BACKGROUND:Acute myocardial infarction can cause cardiac remodeling and heart failure,as well as skeletal myopathy,affecting patients'quality of life.Exercise therapy is an important rehabilitation method for patients with heart failure;however,the optimal exercise prescription has not been clarified. OBJECTIVE:To compare the effects of different exercise modes(aerobic exercise,resistance exercise)on skeletal muscle remodeling in rats with acute myocardial infarction induced heart failure and to explore the possible mechanism,so as to provide a basis for optimizing the exercise rehabilitation program. METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham operation group,myocardial infarction group,aerobic exercise group and resistance exercise group.Coronary artery ligation was used to create model of heart failure.After 3 months,animals in the aerobic exercise group and resistance exercise group underwent 12 weeks of corresponding exercise mode interventions,while those in the sham operation group and myocardial infarction group were kept quietly in mouse cages.After the experiment,maximal running speed and maximal weight-bearing load were measured by graded treadmill exercise test and ladder-climbing test respectively,and heart structure and function were evaluated by echocardiography.The heart was isolated,and hematoxylin-eosin staining and Sirius red staining were performed to detect cardiac remodeling.For the gstrocnemius muscle,ATPase staining was performed to observe changes in muscle fiber type and cell cross-sectional area,dihydroethidium method was used to evaluate reactive oxygen species levels,enzyme-linked immunosorbent method was used to determine malondialdehyde content and antioxidant enzyme activity,western blot was used to determine the expression of ubiquitin-proteasome system proteins,and the number of activated satellite cells(Pax7+/MyoD+)were detected by double immunofluorescence staining. RESULTS AND CONCLUSION:(1)Exercise performance:Compared with the sham operation group,maximal running speed and maximal weight-bearing load in the myocardial infarction group decreased(P<0.05);compared with the myocardial infarction group,the maximal running speed of the aerobic exercise group and the maximal weight-bearing load of the resistance exercise group increased(P<0.05).(2)Cardiac remodeling:Compared with the sham operation group,infarction area,myocardial cell cross-sectional area,and collagen content in the myocardial infarction group increased(P<0.05),while leftventricular ejection fraction and shortening fraction decreased(P<0.05);compared with the myocardial infarction group,there was no statistical difference in the above parameters in both aerobic exercise resistance exercise groups(P>0.05).(3)Skeletal muscle remodeling:Compared with the sham operation group,gastrocnemius muscle mass,gastrocnemius muscle mass index,cell cross-sectional area,superoxide dismutase activity,glutathione peroxidase activity,and the number of activated satellite cells decreased in myocardial infarction group(P<0.05),while reactive oxygen species content,malondialdehyde content,and the protein expression of ubiquitin,MuRF1 and MAFbx increased(P<0.05);compared with the myocardial infarction group,gastrocnemius muscle mass index,superoxide dismutase activity,the number of activated satellite cells increased in both aerobic exercise and resistance exercise groups(P<0.05),while reactive oxygen species content and the protein expression of ubiquitin,MuRF1,and MAFbx decreased(P<0.05);compared with the aerobic exercise group,gastrocnemius muscle mass,gastrocnemius muscle mass index,cell cross-sectional area,reactive oxygen species content,malondialdehyde content,the number of activated satellite cells increased in resistance exercise group(P<0.05),while superoxide dismutase activity,glutathione peroxidase activity down-regulated(P<0.05).To conclude,aerobic exercise and resistance exercise can both improve exercise performance of rats with heart failure,and the mechanism is related to reducing oxidative stress,inhibiting ubiquitin-proteasome system activity and activating satellite cells to improve skeletal muscle remodeling.Aerobic exercise has a better effect on improving skeletal muscle oxidative stress,while resistance exercise has a more significant effect on promoting skeletal muscle regeneration.

