Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-β/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.

ObjectiveTo explore the mechanism of Tibetan medicine Ershiwuwei Guijiuwan against osteoporosis in ovariectomized rats through the classical Wnt/β-catenin signaling pathway. MethodForty-eight 3-month-old SD female rats were randomized into model group （equivalent volume of normal saline）， sham operation group （equivalent volume of normal saline）， estradiol group （0.1 mg·kg^-1 estradiol valerate）， and high-， medium-， low-dose Ershiwuwei Guijiuwan groups （800， 400， 200 mg·kg^-1， respectively）. For the modeling， some adipose tissue near the ovaries was removed in the sham operation group， and ovaries were excised in other groups. Administration （ig， once a day） started two weeks after the operation and lasted 12 weeks. After sampling， based on hematoxylin and eosin （HE） staining， the morphological changes of the right femur and lumbar spine of the rats were observed. The enzyme-linked immunosorbent assay （ELISA） was performed to detect the serum levels of rat tartrate-resistant acid phosphatase 5b （TRAP5b）， collagen type Ⅰ C-terminal peptide （CTX-Ⅰ）， bone alkaline phosphatase （BALP）， amino-terminal propeptide of type Ⅰ procollagen （PINP）， and bone Gla-protein （BGP）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was performed to examine the mRNA expression of β-catenin and Runt-related transcription factor 2 （Runx2） in femur， and Western blot to detect the protein expression of β-catenin， Runx2， and low-density lipoprotein receptor-related protein-5 （Lrp-5）. ResultCompared with the sham operation group， the model group showed disordered and sparse bone trabecula with fewer connections， decrease in serum levels of BALP， BGP， and PINP （P<0.01）， increase in levels of CTX-Ⅰ and TRAP5b （P<0.01）， reduction in mRNA expression of β-catenin and Runx2 in femoral tissue （P<0.01） and protein expression of Lrp-5， β-catenin， and Runx2 （P<0.01）. Compared with the model group， estradiol and each dose of Ershiwuwei Guijiuwan increased the volume of bone trabecula， made thebone trabecula closely arranged， reduced the loss of the trabecular meshwork， raised the serum levels of BALP and BGP （P<0.01）， and lowered TRAP5b level （P<0.01）. PINP level was significantly increased in the high-dose Ershiwuwei Guijiuwan group and estradiol group （P<0.01） and CTX-Ⅰ level was significantly decreased in the high-dose Erwenwuwei Guijiuwan group and the estradiol group （P<0.01） compared with those in the model group. The mRNA expression of β-catenin in femoral tissue and protein expression of Lrp-5 and β-catenin in estradiol group and three Ershiwuwei Guijiuwan groups were significantly increased （P<0.05， P<0.01）， and the levels of Runx2 mRNA and protein were significantly increased in the high-dose Ershiwuwei Guijiuwan group and the estradiol group （P<0.01） compared with those in the model group. ConclusionTibetan medicine Ershiwuwei Guijiuwan is effective for the osteoporosis in ovariectomized rats， which may be related to the classic Wnt/β-catenin signaling pathway. It affects bone metabolism by up-regulating the expression of osteogenesis-related genes in the signaling pathway.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Objective:To analyze the long-term prognosis of undergoing drug-eluting stent implantation (DES) or coronary artery bypass grafting (CABG) in patients with unprotected left main (ULM) coronary artery disease complicated with chronic renal failure (CRF).Methods:Patients with UML coronary artery disease complicated with CRF admitted to the department of cardiology intensive care unit (ICU) and cardiac surgery ICU of Beijing Anzhen Hospital Affiliated to Capital Medical University were enrolled. According to the estimated glomerular filtration rate (eGFR), the patients were divided into two layers, and the clinical characteristics of DES patients and CABG patients were analyzed. Log-Rank method and Cox regression were used to analyze the coronary artery disease and long-term clinical prognosis of patients with two surgical strategies.Results:A total of 353 patients were enrolled, including 150 patients with eGFR < 45 mL·min -1·1.73 m -2 (DES 67 cases, CABG 83 cases), eGFR 45-59 mL·min -1·1.73 m -2 in 203 cases (DES 80 cases, CABG 123 cases). In terms of demography and clinical history, compared with CABG group, DES group had lower proportion of complete revascularization and lower proportion of chronic totalocclusion (CTO) and multi vessel disease in each eGFR level. All patients were followed up for an average of (30.74±15.05) months. Log-Rank analysis showed that there was no significant difference in the incidence of major cardiovascular and cerebrovascular adverse events (MACCE), all-cause death, cardiogenic death and stroke between DES group and CABG group in each eGFR level. In eGFR 45-59 mL·min -1·1.73 m -2, the proportion of target vessel revascularization (TVR) in DES group was higher than that in CABG group (18.8% vs. 0.8%, P < 0.01); in eGFR < 45 mL·min -1·1.73 m -2, the incidence of myocardial infarction in DES group was higher than that in CABG group (10.4% vs. 1.2%, P < 0.05). Cox analysis showed that after adjusting for age, gender, history of hypertension, diabetes, left ventricular ejection fraction, smoking history, previous cerebrovascular disease, complete revascularization, multiple vessel disease and CTO, TVR proportion in DES group was still higher than that in CABG group in eGFR 45-59 mL·min -1·1.73 m -2 [hazard ratio ( HR) = 46.463, 95% confidence interval (95% CI) was 4.558-473.693, P = 0.001]; in eGFR < 45 mL·min -1·1.73 m -2, the incidence of myocardial infarction in DES group was still higher than that in CABG group ( HR = 14.098, 95% CI was 1.123-176.988, P = 0.040), there was no difference in TVR proportion between the two methods. Conclusions:eGFR < 45 mL·min -1·1.73 m -2 is an independent risk factor for DES in ULM patients. DES is safe and effective for ULM patients with CRF, but for patients with more severe CRF (eGFR < 45 mL·min -1·1.73 m -2), there was more myocardial infarction in DES group than that in CABG group, which should be carefully selected.

