OBJECTIVES: To evaluate the protective effect of Bufei Yishen Formula (BYF) against cigarette smoke extract (CSE)-induced injuries in human bronchial epithelial BEAS-2B cells and explore the underlying mechanism. METHODS: BEAS-2B cells exposed to CSE were treated with normal rat serum, BYF-medicated rat serum at low or high doses, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), PDTC combined with high-dose BYF-medicated serum, or S-carbomethyloysteine (S-CMC, as the positive control). CCK-8 assay was used to determine the optimal concentration and treatment time of CSE, BYF-medicated serum and S-CMC. The treated cells were examined for inflammatory factor levels in the supernatant and cellular expressions of MUC5AC and MUC5B using ELISA, cell ultrastructural changes with transmission electron microscopy, and cell apoptosis rate using flow cytometry. The expression levels of TLR4/NF‑κB pathway-associated mRNAs and proteins were determined by qRT-PCR and Western blotting. RESULTS: CSE exposure significantly increased secretions of IL-1β, IL-6 and TNF-α, mRNA and protein expressions of MUC5AC and MUC5B, and early and total apoptosis rates in BEAS-2B cells, where the presence of apoptotic bodies was detected. CSE also significantly enhanced the mRNA and protein expressions of TLR4, I-κB, and NF-κB and reduced mRNA and protein expressions of AQP5. Treatments of the CSE-exposed cells with BYF-medicated serum, PDTC and S-CMC all significantly lowered inflammatory factor levels, MUC5AC and MUC5B expressions, and early and total cell apoptosis rates, and partly reversed the changes in cellular ultrastructure and mRNA and protein expressions of the TLR4/NF-κB pathway, and the effects were the most conspicuous following the combined treatment with high-dose BYF-medicated serum and PDTC. CONCLUSIONS BYF can inhibit cell apoptosis, inflammation and mucus hypersecretion in CSE-induced BEAS-2B cells by inhibiting the TLR4/NF-κB signaling pathway.
Humans ; Epithelial Cells/cytology* ; Drugs, Chinese Herbal/pharmacology* ; NF-kappa B/metabolism* ; Bronchi/cytology* ; Smoke/adverse effects* ; Apoptosis/drug effects* ; Mucin 5AC/metabolism* ; Cell Line ; Toll-Like Receptor 4/metabolism* ; Mucin-5B/metabolism* ; Signal Transduction/drug effects* ; Nicotiana ; Rats ; Thiocarbamates/pharmacology* ; Animals

