Objective To observe the effectiveness and safety of pirfenidone in the prevention and treatment of radiation-induced lung injury in esophageal cancer.Methods We retrospectively analyzed the data of 103 patients with esophageal cancer,of whom 53 in the combined group were treated with simultaneous chemoradiotherapy combined with pirfenidone and 50 in the control group were treated with simultaneous chemoradiotherapy only.The patients were followed up for three years to observe the treatment effects,adverse effects,and survival,as well as the incidence of radiation-induced lung injury,lung function,and changes in lung injury cytokine levels within one year after radiotherapy.Results Treatment efficiency in the combined group was higher than that in the control group(86.8%vs.70.0%,P＜0.05).The two-and three-year survival rates in the combined group were 84.9%and 71.7%,respectively,which were higher than those(68.0%and 52.0%)in the control group(P＜0.05).The one-,two-,and three-year disease-free survival rates in the combined group were 86.8%,67.9%,and 47.2%,respectively,which were higher than those(62.0%,46.0%,and 28.0%)in the control group(P＜0.05).The incidence rates of radiation pneumonitis at three months,pulmonary fibrosis at six months,and one year after radiotherapy in the combined group were 22.6%,13.2%,and 14.0%,respectively,which were lower than those(42.0%,30.0%,and 31.8%)in the control group at the same time(P＜0.05).At the end of radiotherapy and at three months,six months and one year after radiotherapy,the combined group showed higher levels of lung function indicators but lower levels of lung injury-related cytokines than the control group(P＜0.05).The incidence of rash in the combined group was 18.9%,which was higher than that(2.0%)in the control group(P＜0.05).However,no statistically significant difference in the incidence and severity of other adverse reactions was found between the two groups(P＞0.05).Conclusion Pirfenidone not only effectively reduces radiation-induced lung injury and improves lung function in esophageal cancer patients undergoing simultaneous chemoradiotherapy,but also helps improve tumor control rates and patient survival with a good safety profile.

Objective To observe the effectiveness and safety of pirfenidone in the prevention and treatment of radiation-induced lung injury in esophageal cancer.Methods We retrospectively analyzed the data of 103 patients with esophageal cancer,of whom 53 in the combined group were treated with simultaneous chemoradiotherapy combined with pirfenidone and 50 in the control group were treated with simultaneous chemoradiotherapy only.The patients were followed up for three years to observe the treatment effects,adverse effects,and survival,as well as the incidence of radiation-induced lung injury,lung function,and changes in lung injury cytokine levels within one year after radiotherapy.Results Treatment efficiency in the combined group was higher than that in the control group(86.8%vs.70.0%,P＜0.05).The two-and three-year survival rates in the combined group were 84.9%and 71.7%,respectively,which were higher than those(68.0%and 52.0%)in the control group(P＜0.05).The one-,two-,and three-year disease-free survival rates in the combined group were 86.8%,67.9%,and 47.2%,respectively,which were higher than those(62.0%,46.0%,and 28.0%)in the control group(P＜0.05).The incidence rates of radiation pneumonitis at three months,pulmonary fibrosis at six months,and one year after radiotherapy in the combined group were 22.6%,13.2%,and 14.0%,respectively,which were lower than those(42.0%,30.0%,and 31.8%)in the control group at the same time(P＜0.05).At the end of radiotherapy and at three months,six months and one year after radiotherapy,the combined group showed higher levels of lung function indicators but lower levels of lung injury-related cytokines than the control group(P＜0.05).The incidence of rash in the combined group was 18.9%,which was higher than that(2.0%)in the control group(P＜0.05).However,no statistically significant difference in the incidence and severity of other adverse reactions was found between the two groups(P＞0.05).Conclusion Pirfenidone not only effectively reduces radiation-induced lung injury and improves lung function in esophageal cancer patients undergoing simultaneous chemoradiotherapy,but also helps improve tumor control rates and patient survival with a good safety profile.

Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.

