Background:Tumor recurrence after liver transplantation(LT)for selective patients diagnosed with hepatocellular carcinoma(HCC)in the setting of cirrhosis is the greatest challenge effecting the prognosis of these pati...Background:Tumor recurrence after liver transplantation(LT)for selective patients diagnosed with hepatocellular carcinoma(HCC)in the setting of cirrhosis is the greatest challenge effecting the prognosis of these patients.The aim of this study was to evaluate the efficacy of sirolimus on the prognosis for these recipients.Methods:The data from 193 consecutive HCC patients who had undergone LT from January 2015 to December 2019 were retrospectively analyzed.These patients were divided into the sirolimus group[patients took sirolimus combined with calcineurin inhibitors(CNIs)(n=125)]and non-sirolimus group[patients took CNI-based therapy without sirolimus(n=68)].Recurrence-free survival(RFS)and overall survival(OS)were compared between the two groups.The prognostic factors and independent risk factors for RFS and OS were further evaluated.Results:Non-sirolimus was an independent risk factor for RFS(HR=2.990;95%CI:1.050-8.470;P=0.040)and OS(HR=3.100;95%CI:1.190-8.000;P=0.020).A higher proportion of patients beyond Hangzhou criteria was divided into the sirolimus group(69.6%vs.80.9%,P=0.030).Compared with the non-sirolimus group,the sirolimus group had significantly better RFS(P<0.001)and OS(P<0.001).Further subgroup analysis showed similar results.Conclusions:This study demonstrated that sirolimus significantly decreased HCC recurrence and prolonged RFS and OS in LT patients with different stage of HCC.展开更多
AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the i...AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the immunosuppressive compounds sirolimus and tacrolimus alone and in combination on cells of human hepatocellular carcinoma.METHODS: We used the human cell lines SK-Hep 1 and Hep 3B derived from hepatocellular carcinoma. Proliferation analyses after treatment with sirolimus, tacrolimus, or the combination of both were performed. FACS analyses were done to reveal cell cycle changes and apoptotic cell death. The expression of apoptosis-related proteins was estimated by Western blots.RESULTS: Sirolimus alone or combined with tacrolimus inhibited the growth of both cell lines after 5 d by up to 35% in SK-Hep 1 cells, and by up to 68% in Hep 3B cells at 25 ng/mL. Tacrolimus alone stimulated the growth by 12% after 5 ng/mL and by 25% after 25 ng/mL in Hep 3B cells. We found an increase of apoptotic Hep 3B cells from 6 to 16%, and a G1-arrest in SK-Hep 1 cells with an increase of cells from 61 to 82%, when sirolimus and tacrolimus were combined. Bcl-2 was down-regulated in Hep 3B, but not in SK-Hep 1 cells after combined treatment.CONCLUSION: Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.展开更多
A 23-year-old male presented with a three-week-history of crampy abdominal pain and melaena.Colonoscopy revealed a friable mass filling the entire lumen of the cecum;histologically,it was classified as perivascular ep...A 23-year-old male presented with a three-week-history of crampy abdominal pain and melaena.Colonoscopy revealed a friable mass filling the entire lumen of the cecum;histologically,it was classified as perivascular epithelioid cell tumor(PEComa).An magnetic resonance imaging scan showed,in addition to the primary tumor,two large mesenteric lymph node metastases and four metastatic lesions in the liver.The patient underwent right hemicolectomy and left hemihepatectomy combined with wedge resections of metastases in the right lobe of the liver,the resection status was R0.Subsequently,the patient was treated with sirolimus.After 4 mo of adjuvant mammalian target of rapamycin inhibition he developed two new liver metastases and a local pelvic recurrence.The visible tumor formations were again excised surgically,this time the resection status was R2 with regard to the pelvic recurrence.The patient was treated with 12 cycles of doxorubicin and ifosfamide under which the disease was stable for 9 mo.The clinical course was then determined by rapid tumor growth in the pelvic cavity.Second line chemotherapy with gemcitabine and docetaxel was ineffective,and the patient died 23 mo after the onset of disease.This case report adds evidence that,in malignant PEComa,the mainstay of treatment is curative surgery.If not achievable,the effects of adjuvant or palliative chemotherapy are unpredictable.展开更多
AIM： To report a retrospective analysis of preliminary results of 36 patients who received sirolimus （SRL, Rapamune, rapamycin） in a consecutive cohort of 248 liver allograft recipients. METHODS： Thirty-six liver ...AIM： To report a retrospective analysis of preliminary results of 36 patients who received sirolimus （SRL, Rapamune, rapamycin） in a consecutive cohort of 248 liver allograft recipients. METHODS： Thirty-six liver transplant patients with hepatocellular carcinoma （HCC） who were switched to SRL- based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation （OLT） were divided into group A （n = 11）, those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B （n = 18）, and those who developed renal insuffidency caused by caldneurin inhibitor （CNI） were assigned to group C （n = 7） after OLT. RESULTS： The patients were followed up for a median of 10.4 mo （range, 3.8-19.1 mo） after conversion to SRL therapy and 12.3 mo （range, 5.1-34.4 too） after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% （12/18） patients （2 with progressive tumor, 7 with stable tumor and 3 without tumor） were still alive due to conversing to SRL and/ or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia （n = 2）, anemia （n = 8）, and oral aphthous ulcers （n = 7） found in our cohort were easily manageable. CONCLUSION： The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.展开更多
BACKGROUND: Calcineur ininhibitor-related renal toxicity affects patient and graft survival in transplant recipients. This study aimed to determine whether sirolimus is effective and safe in treating renal insufficien...BACKGROUND: Calcineur ininhibitor-related renal toxicity affects patient and graft survival in transplant recipients. This study aimed to determine whether sirolimus is effective and safe in treating renal insufficiency related to tacrolimus after liver transplantation. METHODS: Tacrolimus for primary immunosuppression was used in 16 patients after liver transplantation. Patients with a creatinine level higher than 132.6 mu mol/L were eligible for conversion to sirolimus. Simultaneously, the dose of tacrolimus was decreased to half. Blood urea nitrogen, creatinine, tacrolimus level, liver function and rejection episodes were monitored dynamically. RESULTS: All patients showed improvement of renal function after conversion to sirolimus. Blood creatinine level was reduced from 146.8 +/- 92.4 to 105.3 +/- 71.3 mu mol/L (P<0.05). One patient had an acute rejection episode that was successfully treated with pulsed corticosteroids and low-dose tacrolimus. The side-effects of sirolimus included hyperlipidemia (4 patients) and leukocytopenia (2). CONCLUSION: Sirolimus can be safely used in liver transplant recipients suffering from tacrolimus-related renal insufficiency.展开更多
