Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

OBJECTIVE: To explore the effect and mechanism of DNA methyltransferase 1 (DNMT1) knockout on the inhibition of acute myeloid leukemia (AML) by natural killer (NK) cells. METHODS: The peripheral blood NK cells of AML patients and controls were collected, and the mRNA and protein level of DNMT1 were measured by PCR and Western blot, respectively. The DNMT1 knockout mice were constructed to obtain NK^DNMT1-/- cells. The NK cells were stimulated with interleukin (IL)-12, IL-15, and IL-18 to construct memory NK cells, and then the interferon-γ (IFN-γ) levels were measured by ELISA. After co-culturing with memory NK cells and HL60 cells, the killing effect of NK^DNMT1-/- cells on HL60 cells was detected by LDH assay. Then, the HL60 cell apoptosis and NK cell NKG2D level were measured by flow cytometry. The perforin and granzyme B protein levels of NK cells were measured by Western blot. The AML model mice were constructed by injecting HL60 cells into the tail vein, meanwhile, memory NK cells were also injected, and then the mouse weights, CD33 positive rates, and survival time were detected. RESULTS: The mRNA and protein levels of DNMT1 in NK cells of AML patients were significantly higher than those in the control group (both P < 0.01), while the IFN-γ level induced by interleukin was significantly lower than that in the control group (P < 0.05). Compared with NK^DNMT1+/+ cells, the ability of NK^DNMT1-/- cells to secrete IFN-γ after interleukin stimulation was significantly increased (P < 0.05). The killing and apoptosis-inducing effects of NK^DNMT1-/- cells on HL60 cells were significantly stronger than those of NK^DNMT1+/+ cells (both P < 0.05). The NKG2D level and expression of perforin and granzyme B of NK^DNMT1-/- cells were significantly increased compared with NK^DNMT1+/+ cells (all P < 0.05). Compared with AML mice injected with NK^DNMT1+/+ cells, AML mice injected with NK^DNMT1-/- cells showed significantly increased body weight, decreased CD33 positive rate, and prolonged survival time (all P < 0.05). CONCLUSION Knocking out DNMT1 can enhance the inhibitory effect of NK cells on AML, which may be related to enhancing NK cell memory function.
Killer Cells, Natural/metabolism* ; Animals ; Leukemia, Myeloid, Acute ; Humans ; DNA (Cytosine-5-)-Methyltransferase 1 ; Mice ; Mice, Knockout ; HL-60 Cells ; Apoptosis ; Interferon-gamma/metabolism* ; Granzymes/metabolism* ; Perforin/metabolism* ; NK Cell Lectin-Like Receptor Subfamily K/metabolism*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

BACKGROUND:Chondrocyte apoptosis is an important factor in the development of osteoarthritis,and Complanatoside A has a flavonoid effect,which can inhibit apoptosis of various cells,but its effect on chondrocyte apoptosis and the mechanism of action are not clear. OBJECTIVE:To investigate the intrinsic association and mechanism of Complanatoside A in chondrocyte apoptosis based on the Wnt/β-catenin signaling pathway. METHODS:(1)The cartilage tissues of the femur and tibia transected during knee arthroplasty were collected,and chondrocytes were isolated,cultured in vitro,and identified.(2)Cell counting kit-8 was used to detect the optimal intervention concentration of Complanatoside A in the concentration range of 0-160 μmol/L.(3)Chondrocytes were divided into blank group,sodium nitroprusside(1.5 mmol/L)-induced group,and sodium nitroprusside(1.5 mmol/L)+Complanatoside A(5 μmol/L)group.The viability and apoptosis rate of the cells in each group were detected by cell counting kit-8 and flow cytometry.The expression of type Ⅱ collagen and SOX9 was detected by immunofluorescence staining.The expression of apoptosis-related proteins and Wnt/β-catenin pathway proteins was detected by western blot assay. RESULTS AND CONCLUSION:The cells extracted in vitro were cultured and stained,and were clearly identified as chondrocytes.Complanatoside A had no obvious cytotoxicity to chondrocytes in the concentration range of 0-80 μmol/L,and significantly improved the chondrocyte viability in the concentration range of 2.5-10 μmol/L,especially when the concentration was 5 μmol/L.The apoptotic rate of chondrocytes was higher in the sodium nitroprusside-induced group than the blank control group,while the apoptotic rate was lower in the sodium nitroprusside+Complanatoside A group than the sodium nitroprusside-induced group.The fluorescence intensity of type Ⅱ collagen and SOX9 in chondrocytes was weaker in the sodium nitroprusside-induced group than the blank control group,while the fluorescence intensity of type Ⅱ collagen and SOX9 in the sodium nitroprusside+Complanatoside A group was higher than that of the sodium nitroprusside-induced group.In the sodium nitroprusside-induced group,the protein expression of Bax,Caspase-3,matrix metalloproteinase 13,Wnt3a,Wnt5a and β-catenin was higher than that of the blank control group,while the protein expression of Bcl-2 was lower than that of the blank control group.In the sodium nitroprusside+Complanatoside A group,except for the protein expression of Bcl-2 which was higher than that of the sodium nitroprusside-induced group,the expression of the other aforementioned proteins was lower than that of the sodium nitroprusside-induced group.To conclude,Complanatoside A has a certain inhibitory effect on chondrocyte apoptosis,which could regulate apoptosis-related proteins and promote the expression of chondrocyte regulatory factors,and presumably might play a role through inhibiting the Wnt/β-catenin signaling pathway.

