1.Applicability study of balloon pulmonary angioplasty in residual pulmonary hypertension of chronic thromboembolic pulmonary hypertension after pulmonary endarterectomy
Jinzhi WANG ; Xincao TAO ; Wanmu XIE ; Shuai ZHANG ; Zhu ZHANG ; Yunwei ZHAO ; Yishan LI ; Ana JIANG ; Hao WANG ; Qiang HUANG ; Zhenguo DI
Chinese Journal of Radiology 2024;58(3):318-323
Objective:To investigate the safety and efficacy of balloon pulmonary angioplasty (BPA) for residual pulmonary hypertension (PH) of chronic thromboembolic pulmonary hypertension(CTEPH) after pulmonary endarterectomy (PEA).Methods:Patients diagnosed as PH after PEA in China-Japan Friendship Hospital from Oct 2016 to Jun 2022 were included. The indication for BPA was decided on the basis of a consensus of the multi-disciplinary team for all patients with CTEPH. Before treatment, the patient′s exercise tolerance and pulmonary artery flow parameters were evaluated. A comparative analysis of various parameters before BPA treatment and at the last BPA was conducted. 6-min walk distance (6MWD) was analyzed using the paired Wilcoxon test; N-terminal pro-brain natriuretic peptide (NT-proBNP), mixed venous oxygen saturation, mean pulmonary arterial pressure (mPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were compared using the paired-samples t-test. WHO functional class was compared using McNemar′s test. Results:Twenty patients with a total of 130 vessels underwent 46 sessions of BPA treatment. The postoperative 6-minute walk distance (6MWD) [447 (415, 485) m] showed a significant improvement compared to the preoperative baseline [389 (335, 470) m] ( Z=6.52, P<0.05), Postoperative mixed venous oxygen saturation (72.0%±1.9%) showed a significant improvement compared to the preoperative levels (64.0%±2.7%) ( t=2.14, P<0.05).Postoperatively, plasma NT-proBNP [(351.9±129.9) pg/ml], mPAP [(24.2±1.9) mmHg], and PVR [(3.0±1.4) WU] significantly decreased compared to preoperative levels [(982.5±426.2) pg/ml, (33±2.1) mmHg, (8.0±1.6) WU)] ( t=3.38, 1.22, 2.10, P<0.05 for all). Postoperatively, there was a significant improvement in WHO functional class (Ⅰ,Ⅱ,Ⅲ,Ⅳ: 14, 4, 2, 0 cases) compared to preoperative status (Ⅰ,Ⅱ,Ⅲ,Ⅳ: 0, 13, 5, 2 cases) ( χ2=20.17, P<0.05). Four cases of pulmonary artery dissection and one episode of hemoptysis occurred postoperatively, with no other complications reported. Conclusions:BPA can significantly improve exercise tolerance and hemodynamic parameters for residual PH after PEA. BPA is a relatively safe and effective treatment for residual PH after PEA.
2.Efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children:meta-analysis of single-group rate
Caixia TU ; Danyang REN ; Jianling SHEN ; Yunwei LI ; Yanming YANG ; Aihua YAN ; Lin LI ; Huiying LI
China Pharmacy 2024;35(15):1893-1898
OBJECTIVE To investigate the efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children, and provide reference for clinically safe and rational drug use. METHODS The literatures about additional clobazam treatment for refractory epilepsy in children were searched from PubMed, The Cochrane Library, Embase, CNKI, VIP and Wanfang database during the inception to November 2023. After literature screening and data extraction, the quality of included literature was evaluated according to quality evaluation tool for methodological evaluation indicators of non-randomized controlled trial, and then meta-analysis of single-group rate and sensitivity analysis were performed by using RevMan 5.3 software. RESULTS Finally, 18 one-arm studies were included, with a total of 1 424 children. The results showed that compared with before additional treatment, the proportion of patients with seizures-free (proportion of patients with seizure reduction of 100%) was 24%[95%CI (0.18,0.32), P<0.000 01] after conversion; the proportion of patients with seizure reduction ≥75% was 32%[95%CI(0.25,0.40), P<0.000 1] after conversion; the proportion of patients with seizure reduction ≥50% was 53%[95%CI(0.44,0.61),P<0.000 01]; the proportion of patients with seizure reduction <50% or no change was 35%[95%CI(0.24,0.49),P=0.04] after conversion; the proportion of patients with seizure increase was 9%[95%CI(0.05,0.18),P<0.000 01] after conversion. The proportion of patients with adverse reactions was 31%[95%CI(0.23,0.40),P<0.000 1] after conversion; the proportion of patients with discontinuation due to adverse reactions was 10%[95%CI(0.07, 0.15), P<0.000 01] after conversion. The common adverse drug reactions were drowsiness, fatigue and behavior change, etc. The results of the sensitivity analysis showed that the study was robust. CONCLUSIONS Clobazam is an effective additional therapy for refractory epilepsy in children, but its adverse effects should be vigilant.
