TCM has made constant progress in areas such as the clinical diagnosis, treatment, evidence-based researches, and mechanism exploration of cancer. It has special advantages in aspects such as reducing toxicity, enhancing treatment efficacy, managing symptoms, accelerating recovery, preventing recurrence and metastasis, and prolonging advanced-stage survival. However, there are still bottlenecks for TCM in cancer care. This paper cuts in the key links between TCM and western medicine in their combined application in cancer prevention and treatment, and take the original TCM theories on cancer as the lead, high-quality evidence-based researches as the drive, and analysis on the dynamic mechanism as the core, to show the advantages and effects of TCM in cancer treatment in an all-round way. It also aims to provide novel strategies for sustainable and innovative development and for formulation of comprehensive schemes that integrate TCM and western medicine for cancer prevention and treatment.

Tigecycline(TGC)is a recently developed broad-spectrum and highly effective glycylcy-cline antibiotic that overcomes traditional tetracycline resistance mechanisms.It is widely used in the treatment of complex skin and intra-abdominal infections.However,the emergence of TGC re-sistance in recent years poses a significant challenge,and its underlying resistance mechanisms re-main incompletely understood,warranting further investigation.This study induced TGC resistance in Klebsiella aerogenes(ATCC-43864)under in vitro conditions and evaluated phenotypic chan-ges,including growth curves,motility,multidrug susceptibility,and ultrastructural alterations,be-fore and after induction.Whole-genome sequencing(WGS)and transcriptome sequencing(RNA-seq)were employed to analyze resistance-related genetic changes,which were further validated.Ef-flux pump inhibition assays and Red homologous recombination were used to investigate the roles of efflux pumps,lon deletion,and rpsM mutation in TGC resistance.A stable resistant strain,CF-T-32,was obtained,with a 32-fold increase in TGC minimum inhibitory concentration(MIC).CF-T-32 exhibited an enlarged periplasmic space between the cell wall and membrane,reduced growth and motility,and no significant changes in susceptibility to 28 antimicrobial agents,including doxy-cycline,gentamicin,and ciprofloxacin.Genomic analysis revealed no significant differences in ge-nome composition or interference from exogenous plasmids between the parental and induced strains.However,two missense mutations were identified in rpsM and lon.Transcriptomic analysis and qPCR validation showed significant upregulation of efflux pump genes(acrA and acrB)in the AcrAB-TolC system and downregulation of ribosomal protein genes(rpsM,rpsJ,and rpsC).Ef-flux pump inhibition and Red homologous recombination experiments demonstrated that the rpsM C287T missense mutation,leading to a Pro96Leu substitution and reduced expression,is likely the primary factor contributing to TGC resistance in the induced strain.

Objective:To understand the potential characteristics of decision-making preparation in outpatient hypertensive patients based on latent profile analysis, to identify the influencing factors of different categories of decision-making preparation levels, and to explore the performance of different decision-making preparation types in facilitation of patients involvement in treatment decision-making.Methods:Through a cross-sectional study, 350 hypertensive patients attending outpatient clinics in five different types of healthcare institutions (general hospitals, specialised hospitals and community hospitals) in Tianjin during January to May 2024 who met the inclusion and exclusion criteria were selected by the convenience sampling method as study subjects. General Information Questionnaires, Preparation for Decision Making Scale, and Facilitation of Patient Involvement Scale were used for investigation.Results:Totally 350 valid questionnaires [178 males and 172 females aged 25-89(57.24 ± 13.39)years old] were collected. The decision-making preparation score of outpatient hypertensive patients was (64.19 ± 18.69). The latent profile analysis results showed that the decision-making preparation of outpatient hypertensive patients could be divided into three potential categories: decision-making information scarcity type accounted for 20.0%(70/350), decision-making balance negotiation type accounted for 39.7%(139/350), and decision-making preparation adequacy type accounted for 40.3%(141/350). The results of multiple Logistic regression analysis showed that age, medical insurance type, occupation, and children′s condition were the influencing factors for the potential categories of decision-making preparation in outpatient hypertensive patients (all P<0.05). Age [less than 35 years old: OR(95% CI)=0.127(0.020-0.796)], occupation [on the job: OR(95% CI)=2.010 (1.034-3.906)], were the influencing factors of decision-making balance negotiation group (all P<0.05). Medical insurance type [basic medical insurance for urban employees: OR(95% CI)=0.372(0.193-0.720)], occupation [on the job: OR(95% CI)=2.500(1.270-4.920)], children′s condition[junior and senior high school: OR(95% CI)=0.391(0.190-0.802)] were the influencing factors of decision-making preparation adequacy group (all P<0.05). Conclusions:The level of promoting patient participation among outpatients with hypertension is relatively high, and there are differences in the perceived degree of promoting patient participation among patients with different types of decision preparation.It is recommended that medical staff provide decision-making related information based on the characteristics of different decision-making preparation categories of patients, encourage patients to actively participate in decision-making, and construct targeted decision support plans.

