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Objective:To explore influencing factors affecting the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving immunotherapy based on hematologic indexes, thus to construct and evaluate a nomogram prediction model.Methods:The clinical data of 80 patients with advanced NSCLC treated with programmed death-1 inhibitor monotherapy or combination regimen from January 2018 to June 2020 at the Affiliated Hospital of North China University of Science and Technology and Tangshan People's Hospital were retrospectively analyzed. Hematologic indexes at the baseline, the optimal remission and the progressive disease (PD) were collected separately, and independent influencing factors for patient prognosis were analyzed using Cox proportional hazards regression model. A nomogram prediction model was constructed based on the results of the multifactorial analysis, and the predictive performance of the model was evaluated by receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curves.Results:As of the follow-up cut-off date, of the 80 patients, 63 had PD, with a median overall survival (OS) of 16.9 months. Univariate analysis showed that, age ( HR=2.09, 95% CI: 1.17-3.74, P=0.013) , number of treatment lines ( HR=2.23, 95% CI: 1.21-4.12, P=0.010) , lymphocyte to monocyte ratio (LMR) at the baseline ( HR=0.75, 95% CI: 0.57-0.97, P=0.028) , D-dimer ( HR=1.00, 95% CI: 1.00-1.00, P=0.002) and lactate dehydrogenase (LDH) ( HR=1.01, 95% CI: 1.00-1.01, P=0.006) at the optimal remission, haemoglobin ( HR=0.97, 95% CI: 0.96-0.99, P<0.001) , D-dimer ( HR=1.00, 95% CI: 1.00-1.00, P=0.002) , C-reactive protein ( HR=1.01, 95% CI: 1.00-1.01, P=0.011) , albumin (ALB) ( HR=0.91, 95% CI: 0.87-0.96, P=0.001) , neutrophil to lymphocyte ratio (NLR) ( HR=1.16, 95% CI: 1.05-1.27, P=0.002) and LMR ( HR=0.62, 95% CI: 0.42-0.90, P=0.012) at the PD were all influencing factors for the prognosis of advanced NSCLC patients receiving immunotherapy. Least absolute shrinkage and selection operator regression were used to screen the variables for P<0.10 in the univariate analysis, and nine possible influencing factors were obtained, which were age, fibrinogen and LDH at the optimal remission, haemoglobin, D-dimer, C-reactive protein, LDH, ALB and LMR at the PD. Multivariate analysis of the above variables showed that, age ( HR=0.91, 95% CI: 0.86-0.97, P=0.004) , LDH ( HR=1.01, 95% CI: 1.00-1.01, P=0.013) and ALB ( HR=0.82, 95% CI: 0.67-0.99, P=0.041) at the PD were independent influencing factors for the prognosis of patients with advanced NSCLC who received immunotherapy. The area under curve of the nomogram predicting model based on the above indexes, 1- and 2-year OS rates of patients were 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.66-0.88) , respectively, and C-index was 0.71 (95% CI: 0.64-0.78) , the calibration curves showed good consistency between predicted and actual probability of occurrence. Patients in the low-risk group ( n=40) had a median OS of 29.9 months (95% CI: 22.5 months-NA) , which was significantly better than that of the high-risk group ( n=40) [13.4 months (95% CI: 11.4-23.5 months) , χ2=11.30, P<0.001]. Conclusion:Age, LDH and ALB at the PD are independent influencing factors affecting the prognosis of patients with advanced NSCLC receiving immunotherapy, and the nomogram model constructed based on the above indexes has good differentiation and calibration for predicting 1- and 2-year OS rates in advanced NSCLC patients receiving immunotherapy.
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ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity （COM） model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group （Chow）， a diet-induced obesity group （DIO）， and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group， a COM group， and a tumor necrosis factor-α（TNF-α） knock-down group. In the TNF-α knock-down group， TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis， and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group， a DIO group， a DIO + low-dose tripterine group （0.5 mg·kg-1）， a DIO + high-dose tripterine group （1.0 mg·kg-1）， a COM group， a COM + low-dose tripterine group （0.5 mg·kg-1）， and a COM + high-dose tripterine group （1.0 mg·kg-1）. The body weight， food intake， glucose tolerance， white/brown fat ratio， serum total cholesterol （TC）， triglyceride （TG）， and high-/low-density lipoprotein cholesterol （HDL-C and LDL-C） content were recorded， and obesity of mice in each group was evaluated. Forced swimming test （FST）， tail suspension test （TST）， and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y， tryptophan hydroxylase 2 （TPH2）， and brain-derived neurotrophic factor （BDNF） in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific， obesity was manifested as increased body weight and food intake （P<0.05， P<0.01）， as well as increased NPY expression in the central amygdala， and depression was manifested as prolonged immobility time in FST and TST （P<0.01）， and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus （DRN） and basolateral nucleus of the amygdala （BLA）. The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST （P<0.05， P<0.01）， increased TPH2/BDNF-positive neurons in BLA， and showed no significant changes in obesity. In DIO mice， the administration of 0.5 mg·kg-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance （P<0.01） and food intake （P<0.05）. In COM mice， 1.0 mg·kg-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance （P<0.01）， and food intake （P<0.05）， and immobility time in TST （P<0.01）， increase TPH2-BDNF double-labeled cells in BLA and DRN， and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity， and its mechanism may be related to the inhibition of central nervous system inflammation.
