1.Effects of M2-type macrophages and GKT137831 on oxidative stress in hepatic stellate cells
Ruge SUN ; Jing LI ; Fengjun SHEN
Chinese Journal of Hepatology 2024;32(3):201-207
Objective:To investigate the effects of reduced nicotinamide adenine dinucleotide phosphooxidase 4 (NOX4) inhibitors GKT137831 and M2-type macrophages on oxidative stress markers NOX4, nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the rat hepatic stellate cell line (HSC-T6).Methods:Rat bone marrow macrophages were extracted and induced using interleukin (IL)-4 to differentiate them into M2 phenotype macrophages. HSC-T6 activation was performed with 5 μg/L transforming growth factor β1 (TGF-β1). The proliferation condition of HSC-T6 cells stimulated by the NOX4 inhibitor GKT137831 at a concentration gradient of 5 to 80 μmol/L after 48 hours was detected using the Cell Counting Kit-8 (CCK-8) assay. The optimal drug concentration was chosen and divided into an HSC co-culture group (the control group) and five experimental groups: the TGF-β1 stimulation group, the TGF-β1 +GKT137831 stimulation group, the M2-type macrophage + HSC co-culture group, the M2-type macrophage +TGF-β1 stimulation group, and the M2-type + TGF-β1 + GKT137831 stimulation group. Reactive oxygen species (ROS) production level was detected in each cell using the DCFH-DA probe method. NOX4, α-smooth muscle actin (α-SMA), Nrf2, and HO-1 levels in each group of HSC cells were detected using the qRT-PCR method and the Western blot method. The t-test was used to compare the two groups. The one-way ANOVA method was used to compare multiple groups. Results:Intracellular ROS increased significantly following TGF-β1 stimulation. ROS relative levels in each cell group were 1.03±0.11, 3.88±0.07, 2.90±0.08, 0.99±0.06, 3.30±0.05, 2.21±0.11, F ?=?686.1, P ?=?0.001, respectively. The mRNA and protein expressions of NOX4, α-SMA, Nrf2, and HO-1 were significantly increased ( P ?0.05). After the addition of GKT137831, ROS, and NOX4, α-SMA mRNA and protein expression were comparatively decreased in the TGF-β1 stimulation group ( P ?0.05), while mRNA and protein expressions of Nrf2 and HO-1 were increased ( P ?0.05). The expression of ROS and NOX4, as well as α-SMA mRNA and protein, produced by HSC were significantly decreased in the co-culture group compared to the single culture group after TGF-β1 stimulation ( P ?0.05). After the addition of GKT137831, ROS, NOX4, α-SMA mRNA, and protein expression were further reduced in the co-culture group compared with the single culture group ( P ?0.05), while the mRNA and protein expression of Nrf2 and HO-1 were further increased ( P ?0.05). Conclusion:NOX4 inhibitor GKT137831 can reduce RO, NOX4, and α-SMA levels while increasing Nrf2 and HO-1 levels in hepatic stellate cells. After M2-type macrophage co-culture, GKT137831 assists in lowering ROS, NOX4, and α-SMA levels while accelerating Nrf2 and HO-1 levels in hepatic stellate cells, which regulates the balance between oxidative stress and anti-oxidative stress systems, thereby antagonizing the fibrosis process.
