1.Clinical value of peripheral immune function status in the assessment of ‘Deficiency of Vital Qi’ in lung cancer metastasis
XU Fan1,2 ; TIAN Jianhui1,2 ; LIU Youjun1,2 ; CHENG Zhenyang1,2 ; QUE Zujun2 ; LUO Bin1 ; YANG Yun1 ; YAO Jialiang1 ; YAO Wang1 ; LU Xinyi1,2 ; LIU Yao1,2 ; ZHOU Yiyang1 ; WU Jianchun1 ; LUO Yingbin1 ; LI Minghua1 ; SHI Wenfei1 ; CUI Yajing1 ; SHANGGUAN Wenji3 ; LI Yan1
Chinese Journal of Cancer Biotherapy 2025;32(10):1065-1070
[摘 要] 目的:探索外周免疫功能状态与肺癌转移的关联,筛选可用于肺癌转移“正虚”评估的外周血免疫标志物。方法:回顾性分析2023年3月至2025年4月期间上海中医药大学附属市中医医院收治的肺癌患者治疗前的外周血免疫标志物,根据是否存在远处转移,将患者分为无转移组与转移组,比较两组间免疫细胞和细胞因子的表达差异。将单因素分析P < 0.05的外周血免疫指标纳入多因素二元Logistic回归模型,以识别肺癌转移的独立预测因素。结果:共纳入193例肺癌患者(无转移组101例,转移组92例),两组在性别、年龄、吸烟史、饮酒史、病理类型间的差异均无统计学意义(均P > 0.05)。单因素分析显示,无转移组与转移组间有多项免疫指标存在显著差异(均P < 0.05),包括:淋巴细胞计数,CD3+、CD4+、CD8+ T、CD19+ B细胞及CD3-CD16+56+ NK细胞绝对计数,Treg细胞、CD8+CD28+ Treg细胞、G-MDSC和CD3-CD16+CD56+dim NK细胞百分率,以及细胞因子IL-1β、IL-6和IL-10水平。将差异性指标行二元Logistic回归分析,提示外周血中Treg细胞和CD8+CD28+ Treg细胞百分率是肺癌发生远处转移的独立预测因素[OR = 1.193, 95% CI(1.047, 1.36), P < 0.01; OR = 0.978, 95% CI(0.957, 0.999), P < 0.05]。结论:外周血免疫功能紊乱是肺癌转移“正虚”的生物学基础,本研究以量化指标证实外周免疫功能状态与肺癌转移的相关性,为“正虚伏毒”和“肿瘤转移态”理论提供了实证。
2.Percutaneous coronary intervention vs . medical therapy in patients on dialysis with coronary artery disease in China.
Enmin XIE ; Yaxin WU ; Zixiang YE ; Yong HE ; Hesong ZENG ; Jianfang LUO ; Mulei CHEN ; Wenyue PANG ; Yanmin XU ; Chuanyu GAO ; Xiaogang GUO ; Lin CAI ; Qingwei JI ; Yining YANG ; Di WU ; Yiqiang YUAN ; Jing WAN ; Yuliang MA ; Jun ZHANG ; Zhimin DU ; Qing YANG ; Jinsong CHENG ; Chunhua DING ; Xiang MA ; Chunlin YIN ; Zeyuan FAN ; Qiang TANG ; Yue LI ; Lihua SUN ; Chengzhi LU ; Jufang CHI ; Zhuhua YAO ; Yanxiang GAO ; Changan YU ; Jingyi REN ; Jingang ZHENG
Chinese Medical Journal 2025;138(3):301-310
BACKGROUND:
The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.
METHODS:
This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.
RESULTS:
Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n = 278] vs . 43.7% [ n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses.
CONCLUSION
This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans
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Percutaneous Coronary Intervention/methods*
;
Male
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Female
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Coronary Artery Disease/drug therapy*
;
Retrospective Studies
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Renal Dialysis/methods*
;
Middle Aged
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Aged
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China
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Proportional Hazards Models
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Treatment Outcome
3.Chinese expert consensus on the evaluation of allergen-specific immunotherapy outcomes(Wuhan, 2025).
Yuqin DENG ; Xi LUO ; Zhuofu LIU ; Shuguang SUN ; Jing YE ; Tiansheng WANG ; Jianjun CHEN ; Meiping LU ; Yin YAO ; Ying WANG ; Wei ZHOU ; Bei LIU ; Qingxiang ZENG ; Yuanteng XU ; Qintai YANG ; Yucheng YANG ; Feng LIU ; Chengli XU ; Yanan SUN ; Haiyu HONG ; Haibo YE ; Liqiang ZHANG ; Fenghong CHEN ; Huabin LI ; Hongtian WANG ; Yuncheng LI ; Wenlong LIU ; Yu XU ; Hongfei LOU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(11):1075-1085
Allergen-specific immunotherapy(AIT) remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis(AR). Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group(CRRCG) convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans
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Allergens/immunology*
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China
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Consensus
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Desensitization, Immunologic
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Immunoglobulin E
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Quality of Life
;
Rhinitis, Allergic/therapy*
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Treatment Outcome
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East Asian People
4.Curcumae Rhizoma: An anti-cancer traditional Chinese medicine.
