Objective To identify risk factors for postoperative respiratory failure(PORF)in cardiovascular surgery patients using machine learning algorithms and to construct a specific risk prediction model.Methods A retrospective cohort was conducted on 1 623 patients undergoing cardiovascular surgery between 2011 and 2020 from the INSPIRE database.Following data quality analysis,multiple imputation was employed to handle missing data,and the Boruta algorithm was used for feature selection.Eight machine learning models were constructed based on the selected features,including Gradient Boosting Machine(GBM),Generalized Linear Model(GLM),Extreme Gradient Boosting(XGBoost),K-Nearest Neighbors(KNN),Neural Network(NNET),Naive Bayes(NB),Support Vector Machine(SVM),and Random Forest(RF).Model performance was evaluated using metrics including the area under the curve(AUC),sensitivity,and specificity.Variables significantly influencing PORF were identified using the permutation importance algorithm.Results The overall incidence of PORF was 27.05％(439/1 623).The in-hospital mortality rate was significantly higher in the PORF group than the non-PORF group(12.98％vs 1.60％,P<0.001).Among the developed models,the SVM model demonstrated the best performance,achieving an AUC of 0.705 in the testing set,with a sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of 0.481,0.825,0.504,and 0.812,respectively.Based on feature importance analysis,the top 10 variables most predictive of PORF were anesthesia duration,arterial partial pressure of carbon dioxide(PaCO?),calcium level,lymphocyte percentage,cardiopulmonary bypass duration,intraoperative blood loss,age,creatinine level,aspartate aminotransferase(AST)level,and activated partial thromboplastin time(aPTT).Conclusion A predictieon model for PORF following cardiovascular surgery is successfully developed.This model can identify high-risk patients and estimate their probability of developing respiratory failure,thereby facilitating data-driven clinical decision-making.

[This corrects the article DOI: 10.1016/j.apsb.2022.07.023.].

OBJECTIVE To elucidate the mechanisms responsible for the inhibitory effects of limonene on the proliferation of non-small cell lung cancer(NSCLC) by non-targeted metabolomics and additional approaches. METHODS The CCK-8 assay was utilized to evaluate the inhibitory effects of limonene on NSCLC A549 cell viability and to ascertain the IC50. In vitro experiments, encompassing colony formation, flow cytometry, iron content assessment, and mitochondrial staining, were conducted to assess the anti-lung cancer and iron-induced cell death effects of limonene. Metabolomic analysis was employed to identify potential pathways influenced by limonene, and Western blotting was carried out to validate pivotal proteins within these pathways. RESULTS In comparison to the control group, the limonene-treated group demonstrated a significant, dose-dependent reduction in A549 cell proliferation and colony formation. Optical microscopy revealed cellular detachment and pronounced changes in cellular morphology following exposure to limonene. Limonene induced apoptosis in A549 cells and arrested them in the G0-G1 phase of the cell cycle. Confocal microscopy unveiled diminished mitochondrial fluorescence and an augmented intracellular iron content, indicative of the classical phenomenon of ferroptosis. Metabolomic investigations unveiled divergent metabolic pathways, including glutathione(GSH) metabolism, arginine biosynthesis, D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism, with many of them intricately linked to intracellular GSH synthesis. Western blotting experiments underscored a marked reduction in the levels of SLC40A1, SLC7A11(xCT), and GPX4 proteins within the cells post-limonene treatment. CONCLUSION Limonene may induce ferroptosis in lung cancer cells by reducing GSH synthesis and increasing Fe2+ levels.

