OBJECTIVE To construct a predictive model for evaluating the efficacy of a triple antiemetic regimen （neurokinin- 1 receptor antagonist+5-hydroxytryptamine 3 receptor antagonist+dexamethasone） for preventing nausea and vomiting induced by highly emetogenic chemotherapy （HEC） based on interpretable deep learning algorithms. METHODS Clinical data of cancer patients who received HEC and were treated with the standard triple antiemetic regimen in the oncology department of Tianjin Medical University General Hospital from January 2018 to December 2022 were collected retrospectively. Demographic， clinical and metabolism-related variables were integrated. After data pre-processing， two deep learning algorithms （deep random forest and dense neural network） and four machine learning algorithms （support vector machine， categorical boosting， random forest and decision tree） were used to build predictive models. Subsequently， model performance evaluation and model interpretability analysis were conducted. RESULTS Among the six candidate models， the deep random forest model demonstrated the best predictive performance on the test set， with an area under the receiver operating characteristic curve of 0.850， an accuracy of 0.911， a precision of 0.805， a recall of 0.783， an F1 score of 0.793， and a Brier score of 0.075. Interpretability analysis revealed that creatinine clearance rate （Ccr） was the key predictive factor， and low Ccr levels， female gender， younger age， highly emetogenic drugs （particularly cisplatin-containing chemotherapy regimens）， and anticipatory nausea and vomiting were positively correlated with the risk of HEC-related nausea and vomiting. CONCLUSIONS The deep random forest model exhibits the best performance in predicting the efficacy of triple antiemetic regimen for preventing HEC-related nausea and vomiting. The key predictors in this model primarily include Ccr，anticipatory nausea and vomiting， gender， age， and highly emetogenic drugs.

Objective To assess the accuracy and consistency of point-of-care testing(POCT)technology in detecting D-dimer(DDI),Procalcitonin(PCT),and N-terminal pro B-type natriuretic peptide(NT-proBNP)in whole blood samples,as well as to validate its feasibility for rapid clinical diagnosis.Methods From July 8 to August 22,2022,a total of 104 paired DDI whole blood and plasma samples,496 paired PCT whole blood and serum samples,and 77 paired NT-proBNP whole blood and serum samples were collected.The consistency and accuracy of test results between whole blood and plasma/serum samples were assessed using the Mann-Whitney U test,regression analysis,relative sensitivity,relative specificity,Youden's index,and Kappa value.Results The test results of DDI,PCT,and NT-proBNP in whole blood and plasma/serum samples demonstrated excellent consistency,with correlation coefficients of r2=0.951 2,r2=0.942 8,and r2=0.991 6,respectively,and all P-values exceeding 0.05.At the medical decision levels,for DDI(0.55 μg/mL),the relative sensitivity,rela-tive specificity,Youden index,and Kappa value were 94.3%,94.1%,0.88,and 0.87,respectively.For PCT(0.5 ng/mL and 2.0 ng/mL),the relative sensitivities were 97.4%and 89.0%,the relative specificities were 95.8%and 98.3%,the Youden indices were 0.93 and 0.87,and the Kappa values were 0.93 and 0.89,respectively.For NT-proBNP(125 pg/mL),the relative sensitivity was 94.1%,the relative specificity was 100%,the Youden index was 0.94,and the Kappa value was 0.87.These findings confirm the high accuracy of whole blood sample testing and the strong concordance between the two methods.Conclusions This study confirmed the efficacy of POCT technology for detecting DDI,PCT,and NT-proBNP in whole blood samples.The results showed a high level of consistency compared to traditional plasma/serum methods,thereby reinforcing the clinical applicability of POCT for rapid diagnosis.