Objective:To analyze and compare the interfractional setup errors between two body posi-tioning fixation methods(lithotomy position with carbon fiber full-body fixation frame vs.conventional carbon fiber body fixation frame combined with thermoplastic membrane)in radical radiotherapy for pros-tate cancer,and to calculate the clinical target volume(CTV)to planning target volume(PTV)margin(MPTV)for both methods to optimize immobilization techniques and radiotherapy workflows.Methods:A retrospective analysis was conducted on 37 consecutive patients who underwent radical prostate radio-therapy at Peking University First Hospital between August 2021 and March 2023.The patients were di-vided into two groups based on the immobilization method:Group A(18 patients,450 CBCT image sets)used a carbon fiber whole-body fixator in the lithotomy position,while Group B(19 patients,461 CBCT image sets)used a conventional carbon fiber fixator combined with a thermoplastic mask.All the patients underwent daily cone-beam computed tomography(CBCT)image guidance.Bone registration combined with manual registration was used to obtain the setup error data in the left-right(X),cranio-caudal(Y)and anterior-posterior(Z)directions.The positioning errors of the two groups were compared by using the independent sample t-test,the Mann-Whitney U test and the chi-square test.The average positioning error,systematic positioning error(Σ)and random positioning error(δ)were calculated,and the CTV-PTV extension distance was calculated by using the(MPTV=2.5Σ+0.7δ).Results:The analysis of the setup errors in the three-dimensional direction showed significant differences between the two groups(all P＜0.01).Specifically,the median(quartile)absolute values of the errors in the X,Y,and Z di-rections of group A were[0.40(0.20,0.70)cm,0.50(0.30,0.80)cm,and 0.35(0.20,0.60)cm],respectively.In group B,the corresponding values were significantly reduced to[0.20(0.10,0.40)cm,0.40(0.20,0.70)cm and 0.20(0.10,0.40)cm].The results of Mann-Whitney U test showed that the differences in each direction were highly statistically significant(X:z=-6.86;Y:z=-2.76;Z:z=-5.71).The cumulative distribution ratio of the setup error displacement within 0.5 cm in the X,Y,and Z directions in group A and group B were 297(66.0％)and 408(88.5％)(P＜0.01),250(55.6％)and 285(61.8％)(P=0.055),308(68.4％)and 391(84.8％)(P＜0.01),re-spectively.The CTV-PTV margins in three directions were X 0.66 cm in group A and 0.35 cm in group B;Y0.67 cm and 0.45 cm;Z 0.54 cm and 0.42 cm.Conclusion:Conventional carbon fiber human body fixator combined with thermoplastic film can significantly reduce the setup error.However,the car-bon fiber whole-body fixator in the lithotomy position demonstrated larger setup errors in the X,Y,and Z directions compared with the conventional fixator combined with a thermoplastic mask,indicating the need for further workflow optimization.Given that the lithotomy position is essential for transperineal ultrasound-guided techniques,further research and improvements are required to achieve higher positioning accuracy.