Objective:To investigate the feasibility and clinical effects of the chimeric multi-paddled anteriolateral thigh perforator flap (ALTP) for reconstruction of complex defects in extremities, which was pedicled with the descending branch of lateral circumflex femoral artery (d-LCFA).Methods:From August, 2010 to December, 2017, 11 cases of severe soft-tissue defects were repaired with this flap, including 4 cases of car accident trauma, 2 of machine injury, 2 of fall injuries, 1 of ploughing machine injury, 1 of crushing injury, and 1 of spoke injury. The injuries accompanied with different degrees of infections, dead space and left huge soft-tissue defects after radical debridement (10.0 cm×9.0 cm-20.0 cm×18.0 cm) . Dead cavity was filled by the muscular flap, and the large area soft-tissue defects were repaired by chimeric multi-paddled perforator flap. Appearance, colour and texture of the flap, recurrence of infection and knee extension were recorded at 1, 3, 6, 9 and 12 months follow-up.Results:After the operation, all recipient sites had no hematoma and no infection. Eight flaps survived successfully, and donor sites healed primarily. One flap had partial necrosis because of a mechanical stretch of the perforator during the operation, then repaired by the ipsilateral chimeric perforator flap based on d-LCFA. One flap occurred vascular crisis on the second day after the surgery, and it was rescued and survived completely after surgical exploration. The other flap which repaired wound on hand had partial necrosis too, and then repaired with posterior interosseous artery perforator flap. The follow-up periods ranged from 2 to 32 (mean, 10.2) months. All flaps had satisfactory appearance and texture. Only linear scars left at the donor sites. There were no motion limitations at the hip and knee joints of the effected leg.Conclusion:The anteriolateral thigh perforator flap combined with multi-paddled and chimeric techniques can reduce donor site morbidities, simplify the anastomosis of blood vessel, and improve the appearance and effects of the recipient site. It is a feasible method in repairing severe soft tissue defects of limbs.

Objective To investigate the feasibility and clinical effects of deep femoral artery third perforating artery perforator flap for reconstruction of soft tissue defect in lower limbs.Methods From September,2008 to October,2016,8 cases of soft tissue defect in lower limbs which were repaired by deep femoral artery third perforating artery perforator flap,including 4 cases of traffic accident trauma,2 cases of chronic ulcer,1 case of a fall injury,1 case of the scar after fracture operation.The area of wounds was 8.0 cm×7.0 cm-19.0 cm×8.0 cm.Seven patients were accompanied by different degrees of infections.The deep femoral artery third perforating artery perforator flap was designed to repair,including 5 cases of pedicled flaps and 3 cases of free flaps.The flap's appearance,color,texture,infection recurrence and the recovery of lower limb function were recorded at 1,3,6,9 and 12 months followed-up.Results One flap suffered partial necrosis due to cross-zone backflow disorder,the ipsilateral medial sural artery pedicled perforator flap was used to repair.The rest of the flaps survived successfully.Skin graft was used to close the donor site in 1 case,and other donor sites were closed directly.All patients had no postoperative hematoma or secondary infection.The followed-up periods ranged from 2 to 28 months (mean,8.1 months).All flaps had satisfied appearance and texture.There were no complications such as paresthesia and numbness in the donor sites.And no motion limitations in hip and knee joint of the operated leg.Conclusion Deep femoral artery third perforating artery perforator flap can be used for both free flaps and pedicled flaps,which is a feasible method to repair soft tissue defect in lower limbs.

