To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

Background::Acute pulmonary embolism (APE) is a fatal cardiovascular disease, yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs. A simple, objective technique will help clinicians make a quick and precise diagnosis. In population studies, machine learning (ML) plays a critical role in characterizing cardiovascular risks, predicting outcomes, and identifying biomarkers. This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods::This is a single-center retrospective study. Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets. A total of 8 ML models, including random forest (RF), Na?ve Bayes, decision tree, K-nearest neighbors, logistic regression, multi-layer perceptron, support vector machine, and gradient boosting decision tree were developed based on the training set to diagnose APE. Thereafter, the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies, including the Wells score, revised Geneva score, and Years algorithm. Eventually, the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic (ROC) analysis.Results::The ML models were constructed using eight clinical features, including D-dimer, cardiac troponin T (cTNT), arterial oxygen saturation, heart rate, chest pain, lower limb pain, hemoptysis, and chronic heart failure. Among eight ML models, the RF model achieved the best performance with the highest area under the curve (AUC) (AUC = 0.774). Compared to the current clinical assessment strategies, the RF model outperformed the Wells score ( P = 0.030) and was not inferior to any other clinical probability assessment strategy. The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726. Conclusions::Based on RF algorithm, a novel prediction model was finally constructed for APE diagnosis. When compared to the current clinical assessment strategies, the RF model achieved better diagnostic efficacy and accuracy. Therefore, the ML algorithm can be a useful tool in assisting with the diagnosis of APE.

Quercetin (Que) is a flavonoid compound widely distributed in nature with various biological activities.Its anti-inflammatory effect plays a crucial role in many diseases,closely related to its regula-tion of histone post-translational modifications.However,there have been no detailed reports on the anti-inflammatory effects of quercetin regulating histone post-translational modifications.In this study,we first investigated the effect of quercetin on the M1 macrophages polarization.The results showed that quercetin can significantly down-regulate the levels of interleukin-1β(IL-1β) and interleukin-6 (IL-6 ) in M1 macrophages.Next,we used the super stable isotope labeling by amino acids in cell culture (super-SI-LAC) method derived from SILAC technology based on mass spectrometry to systematically analyze the post-translational modification levels of histone in macrophages treated with quercetin.A total of 30 his-tone modification sites were quantified,of which 12 histone lysine acetylation marks were significantly downregulated and 4 lysine methylation sites were upregulated (fold change>1.2,P<0.05),and some sites were verified by Western blot (WB),which was consistent with the mass spectrometry results.In conclusion,a comprehensive analysis of quercetin on regulating macrophage histone modifications in this study provides reliable data references and new insights for studying its anti-inflammatory mechanism.

In mass spectrometry-based proteomics experiments,achieving high-throughput and efficientproteolytic digestion is crucial to ensure optimal protein cleavage and enhance the depth of protein identi-fication (including the number of identified proteins and the coverage of protein amino acid sequences) .Trypsin is the most widely used protease in mass spectrometry-based proteomics due to its ability to spe-cifically cleave the carboxyl terminus of arginine and lysine.However,it was found that Trypsin has some missed enzymatic efficiency for the cleavage of lysine residues.Therefore,in actual proteomics sample preparation,a combination of Trypsin and LysC will be used to ensure adequate cleavage of lysine resi-dues.Our study revealed that the commonly employed LysC-Trypsin tandem cleavage method exerts an impact on the enzymatic cleavage of protein samples by Trypsin due to the subsequent cleavage of Trypsin by initially added LysC.Consequently,we adjusted the order of LysC and Trypsin tandem digestion,with Trypsin cleavage being performed first followed by the addition of LysC to target any missed lysine resi-dues.We comprehensively compared and analyzed three distinct sequential digestion methods,namely Trypsin-Trypsin (T-T),LysC-Trypsin (L-T),and Trypsin-LysC (T-L),in terms of their effects on pro-tein sample preparation quality.The results demonstrated that the Trypsin-LysC sequential digestion ap-proach not only minimizes missed protein lysine/arginine cleavage sites without increasing experimental costs,at the same time yielding peptides with a moderate amino acid sequence length.The use of Tryp-sin-LysC digestion enhances the adsorption and separation of peptide samples in RP-HPLC,as well as improves the depth of protein detection and amino acid sequence coverage during tandem mass spectrome-try analysis.This research work offers a novel technical solution and serves as a valuable reference for proteome sample preparation.