2.Clinical effect of the giant deep inferior epigastric artery paraumbilical perforator flap in repairing the circular high-voltage electric burn wounds on the wrist
Weili DU ; Yuming SHEN ; Xiaohua HU ; Fengjun QIN ; Lin CHENG
Chinese Journal of Burns 2023;39(6):527-533
Objective:To investigate the clinical effect of the giant deep inferior epigastric artery paraumbilical perforator flap in repairing the circular high-voltage electric burn wounds on the wrist.Methods:A retrospective observational study method was used. From September 2016 to October 2021, thirteen male patients (aged 20-43 years) with annular high voltage (10-100 kV) electrical burns on the wrist were admitted to the Beijing Jishuitan Hospital. At the early stage after injury, the patient's wrist was subjected to incision, tension reduction and debridement, with the wound area after debridement being 27 cm×16 cm-32 cm×19 cm; in 12 patients with vascular injury, the radial or ulnar artery was reconstructed by great saphenous vein transplantation, with the length of 15-25 cm; the wrist wound was repaired by free transplantation of the deep inferior epigastric artery paraumbilical perforator flap (if the wound was giant, the lower abdominal flap carrying other perforators was used), with the area of 30 cm×19 cm-35 cm×20 cm. The donor site was repaired by direct suture+skin grafting or relay flap transplantation. After surgery, the survival of flap in recipient area, as well as survival of the skin or flap in donor site were observed. During follow-up, the appearances of the flap in recipient area and the recovery of hand function, as well as the healing of donor site, occurrence of abdominal wall hernia, and scar in skin graft area were observed.Results:After surgery, all the 13 patients' paraumbilical perforator flaps survived. Among them, 3 patients had subcutaneous fat necrosis at the distal end of the wrist flap, and the wound had mild infection, which healed after re-expansion and dressing change. All the skin grafts in the donor site of 10 patients survived, and the flaps in the donor site of 3 patients survived well. The patients were followed up for 6 months to 3 years. The flaps in recipient area were in good shape, 8 cases had partial recovery of hand function, and 5 cases had loss of finger flexion function; the donor site of abdominal flap healed well with no abdominal hernia occurred, and the skin graft site had no obvious scar hyperplasia and was soft in texture.Conclusions:Early vascular reconstruction after injury, together with free transplantation of the giant deep inferior epigastric artery paraumbilical perforator flap are effective in repairing circular high-voltage electrical burn wounds on the wrist.
3.Application strategy and clinical effects of paraumbilical perforator flap with inferior epigastric vessels in repairing destructive wounds
Fengjun QIN ; Yuming SHEN ; Weili DU ; Lin CHENG ; Ying ZHANG ; Chunxu MA
Chinese Journal of Burns 2021;37(7):606-613
Objective:To explore the application strategy and clinical effects of paraumbilical perforator flap with inferior epigastric vessels in repairing various destructive wounds.Methods:The retrospective observational study method was applied. From January 2015 to December 2020, 28 patients (21 males and 7 females, aged 25 to 66 years) with destructive wounds in various body parts were admitted to Beijing Jishuitan Hospital. The wound areas of patients ranged from 17 cm×8 cm to 35 cm×22 cm after debridement. Pedicled or free paraumbilical perforator flaps with inferior epigastric vessels were used to repair the wounds respectively. The areas of flaps were from 18 cm×10 cm to 37 cm×24 cm, and the lengths of vascular pedicles were 13.0-17.0 (15.1±2.3) cm. For type Ⅲ high-voltage electric burn wounds of wrist, two methods were used to reconstruct the blood flow of hand, one is to bridge the radial artery with saphenous vein grafting and the other one is to design blood flow-through flap. The strength of abdominal wall in the donor site was strengthened by polypropylene patch, and then the wounds were directly sutured. If the wounds could not be sutured directly, then allogenic acellular dermal matrix (ADM) was applied to strengthen the abdominal wall first, and then autologous medium-thickness skin graft was taken from the thigh to cover the wounds. The flap transplantation, hand blood flow reconstruction, the repair of donor site, the flap survival, the wound and donor site healing after operation, the appearance of flaps, and the wound and donor site recovery during follow-up were observed.Results:Among the patients in this group, 13 patients were treated with pedicled flap grafting, while 15 patients were treated with free flap grafting. The hand blood flow of 7 patients with type Ⅲ high-voltage electric burn wounds of wrist was reconstructed by bridging radial artery with saphenous vein grafting. The hand blood flow of 3 patients with type Ⅲ high-voltage electric burn wounds of wrist was reconstructed with blood flow-through flap. In 16 patients, the strength of abdominal wall was strengthened using patch in the donor site,and then the donor sites were sutured directly. In 12 patients, the strength of abdominal wall was strengthened using allogenic ADM, and then the donor sites were covered by skin grafting. All the transplanted flaps survived completely. The wounds of 24 patients were healed, while the wounds of 3 patients with type Ⅲ high-voltage electric burn wounds of wrist and 1 patient with chronic radiation ulcer of ilium failed to heal because of there were still some necrotic tissue and purulent secretion under the flaps. The wounds were healed eventually after debridement and dressing changes. During the follow-up of 6 months to 3 years, the flap survived well with good appearance in all patients, and there was no recurrence, or no abdominal wall hernia occurred in the donor site.Conclusions:Paraumbilical perforator flap with inferior epigastric vessels has flexible design, long vascular pedicle, large area for cut. It can be pedicled or freely transplanted, which is a good choice for repairing destructive wounds in various areas.
