OBJECTIVE To investigate the mechanism by which the traditional Chinese medicine formula Xibining Ⅱ modulates cold-stimulus pain sensitivity in rats with cold-damp obstruction-type knee osteoarthritis （KOA） based on the SET domain bifurcated histone lysine methyltransferase 2 （SETDB2）/histone H3 lysine 9 trimethylation （H3K9me3） signaling axis. METHODS Fifty SD rats were randomly divided into control group （intragastric administration and intrathecal injection of equal volumes of normal saline）， model group （intragastric administration and intrathecal injection of equal volumes of normal saline）， Xibining Ⅱ low- and high-dose groups （4， 8 g/kg Xibining Ⅱ， intragastric administration）， and high-dose of Xibining Ⅱ+small interfering RNA （siRNA） group （8 g/kg of Xibining Ⅱ via intragastric administration and intrathecal injection of SETDB2 siRNA at 0.2 mmol/L， 20 μL per rat）， with 10 rats in each group. Except for the control group， cold-damp obstruction-type KOA model was induced in other groups. Drug administration commenced 14 days post-modeling and continued for 28 days. Following the final administration， the following were assessed： behavioral changes in cold-stimulation pain sensitivity， histopathological changes in the articular cartilage of the knee joint， the contents of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）] and pain mediators [calcitonin gene-related peptide （CGRP）， nerve growth factor （NGF）]， as well as the expressions of SETDB2/H3K9me3 signaling axis，inflammatory factors and pain mediators related proteins and mRNAs in dorsal root ganglion （DRG） tissue. RESULTS After 28 days of drug administration， compared with the model group， Xibining Ⅱ low- and high-dose groups exhibited significantly prolonged cold-stimulus paw withdrawal latency （P＜0.05）； the number of positive responses in the acetone low-temperature test was significantly reduced （P＜0.05）； Mankin score and the Osteoarthritis Research Society International score for knee joint tissue， as well as the levels of inflammatory factors and pain mediators in the serum and their expression in DRG tissue were all significantly decreased （P＜0.05）； the protein expressions of SETDB2 and H3K9me3 in DRG tissue were significantly increased （P＜0.05）. Intrathecal injection of SETDB2 siRNA reversed the above effects of high-dose of Xibining Ⅱ （P＜0.05）. CONCLUSIONS Xibining Ⅱ may alleviate inflammatory and pain responses by activating the SETDB2/H3K9me3 signaling axis， ultimately improving cold-stimulus pain sensitivity in rats with cold-damp obstruction-type KOA.

Objective To explore the application value of different Trocar layouts in retroperitoneal laparoscopic partial nephrectomy for localized renal cell carcinoma, so as to provide reference for the layout of Trocar during operation. Methods The data of 137 patients with localized renal cell carcinoma who underwent retroperitoneal laparoscopic partial nephrectomy in our hospital during Sep. 2021 and Sep. 2024 were retrospectively collected, including 68 patients with umbrella layout(umbrella group)and 69 with trapezoidal layout(trapezoidal group). The operation-related indexes, renal function(glomerular filtration rate, serum creatinine), traumatic stress indexes including C-reactive protein(CRP), cortisol, and interleukin-6(IL-6), complications and recurrence rate were compared between the two groups. Results There were no significant differences in pathological results, negative rate of surgical margins, hospitalization time, complications, 1-year recurrence rate, 6-month glomerular filtration rate and serum creatinine between the two groups(P＞0.05). Compared with the trapezoidal group, the umbrella group had less intraoperative blood loss [(72.11±18.30)mL vs.(87.59±20.63)mL], shorter operation time [(88.15±16.92)min vs.(99.40±20.78)min], renal warm ischemia time [(14.68±4.60)vs.(19.27±6.11)min], bowel sound recovery time [(21.00±5.75)h vs.(25.78±4.89)h] and ambulation time [(1.72±0.48)d vs.(2.04±0.55)d](P＜0.05). The umbrella group had lower CRP [(10.02±2.78)mg/ L vs.(12.00±3.15)mg/ L] on the first day after surgery, lower CRP [(7.89±0.76)vs.(8.77±1.25)mg/L] on the third day after surgery, lower cortisol [(0.67±0.20)μmol/L vs.(0.89±0.28)μmol/L] on the first day after surgery, lower cortisol [(0.58±0.15)μmol/L vs.(0.69±0.12)μmol/L] on the third day after surgery, lower IL-6 [(28.20±6.74)ng/L vs.(35.16±7.30)ng/L] on the first day after surgery, and lower IL-6[(21.25±5.39)ng/L vs.(29.78±4.26)ng/L] on the third day after surgery(P＜0.05). Conclusion Compared with the trapezoidal Trocar layout, the umbrella Trocar layout for retroperitoneal laparoscopic partial nephrectomy in patients with localized renal cell carcinoma offers advantages such as minimal surgical trauma, shorter operation and renal warm ischemia time, and faster postoperative recovery.