BACKGROUND Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α(HIF-1α)in the immune microenvironment promotes the progression of hepatocellular carcinoma(HCC),leading to enhanced ...BACKGROUND Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α(HIF-1α)in the immune microenvironment promotes the progression of hepatocellular carcinoma(HCC),leading to enhanced drug resistance in cancer cells.Therefore,altering the immunosuppressive microenvironment by improving the hypoxic state is a new goal in improving cancer treatment.AIM To analyse the role of HIF-1α,which is closely related to tumour proliferation,invasion,metastasis,and angiogenesis,in the proliferation and invasion of liver cancer,and to explore the HIF-1αpathway-mediated anti-cancer mechanism of sirolimus(SRL)combined with Huai Er.METHODS Previous studies on HCC tissues identified the importance of HIF-1α,glucose transporter 1(GLUT1),and lactate dehydrogenase A(LDHA)expression.In this study,HepG2 and Huh7 cell lines were treated,under hypoxic and normoxic conditions,with a combination of SRL and Huai Er.The effects on proliferation,invasion,cell cycle,and apoptosis were analysed.Proteomics and genomics techniques were used to analyze the HIF-1α-related signalling pathway during SRL combined with Huai Er treatment and its inhibition of the proliferation of HCC cells.RESULTS High levels of HIF-1α,LDHA,and GLUT-1 were found in poorly differentiated HCC,with lower patient survival rates.Hypoxia promoted the proliferation of HepG2 and Huh7 cells and weakened the apoptosis and cell cycle blocking effects of the SRL/Huai Er treatment.This was achieved by activation of HIF-1αand glycolysis in HCC,leading to the upregulation of LDHA,GLUT-1,Akt/mammalian target of rapamycin(mTOR),vascular endothelial growth factor(VEGF),and Forkhead box P3 and downregulation of phosphatase and tensin homolog deleted on chromosome ten(PTEN)and p27.The hypoxia-induced activation of HIF-1αshowed the greatest attenuation in the SRL/Huai Er(S50+H8)group compared to the drug treatments alone(P<0.001).The S50+H8 treatment significantly downregulated the expression of mTOR and HIF-1α,and significantly reduced the expression of VEGF mRNA.Meanwhile,the combined blocking of mTOR and HIF-1αenhanced the downregulation of Akt/mTOR,HIF-1α,LDHA,and GLUT-1 mRNA and resulted in the downregulation of PTEN,p27,and VEGF mRNA(P<0.001).CONCLUSION SRL increases the anti-cancer effect of Huai Er,which reduces the promotion of hypoxia-induced HIF-1αon the Warburg effect by inhibition of the PI3K/Akt/mTOR-HIF-1αand HIF-1α-PTEN signalling pathways in HCC.展开更多
A case of hepatocellular carcinoma (HCC) with pulmonary recurrence after liver transplantation for HCC is presented in this report. The patient showed disease progression on sorafenib therapy demonstrated by computed ...A case of hepatocellular carcinoma (HCC) with pulmonary recurrence after liver transplantation for HCC is presented in this report. The patient showed disease progression on sorafenib therapy demonstrated by computed tomography scans as well as serial serum α-fetoprotein (AFP) elevation. After his immunosuppression therapy was successfully transitioned to sirolimus and a continuation of sorafenib, he achieved partial remission based on RECIST criteria and normalization of AFP. Mammalian target of rapamycin inhibitors including sirolimus alone or in conjunction with sorafenib may be useful in the treatment of post transplant HCC.展开更多
AIM： To evaluate the efficacy and the safety of combined 5-Fluorouracil, irinotecan, bevacizumab and sirolimus in refractory advanced colorectal carcinoma. METHODS： We initiated a regimen with at day 1 an injection ...AIM： To evaluate the efficacy and the safety of combined 5-Fluorouracil, irinotecan, bevacizumab and sirolimus in refractory advanced colorectal carcinoma. METHODS： We initiated a regimen with at day 1 an injection （iv） of bevacizumab at 5 mg/kg, followed by 180 mg/m^2 irinotecan, followed by Leucovorin 400 mg/m^2, followed by a 5-Fluorouracil bolus 400 mg/m^2 and a 46-h infusion 2400 mg/m^2. Sirolimus was given orally as continuous administration of 2 mg twice a day every days. This treatment was repeated every 14 d. RESULTS： A total of 12 patients were enrolled. All patients presented with metastatic disease that had failed at least three lines of chemotherapy that contained oxaliplatin, irinotecan and bevacizumab. Cetuximab failure was also observed in all K-Ras wildtype patients. The median number of cycles was 8.5 （range 2-20） and clinical benefit was observed in eight patients. The median time to progression was 5 mo and the median survival was 8 too. Grade 3 neutropenia developed in four patients, and grade 3 diarrhea and stomatitis in two.CONCLUSION： The combination regimen of 5-Fluorouracil,irinotecan, bevacizumab and sirolimus in advanced colorectal carcinoma after failure of dassical be.absent is feasible and promising. Further evaluation of this combination is required.展开更多
Sirolimus is an immunosuppressant with expanding use in pediatric organ transplantation, dermatology and rheumatology. We report two cases of children who developed asthma like symptoms and were diagnosed with interst...Sirolimus is an immunosuppressant with expanding use in pediatric organ transplantation, dermatology and rheumatology. We report two cases of children who developed asthma like symptoms and were diagnosed with interstitial lung disease, which responded to discontinuation of sirolimus. Pediatricians should be aware about the pulmonary side effects of sirolimus.展开更多