Objective:To explore the clinical effects of sequential treatment of extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defects by free transplantation of anterolateral thigh perforator flap combined with bone transport.Methods:This study was a retrospective observational study. From April 2020 to January 2024, 8 patients with extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defects who met the inclusion criteria were admitted to Beijing Dawanglu Emergency Rescue Hospital. Among them, there were 6 males and 2 females, aged 17 to 58 years. After debridement, the area was 17 cm×8 cm to 30 cm×12 cm, and the length of tibial defect was 9 to 12 cm. Stage Ⅰ surgery was performed by free transplantation of anterolateral thigh perforator flap to repair the extensive skin and soft tissue injuries of the lower leg and using autologous skin graft from the thigh to repair the remaining wound. Stage Ⅱ surgery was performed after wound healing, the external fixation bracket was removed and replaced with an Orthofix unilateral external fixation lengthening frame (hereinafter referred to as external fixation lengthening frame) to transport the proximal tibial osteotomy for repairing the large segmental bone defects. The intraoperative arteriovenous anastomosis and the blood supply of the flap during stage Ⅰ surgery were documented, along with the survival status of the flap/skin graft in the donor and recipient areas postoperatively, and the wound healing time in the recipient area. The time required for bone transport completion, the duration of external fixation retention, and the occurrence of complications during this period were recorded after stage Ⅱ surgery. During follow-up, the occurrence of adverse events in the recipient area was recorded. At the final follow-up, fracture healing of the affected limb was evaluated according to the Paley score, and limb function was observed.Results:In 2 patients, the descending branch of the lateral circumflex femoral artery and the accompanying vein were end-to-end anastomosed with the proximal anterior tibial or posterior tibial artery and vein for antegrade blood supply and antegrade reflux; in 2 patients, the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal anterior tibial artery for retrograde blood supply, and the accompanying vein of the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the proximal anterior tibial vein for antegrade reflux; in 3 patients, the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal posterior tibial artery for retrograde blood supply, and the accompanying vein of the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal posterior tibial vein for retrograde reflux; one patient underwent repair of the injury in the affected lower leg using a free cross-leg vascular pedicle flap from the healthy limb. The flaps/skin grafts in the donor and recipient areas of all 8 patients survived, and the wound healing time in recipient area was 14 to 30 days. The bone transport duration of the patients in this group was 93 to 125 days, and the external fixation lengthening frame was continuously retained for 7 to 14 months after the bone transport was stopped; during the bone transport period, 1 patient had pin tract infection, which was controlled after dressing change and enhanced nursing. During the follow-up, there was no ulceration of the wound surface in recipient area, and no osteomyelitis or fracture developed in the affected limb. At the last follow-up, the bone healing evaluation was all excellent; the walking posture and function of the affected limb were basically normal.Conclusions:The application of free transplantation of anterolateral thigh perforator flap combined with bone transport in the sequential treatment of extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defecst can achieve wound healing and functional reconstruction of bone defects, and has great clinical application value.

Objective:To analyze and compare the interfractional setup errors between two body posi-tioning fixation methods(lithotomy position with carbon fiber full-body fixation frame vs.conventional carbon fiber body fixation frame combined with thermoplastic membrane)in radical radiotherapy for pros-tate cancer,and to calculate the clinical target volume(CTV)to planning target volume(PTV)margin(MPTV)for both methods to optimize immobilization techniques and radiotherapy workflows.Methods:A retrospective analysis was conducted on 37 consecutive patients who underwent radical prostate radio-therapy at Peking University First Hospital between August 2021 and March 2023.The patients were di-vided into two groups based on the immobilization method:Group A(18 patients,450 CBCT image sets)used a carbon fiber whole-body fixator in the lithotomy position,while Group B(19 patients,461 CBCT image sets)used a conventional carbon fiber fixator combined with a thermoplastic mask.All the patients underwent daily cone-beam computed tomography(CBCT)image guidance.Bone registration combined with manual registration was used to obtain the setup error data in the left-right(X),cranio-caudal(Y)and anterior-posterior(Z)directions.The positioning errors of the two groups were compared by using the independent sample t-test,the Mann-Whitney U test and the chi-square test.The average positioning error,systematic positioning error(Σ)and random positioning error(δ)were calculated,and the CTV-PTV extension distance was calculated by using the(MPTV=2.5Σ+0.7δ).Results:The analysis of the setup errors in the three-dimensional direction showed significant differences between the two groups(all P＜0.01).Specifically,the median(quartile)absolute values of the errors in the X,Y,and Z di-rections of group A were[0.40(0.20,0.70)cm,0.50(0.30,0.80)cm,and 0.35(0.20,0.60)cm],respectively.In group B,the corresponding values were significantly reduced to[0.20(0.10,0.40)cm,0.40(0.20,0.70)cm and 0.20(0.10,0.40)cm].The results of Mann-Whitney U test showed that the differences in each direction were highly statistically significant(X:z=-6.86;Y:z=-2.76;Z:z=-5.71).The cumulative distribution ratio of the setup error displacement within 0.5 cm in the X,Y,and Z directions in group A and group B were 297(66.0％)and 408(88.5％)(P＜0.01),250(55.6％)and 285(61.8％)(P=0.055),308(68.4％)and 391(84.8％)(P＜0.01),re-spectively.The CTV-PTV margins in three directions were X 0.66 cm in group A and 0.35 cm in group B;Y0.67 cm and 0.45 cm;Z 0.54 cm and 0.42 cm.Conclusion:Conventional carbon fiber human body fixator combined with thermoplastic film can significantly reduce the setup error.However,the car-bon fiber whole-body fixator in the lithotomy position demonstrated larger setup errors in the X,Y,and Z directions compared with the conventional fixator combined with a thermoplastic mask,indicating the need for further workflow optimization.Given that the lithotomy position is essential for transperineal ultrasound-guided techniques,further research and improvements are required to achieve higher positioning accuracy.