Yu LUO ; Lin ZHU ; Zhengyu REN ; Jian XIAO ; Erwei HAO ; Jiahong LU ; Jinmin ZHAO ; Chun YAO ; Yitao WANG ; Hua LUO
Chinese Herbal Medicines 2025;17(3):428-447
Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.
5.Effects of evodiamine on inflammation and apoptosis of airway epithelial cells in asthma model rats and its mechanism
Jun LEI ; Lijun LU ; Lingyan LUO ; Song QIAO ; Yanan TONG ; Yang ZHENG ; Lei YAO
China Pharmacy 2024;35(11):1351-1356
OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group, model group, evodiamine low-dose group (10 mg/kg), evodiamine high-dose group (20 mg/kg), dexamethasone group (positive control, 0.5 mg/kg), epidermal growth factor (EGF) group [mitogen-activated protein kinase (MAPK) activator, 10 μg], evodiamine high-dose+EGF group (20 mg/kg evodiamine+10 μg EGF), with 10 rats in each group. Except for the control group, the other groups were sensitized by 3-point injection of 10% ovalbumin(OVA)-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells (macrophages and lymphocytes) in bronchoalveolar lavage fluid (BALF) was detected in each group; pathological changes of lung tissue in rats were observed; the apoptosis of airway epithelial cells, the levels of serum inflammatory factors [tumor necrosis factor-α, interleukin-6 (IL-6) and IL-4], the expressions of pathway-related proteins p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK), signal transduction and transcription activating factor 1 (STAT1)] and apoptosis-related proteins [B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax)] were all detected in lung tissue. RESULTS Compared with the control group, bronchial mucosal edema, thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group; the number of inflammatory cells, apoptosis rate of airway epithelial cells, the levels of inflammatory factors, p-38 MAPK/p-38 MAPK, and the protein expressions of Bax and STAT1 were increased significantly; the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly (P<0.05). Compared with the model group, the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups, and dexamethasone groups, and the above indicators were significantly reversed. However, the change trends of corresponding indicators in the EGF group were opposite to the above (P<0.05). EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats (P<0.05). CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats, the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.
6.Effects of evodiamine on inflammation and apoptosis of airway epithelial cells in asthma model rats and its mechanism
Jun LEI ; Lijun LU ; Lingyan LUO ; Song QIAO ; Yanan TONG ; Yang ZHENG ; Lei YAO
China Pharmacy 2024;35(11):1351-1356
OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group, model group, evodiamine low-dose group (10 mg/kg), evodiamine high-dose group (20 mg/kg), dexamethasone group (positive control, 0.5 mg/kg), epidermal growth factor (EGF) group [mitogen-activated protein kinase (MAPK) activator, 10 μg], evodiamine high-dose+EGF group (20 mg/kg evodiamine+10 μg EGF), with 10 rats in each group. Except for the control group, the other groups were sensitized by 3-point injection of 10% ovalbumin(OVA)-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells (macrophages and lymphocytes) in bronchoalveolar lavage fluid (BALF) was detected in each group; pathological changes of lung tissue in rats were observed; the apoptosis of airway epithelial cells, the levels of serum inflammatory factors [tumor necrosis factor-α, interleukin-6 (IL-6) and IL-4], the expressions of pathway-related proteins p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK), signal transduction and transcription activating factor 1 (STAT1)] and apoptosis-related proteins [B cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax)] were all detected in lung tissue. RESULTS Compared with the control group, bronchial mucosal edema, thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group; the number of inflammatory cells, apoptosis rate of airway epithelial cells, the levels of inflammatory factors, p-38 MAPK/p-38 MAPK, and the protein expressions of Bax and STAT1 were increased significantly; the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly (P<0.05). Compared with the model group, the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups, and dexamethasone groups, and the above indicators were significantly reversed. However, the change trends of corresponding indicators in the EGF group were opposite to the above (P<0.05). EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats (P<0.05). CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats, the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.
