AIM:Xiongshi Shiwei Wendan decoc-tion(SWD)comes from Xiong Jibai,a master of tra-ditional Chinese medicine,and has been widely used in the treatment of AS.ABCA1 is an important pathway for macrophages to export cholesterol and plays a protective role in the occurrence and development of AS.The purpose of this study was to study the effects of SWD on ABCA1 expression and cholesterol efflux through network pharmacol-ogy,molecular docking and in vitro experiments,and explore the pathway mechanism of promoting reverse cholesterol transport(RCT).METHODS:The active components of SWD drugs were screened by TCMSP and HERB databases,RCT targets were pre-dicted,the component-target network map was constructed,the PPI network was constructed and the GO and KEGG pathways were enriched and ana-lyzed by STRING database,and the key active com-ponents of SWD were selected for molecular dock-ing with ABCA1 protein and miR-33 by AutoDockVi-na.In vitro,RAW264.7 was used to establish foam cell model,oil red O staining,NBD-cholesterol staining and lentivirus overexpression cell miRNA-33 were used to study the effect of SWD on lipid accumulation and cholesterol outflow rate of RAW264.7 cells.Western blotting was used to de-tect the expression of ABCA1.RESULTS:According to network pharmacology,336 active components of SWD,267 targets of RCT and 46 targets of inter-section of RCT and SWD were obtained,which in-volved multiple signal pathways such as lipid and atherosclerosis.Molecular docking showed that the main active components had stable conforma-tion with ABCA1 and miR-33.In vitro experiment,it was found that the lipid content was significantly decreased(P＜0.01),the cholesterol outflow rate was significantly increased(P＜0.01)and the expres-sion of ABCA1 protein was up-regulated in SWD group(P＜0.01),but the expression of ABCA1 in miR-33 overexpression group was significantly de-creased(P＜0.01).CONCLUSION:SWD has the char-acteristics of multi-components and multi-targets,which can promote RCT and treat AS through miR-NA-33-ABCA1 pathway.

Objective This study analyzes the optical coherence tomography(OCT)characteristics of patients with symptomatic carotid artery stenosis(CAS)prior to carotid stenting and the influencing factors associated with symptomatic CAS.Methods This study retrospectively included consecutive CAS patients who underwent carotid OCT examination prior to carotid stenting at Department of Nerolgical Intervention and Nerological Intensive Care,Central Hospital of Dalian University of Technology(Dalian Municipal Central Hospital)from November 2022 to November 2024.Patients were categorized into symptomatic and asymptomatic CAS groups.General clinical data and laboratory test results were collected and compared between the two groups,including age,sex,body mass index,systolic and diastolic blood pressure(measured on the morning of procedure without antihypertensive medication intervention with patient at resting state for over 30 minutes),medical history(including hypertension,diabetes,atrial fibrillation,coronary heart disease,stroke,and transient ischemic attack),smoking history,alcohol consumption history,and fasting laboratory results obtained on the morning before procedure laboratory results(including,white blood cell count,red blood cell count,monocyte percentage,neutrophil percentage,lymphocyte percentage,platelet count,blood creatinine,blood glucose,international normalized ratio,D-dimer,total cholesterol,triglycerides,homocysteine,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol).Additionally,OCT image parameters were collected and compared between the two groups,including the minimum lumen diameter and minimum lumen area of the target lesion segment,the distal lumen diameter and area of the reference vessel(internal carotid artery),the percentage of lumen area stenosis([reference vessel lumen cross-sectional area-minimum lumen cross-sectional area]/reference vessel lumen cross-sectional area×100%),the lesion length,fibrous cap thickness,lipid arc,and the presence of fibrous plaques,calcified plaques,lipid plaques,white thrombus,cholesterol crystals,macrophage infiltration,microchannels,and plaque rupture.Variables with P＜0.05 from univariate analysis were included in the multivariate Logistic regression analysis to assess the influencing factors of symptomatic CAS.Results A total of 68 patients with CAS were enrolled,comprising 57males and 11females,aged 53 to 84 years with a mean age of(68±7)years.Among them,32 patients were categorized into the symptomatic CAS group and 36 into the asymptomatic CAS group.(1)Compared to the asymptomatic CAS group,patients in the symptomatic CAS group exhibited higher systolic blood pressure([150±23]mmHg vs.