Objective:To explore the clinical effects of sequential treatment of extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defects by free transplantation of anterolateral thigh perforator flap combined with bone transport.Methods:This study was a retrospective observational study. From April 2020 to January 2024, 8 patients with extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defects who met the inclusion criteria were admitted to Beijing Dawanglu Emergency Rescue Hospital. Among them, there were 6 males and 2 females, aged 17 to 58 years. After debridement, the area was 17 cm×8 cm to 30 cm×12 cm, and the length of tibial defect was 9 to 12 cm. Stage Ⅰ surgery was performed by free transplantation of anterolateral thigh perforator flap to repair the extensive skin and soft tissue injuries of the lower leg and using autologous skin graft from the thigh to repair the remaining wound. Stage Ⅱ surgery was performed after wound healing, the external fixation bracket was removed and replaced with an Orthofix unilateral external fixation lengthening frame (hereinafter referred to as external fixation lengthening frame) to transport the proximal tibial osteotomy for repairing the large segmental bone defects. The intraoperative arteriovenous anastomosis and the blood supply of the flap during stage Ⅰ surgery were documented, along with the survival status of the flap/skin graft in the donor and recipient areas postoperatively, and the wound healing time in the recipient area. The time required for bone transport completion, the duration of external fixation retention, and the occurrence of complications during this period were recorded after stage Ⅱ surgery. During follow-up, the occurrence of adverse events in the recipient area was recorded. At the final follow-up, fracture healing of the affected limb was evaluated according to the Paley score, and limb function was observed.Results:In 2 patients, the descending branch of the lateral circumflex femoral artery and the accompanying vein were end-to-end anastomosed with the proximal anterior tibial or posterior tibial artery and vein for antegrade blood supply and antegrade reflux; in 2 patients, the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal anterior tibial artery for retrograde blood supply, and the accompanying vein of the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the proximal anterior tibial vein for antegrade reflux; in 3 patients, the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal posterior tibial artery for retrograde blood supply, and the accompanying vein of the descending branch of the lateral circumflex femoral artery was end-to-end anastomosed with the distal posterior tibial vein for retrograde reflux; one patient underwent repair of the injury in the affected lower leg using a free cross-leg vascular pedicle flap from the healthy limb. The flaps/skin grafts in the donor and recipient areas of all 8 patients survived, and the wound healing time in recipient area was 14 to 30 days. The bone transport duration of the patients in this group was 93 to 125 days, and the external fixation lengthening frame was continuously retained for 7 to 14 months after the bone transport was stopped; during the bone transport period, 1 patient had pin tract infection, which was controlled after dressing change and enhanced nursing. During the follow-up, there was no ulceration of the wound surface in recipient area, and no osteomyelitis or fracture developed in the affected limb. At the last follow-up, the bone healing evaluation was all excellent; the walking posture and function of the affected limb were basically normal.Conclusions:The application of free transplantation of anterolateral thigh perforator flap combined with bone transport in the sequential treatment of extensive skin and soft tissue injuries of the lower leg accompanied by large segmental tibial defecst can achieve wound healing and functional reconstruction of bone defects, and has great clinical application value.

BACKGROUND: Human interleukin (IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes. It has been demonstrated extensive beneficial effects on various diseases; however, its role in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear. METHODS: In vivo, DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibroblasts (CFs) specific hIL-37b overexpression mice (IL-37-Tg). In vitro, primary mouse CFs were isolated from the hearts of adult mice and cultured with high levels of glucose and palmitic acid. Cardiac function of the mice was assessed using echocardiography. Masson staining, immunofluorescence, western blot and RT-PCR assays were employed to evaluate the expression of cardiac fibrosis and SOCS3-JAK2-STAT3 signaling pathway-related proteins. RESULTS: In this study, we found that CFs specific IL-37-Tg significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting the JAK2-STAT3 axis, as evidenced by the decreased levels of p-JAK2 and p-STAT3 in the heart of CFs specific IL-37-Tg DCM mice. The beneficial effects of IL-37 were consistently observed in CFs treated with high glucose (HG) and palmitic acid (PA). Moreover, we also discovered that the presence of IL-37 increased the expression of SOCS3, a crucial regulator of JAK/STAT signaling, in DCM mice and HG and PA-treated CFs. Finally, the anti-fibrotic action of IL-37 in HG and PA-treated CFs was abolished when either SOCS3 was genetically knocked down or JAK2/STAT3 was pharmacologically activated. CONCLUSIONS Our findings indicate that IL-37 exerts its antifibrotic effect by promoting SOCS3-mediated JAK2-STAT3 inactivation and may be considered as a potential therapeutic agent for DCM.