Objective:To explore the changes in number and immune function of mucosal-associated invariant T (MAIT) cells in peripheral blood of patients with newly diagnosed acute myeloid leukemia (AML),and its correlation with the occurrence and development of AML. Methods:Seventy-five clinical samples of patients with newly diagnosed AML and 48 healthy control samples in our hospital from January 2022 to February 2023 were included. Multiparametric flow cytometry was used to detect the number of MAIT cells,membrane surface markers,effector phenotypes and functional indicators in the samples. Results:Compared with healthy controls,the percentage of MAIT cells in CD3+T cells in peripheral blood of newly diagnosed AML patients was significantly reduced (P<0.001). The percentage of MAIT cells in all CD3+T cells in bone marrow of AML patients was similar to that in peripheral blood (P>0.05). Most of MAIT cells in peripheral blood of AML patients were effector memory T cells. Compared with healthy controls,the proportion of effector memory MAIT cells decreased (P<0.05),while the proportion of terminally differentiated effector memory MAIT cells and PD-1+MAIT cells increased significantly (both P<0.05). AML patients' peripheral blood MAIT cells expressed significantly higher levels of granzyme B and perforin than healthy controls (both P<0.05),and secreted significantly lower levels of cytokines such as gamma interferon and tumor necrosis factor α than healthy controls (both P<0.001). Conclusion:Compared with healthy controls,the proportion of MAIT cells in AML patients is reduced and the expression of functional markers is abnormal,suggesting that their function is impaired and may be involved in the occurrence and development of AML.

Objective:To identify the risk factors for intraoperative hemorrhage and transfusion in patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods:A total of 1, 442 patients, regardless of gender, of American Society of Anesthesiologists Physical Status classification≥Ⅱ, scheduled for elective OPCABG from June 7, 2021 to March 8, 2023, were enrolled in a prospective, observational study. Patients′ general characteristics, preoperative hemodynamics, preoperative blood routine, duration of operation, the number of transplanted vessels, intraoperative application of vasoactive agents, intraoperative consumption of crystalloid and colloid, urine volume, blood products, use of tranatemic acid and ulinastatin were collected. Univariable and multiple linear regression models were used to screen the risk factors for intraoperative blood loss and infusion volume of concentrated red blood cell (CRBC), and univariable and multivariable logistic regression models were used to screen the risk factors for intraoperative CRBC infusion requirement.Results:One thousand four hundred and twenty patients were finally included. Prolonged operation duration, increased number of transplanted vessels and older age were risk factors for intraoperative blood loss, while male, increased intraoperative usage of fresh frozen plasma (FFP), increased urine volume, and application of ulinastatin and tranexamic acid were protective factors for intraoperative blood loss in OPCABG patients ( P<0.05). Prolonged operation duration and increased intraoperative usage of FFP were risk factors for intraoperative CRBC transfusion volume, while elevation of preoperative hemoglobin levels was a protective factor for intraoperative CRBC transfusion volume in OPCABG patients ( P<0.05). Prolonged operation duration and increased intraoperative usage of FFP were risk factors for intraoperative CRBC infusion requirement, while increased body mass index, elevation of preoperative hemoglobin levels and application of ulinastatin were protective factors for CRBC infusion requirement ( P<0.05). Conclusions:Prolonged operation duration, increased number of transplanted vessels and older age are risk factors for intraoperative blood loss, and increased intraoperative usage of FFP, increased urine volume, and application of ulinastatin and tranexamic acid are protective factors for intraoperative blood loss in OPCABG patients. Prolonged operation duration and increased intraoperative usage of FFP are risk factors for intraoperative CRBC infusion requirement and transfusion volume, elevation of preoperative hemoglobin levels is a protective factor for intraoperative CRBC infusion volume, and increased body mass index, elevation of preoperative hemoglobin levels and intraoperative application of ulinastatin are protective factors for intraoperative CRBC infusion requirement in patients undergoing OPCABG.