7.Application of 5-point positioning point-contact pedicle navigation template in the case of scoliosis and complex pedicle
Lihang WANG ; Tingsheng LU ; Qiling CHEN ; Shudan YAO ; Xingwei PU ; Linsong JI ; Guoquan ZHAO ; Beiping OUYANG ; Bin ZHANG ; Zaisong YANG ; Chunshan LUO
Chinese Journal of Tissue Engineering Research 2024;28(18):2859-2864
BACKGROUND:The pedicle navigation template has many advantages,but there are still some problems.For example,poor soft tissue dissection leads to poor adhesion of the pedicle navigation template,resulting in screw path deviation;careful dissection of soft tissue to fit the pedicle navigation template leads to prolonged surgery time and increased bleeding;the design of the pedicle navigation template cannot predict the vertebral rotation and the impact of body position changes,resulting in the poor fitting. OBJECTIVE:To explore the utility of a new 5-point positioning point-contact pedicle navigation template in the case of scoliosis and complex pedicle. METHODS:A total of 20 patients with scoliosis and complicated pedicle admitted to the Department of Spinal Surgery,Guizhou Hospital,Beijing Jishuitan Hospital from February 2020 to February 2023 were selected for scoliosis orthopedics.During the operation,the 5-point positioning point-contact pedicle navigation template was used to guide the screws.According to the inclusion and exclusion criteria,34 cases were matched as the empirical nail placement group,and conventional barehanded nail placement was performed.The time of placement,the amount of bleeding,the number of fluoroscopies,the number of manual diversions,the level and accuracy of pedicle screws,the complications of placement,and the rate of correction of main curvature were compared between the two groups. RESULTS AND CONCLUSION:(1)There were no significant differences in sex,age,coronal Cobb's angle of the main curvature,bending Cobb's angle of the main curvature,pedicle variation,apex rotation,fusion segment,number of screws,level of screws,accuracy of screws,and rate of correction of main curvature between the navigation template group and the empirical nail placement group(P>0.05).(2)Compared with the empirical nail placement group,the navigation template group had more advantages in time of placement(P=0.034),amount of bleeding(P=0.036),number of fluoroscopies(P=0.000)and number of manual diversions(P=0.021).(3)There were 0 cases of screw-related complications in both groups.(4)In conclusion,the 5-point positioning point-contact 3D printing pedicle navigation template has a claw-like structure.It can firmly adapt to various deformities of the lamina articular process,avoid drift,and accurately place the screws.It has a point-like contact lamina structure to avoid extensive and complete dissection of the posterior structure,and reduce bleeding,operation time,and trauma.Pre-designed screw entry points and directions can reduce the number of fluoroscopy and operation time.Segmental design can avoid discomfort due to changes in anesthesia position.The operation is simple and the accuracy of screw placement is high.
8.Comparison of clinical characteristics between first-episode and recurrent acute hypertrigly-ceridemic pancreatitis: a national multicenter clinical research
Shuai LI ; Jing ZHOU ; Guixian LUO ; Hongwei ZHANG ; Siyao LIU ; Weijie YAO ; Donghuang HONG ; Kaixiu QIN ; Lanting WANG ; Rong WEI ; Yizhen XU ; Longxiang CAO ; Zhihui TONG ; Yuxiu LIU ; Weiqin LI ; Lu KE
Chinese Journal of Digestive Surgery 2024;23(5):703-711
Objective:To investigate the clinical characteristics of first-episode and recurrent acute hypertriglyceridemic pancreatitis (HTGP).Methods:The retrospective cohort study was con-ducted. The clinical data of 313 patients with HTGP admitted to 26 medical centers in China in the Chinese Acute Pancreatitis Clinical Research Group (CAPCTG)-PERFORM database from November 2020 to December 2021 were collected. There were 219 males and 94 females, aged 38(32,44)years. Of the 313 patients, 193 patients with first-episode HTGP were allocated into the first-episode group and 120 patients with recurrent HTGP were allocated into the recurrent group. Observation indica-tors: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) comparison of severity and prognosis in the course of disease within 14 days between the two groups; (3) the association between recurrent HTGP and the risk of persistent organ failure (POF); (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Wilcoxon rank sum test. The Kaplan-Meier method was used to plot the cumulative recurrence rate curve and Log-Rank test was used for survival analysis. The Logistic regression model was used for multivariate analysis, and continuous variables were converted into categorical variables according to the mean value or common criteria. Propensity score matching was performed by 1∶1 nearest neighbor matching method, with caliper value of 0.02. Paired t test or Wilcoxon rank sum test and McNemar′s test were used for comparison between matched groups. