Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

Objective To investigate the impact of social psychological factors on adherence among subjects with chronic diseases during the early phase of new drug clinical trials and propose strategies to optimize trial outcomes.Methods Between December 2020 to December 2023,observational datas were collected from subjects participating in new drug clinical trials in the Frist Hospital of Jiaxing,including customized sociodemographic informations,Eysenck personality questionnaire(EPQ)survey results,symptom checklist 90(SCL-90)scores,Beck anxiety inventory(BAI)scores,Beck depression inventory(BDI)scores.The SCL-90 was further categorized into ten factor scores,and the EPQ was evaluated based on four dimensional standard T-scores.Univariate and multivariate Logistic regression analyses were conducted to identify the related factors.Results Univariate analyses showed that gender,willingness to go out,EPQ_T neuroticism,SCL-90,SCL somatic,SCL obsessive compulsive,SCL interpersonal,SCL depression,SCL anxiety,SCL psychoticism,SCL other,BAI scores,and BDI scores were associated with adherence in subjects with chronic diseases.Multivariate analysis confirmed that a higher willingness to go out,elevated BAI and BDI scores were positively associated with non-adherence risk,whereas an increase in the SCL-90 somatization factor scores were inversely related to adherence risk in subjects with chronic diseases.Conclusion Identifying and managing anxiety and depression among subjects with chronic diseases,as well as understanding their outdoor plans,are crucial for enhancing adherence during the early stages of new drug clinical trials.In certain instances,subjects with chronic diseases heightened awareness of bodily discomfort may paradoxically promote adherence.

Objective:To explore the role of corticotrophin releasing factor receptor 2 (CRFR2) in regulating pain sensitization and anxiety and its mechanism in chronic migraine mice.Methods:Forty-eight C57BL/6J mice were randomly divided into control group, model group, NBI35965 group and K41498 group ( n=12); chronic migraine models in the later 3 groups were established by intraperitoneally administrating 10 mg/kg nitroglycerin on the 1 st, 3 rd, 5 th, 7 th and 9 th d; mice in the NBI35965 group and K41498 group were injected with 100 nL NBI35965 or K41498 solution into the bilateral trigeminal nucleus caudalis on the 2 nd, 4 th, 6 th and 8 th d, and mice in the control group were injected with same volume of normal saline. Von frey fiber was used to detect the orbitofrontal mechanical pain threshold 2 h after intraperitoneal injection on the 1 st, 3 rd, 5 th, 7 th and 9 th d, and at 11 a.m. on the 10 th d. Elevated plus maze was used to detect the anxiety-like behaviors at 11 a.m. on the 11 th d. Western blotting was performed to detect the protein expressions of corticotrophin releasing factor (CRF), corticotrophin releasing factor receptor 1 (CRFR1), CRFR2 in the trigeminal nucleus caudalis. Real-time quantitative PCR (RT-qPCR) was used to detect the CRFR1 and CRFR2 mRNA expressions in the trigeminal nucleus caudalis. Immunofluorescent staining was used to detect the protein expressions of calcitonin gene-related peptide (CGRP), immediate-early gene c-fos, glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1) in the trigeminal nucleus caudalis. Results:Compared with the control group, the model group, NBI35965 group and K41498 group had significantly decreased orbitofrontal mechanical pain thresholds 3, 5, 7, 9, and 10 d after intraperitoneal injection ( P<0.05); compared with model group, the K41498 group had significantly increased orbitofrontal mechanical pain thresholds 7, 9, and 10 d after intraperitoneal injection ( P<0.05). Compared with control group, the model group, NBI35965 group and K41498 group had significantly decreased entries and shorter time in opened arms ( P<0.05); compared with the model group, the K41498 group had significantly increased entries and shorter time in opened arms ( P<0.05). Compared with the control group, the model group, NBI35965 group and K41498 group had significantly higher CRF and CRFR2 protein expressions in the trigeminal nucleus caudalis ( P<0.05); compared with the model group, the K41498 group had statistically lower CRF protein expression in the trigeminal nucleus caudalis ( P<0.05). Compared with the control group, the model group, NBI35965 group and K41498 group had significantly higher CRFR2 mRNA expression in the trigeminal nucleus caudalis ( P<0.05). Compard with the control group, the model group, NBI35965 group and K41498 group had significantly increased CGRP, c-fos, Iba-1 and GFAP protein expressions in the trigeminal nucleus caudalis ( P<0.05); compared with the model group, the K41498 group had significantly decreased CGRP and c-fos protein expressions in the trigeminal nucleus caudalis ( P<0.05). Conclusion:CRFR2 can alter the orbitofrontal pain sensitization and anxiety-like behaviors in chronic migraine mice by regulating neuronal activation and CGRP release in the trigeminal nucleus caudalis.