[138±21])mmHg,P=0.025).There were no statistically significant differences in general,clinical data,and laboratory test results between the two groups(all P＞0.05).The preoperative OCT imaging parameters comparison between the two groups of CAS patients revealed that the reference vessel distal lumen area was significantly smaller in the symptomatic CAS group([18.67±5.44]mm2 vs.[21.95±5.57]mm2,P=0.017),and the proportion of patients with white thrombus(40.62%[13/32]vs.13.89%[5/36],P=0.013)and microchannels(21.88%[7/32]vs.2.78%[1/36],P=0.014)were higher.(2)A multivariate Logistic regression analysis was conducted using systolic blood pressure,white thrombus,microchannels,and the reference vessel(internal carotid artery)distal lumen area as independent variables.The results indicated that high systolic blood pressure(OR,1.030,95%CI 1.002-1.060,P=0.038),and the presence of white thrombus(OR,3.956,95%CI 1.072-14.600,P=0.039)and microchannels(OR,13.850,95%CI 1.277-150.203,P=0.031)were independent risk factors for symptomatic CAS.Conclusions Compared to patients with asymptomatic CAS,those with symptomatic CAS exhibited higher preoperative(pre-carotid stenting)systolic blood pressure and a smaller distal lumen area of the reference vessel(internal carotid artery),as observed through OCT.Furthermore,a higher proportion of symptomatic CAS patients presented with white thrombus and microchannels.Preoperative systolic blood pressure,along with the presence of white thrombus and microchannels on OCT,are identified as independent risk factors for symptomatic CAS.The conclusions drawn from this study necessitate further validation through large-scale,multicenter,prospective research.

Objective This study analyzes the optical coherence tomography(OCT)characteristics of patients with symptomatic carotid artery stenosis(CAS)prior to carotid stenting and the influencing factors associated with symptomatic CAS.Methods This study retrospectively included consecutive CAS patients who underwent carotid OCT examination prior to carotid stenting at Department of Nerolgical Intervention and Nerological Intensive Care,Central Hospital of Dalian University of Technology(Dalian Municipal Central Hospital)from November 2022 to November 2024.Patients were categorized into symptomatic and asymptomatic CAS groups.General clinical data and laboratory test results were collected and compared between the two groups,including age,sex,body mass index,systolic and diastolic blood pressure(measured on the morning of procedure without antihypertensive medication intervention with patient at resting state for over 30 minutes),medical history(including hypertension,diabetes,atrial fibrillation,coronary heart disease,stroke,and transient ischemic attack),smoking history,alcohol consumption history,and fasting laboratory results obtained on the morning before procedure laboratory results(including,white blood cell count,red blood cell count,monocyte percentage,neutrophil percentage,lymphocyte percentage,platelet count,blood creatinine,blood glucose,international normalized ratio,D-dimer,total cholesterol,triglycerides,homocysteine,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol).Additionally,OCT image parameters were collected and compared between the two groups,including the minimum lumen diameter and minimum lumen area of the target lesion segment,the distal lumen diameter and area of the reference vessel(internal carotid artery),the percentage of lumen area stenosis([reference vessel lumen cross-sectional area-minimum lumen cross-sectional area]/reference vessel lumen cross-sectional area×100%),the lesion length,fibrous cap thickness,lipid arc,and the presence of fibrous plaques,calcified plaques,lipid plaques,white thrombus,cholesterol crystals,macrophage infiltration,microchannels,and plaque rupture.Variables with P＜0.05 from univariate analysis were included in the multivariate Logistic regression analysis to assess the influencing factors of symptomatic CAS.Results A total of 68 patients with CAS were enrolled,comprising 57males and 11females,aged 53 to 84 years with a mean age of(68±7)years.Among them,32 patients were categorized into the symptomatic CAS group and 36 into the asymptomatic CAS group.(1)Compared to the asymptomatic CAS group,patients in the symptomatic CAS group exhibited higher systolic blood pressure([150±23]mmHg vs.[138±21])mmHg,P=0.025).There were no statistically significant differences in general,clinical data,and laboratory test results between the two groups(all P＞0.05).The preoperative OCT imaging parameters comparison between the two groups of CAS patients revealed that the reference vessel distal lumen area was significantly smaller in the symptomatic CAS group([18.67±5.44]mm2 vs.