AIM To investigate the protective effect of Sanfeng Tongqiao Dropping Pills against house dust mite(HDM)-induced allergic asthma in mice.METHODS Compared to the intact BALB/c mice in the blank control group,the BALB/c mice randomly assigned into the model group,the dexamethasone group(0.67 mg/kg),and the low-dose,medium-dose,and high-dose Sanfeng Tongqiao Dropping Pills groups(15,30 and 60 mg/kg),were induced into acute allergic asthma models via weekly intraperitoneal sensitization with 0.1 mL HDM solution(0.5 mg/mL)for three weeks followed by three consecutive daily intranasal challenges with 10 μL HDM solution(2.5 mg/mL)starting in the third week.The drug administered continuously 7 days after the last excitation.The mice had their airway reactive Penh value detected,their pulmonary pathological changes observed by HE staining,their blood eosinophils(EOS)counted,their Th2 cytokines in lung tissue and serum IgE levels detected by ELISA,and their number of peripheral blood mononuclear cells(PBMC)and pulmonary Th2 cells detected by flow cytometry.Chronic allergic asthma was induced in grouped BALB/c mice through repeated intranasal challenges with 10 μL HDM solution(2.5 mg/mL)administered five times weekly for five consecutive weeks.Drug treatment continued for 14 days following the final challenge.After the final treatment,the mice had their pulmonary pathological changes observed by HE staining,and their levels of Th2 cytokines in B ALF and lung tissue and serum IgE detected by ELISA.RESULTS Compared to the blank control group,the acute allergic asthma model group exhibited increases in Penh value,EOS count and IgE level in serum,IL-4 and IL-5 levels in lung tissue(P＜0.01);obvious pulmonary inflammatory cells infiltration,and thickened airway wall;and increase in pulmonary number of Th2 cells(P＜0.01).Compared to the model group,the groups intervened with Sanfeng Tongqiao Dropping Pills demonstrated decreased Penh value,serum EOS count,IgE level and IL-5 level in lung tissue(P＜0.05,P＜0.01);reduced pulmonary inflammatory infiltration and alleviated airway wall thickening;and decreased number of pulmonary Th2 cells.Compared to the blank group,the chronic allergic asthma model group showed obvious pulmonary inflammatory infiltration and airway wall thickening;and increased EOS count and IgE level in serum,IL-4 and IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).Compared to the model group,the groups intervened with either medium-dose or high-dose Sanfeng Tongqiao Dropping Pills demonstrated reduced pulmonary inflammatory infiltration;and decreased serum EOS count,IgE level,IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).CONCLUSION Sanfeng Tongqiao Dropping Pills reduce Th2 cells in peripheral blood and lung tissue,suppress type 2 inflammation,and thereby alleviate allergic asthma.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

Objective:To explore the effect of Simo decoction improving the low duodenal inflammation and protecting the du-odenal mucosal barrier in rats with functional dyspepsia(FD).Methods:Sixty SD rats were randomly divided into control group(10 rats)and model group(50 rats),and the modeling rats were prepared by multivariate intervention method.After successful modeling,the modeling rats were randomly divided into model group,Simo decoction high-dose,medium-dose,low-dose group and mosapride group,with 10 rats in each group.The high-dose,medium-dose,and low-dose groups of Simo decoction were ga-vage given 5.62 g/kg,2.81 g/kg,and 1.40 g/kg,respectively,and the mosapride group was gavage given 0.305 mg/kg of mosapride,and the control group and model group were gavage given the same amount of distilled water for 14 days.The body weight of rats was observed;gastric emptying rate and small bowel propulsion rate were measured;transmission electron microscopy was used to observe the morphology of duodenal epithelial cells;ELISA detected serum levels of IL-17A and IL-22;Western blot and immunohistochemis-try were used to detect the expressions of protease-activated receptor 2(PAR-2)and tight junction protein(ZO-1,claudin-1)in the duodenum.Results:Compared with the control group,the body weight,gastric emptying rate and small intestinal propulsion rate of the model group were significantly reduced(P<0.01),transmission electron microscopy showed widening of the duodenal epithelial cell space,serum IL-17A and IL-22 levels were significantly increased(P<0.01),the expression of PAR-2 in duodenal tissue was in-creased,and the expressions of ZO-1 and claudin-1 were downregulated(P<0.01).Compared with model group,the gastric emptying rate and small intestinal propulsion rate in Simo decoction high-dose,medium-dose and mosapride group were increased(P<0.05,P<0.01),the contents of IL-17A and IL-22 in serum decreased(P<0.05,P<0.01),and the expression of PAR-2 in duodenal tissues was down-regulated,the expressions of ZO-1 and claudin-1 was significantly increased(P<0.01).The low-dose group of Simo soup could improve weight loss(P<0.01),reduce IL-17A content and PAR-2 expression,and increase ZO-1 and claudin-1 expression(P<0.05,P<0.01),while the effect on other indexes was not obvious.Conclusion:Simo decoction may reduce low-grade duodenal in-flammation to repair the mucosal barrier by down-regulating the levels of IL-17A and IL-22 and the expression of PAR-2,and up-regu-lating the expression of ZO-1 and claudin-1,so as to exert the effect of FD treatment.