With the optimization of surgical technologies and postoperative management regimens, the number of lung transplantation has been significantly increased, which has become an important treatment for patients with end-stage lung disease. However, due to the impact of comprehensive factors, such as bronchial ischemia and immunosuppression, the incidence of airway stenosis after lung transplantation is relatively high, which severely affects postoperative survival and quality of life of lung transplant recipients. In recent years, with the improvement of perioperative management, organ preservation and surgical technologies, the incidence of airway stenosis after lung transplantation has been declined, but it remains at a high level. Early diagnosis and timely intervention play a significant role in enhancing clinical prognosis of patients with airway stenosis. In this article, the general conditions, diagnosis, treatment and prevention of airway stenosis after lung transplantation were reviewed, aiming to provide reference for comprehensive management of airway stenosis after lung transplantation and improving clinical prognosis of lung transplant recipients.

Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.

OBJECTIVE To systematically evaluate the effectiveness of different treatment regimens as first-line treatment for metastatic urothelial carcinoma （UC） using a network meta-analysis （NMA） approach. METHODS Electronic databases including PubMed， the Cochrane Library， Embase， Wanfang Data， CNKI， and VIP were searched for randomized controlled clinical trials （RCTs） on first-line treatment for metastatic UC from January 1， 2010 to January 31， 2024. After literature screening and data extraction， a risk of bias assessment of included studies was conducted. R software （version 4.3.2） was used to perform the NMA. RESULTS A total of 11 RCTs involving 14 treatment interventions were included. No significant differences were noted in objective response rate among groups， with the combination of pembrolizumab， gemcitabine and cisplatin having the highest probability of ranking first. Regarding progression-free survival （PFS） and overall survival （OS）， no significant differences were observed among groups， while enfortumab vedotin combined with pembrolizumab showed a trend towards better PFS extension compared to gemcitabine combined with cisplatin [HR＝0.45， 95%CI（0.20，1.06）， P＝0.049]， and it had the highest probability of ranking first in both PFS and OS. CONCLUSIONS The combination of enfortumab vedotin and pembrolizumab may have an advantage in prolonging survival in the first-line treatments for metastatic UC.