3.Current situation of and countermeasures for achievement transformation and management in tertiary medical hospitals in Shanghai
Yunwei ZHANG ; Changying WANG ; Na LI ; Yuhong NIU
Modern Hospital 2024;24(2):300-303
Objective To investigate the current situation of achievement transformation in tertiary medical hospitals in Shanghai and propose countermeasures for the existing problems to enhance the effectiveness of achievement transformation.Methods A questionnaire survey was done on the transformation and management of scientific research achievements in 47 terti-ary hospitals in Shanghai.Meanwhile,interviews were carried out among the managers and researchers from these hospitals.Re-sults In the past three years,the rate of transformation achievements in the hospitals was only 2.8%.In the achievement trans-formation existed such problems as weak awareness of scientific researchers,low patent quality,lack of full-time managers,and inflexible management mode.It was also believed that there is a need to improve main responsibilities,achievement management,system establishment,personnel training,resource sharing,department coordination and other related aspects.Conclusion The rate of achievement transformation in tertiary medical institutions in Shanghai is at a lower level.There are numerous problems and difficulties in the transformation.Therefore,urgent efficient countermeasures are needed to promote the transformation of a-chievement.
4.Comparison of the efficacy between ThuLEP and PKEP in the treatment of large volume benign prostatic hyperplasia
Yunwei LI ; Peiyue LI ; Danbin LI
Journal of Modern Urology 2024;29(8):699-702
Objective To compare the short-term outcomes of thulium laser enucleation of the prostate(ThuLEP)and plasmaknife enucleation of the prostate(PKEP)in the treatment of large volume(≥80 mL)benign prostatic hyperplasia(BPH),so as to provide reference for clinical practice.Methods Clinical data of 100 patients with large volume BPH admitted to the Shandong Provincial Third Hospital affiliated with Shandong University during Jun.2021 and Jun.2023 were retrospectively analyzed.Based on the surgical methods,patients were divided into the ThuLEP group(n=50)and PKEP group(n=50).The following parameters were compared between the two groups,including preoperative maximum flow rate(Qmax),international prostatic symptom score(IPSS),quality of life score(QoL),operation time,intraoperative blood loss,weight of enucleated prostate tissue,postoperative bladder irrigation time,catheterization time,hospital stay,complication rate,and postoperative Qmax,IPSS,and QoL at 3 months.Results The operation time[(79.04±9.42)min vs.(80.10±8.94)min],intraoperative blood loss[(42.86±7.84)mL vs.(43.32±7.36)mL],and postoperative continuous bladder irrigation time[(19.88±4.13)h vs.(20.10±4.04)h]were not statistically different between the ThuLEP and PKEP groups(P>0.05).The weight of enucleated tissue during ThuLEP was higher than that during PKEP[(69.44±4.90)g vs.(65.06±5.25)g],postoperative catheterization time was shorter[(27.20±4.07)h vs.(29.02±4.86)h],and hospital stay was shorter[(3.30±0.66)d vs.(4.05±0.91)d],with statistically significant differences(P<0.05).Three months after operation,the Qmax,IPSS,and QoL score in both groups were significantly improved(P<0.05),but there were no statistically significant differences between the two groups(P>0.05).There was no statistically significant difference in the complication rate between the ThuLEP and PKEP groups(2%vs.4%,P>0.05).Conclusion Both ThuLEP and PKEP have good short-term efficacy and safety in the treatment of large volume BPH,but ThuLEP is superior to PKEP in terms of reducing enucleated prostate weight,and shortening postoperative catheterization time and hospital stay.