Objective:In the context of China's cardiovascular disease(CVD)high-risk population screening and intervention project,this study systematically evaluates the applicability of the EQ-5D-5L and SF-6Dv2 instruments among individuals at high risk of CVD.Methods:Convergent validity was assessed using Spearman's correlation coefficient.Measurement agreement was evaluated through intraclass correlation coefficients(ICC)and Bland-Altman plots.Factors influencing utility differences were explored using multiple linear regression analysis.Kruskal-Wallis test and t-test were used to examine discriminant validity.Sensitivity was compared by effect size(ES),relative efficiency(RE),and the area under the receiver operating characteristic curve(ROC-AUC).Floor and ceiling effects were also compared.Results:Among 5,415 individuals at high risk of CVD,the two instruments showed moderate overall correlation and acceptable convergent validity,but dimension-specific correlations were weak,and measurement consistency was low(ICC=0.367).Both instruments effectively distinguished different health states,yet the SF-6Dv2 demonstrated superior sensitivity and a milder ceiling effect.Conclusion:When measuring the health utility value of CVD patients,scale selection should be cautious,especially for high-risk groups,and SF-6Dv2 is more appropriate.

Objective:To explore the effect of Simo decoction improving the low duodenal inflammation and protecting the du-odenal mucosal barrier in rats with functional dyspepsia(FD).Methods:Sixty SD rats were randomly divided into control group(10 rats)and model group(50 rats),and the modeling rats were prepared by multivariate intervention method.After successful modeling,the modeling rats were randomly divided into model group,Simo decoction high-dose,medium-dose,low-dose group and mosapride group,with 10 rats in each group.The high-dose,medium-dose,and low-dose groups of Simo decoction were ga-vage given 5.62 g/kg,2.81 g/kg,and 1.40 g/kg,respectively,and the mosapride group was gavage given 0.305 mg/kg of mosapride,and the control group and model group were gavage given the same amount of distilled water for 14 days.The body weight of rats was observed;gastric emptying rate and small bowel propulsion rate were measured;transmission electron microscopy was used to observe the morphology of duodenal epithelial cells;ELISA detected serum levels of IL-17A and IL-22;Western blot and immunohistochemis-try were used to detect the expressions of protease-activated receptor 2(PAR-2)and tight junction protein(ZO-1,claudin-1)in the duodenum.Results:Compared with the control group,the body weight,gastric emptying rate and small intestinal propulsion rate of the model group were significantly reduced(P<0.01),transmission electron microscopy showed widening of the duodenal epithelial cell space,serum IL-17A and IL-22 levels were significantly increased(P<0.01),the expression of PAR-2 in duodenal tissue was in-creased,and the expressions of ZO-1 and claudin-1 were downregulated(P<0.01).Compared with model group,the gastric emptying rate and small intestinal propulsion rate in Simo decoction high-dose,medium-dose and mosapride group were increased(P<0.05,P<0.01),the contents of IL-17A and IL-22 in serum decreased(P<0.05,P<0.01),and the expression of PAR-2 in duodenal tissues was down-regulated,the expressions of ZO-1 and claudin-1 was significantly increased(P<0.01).The low-dose group of Simo soup could improve weight loss(P<0.01),reduce IL-17A content and PAR-2 expression,and increase ZO-1 and claudin-1 expression(P<0.05,P<0.01),while the effect on other indexes was not obvious.Conclusion:Simo decoction may reduce low-grade duodenal in-flammation to repair the mucosal barrier by down-regulating the levels of IL-17A and IL-22 and the expression of PAR-2,and up-regu-lating the expression of ZO-1 and claudin-1,so as to exert the effect of FD treatment.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