Background: The efficacy and safety of conversion treatment with sirolimus in renal transplant recipients using the calcineurin inhibitor (CNI) with one or more risk factors was evaluated. Methods: Ninety-three renal ...Background: The efficacy and safety of conversion treatment with sirolimus in renal transplant recipients using the calcineurin inhibitor (CNI) with one or more risk factors was evaluated. Methods: Ninety-three renal transplant recipients were prospectively enrolled. CNIs(CsA and FK506) as main immunosuppressant were converted to SRL immunosuppressant protocol. Rapid conversion with si-rolimus was performed in all patients. The CNI withdrawal was in 2 weeks. At 4 hours after oral administration of cyclosporin A or tacrolimus, the patients took sirolimus. Initial dose of sirolimus was 6 mg, and repeated maintenance dose is 1.0 - 2.0 mg/d. The first concentration of sirolimus was detected at 5 - 7 days after first oral administration, and the target concentration was 6 - 10 μg/L. Results: The symptoms were markedly improved in patients with CNI induced renal toxicity and CNI induced liver toxicity, and the concentration of sirolimus were maintained at (5.1 ± 1.2) μg/L. Serum creatinine levels decreased from (297.72 ± 150.28) μmol/L to (123.76 ± 44.2) μmol/L, and the liver function were recovery in 24 (92.3%) patients. 9 patients with high glucose returned to normal, and 2 patients were improved. Serum creatinine levels decreased more than 25% of primary level in 17 patients, and the effective rate was 51.5%. 10 patients with tumor were appeared 6 - 43 months after renal transplantation, no recurrence was found in 8 of them and 2 patients were dead. Acute rejections were occurred in 3 patients at 6 months after conversion treatment. The complications were included hyperlipidemia and proteinuria. 3 patients were dead, 6 patients returned to dialysis treatment, and 2 patients were removal of grafts. At 3 years after conversion treatment, the survival rates of patients and grafts were 90.9% and 75.8%, respectively. Conclusion: The conversion treatment with SRL and MMF may be a better option for the renal transplant recipients using the CNI with risk factors appeared.展开更多
Since the approval of the first stent by the US Food and Drug Administration,stents have been developed from bare metal stents to advanced forms such as drug-eluting stent(DES).However,after being inserted into damage...Since the approval of the first stent by the US Food and Drug Administration,stents have been developed from bare metal stents to advanced forms such as drug-eluting stent(DES).However,after being inserted into damaged coronary arteries,even modern DES still has some problems such as late thrombosis or irregular drug release[1,2].展开更多
Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipie...Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.展开更多
Objective:To investigate the clinical application of sirolimus (SRL) in renal post-transplant which included sirolimus in place of mycophenolate mofetil. Their clinical course was evaluated during the first 6 months a...Objective:To investigate the clinical application of sirolimus (SRL) in renal post-transplant which included sirolimus in place of mycophenolate mofetil. Their clinical course was evaluated during the first 6 months after surgery. Maintenance immunosuppression included sirolimus, corticosteroid and cyclosporine. Sirolimus dosing was initiated at 6 mg on the first day, from then on 1.2-1.5 mg as a single daily dose and adjusted to maintain the levels at 5-15 ng/ml. 25 cases were treated with SRL combined group). Results: Patients' graft survival rate was 100％. There was no significant difference in average serum creatinine level and incidence of acute rejection between SRL group and MMF group[10.0％ (2/20)vs 11.4％ (4/35), P＞0. 05]. During the follow-up period, the incidence of side effect was similar in SRL group or MMF group, except for hyperlipidemia in SRL group. Sirolimus was discontinued in 5 patients for adverse events predominantly for numbness of oral lip, delayed renal allograft function, poor wound healing, liver or kidney function injury and pneumonitis. Conclusion: Early outcomes with sirolimus were acceptable with 100％ graft survival and 10. 0％ incidence of acute rejection. However, because of adverse events including poor wound healing and pneumonitis, the immunosuppression regimen of SRL combined with low dose of CsA has been limited to clinical application in some degree in early transplant recipients. As one of therapeutical choices, it has been a long way to investigate SRL in clinical extension.展开更多
BACKGROUND Blue rubber bleb naevus syndrome(BRBNS)is a rare disease that usually presents with multiple venous malformations in the skin and gastrointestinal tract.Lesions located in the gastrointestinal tract always ...BACKGROUND Blue rubber bleb naevus syndrome(BRBNS)is a rare disease that usually presents with multiple venous malformations in the skin and gastrointestinal tract.Lesions located in the gastrointestinal tract always result in chronic gastrointestinal bleeding and severe anemia.The successful management of BRBNS with sirolimus had been reported in many institutions,due to its impact on signaling pathways of angiogenesis.However,the experience in treatment of neonates with BRBNS was limited.CASE SUMMARY A 38-day-old premature female infant born with multiple skin lesions,presented to our center complaining of severe anemia and hematochezia.Laboratory examination demonstrated that hemoglobin was 5.3 g/dL and contrast-enhanced abdominal computed tomography showed multiple low-density space-occupying lesions in the right lobe of the liver.She was diagnosed as having BRBNS based on typical clinical and examination findings.The patient was treated by transfusions twice and hemostatic drugs but symptoms of anemia were difficult to alleviate.A review of BRBNS case reports found that patients had been successfully treated with sirolimus.Then the patient was treated with sirolimus at an average dose of 0.95 mg/m2/d with a target drug level of 10-15 ng/mL.During 28 mo of treatment,the lesion was reduced,hemoglobin returned to normal,and there were no adverse drug reactions.CONCLUSION This case highlights the dosing regimen and plasma concentration in neonates,for the current common empiric dose is high.展开更多
Liver transplantation(LT) withstands as the most preferred therapeutic option for patients afflicted with hepatocellular carcinoma(HCC) and cirrhosis. To improve prognosis post-transplant, as well as to prevent the oc...Liver transplantation(LT) withstands as the most preferred therapeutic option for patients afflicted with hepatocellular carcinoma(HCC) and cirrhosis. To improve prognosis post-transplant, as well as to prevent the occurrence of rejection, a lifelong immunosuppression strategy is implemented. The following letter to the editor highlights and provides novel evidence from recently published literature on topics discussed within the review article titled “Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma” in World J Gastrointest Surg 2021;13: 953-966. In the recent manuscript, the authors compared immunosuppressive drugs such as the newer option first-generation mammalian target of rapamycin inhibitor, also known as sirolimus, with the most widely used first-generation calcineurin inhibitors, such as tacrolimus(TAC). TAC is commonly known as the most effective immunosuppressive drug after LT, but it has been reported to cause intolerable side effects such as nephrotoxicity,neurotoxicity, diabetes, hypertension, gastrointestinal disturbances, increased risk of infections, and malignancies. It is necessary for physicians to be aware of recent advances in tacrolimus and sirolimus therapies to compare and understand distinctly the effectiveness and tolerability of these drugs. This will assist clinicians in making the best treatment decisions and improve the clinical prognosis of LT recipients with HCC.展开更多