Objective To investigate the correlation between serum leptin level and body mass index(BMI)in in-fants with cyanosis congenital heart disease,and the relationship between leptin and Ob gene receptor(Ob-R)and hypoxia-inducible factor 1α(HIF-1α)in myocardium.Methods A total of 52 children under 6 months of age with congenital heart disease who underwent surgical treatment in the Department of Congenital Heart Surgery,Fuwai Hospital from January 2019 to October 2020 were included in this study.According to the arterial partial pressure of oxygen(PaO2)of 90 mmHg,they were divided into cyanotic group(n=30)and acyanotic group(n=22).Their height and weight were collected to calculate BMI.The serum leptin level was measured by ELISA.The ex-pressions of HIF-1α and Ob-R in myocardial tissue were detected by RT-PCR and Western blot.In animal mod-el,SD rats were divided into normoxia group and hypoxia intervention group,which were subjected to continuous hypoxia(10％ O2)for 4 weeks.The hypoxia intervention group received intraperitoneal injection of HIF-1α in-hibitor digoxin(2 mg/kg)daily from the 14 th to 21st day of hypoxia,respectively.The body weight of rats was recorded,and the expressions of HIF-1α and Ob-R were detected by RT-qPCR and Western blot.Results Com-pared with the acyanosis group,the cyanosis group had a significantly lower BMI(P<0.05)and a lower leptin/BMI ratio(leptin/BMI)(P<0.05).Spearman correlation analysis confirmed that serum leptin in the circulatory system was positively correlated with BMI(P<0.05).In the cyanosis group,the expression of Ob-R increased with the upregulation of HIF-1α,showing a positive correlation.In animal model,with the down-regulation of HIF-1α expression in digoxin injection,the Ob-R level was significantly lower than that in the control group(P<0.05),the trend of weight loss was significantly inhibited(P<0.05).The right ventricular hypertrophy in-dex was significantly lower than that in the control group(P<0.05).Conclusions HIF-1α regulates the expres-sion of Ob-R in myocardial tissue,and the mechanism of its association with leptin and Ob-R may help to find new therapeutic target for improving the prognosis of infants with congenital heart disease.

Objective:To investigate the long-term effects of metabolically healthy obesity on the risks of type 2 diabetes, cardiovascular disease events, and its mortality over a 23-year follow-up.Methods:Based on the results of an oral glucose tolerance test, there were 519 participants with normal glucose tolerance and 630 with newly diagnosed type 2 diabetes enrolled in 1986 and then given to assess the long-term clinical outcomes during the 23-year follow-up in Daqing. Metabolically healthy obesity was defined as the overweight and obese individuals with no metabolic abnormalities (diabetes, hypertension, hyperlipidemia). Finally, we identified 682 participants (350 with normal glucose tolerance and 332 with newly diagnosed diabetes). They were divided into five groups: 211 individuals with metabolically healthy normal weight (MHNW group), 58 with metabolically healthy overweight and obesity (MHO group), 81, 109, 223 were metabolically unhealthy overweight and obesity with hypertension (MUHO group), type 2 diabetes (MUDO group), hypertension and diabetes (MUHDO group). Incidences of type 2 diabetes, morbidity and mortality of cardiovascular disease were compared among these groups.Results:Over 23 years, instead of the morbidity and mortality of cardiovascular disease, the incidence of type 2 diabetes in MHO group was two times higher than in MHNW group ( 24.1%, 12.5/1 000 person years vs 10.9%, 5.2/1 000 person years, P=0.01), with an age, sex, and smoking history-adjusted hazard ratio ( HR) of 2.42 (95% CI 1.24-4.74, P=0.01). The morbidity and mortality of cardiovascular disease in the groups of overweight and obesity with metabolically unhealthy were higher than in MHNW group, and increased across the subjects with MUHO, MUDO, MUHDO ( P<0.05). Conclusion:Compared with metabolically healthy normal weight participants, the metabolically healthy obese group was at increased risk of type 2 diabetes but not cardiovascular disease events and its mortality. On the contrary, the overweight and obese groups with metabolic abnormalities had significant higher incidence of type 2 diabetes, morbidity and mortality of cardiovascular diseases.

Objectives: To evaluate the effect and safety of 14-day continuous subcutaneous insulin infusion (CSII) in type 2 diabetes patients with heart diseases.
Methods: A total of 22 consecutive type 2 diabetes patients (history ≤ 5 years) with heart diseases treated in our hospital from 2011-03 to 2013-08 were studied. There were 20 male, and the with the mean age of patieuts (48.15 ± 9.80) years, all patients without standard hypoglycemic treatment before admission. The patients received 14-day CSII for enhanced treatment and the blood glucose level, insulin function and insulin sensitivity were compared before and after the treatment.
Results: After CSII treatment, the blood glucose level was obviously decreased, fasting blood glucose (FBG) and postprandial blood glucose at 30, 60 and 120 min were improved, all P<0.001. The C peptide level was higher at 60 and 120 min alter treatweut as 2.73 (1.05-7.05)ng/ml vs 3.84 (1.22-63.39)ng/ml, P=0.004 and 3.34 (1.42-9.61)ng/ml vs 6.27 (0.93-47.39)ng/ml, P=0.004. The insulin sensitivity was improved as -1.89 ± 0.29 vs -1.70±0.31, P=0.008. With CSII treatment, there were 22.73% patients (5/22) at remission by controlling the diet and excise and 77.27% (17/22) with continuing medication. The patients were followed-up for (12.4 ± 8.5) months, there were 4/5 patients with euglycemia, 1/5 with increase blood sugar and received medication at 2 months after discharge, the rest 17 patients remained oral hypoglycemic medication.
Conclusion: CSII may quickly relieve glucotoxicity and improve insulin sensitivity in type 2 diabetes patients with heart diseases. Some patients may alleviate drug burden in clinical practice.