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Background : Studies showed that esophageal body dysmotility is associated with gastroesophageal reflux disease (GERD), however, their interactions are still unclear. Aims: To explore the influence of proportion of ineffective swallows on esophageal motility and gastroesophageal reflux in esophageal high-resolution manometry (HRM). Methods: Patients who completed esophageal HRM and 24 h esophageal impedanee-pH monitoring and were identified as normal esophageal motility or mild dysmotility from March 2018 to December 2019 at the First Affiliated Hospital of Nanjing Medical University were recruited retrospectively. According to the times of ineffective swallows in 10 warm water swallows in HRM, these patients were allocated into four groups; Group A (0 times), Group B (1-4 times), Group C (5-7 times), Group D (8-10 times). The parameters of esophageal HRM and 24 h esophageal impedance-pH monitoring were analyzed, and the value of ineffective swallows for assistant diagnosis of pathological acid reflux was assessed. Results: A total of 142 patients were included. There were no significant differences in abnormal manometric parameters between the four groups (all P > 0. 05). In Group D, the number of weak and non-peristalsis were increased, while the mean and maximum value of distal contractile integral (DCI) were decreased as compared with those in Group A and Group B (all P 70 % might be most significant, and to a certain extent, can predicts pathological acid reflux.
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OBJECTIVE：To prepare GGPFV-modified Daunorubicin/dioscin liposomes ，and to optimize their formulation and to preliminarily evaluate their cytotoxicity to breast cancer cells in vitro . METHODS ：Daunorubicin and diosgenin were wrapped by thin film dispersion method and ammonium sulfate hydration method ；the surface was modified with DSPE-PEG2000-GGPFV to prepare GGPFV-modified Daunorubicin/dioscin liposomes. Taking encapsulation rate as index ，Box-Behnken response surface methodology was used to optimize the film hydration volume ，cholesterol amount and daunorubicin amount in the formulation. The entrapment efficiency of 3 batches of liposomes prepared according to the optimal formulation was determined. The effects of Daunorubicin/dioscin liposomes ，GGPFV-modified Daunorubicin/dioscin liposomes and blank liposomes on the survival rate of human breast cancer MDA-MB- 435S cells were compared. RESULTS ：The optimal formulation was as film hydration volume of 5 mL，cholesterol of 4 mg，yolk lecithin of 22 mg，daunorubicin of 0.55 mg，dioscin of 0.85 mg，DSPE-PEG2000 of 3.5 mg， DSPE-PEG2000-GGPFV of 2 mg. The encapsulation rate of daunorubicin was （96.21±1.54）％ and that of dioscin was （95.39± 2.48）％ in the 3 batches of liposomes prepared. The in vitro cytotoxicity tests showed that the inhibition effect of GGPFV-modified Daunorubicin/dioscin liposome on MDA-MB-435S cells was significantly stronger than that of Daunorubicin/dioscin liposome （P＜ 0.05）. There was no cytotoxicity in the membrane. CONCLUSIONS ：GGPFV-modified Daunorubicin/dioscin liposomes are successfully prepared ，and its inhibitory effect on human breast cancer MDA-MB- 435S cells in vitro was significantly enhanced.
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ObjectiveTo analyze Rome Ⅱ and Rome Ⅲ criteria in clinical characteristics of functional dyspepsia (FD) diagnosis and the differences in subtypes of FD,and to assess the psychosocial status of FD patients.Methods From June 2008 to December 2008,1600 random outpatients who underwent upper gastrointestinal endoscopy in department of gastroenterology fulfilled the inquiry questionnaire.The subtype was diagnosed according to Rome Ⅲ and the Rome Ⅱ criteria and the results were analyzed.ResultsA total of 215 patients (13.44％) were in accordance with Rome Ⅱ criteria and 249 patients (15.56 ％) were in accordance with Rome Ⅲ criteria,there was no difference in FD detection rate between these two criteria (x2=2.176,P＞0.05).About 71.16％(153/215) of the FD patients diagnosed according to Rome Ⅱ criteria were also in accordance with Rome Ⅲ criteria,and 23.26％ (50/215) who had bothersome postprandial fullness,early satiation,epigastic pain or epigastric burning did not meet Rome Ⅲ criteria.About 61.45 ％ (153/249) of the FD patients diagnosed according to Rome Ⅲ criteria were also in accordance with Rome Ⅱ criteria,and the courses of disease of 28.92％(72/249) patients didn't met Rome Ⅱ criteria.According to RomeⅡ,51 (23.72％) patients were ulcer-like type,103 (47.91％)patients were dysmotility-like type,and 61 (28.37％) patients were non-idiotype.According to Rome Ⅲ criteria,76.31％ (190/249) patients were consistent with postprandial distress syndrome (PDS),52.61％ (131/249) patients were consistent with epigastric pain syndrome (EPS),and 28.92％ (72/249) patients met both PDS and EPS.The percentage of the FD patients with anxiety and depression was 16.83％ and 47.52％respectively.Of the FD patients in accordance with Rome Ⅲ criteria who were with both anxiety and depression,the total symptom scores of bothersome postprandial fullness,early satiation,epigastic pain or epigastic burning were the highest (x2 =49.637,P＜0.05).ConclusionsRome Ⅲ criteria is easier to understand and more practical.FD patients always have psychosocial disorders,which may worsen the clinical symptoms.