Objective To construct a machine learning algorithm using biomarkers to predict the risk of sepsis-induced respiratory tract infection in order to assist clinicians in making decisions.Methods Based on the diagnostic criteria of the research subjects,and the basic clinical data of the participants were collected.The data set was randomly split into a training set(80％)and a validation set(20％).Use feature filtering algorithms to select the best subset of variables from the training set,and use this subset to construct random forest(RF),extreme gradient boosting(XGBoost),adaptive boosting(AdaBoost),Logistic regression(LR),ridge regression(Ridge),and support vector machine(SVM)classifiers.Then,evaluate the model's generalization ability using a validation dataset.Evaluate the performance of the model comprehensively through accuracy,precision,recall,and area under the curve.Results A total of 377 patients with sepsis-induced respiratory tract infection(case group)and 564 patients with respiratory tract infection(control group)were included,and 17 variables were found to be suitable for the initial model construction.Using feature screening algorithm,we found that the predictive performance of tree models(RF,XGboost,and AdaBoost)was better than that of linear models(LR,SVM,and Ridge).The AdaBoost model included 14 biomarkers,and its prediction accuracy was better than RF,XGBoost,LR,SVM,Ridge models,its precision,recall,accuracy and area under the curve were 0.90,0.84,91.75％and 0.950,respectively.The Ridge model had the worst prediction performance,with an accuracy of 82.97％,its precision,recall and area under the curve were 0.90,0.72 and 0.835 respectively.Conclusion In this study,six predictive models of sepsis-induced respiratory tract infection were developed,among which AdaBoost model could more accurately predict the risk of sepsis-induced respiratory tract infection and help to assist clinical decision-making.

Objective:To evaluate the predictive value of simplified geriatric assessment (sGA) in elderly Chinese patients diagnosed with diffuse large B-cell lymphoma (DLBCL) .Methods:It retrospectively analyzed the relationships of sGA with the clinical characteristics, outcome, and prognosis of 219 patients aged ≥60 years who were newly diagnosed with DLBCL at six hospitals in Jiangsu province between January 2018 and December 2022.Results:The median age of 219 patients was 68 years (60-87 years). According to the sGA system criteria, 101 (46.1%), 103 (47.0%), and 15 (6.8%) elderly patients with DLBCL were categorized as fit, unfit, and frail, respectively. The most common adverse reactions after chemotherapy were hematologic, and the incidence of grade >2 hematologic adverse reactions was similar among the three groups (47.5% vs 41.7% vs 46.7%, respectively; χ2=0.712, P=0.700). Compared with the fit and unfit groups, the frail group showed tendencies toward for higher proportions of grade >2 gastrointestinal, pulmonary, and infectious adverse reactions ( P>0.05 for all). The fit, unfit, and frail groups had respective remission rates of 74.3%, 46.6%, and 20.0% ( χ2=25.249, P<0.001) ; disease progression rates of 5.9%, 11.7%, and 26.7% ( χ2=6.763, P<0.05) ; 2-year overall survival rates of 92.1% (95% CI 86.6% to 97.9%), 77.6% (95% CI 69.5% to 86.6%), and 70.1% (95% CI 49.4% to 99.6%) ( P<0.05) ; and 2-year progression-free survival rates of 76.8% (95% CI 67.0% to 84.8%), 69.7% (95% CI 61.8% to 82.0%), and 65.7% (95% CI 53.3% to 100%) ( P=0.399) . Conclusion:sGA can effectively predict treatment adverse effects and efficacy, disease progression, and long-term survival in elderly DLBCL.