5.Influences and mechanism of extracellular vesicles from dermal papilla cells of mice on human hypertrophic scar fibroblasts
Yunwei WANG ; Hao ZHANG ; Peng CAO ; Wanfu ZHANG ; Lin TONG ; Shaohui LI ; Yang CHEN ; Chao HAN ; Hao GUAN
Chinese Journal of Burns 2024;40(3):258-265
Objective:To investigate the influences and mechanism of extracellular vesicles from dermal papilla cells (DPC-EVs) of mice on human hypertrophic scar fibroblasts (HSFs).Methods:The study was an experimental research. The primary dermal papilla cells (DPCs) of whiskers were extracted from 10 6-week-old male C57BL/6J mice and identified successfully. The DPC-EVs were extracted from the 3 rd to 5 th passage DPCs by ultracentrifugation, and the morphology was observed through transmission electron microscope and the particle diameter was detected by nanoparticle tracking analyzer ( n=3) at 24 h after culture. The 3 rd passage of HSFs were divided into DPC-EV group and phosphate buffer solution (PBS) group, which were cultured with DPC-EVs and PBS, respectively. The cell scratch test was performed and cell migration rate at 24 h after scratching was calculated ( n=5). The cell proliferation levels at 0 (after 12 h of starvation treatment and before adding DPC-EVs or PBS), 24, 48, 72, and 96 h after culture were detected by using cell counting kit 8 ( n=4). The protein expressions of α-smooth muscle actin (α-SMA) and collagen typeⅠ (ColⅠ) in cells at 24 h after culture were detected by immunofluorescence method and Western blotting, and the protein expression of Krüppel-like factor 4 (KLF4) in cells at 24 h after culture was detected by Western blotting. After the 3 rd passage of HSFs were cultured with DPC-EVs for 24 h, the cells were divided into blank control group, KLF4 knockdown group, and KLF4 overexpression group according to the random number table. The cells in blank control group were only routinely cultured for 48 h. The cells in KLF4 knockdown group and KLF4 overexpression group were incubated with KLF4 knockdown virus for 24 h, then the cells in KLF4 knockdown group were routinely cultured for 24 h while the cells in KLF4 overexpression group were incubated with KLF4 overexpression virus for 24 h. The protein expressions of KLF4, α-SMA, and ColⅠ in cells were detected by Western blotting at 48 h after culture. Results:At 24 h after culture, the extracted DPC-EVs showed vesicular structure with an average particle diameter of 108.8 nm. At 24 h after scratching, the migration rate of HSFs in PBS group was (54±10)%, which was significantly higher than (29±8)% in DPC-EV group ( t=4.37, P<0.05). At 48, 72, and 96 h after culture, the proliferation levels of HSFs in DPC-EV group were significantly lower than those in PBS group (with t values of 4.06, 5.76, and 6.41, respectively, P<0.05). At 24 h after culture, the protein expressions of α-SMA and ColⅠ of HSFs in DPC-EV group were significantly lower than those in PBS group, while the protein expression of KLF4 was significantly higher than that in PBS group. At 48 h after culture, compared with those in blank control group, the protein expression of KLF4 of HSFs in KLF4 knockdown group was down-regulated, while the protein expressions of α-SMA and ColⅠ were both up-regulated; compared with those in KLF4 knockdown group, the protein expression of KLF4 of HSFs in KLF4 overexpression group was up-regulated, while the protein expressions of ColⅠ and α-SMA were down-regulated. Conclusions:The DPC-EVs of mice can inhibit the proliferation and migration of human HSFs and significantly inhibit the expressions of fibrosis markers α-SMA and ColⅠ in human HSFs by activating KLF4.
