ObjectiveTo investigate the potential mechanism of action of the Qufeng Tongqiao Cough-relieving Decoction （祛风通窍止咳方， QTCD） in the treatment of upper airway cough syndrome （UACS）. MethodsTwenty-four guinea pigs were randomly divided into blank group， model group， traditional Chinese medicine （TCM） group， and inhibitor group， with six guinea pigs in each group. Except for the blank group， guinea pigs were sensitized with ovalbumin and aluminum hydroxide via intraperitoneal injection， followed by ovalbumin nasal drops combined with smoke exposure to establish the UACS model. After modeling， the TCM group was administered QTCD 0.9 g/（100 g·d） by gavage， the inhibitor group received the transient receptor potential vanilloid receptor 4 （TRPV4） inhibitor GSK2193874 1 mmol/L， 5 min by nebulisation， and the blank group and model group were given 2 ml/（100 g·d） normal saline by gavage once daily. After 7 days of treatment， a cough provocation test was performed using 0.4 mol/L citric acid. The levels of IgE in serum and inflammatory cytokines， including interleukin-6 （IL-6）， interleukin-8 （IL-8） in serum， bronchoalveolar lavage fluid （BALF）， and nasal lavage fluid （NLF） were detected by enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in lung and nasal mucosal tissues were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry was used to detect the protein levels of TRPV4， substance P （SP）， and calcitonin gene-related peptide （CGRP） in lung and nasal mucosal tissues. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of TRPV4， SP， and CGRP in lung tissues. ResultsHE staining showed significant structural damage and infiltration of inflammatory cells in the lung and nasal mucosal tissues in the model group， while the TCM group and inhibitor group showed improved pathological changes. Compared with the blank group， the model group showed increased cough frequency， serum IgE level， and IL-6 and IL-8 levels in serum， BALF， and NLF. The protein levels of TRPV4， SP， and CGRP in lung and nasal mucosal tissues and their mRNA expression were elevated （P＜0.05 or P＜0.01）. Compared with the model group， the TCM group and inhibitor group showed reduced cough frequency， serum IgE level， and TRPV4 and SP mRNA expression in lung tissues. The TCM group showed reduced IL-6 and IL-8 levels in serum， BALF， and NLF， and reduced TRPV4 and CGRP protein levels in lung and nasal mucosal tissues. The inhibitor group showed reduced IL-6 and IL-8 levels in serum， BALF， and NLF， reduced IL-6 in BALF， reduced IL-8 in NLF， and decreased TRPV4， SP， and CGRP protein levels in lung tissues and SP and CGRP protein levels in nasal mucosal tissues （P＜0.05 or P＜0.01）. Compared with the TCM group， the inhibitor group had increased serum IgE， IL-6， and IL-8 levels， increased IL-6 level in BALF， and increased IL-8 levle in NLF， but decreased SP protein level in lung tissues and increased TRPV4 and SP mRNA expression in lung tissues （P＜0.01）. ConclusionQTCD effectively reduces cough frequency in the UACS guinea pig model. Its mechanism may involve inhibiting the activation of the TRPV4 pathway， improving airway neurogenic inflammation， alleviating inflammatory responses， and reducing cough hypersensitivity.

