1.RUNX3 regulates FAP to influence the proliferation of mouse lung primary fibroblasts
Junbo YOU ; Xianchen WANG ; Hui LING ; Jiahao FAN ; Qi CHEN ; Hui TAO ; Jiming SHA
Acta Universitatis Medicinalis Anhui 2026;61(4):606-611
ObjectiveTo investigate the role of runt-related transcription factor 3 (RUNX3) in transforming growth factor-β1 (TGF-β1)-induced activation of mouse primary pulmonary fibroblasts (PFs), and its effects on fibroblast activation protein (FAP) expression, cell proliferation, and collagen synthesis. MethodsPFs were isolated from C57BL/6 mice and cultured. A RUNX3 knockdown model was established using small interfering RNA (siRNA). Cells were assigned to the control group (Control), TGF-β1-treated group (TGF-β1), negative control group (TGF-β1+siRNA-NC), and RUNX3-silenced group (TGF-β1+si-RUNX3). In addition, a RUNX3 overexpression rescue experiment was performed based on TGF-β1 stimulation. Protein and mRNA levels of RUNX3, FAP, and typeⅠcollagen (COL1A1) were measured by Western blot and reverse transcription quantitative real-time PCR (RT-qPCR). Cell proliferation was assessed using CCK-8 and EdU assays. Co-expression of COL1A1 and FAP was examined by double immunofluorescence staining. ResultsCompared with the Control group, RUNX3, FAP, and COL1A1 expression levels were upregulated in PFs in the TGF-β1 group (P<0.01). The CCK-8 assay showed that the absorbance value was reduced in the RUNX3 knockdown group compared with the negative control group (P<0.01). Consistently, the EdU assay demonstrated a lower proportion of EdU-positive cells in the RUNX3 knockdown group than in the negative control group (P<0.01). Immunofluorescence double staining revealed decreased fluorescence intensities of COL1A1 and FAP in the RUNX3 knockdown group relative to the negative control. Under RUNX3 overexpression conditions, these fluorescence signals exhibited a partial rebound (P<0.01). ConclusionRUNX3 in TGF-β1-induced PFs may promote cell proliferation and collagen synthesis by positively regulating FAP expression. Targeting the RUNX3/FAP axis may represent a potential therapeutic strategy for pulmonary fibrosis.
2.Effect of targeted silencing of DNMT3A on collagen deposition, proliferation and migration activity of mouse lung fibroblasts
Xianchen Wang ; Junbo You ; Hui Ling ; Jiahao Fan ; Qi Chen ; Hui Tao ; Jiming Sha
Acta Universitatis Medicinalis Anhui 2025;60(1):66-72
Objective:
To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs).
Methods:
In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test.
Results:
Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group.
Conclusion
Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.
3.Application of cross bar technique in repair of pectus excavatum
Tianjun ZHOU ; Dan TIAN ; Ruiqing SHI ; Zihao ZHOU ; Jiming TANG ; Dongkun ZHANG ; Xiaosong BEN ; Guibin QIAO ; Gang CHEN ; Liang XIE
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1572-1578
Objective To explore the indication, surgical technique, and clinical efficacy of the cross bar based on the Nuss procedure in pectus excavatum. Methods The clinical data of patients who underwent cross bar based on the Nuss procedure from August 2023 to August 2024 in Guangdong Provincial People's Hospital were retrospectively analyzed. Results A total of 88 patients including 85 males and 3 females with a mean age of (17.56±5.20) years were enrolled. All operations were performed successfully without intraoperative cardiac injury, pericardial injury or diaphragmatic injury. The mean operation time was (147.65±47.75) min. The mean blood loss was (13.30±9.06) mL. The mean postoperative hospitalization stay was (4.81±1.55) days, without perioperative death. Six (6.82%) patients developed early postoperative complications, including 3 patients of pleural effusion, 1 patient of subcutaneous hematoma, 1 patient of suffocation and 1 patient of bar rotation. The postoperative outcomes were excellent in 71 (80.68%) patients, good in 16 (18.18%) patients and moderate in 1 (1.13%) patient. The excellent and good rate was 98.86%. Conclusion The cross bar technique is safe and convenient, with satisfactory results. It is worth promoting in clinical application.
4.Effect of WTAP on collagen deposition in bleomycin-induced pulmonary fibrosis
Yunsen Yunsen ; Zhenyu Liu ; Zhiyan Liu ; Lichan Lin ; Jiming Sha ; Hui Tao ; Qi Chen
Acta Universitatis Medicinalis Anhui 2025;60(2):266-271
Objective :
To explore the effect of Wilms′ tumor 1-associated protein(WTAP) on tissue collagen deposition in pulmonary fibrosis caused by bleomycin.