Background:To investigate the effect of sirolimus(SRL)eye drops on acute alkali-burn-induced corneal neovascularization(CNV)and explore its possible mechanism.Methods:A total of 57 male Sprague-Dawley rats weighing 16...Background:To investigate the effect of sirolimus(SRL)eye drops on acute alkali-burn-induced corneal neovascularization(CNV)and explore its possible mechanism.Methods:A total of 57 male Sprague-Dawley rats weighing 160-180 g were randomly divided into four groups including a normal control group(NC group,n=12),an untreated alkali-burned model control group(MC group,n=15),a blank eye drop treatment group(BT group,n=15),and an SRL eye drop treatment group(ST group,n=15).Corneal inflammation and CNV were observed and scored under a slit-lamp microscope 3,7,and 14 days after alkali exposure.Three rats were randomly sacrificed in each group before modeling and 3,7,14 days after modeling,and the corneas of right eyes were harvested for Western blotting to compare the expression levels of VEGFR2 and caspase-3.Results:Corneal inflammation scoring showed that the corneal edema and conjunctival congestion were severe in the MC,BT,and ST groups 1 day after alkali exposure but were alleviated at day 3.The corneal transparency was significantly higher in the ST group than in the MC and BT groups at days 7(F=9.77,P<0.05)and 14(F=5.81,P<0.05).At day 1,the corneal limbal vascular network was markedly filled.SNV was obvious at days 3,7,and 14.The new blood vessels were shorter and sparser in the ST group than in the MC and BT groups,and the CNV scores showed significant differences among these groups(day 3:F=8.60,P<0.05;day 7:F=11.40,P<0.05;and day 14:F=41.59,P<0.01).Western blotting showed that the expressions of VEGFR2 and caspase-3 were low before modeling and showed no significant difference among the different groups(F=0.52,P>0.05;F=0.98,P>0.05).The corneal expression of VEGFR2 became significantly higher in the MC and BT groups than in the ST group 3,7,and 14 days after alkali exposure,and there were significant differences in relative gray-scale values among these groups(day 3:F=32.16,P<0.01;day 7:F=85.96,P<0.01;day 14:F=57.68,P<0.01).The increase in the corneal expression of caspase-3 was significantly larger in the ST group than in the MC and BT groups at days 3,7,and 14,and there were significant differences in relative gray-scale values among groups(day 3:F=32.16,P<0.01;day 7:F=53.02,P<0.01;day 14:F=38.67,P<0.01).Conclusions:SRL eye drops can alleviate acute alkali-burn-induced corneal inflammation and inhibit alkali-burn-induced CNV in rat models.It can reduce VEGFR2 expression and increase caspase-3 expression in the corneal tissue,which may contribute to the inhibition of alkali-burn-induced CNV.展开更多
BACKGROUND Biodegradable polymer drug-eluting stents(BP-DES)have shown to reduce restenosis rates and have low rates of stent thrombosis.The present postmarketing surveillance assessed 1-year clinical outcomes of pati...BACKGROUND Biodegradable polymer drug-eluting stents(BP-DES)have shown to reduce restenosis rates and have low rates of stent thrombosis.The present postmarketing surveillance assessed 1-year clinical outcomes of patients who had received Neo Hexa DES in real practice.AIM To investigate 1-year clinical outcomes of Neohexa DES in real practice.METHODS Data obtained from a single-center cohort of patients who had received Neo Hexa stents as part of routine treatment of coronary artery disease(CAD)were retrospectively investigated.The primary study endpoint was the rate of major adverse cardiac events(MACEs)defined as the composite of death,myocardial infarction(MI),and target lesion revascularization(TLR)during the follow-up at1 mo,6 mo,and 1 year after the index procedure.RESULTS A total of 129 patients with 172 lesions were enrolled.The most common comorbid conditions were hypertension(49.61%)and diabetes mellitus(39.53%).Procedural success was achieved in all patients,and no in-hospital MACE was reported.The incidence of composite MACE at 30 d,6 mo,and 1 year was 0.78%,3.94%,and 4.87%,respectively.The rate of possible and probable late stent thrombosis was 0.78%.The cumulative incidences of death,MI,and TLR at 1 year were 2.44%,0.81%,and 1.63%,respectively.CONCLUSION The relatively low rates of MACE and stent thrombosis in this study support safety and performance of Neo Hexa stents,suggesting it to be an effective alternative to other contemporary stents for the treatment of de novo lesions in native coronary arteries.展开更多
Objective To investigate the effect of sirolimus ( SRL) on the expression of integrin αυβ3 mRNA in vascular smooth muscle cells of cardiac allografts in rats, and the possible mechanism of SRL in the prevention of ...Objective To investigate the effect of sirolimus ( SRL) on the expression of integrin αυβ3 mRNA in vascular smooth muscle cells of cardiac allografts in rats, and the possible mechanism of SRL in the prevention of cardiac allograft vasculopathy. Methods Heterotopic heart transplantation models were established Hearts展开更多