Objective To investigate the roles of three Tiao-Bu Fei-Shen Traditional Chinese Medicine(TCM)therapies in improving airway mucus hypersecretion in rats with stable chronic obstructive pulmonary disease(COPD).Methods Ninety rats were divided randomly into nine groups:control(Control)group,model(COPD)group,Bu-Fei Jian-Pi Formula(BJF)group,Bu-Fei Yi-Shen Formula(BYF)group,Yi-Qi Zi-Shen Formula(YZF)group,ERK1/2 inhibitor(PD98059)group,Bu-Fei Jian-Pi combined with inhibitor(BJF+PD98059)group,Bu-Fei Yi-Shen combined with inhibitor(BYF+PD98059)group,and Yi-Qi Zi-Shen combined with inhibitor(YZF+PD98059)group.A rat model of COPD was established by exposing rats to cigarette smoke followed by repeated bacterial infection from weeks 1～8.From weeks 9～16,rats in the control and COPD groups were given 2 mL normal saline,rats in the BJF,BYF,and YZF groups were given the three Tiao-Bu Fei-Shen formulas by gavage,and rats in the PD98059,BJF+PD98059,BYF+PD98059,and YZF+PD98059 groups were given PD98059 by intraperitoneal injection for 7 days at the 16th week.Lung function tests were conducted after 16 weeks and lung tissue morphology,lung water content,inflammatory cell count in bronchoalveolar lavage fluid,and serum levels of inflammatory factors were also assessed.Goblet cell proportion was determined by Alcian blue-periodic acid-Schiff staining,and Muc5AC and Muc5B expression levels were detected by immunohistochemistry.mRNA expression levels of ERK1,ERK2,ENaC,CFTR,and AQP5 were detected by polymerase chain reaction and protein expression levels of ERK1/2 and P-ERK1/2 in lung tissue were determined by Western Blot.Results TV,MV,FVC,FEV0.1,FEV0.1/FVC were significantly decreased(P＜0.01)in COPD rats compared with those in the control group.Lung pathology revealed alveolar disorder,massive fracture of the alveolar wall,and severe shrinkage/thickening of the airway wall accompanied by extensive infiltration of inflammatory cells.Lung tissue water content was significantly increased in COPD rats(P＜0.01),while the proportion of macrophages in BALF was significantly reduced(P＜0.01)and the proportions of neutrophils and lymphocytes were significantly increased(P＜0.01).Serum levels of TNF-α and IL-1β were significantly increased in COPD rats(P＜0.05,P＜0.01).The percentage of goblet cells and expression levels of Muc5AC and Muc5B in airway epithelial cells were significantly increased(P＜0.01),mRNA expression levels of ERK1,ERK2,and ENaC in lung tissue were significantly elevated(P＜0.01),while mRNA expression levels of CFTR and AQP5 were significantly decreased(P＜0.01)in COPD rats compared with levels in the control group.The expression of P-ERK1/2,ERK1/2 in lung tissue was significantly increased(P＜0.01)Rats in the treatment groups demonstrated improvements in the above indicators(P＜0.05,P＜0.01)compared with the COPD group,the groups receiving the three Tiao-Bu Fei-Shen formulas combined with PD98059 showing superior efficacy compared with the single treatment groups(P＜0.05,P＜0.01).Conclusions The three tested Tiao-Bu Fei-Shen therapies can ameliorate airway mucus hypersecretion in COPD rats by inhibiting the ERK1/2 signaling pathway.

AIM:To investigate the effects of the three Tiao-Bu Fei-Shen therapies on renal injury in rats with chronic obstructive pulmonary disease(COPD),and to explore the mechanisms.METHODS:SPF-grade SD rats were randomly divided into control,COPD,pyrrolidinedithiocarbamate ammonium(PDTC),Bufei-Jianpi formula(BJF),Bu-fei-Yishen formula(BYF),Yiqi-Zishen formula(YZF),BJF combined with PDTC(BJF+PDTC),BYF combined PDTC(BYF+PDTC),and YZF combined PDTC(YZF+PDTC)groups.Cigarette smoke exposure combined with bacterial infec-tion were used to develop a stable-phase rat model of COPD,and kidney-injured rats were screened for subsequent treat-ment.Pulmonary and renal functions,pathological changes in lung and kidney tissues,24 h urine volume,urine biochem-ical indexes,aquaporin(AQP)levels,ratio of inflammatory cells in the bronchoalveolar lavage fluid(BALF),serum in-flammatory factor levels,and mRNA and protein expressions of IκB kinase(IKK)and nuclear factor-κB(NF-κB)were observed at the end of the 16th week.RESULTS:Compared with control group,the rats in COPD group showed reduced lung function indexes of forced expiratory vital capacity(FVC),forced expiratory volume in 0.1 second(FEV0.1)and FEV0.1/FVC(P<0.05).The lung histopathology exhibited alveolar wall fracture and fusion and airway inflammatory cell infiltration.The renal function indexes serum creatinine,blood urea nitrogen and serum cystatin C(Cys-C)were signifi-cantly increased(P<0.01).The renal histopathology showed swollen and disorderly arranged tubular epithelial cells.The 24 h urine volume decreased(P<0.01).The urinary biochemical indexes 24 h urinary total protein,urinary kidney injury molecule-1(KIM-1),urinary Cys-C,and urinary N-acetyl-β-D-glucosaminidase significantly increased(P<0.01).The protein levels of AQP1～4 were significantly increased(P<0.01).The ratio of neutrophils and lymphocytes in the BALF were increased(P<0.01).The ratio of monocytes was decreased(P<0.01).The serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-13,IL-1β,and transforming growth factor-β1(TGF-β1)were significantly increased(P<0.01).And the mRNA and protein expression levels of IKK,NF-κB were significantly elevated in the renal tissue(P<0.05).Compared with COPD group,the above symptoms and indexes of the rats were improved to different degrees after the intervention in treatment groups,among which BJF,BYF and YZF demonstrated similar effects to PDTC,and BJF+PDTC,BYF+PDTC and YZF+PDTC exhibited better improvements than the corresponding monotherapy.CONCLU-SION:The three Tiao-Bu Fei-Shen therapies can reduce the airway and systemic inflammatory response,improve renal function and attenuate renal injury in COPD rats.The mechanism may be related to the inhibition of NF-κB signaling path-way.