Objective To explore the mechanism of Zhuangxuan Yin in the treatment of children with H1N1 pneumonia through regulating gut microbiota mediated by p38 mitogen-activated protein kinase(p38-MAPK)pathway.Methods A BALB/c mouse model of H1N1 pneumonia was prepared using the H1N1 influenza virus allantoic solution for nasal drop.The model was randomly separated into 5 groups:model group,Zhuangxuan Yin low-,medium-and high-dose groups,and high-dose Zhuangxuan Yin(28.66 g·kg-1)+anisomycin(10 mg·kg-1)group.The control group was infused with sterile physiological saline of equal volume using the same method.After treatment with Zhuangxuan Yin and anisomycin,the lung index of mice in each group was measured,and HE staining was applied to detect the pathological morphology of lung and large intestine tissues.16SrRNA gene sequencing was applied to detect the structural difference of gut microbiota in mice of each group.Enzyme-linked immunosorbent assay(ELASA)was applied to measure the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-4,IL-6,and IL-1β in bronchoalveolar lavage fluid(BALF)and large intestine tissue of mice in each group.Western Blot was applied to detect the expression of p38-MAPK pathway-related proteins in lung and large intestine tissues of mice in each group.Results Compared with the control group,the lung and large intestine tissues of the model group mice showed obvious pathological damage,the lung index,pathological score of lung and large intestine,ACE index,Shannon index,abundance of class Clostridia,the levels of TNF-α,IL-4,IL-6,and IL-1β in BALF and large intestine tissues,and p-p38-MAPK/p38-MAPK in lung and large intestine tissues increased(P＜0.05).The abundance of class Bacteroidales decreased(P＜0.05).Compared with the model group,the pathological damage in the lung and large intestine tissues of mice in the Zhuangxuan Yin low-,medium-and high-dose groups were reduced.The lung index,pathological score of lung and large intestine,ACE index,Shannon index,abundance of class Clostridia,the levels of TNF-α,IL-4,IL-6,and IL-1β in BALF and large intestine tissues,and p-p38-MAPK/p38-MAPK in lung and large intestine tissues decreased(P＜0.05),the abundance of class Bacteroidales increased(P＜0.05),and in a dose-dependent manner(P＜0.05).Compared with the high-dose Zhuangxuan Yin group,the pathological damage in the lung and large intestine tissues of mice in the high-dose Zhuangxuan Yin+anisomycin group was aggravated,the lung index,pathological score of lung and large intestine,ACE index,Shannon index,abundance of class Clostridia,the levels of TNF-α,IL-4,IL-6,and IL-1β in BALF and large intestine tissues,and p-p38-MAPK/p38-MAPK in lung and large intestine tissues increased(P＜0.05),and the abundance of class Bacteroidales decreased(P＜0.05).Conclusion Zhuangxuan Yin can improve the imbalance of intestinal microbiota in H1N1 pneumonia mice by inhibiting p38-MAPK signal activation,thereby inhibiting inflammation and reducing lung and large intestine tissue damage in mice,which may have a therapeutic effect on children with H1N1 pneumonia.

