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.

ObjectiveTo investigate the impact of preoperative frailty on the prognosis of patients with pancreatic cancer who underwent pancreaticoduodenectomy. MethodsA retrospective analysis was conducted on the clinical data of 435 pancreatic cancer patients who underwent pancreaticoduodenectomy at Sun Yat-sen Memorial Hospital of Sun Yat-sen University. Preoperative frailty was assessed using the FRAIL questionnaire. Binary logistics regression analysis was employed to identify factors influencing frailty， and Cox regression analysis was used to evaluate the effect of frailty on survival. According to the demographic characteristics， subgroup analyses were performed on the effect of frailty on prognosis of patients with pancreatic cancer with pancreaticoduodenectomy. ResultsAmong the 435 patients enrolled， 119 （27.4%） exhibited frailty， while 316 （72.6%） did not. Significant differences were observed between the two groups in various clinical parameters， including age， body mass index， American Society of Anesthesiologists （ASA） score， postoperative red blood cell transfusion， postoperative abdominal abscess， serum levels of glycoantigens 199， glycoantigens 125， and alpha fetoprotein， leukocyte count， neutrophil， high density lipoprotein （HDL） level， and pain intensity （P＜0.05）. Advanced age and an ASA score of Ⅲ were identified as risk factors for frailty， whereas HDL level was a protective factor. Non-frail patients had better postoperative survival times than frail patients. HDL was determined to be an independent protective factor for prognosis， while LDL was an independent risk factor. ConclusionsThis study demonstrates that preoperative frailty is a significant predictor of poor prognosis in pancreatic cancer patients who underwent pancreaticoduodenectomy.These findings suggest that preoperative frailty assessment and targeted interventions to improve nutritional and metabolic status could potentially enhance postoperative survival and quality of life in pancreatic cancer patients.

Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was 0.9341, MIOU was 0.8762, and mean HD95 was 2.516. The mean time of manual segmentation was 1187 s, and the mean time of AI segmentation was 145 s (P < 0.01). The mean time of manual modeling was 321 s, and the mean time of modeling with Python automated scripts was 18 s (P < 0.01). Conclusion The application of Transformer + U-Net automatic segmentation and Python automated scripts can effectively improve work efficiency in the 3D printing brachytherapy for cervical cancer.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg^-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg^-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg^-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

Objective     To construct a radiomics model for identifying clinical high-risk carotid plaques. Methods     A retrospective analysis was conducted on patients with carotid artery stenosis in China-Japan Friendship Hospital from December 2016 to June 2022. The patients were classified as a clinical high-risk carotid plaque group and a clinical low-risk carotid plaque group according to the occurrence of stroke, transient ischemic attack and other cerebrovascular clinical symptoms within six months. Six machine learning models including eXtreme Gradient Boosting, support vector machine, Gaussian Naive Bayesian, logical regression, K-nearest neighbors and artificial neural network were established. We also constructed a joint predictive model combined with logistic regression analysis of clinical risk factors. Results    Finally 652 patients were collected, including 427 males and 225 females, with an average age of 68.2 years. The results showed that the prediction ability of eXtreme Gradient Boosting was the best among the six machine learning models, and the area under the curve (AUC) in validation dataset was 0.751. At the same time, the AUC of eXtreme Gradient Boosting joint prediction model established by clinical data and carotid artery imaging data validation dataset was 0.823. Conclusion     Radiomics features combined with clinical feature model can effectively identify clinical high-risk carotid plaques.

【Objective】 To comprehensively explore the serological characteristics of anti-PP1P^k and potential therapeutic strategies for recurrent miscarriage in p-blood type pregnant women. 【Methods】 Neutralization with pigeon egg white and human plasma, disruption of IgM antibodies by 2-mercaptoethanol reagent, and complement adding were conducted. Anti-PP1P^k titers under different processing conditions, media and temperatures were determined, and neutralizing effect of human plasma on anti-PP1P^k and its sensitization complement ability were analyzed. 【Results】 The titers of anti-PP1P^k in saline and column agglutination were 4 and 8, respectively. Low temperature increased titers, while β-mercaptoethanol treatment significantly reduced them. Pigeon egg white partially neutralized anti-PP1P^k antibodies. Human plasma was also capable of reducing anti-PP1P^k titers with neutralization capability surpassing that of pigeon egg white, and there were individual differences in neutralization capability. 【Conclusion】 The anti-PP1P^k was a blend of antibodies encompassing both IgM and IgG types, exhibiting cold reactivity, and having the potential for complement activation. Human plasma emerges as an effective modulator for diminishing the efficacy of anti-PP1P^k. Plasma transfusion holds promise as a therapeutic avenue for addressing recurrent miscarriages in pregnant individuals with the p phenotype.

Objective : To examine the causal relationship between ulcerative colitis (UC) and pancreatitis, to provide basis for early screening of pancreatitis among UC patients. Methods: Genomic data of UC were obtained from 47 745 European individuals pooled by the International Inflammatory Bowel Disease Genetics Consortium, including 156 116 single nucleotide polymorphism (SNP), and genomic data of pancreatitis were obtained from 198 166 European individuals pooled from FinnGen, including 16 380 428 SNPs. Mendelian randomization (MR) analysis was performed using the inverse variance weighted (IVW) method with 72 UC-associated SNPs as instrumental variables and pancreatitis as the study outcome. The heterogeneity was assessed using Cochran Q test, the horizontal pleiotropy was assessed using MR-Egger regression, MR-PRESSO was performed with the exclusion of outliers, and effect of individual SNP on the results was tested with the leave-one-out method. Results: MR analysis results showed that patients with genetically predicted UC had an increased risk of pancreatitis relative to those without UC (OR=1.076, 95%CI: 1.019-1.136, P<0.05). Cochran Q test showed no heterogeneity (P>0.05), and MR-Egger regression did not reveal horizontal pleiotropy of instrumental variables (P>0.05). The MR analysis results were robust after removing SNP one by one. Conclusions Genetically predicted UC is associated with an increased risk of pancreatitis. The screening for pancreatitis risk should be enhanced in patients with UC.