[21.95±5.57]mm2,P=0.017),and the proportion of patients with white thrombus(40.62%[13/32]vs.13.89%[5/36],P=0.013)and microchannels(21.88%[7/32]vs.2.78%[1/36],P=0.014)were higher.(2)A multivariate Logistic regression analysis was conducted using systolic blood pressure,white thrombus,microchannels,and the reference vessel(internal carotid artery)distal lumen area as independent variables.The results indicated that high systolic blood pressure(OR,1.030,95%CI 1.002-1.060,P=0.038),and the presence of white thrombus(OR,3.956,95%CI 1.072-14.600,P=0.039)and microchannels(OR,13.850,95%CI 1.277-150.203,P=0.031)were independent risk factors for symptomatic CAS.Conclusions Compared to patients with asymptomatic CAS,those with symptomatic CAS exhibited higher preoperative(pre-carotid stenting)systolic blood pressure and a smaller distal lumen area of the reference vessel(internal carotid artery),as observed through OCT.Furthermore,a higher proportion of symptomatic CAS patients presented with white thrombus and microchannels.Preoperative systolic blood pressure,along with the presence of white thrombus and microchannels on OCT,are identified as independent risk factors for symptomatic CAS.The conclusions drawn from this study necessitate further validation through large-scale,multicenter,prospective research.

AIM:Xiongshi Shiwei Wendan decoc-tion(SWD)comes from Xiong Jibai,a master of tra-ditional Chinese medicine,and has been widely used in the treatment of AS.ABCA1 is an important pathway for macrophages to export cholesterol and plays a protective role in the occurrence and development of AS.The purpose of this study was to study the effects of SWD on ABCA1 expression and cholesterol efflux through network pharmacol-ogy,molecular docking and in vitro experiments,and explore the pathway mechanism of promoting reverse cholesterol transport(RCT).METHODS:The active components of SWD drugs were screened by TCMSP and HERB databases,RCT targets were pre-dicted,the component-target network map was constructed,the PPI network was constructed and the GO and KEGG pathways were enriched and ana-lyzed by STRING database,and the key active com-ponents of SWD were selected for molecular dock-ing with ABCA1 protein and miR-33 by AutoDockVi-na.In vitro,RAW264.7 was used to establish foam cell model,oil red O staining,NBD-cholesterol staining and lentivirus overexpression cell miRNA-33 were used to study the effect of SWD on lipid accumulation and cholesterol outflow rate of RAW264.7 cells.Western blotting was used to de-tect the expression of ABCA1.RESULTS:According to network pharmacology,336 active components of SWD,267 targets of RCT and 46 targets of inter-section of RCT and SWD were obtained,which in-volved multiple signal pathways such as lipid and atherosclerosis.Molecular docking showed that the main active components had stable conforma-tion with ABCA1 and miR-33.In vitro experiment,it was found that the lipid content was significantly decreased(P＜0.01),the cholesterol outflow rate was significantly increased(P＜0.01)and the expres-sion of ABCA1 protein was up-regulated in SWD group(P＜0.01),but the expression of ABCA1 in miR-33 overexpression group was significantly de-creased(P＜0.01).CONCLUSION:SWD has the char-acteristics of multi-components and multi-targets,which can promote RCT and treat AS through miR-NA-33-ABCA1 pathway.

Objective To measure vaginal wall parameters including vaginal wall thickness,length and number of rugae in normal childbearing period women using transrectal biplane high-frequency ultrasonography,and to establish normal reference ranges of the above indexes.Methods Totally 245 normal childbearing period female volunteers were prospectively recruited.The thickness and length of vaginal wall were measured,and number of rugae were counted with transrectal biplane high-frequency ultrasound,and the normal reference ranges were established.The correlations of the above indexes with age,height,body mass and body mass index(BMI)were explored.Results The thickness and length of vaginal wall was(7.50-16.20)mm(95％CI[11.43,11.92]mm)and(3.30-7.61)cm(95％CI[5.35,5.74]cm),respectively,and number of rugae was 5.00±15.00(95％CI[8.42,9.13]).Both the length of vaginal wall and the number of rugae were negatively correlated with age(r=-0.145,-0.178;P=0.024,0.005),while the thickness of vaginal wall was not obviously correlated with age,height,body mass and BMI of normal childbearing period women(all P＞0.05).Conclusion The normal reference ranges of the thickness and length of vaginal wall,as well as the number of rugae in normal childbearing period established women obtained with transrectal biplane high-frequency ultrasonography could provide references for clinical assessment of vaginal condition.