Background Renal angiomyolipoma(RAML)is the most common kidney lesion in patients with tuberous sclerosis complex(TSC),affecting about 80%of patients.It is a benign tumor that grows over time,usually bilaterally,and c...Background Renal angiomyolipoma(RAML)is the most common kidney lesion in patients with tuberous sclerosis complex(TSC),affecting about 80%of patients.It is a benign tumor that grows over time,usually bilaterally,and can easily lead to kidney complications such as acute hemorrhage.Herein,we investigated the efficacy and safety of sirolimus in children with TSC-associated RAML and explored the factors affecting tumor disappearance under sirolimus treatment through subgroup analysis.Methods A prospective cohort study was conducted.Sirolimus was initiated at 1 mg/(m^(2)×day),and dose adjustments were made by a 2-week titration period to attain a trough blood concentration of 5-10 ng/mL.The disappearance of RAML in chil-dren after sirolimus treatment was observed,and Cox regression was used to screen the factors affecting tumor disappearance.Results One hundred and twenty-six patients who met the criteria were analyzed.After 3 months,6 months,12 months,and 24 months of follow-up,tumors disappeared in 18(14.3%),30(23.8%),39(31.0%),and 42(33.3%)children,respec-tively.Tumors disappeared in 50(39.7%)children by the last visit of each individual,and 30(60%)of them occurred within 6 months.The multivariate Cox regression analysis showed that patients with a smaller maximum tumor diameter at baseline had a higher tumor disappearance rate.Thirty-six(29%)patients had stomatitis during the entire treatment period,and no serious adversereactionswereobserved.Conclusions Sirolimus could promote the disappearance of TSC-related RAML.The disappearance rate was correlated with the maximum diameter at baseline,and the smaller the tumor was,the higher the disappearance rate.It is well tolerated in the treatment of RAML associated with TSC.展开更多
基金supported by a grant from Post-Doctoral Applied Research Project of Qingdao City(RZ2000002871)。
文摘Background:Tumor recurrence after liver transplantation(LT)for selective patients diagnosed with hepatocellular carcinoma(HCC)in the setting of cirrhosis is the greatest challenge effecting the prognosis of these patients.The aim of this study was to evaluate the efficacy of sirolimus on the prognosis for these recipients.Methods:The data from 193 consecutive HCC patients who had undergone LT from January 2015 to December 2019 were retrospectively analyzed.These patients were divided into the sirolimus group[patients took sirolimus combined with calcineurin inhibitors(CNIs)(n=125)]and non-sirolimus group[patients took CNI-based therapy without sirolimus(n=68)].Recurrence-free survival(RFS)and overall survival(OS)were compared between the two groups.The prognostic factors and independent risk factors for RFS and OS were further evaluated.Results:Non-sirolimus was an independent risk factor for RFS(HR=2.990;95%CI:1.050-8.470;P=0.040)and OS(HR=3.100;95%CI:1.190-8.000;P=0.020).A higher proportion of patients beyond Hangzhou criteria was divided into the sirolimus group(69.6%vs.80.9%,P=0.030).Compared with the non-sirolimus group,the sirolimus group had significantly better RFS(P<0.001)and OS(P<0.001).Further subgroup analysis showed similar results.Conclusions:This study demonstrated that sirolimus significantly decreased HCC recurrence and prolonged RFS and OS in LT patients with different stage of HCC.
文摘AIM: Standard immunosuppression after organ transplantation stimulates tumor growth. Sirolimus has a strong antiproliferative and a tumor inhibiting effect. The purpose is to assess the effect on tumor growth of the immunosuppressive compounds sirolimus and tacrolimus alone and in combination on cells of human hepatocellular carcinoma.METHODS: We used the human cell lines SK-Hep 1 and Hep 3B derived from hepatocellular carcinoma. Proliferation analyses after treatment with sirolimus, tacrolimus, or the combination of both were performed. FACS analyses were done to reveal cell cycle changes and apoptotic cell death. The expression of apoptosis-related proteins was estimated by Western blots.RESULTS: Sirolimus alone or combined with tacrolimus inhibited the growth of both cell lines after 5 d by up to 35% in SK-Hep 1 cells, and by up to 68% in Hep 3B cells at 25 ng/mL. Tacrolimus alone stimulated the growth by 12% after 5 ng/mL and by 25% after 25 ng/mL in Hep 3B cells. We found an increase of apoptotic Hep 3B cells from 6 to 16%, and a G1-arrest in SK-Hep 1 cells with an increase of cells from 61 to 82%, when sirolimus and tacrolimus were combined. Bcl-2 was down-regulated in Hep 3B, but not in SK-Hep 1 cells after combined treatment.CONCLUSION: Sirolimus appears to inhibit the growth of hepatocellular carcinoma cells alone and in combination with tacrolimus. Sirolimus seems to inhibit the growth stimulation of tacrolimus.
文摘A 23-year-old male presented with a three-week-history of crampy abdominal pain and melaena.Colonoscopy revealed a friable mass filling the entire lumen of the cecum;histologically,it was classified as perivascular epithelioid cell tumor(PEComa).An magnetic resonance imaging scan showed,in addition to the primary tumor,two large mesenteric lymph node metastases and four metastatic lesions in the liver.The patient underwent right hemicolectomy and left hemihepatectomy combined with wedge resections of metastases in the right lobe of the liver,the resection status was R0.Subsequently,the patient was treated with sirolimus.After 4 mo of adjuvant mammalian target of rapamycin inhibition he developed two new liver metastases and a local pelvic recurrence.The visible tumor formations were again excised surgically,this time the resection status was R2 with regard to the pelvic recurrence.The patient was treated with 12 cycles of doxorubicin and ifosfamide under which the disease was stable for 9 mo.The clinical course was then determined by rapid tumor growth in the pelvic cavity.Second line chemotherapy with gemcitabine and docetaxel was ineffective,and the patient died 23 mo after the onset of disease.This case report adds evidence that,in malignant PEComa,the mainstay of treatment is curative surgery.If not achievable,the effects of adjuvant or palliative chemotherapy are unpredictable.
基金Supported by the key project grant of the Science and Technological Committee of Shanghai Municipality, No.024001119the Foundation for "New Star of Medicine" of Shanghai Health Bureau, No. 1999-59
文摘AIM： To report a retrospective analysis of preliminary results of 36 patients who received sirolimus （SRL, Rapamune, rapamycin） in a consecutive cohort of 248 liver allograft recipients. METHODS： Thirty-six liver transplant patients with hepatocellular carcinoma （HCC） who were switched to SRL- based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation （OLT） were divided into group A （n = 11）, those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B （n = 18）, and those who developed renal insuffidency caused by caldneurin inhibitor （CNI） were assigned to group C （n = 7） after OLT. RESULTS： The patients were followed up for a median of 10.4 mo （range, 3.8-19.1 mo） after conversion to SRL therapy and 12.3 mo （range, 5.1-34.4 too） after OLT. Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% （12/18） patients （2 with progressive tumor, 7 with stable tumor and 3 without tumor） were still alive due to conversing to SRL and/ or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia （n = 2）, anemia （n = 8）, and oral aphthous ulcers （n = 7） found in our cohort were easily manageable. CONCLUSION： The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.