6.Risk factors for hemodynamically significant patent ductus arteriosus in preterm infants requiring surgical ligation: a nested case-control study
Jingjing JIANG ; Zhenghong LI ; Zhenjie ZHANG ; Yunwei LI ; Juan DING ; Jiaxin LI ; Weilin WAN
Chinese Journal of Applied Clinical Pediatrics 2023;38(3):210-214
Objective:To analyze the risk factors for premature infants with hemodynamically significant patent ductus arteriosus (hs-PDA) requiring surgical treatment, and to explore the indications for surgical treatment in premature infants with hs-PDA.Methods:A nested case-control study was conducted.The data of premature infants with gestational age<30 weeks who were diagnosed with hs-PDA in the Neonatal Intensive Care Unit of Peking Union Medical College Hospital from January 2007 to May 2020 were analyzed retrospectively.The hs-PDA patients treated surgically were included in the operation group.The hs-PDA patients of the same gestational age and gender who were not treated surgically were taken as the control group.The ratio of the case number between the operation and control groups was 1∶2.The clinical data during pregnancy, at birth and after birth of premature infants were compared between the 2 groups.The measurement data were tested by the independent sample t test or Mann- Whitney U test.The classification and enumeration data were compared by the Fisher′ s exact probability method.The risk factors for premature infants with hs-PDA requiring surgical treatment were analyzed by the conditional Logistic regression method. Results:A total of 182 premature infants with hs-PDA were enrolled in the study, including 10 in the operation group and 20 in the control group.The patients underwent PDA ligation 30.5(22.7, 37.0) d after birth, and the median preo-perative invasive ventilation duration was 9.7(17.5, 27.2) d. Compared with the control group(20 cases), the preterm infants in the operation group had a lower birth weight [(891.5±118.0) g vs.(1 054.4±230.2) g, t=2.091], a wider arterial duct diameter [3.2(2.8, 4.0) mm vs.2.0(2.0, 3.0) mm, Z=-3.300], and longer invasive ventilation duration [25.0(18.7, 38.2) d vs.3.0(1.0, 7.5) d, Z=-3.688]. Besides, the operation group applied the pulmonary surfactant for more times [2(1, 3) times vs.1(1, 2) times, Z=-2.440], and inhaled a higher concentration of oxygen on the 14 th day after birth [29(25, 36)% vs.21(21, 29)%, Z=-2.358] than the control group.Moreover, compared with the control group, the operation group took longer to achieve adequate enteral feeding [48.2(51.5, 63.5) d vs.42.5(23.5, 48.0) d, Z=2.789], and gained a higher maximum vasoactive inotropic score (VIS) [3.0(0, 3.5) points vs.0(0, 0) points, Z=-2.630]. The difference in all the above-mentioned indicators between the 2 groups was statistically significant (all P<0.05). Univariate Logistic regression analysis showed that the arterial duct diameter, application times of the pulmonary surfactant, the maximum VIS score, and the time taken to achieve sufficient enteral feeding were all related to the need for surgical treatment of hs-PDA in the operation group (all P<0.05). Multivariate Logistic regression analysis revealed that the invasive ventilation duration ( OR=0.747, 95% CI: 0.560-0.998, P=0.048) was an independent risk factor for hs-PDA premature infants requiring surgical treatment. Conclusions:The factors related to the need for surgical treatment in preterm infants with hs-PDA include a wide arterial duct diameter, multiple applications of the pulmonary surfactant, a high concentration of inhaled oxygen on the 14 th day, and the long time to achieve sufficient enteral feeding.The independent risk factor for the surgical treatment in hs-PDA children is the long invasive ventilation duration.
7.Efficacy and safety of different doses of zinc in the treatment of diarrhea in children:a systematic review
Caixia TU ; Danyang REN ; Yunwei LI ; Yanming YANG ; Jianling SHEN ; Yan LIU ; Ting LIU ; Huiying LI
China Pharmacy 2023;34(17):2154-2161