ObjectiveTo study the bioactive secondary metabolites of Talaromyces sp. TP21 and their bioactivities. MethodThe secondary metabolites of Talaromyces sp. TP21 were isolated by high performance liquid chromatography （HPLC）， normal phase and reversed phase column chromatography combined with molecular networking and bioassay-guided fractionation， and their structures were determined by nuclear magnetic resonance （NMR） and high resolution mass spectrometry （HR MS）. The inhibitory effects of the compounds on the growth of the lung cancer cell line A549 and the liver cancer cell line Hep G2 were measured by themethyl thiazolyl tetrazolium （MTT） method. The antimicrobial activities of the compounds were measured with Staphylococcus aureus and human oral cavity-derived Saccharomyces cerevisiae as the indicator microorganisms. ResultSeventeen compounds were isolated from the secondary metabolites of Talaromyces sp. TP21 and identified as ergochrome C （1）， daldiniaeschsone A （2）， seco-blennolide B （3）， penitholabene （4）， penicichrysogene A （5）， orsellinic acid （6）， griseofulvin （7）， isorhodoptilometrin （8）， （+）-5-chloromitorubrinic acid （9）， penicillixanthone A （10）， pentacecilide B （11）， pentacecilide C （12）， chrodrimanin C （13）， chrodrimanin E （14）， chrodrimanin H （15）， chrodrimanin F （16）， and 3-hydroxypentacecilide A （17）. ConclusionCompounds 1-5， 11-12， and 17 were isolated from Talaromyces for the first time. Among them， compounds 4， 7， and 10-12 exhibited inhibitory activities against the growth of A549 and Hep G2 cells， with the median inhibitory concentration below 50 μmol·L^-1. Furthermore， compounds 9 and 10 showed inhibitory activities against S. aureus and human oral cavity-derived S. cerevisiae， with the minimum inhibitory concentration of 8-128 mg·L^-1.

Objective:To summarize the thinking and compatibility law of TCM in the treatment of stable angina pectoris (SAP) based on syndrome differentiation using data mining technology.Methods:The clinical studies of TCM treatment for SAP in databases of CNKI, Wanfang Data, VIP and SinoMed China Biomedical Literature Service System were retrieved from the establishment of the databases to February 28, 2022. The frequency statistic, clustering analysis and association rule analysis of TCM data were conducted using Clementine 12.0, Excel 2016, SPSS Statistics 22.0 software, and core prescriptions were summarized.Results:Totally 289 prescriptions were included, involving 185 kinds of Chinese materia medica, including 38 TCM syndrome types. Based on the overall study of SAP "disease", the clinical treatment of SAP was mainly based on the drugs for activating blood circulation and removing blood stasis, tonifying deficiency and strengthening healthy qi, and regulating qi and resolving phlegm. The single Chinese materia medica with high frequency of use were Chuanxiaong Rhizoma, Salviea Miltiorrhizae Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Angelicae Sinensis Radix, etc. The commonly used drug pairs included Chuanxiaong Rhizoma-Angelicae Sinensis Radix, Chuanxiaong Rhizoma-Carthami Flos, Chuanxiaong Rhizoma-Aurantii Fructus Immaturus, etc. The drug complex network diagram and clustering analysis showed that the prescription of Buyang Huanwu Decoction was the basic prescription for the treatment of SAP; based on the specific research of SAP "syndrome", the most common TCM syndromes of SAP were qi deficiency and blood stasis, phlegm and blood stasis, and qi stagnation and blood stasis. The drug properties of the three drugs were mainly warm and mild; the tastes were mainly sweet, pungent and bitter, and most of them belong to the liver, spleen, lung and heart meridian; in terms of specific medication, the basic prescription of qi deficiency and blood stasis syndrome was Buyang Huanwu Decoction, which was composed of high-frequency drugs such as Angelicae Sinensis Radix, Chuanxiaong Rhizoma, Salviea Miltiorrhizae Radix et Rhizoma, etc; The phlegm and blood stasis syndrome was often based on the Gualou Xiebai Banxia Decoction and Taohong Siwu Decoction, which were composed of high frequency drugs such as Pinelliae Rhizoma, Chuanxiaong Rhizoma, Allii Macrostemonis Bulbus, etc; the basic prescription of qi stagnation and blood stasis syndrome was Xuefu Zhuyu Decoction, which was composed of high frequency drugs such as Chuanxiaong Rhizoma, Angelicae Sinensis Radix, Aurantii Fructus. Drug clustering analysis showed that both qi deficiency and blood stasis syndrome and qi stagnation and blood stasis syndrome were divided into 3 categories, and phlegm and blood stasis syndrome were divided into 4 categories.Conclusions:Deficiency, blood stasis, phlegm and stagnation are important pathological factors of SAP, in which qi deficiency is the basis of SAP, blood stasis runs through the disease, or both phlegm and qi stagnation. Focusing on the pathogenesis of deficiency in root and excess in superficiality, drugs with the efficacy of tonifying the deficiency and promoting blood circulation and removing blood stasis are used in clinical treatment, according to different syndrome differentiation of prescription selection.