Objective To assess the accuracy and consistency of point-of-care testing(POCT)technology in detecting D-dimer(DDI),Procalcitonin(PCT),and N-terminal pro B-type natriuretic peptide(NT-proBNP)in whole blood samples,as well as to validate its feasibility for rapid clinical diagnosis.Methods From July 8 to August 22,2022,a total of 104 paired DDI whole blood and plasma samples,496 paired PCT whole blood and serum samples,and 77 paired NT-proBNP whole blood and serum samples were collected.The consistency and accuracy of test results between whole blood and plasma/serum samples were assessed using the Mann-Whitney U test,regression analysis,relative sensitivity,relative specificity,Youden's index,and Kappa value.Results The test results of DDI,PCT,and NT-proBNP in whole blood and plasma/serum samples demonstrated excellent consistency,with correlation coefficients of r2=0.951 2,r2=0.942 8,and r2=0.991 6,respectively,and all P-values exceeding 0.05.At the medical decision levels,for DDI(0.55 μg/mL),the relative sensitivity,rela-tive specificity,Youden index,and Kappa value were 94.3%,94.1%,0.88,and 0.87,respectively.For PCT(0.5 ng/mL and 2.0 ng/mL),the relative sensitivities were 97.4%and 89.0%,the relative specificities were 95.8%and 98.3%,the Youden indices were 0.93 and 0.87,and the Kappa values were 0.93 and 0.89,respectively.For NT-proBNP(125 pg/mL),the relative sensitivity was 94.1%,the relative specificity was 100%,the Youden index was 0.94,and the Kappa value was 0.87.These findings confirm the high accuracy of whole blood sample testing and the strong concordance between the two methods.Conclusions This study confirmed the efficacy of POCT technology for detecting DDI,PCT,and NT-proBNP in whole blood samples.The results showed a high level of consistency compared to traditional plasma/serum methods,thereby reinforcing the clinical applicability of POCT for rapid diagnosis.

ObjectiveTo observe the effect of Zuoguiwan on ovarian reserve in the female offspring rat model of prenatal stress （PS） and explore the mechanism based on Toll-like receptor 4/nuclear factor-κB p65 （TLR4/NF-κB p65） signaling pathway. MethodThirty-two pregnant rats were prepared and randomized into four groups （n=8）： control， model， Zuoguiwan （18.9 mg·kg^-1）， and vitamin E （1.44 mg·kg^-1）. Except the control group， the other three groups were subjected to chronic unpredictable mild stress （CUMS） from day 11 of pregnancy， and the modeling was accompanied by gavage with corresponding drugs until delivery. The PS model was evaluated by the sucrose preference test， open field test， and serum corticosterone （CORT） level. The estrous cycle was monitored and the morphological changes in the ovarian tissue were observed. The serum levels of estradiol （E₂）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， and anti-Mullerian hormone （AMH） in the 75-day-old offspring rats were measured by enzyme-linked immunosorbent assay （ELISA） to evaluate the ovarian reserve. The ovary and uterus indices were calculated. The serum levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. The morphology of the ovarian tissue in the offspring on the day of birth and day 75 after birth was observed by hematoxylin-eosin staining. The transport of NF-κB p65 to the nucleus in the ovaries of the 75-day-old offspring was detected by the immunofluorescence （IF） assay. The expression of TLR4， NF-κB p65 and other related proteins in the ovarian tissue was determined by Western blot. ResultCompared with the control group， the model group showed reduced primordial follicles in the offspring on the day of birth （P<0.01） as well as disturbed estrous cycle， decreased ovary index and uterus index （P<0.01）， reduced corpus luteum， increased atretic follicles （P<0.01）， lowered serum levels of AMH and E₂ （P<0.01）， elevated serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and up-regulated protein levels of TLR4， NF-κB p65， recombinant myeloid differentiation factor 88 （MyD88）， and phosphorylated NF-κB inhibitor （p-IκBα） （P<0.01） in the 75-day-old offspring rats. Compared with the model group， Zuoguiwan and vitamin E increased the primordial follicles in the offspring on the day of birth （P<0.01）. Moreover， they resumed the estrous cycle， increased the ovary and uterine indices （P<0.05， P<0.01） and corpus luteum （P<0.01）， reduced atretic follicles （P<0.01）， elevated the serum levels of AMH and E₂ （P<0.05， P<0.01）， lowered the serum levels of LH， FSH， IL-1β， and TNF-α （P<0.05， P<0.01）， and down-regulated the expression of TLR4， NF-κB p65， MyD88， and p-IκB-α （P<0.05， P<0.01） in the 75-day-old offspring. ConclusionZuoguiwan can improve the ovarian reserve in the offspring rat model of congenital kidney deficiency by regulating the TLR4/NF-κB p65 signaling pathway.