Objective To investigate the feasibility and clinical effects of chimeric perforator flap based on the descending branch of lateral circumflex femoral artery (d-LCFA) for reconstructing the three-dimensional tissue defect in lower extremities. Methods From May, 2008 to June, 2017, 79 cases of soft tissue defects with dead space were repaired by using a d-LCFA chimeric perforator flap, in which 33 cases of car accident trauma, 12 cases of chronic tibial osteomyelitis, 10 cases of plowing machine injury, 9 cases of chronic calcaneal osteomyelitis, 6 cases of falling injury, 5 cases of crushing injury, 3 cases of spoke injury, and 1 case of suppurative knee arthritis. These patients were accompany with different degrees of infection and dead space after radical debridement. The dead cavity was filled by muscular flap, and perforator flap covered the superficial wound. Recording the flap 's appearance, color, texture, osteomyelitis recurrence and the patient 's knee extension at 1, 3, 6, 9 and 12 months followed-up. Results Seventy-five flaps survived without complications, and the donor sites were closed directly. All patients had no post-operative hematoma or secondary infection. Vascular crisis occurred in 2 days after the operation in 4 flaps, 1 flap had an arterial crisis on the second-postoperative-day, and the flap was necrotic after surgical exploration. The deep cir-cumflex iliac artery chimeric perforator flap was used for repairing. Three flaps with venous crisis during 48 h after operation, in which 2 flaps survived eventually after surgical exploration, and another flap was necrosis and repaired by skin graft. The followed-up periods ranged from 3 months to 30 months (mean, 9.7 months). All flaps had satisfied with appearance and texture. There were no osteomyelitis recurrence and any ranges of motion limitations in the hip and knee joints of the operated leg. Conclusion The chimeric perforator flap with d-LCFA merely anastomosed 1 group vascular pedicle can make the dead space be filled and cover the superficial wound simultaneously. It is an ideal option for reconstructing the skin defect with dead space in lower extremity, which can improve the quality of restoration of recipient site and reduce the damage of donor site.

Objective To explore a reliable parameter for primary closure of the donor site of the descending branch of the circumflex femoral lateral artery perforator flap and analysis its effective factors.Methods Between August,2014 and December,2015,149 patients undergoing reconstructive procedures using the descending branch of the circumflex femoral lateral artery perforator flaps were included in the study.All patients were divided into two groups:primary closure of the donor site (135 cases) and none primary closure of the donor site (14 cases).The receiver operating characteristic curve for biostatistical analysis was performed to identify the reliable width of the descending branch of the circumflex femoral lateral artery perforator flap.The parameter,including the age,patients' body mass index,subcutaneous fat thickness,thigh circumference and the maximum flap width,were recorded in 79 patients who were randomly choose from all patients.The method through stretching donor site skin was used to assess the maximum flap width.The maximum flap width-to-thigh circumference ratio was calculated.The Pearson test was used to analysis the correction between those parameters.Results Primary closure of the donor site was possible in 135 patients and impossible in 14 patients.The receiver operating characteristic curve for biostatistical analysis identifying the reliable width of the descending branch of the circumflex femoral lateral artery perforator flap was 8.75cm.The method assessed the reliable width of the flap was (8.37±1.67) cm through stretching donor site skin.the reliable width of the flap was (8.55±1.65) cm in the male patients and (7.42±1.5) cm in the female patients.There was significant different between the two group (P ＜ 0.05).Primary closure can be achieved if the flap width-to-thigh circumference ratio was less than (17.23±3.84) percent.There was a significant negative correlation between subcutaneous fat thickness and the ratio (R=-0.299,P ＜ 0.05) and between body mass index and the ratio (R=-0.21,P ＜ 0.05).Conclusion The width of flap less than 8.75 cm is a reliable parameter for primary closure of the descending branch of the circumflex femoral lateral artery perforator flap donor site.The patient's body mass index and subcutaneous fat thickness of the thigh should be taken into consideration.