Chronic obstructive pulmonary disease(COPD)is a disease characterized by persistent respiratory symptoms and airflow limitation,and also associated with a variety of comorbidities.As one of the important extrapulmonary comorbidities of COPD,kidney injury has a high incidence and insidious onset,which will develop into chronic kidney disease without timely intervention,greatly increasing the risk of mortality and economic burden of COPD patients.There exist physiological and pathological relations between lung and kidney functions.However,the mechanisms underlying COPD-associated kidney injury remain unclear.This article provides a review of the research progress on the mechanisms of COPD-associated kidney injury,in order to provide reference for the clinical prevention and treatment and basic research.

The global production and consumption of sugar-sweetened beverages (SSBs) has been on the rise in recent decades. The intake of SSBs has been increasing in China, and it is more prevalent among children and adolescents. As research continues to intensify, more and more studies have shown that, in addition to the increased risks of dental caries and obesity reported by the World Health Organization (WHO), SSBs intake can also increase risks of chronic diseases such as diabetes, cardiovascular disease, gout, and cancer, and early death, adding to the burden of disease. Due to the health risks associated with the overconsumption of SSBs, many countries around the world have taken measures to control the intake. The main measures currently in place are taxation of SSBs, restrictions on marketing and sales of SSBs, front-of-package labeling and reducing availability of SSBs in schools. In China, the main measures currently in place are to control the sales of beverages in schools, with Shenzhen taking the lead in implementing health warning labeling to alcoholic beverages and carbonated beverages, extending the measures to reduce SSBs intake beyond school grounds.

Thyroid carcinoma is a common cervical tumor. Its occurrence is associated with genetic and environmental factors. The incidence rate of thyroid cancer is increasing. However, the pathogenesis and the influencing factors of thyroid carcinoma are not yet fully understood. Many clinical studies and epidemiological investigations have found that such factors as radiation exposure, female hormone metabolism, and obesity have important links with the occurrence of thyroid cancer, but its association with factors such as dietary factors remains controversial. Therefore, it is urgent to explore and validate the relationship between various factors and thyroid cancer through epidemiological studies. In order to provide reference for the prevention of thyroid cancer, this special column “Thyroid carcinoma and associated risk factors” focused on the associations of female reproductive factors and dietary factors (including intake of iodine-rich foods) with thyroid carcinoma (nodules).

Background Papillary thyroid cancer is the result of a variety of pathogenic factors. The prevalence of papillary thyroid cancer varies greatly in different regions, and the disease is more harmful to women. Objective This study aims to explore the relationship between reproductive factors and papillary thyroid cancer, and to provide basic data for prevention and control of the disease. Methods A 1∶1 age (±3 years) matched case-control study was conducted in 331 pairs of newly confirmed papillary thyroid cancer cases and controls from two hospitals in Shanghai from November 2012 to December 2013. Comparisons were made in the history of menstruation, pregnancy, gynecological and breast diseases, and other variables between the two groups. Results The results of univariate analysis indicated that the proportions of education below bachelor degree, married, and mainly manual workers in the case group were significantly higher than those in the control group (P<0.05); the proportion of those with a family history of thyroid diseases in the case group was significantly higher than that in the control group (P<0.05); the proportions of the cases with irregular menstruation (77.34%), a history of using oral contraceptive or hormone drugs (24.77%), a history of benign gynecological diseases (31.72%), and a history of gynecological surgery (9.67%) were significantly higher than the proportions in the control group (P<0.05). After adjusting potential confounding factors such as history of CT examination, age, kinds of family salt, total iodine intake every day, education level, occupation, marital status, body mass index, and family history of thyroid diseases, the results of multiple logistic regression analysis showed that irregular menstruation (OR=1.767, 95%CI: 1.122-2.782; P=0.014), surgical menopause (OR=12.787, 95%CI: 3.202-51.057; P<0.001), pregnancy >1 time (OR =2.490, 95%CI: 1.196-5.184; P=0.015), and the history of using oral contraceptive or hormone drugs (OR=2.389, 95%CI: 1.338-4.268; P=0.003) were the risk factors of papillary thyroid cancer. Conclusion Irregular menstruation, surgical menopause, history of pregnancy, and history of using oral contraceptive or hormone drugs might be the risk factors of papillary thyroid cancer. To reduce the incidence of papillary thyroid cancer, strengthened health education and rational use of contraceptives are recommended.