Objective To establish an HPLC-based method for the determination of α-obscurine,ferulic acid,hydroxysafflower yellow A,benzoylneaconitine,benzoylaconitine,periplosin,4-methoxysalicylsalicylate,kaempferol and oleanolic acid simultaneously in Shujin Tongluo Black Plaster.Methods HPLC method was used to determine the 9 components in Shujin Tongluo Black Plaster simultaneously.The 70%methanol extracts were analyzed using Waters SunFire C18 chromatography column(4.6 mm×250 mm,5 μm),in mobile phase containing acetonitrile-0.2%phosphoric acid solution for gradient elution with volume flow rate of 1.0 mL/min;column temperature was set at 25℃;detection wavelength was set at 230 nm.Results The 9 components had good linear relationship in their respective ranges(r≥0.999 7).The average recoveries were between 98.06%-100.56%and RSD was between 0.48%-2.56%,respectively.Conclusion The method has the advantage of repeatability,simple and fast,and can be used as the quality control of Shujin Tongluo Black Plaster.

Objective:To explore the dosimetric advantages of 3D printed individualized molds in assisting postoperative three-dimensional brachytherapy (3D BT) for endometrial cancer.Methods:The 3D BT plans of 21 postoperative patients with early-stage endometrial cancer at the First Affiliated Hospital of Ningbo University were retrospectively selected as the individualized mold group (the mold group). On this basis, virtual single-channel cylindrical applicator plans that employed a 3D inverse simulated annealing algorithm were designed for all the patients using the Beijing Colins Planning System (the single-channel group). Comparisons were made between the two groups of plans regarding the minimum doses exposed to 90%, 98%, and 100% of target area ( D90, D98, and D100), conformity index (CI), homogeneity index (HI), and overdose index (OI), as well as the maximum doses exposed to 0.01, 1, 2, and 5 cm 3organs at risk (bladder, rectum, small intestine, and urethra) ( D0.01 cm 3, D1 cm 3, D2 cm 3, and D5 cm 3). Results:Both groups met clinical requirements. For doses to target volumes, there was no significant difference in D90, D98, and D100 between both groups, with the mold group demonstrating superior CI and HI but lower OI compared to the single-channel group ( t = -3.21, -5.99, 6.25, P < 0.05). Concerning the doses exposed to organs at risk, the mold group displayed significantly reduced D1 cm 3, D2 cm 3, and D5 cm 3 for the bladder, rectum, and urethra compared to the single-channel group ( t = 3.18, 3.21, 3.77, 7.97, 8.92, 10.92, 2.54, 3.46, 4.28, P < 0.05). There was no significant difference in the doses exposed to the small intestine between both groups ( P > 0.05) due to the large distance from the small intestine to the target volumes. Conclusions:3D printed individualized molds exhibit advantages in terms of the homogeneity and conformity indices of target volumes in postoperative three-dimensional brachytherapy for endometrial cancer, accompanied by low doses exposed to the bladder, rectum, and urethra, thereby holding the potential for broader application.

Objective:To identify the dosimetric and radiobiological differences of three radiotherapy techniques of whole breast irradiation with simultaneous integrated boost (WBI-SIB) following breast-conserving surgery for early breast cancer (EBC).Methods:The data of 20 patients with early left-sided breast cancer who received radiotherapy following breast-conserving surgery were retrospectively analyzed. Three radiotherapy techniques, namely hybrid intensity-modulated radiotherapy (HIMRT), intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), were redesigned with the same prescription dose and target conditions. Then, doses to target volume (TV) and organs at risk (OAR), along with the normal tissue complication probability (NTCP) and secondary cancer risk (SCR) for specific organs, were compared.Results:Compared to HIMRT and IMRT, VMAT led to significant decreases in various dosimetric indices of the affected lung and heart and increases in the Dmean doses to the healthy lung and healthy breast and V5 Gy doses to the healthy breast, with the differences being significantly different ( P < 0.05). The average NTCP values of cardiac death, radiation pneumonitis, and pulmonary fibrosis induced by VMAT were 0.41%, 1.62%, and 23.59%, respectively, significantly lower than those caused by other two techniques ( P < 0.05). No statistical differences were found in 10 dosimetric indices of OAR between IMRT and HIMRT, while the NTCP analysis suggested that the risks of cardiac death ( t = 2.70, P < 0.05) and pulmonary fibrosis ( t =4.11, P < 0.05) induced by IMRT were slightly lower than those caused by HIMRT. In addition, the excess absolute risk (EAR) to the healthy lung posed by VMAT was 1.65 and 1.83 times those induced by HIMRT and IMRT, respectively ( z = -3.92, t = -6.43, P < 0.05). In contrast, the EAR to the healthy breast induced by VMAT was 2.79 and 2.65 times those posed by HIMRT and IMRT, respectively ( z = -3.21, -3.70, P < 0.05). Conclusions:Among three intensive-modulated radiotherapy techniques of WBI-SIB for EBC, VMAT provides the optimal protection for the heart and affected lung but leads to the highest SCR to the healthy lung and breast. When VMAT is employed for young EBC patients or those with normal cardiopulmonary function, special attention should be paid to reducing low-dose irradiations to the healthy breast and thereby minimizing SCR. In contrast, VMAT might be more favorable for patients with pronounced cardiopulmonary risks or aged patients.