Objective:In the context of China's cardiovascular disease(CVD)high-risk population screening and intervention project,this study systematically evaluates the applicability of the EQ-5D-5L and SF-6Dv2 instruments among individuals at high risk of CVD.Methods:Convergent validity was assessed using Spearman's correlation coefficient.Measurement agreement was evaluated through intraclass correlation coefficients(ICC)and Bland-Altman plots.Factors influencing utility differences were explored using multiple linear regression analysis.Kruskal-Wallis test and t-test were used to examine discriminant validity.Sensitivity was compared by effect size(ES),relative efficiency(RE),and the area under the receiver operating characteristic curve(ROC-AUC).Floor and ceiling effects were also compared.Results:Among 5,415 individuals at high risk of CVD,the two instruments showed moderate overall correlation and acceptable convergent validity,but dimension-specific correlations were weak,and measurement consistency was low(ICC=0.367).Both instruments effectively distinguished different health states,yet the SF-6Dv2 demonstrated superior sensitivity and a milder ceiling effect.Conclusion:When measuring the health utility value of CVD patients,scale selection should be cautious,especially for high-risk groups,and SF-6Dv2 is more appropriate.

AIM To investigate the protective effect of Sanfeng Tongqiao Dropping Pills against house dust mite(HDM)-induced allergic asthma in mice.METHODS Compared to the intact BALB/c mice in the blank control group,the BALB/c mice randomly assigned into the model group,the dexamethasone group(0.67 mg/kg),and the low-dose,medium-dose,and high-dose Sanfeng Tongqiao Dropping Pills groups(15,30 and 60 mg/kg),were induced into acute allergic asthma models via weekly intraperitoneal sensitization with 0.1 mL HDM solution(0.5 mg/mL)for three weeks followed by three consecutive daily intranasal challenges with 10 μL HDM solution(2.5 mg/mL)starting in the third week.The drug administered continuously 7 days after the last excitation.The mice had their airway reactive Penh value detected,their pulmonary pathological changes observed by HE staining,their blood eosinophils(EOS)counted,their Th2 cytokines in lung tissue and serum IgE levels detected by ELISA,and their number of peripheral blood mononuclear cells(PBMC)and pulmonary Th2 cells detected by flow cytometry.Chronic allergic asthma was induced in grouped BALB/c mice through repeated intranasal challenges with 10 μL HDM solution(2.5 mg/mL)administered five times weekly for five consecutive weeks.Drug treatment continued for 14 days following the final challenge.After the final treatment,the mice had their pulmonary pathological changes observed by HE staining,and their levels of Th2 cytokines in B ALF and lung tissue and serum IgE detected by ELISA.RESULTS Compared to the blank control group,the acute allergic asthma model group exhibited increases in Penh value,EOS count and IgE level in serum,IL-4 and IL-5 levels in lung tissue(P＜0.01);obvious pulmonary inflammatory cells infiltration,and thickened airway wall;and increase in pulmonary number of Th2 cells(P＜0.01).Compared to the model group,the groups intervened with Sanfeng Tongqiao Dropping Pills demonstrated decreased Penh value,serum EOS count,IgE level and IL-5 level in lung tissue(P＜0.05,P＜0.01);reduced pulmonary inflammatory infiltration and alleviated airway wall thickening;and decreased number of pulmonary Th2 cells.Compared to the blank group,the chronic allergic asthma model group showed obvious pulmonary inflammatory infiltration and airway wall thickening;and increased EOS count and IgE level in serum,IL-4 and IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).Compared to the model group,the groups intervened with either medium-dose or high-dose Sanfeng Tongqiao Dropping Pills demonstrated reduced pulmonary inflammatory infiltration;and decreased serum EOS count,IgE level,IL-13 in lung tissue and IL-14 in BALF(P＜0.05,P＜0.01).CONCLUSION Sanfeng Tongqiao Dropping Pills reduce Th2 cells in peripheral blood and lung tissue,suppress type 2 inflammation,and thereby alleviate allergic asthma.