OBJECTIVE To investigate the efficacy and safety of different doses of zinc in the treatment of diarrhea in children, and to provide a reference for clinical safe and rational drug use. METHODS Retrieved from PubMed, Cochrane Library, Embase database, randomized controlled trials about zinc (zinc group) versus placebo or conventional treatment (control group) in the treatment of diarrhea in children were collected from the inception to October 2022. Then, the quality of the included literature was evaluated by the Cochrane Handbook 6.0, and meta-analysis and sensitivity analysis were performed by RevMan 5.3 software. RESULTS Finally, 25 RCTs were included, with a total of 8 618 children. The results of meta-analysis showed that in terms of duration of diarrhea, in zinc <20 mg group, the zinc group was significantly shorter than the control group [SMD= -0.39, 95%CI(-0.71, -0.08), P=0.01], but in subgroups of <6 months old, there was no significant difference between the two groups [SMD=0.01, 95%CI(-0.10, 0.11), P=0.88]. In zinc 20 mg group, the zinc group was significantly shorter than the control group [SMD=-0.52, 95%CI(-0.80, -0.23), P=0.000 3]. In zinc >20 mg group, the zinc group was significantly shorter than the control group [SMD=-0.83, 95%CI(-1.39, -0.27), P=0.004]. In zinc >10 mg (age ≤12 months) or zinc > 20 mg (age >12 months) group (short for “constant dose group”), the zinc group was significantly shorter than the control group [SMD=-0.16, 95%CI(-0.27, -0.06), P= 0.003]. In the aspect of diarrhea rate after 7 days of treatment,there was no significant difference in the diarrhea rate after 7 E-mail:lihuiying@etyy.cn days of treatment between the zinc group and the control group: in zinc <20 mg group[OR=1.28,95%CI (0.96,1.70),P=0.09], in zinc 20 mg group [OR=0.40, 95%CI (0.15,1.01),P= 0.05], in constant dose group [OR=0.64, 95%CI (0.28, 1.44), P=0.28]. In terms of vomiting rate, in zinc <20 mg group, the vomiting rate of zinc group was significantly higher than that of the control group [OR=2.13, 95%CI (1.68, 2.70), P<0.001]; in constant dose group, vomiting rate of zinc group was significantly higher than that of the control group [OR=1.84, 95%CI (1.44, 2.34), P<0.001]. CONCLUSIONS Zinc can significantly shorten the duration of diarrhea in children(6 months and above), but low doses can increase the risk of vomiting, which should be taken attention in clinical.
8.Predictive value of anthropometric indicators for cardiovascular risk in metabolic syndrome
Qiyun LU ; Anxiang LI ; Benjian CHEN ; Qingshun LIANG ; Guanjie FAN ; Yiming TAO ; Ronghua ZHANG ; Fangfang DAI ; Xiaoling HU ; Yunwei LIU ; Yingxiao HE ; Ying ZHU ; Zhenjie LIU
Chinese Journal of Endocrinology and Metabolism 2023;39(1):26-33
Objective:To evaluate the predictive value of anthropometric indicators in predicting cardiovascular risk in the population with metabolic syndrome(MS).Methods:A cross-sectional study was used to analyze the correlation between anthropometric measures and cardiovascular risk in subjects with MS. Cardiometabolic risk was assessed with cardiometabolic risk index(CMRI). Receiver operating characteristic(ROC) curve analysis was used to assess the predictive power of anthropometric measures for cardiometabolic risk.Results:(1) The anthropometric measures [body mass index(BMI), waist-hip ratio(WHR), waist-to-height ratio(WtHR), body fat percentage(BFP), visceral fat index(VFI), conicity index(CI), a body shape index(ABSI), body roundness index(BRI), abdominal volume index(AVI)] in the MS group were significantly higher than those in the non-MS group( P<0.05). Moreover, there were significant differences in CMRI score and vascular risk between the two groups( P<0.05). (2) Logistic regression analysis showed that the cardiovascular risk was increased with the increases of BMI, VFI, WHR, WtHR, CI, BRI, and AVI after adjusting for confounding factors in the overall population, the non-MS population, and the MS population( P<0.05). (3) In the ROC analysis, the AUC values of BMI, VFI, and AVI were 0.767, 0.734, and 0.770 in the overall population; 0.844, 0.816, and 0.795 in the non-MS population; 0.701, 0.666, and 0.702 in the MS population, respectively. For the overall population and non-MS population, the optimal cut points of BMI to diagnose high cardiovascular risk were 26.04 kg/m 2 and 24.36 kg/m 2; the optimal cut points of VFI were 10.25 and 9.75; the optimal cut points of AVI were 17.3 cm 2 and 15.53 cm 2, respectively. In the MS population, the optimal cut point as a predictor of high cardiovascular risk in young and middle-aged men with MS was 27.63 kg/m 2, and the optimal cut point of AVI in women was 18.08 cm 2. Conclusion:BMI, VFI, and AVI can be used as predictors of cardiovascular risk in the general population. BMI can be used as a predicator of high cardiovascular risk in young and middle-age men with MS. AVI can be used as a predicator of high cardiovascular risk in women with MS.