Methods :
60 mice were randomly divided into four groups: control group(Control group), Bleomycin-induced pulmonary fibrosis group(BLM group), pulmonary fibrosis lentivirus empty vector control group(BLM+LV-NC group), pulmonary fibrosis WTAP lentivirus group virus group(BLM+LV-WTAP group). Experimental pulmonary fibrosis mouse model was established by subcutaneous injection of bleomycin(35 mg/kg) into the abdomen, twice a week for a total of 8 times. After modeling, Western Blot was used to detect the protein expression of fibrosis-related markers α-smooth muscle actin(α-SMA), type I collagen(Collagen Ⅰ), fibronectin(Fibronectin), and WTAP protein. Masson staining and Sirius Red staining were used to detect collagen deposition. RT-qPCR was used to detect WTAP mRNA expression, WTAP lentivirus infection effect, and Collagen Ⅰ mRNA expression.
Results:
Compared with the Control group, the expression of pulmonary fibrosis markers α-SMA(P<0.001), Collagen Ⅰ(P<0.001), and Fibronectin(P<0.01) protein in the BLM group all increased. Masson staining(P<0.001) and Sirius Red staining(P<0.001) confirmed that significant collagen deposition occurred in the lung tissue of the BLM group. In addition, the expression of WTAP protein in the lung tissue of the BLM group increased(P<0.01). Compared with the Control group, the expression of WTAP mRNA in the BLM group increased(P<0.001). Compared with the BLM+LV-NC group, the expression of WTAP mRNA in the tissues of the BLM+LV-WTAP group decreased(P<0.001), proving that virus infection is effective. After infection with WTAP lentivirus, collagen fiber deposition decreased(P<0.001), Collagen Ⅰ mRNA(P<0.001) level decreased, and protein(P<0.001) expression decreased in the BLM+LV-WTAP group.
Conclusion
Knocking down of WTAP can reduce collagen deposition in bleomycin-induced pulmonary fibrosis tissue in mice and improve experimental pulmonary fibrosis.
5.Subchondral bone intravoxel incoherent motion diffusion weighted imaging for quantitatively evaluating knee joint cartilage degeneration
Kai GAO ; Jiming CHEN ; Xianfei WEI ; Yongkang SONG ; Jian ZHAI
Chinese Journal of Medical Imaging Technology 2025;41(7):1129-1133
Objective To observe the value of subchondral bone(SB)intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)for quantitatively evaluating knee joint cartilage degeneration.Methods Totally 125 patients with knee cartilage degeneration were prospectively enrolled and divided into mild group(n=65,Outerbridge grades Ⅰ-Ⅱ)and moderate-severe group(n=60,Outerbridge grades Ⅲ-Ⅳ)based on arthroscopic findings.Additionally,30 healthy young subjects were recruited as control group.The apparent diffusion coefficient(ADC),true diffusion coefficient(D),pseudo diffusion coefficient(D*)and perfusion fraction(f)values of medial condyle of SB of femur,lateral condyle of femur,medial tibial plateau and lateral tibial plateau,as well as the mean values of each parameter of the above 4 regions were obtained based on knee joint IVIM-DWI and compared within and among groups.Spearman correlation analysis was used to observe the correlations between quantitative parameters and Outerbridge grading.The area under the receiver operating characteristic curve(AUC)was calculated to evaluate the efficacy of each quantitative parameter alone and their combination for assessing knee cartilage degeneration.Results Significant differences of D*values were found among different parts of knee joint SB in moderate-severe group,also of D value,D* value and f value among different parts of knee joint SB in mild group(all P<0.05).Significant differences of IVIM-DWI parameter were found among different parts of knee joint SB in control group(all P<0.05).ADC value of knee joint SB in moderate-severe group,mild group and control group decreased successively,while D value increased successively(all P<0.001).D* values of knee joint SB in moderate-severe group was higher than that in mild group and control group(both P<0.05).No significant difference of f value of knee joint SB was found between moderate-severe group and mild group(P>0.05),while both the latter two were higher than that in control group(both P<0.05).ADC value,D value and f value of knee joint SB were positively correlated(rs=0.671,0.634,0.416,all P<0.01),while D* value of knee joint SB was negatively correlated with Outerbridge grading(rs=-0.729,P<0.01).AUC of combination of parameters for distinguishing mild group from control group,and mild group from moderate-severe group was 0.859 and 0.808,respectively.Conclusion SB IVIM-DWI could be used for quantitatively evaluation of knee cartilage degeneration.