BACKGROUND:Stem cell transplantation is a novel therapy for myocardial infarction,but the extremely hostile microenvironment in the infarct area results in low survival rate of stem cells and little long-term effect.Exercise preconditioning is a way to induce endogenous protective effects through exercise,which can be used as a new strategy for prevention and treatment of cardiac rehabilitation. OBJECTIVE:To evaluate whether exercise preconditioning potentiates the cardioprotective effects of adipose-derived stem cell transplantation following myocardial infarction in rats and to explore the mechanism of angiogenesis. METHODS:Six-week-old male SD rats were randomly divided into control group,modeling group,stem cell group,and stem cell plus exercise group.Acute myocardial infarction model was made by coronary artery occlusion,and sham operation was performed in control group.The stem cell plus exercise group underwent aerobic exercise for 8 weeks before modeling,and adipose-derived stem cell transplantation was performed 30 minutes after modeling.The stem cell group performed only adipose-derived stem cell transplantation.One and seven days after stem cell transplantation,the expression levels of myocardial total Akt(t-Akt),phosphorylated Akt(p-Akt),vascular endothelial growth factor(VEGF),total endothelial nitric oxide synthase(t-eNOS),and phosphorylated endothelial nitric oxide synthase(p-eNOS)protein were measured by western blotting,and the ratios of p-Akt/t-Akt and p-eNOS/t-eNOS were calculated.At 4 weeks after stem cell transplantation,the heart structure and function as well as myocardial blood flow were detected by color Doppler ultrasound diagnostic system.Myocardial infarction area was measured by TTC staining.Myocardial interstitial collagen deposition was examined by Masson staining.Myocardial capillary density was detected by immunofluorescence staining,and myocardial apoptosis was measured by TUNEL staining. RESULTS AND CONCLUSION:(1)Four weeks after stem cell transplantation:Compared with control group,left ventricular shortening fraction,left ventricular ejection fraction,myocardial capillary density,and myocardial blood flow decreased(P<0.05),myocardial infarction area,collagen volume fraction,and apoptosis increased(P<0.05)in the modeling group.Compared with the modeling group,the above indexes(except for left ventricular fractional shortening and left ventricular ejection fraction)in the stem cell group improved(P<0.05).Compared with the stem cell group,the above parameters were further improved in the stem cell plus exercise group(P<0.05).(2)One day after stem cell transplantation:Compared with the control group,the protein expression of t-Akt,p-Akt,VEGF,t-eNOS,p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS had no significant changes in the modeling group(P>0.05).Compared with the modeling group,there were no significant changes in the above indexes in the stem cell group(P>0.05),and p-Akt protein expression and the ratio of p-Akt/t-Akt were up-regulated in the stem cell plus exercise group(P<0.05).(3)Seven days after stem cell transplantation:Compared with the control group,the protein expression of p-Akt,VEGF,p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were decreased in the modeling group(P<0.05).Compared with the modeling group,there were no significant changes in all parameters in the stem cell group(P>0.05),and the protein expression of p-Akt,VEGF p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were increased in the stem cell plus exercise group(P<0.05).These findings confirm that exercise preconditioning can potentiate the therapeutic effect of adipose-derived stem cells on cardiac remodeling in rats with myocardial infarction,and its mechanism is associated with the promotion of myocardial angiogenesis and blood perfusion.