9.Effects of mechanical tension on the formation of hypertrophic scars in rabbit ears and transforming growth factor-β 1/Smad signaling pathway
Peng CAO ; Yunwei WANG ; Hao GUAN ; Yunshu YANG ; Shaohui LI ; Yang CHEN ; Chan ZHU ; Yu WAN ; Liying REN ; Ming YAO
Chinese Journal of Burns 2022;38(12):1162-1169
Objective:To explore the effects of mechanical tension on the formation of hypertrophic scars in rabbit ears and transforming growth factor-β 1 (TGF-β 1)/Smad signaling pathway. Methods:The experimental research method was adopted. Six New Zealand white rabbits, male or female, aged 3-5 months were used and 5 full-thickness skin defect wounds were made on the ventral surface of each rabbit ear. The appearance of all rabbit ear wounds was observed on post surgery day (PSD) 0 (immediately), 7, 14, 21, and 28. On PSD 28, the scar formation rate was calculated. Three mature scars in the left ear of each rabbit were included in tension group and the arch was continuously expanded with a spiral expander. Three mature scars in the right ear of each rabbit were included in sham tension group and only the spiral expander was sutured without expansion. There were 18 scars in each group. After mechanical tension treatment (hereinafter referred to as treatment) for 40 days, the color and texture of scar tissue in the two groups were observed. On treatment day 40, the scar elevation index (SEI) was observed and calculated; the histology was observed after hematoxylin eosin staining, and the collagen morphology was observed after Masson staining; mRNA expressions of TGF-β 1, Smad3, collagen Ⅰ, collagen Ⅲ, and α-smooth muscle actin (α-SMA) in scar tissue were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction; and the protein expressions of TGF-β 1, collagen Ⅰ, collagen Ⅲ, and α-SMA, and phosphorylation level of Smad3 in scar tissue were detected by Western blotting. The number of samples of each group in the experiments was 3. Data were statistically analyzed with independent sample t test. Results:On PSD 0, 5 fresh wounds were formed on all the rabbit ears; on PSD 7, the wounds were scabbed; on PSD 14, most of the wounds were epithelialized; on PSD 21, all the wounds were epithelialized; on PSD 28, obvious hypertrophic scars were formed. The scar formation rate was 75% (45/60) on PSD 28. On treatment day 40, the scar tissue of rabbit ears in tension group was more prominent than that in sham tension group, the scar tissue was harder and the color was more ruddy; the SEI of the scar tissue of rabbit ears in tension group (2.02±0.08) was significantly higher than 1.70±0.08 in sham tension group ( t=5.07, P<0.01). On treatment day 40, compared with those in sham tension group, the stratum corneum of scar tissue became thicker, and a large number of new capillaries, inflammatory cells, and fibroblasts were observed in the dermis, and collagen was more disordered, with nodular or swirling distribution in the scar tissue of rabbit ears in tension group. On treatment day 40, the mRNA expressions of TGF-β 1, Smad3, collagen Ⅰ, collagen Ⅲ, and α-SMA in the scar tissue of rabbit ears in tension group were respectively 1.81±0.25, 5.71±0.82, 7.86±0.56, 4.35±0.28, and 5.89±0.47, which were significantly higher than 1.00±0.08, 1.00±0.12, 1.00±0.13, 1.00±0.14, and 1.00±0.14 in sham tension group (with t values of 5.36, 9.82, 20.60, 18.26, and 17.13, respectively, all P<0.01); the protein expressions of TGF-β 1, collagen Ⅰ, collagen Ⅲ, and α-SMA, and phosphorylation level of Smad3 in the scar tissue of rabbit ears in tension group were respectively 0.865±0.050, 0.895±0.042, 0.972±0.027, 1.012±0.057, and 0.968±0.087, which were significantly higher than 0.657±0.050, 0.271±0.029, 0.631±0.027, 0.418±0.023, and 0.511±0.035 in sham tension group (with t values of 5.08, 21.27, 15.55, 16.70, and 8.40, respectively, all P<0.01). Conclusions:Mechanical tension can inhibit the regression of hypertrophic scars in rabbit ears through stimulating the hyperplasia of scars, inhibiting the normal arrangement of dermal collagen fibers, and intensifying the deposition of collagen fibers, and the mechanism may be related to the activation of TGF-β 1/Smad signaling pathway by mechanical tension.