文摘BACKGROUND: Calcineur ininhibitor-related renal toxicity affects patient and graft survival in transplant recipients. This study aimed to determine whether sirolimus is effective and safe in treating renal insufficiency related to tacrolimus after liver transplantation. METHODS: Tacrolimus for primary immunosuppression was used in 16 patients after liver transplantation. Patients with a creatinine level higher than 132.6 mu mol/L were eligible for conversion to sirolimus. Simultaneously, the dose of tacrolimus was decreased to half. Blood urea nitrogen, creatinine, tacrolimus level, liver function and rejection episodes were monitored dynamically. RESULTS: All patients showed improvement of renal function after conversion to sirolimus. Blood creatinine level was reduced from 146.8 +/- 92.4 to 105.3 +/- 71.3 mu mol/L (P<0.05). One patient had an acute rejection episode that was successfully treated with pulsed corticosteroids and low-dose tacrolimus. The side-effects of sirolimus included hyperlipidemia (4 patients) and leukocytopenia (2). CONCLUSION: Sirolimus can be safely used in liver transplant recipients suffering from tacrolimus-related renal insufficiency.
基金Supported by the Natural Science Foundation of Capital Medical University,No.PYZ20014 and No.PYZ21074。
文摘BACKGROUND Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α(HIF-1α)in the immune microenvironment promotes the progression of hepatocellular carcinoma(HCC),leading to enhanced drug resistance in cancer cells.Therefore,altering the immunosuppressive microenvironment by improving the hypoxic state is a new goal in improving cancer treatment.AIM To analyse the role of HIF-1α,which is closely related to tumour proliferation,invasion,metastasis,and angiogenesis,in the proliferation and invasion of liver cancer,and to explore the HIF-1αpathway-mediated anti-cancer mechanism of sirolimus(SRL)combined with Huai Er.METHODS Previous studies on HCC tissues identified the importance of HIF-1α,glucose transporter 1(GLUT1),and lactate dehydrogenase A(LDHA)expression.In this study,HepG2 and Huh7 cell lines were treated,under hypoxic and normoxic conditions,with a combination of SRL and Huai Er.The effects on proliferation,invasion,cell cycle,and apoptosis were analysed.Proteomics and genomics techniques were used to analyze the HIF-1α-related signalling pathway during SRL combined with Huai Er treatment and its inhibition of the proliferation of HCC cells.RESULTS High levels of HIF-1α,LDHA,and GLUT-1 were found in poorly differentiated HCC,with lower patient survival rates.Hypoxia promoted the proliferation of HepG2 and Huh7 cells and weakened the apoptosis and cell cycle blocking effects of the SRL/Huai Er treatment.This was achieved by activation of HIF-1αand glycolysis in HCC,leading to the upregulation of LDHA,GLUT-1,Akt/mammalian target of rapamycin(mTOR),vascular endothelial growth factor(VEGF),and Forkhead box P3 and downregulation of phosphatase and tensin homolog deleted on chromosome ten(PTEN)and p27.The hypoxia-induced activation of HIF-1αshowed the greatest attenuation in the SRL/Huai Er(S50+H8)group compared to the drug treatments alone(P<0.001).The S50+H8 treatment significantly downregulated the expression of mTOR and HIF-1α,and significantly reduced the expression of VEGF mRNA.Meanwhile,the combined blocking of mTOR and HIF-1αenhanced the downregulation of Akt/mTOR,HIF-1α,LDHA,and GLUT-1 mRNA and resulted in the downregulation of PTEN,p27,and VEGF mRNA(P<0.001).CONCLUSION SRL increases the anti-cancer effect of Huai Er,which reduces the promotion of hypoxia-induced HIF-1αon the Warburg effect by inhibition of the PI3K/Akt/mTOR-HIF-1αand HIF-1α-PTEN signalling pathways in HCC.
文摘A case of hepatocellular carcinoma (HCC) with pulmonary recurrence after liver transplantation for HCC is presented in this report. The patient showed disease progression on sorafenib therapy demonstrated by computed tomography scans as well as serial serum α-fetoprotein (AFP) elevation. After his immunosuppression therapy was successfully transitioned to sirolimus and a continuation of sorafenib, he achieved partial remission based on RECIST criteria and normalization of AFP. Mammalian target of rapamycin inhibitors including sirolimus alone or in conjunction with sorafenib may be useful in the treatment of post transplant HCC.
基金Supported by A Grant From Association Pour la Recherche Contre le Cancer,Ligue Régionale De Bourgogne Contre le Cancer,INSERM,Fondation de France and GERTI(Grouped' Etudeen Thérapeutique Inovante)Study number GERTI-P001
文摘AIM： To evaluate the efficacy and the safety of combined 5-Fluorouracil, irinotecan, bevacizumab and sirolimus in refractory advanced colorectal carcinoma. METHODS： We initiated a regimen with at day 1 an injection （iv） of bevacizumab at 5 mg/kg, followed by 180 mg/m^2 irinotecan, followed by Leucovorin 400 mg/m^2, followed by a 5-Fluorouracil bolus 400 mg/m^2 and a 46-h infusion 2400 mg/m^2. Sirolimus was given orally as continuous administration of 2 mg twice a day every days. This treatment was repeated every 14 d. RESULTS： A total of 12 patients were enrolled. All patients presented with metastatic disease that had failed at least three lines of chemotherapy that contained oxaliplatin, irinotecan and bevacizumab. Cetuximab failure was also observed in all K-Ras wildtype patients. The median number of cycles was 8.5 （range 2-20） and clinical benefit was observed in eight patients. The median time to progression was 5 mo and the median survival was 8 too. Grade 3 neutropenia developed in four patients, and grade 3 diarrhea and stomatitis in two.CONCLUSION： The combination regimen of 5-Fluorouracil,irinotecan, bevacizumab and sirolimus in advanced colorectal carcinoma after failure of dassical be.absent is feasible and promising. Further evaluation of this combination is required.
文摘Sirolimus is an immunosuppressant with expanding use in pediatric organ transplantation, dermatology and rheumatology. We report two cases of children who developed asthma like symptoms and were diagnosed with interstitial lung disease, which responded to discontinuation of sirolimus. Pediatricians should be aware about the pulmonary side effects of sirolimus.