Objective To observe the value of ultrasonic parameters for predicting whether patients with cesarean scar pregnancy(CSP)would benefit from ultrasound-guided suction curettage alone.Methods Totally 140 CSP patients diagnosed by transvaginal ultrasound and initially treated with ultrasound-guided suction curettage alone were prospectively recruited and categorized into benefited group(n=103)and non-benefited group(n=37)according to bleeding during suction curettage and prognoses.The ultrasonic manifestations of CSP were observed,and the thickness of chorionic villi at the scar,as well as of residual myometrium of the anterior wall in the lower segment of the uterus,also the maximum diameter of the gestational sac were measured and compared between groups,and the parameters with quantitative data being statistically different between groups were converted into categorical predictor through analyzing of the receiver operating characteristic(ROC)curves and the optimal cut-off values.The independent predictors were selected among ultrasonic features and categorical predictor variables being statistically different between groups using multivariate logistic regression,and a combined predicting model was then constructed,and the predicting efficacy of the combined model and each categorical predictor alone was assessed according to the area under curve(AUC)and then were compared.Results Compared with non-benefited group,the gestational weeks in benefited group were smaller(P＜0.05),and the percentages of rich blood supply and the presence of embryos and fetal heartbeats were lower,with thinner chorionic villi at the scar,thicker residual myometrium and smaller maximal diameter of the gestational sac in benefited group(all P＜0.05).ROC curves analyses yielded the best cut-off value for dichotomy of chorionic villi thickness at the scar was 4.7 mm,of residual myometrium thickness was 1.8 mm and of the maximum diameter of the gestational sac was 29 mm,respectively,and then categorical predictor variable were obtained.Multivariate logistic regression showed that the transformed categorical predictors,i.e.the thickness degree of the chorionic villi at the scar,the thickness degree of the residual muscle layer and the size degree of the gestational sac,were all independent predictors of whether CSP patients would benefit from ultrasound-guided suction curettage alone(all P＜0.05).The AUC of the combined predicting model was 0.918,higher than that of each transformed categorical predictor alone(all P＜0.05).Conclusion The thickness of the chorionic villi at the scar ≤4.7 mm,the thickness of the residual muscle layer＞1.8 mm and the maximum diameter of the gestational sac≤29 mm were all independent predictors of CSP patients would benefit from ultrasound-guided suction curettage alone,and the predicting efficacy of the combined model was higher than that of each alone.

Objective To establish a risk prediction model,and to observe its value for predicting retained cesarean scar pregnancy(CSP)after ultrasound-guided curettage.Methods Data of 401 CSP patients who received ultrasound-guided curettage were retrospectively analyzed.The patients were randomly divided into training set(n=264)or validation set(n=137)at a ratio of 7:3.According to whether there was retained CSP at the lower segmental scar of uterine after ultrasound-guided curettage,the patients were divided into retained group or non-retained group.The variables with the biggest predictive value for retained CSP after ultrasound-guided curettage were selected with LASSO regression,and the independent risk factors were screened using multivariate logistic regression,and then a nomogram model was established.Results The results of LASSO regression and multivariate logistic regression indicated that embedded depth of gestational sac in cesarean scar more than 1.13 cm,convexity of gestational sac,rich blood supply(Adler degree Ⅱ-Ⅲ),and pre-curettage serum β-human chorionic gonadotropin(HCG)more than 33 063.50 U/L were all independent risk factors for retained CSP after curettage(all P＜0.05).The calibration curve of nomogram predictive model established based on the above indexes was basically consistent with the ideal curve,and the model had good clinical benefits.Conclusion The established nomogram predictive model had good predictive ability for retained CSP after curettage.