Objective:To compare the clinical efficacy between microscopic varicocelectomy and laparoscopic varicocelectomy in the treatment of varicocele(VC)with male infertility.Methods:A total of 307 patients who were diagnosed with VC complicated with male infertility and admitted to the Affiliated Hospital of Qingdao University from October 2018 to October 2022 were recruited for retrospective analysis.The patients were divided into the microscopic group(180 cases)and laparoscopic group(127 cases)according to the surgery method.The pre-and postoperative clinical data of these two groups were analyzed,including the degree of dilatation and reflux time of internal spermatic vein,hemodynamic parameters of testicular capsular artery,proportion of progressive motility spermato-zoa(PR),concentration of spermatozoa,proportion of normal morphology sperm,the pregnancy outcome of spouses and the incidence of complications related with surgery within 2 years postoperatively.Results:All the surgeries for the 307 patients in this study were successful.There was no significant difference in operation time,hospitalization time and management expenses between the microscop-ic group and the laparoscopic group(P＞0.05).Compared to the patients in laparoscopic group,the patients in the microscopic group received a better improvement in venous diameter,reflux time of spermatic veins and hemodynamic parameters of testicular capsular ar-tery(P＜0.05).Moreover,the semen analysis showed that the PR,spermatozoa concentration and proportion of normal morphology sperm in the microscopic group were also obviously increased than those in the laparoscopic group(P＜0.05).During the 2-year fol-low-up period,the conception rate of spouses in the microscopic group was 67.2％,while only 47.2％in the laparoscopic group,in which the difference was statistically significant(P＜0.05).Besides,the time-to-pregnancy(TTP)within 2 years postoperatively in the microscopic group was significantly shorter than that in the laparoscopic group(P＜0.05).Meanwhile,the incidence of adverse pregnancy outcomes in the microscopic group was also significantly lower than that in the laparoscopic group(P＜0.05).It is worth mentioned that the spontaneous conception rate of spouses with successful pregnancy in the microscopic group was also significantly higher than that in the laparoscopic group(P＜0.05).Severe complication such as testicular atrophy,bleeding and infection did not appear in both of two groups.However,the incidences of testicular hydrocele and recurrence of VC postoperatively in the laparoscopic group were significantly higher than those in the microscopic group(P＜0.05).Conclusion:Both microscopic varicocelectomy and laparoscopic varicocelectomy can be applied to the management of VC combined with male infertility.But microscopic varicocelectomy showed better clinical efficacy in improving the testicular hemodynamic parameters,semen quality,pregnancy outcome and postopera-tive complications,which is worthy of further clinical applications.

OBJECTIVE: Tumor-derived exosomes (TDEs) play crucial roles in intercellular communication. Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis. Jiedu recipe (JR), a traditional Chinese medicinal formula, has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unknown. METHODS: Animal experiments were performed to investigate the metastasis-preventing effects of JR. Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR. TDEs were assessed using nanoparticle tracking analysis (NTA) and Western blotting (WB). Exosomes derived from normoxic or hypoxic HCC cells (H-TDEs) were collected to establish premetastatic mouse models. JR was intragastrically administered to evaluate its metastasis-preventive effects. WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy. Bioinformatics analysis, WB, NTA, and immunofluorescence staining were used to identify the active components and potential targets of JR. RESULTS: JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis. It inhibited the release of exosomes from tumor cells under hypoxic condition. JR treatment promoted both lysosomal acidification and suppressed secretory autophagy, which were dysregulated in hypoxic tumor cells. Quercetin was identified as the active component in JR, and the epidermal growth factor receptor (EGFR) was identified as a potential target. Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB (TFEB). Hypoxia-impaired lysosomal function was restored, and secretory autophagy was alleviated by quercetin treatment. CONCLUSION JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release, restoring lysosomal function, and suppressing secretory autophagy. Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling. Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion. Please cite this article as: Jia WT, Xiang S, Zhang JB, Yuan JY, Wang YQ, Liang SF, Lin WF, Zhai XF, Shang Y, Ling CQ, Cheng BB. Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment through the EGFR-TFEB signaling pathway. J Integr Med. 2024; 22(6): 697-709.
Exosomes/drug effects* ; Animals ; Carcinoma, Hepatocellular/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Liver Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Mice ; Humans ; Cell Line, Tumor ; Mice, Inbred BALB C ; Neoplasm Metastasis ; Male ; Mice, Nude