Objective:To develop and validate a combined model integrating radiomics, dosiomics, and clinical parameters based on CT simulation and dosimetric images in order to predict the occurrence of radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC).Methods:A retrospective study was conducted on the clinic data of 143 NSCLC patients who received radiotherapy at the Affiliated Hospital of Jining Medical University from January 2016 to December 2022. Patients were randomly stratified into a training group ( n = 100) and an internal validation group ( n = 43) at a 7∶3 ratio. Moreover, clinic data were collected from 34 NSCLC patients who received radiotherapy at the Jining Cancer Hospital between January 2019 and December 2022 as an external validation group. All three groups (the training group, internal validation, and external validation groups) were further categorized into two groups based on the RP severity (i.e., RP ≥ grade 2 and RP < grade 2). Their radiotherapy dose, CT simulation, and 3D dose distribution images were collected. Then, the total lung minus planning target volume (TL-PTV) was defined as the region of interest (ROI) for radiomics and dosiomic feature extraction, followed by feature dimensionality reduction. Consequently, key features associated with RP were determined. Four predictive models were developed using machine learning approaches (especially multilayer perceptron, MLP): a clinical model (CM), a radiomics model (RM), a dosiomics model (DM), and a radiomics and dosiomics nomogram (RDN), with a nomogram subsequently constructed. Ultimately, the performance and clinical feasibility of these models were assessed using receiver operating characteristic (ROC), area under the curve (AUC), and decision curve analysis (DCA). Results:A total of 1 834 radiomic features and 1 834 dosiomic features were extracted. Using the occurrence of RP ≥ grade 2 as the marker variable, 14 radiomic features, 15 dosiomic features, and three clinical features were selected from the training group to construct the prediction models (CM, RM, DM, and RDN). The performance and generalizability of these models were subsequently validated in both the internal validation and external validation groups. Specifically, the RDN exhibited AUCs of 0.915 (95% CI: 0.852-0.978), 0.879 (95% CI: 0.777-0.982), and 0.838 (95% CI: 0.701-0.975) in the three groups, respectively. A nomogram was established for RDN by integrating the radiomics score (R-score), dosiomics score (D-score), mean lung dose (MLD), V20, and V30. This nomogram allowed for individualized risk estimation of RP and facilitated personalized radiotherapy planning. Conclusions:The RDN model that is developed based on CT simulation and 3D dose distribution images and integrates radiomics, dosiomics, and clinical features can effectively predict the RP risk of NSCLC patients. The integration of multidimensional data contributes to the formation of the optimal predictive model, offering guidance for clinicians.