Objective To investigate whether degradation of bromodomain-containing protein 4(BRD4)protein with dBET1 can inhibit neuroinflammation and oxidative stress caused byα-synuclein(α-syn)oligomers.Methods After BV2 cells or SH-SY5Y cells were treated with dBET1 and α-syn oligomers,the cells were divided into Control group,α-syn group,α-syn+500 and 1000 nmol/L dBET1 groups,and dBET1 group(1000 nmol/L).Real-time quantitative fluo-rescent PCR(qPCR)was used to detect the expression of inflammatory factors and anti-inflam-matory factors,and Western blotting was employed to measure the expression of BRD4,nuclear factor 2 associated factor 2(Nrf2),phosphorylated nuclear transcription factor-κB(p-NF-κB)and phosphorylated α-synuclein(p-α-synuclein).Results The α-syn+1000 nmol/L dBET1 group had lower mRNA levels of inflammatory factors and reduced protein levels of BRD4,p-NF-κB and p-α-synuclein,but higher mRNA levels of anti-inflammatory factors and decreased Nrf2 protein level(2.02±0.14 vs 0.96±0.24,P＜0.05)when compared with the α-syn group.Conclusion dBET1 can inhibit neuroinflammation and oxidative stress caused by α-synuclein through p-NF-KB and Nrf2 to a certain extent,which further provides a theoretical basis for its application in the treatment of Parkinson's disease.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective:To investigate the correlation between the level of treponema pallidum specific antibodies(TPAb)and immunoglobulin A/E/M/G(IgA/E/M/G)and IgG subtypes in active syphilis patients,so as to provide a basis for the comprehensive di-agnosis and treatment and prognosis evaluation of clinical syphilis.Methods:Active syphilis patients admitted to the First Affiliated Hospital of Soochow University in 2023 were divided into 1∶4+and 1∶16+groups according to the syphilis toluidine red unheated se-rum test(TRUST),and healthy control group were selected for the detection of TPAb by chemiluminescence microparticle immunoas-say(CMIA).The contents of IgA/E/M/G and IgG1/2/3/4 were determined by immunoturbidimetry.Results:A total of 206 patients with active syphilis(125 males and 81 females)aged(46.05±19.58)years were included in this study.Compared with the healthy control group,IgG2 was decreased and TPAb,IgA/E/M/G and IgG1/3/4 levels were increased in the active syphilis group,with statistically significant differences in TPAb,IgE and IgG1/2/3 levels(P<0.05).Compared with the healthy control group,TRUST 1∶4+group had statistical differences in TPAb,IgE and IgG2,and TPAb was significantly correlated with IgE and IgG2/4.The levels of TPAb,IgA/E/M/G and IgG1/2/3 in TRUST 1∶16+group were statistically significant,and TPAb was significantly correlated with IgE and IgG4(P<0.05).In addition,there were significant differences in TPAb,IgG and IgG1/3 between the two positive groups(P<0.05).Conclu-sion:The levels of TPAb and Ig in active syphilis patients with different TRUST titers are significantly different.TPAb combined with Ig can be used to monitor the strength of syphilis activity,IgA/M/G and IgG1/3 may be candidate biomarkers.

Objective:To investigate the genetic and evolutionary characteristics of hemagglutinin (HA) and neuraminidase (NA) genes of influenza B/Victoria (BV) virus in Xi′an city from 2019 to 2023.Methods:Twenty-five BV strains isolated from the Xi′an influenza surveillance network laboratory between 2019 and 2023 were collected. The HA and NA genes were sequenced using MiniSeq high-throughput sequencing platform. An evolutionary tree was constructed using bioinformatics software to analyze homology and mutation sites, and to predict N-glycosylation sites online. The antigenicity of the strains was analyzed through hemagglutination inhibition tests.Results:The BV influenza in Xi′an exhibited a distinct seasonal transmission pattern from 2019 to 2023, with peak prevalence occurring during the winter and spring seasons. The evolutionary analysis of the HA genes shows that the strains from Xi′an in 2019 belong to the V1A.3 branch, and the strains from 2021 to 2023 belong to the V1A.3a.2 branch. Analysis of antigenic sites showed that there were variations in 6 sites of 3 antigenic determinants in the HA proteins of the BV strains from 2021-2022 compared to 2019, and 2 sites of 1 antigenic determinant changed in the HA proteins in 2023 compared to 2021-2022. The evolutionary analysis of the NA genes indicates that the BV strains from Xi′an in 2019 belong to the A. 1.1 branch. By 2021 and 2022, it had evolved into the A. 1.2 clade, and by 2023, it had further evolved into the B clade and its derivatives, with no strains showing mutations associated with resistance to NA inhibitors. Antigenic analysis indicated that the majority of BV strains in Xi′an were similar to the strains included in the vaccine composition. Furthermore, glycosylation analysis showed that the potential N-glycosylation sites in the HA proteins of BV strains from 2021-2023 were reduced by one compared to those from 2019, and only a few strains from 2023 displayed alterations in the potential N-glycosylation sites of the NA proteins.Conclusions:The HA and NA genes of the BV strains from 2019 to 2023 are continuously mutating and evolving into new branches. Since 2021, V1A.3a.2 has become the dominant evolutionary branch of the HA genes, while the evolutionary branches of the NA genes from 2019 to 2023 have been continuously changing.