Objective : To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN). Methods : Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays. Results : Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01). Conclusion Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.

Objective : To investigate the therapeutic effects and underlying mechanisms of cannabidiol(CBD) and its nano-formulations on depression-like behaviors in mice. Methods : A murine model of acute anxiety and depression was established by intraperitoneal administration of lipopolysaccharide(LPS). A total of 55 mice were randomly assigned into several groups: for the long-term study, a control group(Con), a model group(LPS), a cannabidiol group(CBD), a nano-cannabidiol group(NCBD), and a sertraline(SER) group, each consisting of 7 mice. In the short-term study, mice were divided into four groups: the Con group, LPS group, CBD group, and NCBD group, with 5 mice in each group. Except for the Con group and LPS group, which were given distilled water, the remaining groups were administered 25 and 50 mg/kg of cannabidiol and its nano-formulationviaoral gavage. The open field and forced swimming tests were employed to assess anxiety-and depression-like behaviors inmice. Luxol Fast Blue myelin staining was employed to evaluate myelin sheath morphology in the prefrontal cortex, and immunofluorescence staining was utilized to quantify the protein expression levels of silencing information regulator(SIRT2), ionized calcium binding adaptor molecule-1(Iba-1), and interleukin-1β(IL-1β) in the prefrontal cortex. Results : In the long-term experiment, the LPS group exhibited a significant reduction in shuttle times(P<0.05), an increase in immobility time(P<0.01), and a decrease in the number and length of myelin sheaths(P<0.05) compared to the Con group. Compared to the LPS group, the depressive behaviors in the CBD, NCBD, and SER groups were significantly alleviated(P<0.01), and the number and length of myelin sheaths increased(P<0.05). In the short-term experiment, compared to the Con group, the LPS group exhibited significantly increased anxiety-and depression-like behaviors(P<0.05), downregulated SIRT2 expression(P<0.01), and upregulated Iba-1 and IL-1β expression(P<0.01). The CBD and NCBD groups demonstrated a reduction in anxiety and depression-like behaviors(P<0.05), an increase in SIRT2 expression(P<0.01), and a decrease in Iba-1 and IL-1β expressions(P<0.05) compared to the LPS group. Conclusion CBD and its nano-formulations effectively mitigate anxiety and depression-like behaviors in mice. The underlying mechanisms may be associated with the reversal of SIRT2 protein expression, demyelination changes, microglial activation, and the levels of inflammatory factors in the prefrontal cortex.