Objective Kisspeptin,a protein encoded by the KISS1 gene,functions as an essential factor in suppressing tumor growth.The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway,which assumes a central role in maintaining cellular homeostasis.In the specific context of this investigation,the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization.This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway,aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion(RSA).Methods We enrolled a cohort comprising 45 individuals diagnosed with RSA,who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020.On the other hand,an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included.To comprehensively assess the molecular landscape,Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin(and its gene KISS1),IGFBP1(an established marker of decidualization),Notch1,Akt,and Foxo1 within the decidua.Human endometrial stromal cells(hESC)were given targeted interventions,including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10(the bioactive fragment of kisspeptin),and were subsequently designated as the siKP group or the KP10 group,respectively.A control group comprised hESC was transfected with blank siRNA,and cell proliferation was meticulously evaluated with CCK8 assay.Following in vitro induction for decidualization across the three experimental groups,immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups.Furthermore,RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1,Notch1,Akt,and Foxo1 across the three cell groups.Subsequently,decidualization was induced in hESC by adding inhibitors targeting Notch1,Akt,and Foxo1.The expression profiles of the aforementioned proteins and genes in the four groups were then examined,with hESC induced for decidualization without adding inhibitors serving as the normal control group.To establish murine models of normal pregnancy(NP)and RSA,CBA/J×BALB/c and CBA/J×DBA/2 mice were used.The mice were respectively labeled as the NP model and RSA model.The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234(acting as a blocker)and were designated as RSA-KP10 and NP-KP234 groups.On the other hand,the control groups received intraperitoneal injections of normal saline(NS)and were referred to as RSA-NS and NP-NS groups.Each group comprised 6 mice,and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes.Results The analysis revealed that the expression levels of kisspeptin,IGFBP1,Notch1,Akt,and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP(P<0.01 for kisspeptin and P<0.05 for IGFBP1,Notch1,Akt,and Foxo1).After the introduction of kisspeptin10 to hESC,there was an observed enhancement in decidualization capability.Subsequently,the expression levels of Notch1,Akt,and Foxo1 showed an increase,but they decreased after interference with KISS1.Through immunofluorescence analysis,it was observed that proliferative hESC displayed a slender morphology,but they transitioned to a rounder and larger morphology post-decidualization.Concurrently,the expression of Notch1 increased,suggesting enhanced decidualization upon the administration of kisspeptin10,but the expression decreased after interference with KISS1.Further experimentation involved treating hESC with inhibitors specific to Notch1,Akt,and Foxo1 separately,revealing a regulatory sequence of Notch1/Akt/Foxo1(P<0.05).In comparison to the NS group,NP mice administered with kisspeptin234 exhibited increased fetal absorption rates(P<0.001)and decreased expression of IGFBP1,Notch1,Akt,and Foxo1(P<0.05).Conversely,RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates(P<0.001)and increased expression levels of the aforementioned molecules(P<0.05).Conclusion It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade.A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization,which in turn might contribute to the development or progression of RSA.