Objective To understand the epidemiological and clinical characteristics of healthcare-associated infec-tion(HAI)in neonates with different gestational ages and birth weights,and provide guidance for personalized cli-nical diagnosis and treatment.Methods According to the inclusion and exclusion criteria,240 neonates with HAI in the neonatal intensive care unit(NICU)of a hospital in Handan City from January 2018 to December 2022 were selected as the study group,720 neonates without HAI were selected as the control group based on systematic sam-pling method with a ratio of 1∶3.The incidence of HAI,distribution characteristics of infection site,pathogenic features of HAI,as well as the effect of different delivery modes on HAI in neonates with different gestational ages and birth weights were analyzed.Results Neonates with gestational age＜28 weeks and birth weight＜1 000 g had the highest incidence of HAI,which were 19.48％and 20.41％,respectively.Among neonates with gestational age＜28 weeks,unidentified site infection were the most(37.50％),while in all gestational age groups within 28-36+6 weeks,bloodstream infection(BSI)and respiratory system infection were predominant.For neonates with gestational age ≥37 weeks,BSI and unidentified site infection occurred frequently.Among neonates in all weight groups,BSI was the most frequent,followed by respiratory system infection.Pathogens from different sites of in-fections in neonates with different gestational ages and birth weights varied.Among neonates with gestational age of 28-31+6 weeks and birth weight of 1 000-1 499 g,the constituent of birth modes showed statistically significant difference between neonates with and without HAI(both P＜0.05).Conclusion Epidemiological and clinical chara-cteristics of HAI in neonates with different gestational ages and birth weights are different.For the prevention and control of HAI,individualized diagnosis and treatment plans should be developed to achieve precise prevention and control,reduce the incidence of HAI,and improve the overall treatment level of neonates.

Objective To investigate the expression of lymphoid enhancer binding factor 1(LEF1)in B cell chronic lymphoproliferative disorders(B-CLPD)and estimate its value in the differential diagnosis of the subtype of B-CLPD.Methods A retrospective study was conducted on 58 patients diagnosed with B-CLPD by using bone marrow biopsy samples or lymphnode biopsy samples from Hematology Department of The Second People′s Hospital of Wuhu from September 2018 to June 2023,as well as 20 bone marrow biopsy samples which were diagnosis as non-hematologic malignancy in the control group.Immunohistochemical method was used to detect the expression of LEF1 in 78 samples,and statistical analysis was conducted.Results In all 78 cases,16 of 20 chronic lymphocytic leukemia(CLL)patients were LEF1 positive,the positive rate was 80%;mantle cell lymphoma 1/12;Follicular lymphoma 1/5;marginal zone cell lymphoma 0/11;Lymphoplasmacyticlymphom 0/8;hairy cell leukemia 0/2;in Control group no patient was LEF1 positive(P = 0.000).The expression of LEF1 is correlated with CD200 and CLL score(P<0.05).In the LEF1 negative group with 4 CLL patients,2 were detected with +12 chromosomal abnormality,the detective rate was higher than that of the LEF1 positive group(P>0.05).Conclusion LEF1 was a sensitive and specific diagnosis marker in CLL and B-CLPD subtype.

Objective To understand the spectrum and changes of pathogens causing healthcare-associated infec-tion(HAI)in neonatal intensive care unit(NICU).Methods Clinical medical records of neonates with HAI in a hospital from January 2018 to December 2022 were collected,spectrum of pathogens causing HAI were and analyzed retrospectively.Results A total of 7 597 hospitalized neonates were investigated,and 240 of whom had 263 cases of HAI,with an HAI incidence of 3.16％and healthcare-associated case infection incidence of 3.46％.96 cases(36.50％)were bloodstream infection,70(26.62％)were respiratory system infection,and 57(21.67％)were in-fection without clear sites.A total of 170 pathogens were detected from specimens,78(45.88％)of which were Gram-positive bacteria,with Staphylococcus spp.accounting for the highest proportion,78(45.88％)were Gram-negative bacteria,mainly Klebsiella pneumoniae,and 14(8.24％)were fungi.The detection rate of Gram-negative bacteria showed an upward trend from 2018 to 2022(P＜0.01).Conclusion The majority of HAI in NICU is bloodstream infection.In recent years,the detection rate of Gram-negative bacteria has been increasing year by year,and it is necessary to streng-then the prevention and control of HAI in clinical practice.