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1^Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1^Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Objective:To observe the incidence of syncope in patients with acute and critical cardiovascular diseases and to explore the risk factors of death.Methods:925 cases of acute heart failure, acute myocardial infarction, pulmonary embolism, arrhythmia and aortic dissection rupture who participated in Prospective, Multi-CenterRegistered Research Project for Chinese Syncope Patients from March 2018 to March 2020, admitted to the department of emergency of Nanyang Second General Hospital were selected as the research objects. The incidence and mortality of syncope were recorded, and the patients were divided into syncope group and non-syncope group according to whether they were accompanied by syncope or not. The incidence of syncope in male and female patients with different cardiovascular critical diseases, the age and mortality of cardiovascular critical patients with syncope or not were analyzed and compared. Multivariate Logistic regression analysis was used to analyze the risk factors of death, and receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of risk factors on the prognosis of patients.Results:The incidence of syncope in 5 kinds of cardiovascular critical patients from high to low was: acute myocardial infarction 3.03% (28/925), arrhythmia 2.70% (25/925), pulmonary embolism 1.51% (14/925), aortic dissection rupture 1.41% (13/925), acute heart failure 0.65% (6/925), with statistically significant differences ( χ2 = 10.765, P = 0.010). There was no significant difference in the incidence of syncope between male and female patients with pulmonary embolism, aortic dissection rupture, acute myocardial infarction, arrhythmia and acute heart failure. The age of patients with aortic dissection rupture, acute myocardial infarction and arrhythmia in syncope group were significantly higher than those in non-syncope group [aortic dissection rupture (years old): 66.29±15.64 vs. 57.63±14.23, acute myocardial infarction (years old): 69.55±15.13 vs. 62.10±15.75, arrhythmia (years old): 70.48±14.93 vs. 60.29±16.31, all P < 0.05]. The mortality of patients with pulmonary embolism, aortic dissection rupture, acute myocardial infarction, arrhythmia, acute heart failure in syncope group were significantly higher than those in non-syncope group [pulmonary embolism: 5.81% (5/86) vs. 0.95% (8/839), aortic dissection rupture: 4.65% (4/86) vs. 0.60% (5/839), acute myocardial infarction: 4.65% (4/86) vs. 1.19% (10/839), arrhythmia: 2.33% (2/86) vs. 0.95% (8/839), acute heart failure: 2.33% (2/86) vs. 0.60% (5/839), all P < 0.05]. Multivariate Logistic regression analysis showed that age [odds ratio ( OR) = 2.158, 95% confidence interval (95% CI) was 0.921-4.785, P = 0.000], pulmonary embolism ( OR = 15.391, 95% CI was 8.904-27.314, P = 0.001), aortic dissection rupture ( OR = 13.079, 95% CI was 6.237-25.509, P = 0.000), acute myocardial infarction ( OR = 18.826, 95% CI was 10.420-32.921, P = 0.000), syncope ( OR = 4.940, 95% CI was 1.764-9.287, P = 0.000) were risk factors for the prognosis of patients with acute and critical cardiovascular diseases. ROC curve analysis showed that syncope had a certain predictive value for 28-day prognosis of patients [the area under the ROC curve (AUC) = 0.760, P = 0.000], when the cut-off value was 4.12, the sensitivity was 88.51%, the specificity was 78.05%, the positive predictive value was 81.31%, and the negative predictive value was 84.27%. Conclusions:Syncope is an independent risk factor of death in patients with acute and critical cardiovascular diseases. For patients with syncope as the chief complaint, we should quickly identify the types of acute and critical diseases and assess the risk of sudden death.