4. Exploration on the method of aesthetic repair of the donor sites of flaps
Weili DU ; Yuming SHEN ; Xiaohua HU ; Fengjun QIN ; Kai YIN
Chinese Journal of Burns 2020;36(2):97-105
Objective:
To explore the excellent methods for aesthetic repair of the donor sites of flaps.
Methods:
From January 2013 to March 2018, 120 patients (94 males and 26 females, aged from 3 to 60 years) were admitted to the Department of Burns of Beijing Jishuitan Hospital. Wounds areas after debridement or removing scar were ranged from 8.0 cm×3.5 cm to 24.0 cm×18.0 cm. Twenty patients with facial and neck scar were repaired with expanded flaps, including 4 scalp flaps, 8 supraclavicular flaps, 4 deltoid flaps, and 4 trapezius myocutaneous flaps. The flaps in ideal donor sites were selected to repair the wounds in 40 patients, including 20 cases of hand wounds or scars repaired with inguinal flaps, 10 children of foot skin defects or scars repaired with cross inguinal skin flap, 10 cases of knee joint wounds repaired with medial or lateral thigh flaps. The optimal flap design was used to repair wounds in 50 patients. Among the patients, wounds of 36 patients were repaired with relaying flaps, including donor sites of free anterolateral thigh flaps of 8 patients repaired with anteromedial thigh perforator flaps and donor sites of free anterolateral thigh flaps of 8 patients repaired with ilioinguinal flaps or superficial abdominal artery flaps, and donor sites of flaps of 20 patients repaired with peroneal perforator relaying flaps. Besides, wounds of 9 patients were repaired with free lobulated anterolateral thigh flaps, and wounds of 5 patients were repaired with modified V-Y propelling latissimus dorsi myocutaneous flaps. The donor sites of flaps were repaired with allogenic acellular dermal matrix combined with autologous split-thickness skin grafts in 10 cases. The areas of the flaps or myocutaneous flaps were ranged from 6.0 cm×4.0 cm to 30.0 cm×20.0 cm. The survival of flap, myocutaneous flap, or skin graft and the repair of donor site after operation and during follow-up were observed.
Results:
Blood flow obstacle at 0.5 cm to the distal margin of the flap occurred in 1 patient repaired with expanded flap, which were healed after dressing change. Blood supply disorder occurred at the tip of the anteromedial thigh perforator flap of 1 patient repaired by optimal flap design, which were healed completely after second debridement and restitching. The other flaps or myocutaneous flaps survived well. The allogenic acellular dermal matrix and the autologous split-thickness skin graft survived with good color and texture. During follow-up of 3 months to 4 years, the donor sites of flaps had good appearance, only with linear scar and the function recovered well. The donor sites of skin grafts had no scar hyperplasia, only with scattered pigmentation.
Conclusions
According to the characteristics of donor sites of flaps, individualized and reasonable design before the operation such as pre-expanding of the flaps, selecting the ideal donor sites, optimization of the flap design or allogenic acellular dermal matrix combined with autologous split-thickness skin graft to repair donor sites of flaps can minimize the damage for function and appearance of donor sites of flaps and achieve aesthetic effects of donor sites of flaps.