Objective To construct a machine learning algorithm using biomarkers to predict the risk of sepsis-induced respiratory tract infection in order to assist clinicians in making decisions.Methods Based on the diagnostic criteria of the research subjects,and the basic clinical data of the participants were collected.The data set was randomly split into a training set(80％)and a validation set(20％).Use feature filtering algorithms to select the best subset of variables from the training set,and use this subset to construct random forest(RF),extreme gradient boosting(XGBoost),adaptive boosting(AdaBoost),Logistic regression(LR),ridge regression(Ridge),and support vector machine(SVM)classifiers.Then,evaluate the model's generalization ability using a validation dataset.Evaluate the performance of the model comprehensively through accuracy,precision,recall,and area under the curve.Results A total of 377 patients with sepsis-induced respiratory tract infection(case group)and 564 patients with respiratory tract infection(control group)were included,and 17 variables were found to be suitable for the initial model construction.Using feature screening algorithm,we found that the predictive performance of tree models(RF,XGboost,and AdaBoost)was better than that of linear models(LR,SVM,and Ridge).The AdaBoost model included 14 biomarkers,and its prediction accuracy was better than RF,XGBoost,LR,SVM,Ridge models,its precision,recall,accuracy and area under the curve were 0.90,0.84,91.75％and 0.950,respectively.The Ridge model had the worst prediction performance,with an accuracy of 82.97％,its precision,recall and area under the curve were 0.90,0.72 and 0.835 respectively.Conclusion In this study,six predictive models of sepsis-induced respiratory tract infection were developed,among which AdaBoost model could more accurately predict the risk of sepsis-induced respiratory tract infection and help to assist clinical decision-making.

Objective:To evaluate the predictive value of simplified geriatric assessment (sGA) in elderly Chinese patients diagnosed with diffuse large B-cell lymphoma (DLBCL) .Methods:It retrospectively analyzed the relationships of sGA with the clinical characteristics, outcome, and prognosis of 219 patients aged ≥60 years who were newly diagnosed with DLBCL at six hospitals in Jiangsu province between January 2018 and December 2022.Results:The median age of 219 patients was 68 years (60-87 years). According to the sGA system criteria, 101 (46.1%), 103 (47.0%), and 15 (6.8%) elderly patients with DLBCL were categorized as fit, unfit, and frail, respectively. The most common adverse reactions after chemotherapy were hematologic, and the incidence of grade >2 hematologic adverse reactions was similar among the three groups (47.5% vs 41.7% vs 46.7%, respectively; χ2=0.712, P=0.700). Compared with the fit and unfit groups, the frail group showed tendencies toward for higher proportions of grade >2 gastrointestinal, pulmonary, and infectious adverse reactions ( P>0.05 for all). The fit, unfit, and frail groups had respective remission rates of 74.3%, 46.6%, and 20.0% ( χ2=25.249, P<0.001) ; disease progression rates of 5.9%, 11.7%, and 26.7% ( χ2=6.763, P<0.05) ; 2-year overall survival rates of 92.1% (95% CI 86.6% to 97.9%), 77.6% (95% CI 69.5% to 86.6%), and 70.1% (95% CI 49.4% to 99.6%) ( P<0.05) ; and 2-year progression-free survival rates of 76.8% (95% CI 67.0% to 84.8%), 69.7% (95% CI 61.8% to 82.0%), and 65.7% (95% CI 53.3% to 100%) ( P=0.399) . Conclusion:sGA can effectively predict treatment adverse effects and efficacy, disease progression, and long-term survival in elderly DLBCL.

Objective To explore application value of transaxillary single-port gasless endoscopic-assisted fibroadenomas excision in adolescents.Methods A retrospective analysis was conducted on clinical data of 60 cases of fibroadenoma from June 2019 to June 2023.The patients were 17.3(range,13-19)years old.There were 54 cases of unilateral tumors and 6 cases of bilateral tumors.The average number of tumors was 2.5(range,1-13),and the mean tumor diameter was 4.0(range,3-10)cm.The fibroadenoma excision was performed by using transaxillary single-port gasless endoscopy.Results Of the 60 patients,the average operation time was 64.9(range,35-130)min and the intraoperative blood loss was less than 20 ml.Postoperative complications occurred in 5 cases(8.3％).At 3 months after surgery,the psychosocial well-being scores of BREAST-Q Scale were increased from(79.2±8.9)to(83.4±9.9)(P＜0.001).Conclusion Transaxillary single-port gasless endoscopic-assisted fibroadenomas excision is safe and effective for multiple or large fibroadenomas in adolescents,offering minimal invasion and concealed incision.