Objective:To evaluate the effectiveness of syncope unit in improving the diagnosis efficiency and treatment prognosis of patients with suspected syncope.Methods:The standardized syncope unit was established in the Affiliated Nanyang Second General Hospital of Xinxiang Medical College in 2018. Patients with suspected syncope attending from November 2018 to April 2019 (before the establishment of syncope unit) and from May to October 2019 (after the establishment of syncope unit) were enrolled in the study. There were 109 cases attending before the establishment of syncope unit (control group) and 126 cases attending after establishment (syncope unit group). The positive rate of examination, the treatment and its cost before and after the establishment of syncope unit were compared. After one year, the follow-up rate, recurrence rate, rehospitalization rate, treatment satisfaction and quality of life of patients were documented and compared between two periods.Results:The positive rates of tilt table test [61.90%), Holter monitoring [64.29%(81/126)], exercise stress test [7.14%(9/126)] invasive electrophysiology [40.48%(51/126)], cardiac imaging [9.52%(12/126)] and 24-h blood pressure monitoring [55.56%(70/126)] in syncope unit group were significantly higher than those in control group [44.95%(49/109), 36.70%(40/109), 5.50%(6/109), 10.09%(11/109), 2.75%(3/109) and 40.37%(44/109); χ2=19.28, 23.11, 6.93, 28.18, 15.85 and 11.61,respectively; all P<0.01]. The diagnostic rate of etiology in syncope unit group was significantly higher than that in control group [87.30%(110/126) vs. 77.06%(84/109), χ2=21.70, P<0.01].The time from onset to cardiac assessment and hospitalization time in syncope unit group were significantly shorter than those in control group[(3.68±1.93)h vs. (7.31±2.64)h;(6.17±1.52)d vs. (10.83±2.09)d]. The hospitalization rate [3.17%(4/126) vs. 8.26%(8/109)], hospital mortality [0.79%(1/126) vs. 2.75%(3/109)] and treatment cost [(4.91±1.14) thousands Yuan vs. (7.05±2.53) thousands Yuan] in syncope unit group were significantly lower than those in control group ( t=14.49, P<0.01; t=8.62, P=0.02;χ2=15.83, P<0.01;χ2=10.03, P=0.01; t=6.17, P=0.03).The outpatient follow-up rate [82.54%(104/126)] and treatment satisfaction rate [91.35%(95/104)] in syncope unit group were significantly higher than those in control group [61.47%(67/109) and 64.18%(43/67)]; and the recurrence rate [14.42%(15/104)] and rehospitalization rate [7.69%(8/104)] in syncope unit group were significantly lower than those in control group [40.30%(27/67) and 23.88%(16/67)](χ2=17.30, 20.37, 18.56, 15.08,all P<0.01). The scores of psychological status, physiological status, environmental status, social relations and overall quality of life in contral group were significantly lower than those in syncope unit group (43.62±12.84 vs. 59.13±13.95,43.10±11.31 vs. 5.86±12.09,52.35±12.76 vs. 63.58±13.05,54.87±12.08 vs. 67.91±14.23,58.42±11.87 vs. 69.28±13.51; t=7.74, P=0.03; t=7.50, P=0.03; t=8.66, P=0.02; t=9.77, P=0.01; t=8.46, P=0.02, respectively). Conclusion:The establishment of standardized syncope unit is helpful to improve the diagnosis efficiency and the prognosis of patients with suspected syncope, and also reduce the cost of diagnosis and treatment.

Objective:To compare the surgical efficacy and cosmetic satisfaction of the transoral endoscopic thyroidectomy by vestibular approach (TOETVA), endoscopic thyroidectomy via bilateral areola approach (BAA), and open thyroidectomy (OT) in the treatment of papillary thyroid carcinoma (PTC) in stage T1b.Methods:A total of 178 patients with PTC in stages pT1bN0M0 and pT1bN1aM0 treated from January 2017 to December 2018 were divided into TOETVA group ( n=59), BAA group ( n=43), and OT group ( n=76). The baseline characteristics, relevant indexes of surgical efficacy and follow-up data were compared between the three groups, and also the surgical efficacy indexes were compared between unilateral lobectomy + central lymph node dissection (unilateral lobectomy subgroup) and bilateral lobectomy + central lymph nodes dissection (total resection subgroup). SPSS 19.0 statistical software was used for data analysis. Results:The mean ages of patients in TOETVA group and BAA group were significantly younger than those in OT group, and the proportion of women in TOETVA group and BAA group was significantly higher than that in OT group, all P<0.05. None of patients in TOETVA and BAA groups were converted to open surgery. Among TOETVA, BAA and OT groups, there were significant differences in the mean operation time [unilateral lobectomy subgroup: (198.0±45.2) min, (162.0±36.9) min and (79.4±28.6) min, P<0.05; total resection subgroup: (230.0±36.0) min, (219.8±68.1) min and (102.8±40.0) min, P<0.05], in total drainage volume [unilateral lobectomy subgroup: (195.0±55.6) ml, (178.1±50.4) ml and (127.0±30.1) ml, P<0.05; total resection subgroup: (221.1±46.7) ml, (245.3±71.2) ml and (137.7±41.6) ml, P<0.05], and the incidence of subcutaneous ecchymosis in TOETVA group or BAA group was higher than that in the OT group [5.1% (3/59), 11.6% (5/43) vs. 0, χ 2=3.952 and 9.225 respectively, both P<0.05]. The mean level of C-reactive protein in TOETVA group was higher than that in OT group [(16.8±10.7) vs. (9.5±6.9), P<0.05]. Following-up in the third month after surgery between three groups in cosmetic satisfaction scores [(2.7±0.5) vs. (2.6±0.7) vs. (1.7±0.8)], scar self-consciousness scores (0[0,1] vs. 1[0,2] vs. 2[1,2]), and quality of life scores [(9.1±1.1) vs. (8.9±1.1) vs. (7.5±0.8)], cosmetic satisfaction and quality of life in TOETVA and BAA group were better than that in OT group, in terms of scar self-consciousness: TOETVA0.05). The median follow-up time of the three groups was 25 months (TOETVA group), 28 months (BAA group), and 32 months (OT group) respectively, without disease progression. Conclusion:TOETVA and BAA are optional surgical methods for PTC in stages pT1bN0M0 and pT1bN1aM0, with good safety and patient's cosmetic satisfaction.