Objective:To develop and validate a combined model integrating radiomics, dosiomics, and clinical parameters based on CT simulation and dosimetric images in order to predict the occurrence of radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC).Methods:A retrospective study was conducted on the clinic data of 143 NSCLC patients who received radiotherapy at the Affiliated Hospital of Jining Medical University from January 2016 to December 2022. Patients were randomly stratified into a training group ( n = 100) and an internal validation group ( n = 43) at a 7∶3 ratio. Moreover, clinic data were collected from 34 NSCLC patients who received radiotherapy at the Jining Cancer Hospital between January 2019 and December 2022 as an external validation group. All three groups (the training group, internal validation, and external validation groups) were further categorized into two groups based on the RP severity (i.e., RP ≥ grade 2 and RP < grade 2). Their radiotherapy dose, CT simulation, and 3D dose distribution images were collected. Then, the total lung minus planning target volume (TL-PTV) was defined as the region of interest (ROI) for radiomics and dosiomic feature extraction, followed by feature dimensionality reduction. Consequently, key features associated with RP were determined. Four predictive models were developed using machine learning approaches (especially multilayer perceptron, MLP): a clinical model (CM), a radiomics model (RM), a dosiomics model (DM), and a radiomics and dosiomics nomogram (RDN), with a nomogram subsequently constructed. Ultimately, the performance and clinical feasibility of these models were assessed using receiver operating characteristic (ROC), area under the curve (AUC), and decision curve analysis (DCA). Results:A total of 1 834 radiomic features and 1 834 dosiomic features were extracted. Using the occurrence of RP ≥ grade 2 as the marker variable, 14 radiomic features, 15 dosiomic features, and three clinical features were selected from the training group to construct the prediction models (CM, RM, DM, and RDN). The performance and generalizability of these models were subsequently validated in both the internal validation and external validation groups. Specifically, the RDN exhibited AUCs of 0.915 (95% CI: 0.852-0.978), 0.879 (95% CI: 0.777-0.982), and 0.838 (95% CI: 0.701-0.975) in the three groups, respectively. A nomogram was established for RDN by integrating the radiomics score (R-score), dosiomics score (D-score), mean lung dose (MLD), V20, and V30. This nomogram allowed for individualized risk estimation of RP and facilitated personalized radiotherapy planning. Conclusions:The RDN model that is developed based on CT simulation and 3D dose distribution images and integrates radiomics, dosiomics, and clinical features can effectively predict the RP risk of NSCLC patients. The integration of multidimensional data contributes to the formation of the optimal predictive model, offering guidance for clinicians.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Objective The objective of this study was to compare the short-term efficacy and adverse reactions of nituzum-ab combined with synchronous radiotherapy and chemotherapy and bevacizumab combined with synchronous radiotherapy and chemo-therapy in the treatment of locally advanced cervical cancer.Methods A total of 100 locally advanced cervical cancer patients with pathological type of squamous cell carcinoma were collected from 1 September 2020 to 31 December 2021.They were divided into a control group(synchronous radiotherapy and chemotherapy group),a nituzumab group(nituzumab combined synchronous radiotherapy group)and a bevacizumab group(bevacizumab combined synchronous radiotherapy and chemotherapy group).The total effective rate of short-term treatment,changes in tumor volume before and after treatment,serum squamous cell carcinoma antigen(SCC)levels be-fore and after treatment,and adverse reactions after treatment were compared among patients of the three groups.Results The short-term total effective rates of the Nitro group,Bevar group and control group were 90.3％,87.2％and 60.0％,respectively.The total effective rates of the Nitro and Bevar groups were significantly higher than those of the control group,and the differences were statisti-cally significant(P＜0.001).There was no statistically significant difference in the total effective rates of the Nitro and Bevar groups(P＞0.05);The degree of tumor volume reduction and SCC reduction in the Nituo group and Bevac group after treatment was higher than those in the control group(P＜0.05),and there was no statistically significant difference between the two groups(P＞0.05).The incidence of hypertension in the Bevar group was 33.4％,significantly higher than that in the control group(10.0％)and the Ni-tro group(12.9％)(P＜0.05).There was no statistically significant difference in the incidence of hypertension between the Nito group and the control group(P＞0.05);There was no statistically significant difference in the incidence of adverse reactions among the three groups except hypertension(P＞0.05).Conclusion Nituzumab combined with synchronous radiotherapy and chemothera-py,as well as bevacizumab combined with synchronous radiotherapy and chemotherapy,can improve the short-term efficacy of locally advanced cervical cancer,effectively reduce tumor volume and inhibit the expression of tumor markers,both of which are superior to synchronous radiotherapy and chemotherapy alone.Compared to bevacizumab,nituzumab has fewer adverse reactions.For patients with locally advanced cervical cancer,the combination of nituzumab and concurrent radiotherapy and chemotherapy is more reliable in terms of safety.

Objective: To analyze the changes of peripheral blood leukocyte in patients with Behçet uveitis (BU) at different stages. Methods: Case control study was performed.Twenty active stage BU patients and 21 quiet stage BU patients were enrolled from July to November 2015 in Peking Union Medical College Hospital.Ten active stage BU patients treated with glucocorticoid and/or immunosuppressive agents were served as improvement stage BU patients.Meanwhile, 82 healthy controls were collected from the physical examination center.Peripheral blood was obtained and then analyzed by using Hematoflow method.The percentages of leukocytes in peripheral blood of different stage BU patients were compared.This study was approved by the Ethics Committee of Peking Union Medical College Hospital (ZS-1341) and all participants signed informed consent. Results: The percentage of mature neutrophils, eosinophils, basophils, B lymphocytes, non-cytotoxic T and NK lymphocytes, granular T and NK lymphocytes, T blasts, B blasts and immature granulocytes were all significantly different among active stage BU group, quiet stage BU group and healthy control group (F=42.324, 10.220, 8.660, 11.254, 29.795, 31.305, 23.742, 27.738 and 34.638, all at P<0.001). The percentage of mature neutrophils in active stage BU group and quiet stage BU group were (73.10±10.21)% and (62.40±12.09)%, which were significantly higher than (54.95±6.07)% in healthy control group.The percentage of mature neutrophils in active stage BU group was significantly higher than that in quiet stage BU group (P<0.05). The percentages of non-cytotoxic T, NK lymphocytes, granular T and NK lymphocytes in active stage BU group and quiet stage BU group were significantly lower than that in healthy control group, the percentage of non-cytotoxic T, NK lymphocytes and granular T, NK lymphocytes in active stage BU group were significantly lower than those in quiet stage BU group (all at P<0.05). The percentage of immature granulocytes after treatment was significantly higher than that before treatment in improvement stage BU group (t=-2.469, P=0.036). Conclusions Increase of peripheral blood mature neutrophil was observed in BU patients, which may help to monitor the inflammatory activity of BU.