Background and aim:A genome-wide association study has indicated the association of numerous genes in the 6p21.3 region with chronic hepatitis B virus(HBV)infection.In this study,we screened 12 representative single-nucleotide polymorphisms(SNPs)from the 6p21.3 region and investigated their association with the risk of chronic hepatitis B(CHB)to better understand the molecular etiology un-derlying CHB risk in the Han Chinese population. Methods:Between March 2021 and November 2022,we included 183 patients with CHB(case group)and 196 with natural HBV clearance(control group).Allele typing of the selected SNPs was performed using snapshot technology.The correlation between the 12 chosen SNPs and the risk of chronic HBV infection was examined using binary logistic regression analysis.Interacting genes of the variants were identified,and expression quantitative trait loci(eQTL)were analyzed using the 3DSNP database. Results:We validated 12 previously reported CHB susceptibility sites,including rs1419881 of tran-scription factor 19(TCF19),rs3130542 and rs2853953 of human leukocyte antigen(HLA)-C,rs652888 of euchromatic histone-lysine-methyltransferase 2(EHMT2),rs2856718,rs9276370,rs7756516,and rs7453920 of HLA-DQ,rs378352 of HLA-DOA,and rs3077,rs9277535,and rs9366816 of HLA-DP.Logistic regression analyses revealed that polymorphisms such as rs9276370,rs7756516,rs7453920,rs3077,rs9277535,and rs9366816 were positively correlated with natural HBV clearance in the dominant model.Conversely,rs3130542 and rs378352 were identified as risk factors for CHB.Haplotype analysis revealed that rs9276370,rs7756516,and rs7453920 in HLA-DQ were TTG and GCA haplotypes.Although the TTG haplotype was positively correlated with a higher risk of CHB,the GCA haplotype significantly influenced the natural clearance of HBV.Bioinformatics analysis demonstrated that rs378352,rs3077,and rs9366816 were located within enhancer states;rs3077 and rs9366816 overlapped with nine tran-scription factor-binding sites,whereas rs378352 altered five sequence motifs.Furthermore,eQTL analysis demonstrated the functional tendencies of eight statistically significant SNPs(rs3130542,rs9276370,rs7756516,rs7453920,rs378352,rs3077,rs9277535,and rs9366816). Conclusions:Genetic variations within the 6p21.3 region were associated with chronic HBV infection in the Han Chinese population in southern China.Furthermore,the GCA haplotype including rs9276370,rs7756516,and rs7453920 of HLA-DQ contributed significantly to natural HBV clearance,implying that multiple SNPs exert a cumulative allelic effect on HBV infection.

Ferroptosis,a programmed cell death induced by iron-dependent lipid peroxidation and excessive accumulation of reactive oxygen species,is a key pathological mechanism of neuronal death during the progression of Alzheimer's disease(AD),contributing to the formation of"Ferroptosis Hypothesis"for AD pathogenesis.In recent years,there has been extensive research on therapeutic strategies for AD based on the pathogenic mechanism of ferroptosis,focusing primarily on the dysregulation of brain iron metabolism and redox regulation in microenvironment.However,presence of blood-brain barrier and intricate pathological environment within brain impose limitations on intracranial drug transportation,distribution and therapeutic efficacy,thereby necessitating advancements in drug delivery technology.Based on description of ferroptosis process and its regulatory mechanisms,this review explores the association between iron overload and redox imbalance with neuronal loss and AD development,and additionally,summarizes the advancements in nano drug delivery systems targeting iron overload and redox imbalance for potential anti-AD treatments,so as to offer some novel perspectives for AD treatment and drug development.

Objective:To investigate the mechanism of miR-218-5p regulating the glycolytic process in human non-small cell lung cancer A549 cells by targeting phosphodiesterase 7A(PDE7A).Methods:A549 cells were routinely cultured,and miR-218-5p mimic,mimic-NC,PDE7A overexpression plasmid(PDE7A-oe)and PDE7A control plasmid(PDE7A-NC)were transfected into A549 cells using Lipo3000,and recorded as the miR-218-5p mimic group,the mimic-NC group,the PDE7A-oe group and the PDE7A-NC group.The transfection efficiency was verified by qPCR assay;the expressions of glycolysis key enzyme proteins were detected by WB assay;the 2-deoxyglucose and lactate contents in A549 cells of each transfection group were detected by glucose assay and lactate production assay;the target binding relationship between miR-218-5p and PDE7A was verified by dual-luciferase reporter gene assay,and the data from the TCGA database were used to analyze the expression level of PDE7A mRNA in lung cancer tissues.Results:miR-218-5p was successfully overexpressed in A549 cells(P<0.01).Overexpression of miR-218-5p significantly inhibited the expressions of PDE7A,HK2,PKM2 proteins(all P<0.01),glucose uptake and lactate production(both P<0.01)in A549 cells.Overexpression of PDE7A significantly promoted the expressions of PDE7A,HK2,and PKM2 proteins(all P<0.01),as well as glucose uptake and lactate production(both P<0.01)in A549 cells.miR-218-5p in A549 cells could directly bind to the 3′-UTR of PDE7A mRNA.Database data analysis showed that PDE7A mRNA was highly expressed in lung squamous cell carcinoma tissues(P<0.01).Conclusion:miR-218-5p targets PDE7A to regulate the expression levels of HK2 and PKM2 in A549 cells,which in turn inhibits the glycolytic process.miR-218-5p/PDE7A may be a potential target for clinical diagnosis and treatment of NSCLC.