Background There are few studies on the diet quality of patients with thyroid cancer, and the relationship between diet quality and thyroid cancer remains uncertain. Objective This study aims to assess the diet quality with the Chinese Health Diet Index (CHDI) and to explore the relationship between diet quality and papillary thyroid carcinoma (PTC). Methods A 1∶1 gender- and age-matched hospital-based case-control study included newly diagnosed PTC patients and matched controls from Shanghai Cancer Hospital and Renji Hospital (East) in Shanghai, China. A structured questionnaire was applied to collect data on general characteristics, history of diseases, dietary intakes, and lifestyles. Food intakes in the past one year were assessed using a validated food frequency questionnaire, from which the CHDI score was calculated. The CHDI, according to the Dietary Guidelines for Chinese Residents, was employed to evaluate the diet quality of the two groups. A multiple conditional logistic regression model was conducted to explore the relationship between diet quality and PTC. Results A total of 350 pairs of cases and controls were recruited. The overall median CHDI score of the cases was lower than that of the controls (67.8 vs. 73.4, P<0.001). The cases had lower median scores of fruits (6.8 vs. 9.5), dairy products (3.6 vs. 5.6), and soybeans (4.6 vs. 5.5) than the controls (P<0.05); the cases had a higher median score of refined grains than the controls (5.0 vs. 4.9), and the percentage of the cases that met diet recommendations for refined grains was higher than the percentage of the controls (65.4% vs. 48.6%) (P<0.05); the cases showed lower median scores of whole grains/beans/tubers, total vegetables, dark vegetables, and fish/shrimps (0.9 vs. 1.4, 3.1 vs. 4.4, 3.6 vs. 5.0, and 3.3 vs. 4.0, respectively), and the percentages of the cases meeting their diet recommendations were lower than the percentages of the controls (6.3% vs. 8.6%, 32.6% vs. 42.0%, 38.6% vs. 50.6%, and 34.0% vs. 40.3%, respectively, P<0.05). The results of multiple conditional logistic regression analysis suggested that qualified and good diet quality were associated with a reduced the risk of PTC (qualified diet quality, OR=0.37, 95%CI: 0.23−0.62; good diet quality, OR=0.19, 95%CI: 0.10−0.36); the statistical significance remained after excluding patients who had a history of benign thyroid conditions (qualified diet quality, OR=0.28, 95%CI: 0.15−0.52; good diet quality, OR=0.20, 95%CI: 0.09−0.43). Conclusion Those with qualified or good diet quality have a lower risk of PTC. PTC patients have insufficient intakes of fruits, dairy, soybeans, whole grains/beans/tubers, vegetables, and fish/shrimps.