Objective:To investigate the effects of hydroxysafflor yellow A (HSYA) on depressive-like behavior and expression of type A γ-aminobutyric acid receptor(GABAAR)in hippocampus of chronic restraint stress model mice.Methods:The SPF grade male C57BL/6C mice were divided into Control group, HSYA group, Model group, Model + HSYA group and Model + fluoxetine group according to random number table method, with 12 mice in each group.Mice model of depression was established by chronic restraint stress.Mice in HSYA group and Model+ HSYA group were intraperitoneally injected with HSYA(20 mg/kg), mice in Model+ fluoxetine group were injected intraperitoneally with fluoxetine (10 mg/kg), and mice in Control group and Model group administered with 0.9% sodium chloride solution intraperitoneally once a day for 14 days.Then, the forced swimming test (FST) and tail suspension test (TST) were performed to evaluate the depressive-like behavior of mice, and the protein expression levels of different subtypes of GABAAR in the hippocampus of mice were determined by Western blot.SPSS 19.0 and GraphPad Prism 8.0 software were used for data statistical analysis and mapping.One-way ANOVA was used for comparison among groups, and Tukey-HSD test was used for further pairwise comparison.Results:(1) In the behavioral tests, there were significant differences in swimming immobility time of FST and tail suspension immobility time of TST among the five groups ( F=21.59, 20.81, both P<0.05). The swimming immobility time ((143.91±9.97) s) and tail suspension immobility time (( 107.00±6.54) s) in Model group were higher than those in Control group ((52.92±6.70) s, ( 43.50±5.96) s, both P<0.05). There were no significant difference in swimming immobility time and tail suspension immobility time between Model+ HSYA group ((26.17±7.69)s, ( 20.17±7.89)s) and Model+ fluoxetine group ((61.60±16.22)s, (34.14±10.74)s)(both P>0.05), but the swimming immobility time and tail suspension immobility time in these two groups were lower than those in Model group (both P<0.05). (2) The Western blot results showed that there were significant differences in the expression of GABAARβ1 and GABAARβ2 protein in hippocampus among the four groups ( F=12.21, 11.40, both P<0.05). The expression levels of GABAARβ1(45.60±10.76) and GABAARβ2 (46.27±4.82) protein in hippocampus of Model group were lower than those in Control group ((100.00±3.44), (100.00±3.26), both P<0.05). Compared to Model group, the expression of GABAARβ1 (79.91±5.00) and GABAARβ2 (79.08±5.53) protein in hippocampus of Model+ HSYA group were higher (both P<0.05). In addition, the expression of GABAARα1 and GABAARγ1 proteins in hippocampus were not significantly different among the four groups( F=0.23, 0.10, both P>0.05). Conclusion:HSYA can effectively alleviate depressive-like behavior in depression model mice, which may be related with the upregulation of GABAARβ1 and GABAARβ2 of hippocampus tissue.