10.The effect of pressure therapy on the formation of hypertrophic scar and TGF-β1/Smad signaling pathway
Peng CAO ; Yunwei WANG ; Ming YAO ; Shaohui LI ; Yang CHEN ; Chan ZHU ; Qian LENG ; Liying REN ; Hao GUAN
Chinese Journal of Plastic Surgery 2022;38(7):804-813
Objective:To observe the effect of pressure therapy on the formation of hypertrophic scars(HTS) and transforming growth factor beta 1 (TGF-β1) / Sma and Mad homolog proteins (Smad) signaling pathway.Methods:Twelve adult healthy New Zealand white rabbits(provided by the Animal Experiment Center of the Air Force Military Medical University) were wounded with 1 cm round punch on 4 sites of the ventral side of each ear. Round scalpels were used to make incisions along the marked lines, dissect the skin and perichondrium. The remaining tissue was scraped off to expose the wound surface. Scar formation was observed on the 28th day after surgery. After the establishment of rabbit ear HTS models, the right ears were used as self-controls, while the left ears were set as the experimental group. Two hypertrophic scars were randomly selected from each rabbit ear, 24 per group. Experimental group: 4-0 nylon silk thread was used to sew the pressure pad on the circular NdFeB magnets pad with a diameter of 1.5 cm to the rabbit ear cartilage. Flexiforce pressure sensor was used to measure the pressure, and the pads were adjusted to maintain a pressure of 20-25 mmHg (1 mmHg=0.133 kPa) for more than 23 h per day. Control group: no treatment. On the 40th day of pressure therapy, the general morphology of rabbit ear scars were observed, and the tissues were harvested for hematoxylin and eosin (HE) staining and Masson’s Trichrome staining for histological study. The scar elevation index (SEI), the number of fibroblasts, and the thickness of the stratum corneum were calculated. The relative mRNA expression levels of TGF-β1, Smad3, collagen type (Collagen )Ⅰ, Collagen Ⅲ, α-smooth muscle actin (α-SMA) were measured with qPCR; Western blotting was used to detect the relative protein expression levels of TGF-β1, Collagen Ⅰ, Collagen Ⅲ, α-SMA and the phosphorylation level of Smad3 (the ratio of p-Smad3 and Smad3 proteins). Statistical analysis was performed with Excel 2019 and GraphPad Prism 8.0. The measurement data conformed to normal distribution and was expressed as Mean±SD. Student’s t-test was used for the comparison between two groups. P<0.05 was considered statistically significant. Results:A total of 96 wounds were formed in 12 rabbits, 27 wounds had no obvious hyperplasia, and the remaining 69 wounds formed hypertrophic scar tissue blocks with a prominent skin surface, firm texture, and dark red appearance. The scars formation rate was 71.9% (69/96). On the 40th day after the application of pressure, the scars in the experimental group were significantly reduced, softer, and the color was slightly lighter compared with the control group. The results of HE staining and Masson’s Trichrome staining showed that the thickness of the stratum corneum, SEI, and the number of fibroblasts were (69.33±6.03) μm, 1.30±0.08, and (236.30±14.64) cells/field, respectively, which were significantly lower than those in the control group [(114.00±10.15) μm, 1.72±0.05, (320.30±14.57) cells/field] (all P<0.01). Abundance in capillaries, inflammatory cells, and fibroblasts were not observed in the dermal layer. The collagen fibers were orderly arranged and sparse. The results of fluorescence quantitative PCR showed that the relative expression levels of TGF-β1, Smad3, Collagen Ⅰ, Collagen Ⅲ, and α-SMA mRNA in the experimental group were 0.48±0.08, 0.58±0.05, 0.04±0.01, 0.15±0.02, 0.31±0.03, respectively, lower than those of the control group(1.00±0.07, 1.00±0.05, 1.00±0.08, 1.00±0.10, 1.00±0.06) (all P<0.01). The results of Western blotting showed that the relative protein expression of TGF-β1, Collagen Ⅰ, Collagen Ⅲ, α-SMA and the phosphorylation level of Smad3 in the experimental group were 0.65±0.03, 0.07±0.01, 0.43±0.03, 0.53±0.03, 0.54±0.03, all lower than the control group’s 1.02±0.06, 0.93±0.05, 0.92±0.03, 0.82±0.03, 0.92±0.03 (all P<0.01). Conclusions:Pressure therapy can significantly inhibit the hyperplasia of scars, improve the structure of HTS tissue, facilitate the normal arrangement of collagen fiber, and reduce the excessive deposition of collagen. Pressure therapy may inhibit scar proliferation by regulating the TGF-β1/Smad signaling pathway.

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