Objective:To analyze the clinical data and genetic characteristics of a child with CLN1 neuronal ceroid lipofuscinosis in conjunct with hereditary hyperferritinemia cataract syndrome (HHCS).Methods:A child who was admitted to the PICU of the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the child was collected. Genetic testing was carried out for the child, and the result was analyzed in the light of literature review to explore the clinical and genetic characteristics to facilitate early identification.Results:The patient, a 3-year-old male, had mainly presented with visual impairment, progressive cognitive and motor regression, and epilepsy. Cranial magnetic resonance imaging revealed deepened sulci in bilateral cerebral hemispheres, and delayed myelination. The activity of palmitoyl protein thioesterase was low (8.4 nmol/g/min, reference range: 132.2 ~ 301.4 nmol/g/min), whilst serum ferritin was increased (2 417.70 ng/mL, reference range: 30 ~ 400 ng/mL). Fundoscopy has revealed retinal pigment degeneration. Whole exome sequencing revealed that he has harbored c. 280A>C and c. 124-124+ 3delG compound heterozygous variants of the PPT1 gene, which were respectively inherited from his father and mother. Neither variant has been reported previously. The child has also harbored a heterozygous c. -160A>G variant of the FTL gene, which was inherited from his father. Based on the clinical phenotype and results of genetic testing, the child was diagnosed as CLN1 and HHCS. Conclusion:The compound heterozygous variants of the PPT1 gene probably underlay the disorders in this child. For children with CLN1 and rapidly progressing visual impairment, ophthalmological examination should be recommended, and detailed family history should be taken For those suspected for HHCS, genetic testing should be performed to confirm the diagnosis.

Objective To explore the correlation between human papilloma virus (HPV) infection and the vaginal environment as well as serum microRNA (miRNA) expression in patients with cervical cancer. Methods A total of 100 patients with cervical cancer admitted to our hospital between October 2020 and June 2023 were enrolled and categorized into two groups:FIGO stage ⅠB (38 patients) and FIGO stage ⅡA (62 patients). Additionally,80 patients diagnosed with cervical intraepithelial neoplasia (CIN) during the same period were included as the precancerous lesion group. Positive rates of vaginal microenvironmental factors and serum miRNA expression levels were compared across the three groups,considering their different pathological characteristics. Results The high-risk HPV infec-tion rate was significantly higher in the FIGO stage ⅡA group compared to both the FIGO stage ⅠB and precancerous lesion groups (P<0.05). The proportion of patients with HPV viral load level 1 was significantly lower in the FIGO stage ⅡA group than in the FIGO stage ⅠB and precancerous lesion groups (P<0.05). The positivity rates of H2O2,SNA,pH,and LE in the FIGO stage ⅡA group were higher than those in the FIGO stage ⅠB and precancerous lesion groups (P<0.05). Serum miR-3607-3p and miR-497-5p levels in the FIGO ⅡA stage group were lower than those in the FIGO stage ⅠB and precancerous lesion groups,whereas serum miR-501 levels were higher compared with FIGO stage ⅠB and precancerous lesion groups (P<0.05). Significant differences in the expression levels of H2O2,SNA,pH,LE,serum miR-3607-3p,miR-497-5p,and miR-501 were observed across groups with varying pathological characteristics (P<0.05). Conclusion Tumor differentiation,HPV viral load,lymph node metastasis,FIGO stage,and levels of H2O2,SNA,pH,LE,serum miR-3607-3p,miR-497-5p,and miR-501 were closely correlated in patients with cervical cancer.