Background Thyroid carcinoma is a serious threat to human health in Shanghai and a focus of cancer prevention and treatment. Objective This study aims to assess the relationship between foods rich in iodine and papillary thyroid carcinoma (PTC)．Methods In a hospital-based case-control study matched by gender and age (±3 years old), 402 pairs of cases (new incidences) and controls were included and studied. A validated questionnaire and food frequency questionnaire survey was conducted face to face to obtain demographic characteristics and dietary intake. A multiple conditional logistic regression model was applied to explore the relationship between foods rich in iodine (including seaweeds, kelp, and dried shrimps) and PTC. Results The mean age of the participants was (41.17±11.51) years in this study. Compared with the controls, more cases had a lower education and a manual occupation (P<0.05); more cases were overweight or obese, had a history of benign thyroid conditions, and had a family history of thyroid diseases (P<0.05); the two groups were different in the frequency of CT examination in the past ten years (P<0.05). The results of multiple conditional logistic regression analysis showed that consumption of iodine-rich foods was associated with a lower risk of PTC (for <1 time per week, OR=0.20, 95%CI: 0.12−0.35; for 1−2 times per week, OR=0.18, 95%CI: 0.10−0.33; for ≥3 times per week, OR=0.13, 95%CI: 0.04−0.44) (P<0.05). Specifically, those who consumed seaweeds (for <1 time per week, OR=0.18, 95%CI: 0.11−0.30; for 1−2 times per week, OR=0.11, 95%CI: 0.05−0.23; for ≥3 times per week, OR=0.15, 95%CI: 0.03−0.75), kelp (for <1 time per week, OR=0.28, 95%CI: 0.18−0.43; for ≤2 times per week, OR=0.24, 95%CI: 0.11−0.50), and dried shrimps (for <1 time per week, OR=0.44, 95%CI: 0.29−0.69; for ≤2 times per week: OR=0.34, 95%CI: 0.18−0.65) had a lower risk of PTC (P<0.05). After excluding patients who had a history of benign thyroid conditions, the favorable association remained significant among patients who had consumption of iodine-rich foods, seaweeds, shrimps, and kelp (P<0.05). Conclusion Less PTC patients consume iodine-rich foods than the controls.

Background Both domestic and foreign studies on the diet quality of patients with thyroid nodules are rare at present, and the relationship between thyroid nodules and diet quality is still unclear. Objective This study aims to evaluate the diet quality of thyroid nodules with the China Healthy Diet Index (CHDI) and to explore the relationship between diet quality and thyroid nodules. Methods We conducted a hospital-based case-control study in which 387 patients with thyroid nodules were matched individually (1∶1) by gender and age (±3 years) to the controls who ordered a routine physical examine and with negative thyroid nodules reported by B-ultrasound in the same hospital. A structured questionnaire was applied to collect data on general characteristics and diet. CHDI was employed to evaluate the diet quality of the two groups. CHDI is based on the Dietary Guidelines for Chinese Residents and the recommended food intake in the balanced diet pagoda, combined with the dietary nutritional status of Chinese population. The index contains 13 scoring components, and the highest total score is 100, with a higher score representing better dietary quality. CHDI scores < 60, 60-<80, and ≥80 are recognized as unqualified, qualified, and good diet quality, respectively. Results The scores of the thyroid nodule cases were lower than the scores of the controls in total vegetables, dark vegetables, fruits, and fish/shrimps (all Ps<0.05). The nonparametric test results found that there were significant differences in the distributions of scores in total vegetables, dark vegetables, fruits, soybeans, and fish/shrimps between the case and the control groups (all Ps<0.05). The percentages reaching the full scores in food variety, meat and eggs, and empty calories in both groups exceeded 60%, while the percentages reaching the full scores in whole grains/beans/tubers, dairy, soybeans, and sodium were lower than 30% in the two groups. The median CHDI scores of the thyroid nodule cases and the controls were 69.1 and 72.9, respectively; the cases' CHDI score was lower than the controls' (P<0.05). The proportions of unqualified diet in the case and the control groups accounted for 23.0% and 13.7% respectively (P=0.001). After being adjusted for education level, marital status, occupation, monthly household income per capita, body mass index, hypertension/diabetes, energy, and iodine intake, the results of logistic regression analysis showed that the risk for thyroid nodules was negatively associated with CHDI score (CHDI qualified group vs. CHDI unqualified group, OR=0.484, 95%CI: 0.291-0.804; CHDI good dietary quality group vs. CHDI unqualified group, OR=0.414, 95%CI: 0.230−0.746). Conclusion The diet quality of patients with thyroid nodules is lower than that of the control group, as the former reported lower consumptions of total vegetables, dark vegetables, fruits, and fish/shrimps. Those who have good or qualified diet quality show a reduced risk of thyroid nodules than those with unqualified dietary quality.