ObjectiveTo establish and evaluate different disease-syndrome combination mice models of knee osteoarthritis （KOA） with cold-dampness obstruction syndrome， and to identify the optimal modeling method. MethodsEighty mice were randomly divided into a control group， a treadmill plus climate chamber group， an anterior cruciate ligament transection （ACLT） plus climate chamber group， an ACLT group， a destabilization of the medial meniscus （DMM） plus climate chamber group， a DMM group， an intra-articular injection plus climate chamber group， and an intra-articular injection group， with 10 mice in each group. Mice in the ACLT group underwent surgical transection of the knee anterior cruciate ligament to establish the model， while those in the DMM underwent surgical transection of the medial meniscal tibial ligament of the knee， and those in the intra-articular injection group were modeled by an intra-articular injection of 50 μl of normal saline containing 1mg of monosodium iodoacetate （MIA） into the medial side of the patellar ligament. Mice in the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups were placed in an artificial climate chamber （relative humidity 60%， temperature 4 ℃， wind speed 6 m/s） simultaneously with aforementioned interventions， once daily for 2 h each time， for 14 consecutive days. Mice in the control group underwent sham surgery， involving only the incision of the skin and subcutaneous tissue at the knee joint to expose the articular cavity， followed by layer-by-layer suturing. Mice in the treadmill plus climate chamber group were placed on an animal treadmill starting on the 4th day after the sham operation， undergoing high-intensity treadmill exercise at a speed of 20 m/min， an inclination of 5°， for 30min per session， 5 times per week for 28 consecutive days， while being housed in the artificial climate chamber. Cold pain thresholds of the mice in each group were compared using the cold plate test and the acetone low-temperature test before and after modeling. Following modeling， knee joint pathological changes were observed using HE and Safranin O-Fast Green staining， and quantified using Mankin and Osteoarthritis Research Society International （OARSI） scores. Serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were measured by ELISA. Protein and mRNA expression levels of pain-related markers， including calcitonin gene-related peptide （CGRP）， protein gene product 9.5 （PGP9.5）， and cellular proto-oncogene Fos （c-Fos）， and the cold hyperalgesia-related markers including transient receptor potential ankyrin 1 （TRPA1） and transient receptor potential melastatin 8 （TRPM8） in the dorsal root ganglion （DRG） tissues were detected by Western Blot and qPCR. TRPA1 and TRPM8 fluorescent intensity in the DRG was detected by immunofluorescence assay. ResultsCompared to the control group， the remaining groups showed decreased cold pain thresholds in the cold plate tese， increased cold pain thresholds in the acetone low-temperature test， elevated Mankin and OARSI scores， and increased serum TNF-α and IL-1β levels， upregulated protein and mRNA expression levels of CGRP， PGP9.5， c-Fos， TRPA1， and TRPM8 in the DRG， and increased immunofluorescence intensities of TRPA1 and TRPM8 in the DRG tissue （P＜0.05 or P＜0.01）， along with severe pathological damage and cartilage degeneration in the knee joints. Compared to the ACLT， DMM， and intra-articular injection groups， the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups exhibited more significant changes in all the aforementioned indicators （P＜0.01）. Furthermore， changes in the aforementioned indicators were more pronounced in the ACLT plus climate chamber group compared to the Treadmill plus climate chamber group， DMM plus climate chamber and intra-articular injection plus climate chamber group （P＜0.01）， exhibiting the most severe degree of pathological damage and cartilage degeneration. ConclusionThe combination of an artificial climate chamber can successfully establish a disease-syndrome combined animal model of KOA with cold-damp obstruction syndrome， with the ACLT combined with the artificial climate chamber being the optimal modeling approach.