BACKGROUND:Exercise is an effective strategy to prevent and treat various cardiovascular diseases and protect the heart from ischemia-reperfusion injury.Its mechanism of action needs to be studied in depth. OBJECTIVE:To observe the effect of aerobic exercise preconditioning on myocardial ischemia-reperfusion injury and to explore the effect of endothelial nitric oxide synthase(eNOS)activation(including coupling and phosphorylation). METHODS:Eighty adult Wistar rats were randomly divided into sedentary(n=40)and exercise(n=40)groups.The rats in the exercise group were subjected to aerobic exercise for 8 weeks while those in the sedentary group were quietly fed and caged.After 8 weeks of intervention,three experiments were performed.(1)Experiment 1:After the last training,cardiac function,cardiac nitric oxide metabolite content and cardiac eNOS,phosphorylated eNOS-S1177,eNOS dimer and eNOS monomer protein expression levels were detected.(2)Experiment 2:Rats were divided into sedentary control group,exercise control group,sedentary+eNOS inhibitor group,exercise+eNOS inhibitor group,all of which were subjected to an in vitro myocardial ischemia-reperfusion injury experiment.eNOS inhibitor was continuously infused into the sedentary+eNOS inhibitor group and exercise+eNOS inhibitor group 10 minutes before reperfusion,and cardiac function and myocardial infarction area were detected 3 hours after reperfusion.(3)Experiment 3:Rats were divided into sedentary control group,exercise control group,sedentary+eNOS coupler group and exercise+eNOS coupler group,all of which were subjected to an in vitro myocardial ischemia-reperfusion injury experiment.The rats in the sedentary+eNOS coupler group and exercise+eNOS coupler group were treated with eNOS coupler.Myocardial infarct area,cardiac nitric oxide metabolite content,cardiac protein expression of eNOS,phosphorylated eNOS-S1177,eNOS dimer,eNOS monomer and 3-nitrotyrosine were detected 3 hours after reperfusion.The phosphorylated eNOS-S1177/eNOS ratio reflected the phosphorylated/dephosphorylated level of eNOS and eNOS dimer/monomer ratio reflected eNOS coupling/uncoupling level. RESULTS AND CONCLUSION:Experiment 1:Compared with the sedentary group,the exercise group had increased cardiac output and left ventricular ejection fraction(P<0.05),increased nitrite and S-nitrosothiol contents(P<0.05),upregulated phosphorylated eNOS-S1177,eNOS protein expression and phosphorylated eNOS-S1177/eNOS ratio(P<0.05),eNOS dimer protein expression and eNOS dimer/monomer ratios were elevated(P<0.05).Experiment 2:Compared with the sedentary control group,left ventricular development pressure increased(P<0.05)and myocardial infarct area decreased(P<0.05)in the exercise control group.Compared with the exercise control group,left ventricular development pressure decreased(P<0.05)and myocardial infarct area increased(P<0.05)in the exercise+eNOS inhibitor group.Experiment 3:Compared with the sedentary control group,the exercise control group had increased left ventricular developmental pressure(P<0.05),decreased myocardial infarct area(P<0.05),decreased phosphorylated eNOS-S1177/eNOS ratio(P<0.05),decreased eNOS dimer/monomer ratio(P<0.05),increased S-nitrosothiol content(P<0.05),and decreased 3-nitrotyrosine protein expression(P<0.05).Compared with the exercise control group,the exercise+eNOS coupler group had decreased left ventricular developmental pressure(P<0.05),increased myocardial infarct area(P<0.05),increased phosphorylated eNOS-S1177/eNOS ratio(P<0.05),increased eNOS dimer/monomer ratio(P<0.05),and elevated 3-nitro tyrosine protein expression(P<0.05).To conclude,aerobic exercise preconditioning could induce cardioprotection,which is related to uncoupling and dephosphorylation of eNOS during cardiac ischemia-reperfusion,thereby inhibiting the excessive production of nitric oxide and reducing nitro-oxidative stress.