Objective:To analyze clinical characteristics of recurrent appendicitis.Methods:A retrospective cohort study was carried out. Clinical data of patients who underwent appendectomy due to acute appendicitis confirmed by pathology in the Affiliated Hospital of Qingdao University from January 2011 to December 2015 were analyzed retrospectively. Exclusion criteria: (1) age of less than 18 years;(2) chronic appendicitis; (3) periappendiceal abscess; (4) appendiceal mucocele or mucinous neoplasms; (5) appendiceal neuroendocrine tumors or cancers; (6) appendicitis during pregnancy; (7) concurrent AIDS, hematological disease, autoimmune disease, inflammatory bowel disease or advanced cancer; (8) other simultaneous surgery. A total of 373 patients were enrolled the study. These patients were divided into the recurrent group (133 cases) and the first episode group (240 cases) according to the previous history of antibiotic therapy for acute appendicitis. The prevalence of recurrent appendicitis was calculated, and the clinical characteristics were analyzed, including gender, age, comorbidities and preoperative CT images.Results:Of 373 patients, 209 were male and 164 were female, with a median age of 42 (18 to 88) years. Median recurrent time of the recurrent group was 4 (1 to 60) months. Compared to the first episode group, the recurrent group had higher proportion of age <50 years [71.4% (95/133) vs. 57.5% (138/240), χ 2=7.081, P=0.008], higher proportion of concurrent diabetes [13.5% (18/133) vs. 5.4% (13/240), χ 2=7.399, P=0.007], shorter onset time [(41.7±13.6) hours vs. (59.4±56.2) hours, t=-3.286, P=0.001], lower proportion of abdominal tension and rebound pain [57.9% (77/133) vs. 66.7% (160/240), χ 2=5.065, P=0.024], lower score of modified Alvarado score [(5.6±1.9) point vs. (6.1±1.9) point, t=-2.417, P=0.016], lower WBC count [(10.5±4.6) ×10 9/L vs. (11.5±4.5)×10 9/L, t=-1.190, P=0.047], higher percentage of lymphocyte [(19.4±14.7)% vs. (16.1±13.3)%, t=2.069, P=0.039]. In the recurrent group, ratio of length of removed appendix ≥7 cm was higher as compared with the first episode group [44.4% (59/133) vs. 32.9% (79/240), χ 2=4.808, P=0.028], while the ratio of complicated appendicitis was significantly lower [8.3% (11/133) vs. 22.9% (55/240), χ 2=10.823, P=0.001]. CT images were available in 129 patients, intraluminal appendicoliths was found in 19 of 50 patients (38%) in the recurrent group, while in 16 of 79 patients (20.3%) in the first episode group, and there was statistically significant difference between the two groups (χ 2=4.880, P=0.027). Conclusions:Clinical characteristics of recurrent acute appendicitis include age less than 50 years, concurrent diabetes, short onset time, less abdominal tension or rebound pain, low modified Alvarado score, low WBC count, high percentage of lymphocyte, appendix length longer than 7 cm, non-complicated appendicitis and intraluminal appendicoliths.

Objective:To analyze clinical characteristics of recurrent appendicitis.Methods:A retrospective cohort study was carried out. Clinical data of patients who underwent appendectomy due to acute appendicitis confirmed by pathology in the Affiliated Hospital of Qingdao University from January 2011 to December 2015 were analyzed retrospectively. Exclusion criteria: (1) age of less than 18 years;(2) chronic appendicitis; (3) periappendiceal abscess; (4) appendiceal mucocele or mucinous neoplasms; (5) appendiceal neuroendocrine tumors or cancers; (6) appendicitis during pregnancy; (7) concurrent AIDS, hematological disease, autoimmune disease, inflammatory bowel disease or advanced cancer; (8) other simultaneous surgery. A total of 373 patients were enrolled the study. These patients were divided into the recurrent group (133 cases) and the first episode group (240 cases) according to the previous history of antibiotic therapy for acute appendicitis. The prevalence of recurrent appendicitis was calculated, and the clinical characteristics were analyzed, including gender, age, comorbidities and preoperative CT images.Results:Of 373 patients, 209 were male and 164 were female, with a median age of 42 (18 to 88) years. Median recurrent time of the recurrent group was 4 (1 to 60) months. Compared to the first episode group, the recurrent group had higher proportion of age <50 years [71.4% (95/133) vs. 57.5% (138/240), χ 2=7.081, P=0.008], higher proportion of concurrent diabetes [13.5% (18/133) vs. 5.4% (13/240), χ 