6.Diagnosis and treatment analysis of Scimitar syndrome in 21 children
Jiming CAI ; Yujie LIU ; Bin CHEN ; Zhuoming XU ; Haibo ZHANG ; Zhihao LI ; Kai LUO
Chinese Pediatric Emergency Medicine 2025;32(3):212-216
Objective:To investigate the diagnosis,therapeutic strategy and early prognosis of Scimitar syndrome in pediatric patients.Methods:Clinical data of 21 children with Scimitar syndrome admitted to the Department of Cardiothoracic Surgery of Shanghai Children's Medical Center from January 2014 to December 2021 were retrospectively analyzed,and divided into 11 cases in the infantile-type group and 10 cases in the adult-type group.Results:Twenty-one children with Scimitar syndrome,10 males and 11 females,aged 5 days to 10 years old. Compared with the adult-type group,the infant-type group had a high proportion of preoperative clinical symptoms( P<0.05),a high concomitant rate of intracardiac malformations (100% vs. 40%, P=0.002),a big size of aortopulmonary collateral(APC)[(0.77±0.25) mm/kg vs.(0.36±0.13) mm/kg, P=0.016],a high incidence of pulmonary hypertension(91.0% vs. 50.0%, P=0.038), and a high proportion of severe pulmonary hypertension(50 % vs. 0). There was a high rate of postoperative complications of low cardiac output syndrome (36.4% vs. 0, P=0.034),prolonged postoperative mechanical ventilation [(73.22±44.75) h vs. (19.5±12.79) h, P=0.007],and prolonged length of ICU stay[(7.89±3.37) d vs. (2.50±1.26) d, P<0.001]. Eleven cases underwent surgical treatment only,and 10 cases received hybrid operation with APC occlusion. The survival rate of the whole group was 90.5%,and there was no case of pulmonary venous obstruction in the early postoperative period. Systolic pulmonary artery pressure/systolic artery pressure decreased significantly after surgery in 15 children with pulmonary arterial hypertension( P<0.01).Five cases in the infantile-type group still had pulmonary hypertension. Conclusion:Surgical effect of Scimitar syndrome in pediatric patients is satisfactory. Infants with Scimitar syndrome usually have more severe symptoms, higher incidence of severe pulmonary hypertension and relatively longer postoperative recovery time.
7.Diagnosis and treatment analysis of Scimitar syndrome in 21 children
Jiming CAI ; Yujie LIU ; Bin CHEN ; Zhuoming XU ; Haibo ZHANG ; Zhihao LI ; Kai LUO
Chinese Pediatric Emergency Medicine 2025;32(3):212-216
Objective:To investigate the diagnosis,therapeutic strategy and early prognosis of Scimitar syndrome in pediatric patients.Methods:Clinical data of 21 children with Scimitar syndrome admitted to the Department of Cardiothoracic Surgery of Shanghai Children's Medical Center from January 2014 to December 2021 were retrospectively analyzed,and divided into 11 cases in the infantile-type group and 10 cases in the adult-type group.Results:Twenty-one children with Scimitar syndrome,10 males and 11 females,aged 5 days to 10 years old. Compared with the adult-type group,the infant-type group had a high proportion of preoperative clinical symptoms( P<0.05),a high concomitant rate of intracardiac malformations (100% vs. 40%, P=0.002),a big size of aortopulmonary collateral(APC)[(0.77±0.25) mm/kg vs.(0.36±0.13) mm/kg, P=0.016],a high incidence of pulmonary hypertension(91.0% vs. 50.0%, P=0.038), and a high proportion of severe pulmonary hypertension(50 % vs. 0). There was a high rate of postoperative complications of low cardiac output syndrome (36.4% vs. 0, P=0.034),prolonged postoperative mechanical ventilation [(73.22±44.75) h vs. (19.5±12.79) h, P=0.007],and prolonged length of ICU stay[(7.89±3.37) d vs. (2.50±1.26) d, P<0.001]. Eleven cases underwent surgical treatment only,and 10 cases received hybrid operation with APC occlusion. The survival rate of the whole group was 90.5%,and there was no case of pulmonary venous obstruction in the early postoperative period. Systolic pulmonary artery pressure/systolic artery pressure decreased significantly after surgery in 15 children with pulmonary arterial hypertension( P<0.01).Five cases in the infantile-type group still had pulmonary hypertension. Conclusion:Surgical effect of Scimitar syndrome in pediatric patients is satisfactory. Infants with Scimitar syndrome usually have more severe symptoms, higher incidence of severe pulmonary hypertension and relatively longer postoperative recovery time.