5.Association between nuclear factor-erythroid 2-related factor-2 antioxidant pathway and liver diseases
Journal of Clinical Hepatology 2019;35(4):930-933
Nuclear factor-erythroid 2-related factor-2 (Nrf2) is an important transcription factor for cells to resist oxidative stress. It interacts with antioxidant response elements to induce the expression of downstream protective phase II detoxification enzymes and antioxidant enzymes and thus exerts a protective effect on cells. Oxidative stress is the common pathogenesis of many liver diseases, and the Nrf2-ARE antioxidant pathway is an important anti-oxidative stress pathway in vivo. It can induce the expression of downstream target genes and thus plays an important role in the development, progression, and prevention of liver diseases. This article briefly describes the mechanism of action of the Nrf2 antioxidant pathway in the development and progression of liver diseases and points out that Nrf2 may be a potential target for the prevention or treatment of liver diseases.
6. Limb salvage strategies for patients with high voltage electric burns of extremities on the verge of amputation
Yuming SHEN ; Fengjun QIN ; Weili DU ; Cheng WANG ; Cong ZHANG ; Hui CHEN ; Chunxu MA ; Xiaohua HU
Chinese Journal of Burns 2019;35(11):776-783
Objective:
To explore the limb salvage strategies for patients with high voltage electric burns of extremities on the verge of amputation.
Methods:
From January 2003 to March 2019, 61 patients with high voltage electric burns of extremities on the verge of amputation were treated in our hospital. All of them were male, aged 15-58 years, including 49 cases of upper limbs and 12 cases of lower limbs. The wound area after thorough debridement ranged from 15 cm×11 cm to 35 cm×20 cm. Emergency surgery for reconstruction of the radial artery with saphenous vein graft under eschar was performed in 5 cases. The arteries of 36 patients (including 7 cases with simultaneous ulnar artery and radial artery reconstruction) were reconstructed with various forms of blood flow-through after debridement, among them, the radial artery of 13 cases, the ulnar artery of 8 cases, the brachial artery of 8 cases, and the femoral artery of 2 cases were reconstructed with saphenous vein graft; the radial artery of 3 cases and the ulnar artery of 7 cases were reconstructed with the descending branch of the lateral circumflex femoral artery graft; the radial artery of 2 cases were reconstructed with greater omentum vascular graft; the reflux vein of 3 cases with wrist and forearm annular electric burns were reconstructed with saphenous vein graft. According to the actual situation of the patients, 12 cases of latissimus dorsi myocutaneous flap, 6 cases of paraumbilical flap, 28 cases of anterolateral thigh flap, 10 cases of abdominal combined axial flap, 5 cases of greater omentum combined with flap and/or skin grafts were used to repair the wounds after debridement and cover the main wounds as much as possible. Some cases were filled with muscle flap in deep defect at the same time. The area of tissue flaps ranged from 10 cm×10 cm to 38 cm×22 cm. For particularly large wounds and annular wounds, the latissimus dorsi myocutaneous flap, the paraumbilical flap, the abdominal combined axial flap, and the greater omentum combined with flap and/or skin grafts were used more often. Donor sites of three patients were closed directly, and those of 58 patients were repaired with thin and medium split-thickness skin or mesh skin grafts. The outcome of limb salvage, flap survival, and follow-up of patients in this group were recorded.