ObjectiveTo establish and evaluate different disease-syndrome combination mice models of knee osteoarthritis （KOA） with cold-dampness obstruction syndrome， and to identify the optimal modeling method. MethodsEighty mice were randomly divided into a control group， a treadmill plus climate chamber group， an anterior cruciate ligament transection （ACLT） plus climate chamber group， an ACLT group， a destabilization of the medial meniscus （DMM） plus climate chamber group， a DMM group， an intra-articular injection plus climate chamber group， and an intra-articular injection group， with 10 mice in each group. Mice in the ACLT group underwent surgical transection of the knee anterior cruciate ligament to establish the model， while those in the DMM underwent surgical transection of the medial meniscal tibial ligament of the knee， and those in the intra-articular injection group were modeled by an intra-articular injection of 50 μl of normal saline containing 1mg of monosodium iodoacetate （MIA） into the medial side of the patellar ligament. Mice in the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups were placed in an artificial climate chamber （relative humidity 60%， temperature 4 ℃， wind speed 6 m/s） simultaneously with aforementioned interventions， once daily for 2 h each time， for 14 consecutive days. Mice in the control group underwent sham surgery， involving only the incision of the skin and subcutaneous tissue at the knee joint to expose the articular cavity， followed by layer-by-layer suturing. Mice in the treadmill plus climate chamber group were placed on an animal treadmill starting on the 4th day after the sham operation， undergoing high-intensity treadmill exercise at a speed of 20 m/min， an inclination of 5°， for 30min per session， 5 times per week for 28 consecutive days， while being housed in the artificial climate chamber. Cold pain thresholds of the mice in each group were compared using the cold plate test and the acetone low-temperature test before and after modeling. Following modeling， knee joint pathological changes were observed using HE and Safranin O-Fast Green staining， and quantified using Mankin and Osteoarthritis Research Society International （OARSI） scores. Serum levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） were measured by ELISA. Protein and mRNA expression levels of pain-related markers， including calcitonin gene-related peptide （CGRP）， protein gene product 9.5 （PGP9.5）， and cellular proto-oncogene Fos （c-Fos）， and the cold hyperalgesia-related markers including transient receptor potential ankyrin 1 （TRPA1） and transient receptor potential melastatin 8 （TRPM8） in the dorsal root ganglion （DRG） tissues were detected by Western Blot and qPCR. TRPA1 and TRPM8 fluorescent intensity in the DRG was detected by immunofluorescence assay. ResultsCompared to the control group， the remaining groups showed decreased cold pain thresholds in the cold plate tese， increased cold pain thresholds in the acetone low-temperature test， elevated Mankin and OARSI scores， and increased serum TNF-α and IL-1β levels， upregulated protein and mRNA expression levels of CGRP， PGP9.5， c-Fos， TRPA1， and TRPM8 in the DRG， and increased immunofluorescence intensities of TRPA1 and TRPM8 in the DRG tissue （P＜0.05 or P＜0.01）， along with severe pathological damage and cartilage degeneration in the knee joints. Compared to the ACLT， DMM， and intra-articular injection groups， the ACLT plus climate chamber， DMM plus climate chamber， and intra-articular injection plus climate chamber groups exhibited more significant changes in all the aforementioned indicators （P＜0.01）. Furthermore， changes in the aforementioned indicators were more pronounced in the ACLT plus climate chamber group compared to the Treadmill plus climate chamber group， DMM plus climate chamber and intra-articular injection plus climate chamber group （P＜0.01）， exhibiting the most severe degree of pathological damage and cartilage degeneration. ConclusionThe combination of an artificial climate chamber can successfully establish a disease-syndrome combined animal model of KOA with cold-damp obstruction syndrome， with the ACLT combined with the artificial climate chamber being the optimal modeling approach.