文摘Background: The efficacy and safety of conversion treatment with sirolimus in renal transplant recipients using the calcineurin inhibitor (CNI) with one or more risk factors was evaluated. Methods: Ninety-three renal transplant recipients were prospectively enrolled. CNIs(CsA and FK506) as main immunosuppressant were converted to SRL immunosuppressant protocol. Rapid conversion with si-rolimus was performed in all patients. The CNI withdrawal was in 2 weeks. At 4 hours after oral administration of cyclosporin A or tacrolimus, the patients took sirolimus. Initial dose of sirolimus was 6 mg, and repeated maintenance dose is 1.0 - 2.0 mg/d. The first concentration of sirolimus was detected at 5 - 7 days after first oral administration, and the target concentration was 6 - 10 μg/L. Results: The symptoms were markedly improved in patients with CNI induced renal toxicity and CNI induced liver toxicity, and the concentration of sirolimus were maintained at (5.1 ± 1.2) μg/L. Serum creatinine levels decreased from (297.72 ± 150.28) μmol/L to (123.76 ± 44.2) μmol/L, and the liver function were recovery in 24 (92.3%) patients. 9 patients with high glucose returned to normal, and 2 patients were improved. Serum creatinine levels decreased more than 25% of primary level in 17 patients, and the effective rate was 51.5%. 10 patients with tumor were appeared 6 - 43 months after renal transplantation, no recurrence was found in 8 of them and 2 patients were dead. Acute rejections were occurred in 3 patients at 6 months after conversion treatment. The complications were included hyperlipidemia and proteinuria. 3 patients were dead, 6 patients returned to dialysis treatment, and 2 patients were removal of grafts. At 3 years after conversion treatment, the survival rates of patients and grafts were 90.9% and 75.8%, respectively. Conclusion: The conversion treatment with SRL and MMF may be a better option for the renal transplant recipients using the CNI with risk factors appeared.
文摘Since the approval of the first stent by the US Food and Drug Administration,stents have been developed from bare metal stents to advanced forms such as drug-eluting stent(DES).However,after being inserted into damaged coronary arteries,even modern DES still has some problems such as late thrombosis or irregular drug release[1,2].
基金supported by grants from the National S&T Major Project (2017ZX10203205)Key Program,National Natural Science Foundation of China (81930016)Zhejiang Provincial Natural Science Foundation of China (LY21H160026)。
文摘Mammalian target of rapamycin(m TOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant(LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival(RFS) in hepatocellular carcinoma(HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specifc for the frst 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefts for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data.
文摘Objective:To investigate the clinical application of sirolimus (SRL) in renal post-transplant which included sirolimus in place of mycophenolate mofetil. Their clinical course was evaluated during the first 6 months after surgery. Maintenance immunosuppression included sirolimus, corticosteroid and cyclosporine. Sirolimus dosing was initiated at 6 mg on the first day, from then on 1.2-1.5 mg as a single daily dose and adjusted to maintain the levels at 5-15 ng/ml. 25 cases were treated with SRL combined group). Results: Patients' graft survival rate was 100％. There was no significant difference in average serum creatinine level and incidence of acute rejection between SRL group and MMF group[10.0％ (2/20)vs 11.4％ (4/35), P＞0. 05]. During the follow-up period, the incidence of side effect was similar in SRL group or MMF group, except for hyperlipidemia in SRL group. Sirolimus was discontinued in 5 patients for adverse events predominantly for numbness of oral lip, delayed renal allograft function, poor wound healing, liver or kidney function injury and pneumonitis. Conclusion: Early outcomes with sirolimus were acceptable with 100％ graft survival and 10. 0％ incidence of acute rejection. However, because of adverse events including poor wound healing and pneumonitis, the immunosuppression regimen of SRL combined with low dose of CsA has been limited to clinical application in some degree in early transplant recipients. As one of therapeutical choices, it has been a long way to investigate SRL in clinical extension.
文摘BACKGROUND Blue rubber bleb naevus syndrome(BRBNS)is a rare disease that usually presents with multiple venous malformations in the skin and gastrointestinal tract.Lesions located in the gastrointestinal tract always result in chronic gastrointestinal bleeding and severe anemia.The successful management of BRBNS with sirolimus had been reported in many institutions,due to its impact on signaling pathways of angiogenesis.However,the experience in treatment of neonates with BRBNS was limited.CASE SUMMARY A 38-day-old premature female infant born with multiple skin lesions,presented to our center complaining of severe anemia and hematochezia.Laboratory examination demonstrated that hemoglobin was 5.3 g/dL and contrast-enhanced abdominal computed tomography showed multiple low-density space-occupying lesions in the right lobe of the liver.She was diagnosed as having BRBNS based on typical clinical and examination findings.The patient was treated by transfusions twice and hemostatic drugs but symptoms of anemia were difficult to alleviate.A review of BRBNS case reports found that patients had been successfully treated with sirolimus.Then the patient was treated with sirolimus at an average dose of 0.95 mg/m2/d with a target drug level of 10-15 ng/mL.During 28 mo of treatment,the lesion was reduced,hemoglobin returned to normal,and there were no adverse drug reactions.CONCLUSION This case highlights the dosing regimen and plasma concentration in neonates,for the current common empiric dose is high.
文摘Liver transplantation(LT) withstands as the most preferred therapeutic option for patients afflicted with hepatocellular carcinoma(HCC) and cirrhosis. To improve prognosis post-transplant, as well as to prevent the occurrence of rejection, a lifelong immunosuppression strategy is implemented. The following letter to the editor highlights and provides novel evidence from recently published literature on topics discussed within the review article titled “Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma” in World J Gastrointest Surg 2021;13: 953-966. In the recent manuscript, the authors compared immunosuppressive drugs such as the newer option first-generation mammalian target of rapamycin inhibitor, also known as sirolimus, with the most widely used first-generation calcineurin inhibitors, such as tacrolimus(TAC). TAC is commonly known as the most effective immunosuppressive drug after LT, but it has been reported to cause intolerable side effects such as nephrotoxicity,neurotoxicity, diabetes, hypertension, gastrointestinal disturbances, increased risk of infections, and malignancies. It is necessary for physicians to be aware of recent advances in tacrolimus and sirolimus therapies to compare and understand distinctly the effectiveness and tolerability of these drugs. This will assist clinicians in making the best treatment decisions and improve the clinical prognosis of LT recipients with HCC.