Objective To evaluate the effectiveness of spectral CT with multiple parameters on the diagnosis of ovarian cancer. Methods The data of 22 patients with spectral CT enhanced scan were analyzed retrospectively.The patients were divided into two groups:ovarian cancer group (n=11)and benign tumor group (n=11),according to the pathologic results.CT values at 40 keV,iodine concentration (IC),water concentration(WC)and spectral curve slope (λHU)of arterial phase and venous phase in the tumors of two groups were measured with gemstone spectral imaging(GSI)post-processing software.The independent samples t test was used to compare these multiple parameters above between two groups.Interobserver agreement with regard to various parameters was assessed using Cohen’s Kappa . For the parameters which showed statistically different,the receiver operating characteristic(ROC)curves were further generated to calculate their diagnostic effectiveness respectively.Results CT values at 40 keV,IC andλHUmeasured in arterial and venous phases were higher in ovarian cancer group than those in benign tumor group.There were significant differences between these two groups(P<0.05). While WC had no significant difference in these two groups (P>0.05).Interobserver agreement with regard to various parameters was excellent (Kappa>0.80).CT values at 40 keV,IC andλHUhad high effectiveness on the diagnosis of ovarian cancer according to ROC curves.The optimal parameter among them was IC in arterial phase with AUC of 0.90.Using 10.92 (100 μg/cm3)as a threshold value,the sensitivity and specificity for diagnosis were 90.9% and 90.9%.Conclusion Spectral CT with multiple parameters,including CT values at 40 keV,IC and λHUhave significant differences between benign and malignant ovarian tumors.IC in arterial phase has the highest effectiveness on the diagnosis of ovarian cancer.

Objective To investigate the role of different parenting styles plays in conduct problems of 3-years-old preschool children.Methods Participants were from 148 preschools in Longhua Shenzhen,China.A structured questionnaire covering family demographic characteristics,Conners' Parent Symptom Questionnaire and Egna Minnen Betraffande Uppfostran-Parents (EMBU-P) were conducted among primary caregivers of each child.There were 9289 valid participants in the analysis and logistic regression was used to assess the relationship between three dimensions of parenting (rejection,emotional warmth and control/overprotection) and conduct problems.Results After allowing for certain confounders,parental rejection (OR =1.17,P＜0.01) and control/overprotection (OR =1.03,P＜0.01) was positively associated with conduct problems and emotional warmth was negatively related to conduct problems (OR=0.98,P＜0.01).Stratified analysis showed a significant relationship between conduct problems and both parents' rejection (OR father=1.16,P＜0.01;OR motber=1.17,P＜0.01),father's emotional warmth (OR=0.96,P＜0.01) and mother's control/overprotection (OR=1.04,P＜0.01).This relationship did not vary between boys and girls and between single and not single children.Conclusion Influence of parenting should be taken into consideration in the prevention and intervention of conduct problems.