Objective To investigate the efficacy and safety of fluzopril in the treatment of platinum-sensitive recurrent epithelial ovarian cancer.Methods A total of 107 patients with platinum-sensitive recurrent epithelial ovarian cancer admitted to the First Affiliated Hospital of Henan University of Science and Technology from January 2019 to December 2020 were selected as the subjects.According to treatment methods,the patients were divided into control group(n=50)and observation group(n=57).The patients in the control group received a first-line chemotherapy regimen of paclitaxel combined with platinum:on the first day,intravenous infusion with paclitaxel injection 135 mg·m-2 was administered;on day 1-3,intravenous drip with cisplatin 50-60 mg·m-2 was administered;21 days was one chemotherapy cycle.On the basis of the treatment in the control group,the patients in the observation group were given fluzoparide capsules orally,150 mg each time,twice a day,and the treatment continued until disease progression or unacceptable toxic reactions occurred;21 days was one chemotherapy cycle.The patients in both groups received three consecutive chemotherapy cycles.The clinical efficacy,prognosis within 2 years after chemotherapy,Karnofsky Performance Status(KPS)score before and after chemotherapy,and incidence of adverse reactions during chemotherapy of patients between the two groups were compared.Results After 3 cycles of chemo-therapy,the disease control rate and objective remission rate of patients in the observation group were significantly higher than those in the control group(x2=5.420,4.220;P＜0.05).Following up to 24 months,the progression free survival of patients in the observation group was significantly longer than that in the control group(t=6.702,P＜0.05);there was no statistically significant difference in 1-year survival rate of patients between the two groups(x2=0.415,P＞0.05);the 2-year survival rate of patients in the observation group was significantly higher than that in the control group(x2=5.420,P＜0.05).Before chemotherapy,there was no statistically significant difference in KPS scores of patients between the two groups(t=0.537,P＞0.05);the KPS scores of patients in the two groups after three cycles of chemotherapy were significantly higher than those before chemotherapy(t=5.604,9.378;P＜0.05);after three cycles of chemotherapy,the KPS score of patients in the observation group was significantly higher than that in the control group(t=2.608,P＜0.05).The patients in both groups experienced hematological and non-hematological adverse reactions during chemotherapy;the main hematological adverse reactions was bone marrow suppression,most of which were Ⅲ ° and Ⅳ ° adverse reactions;the non-hematological adverse reactions included alo-pecia,gastrointestinal reactions,and liver and kidney dysfunction,most of which were Ⅰ°and Ⅱ°adverse reactions.There were no chemotherapy related deaths of patients in both groups.The incidence rates of anemia,thrombocytopenia,neutropenia,leuko-penia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated alanine amino-transferase(ALT)of patients during chemotherapy in the control group were 68.00％(34/50),72.00％(36/50),58.00％(29/50),68.00％(34/50),22.00％(11/50),26.00％(13/50),24.00％(12/50),46.00％(23/50),30.00％(15/50),50.00％(25/50),20.00％(10/50),10.00％(5/50),respectively;the incidence rates of anemia,thrombocytopenia,neutropenia,leukopenia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated ALT of patients during chemotherapy in the observation group were 61.40％(35/57),63.16％(36/57),49.12％(28/57),52.63％(30/57),21.05％(12/57),22.81％(13/57),24.56％(14/57),42.11％(24/57),29.82％(17/57),47.37％(27/57),21.05％(12/57),10.53％(6/57),respectively.There was no statistically significant difference in the incidences of anemia,thrombocytopenia,neutropenia,leukopenia,lymphopenia,nausea,vomiting,fatigue,loss of appetite,hair loss,elevated serum creatinine,and elevated ALT of patients during chemotherapy between the control group and the observation group(x2=0.047,0.000,0.041,0.694,0.056,0.000,0.208,0.041,0.184,0.160,0.233,0.102;P＞0.05).Conclusion For patients with platinum-sensitive recurrent ovarian cancer,the combination of paclitaxel and platinum chemo-therapy combined with fluzopril can effectively improve the anti-tumor effect,prolong the progression-free survival,improve survival rate and quality of life,and the adverse reactions are controllable.

Objective To investigate the preventive therapeutic effect and possible mechanism of single chain variable fragments chimeric protein (SD) of ovalbumin epitopes internalizing receptor DEC-205 antibody on food allergy in mice. Methods Mice were randomly divided to five groups (control, PBS, scFv DEC 100 μg, SD 50 μg, SD 100 μg) and treated for 24 hours before OVA administration. After challenge, the serum level of OVA-specific IgE, IgG1, IgG2a and IL-4 were detected by ELISA. Infiltration of eosinophils and mast cells in the jejunum was observed by HE staining and toluidine blue staining respectively. The bone marrow of tibia and femur was isolated and cultured to obtain immature dendritic cells(BMDCs), which were further treated with LPS (10 ng/mL), TSLP (50 ng/mL), scFv DEC protein (1000 ng/mL) and SD protein (10,100,1000)ng/mL for 24 hours, and the IL-10 level of supernatant was assayed by ELISA. Results Compared with PBS group, the number of SD-treated mice with diarrhea was markedly reduced. The difference in rectal temperature and the levels of serum OVA-specific IgE, IgG1, IgG2a and IL-4 decreased significantly after prophylactic administration of SD; The number of eosinophils and mast cells in jejunum also decreased significantly while the IL-10 level in the supernatant of BMDCs increased significantly after SD intervention. Conclusion SD mitigates experimental FA response by fosters the immune tolerance property of dendritic cells.
Mice ; Animals ; Ovalbumin ; Interleukin-10 ; Single-Chain Antibodies/genetics* ; Immunoglobulin E ; Epitopes/therapeutic use* ; Interleukin-4 ; Food Hypersensitivity/prevention & control* ; Immunoglobulin G ; Recombinant Fusion Proteins/genetics* ; Mice, Inbred BALB C ; Disease Models, Animal