Objective: To analyze the trend and characteristics of school tuberculosis epidemic in Shijiazhuang from 2011 to 2020, and to provide reference for school tuberculosis prevention and control. Methods: Descriptive methods were used to analyze the epidemiological characteristics of tuberculosis among students and the epidemic situation of tuberculosis in schools in Shijiazhuang from 2011 to 2020. The χ 2 test and χ 2 trend test were used to analyze the characteristics and trend of school tuberculosis. Results: A total of 4 896 cases of tuberculosis were registered among students in Shijiazhuang from 2011 to 2020. The average annual registered incidence rate of students was 24.69/100 000, and the difference in incidence rate was statistically significant ( χ 2=318.50, P <0.01) the overall registered incidence rate of tuberculosis among students in the past 10 years was on the rise ( χ 2 trend =87.79, P <0.01). Among the student cases, male accounted for 53.89%, female accounted for 46.11%. The age group of students aged >18 and above accounted for the largest proportion(50.35%), followed by the age group aged 16-18( 35.80 %). Most students cases occurred in April and September-November, with September the highest(12.03%). A total of 22 clustered outbreaks (174 cases) and the aggregate epidemic accounted for 3.55% of the total number of students with tuberculosis. Conclusion The prevention and control of tuberculosis epidemic in schools in Shijiazhuang should not be underestimated, and strengthen the supervision, management, publicity and education of students in key age groups to avoid clusters of outbreaks.

Objective:Topredict the three-dimensional dose distribution of regions of interest (ROI) with brachytherapy for cervical cancer based on U-Net fully convolutional network, and evaluate the accuracy of prediction model.Methods:First, 100 cases of cervical cancer intracavity combined with interstitial implantation were selected as the entire research data set, and divided into the training set ( n=72), validation set ( n=8), and test set ( n=20). Then the U-Net was used to construct two models based on whether the uterine tandem and the implantation needles were included as the distinguishing factors. Finally, dose distribution of 20 cases in the test set were predicted using the trained model, and comparative analysis was performed. The performance of the model was jointly evaluated by , and the mean absolute deviation (MAD). Results:Compared with the model without the uterine tandem and the implantation needles, the of the rectum was increased by (16.83±1.82) cGy ( P<0.05), and the or of the other ROI were not different significantly (all P>0.05). The MAD of the high-risk clinical target volume, rectum, sigmoid, small bowel, and bladder was increased by (11.96±3.78) cGy, (11.43±0.54) cGy, (24.08±1.65) cGy, (17.04±7.17) cGy and (9.52±4.35) cGy, respectively (all P<0.05). The MAD of the intermediate-risk clinical target volume was decreased by (120.85±29.78) cGy ( P<0.05). The mean value of MAD for all ROI was decreased by (7.8±53) cGy ( P<0.05), which was closer to the actual plan. Conclusions:U-Net fully convolutional network can be used to predict three-dimensional dose distribution of patients with cervical cancer undergoing brachytherapy. Combining the uterine tube with the implantation needles as the input parameters yields more accurate predictions than a single use of the ROI structure as the input.

As a promising modality for cancer therapy, photodynamic therapy (PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles via hydrophilic and hydrophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin (BSA-MHI148) and multi-kinase inhibitor Sorafenib (SRF) as a novel tumor oxygen and immune microenvironment regulation drug. Benefiting from the accumulation of SRF in tumors, BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms: (i) SRF decreased tumor oxygen consumption via inhibiting mitochondria respiratory. (ii) SRF increased the oxygen supply via inducing tumor vessel normalization. Meanwhile, the immunosuppression micro-environment was also obviously reversed by two-stage immune re-sensitization as follows: (i) Enhanced immunogenic cell death (ICD) production amplified by BSA-MHI148@SRF induced reactive oxygen species (ROS) generation enhanced T cell infiltration and improve its tumor cell killing ability. (ii) BSA-MHI148@SRF amplified tumor vessel normalization by VEGF inhibition also obviously reversed the tumor immune-suppression microenvironment. Finally, the growth of solid tumors was significantly depressed by such well-designed BSA-MHI148@SRF nanoparticles, which could be potential for clinical cancer therapy.