Objective To explore the interaction between passive smoking and folic acid supplement during pregnancy on children autism spectrum disorder (ASD) behaviors.Methods Children aged about 3 years were enrolled at kindergarten entrance in Longhua district of Shenzhen in 2014.Self-administered questionnaires were completed by their primary caregivers and the information about children' s age,gender,history of preterm birth and low birth weight,parents' education level,parents' reproductive age and family income were collected.The children ASD behaviors were assessed with Autism Behavior Checklist (ABC).According to the cut point of ABC,the children were divided into normal group with score less than 31,sub-clinical group with score ranging from 31 to 61 and suspect clinical group with score no less than 62.After controlling for potential confounders,multivariate logistic regression analysis was performed to evaluate the main effects and the interaction between passive smoking and folic acid supplement during pregnancy on children ASD behaviors.Results Maternal passive smoking during pregnancy was significantly associated with children ASD behaviors (sub-clinical group:OR=1.48;suspect clinical group:OR=2.85),and maternal folic acid supplement during pregnancy was not related to children ASD behaviors (sub-clinical group:OR=1.04;suspect clinical group:OR=0.75).Stratified analysis showed that folic acid supplement during pregnancy was negatively associated with children ASD behaviors (suspect clinical group:OR=0.30) among children without mothers' passive smoking during pregnancy,and that mothers' passive smoking during pregnancy was positively associated with children ASD behaviors (sub-clinical group:OR=1.52;suspect clinical group:OR=4.45) among the children whose mothers had folic acid supplement during pregnancy.Furthermore,an interaction effect on children ASD behaviors was found between passive smoking and folic acid supplement during pregnancy (suspect clinical group:OR=5.30).Conclusion Passive smoking and folic acid supplement during pregnancy were related to children ASD behaviors and had an interaction on children ASD behaviors.

OBJECTIVETo detect the expression of transient receptor potential canonical 1 (TRPC1) in a mouse model of ozone-induced lung inflammation and explore its role in lung inflammation.

METHODSIn a mouse model of lung inflammation established by ozone exposure, the expression of TRPC1 in the inflammatory lung tissues was detected by RT-PCR, Wstern blotting and immunohistochemistry.

RESULTSCompared to the control mice, the mice exposed to ozone showed significantly increased expression level of TRPC1 mRNA and protein in the inflammatory lung tissues (P<0.05). Immunohistochemistry showed increased TRPC1 protein expressions in the alveolar epithelial cells, bronchial epithelial cells, and inflammatory cells in the inflammatory lung tissues (P<0.05). The mRNA and protein expression levels of TRPC1 were positively correlated with the counts of white blood cells, macrophages, neutrophils and lymphocytes in the bronchoalveolar lavage fluid of the exposed mice (P<0.01).

CONCLUSIONTRPC1 may play a role in ozone-induced lung inflammation in mice.

Animals ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Gene Expression ; Inflammation ; pathology ; Lung ; metabolism ; pathology ; Mice ; Ozone ; adverse effects ; Pneumonia ; metabolism ; pathology ; RNA, Messenger ; TRPC Cation Channels ; metabolism

Objective To detect the expression of transient receptor potential canonical 1 (TRPC1) in a mouse model of ozone-induced lung inflammation and explore its role in lung inflammation. Methods In a mouse model of lung inflammation established by ozone exposure, the expression of TRPC1 in the inflammatory lung tissues was detected by RT-PCR, Wstern blotting and immunohistochemistry. Results Compared to the control mice, the mice exposed to ozone showed significantly increased expression level of TRPC1 mRNA and protein in the inflammatory lung tissues (P<0.05). Immunohistochemistry showed increased TRPC1 protein expressions in the alveolar epithelial cells, bronchial epithelial cells, and inflammatory cells in the inflammatory lung tissues (P<0.05). The mRNA and protein expression levels of TRPC1 were positively correlated with the counts of white blood cells, macrophages, neutrophils and lymphocytes in the bronchoalveolar lavage fluid of the exposed mice (P<0.01). Conclusion TRPC1 may play a role in ozone-induced lung inflammation in mice.