基金Supported by the Guangdong Natural Science Foundation(2016A030313294).
文摘Background:To investigate the effect of sirolimus(SRL)eye drops on acute alkali-burn-induced corneal neovascularization(CNV)and explore its possible mechanism.Methods:A total of 57 male Sprague-Dawley rats weighing 160-180 g were randomly divided into four groups including a normal control group(NC group,n=12),an untreated alkali-burned model control group(MC group,n=15),a blank eye drop treatment group(BT group,n=15),and an SRL eye drop treatment group(ST group,n=15).Corneal inflammation and CNV were observed and scored under a slit-lamp microscope 3,7,and 14 days after alkali exposure.Three rats were randomly sacrificed in each group before modeling and 3,7,14 days after modeling,and the corneas of right eyes were harvested for Western blotting to compare the expression levels of VEGFR2 and caspase-3.Results:Corneal inflammation scoring showed that the corneal edema and conjunctival congestion were severe in the MC,BT,and ST groups 1 day after alkali exposure but were alleviated at day 3.The corneal transparency was significantly higher in the ST group than in the MC and BT groups at days 7(F=9.77,P<0.05)and 14(F=5.81,P<0.05).At day 1,the corneal limbal vascular network was markedly filled.SNV was obvious at days 3,7,and 14.The new blood vessels were shorter and sparser in the ST group than in the MC and BT groups,and the CNV scores showed significant differences among these groups(day 3:F=8.60,P<0.05;day 7:F=11.40,P<0.05;and day 14:F=41.59,P<0.01).Western blotting showed that the expressions of VEGFR2 and caspase-3 were low before modeling and showed no significant difference among the different groups(F=0.52,P>0.05;F=0.98,P>0.05).The corneal expression of VEGFR2 became significantly higher in the MC and BT groups than in the ST group 3,7,and 14 days after alkali exposure,and there were significant differences in relative gray-scale values among these groups(day 3:F=32.16,P<0.01;day 7:F=85.96,P<0.01;day 14:F=57.68,P<0.01).The increase in the corneal expression of caspase-3 was significantly larger in the ST group than in the MC and BT groups at days 3,7,and 14,and there were significant differences in relative gray-scale values among groups(day 3:F=32.16,P<0.01;day 7:F=53.02,P<0.01;day 14:F=38.67,P<0.01).Conclusions:SRL eye drops can alleviate acute alkali-burn-induced corneal inflammation and inhibit alkali-burn-induced CNV in rat models.It can reduce VEGFR2 expression and increase caspase-3 expression in the corneal tissue,which may contribute to the inhibition of alkali-burn-induced CNV.
基金Supported by the Sahajanand Laser Technology Ltd,India
文摘BACKGROUND Biodegradable polymer drug-eluting stents(BP-DES)have shown to reduce restenosis rates and have low rates of stent thrombosis.The present postmarketing surveillance assessed 1-year clinical outcomes of patients who had received Neo Hexa DES in real practice.AIM To investigate 1-year clinical outcomes of Neohexa DES in real practice.METHODS Data obtained from a single-center cohort of patients who had received Neo Hexa stents as part of routine treatment of coronary artery disease(CAD)were retrospectively investigated.The primary study endpoint was the rate of major adverse cardiac events(MACEs)defined as the composite of death,myocardial infarction(MI),and target lesion revascularization(TLR)during the follow-up at1 mo,6 mo,and 1 year after the index procedure.RESULTS A total of 129 patients with 172 lesions were enrolled.The most common comorbid conditions were hypertension(49.61%)and diabetes mellitus(39.53%).Procedural success was achieved in all patients,and no in-hospital MACE was reported.The incidence of composite MACE at 30 d,6 mo,and 1 year was 0.78%,3.94%,and 4.87%,respectively.The rate of possible and probable late stent thrombosis was 0.78%.The cumulative incidences of death,MI,and TLR at 1 year were 2.44%,0.81%,and 1.63%,respectively.CONCLUSION The relatively low rates of MACE and stent thrombosis in this study support safety and performance of Neo Hexa stents,suggesting it to be an effective alternative to other contemporary stents for the treatment of de novo lesions in native coronary arteries.
文摘Objective To investigate the effect of sirolimus ( SRL) on the expression of integrin αυβ3 mRNA in vascular smooth muscle cells of cardiac allografts in rats, and the possible mechanism of SRL in the prevention of cardiac allograft vasculopathy. Methods Heterotopic heart transplantation models were established Hearts
基金funded by the Capital's Funds for Health Improvement and Research(No.2022-1-5081)National Key Research and Development Program of China(No.2016YFC1000707).
文摘Background Renal angiomyolipoma(RAML)is the most common kidney lesion in patients with tuberous sclerosis complex(TSC),affecting about 80%of patients.It is a benign tumor that grows over time,usually bilaterally,and can easily lead to kidney complications such as acute hemorrhage.Herein,we investigated the efficacy and safety of sirolimus in children with TSC-associated RAML and explored the factors affecting tumor disappearance under sirolimus treatment through subgroup analysis.Methods A prospective cohort study was conducted.Sirolimus was initiated at 1 mg/(m^(2)×day),and dose adjustments were made by a 2-week titration period to attain a trough blood concentration of 5-10 ng/mL.The disappearance of RAML in chil-dren after sirolimus treatment was observed,and Cox regression was used to screen the factors affecting tumor disappearance.Results One hundred and twenty-six patients who met the criteria were analyzed.After 3 months,6 months,12 months,and 24 months of follow-up,tumors disappeared in 18(14.3%),30(23.8%),39(31.0%),and 42(33.3%)children,respec-tively.Tumors disappeared in 50(39.7%)children by the last visit of each individual,and 30(60%)of them occurred within 6 months.The multivariate Cox regression analysis showed that patients with a smaller maximum tumor diameter at baseline had a higher tumor disappearance rate.Thirty-six(29%)patients had stomatitis during the entire treatment period,and no serious adversereactionswereobserved.Conclusions Sirolimus could promote the disappearance of TSC-related RAML.The disappearance rate was correlated with the maximum diameter at baseline,and the smaller the tumor was,the higher the disappearance rate.It is well tolerated in the treatment of RAML associated with TSC.