AIM:To investigate whether Xibining Ⅱ(XBN Ⅱ)attenuates cartilage damage in rats with knee osteoarthritis(KOA)by modulating glycolysis via the AMP-activated protein kinase(AMPK)/peroxisome proliferator-acti-vated receptor γ coactivator 1α(PGC1α)signaling pathway.METHODS:Thirty-two SD rats were randomly divided into sham group,KOA group,XBN Ⅱ group and metformin(AMPK activator)group,with 8 rats in each group.The rats in KOA group were subjected to the anterior cruciate ligament transection procedure to establish the KOA model.Starting from the 14th day after modeling,the rats in XBN Ⅱ group received a daily dose of XBN Ⅱ via gavage once a day,and those in metformin group were administered metformin via intraperitoneal injection once a day for 4 weeks.Subsequently,the histopathological changes of the cartilage were examined by HE and safranin O-fast green staining with matching Mankin and OARSI scores.The protein levels of phosphorylated AMPK(p-AMPK)and PGC1α in cartilage were quanti-fied through immunohistochemistry.In addition,RT-qPCR and Western blot were conducted to measure the mRNA and protein expression levels of glycolysis-related factors,including glucose transporter 1,hexokinase 2 and lactate dehydroge-nase A,biomarkers related to cartilage synthesis and catabolism,such as collagen type Ⅱ,aggrecan,matrix metallopro-teinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5,and AMPK/PGC1α signaling pathway-re-lated indicators.RESULTS:Lactate levels in cartilage and serum were higher in KOA group compared with sham group(P<0.05).Similarly,the cartilage in KOA group exhibited significant surface abrasion and structural damage,with faint-stained matrix and significantly higher Mankin and OARSI scores compared with sham group(P<0.05).Further analysis revealed significant decreases in the mRNA and protein expression levels of factors related to cartilage anabolism and AMPK/PGC1α signaling pathway in KOA group compared with sham group(P<0.05).In contrast,there were marked in-creases in the mRNA and protein expression levels of factors related to cartilage catabolism and glycolysis(P<0.05).No-tably,XBN Ⅱ and metformin treatments significantly improved the cartilage morphology,reduced Mankin and OARSI scores,and reversed the changes in mRNA and protein levels of the aforementioned indexes(P<0.05).CONCLU-SION:Treatment with XBN Ⅱ can alleviate cartilage damage in KOA rats by inhibiting glycolysis,through a mechanism involving activation of the AMPK/PGC1α signaling pathway.

AIM:This study aimed to investigate the inhibitory effects and potential mechanisms of cyasterone(CYA)on inflammation and apoptosis of chondrocytes in knee osteoarthritis(KOA).METHODS:A rat model of KOA was established through anterior cruciate ligament transection(ACLT).Rats were randomly divided into 5 groups(n=6 in each group):normal control(NC),ACLT,ACLT+CYA(10 mg/kg),ACLT+CYA+SR9009(BMAL1 inhibitor),and ACLT+CYA+LY294002(PI3K inhibitor).Pathological changes in cartilage were evaluated using hematoxylin-eosin(HE)and safranin O/fast green staining,graded according to the Osteoarthritis Research Society International(OARSI)system.Immunohistochemistry was employed to measure the expression levels of BMAL1,phosphorylated phosphati-dylinositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-AKT)and phosphorylated nuclear factor-κB(p-NF-κB)in cartilage.An in vitro KOA model was created by stimulating rat chondrocytes with interleukin-1β(IL-1β).Cell vi-ability was assessed using the CCK-8 assay,while enzyme-linked immunosorbent assay(ELISA)was used to quantify pro-inflammatory cytokines(IL-6,IL-1β and TNF-α).Apoptosis was analyzed via flow cytometry,and the protein expression levels of BMAL1,PI3K,p-PI3K,AKT,p-AKT,NF-κB and p-NF-κB were evaluated using Western blot.RESULTS:In vivo,the rats in ACLT group exhibited significant chondrocyte degradation and lacunae formation compared with NC group,confirming the successful establishment of the KOA model.The rats in ACLT+CYA,ACLT+CYA+SR9009 and ACLT+CYA+LY294002 groups showed improved cartilage integrity compared with ACLT group,with reduced OARSI scores(P<0.05),increased BMAL1 expression(P<0.05),and decreased levels of p-PI3K,p-AKT and p-NF-κB(P<0.05).In vitro,the chondrocytes in IL-1β+CYA,IL-1β+CYA+SR9009 and IL-1β+CYA+LY294002 groups exhibited lower levels of IL-6,IL-1β and TNF-α(P<0.05),decreased apoptosis rates(P<0.01),increased BMAL1 protein ex-pression(P<0.05),and reduced p-PI3K/PI3K,p-AKT/AKT and p-NF-κB/NF-κB ratios(P<0.05),compared with IL-1β group.CONCLUSION:Cyasterone alleviates chondrocyte inflammation and apoptosis in KOA by activating BMAL1,which subsequently inhibits the phosphorylation of PI3K/AKT/NF-κB signaling pathway.