OBJECTIVE： To establish the method for simultaneous determination of saikosaponin a and saikosaponin d in Bupleurum chinense water extract， and to optimize its water extraction technology for electromagnetic cracking. METHODS： HPLC method was used. The determination was performed on SB-C18 column with mobile phase consisted of acetonitrile-water （gradient elution） at the flow rate of 1.0 mL/min. The column temperature was 40 ℃. The detection wavelength was set at 210 nm， and  the sample size was 10 μL. Based on single factor experiment， using extraction time， particle size， solide-liquid ratio as factors， total extraction rate of saikosaponin a to saikosaponin d as indexes， the extraction technology was optimized by using Box-Behnken response surface methdology， and compared with the results of ultrasound method and decoction method. RESULTS： The linear range of saikosaponin a and saikosaponin d were 50.70-202.80 μg/mL （r＝0.999 9） and 50.50-202.00 μg/mL （r＝0.999 9）， respectively. The quantitation limits were 0.16 and 0.13 μg/mL， respectively. The detection limits were 0.05 and 0.04 μg/mL，respectively. RSDs of precision， stability and reproducibility tests were all lower than 2％. The average recoveries were 98.23-102.47％ （RSD＝1.80％， n＝6） and 98.84％-102.06％ （RSD＝1.60％， n＝6）. The optimal extraction technology was as follows： the extraction time of 2.50 min； the particle size of 80 mesh， solid-liquid ratio of 1 ∶ 28 （g/mL）. Results of 3 times of validation tests showed that the optimal technology included the average total extraction rates of saikosaponin a and saikosaponin d were 8.42 mg/g， which was higher than that of ultrasonic method （8.34 mg/g） and decoction method （8.06 mg/g）， and the extration time was shorter. CONCLUSIONS： Established method is simple and accurate， and can be used for simultaneous determination of saikosaponin a and saikosaponin d in B. chinense water extract. The optimized water extraction technology for electromagnetic cracking is stable and feasible.

Objective To explore the value of predicting fluid responsiveness using velocity time index variation (△VTI) and stroke volume variation (△SV) before and after passive leg raising (PLR)monitored by bedside temporary test equipment (TTE).Methods A cohort of 42 patients supported with mechanical ventilation in our hospital admitted from October 2014 to October 2015 were prospectively selected.The hemodynamic variables including heart rate (HR),mean arterial pressure (MAP),central venous pressure (CVP),VTI,SV and other parameters were monitored before and after after undergoing PLR.Fluid resuscitation volume expansion test was carried out after stroke volume index (SVI) monitored by pulse indicator continuous cardiac output monitoring (PICCO).Patients were divided into fluid responsiveness positive group and fluid responsiveness negative group according to presence or absence of SVI ≥ 15％ after fluid resuscitation volume expansion.Results Of 42 patients,22 belonged to fluid responsiveness positive group,20 got into fluid responsiveness negative group.There were no significant differences in basic clinical data between two groups.Before and after PLR,there were no distinct changes in HR and CVP (P ＞ 0.05),while MAP,VTI and SV increased significantly (P ＜ 0.05) after PLR in fluid responsiveness positive group.Contrarily,there were no noticeable changes in MAP and SV after PLR (P ＞ 0.05),but HR,CVP and VTI increased significantly (P ＜ 0.05) in fluid responsiveness negative group.The degrees of △VTI and △SV in fluid responsiveness positive group were much higher than those in fluid responsiveness negative group (P ＜0.05).According to SVI ≥ 15％ monitored by PICCO after fluid resuscitation volume expansion test as a standard,the area under the ROC (AUC) of △VTI between prePLR and post-PLR was 0.75 (95％ CI:O.593-0.907,P ＜ 0.01),the sensitivity and specificity were 63.6％ and 95％ respectively using △VTI 15.6％ as threshold value.The AUC of △SV was 0.844 (95％CI:O.716-0.972,P ＜0.01),the sensitivity and specificity were 81.8％ and 85.0％ respectively using △SV 10.5％ as threshold value.Conclusion △VTI and △SV monitored by TTE before and after PLR could be employed for predicting fluid responsiveness of critical patients under the status of spontaneous respiration.Their value for prediction of critical patients could be further improved by combined employment of these two indexes of variation.