Results:
All the transplanted tissue flaps survived in 61 patients. Fifty-six patients had successful limb salvage, among them, 31 limbs were healed after primary surgery; 20 limbs with flap infection and tissue necrosis survived after debridement and flap sutured in situ; 5 limbs with flap infection, radial artery thrombosis, and hand blood supply crisis survived after debridement and radial artery reconstruction with saphenous vein graft. Five patients had limb salvage failure, among them, 3 patients with wrist electric burns had embolism on the distal end of the transplanted blood vessels, without condition of re-anastomosis, and the hands gradually necrotized; although the upper limb of one patient was salvaged at first, due to the extensive necrosis and infection at the distal radius and ulna and the existence of hand blood supply under flap, considering prognostic function and economic benefits, amputation was required by the patient; although the foot of one patient was salvaged at first, due to the repeated infection, sinus formation, extensive bone necrosis of foot under flap, dullness of sole and dysfunction in walking for a long time, amputation was required by the patient. During the follow-up of 6 months to 5 years, 56 patients had adequate blood supply in the salvaged limbs, satisfied appearance of flaps, and certain recovery of limb function.
Conclusions
Timely revascularization, early thorough debridement, and transplantation of large free tissue flap, combined tissue flap, or blood flow-through flap with rich blood supply are the basic factors to get better limb preservation and recovery of certain functions for patients with high voltage electric burns of limbs on the verge of amputation.
7. Effects of perforator flaps in the reconstruction of hypertrophic scar contracture deformities in the large joints of extremities of patients after severe burns
Xiaohua HU ; Fengjun QIN ; Juan LI ; Chunxu MA ; Yuming SHEN
Chinese Journal of Burns 2019;35(6):417-422
Objective:
To explore the clinical effects of perforator flaps in the reconstruction of hypertrophic scar contracture deformities in the large joints of extremities after severe burns.
Methods:
From January 2008 to January 2018, 72 patients (53 males and 19 females, aged 5 to 63 years) with hypertrophic scar contracture deformities and functional disorder in the large joints of extremities after severe burns were admitted to the Department of Burns of Beijing Jishuitan Hospital. Scar hyperplasia and contracture deformity were located at shoulder joints of 28 patients, elbow joints of 15 patients, hip joints of 7 patients, knee joints of 17 patients, and ankle joints of 5 patients. The wound area of patients after the scars were excised and released ranged from 7 cm×6 cm to 34 cm×12 cm. The wounds were repaired with corresponding unexpanded perforator flaps or expanded perforator flaps according to the joint location and existing soft tissue conditions. The size of flaps ranged from 7 cm×6 cm to 35 cm×14 cm. The donor sites of 51 patients were sutured directly; the donor sites of 21 patients were repaired by segmented grafts or mesh grafts. The adopted surgeries, the survival of flaps after surgery, and the functional recovery of the joints during follow-up were recorded.
Results:
Among the 72 patients, 53 patients had perforator flap repairing surgery only; 19 patients had perforator flap repairing surgery and skin grafting. Among them, 12 patients had expanded perforator flaps, 60 patients had unexpanded perforator flaps. The perforator flaps were performed free transplantation in 9 patients, pedicled transplantation in 61 patients, and groin transplantation in 2 patients. At last, 67 flaps survived completely, while 5 flaps had distal-end necrosis which were healed after dressing change or skin grafting after debridement. During follow-up of 6 months to 3 years, the joint function of all the patients was obviously improved. The abduction angles of shoulder joints were over 110°; the hip, knee, and elbow joints could reach the straight position, and the flexion was normal; the foot drop deformity was corrected, and the appearance of flaps was good with obvious extension compared with the original state.
Conclusions
Perforator flaps are suitable for reconstruction of hypertrophic scar contracture deformities in the large joints of extremities of patients after severe burns. They can restore the joint function to the greatest extent as well as repair the wounds.
8. Efficacy and safety of endoscopic and laparoscopic treatment for gastric stromal tumor: a meta-analysis
Fumei YIN ; Fengjun SHEN ; Jiang RUAN
Chinese Journal of Digestive Endoscopy 2019;36(10):755-760
Objective:
To systematically evaluate the efficacy and safety of endoscopic resection and laparoscopic surgery for gastrointestinal stromal tumors(GIST) (diameter<3.5 cm).