AIM:This study aimed to investigate the inhibitory effects and potential mechanisms of cyasterone(CYA)on inflammation and apoptosis of chondrocytes in knee osteoarthritis(KOA).METHODS:A rat model of KOA was established through anterior cruciate ligament transection(ACLT).Rats were randomly divided into 5 groups(n=6 in each group):normal control(NC),ACLT,ACLT+CYA(10 mg/kg),ACLT+CYA+SR9009(BMAL1 inhibitor),and ACLT+CYA+LY294002(PI3K inhibitor).Pathological changes in cartilage were evaluated using hematoxylin-eosin(HE)and safranin O/fast green staining,graded according to the Osteoarthritis Research Society International(OARSI)system.Immunohistochemistry was employed to measure the expression levels of BMAL1,phosphorylated phosphati-dylinositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-AKT)and phosphorylated nuclear factor-κB(p-NF-κB)in cartilage.An in vitro KOA model was created by stimulating rat chondrocytes with interleukin-1β(IL-1β).Cell vi-ability was assessed using the CCK-8 assay,while enzyme-linked immunosorbent assay(ELISA)was used to quantify pro-inflammatory cytokines(IL-6,IL-1β and TNF-α).Apoptosis was analyzed via flow cytometry,and the protein expression levels of BMAL1,PI3K,p-PI3K,AKT,p-AKT,NF-κB and p-NF-κB were evaluated using Western blot.RESULTS:In vivo,the rats in ACLT group exhibited significant chondrocyte degradation and lacunae formation compared with NC group,confirming the successful establishment of the KOA model.The rats in ACLT+CYA,ACLT+CYA+SR9009 and ACLT+CYA+LY294002 groups showed improved cartilage integrity compared with ACLT group,with reduced OARSI scores(P<0.05),increased BMAL1 expression(P<0.05),and decreased levels of p-PI3K,p-AKT and p-NF-κB(P<0.05).In vitro,the chondrocytes in IL-1β+CYA,IL-1β+CYA+SR9009 and IL-1β+CYA+LY294002 groups exhibited lower levels of IL-6,IL-1β and TNF-α(P<0.05),decreased apoptosis rates(P<0.01),increased BMAL1 protein ex-pression(P<0.05),and reduced p-PI3K/PI3K,p-AKT/AKT and p-NF-κB/NF-κB ratios(P<0.05),compared with IL-1β group.CONCLUSION:Cyasterone alleviates chondrocyte inflammation and apoptosis in KOA by activating BMAL1,which subsequently inhibits the phosphorylation of PI3K/AKT/NF-κB signaling pathway.

AIM:To investigate whether Xibining Ⅱ(XBN Ⅱ)attenuates cartilage damage in rats with knee osteoarthritis(KOA)by modulating glycolysis via the AMP-activated protein kinase(AMPK)/peroxisome proliferator-acti-vated receptor γ coactivator 1α(PGC1α)signaling pathway.METHODS:Thirty-two SD rats were randomly divided into sham group,KOA group,XBN Ⅱ group and metformin(AMPK activator)group,with 8 rats in each group.The rats in KOA group were subjected to the anterior cruciate ligament transection procedure to establish the KOA model.Starting from the 14th day after modeling,the rats in XBN Ⅱ group received a daily dose of XBN Ⅱ via gavage once a day,and those in metformin group were administered metformin via intraperitoneal injection once a day for 4 weeks.Subsequently,the histopathological changes of the cartilage were examined by HE and safranin O-fast green staining with matching Mankin and OARSI scores.The protein levels of phosphorylated AMPK(p-AMPK)and PGC1α in cartilage were quanti-fied through immunohistochemistry.In addition,RT-qPCR and Western blot were conducted to measure the mRNA and protein expression levels of glycolysis-related factors,including glucose transporter 1,hexokinase 2 and lactate dehydroge-nase A,biomarkers related to cartilage synthesis and catabolism,such as collagen type Ⅱ,aggrecan,matrix metallopro-teinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5,and AMPK/PGC1α signaling pathway-re-lated indicators.RESULTS:Lactate levels in cartilage and serum were higher in KOA group compared with sham group(P<0.05).Similarly,the cartilage in KOA group exhibited significant surface abrasion and structural damage,with faint-stained matrix and significantly higher Mankin and OARSI scores compared with sham group(P<0.05).Further analysis revealed significant decreases in the mRNA and protein expression levels of factors related to cartilage anabolism and AMPK/PGC1α signaling pathway in KOA group compared with sham group(P<0.05).In contrast,there were marked in-creases in the mRNA and protein expression levels of factors related to cartilage catabolism and glycolysis(P<0.05).No-tably,XBN Ⅱ and metformin treatments significantly improved the cartilage morphology,reduced Mankin and OARSI scores,and reversed the changes in mRNA and protein levels of the aforementioned indexes(P<0.05).CONCLU-SION:Treatment with XBN Ⅱ can alleviate cartilage damage in KOA rats by inhibiting glycolysis,through a mechanism involving activation of the AMPK/PGC1α signaling pathway.