2=7.399, P=0.007], shorter onset time [(41.7±13.6) hours vs. (59.4±56.2) hours, t=-3.286, P=0.001], lower proportion of abdominal tension and rebound pain [57.9% (77/133) vs. 66.7% (160/240), χ 2=5.065, P=0.024], lower score of modified Alvarado score [(5.6±1.9) point vs. (6.1±1.9) point, t=-2.417, P=0.016], lower WBC count [(10.5±4.6) ×10 9/L vs. (11.5±4.5)×10 9/L, t=-1.190, P=0.047], higher percentage of lymphocyte [(19.4±14.7)% vs. (16.1±13.3)%, t=2.069, P=0.039]. In the recurrent group, ratio of length of removed appendix ≥7 cm was higher as compared with the first episode group [44.4% (59/133) vs. 32.9% (79/240), χ 2=4.808, P=0.028], while the ratio of complicated appendicitis was significantly lower [8.3% (11/133) vs. 22.9% (55/240), χ 2=10.823, P=0.001]. CT images were available in 129 patients, intraluminal appendicoliths was found in 19 of 50 patients (38%) in the recurrent group, while in 16 of 79 patients (20.3%) in the first episode group, and there was statistically significant difference between the two groups (χ 2=4.880, P=0.027). Conclusions:Clinical characteristics of recurrent acute appendicitis include age less than 50 years, concurrent diabetes, short onset time, less abdominal tension or rebound pain, low modified Alvarado score, low WBC count, high percentage of lymphocyte, appendix length longer than 7 cm, non-complicated appendicitis and intraluminal appendicoliths.

OBJECTIVE: To investigate the effect of acupuncture on TGF-β1/Smads signaling pathway in the lung tissue of mice with airway remodeling. METHODS: Thirty specific pathogen-free mice were randomly divided into blank group, model group and acupuncture group (=10). Mouse models of asthma were established in the model group and the acupuncture group, and the mice in the latter group received 7 acupuncture therapies (at bilateral Fei Shu, Da Zhui and Zu Sanli, 20 min each time) every other day, starting on the 10th day after the modeling. At 24 h after the last acupuncture, the mice were subjected to inhalation of 1% OVA for 3 days, and 24 h after the last challenge, the mice were given methacholine chloride (Mch) inhalation at different concentrations for measurement of lung resistance using a noninvasive stroke volume meter. HE staining was used to observe the pathological changes in the lung tissues, and TGF-β1 levels in the the bronchoalveolar lavage fluid (BALF) and serum were detected using ELISA; Western blotting was used to detect the differential protein expressions in the airway smooth muscles between the two groups. The airway smooth muscle cells were isolated from the mice in the acupuncture group and treated with a TGF- β1 inhibitor (LY2157299), and the relative expressions of type-Ⅰ and Smads proteins were detected using Western blotting. RESULTS: The mice in the model showed obvious tracheal fistula with airway pathologies including lumen narrowing, bronchial mucosa thickening, dissociation of the epithelial cells, and thickening of the alveolar septum and airway smooth muscles. These pathological changes were obviously milder in the acupuncture group. The asthmatic mice exhibited significantly increased lung resistance in positive correlation with Mch concentration. Serum TGF-β1 level was significantly elevated in asthmatic mice ( < 0.05); TGF-β1 levels in the serum and BALF were significantly lower in the acupuncture group than in the model group ( < 0.05). In the model group, the expressions of -SMA, TGF-β1 and Smads in the airway smooth muscles were significantly higher than those in the other two groups (both < 0.05). In cultured airway smooth muscle cells, the expressions of type-Ⅰ and Smads were significantly higher in cells treated with LY2157299 than in the control cells (>0.05). CONCLUSIONS Acupuncture can inhibit airway remodeling by inhibiting the expression of airway TGF-β1 and down-regulating the expression of Smads and -SMA to reduce airway inflammatory response. Airway expressions of type-Ⅰ and Smads proteins remain high after inhibiting TGF-β1. Acupuncture may control asthma progression through the TGF-β1/Smads pathway.
Acupuncture Points ; Acupuncture Therapy ; Airway Remodeling ; Airway Resistance ; Animals ; Asthma ; metabolism ; pathology ; therapy ; Bronchi ; pathology ; Disease Progression ; Lung ; metabolism ; physiopathology ; Mice ; Muscle, Smooth ; Random Allocation ; Smad Proteins ; analysis ; metabolism ; Transforming Growth Factor beta1 ; analysis ; metabolism