Objective:To explore the mechanism of dendritic cells(DCs),novel regulatory B cells(B10 cells)and Th17/Treg imbalance in the pathogenesis of patients with chronic obstructive pulmonary disease(COPD)and their correlation with lung function.Methods:According to the"Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease"a total of 93 COPD patients were prospectively selected from the Ninth People's Hospital of Suzhou from May 2019 to December 2021,and 50 healthy subjects were selected as the control group.The patients were followed up for 1 year to observe the occurrence of acute exacer-bation COPD(AECOPD),and divided them into stable COPD group and AECOPD group.The course of disease,modified British Medical Research Society dyspnea index(mMRC)classification,COPD assessment test(CAT)score,BODE index score,6 min walking distance(6MWD),arterial partial pressure of oxygen(PaO2),arterial carbon dioxide Partial pressure(PaCO2)were com-pared between the two groups;compared the levels of FEV1,FVC,FEV1/FVC,and the percentage of FEV1 to predicted value(FEV1/Pred)in the three groups with peripheral blood DCs,B10 cells,Th17 cells,Treg cells and Th17/Treg,IL-12,IL-10,IL-17A and TGF-β1 levels.To analyze the correlation between peripheral blood DCs cells,B10 cells and Th17/Treg imbalance and pulmonary function indexes in AECOPD group.Logistic regression analysis of independent risk factors for AECOPD.Results:A total of COPD pa-tients had AECOPD events(40.86%).The course of disease,mMRC grade,CAT score,BODE index score,and PaCO2 in AECOPD group were significantly higher than those in COPD stable group(P<0.05),6MWD and PaO2 were significantly lower than those in COPD group.The levels of FEV1,FVC,FEV1/FVC and FEV1/Pred in the AECOPD group were significantly lower than those in the stable COPD group and control group(P<0.05);the levels of FEV1,FVC,FEV1/FVC and FEV1/Pred in the stable COPD group were significantly lower than those in control group(P<0.05).DCs,B10 cells and Treg cells in AECOPD group were significantly lower than those in stable COPD group and control group,while Th17 expression level and Th17/Treg were significantly higher than that in stable COPD group and control group(P<0.05).DCs,B10 cells and Treg cells in stable COPD phase were significantly lower than those in control group,while Th17 expression level and Th17/Treg were significantly higher than control group(P<0.05).The ex-pression levels of IL-12,IL-10 and TGF-β1 in the AECOPD group were significantly lower than those in the stable COPD group and control group(P<0.05),while IL-17A was significantly higher than that in the stable COPD group and control group.The expression levels of IL-12,IL-10 and TGF-β1 in patients with stable COPD were significantly lower than control group,while IL-17A was signifi-cantly higher than control group(P<0.05).Pearson analysis showed that peripheral blood DCs,B10 cells were positively correlated with FEV1,FVC,FEV1/FVC and FEV1/Pred levels(P<0.05),while Th17/Treg was positively correlated with FEV1,FVC,FEV1/FVC and FEV1/Pred levels all were negatively correlated(P<0.05).Logistic regression analysis found that mMRC grade and Th17/Treg were independent risk factors of AECOPD(P<0.05).Conclusion:With the progression of COPD,DCs,B10 cells,Th17 cells,Treg cells and Th17/Treg gradually become unbalanced,resulting in disordered expression levels of pro-inflammatory and anti-inflamma-tory factors.Peripheral blood DCs and B10 cells were positively correlated with lung function levels,while Th17/Treg were negatively correlated with lung function levels.mMRC grade and Th17/Treg are independent risk factors of AECOPD.Therefore,actively inter-vening in the imbalanced state of immune function in patients has specific and important clinical significance in reducing the immune damage of lung tissue and promoting the improvement of lung function.