Objective To investigate the predictive ability of cyst fluid characteristics for malignant intraductal papillary mucinous neoplasms (IPMNs). Methods We prospectively collected fresh cyst fluid from patients undergoing pancreatic resection at the Department of Hepatobiliary Pancreatic Spleen Surgery, Changhai Hospital, Shanghai, from September 2023 to December 2024, who were ultimately pathologically confirmed with IPMN. We assessed the characteristics of cyst fluid, including viscosity, clarity, and color, and explored its predictive performance for benign or malignant. Results A total of 40 patients with IPMN were included. The sensitivity of the string sign （+） for diagnosing high-grade dysplasia/ invasive carcinoma （HGD/IC） was 90.9%, specificity was 92.9%, and accuracy was 76.0%. The cyst fluid of intestinal-type IPMN often exhibited a gelatinous consistency, and there was no significant difference in the distribution of gelatinous consistency between the HGD/IC group and the low-grade dysplasia （LGD） group. There were no significant differences in CEA, glucose, and amylase levels in the cyst fluid between the HGD/IC group and the LGD group. Conclusions The characteristics of pancreatic cyst fluid, especially viscosity, can effectively predict the benign or malignant nature of IPMN.

Tigecycline(TGC)is a recently developed broad-spectrum and highly effective glycylcy-cline antibiotic that overcomes traditional tetracycline resistance mechanisms.It is widely used in the treatment of complex skin and intra-abdominal infections.However,the emergence of TGC re-sistance in recent years poses a significant challenge,and its underlying resistance mechanisms re-main incompletely understood,warranting further investigation.This study induced TGC resistance in Klebsiella aerogenes(ATCC-43864)under in vitro conditions and evaluated phenotypic chan-ges,including growth curves,motility,multidrug susceptibility,and ultrastructural alterations,be-fore and after induction.Whole-genome sequencing(WGS)and transcriptome sequencing(RNA-seq)were employed to analyze resistance-related genetic changes,which were further validated.Ef-flux pump inhibition assays and Red homologous recombination were used to investigate the roles of efflux pumps,lon deletion,and rpsM mutation in TGC resistance.A stable resistant strain,CF-T-32,was obtained,with a 32-fold increase in TGC minimum inhibitory concentration(MIC).CF-T-32 exhibited an enlarged periplasmic space between the cell wall and membrane,reduced growth and motility,and no significant changes in susceptibility to 28 antimicrobial agents,including doxy-cycline,gentamicin,and ciprofloxacin.Genomic analysis revealed no significant differences in ge-nome composition or interference from exogenous plasmids between the parental and induced strains.However,two missense mutations were identified in rpsM and lon.Transcriptomic analysis and qPCR validation showed significant upregulation of efflux pump genes(acrA and acrB)in the AcrAB-TolC system and downregulation of ribosomal protein genes(rpsM,rpsJ,and rpsC).Ef-flux pump inhibition and Red homologous recombination experiments demonstrated that the rpsM C287T missense mutation,leading to a Pro96Leu substitution and reduced expression,is likely the primary factor contributing to TGC resistance in the induced strain.

OBJECTIVE To optimize the water extraction technology for Kaixin granules. METHODS UPLC-MS/MS method was established for the simultaneous determination of ginsenoside Rg1， ginsenoside Re， ginsenoside Rb1， tenuifolin， polygalaxanthone Ⅲ and 3， 6′-disinapoyl-sucrose. An orthogonal test was designed with extraction times， extraction duration， and the volume of added water as factors. Using the contents of the aforementioned six indicator components and the extract yield as evaluation indexes， analytic hierarchy process-entropy weight method was employed to determine the combined weights of each indicator. Subsequently， process optimization and validation were conducted by integrating grey relational analysis （GRA） and back propagation （BP） neural network. RESULTS The water extraction technology optimized by the orthogonal test and GRA was 10- fold water for the first decoction and 8-fold water for the subsequent two， extracting 3 times，extracting for 1 h each time； the average comprehensive score of the validation experiment was 91.10 （RSD＝0.31%， n＝3）. The water extraction technology optimized by BP neural network was extracting 3 times with 10-fold water added each time， extracting for 1.5 h each time； the average comprehensive score of the validation experiment was 95.89 （RSD＝0.73%， n＝3）. Considering practical production requirements， the optimal water extraction technology was extraction performed three times， with 10-fold water for the first decoction and 8-fold water for the subsequent two extractions， with an extraction time of 1 h each. CONCLUSIONS The optimized water extraction technology for Kaixin granules is stable and feasible.