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 313 patients,208 cases were successfully matched, including 104 cases in the first-episode group and 104 cases in the recurrent group. After propensity score matching, there was no significant difference in demographic characteristics, severity of illness scores and laboratory test between the two groups ( P>0.05). The elimination of gender, acute physiology and chornic health evaluation (APACHE) Ⅱ score, computed tomography severity index score, systemic inflammatory response syndrome score, sequential organ failure assessment score, apolipoprotein E, C-reactive protein, creatinine, lactic acid dehydrogenase, procal-citonin confounding bias ensured comparability between the two groups. (2) Comparison of severity and prognosis in the course of disease within 14 days between the two groups. There were signifi-cant differences in POF and local complications between the first-episode group and the recurrent group ( P<0.05). (3) The association between recurrent HTGP and the risk of POF. Results of uncor-rected univariate analysis showed that there was no association between recurrent HTGP and the risk of POF ( odds ratio=0.78, 95% confidence interval as 0.46-1.30, P>0.05). Results of multivariate analysis after adjusting for covariates such as gender, age, APACHE Ⅱ score, C-reactive protein, triglyceride and total cholesterol showed that compared with first-episode HTGP, recurrent HTGP was associated with a higher risk of POF ( odds ratio=2.22, 95% confidence interval as 1.05-4.71, P<0.05). Results of subgroup analysis showed that age<40 years was associated with an increased risk of POF ( odds ratio=3.31, 95% confidence interval as 1.09-10.08, P<0.05). (4) Follow-up. Twelve of the 313 patients died during hospitalization, including 9 cases in the first-episode group and 3 cases in the recurrent group. The rest of 301 surviving patients, including 184 cases in the first-episode group and 117 cases in the recurrent group, were followed up for 19.2(15.5, 21.9)months. Results of follow-up showed that for 184 survived patients of the first-episode group, 164 cases were followed up and 24 cases experienced recurrence, for 117 survived patients of the recurrent group,29 cases experienced recurrence, showing a significant difference between the two groups ( χ2=4.67, P<0.05). Conclusion:Compared with first-episode HTGP, patients with recurrent HTGP are more prone to POF and local complications, and are more prone to recurrence after discharge. The risk of POF in recurrent HTGP patients is 2.22 times that of those with first-episode, and the risk is higher in patients with age <40 years.
9.Analysis and summary of clinical characteristics of 289 patients with paroxysmal nocturnal hemoglobinuria in Zhejiang Province
Gaixiang XU ; Weimei JIN ; Baodong YE ; Songfu JIANG ; Chao HU ; Xin HUANG ; Bingshou XIE ; Huifang JIANG ; Lili CHEN ; Rongxin YAO ; Ying LU ; Linjie LI ; Jin ZHANG ; Guifang OUYANG ; Yongwei HONG ; Hongwei KONG ; Zhejun QIU ; Wenji LUO ; Binbin CHU ; Huiqi ZHANG ; Hui ZENG ; Xiujie ZHOU ; Pengfei SHI ; Ying XU ; Jie JIN ; Hongyan TONG
Chinese Journal of Hematology 2024;45(6):549-555
Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.
10.The role of β2 adrenergic receptor in fibrogenesis during wound healing via TGF-β1/Smad3 signaling pathway
Junhao ZENG ; Zucheng LUO ; Yao LU ; Wenjie LUAN ; Fazhi QI
Chinese Journal of Clinical Medicine 2024;31(2):169-176
Objective To explore the underlying mechanism of β2 adrenergic receptor(ADRB2)in fibrogenesis during wound healing.Methods Non-specific ADRB2 gene knockdown adeno-associated virus(AAV-ADRB2 group,6 mice)and control virus(AAV-NC group,6 mice)was injected randomly into the back skin of 12 mice for 21 days,a full-thickness skin defected wound healing murine model was established.Wound healing rates were recorded at the 1st,3rd,5th,and 7th day after operation.Histological examinations by H-E staining,Masson staining,and immunohistochemistry were conducted to observe wounded skin tissue structure,fibrosis,and α-SMA protein expression;quantitative PCR was employed to analyze ADRB2 and matrix metalloproteinase(MMP)mRNA levels;Western blotting was utilized to assess the protein expression levels of COL1A1,COL3A1,TGF-β1,and Smad3.Results On postoperative day 5 and 7,the wound healing rate of the AAV-ADRB2 group significantly decreased(P<0.05),accompanied by a series pathological changes,including thickened epidermis,exaggerated inflammation,reduced fibroblast count,and inhibited collagen deposition;the α-SMA expression showed a significant decrease(P<0.05),and the ratio of COL1A1 to COL3A1 decreased(P<0.05);ADRB2 mRNA levels significantly decreased(P<0.01),while MMP-1 and MMP-8 mRNA levels increased(P<0.01);the protein levels of TGF-β1 and Smad3 exhibited a significant decrease(P<0.05).Conclusions ADRB2 knockdown reduced fibrosis during wound healing and degenerated connective tissue content around the wound bed by inhibiting the TGF-β1/Smad3 signaling pathway,which leads to an increase in MMP mRNA levels and a decrease in the ratio of type Ⅰ to type Ⅲ collagen.

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