ObjectiveTo observe the effects of Xibining （XBN） and adipose stem cell exosome （ADSC-Exos） in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis （KOA）. MethodSD rats were divided into a sham operation group （sham group）， a model group， an ADSC-Exos group （Exos group）， an XBN group， and an ADSC-Exos+XBN group （Exos+XBN group）. KOA model was established by using anterior cruciate ligament transection （ACLT）. The pain sensitivity status of rats was evaluated， and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence， and the serum levels of TNF-α， IL-1β， IL-6， and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3， MMP-13， ADAMTS5， ColⅡ， TIMP， ACAN， PINK1， Parkin， p62， and LC3A/B. ResultCompared with the sham group， rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， varying degrees of abrasion and loss of cartilage tissue， degeneration of cartilage tissue， elevated serum IL-1β， IL-6， IL-15， and TNF-α levels （P<0.01）， and increased protein expression of MMP-3， MMP-13， and ADAMTS5 in cartilage tissue. In addition， the protein expression of ColⅡ， TIMP1， and ACAN was decreased （P<0.01）. Compared with the model group， rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， reduced cartilage tissue degeneration， lower serum levels of IL-1β， IL-6， IL-15， and TNF-α （P<0.05，P<0.01）， decreased protein expression of MMP-3， MMP-13， and ADAMTS5， and higher protein expression of Cold， TIMP1， and ACAN in cartilage tissue （P<0.05，P<0.01）. Moreover， the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway， and the combination of the two can enhance the therapeutic effect.

Objective::To evaluate the feasibility, safety, and effectiveness of a novel edge-to-edge mitral valve repair system (the NovoClasp system) in patients with severe mitral regurgitation.Methods::In this prospective, single-arm, first-in-human study conducted at Beijing Anzhen Hospital, data were collected from patients undergoing transcatheter edge-to-edge repair using the NovoClasp system. The study candidates were patients exhibiting a mitral regurgitation severity of 3+ or more and were at high-risk or contraindicated for surgical intervention. Technical success and device success according to the Mitral Valve Academic Research Consortium definitions were used as primary outcomes. Other safety and efficacy outcomes were prospectively assessed at device implantation, discharge, and 30 d, 6 months, and 12 months post-procedure.Results::Between October 1, 2021, and January 31, 2022, 11 patients were treated for moderate-to-severe (grade 3+) or severe (grade 4+) mitral regurgitation using the NovoClasp system. All patients had a baseline New York Heart Association functional class of III-IV, with 7/11 exhibiting complex mitral valve disease. All patients achieved the primary endpoints of technical and device success, with a post-operative 30-d mitral regurgitation grade reduction to 2+ or lower, which was maintained at 12 months. One patient had minor bleeding and hematoma at the access site before discharge, and 2 patients were readmitted due to fast atrial fibrillation within 12 months post-discharge. No additional cases of death, adverse cerebral or cardiovascular events, or device-related complications was observed during the follow-up.Conclusion::This study suggested the potential feasibility and safety of the NovoClasp system, showing a promising technical and device success rate, along with a decrease in mitral regurgitation severity. A further pivotal study is needed to assess the procedural and long-term outcomes.