Methods:
According to the Cocharane system search strategy, Chinese and English literature comparing endoscopic with laparoscopic treatment of GIST published from January 2000 to March 2018 were collected. Ten articles meeting the inclusion criteria were included and analyzed with Revman 5.3.
Results:
Of the 10 articles, 1 was a prospective randomized controlled trial and 9 were retrospective non-randomized controlled trials. The total number of patients was 1 062. There were 732 cases in the endoscopic treatment group, and 330 cases in the laparoscopic surgery group. The meta-analysis results showed that the endoscopic treatment group had shorter operation time (
9. Effect of benazepril on nuclear factor E2 related factor 2, nicotinamide adenine dinucleotide phosphate oxidase and reactive oxygen species in rats with hepatic fibrosis
Yingying XU ; Fengjun SHEN ; Longlong WU
Chinese Journal of Hepatology 2019;27(9):677-680
Objective:
To study the effect of benazepril on the expression of nuclear factor E2 related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and reactive oxygen species (ROS) concentration in rats with hepatic fibrosis and to explore the possible antifibrotic mechanism of benazepril.
Methods:
Twenty-two healthy male Sprague-Dawley rats were randomly divided into 3 groups: control group (6 rats), model group (8 rats) and benazepril treatment group (8 rats). Two rats died during modeling and treatment in the model group and the benazepril treatment group, and a model of hepatic fibrosis induced by carbon tetrachloride (CCL4) was established. The rats in benazepril group were given benazepril for 8 weeks by gastric gavage. The assessment of liver tissue damage in each group was measured using conventional hematoxylin-eosin and Masson staining. The mRNA level of Nrf2, NOX4 in liver tissue was detected by RT-PCR, and serum ROS concentration was determined by colorimetry. All data were expressed in mean ± standard deviations, and were analyzed using SPSS21.0 statistical software. The data were compared using one-way analysis of variance, and the LSD-t method was used for pairwise comparison between the two groups. The correlation analysis was performed by Spearman’s correlation analysis.
Results:
In the liver of the model group, with the aggravation of liver fibrosis the expression of Nrf2mRNA, NOX4 mRNA and ROS concentration were higher than control group [(4.01 ± 3.40), (31.78 ± 3.96), (1.82 ± 0.46) μg/ ml vs. (0.12 ± 0.11), (2.03 ± 0.31), (1.56±0.84) μg/ml,
10. Effect of valsartan on the expression of leptin, leptin receptor and collagen in rats with hepatic fibrosis
Huifang HUANG ; Xinmei HUO ; Lijuan HUO ; Fengjun SHEN ; Longlong WU
Chinese Journal of Hepatology 2018;26(2):119-124
Objective:
To investigate the effects of angiotensin II type 1 receptor antagonist valsartan on leptin, leptin receptor and collagen in rats with hepatic fibrosis.
Methods:
Thirty-six male wistar rats were randomly divided into control group, model group and drug-treated group, with 12 rats in each group. Liver fibrosis models were made by subcutaneous injection of carbon tetrachloride on the dorsal of the rats, simultaneously gastric gavage with Valsartan and were killed at the end of 8th week. The degree of liver fibrosis was observed by HE and Masson staining. The serum leptin (LP) and TGFβ1 were determined by ELISA. Liver LP mRNA and leptin receptor mRNA (OB-R mRNA) were detected by RT-PCR. Liver LP, OB-R and collagen I were detected by Western blot. The data of multiple groups were analyzed by one-way analysis variance (ANOVA), and linear correlation was performed between serum LP and TGF β1.
Results:
After the intervention of valsartan, HE and Masson staining showed that the degree of liver fibrosis was significantly reduced. The levels of serum LP and TGFβ1 in the control group were (18.92 ± 7.10) ng/ml and (9.13 ± 1.58) pg/ml respectively, which were significantly lower than those in the model group (46.92 ± 28.54) ng/ml and (16.39 ± 3.56) pg/ml, And (29.27 ± 7.27) ng/ml and (12.24 ± 2.94) pg/ml in the drug-treated group, respectively. The

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