Humans ; East Asian People ; Nausea/drug therapy* ; Vomiting/drug therapy* ; Antineoplastic Agents/adverse effects* ; Neoplasms/drug therapy*

Objective:To provide a basis for the selection of antiemetic regimen by establishing an artificial intelligence model for predicting chemotherapy-induced nausea and vomiting (CINV) in cancer patients receiving platinum-based chemotherapy with high emetic risk.Methods:The clinical information on cancer patients who received cisplatin or carboplatin with area under the blood concentration-time curve (AUC) ≥4 and registered in the Department of Oncology, Tianjin Medical University General Hospital from January 2018 to December 2022 was collected, including gender, age, history of alcohol consumption, history of vomiting in pregnancy, chemotherapy cycle, patient expects to have CINV, chemotherapeutic agents, antiemetic regimen, out-of-hospital antiemetic treatment, sleep of less than 7 hours on the night before chemotherapy, occurrence of CINV in the previous cycle, and creatinine clearance (Ccr). After pre-processing, the data were randomly divided into the training set and the test set. The training set was used to construct the prediction model, and the test set was used to evaluate the prediction efficiency of the model. Three algorithms, gradient boosting decision tree (GBDT), random forest (RF), and logistic regression (LR), were used to build a prediction model and evaluate the model performance, respectively. The evaluation metrics included accuracy, sensitivity, recall, F1 value (the reconciled mean of sensitivity and recall), and area under the receiver operating characteristic curve (AUROC). Finally, Shapley Additive exPlanation (SHAP) was applied to analyze the interpretability of the clinical features with predictive significance.Results:A total of 698 patients, 439 males (62.9%) with a median age of 64 (21, 84) years, were included in this study and received a total of 1 654 cycles of chemotherapy. The chemotherapy regimen contained cisplatin in 364 cases with 864 cycles of chemotherapy, and carboplatin with AUC ≥4 in 361 cases with 790 cycles of chemotherapy. The number of treatment cycles in which neurokinin-1 receptor antagonist (NK-1 RA), 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), and dexamethasone were selected as the antiemetic regimen was 1 347, and in those with the selection of 5-HT3 RA and dexamethasone was 307. The Spearman′s correlation analysis showed no strong correlation between the feature variables in the patients, and all of them could be used for model building. GBDT optimal hyperparameters n_estimators=500, max_depth=9; RF optimal hyperparameters max_depth=5; LR optimal hyperparameters penalty=L2. Three prediction models, GBDT, RF and LR, were established based on the optimal hyperparameter training data, respectively. The accuracy of GBDT model was 0.903, sensitivity was 0.882, recall was 0.903, F1 value was 0.883, and AUROC was 0.778±0.036 (95% CI: 0.739-0.814); the accuracy of RF model was 0.885, sensitivity was 0.861, recall was 0.885, F1 value was 0.870, and AUROC was 0.679±0.041 (95% CI: 0.636-0.720); the LR model had an accuracy of 0.817, a sensitivity of 0.851, a recall of 0.817, an F1 value of 0.832, and an AUROC of 0.682±0.042 (95% CI: 0.639-0.723). Ccr, age, chemotherapy cycle, history of alcohol consumption, and patient expects to have CINV were the main features predicted by the model. The risk of CINV was negatively associated with Ccr, age, and chemotherapy cycle. And the risk of CINV was lower in patients with no history of drinking alcohol and patient expects to have CINV. Conclusion:The GBDT, RF, and LR models could all predict the risk of CINV in patients receiving platinum-based chemotherapy with high emetic risk, with the GBDT model having the best predictive effect.