Objective: To compare the long-term clinical outcomes of consecutive patients treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention(PCI) with drug-eluting stents (DES) for bifurcation lesions in unprotected left main coronary artery (ULMCA). Methods: A total of 663 consecutively patients with unprotected left main bifurcation disease (defined as stenosis≥50%) who received either drug-eluting stents (DES) implantation (n=316) or underwent CABG (n=347) between January 2003 and July 2009 in Beijing Anzhen Hospital were enrolled retrospectively in this study.The endpoints of the study were death, repeat revascularization, myocardial infarction (MI), stroke, the composite of cardiac death, MI or stroke and MACCE (major adverse cardiac and cerebrovascular events, the composite of cardiac death, MI, stroke or repeat revascularization). To reduce the bias between two compared groups , our study applid propensity score matching by logistic regression.Cumulative survival rate was calculated by Kaplan-Meier method.Multiple regression analyses, hazard ratio(HR) and 95%CI were tested by Cox proportional hazard models with the CABG group as the reference category. Results: The median follow-up was 7.2 years (interquartile range 5.1 to 8.3 years) in the overall patients.Unadjusted analysis showed that MACCE rate (PCI 44.5% vs. CABG 45.7%, P=0.036), the rate of repeat revascularization (PCI 33.7% vs. CABG 19.5%, P<0.001), the composite rate of serious outcomes (cardiac death, MI or stroke) (PCI 20.4% vs. CABG 34.3%, P=0.032), stroke rate (PCI 3.7% vs. CABG 23.5%, P<0.001) were significantly different for patients undergoing PCI or CABG. Death rate (PCI 13.0% vs. CABG 18.9%, P=0.12) and MI rate (PCI 11.3% vs. CABG 6.1%, P=0.108) were similar between PCI and CABG group.After adjusting covariates with multivariate Cox hazard regression model, there was no significant difference in rates of death (P=0.286), MI(P=0.165) and the composite rate of serious outcomes (cardiac death, MI or stroke) (P=0.305) between the two groups. Patients in PCI group suffered significant higher rates of MACCE(P=0.011), mainly driven by the significant higher rates of repeat revascularization(HR=2.46, 95%CI 1.662-3.642, P<0.001). However, stroke rate was still significantly higher in CABG group than in PCI group(P=0.001)after multivariate adjusting. After propensity score matching (PSM), there was no more significant difference for all covariates in the matched cohorts (202 pairs). Further PSM analysis showed that overall findings were consistent with multivariate Cox hazard regression model except for MI (PCI 12.7% vs. CABG 3.8%, P=0.039). Conclusions During a follow-up up to 8.3 years, the survival rate is similar between the PCI and the CABG group in patients with unprotected left main bifurcation disease.The rate of repeat revascularization is significantly higher whereas stroke rate is significantly lower in the PCI group compared to CABG group.After propensity score matching, PCI group not only had a significant higher rate of repeat revascularization, but also had significantly higher risk of MI in the matched cohorts; while they did not seem to translate into any disparity of mortality in ULMCA bifurcation disease patients.Accordingly, PCI for ULMCA disease can be used as a reasonable treatment option alternative to CABG.

Objective: To observe the predictive value of serial platelet function testing (PFT) on outcome in patients undergoing complex percutaneous coronary intervention (PCI). Methods: Six hundred and two consecutive patients undergoing complex PCI in Anzhen hospital were enrolled during October 2011 to June 2012.Adenosine diphosphate(ADP)-induced platelet aggregation was measured by light transmission aggregometry on the first, sixth and twelfth month after PCI and the mean value was calculated.The cut-off value of high on-treatment platelet reactivity (HTPR) was defined as 40%.The primary endpoint was major adverse cardiovascular and cerebral event (MACCE). Clinical outcomes were analyzed by the Kaplan-Meier method and differences were compared using the log-rank test.Multivariate analyses by Cox proportion hazards regression were applied to identify variables independently associated with the adverse outcomes. Results: Five hundred and eighty-five patients (HTPR, n=285; non-HTPR, n=280) finished the follow-up ((28.47±7.45) months). A total of 33 cases of MACCE were observed during the follow-up, among which 29 cases(8.42%) were in HTPR group and 9 cases (3.21%) in the non-HTPR group.Kaplan-Meier analysis suggested that HTPR was associated with an increased incidence of MACCE (log-rank test, P=0.01). The Cox multivariate analysis indicated that HTPR was an independent risk factor of MACCE (HR=2.69, 95%CI 1.23-5.85, P=0.01) in patients undergoing complex PCI.Incidence of MACCE was similar between HTRP patients receiving standard dual antiplatelet therapy (DAPT) or prolonged DAPT (>12 months). Conclusion Serial PFT could predict the long-term prognosis of patients underwent complex PCI.