Objective To compare the accuracy of ultrasound,pulse indicator continuous cardiac output monitoring (PiCCO) and traditional methods in predicting fluid responsiveness in septic patients.Methods Forty-six septic patients of both sexes,aged 18-72 yr,requiring mechanical ventilation treatment in the intensive care unit,were enrolled in the study.Venous blood samples were collected for determination of plasma B-type natriuretic peptide (BNP) concentrations by chemiluminescence assay,and central venous pressure (CVP) was recorded.Stroke volume variation (SVVTTE),distensibility index of inferior vena cava (dIVC) and velocity time integral changes of aortic blood flow (△VTI) were measured by ultrasound method.SVVPiCCO and global end-diastolic volume index (GEDVI) were measured by PiCCO method.The patients were divided into negative fluid responsiveness group and positive fluid responsiveness group according to the fluid responsiveness after volume expansion.The receiver operating characteristic curves of the parameters mentioned above in predicting fluid responsiveness were drawn.A consistency check for dIVC,△VTI and SVVPiCCO thresholds was conducted by using Kappa statistics.The agreement between SVVTTEand SVVPiCCO was analyzed by the Bland-Altman analysis.Results There were 24 patients in positive fluid responsiveness group and 22 patients in negative fluid responsiveness group.Compared with negative fluid responsiveness group,the plasma BNP concentration,CVP and GEDVI were significantly decreased,and SVVPiCCO,SVVTTE,dIVC and △VTI were increased before volume expansion in positive fluid responsiveness group (P＜0.05).The area under the curve (95％ confidence interval),sensitivity and specificity of the plasma BNP concentration were 0.894 (0.807-0.981),81.8％ and 79.2％,respectively,of CVP 0.859 (0.752-0.965),81.8％ and 79.2％,respectively,of GEDVI 0.772 (0.628-0.915),72.7％ and 75.0％,respectively,of SVVPiCCO 0.965 (0.922-1.008),95.8％ and 81.8％,respectively,of SVVTTE 0.940 (0.874--1.006),91.7％ and 86.4％,respectively,of dIVC 0.964 (0.920-1.008),83.3％ and 95.5％,respectively,and of △VTI 0.958 (0.909-1.008),87.5％ and 90.9％,respectively.The Kappa value for dIVC threshold and SVVPiCCO threshold was 0.826,and for △VTI threshold and SVVPiCCO threshold was 0.743 (P＜0.01).The mean deviation of SVVTTE and SVVPiCCO was 0.209,95％ confidence interval (-2.967-3.385)％,and the limit of agreement (-2.46-2.62)％ (P＜ 0.05).Conclusion Ultrasound and PiCCO methods can accurately predict fluid responsiveness,have a good agreement and are superior to the traditional method in septic patients.

Objective To observe the effect of Bacillus coagulans tablets Combined with minus Xiaoyao powder, Nifuratel nystatin soft capsule in treatment of VVC. Methods A total of 108 cases of VVC. patients were randomly divided into 2 groups:observation group and control group. In the observation group (n=54), patients were given vaginal placement of Nifuratel nystatin soft capsule, 1 capsule daily, for 6 days;oral administration of minus Xiaoyao powder, 1 agent daily, for 7 days; and oral administration of Bacillus coagulans tablets, 3 tablets one time, 3 times a day, for 14 days, double dose at first. In control group (54 cases), patients were given vaginal placement of Nifuratel nystatin soft capsule, 1 capsule daily, for 6 days;and oral placement of vitamin C tablet, 1 tablet one time, 3 times a day,for 14 days. The short-term effect and the long-term recurrence of were observed 3-7 days, 1 months, 3 months, 6 months after stopping drug treatment. Results 3 days after stopping drugs, the effective rate in the observation group and the control group was 92.59%and 81.48%, respectively, the difference between the two groups was statistically significant (P<0.05) . 6 months after stopping drugs, the recurrence rate was 9.26% in the observation group, and 20.37% in the control group, the difference was statistically significant (P<0.05) . Conclusion For Vaginal candidiasis, on the basis of antifungal therapy, giving Bacillus coagulans tablets for regulation of intestinal micro ecological environment, and traditional Chinese medicine minus Xiaoyao powder for clearing heat and removing dampness, soothing the liver, can significantly improve the short term and long term curative effects,and reduce the recurrence rate.

Objective To explore the value of BI-RADS scoring system based on the sonographic features in the breast nodules.Methods In order to build a Logistic regression model,regression was made to analyse 401 patients ' sonographic features of breast nodules.A scoring system was developed based on the results of regression's filter and the weight of each factor,used to score and classify the other 243 patients.It's diagnostic value was evaluated through comparing all types of theoretic risk ranges of BI-RADS.Results Age,morphology,orientation,margin,echo pattern and microcalcifications in a mass were selected in the final step of the logistic regression analysis.By means of scoring system,the scores corresponding to BI-RADS 3,4a,4b,4c,5 classes are 6,7-8,9-15,16-22 and ≥23 respectively.Case study comprehensive score of BI-RADS 3-5 classification' s positive predictive values were 0,4.17％,21.43％,84.85％,1 00％,and the area under the ROC curve scoring system was 0.947.Conclusions The scoring system can objectively score and classify breast nodules,and therefore provide an effective reference for clinical evaluation of benign and malignant breast.