8.Subchondral bone intravoxel incoherent motion diffusion weighted imaging for quantitatively evaluating knee joint cartilage degeneration
Kai GAO ; Jiming CHEN ; Xianfei WEI ; Yongkang SONG ; Jian ZHAI
Chinese Journal of Medical Imaging Technology 2025;41(7):1129-1133
Objective To observe the value of subchondral bone(SB)intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI)for quantitatively evaluating knee joint cartilage degeneration.Methods Totally 125 patients with knee cartilage degeneration were prospectively enrolled and divided into mild group(n=65,Outerbridge grades Ⅰ-Ⅱ)and moderate-severe group(n=60,Outerbridge grades Ⅲ-Ⅳ)based on arthroscopic findings.Additionally,30 healthy young subjects were recruited as control group.The apparent diffusion coefficient(ADC),true diffusion coefficient(D),pseudo diffusion coefficient(D*)and perfusion fraction(f)values of medial condyle of SB of femur,lateral condyle of femur,medial tibial plateau and lateral tibial plateau,as well as the mean values of each parameter of the above 4 regions were obtained based on knee joint IVIM-DWI and compared within and among groups.Spearman correlation analysis was used to observe the correlations between quantitative parameters and Outerbridge grading.The area under the receiver operating characteristic curve(AUC)was calculated to evaluate the efficacy of each quantitative parameter alone and their combination for assessing knee cartilage degeneration.Results Significant differences of D*values were found among different parts of knee joint SB in moderate-severe group,also of D value,D* value and f value among different parts of knee joint SB in mild group(all P<0.05).Significant differences of IVIM-DWI parameter were found among different parts of knee joint SB in control group(all P<0.05).ADC value of knee joint SB in moderate-severe group,mild group and control group decreased successively,while D value increased successively(all P<0.001).D* values of knee joint SB in moderate-severe group was higher than that in mild group and control group(both P<0.05).No significant difference of f value of knee joint SB was found between moderate-severe group and mild group(P>0.05),while both the latter two were higher than that in control group(both P<0.05).ADC value,D value and f value of knee joint SB were positively correlated(rs=0.671,0.634,0.416,all P<0.01),while D* value of knee joint SB was negatively correlated with Outerbridge grading(rs=-0.729,P<0.01).AUC of combination of parameters for distinguishing mild group from control group,and mild group from moderate-severe group was 0.859 and 0.808,respectively.Conclusion SB IVIM-DWI could be used for quantitatively evaluation of knee cartilage degeneration.
9.The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"
Wanjie YANG ; Xianduo LIU ; Ximo WANG ; Weiguo XU ; Lei ZHANG ; Qiang FU ; Jiming YANG ; Jing QIAN ; Fuyu ZHANG ; Li TIAN ; Wenlong ZHANG ; Yu ZHANG ; Zheng CHEN ; Shifeng SHAO ; Xiang WANG ; Li GENG ; Yi REN ; Ying WANG ; Lixia SHI ; Zhen WAN ; Yi XIE ; Yuanyuan LIU ; Weili YU ; Jing HAN ; Li LIU ; Huan ZHU ; Zijiang YU ; Hongyang LIU ; Shimei WANG
Chinese Critical Care Medicine 2024;36(2):195-201
The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.
10.Efficacy, safety, and pharmacokinetics of capsid assembly modulator linvencorvir plus standard of care in chronic hepatitis B patients
Jinlin HOU ; Edward GANE ; Rozalina BALABANSKA ; Wenhong ZHANG ; Jiming ZHANG ; Tien Huey LIM ; Qing XIE ; Chau-Ting YEH ; Sheng-Shun YANG ; Xieer LIANG ; Piyawat KOMOLMIT ; Apinya LEERAPUN ; Zenghui XUE ; Ethan CHEN ; Yuchen ZHANG ; Qiaoqiao XIE ; Ting-Tsung CHANG ; Tsung-Hui HU ; Seng Gee LIM ; Wan-Long CHUANG ; Barbara LEGGETT ; Qingyan BO ; Xue ZHOU ; Miriam TRIYATNI ; Wen ZHANG ; Man-Fung YUEN
Clinical and Molecular Hepatology 2024;30(2):191-205
Background/Aims:
Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients.
Methods:
This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks.
Results:
68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported.
Conclusions
48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.


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