BACKGROUND:Postmenopausal osteoporosis significantly increases the risk of fracture,which seriously affects the quality of life of patients.Exercise therapy is an important non-drug means and prevention and treatment strategy for patients with osteoporosis,in which strength training is the best mode,but its specific biological mechanism has not been determined. OBJECTIVE:To investigate the effects of strength training on bone morphology,materials and biomechanics in ovariectomized rats and to explore the mechanism of extracellular matrix remodeling. METHODS:Forty-eight female Sprague-Dawley rats were divided into sham operation group,sham operation exercise group,ovariectomized group and ovariectomized exercise group according to the random number table method.The menopausal animal model was established by bilateral ovariectomy in the ovariectomized group and ovariectomized exercise group,while sham operation was performed in the sham operation group and sham operation exercise group.Four weeks after operation,the sham operation exercise group and the ovariectomized exercise group underwent 12-week tail weight-bearing ladder training,and the sham operation group and the ovariectomized group were raised quietly in the cage.The bilateral femur and tibia were separated after training.The right tibia was used for dual-energy X-ray densitometry and biomechanical,biophysical and biochemical analyses,the left tibia was detected using micro-computed tomography for bone microstructural examination,the right femur was subjected to hematoxylin-eosin staining for histological observation,and the left femur was used for western blot and gelatin zymography detection of protein expression and enzyme activity of extracellular matrix metabolism-related factors,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximal load and stiffness decreased(P＜0.05),bone density,bone mineral density,bone inorganic matter content,bone calcium content decreased(P＜0.05),bone water content increased(P＜0.05),trabecular bone volume fraction,trabecular connectivity density,and trabecular number decreased(P＜0.05),trabecular separation,structural model index increased(P＜0.05),bone adipocyte number and cross-sectional area increased(P＜0.05),matrix metalloproteinase-2 activity decreased(P＜0.05),and protein expression of tissue inhibitor of metalloproteinase-1 and osteoprotegerin increased(P＜0.05)in the ovariectomized group.Compared with the ovariectomized group,the maximal load,stiffness,fracture load and resilience increased(P＜0.05),bone mineral density,bone mineral content,bone mineral density,bone inorganic matter content,and bone calcium content increased(P＜0.05),bone water content decreased(P＜0.05),trabecular separation and bone marrow area decreased(P＜0.05),trabecular bone thickness,cortical bone volume fraction,cortical bone area fraction,cortical bone thickness,and cortical bone porosity increased(P＜0.05),bone adipocyte number and cross-sectional area reduced(P＜0.05),matrix metalloproteinase-2 activity increased(P＜0.05),and protein expression of tissue inhibitor of metalloproteinase-1,Runt-related transcription factor 2 and osteoprotegerin decreased(P＜0.05)in the ovariectomized exercise group.To conclude,strength training can protect against bone injury caused by estrogen deficiency,which is characterized by improvement of bone biomechanical properties,bone tissue composition and bone microstructure,and its mechanism is related to the regulation of extracellular matrix remodeling.

BACKGROUND:Stem cell therapy is an alternative treatment strategy for restoring damaged myocardial tissue after acute myocardial infarction.Exercise preconditioning can induce endogenous cardioprotective effects in the body.However,the efficacy and mechanism of the combined application are still unclear. OBJECTIVE:To explore the effect and possible mechanism of exercise preconditioning combined with bone marrow mesenchymal stem cells on the therapeutic effect in rats with acute myocardial infarction. METHODS:Seventy male SD rats were randomly divided into sham operation group,model group,stem cell therapy group,exercise preconditioning group,and combined intervention group.Rats in the exercise preconditioning group and combined intervention group underwent 8-week aerobic exercise on the treadmill before modeling.The animal model of acute myocardial infarction was made by ligating the anterior descending coronary artery.The stem cell therapy group and the combined intervention group were injected with bone marrow mesenchymal stem cells(1×109 L-1,1 mL)through the tail vein the next day after modeling.After 4 weeks of treatment,the exercise performance was evaluated by a graded treadmill exercise test.The cardiac structure and function were detected by echocardiography.The left ventricle was isolated.2,3,5-Triphenyltetrazolium chloride staining was used to evaluate myocardial infarct size.Masson staining was used to obtain collagen volume fraction.CD31 immunohistochemical staining was used to detect myocardial capillary density.TUNEL staining was used to detect myocardial cell apoptosis.Immunoblotting was used to detect protein expression levels of stromal cell-derived factor 1,CXC chemokine receptor protein 4,tumor necrosis factor-α,interleukin-10,and vascular endothelial growth factor. RESULTS AND CONCLUSION:(1)Intervention efficacy:Compared with the sham operation group,exercise performance,left ventricular ejection fraction,left ventricular fractional shortening,and CD31 positive cell rate decreased(P<0.05);myocardial infarct size,collagen volume fraction,and myocardial apoptotic rate increased(P<0.05)in the model group.Compared with the model group,exercise performance was not statistically significant(P>0.05)in the stem cell therapy group,and the exercise performance improved(P<0.05)in the exercise preconditioning and combined intervention groups;left ventricular ejection fraction,left ventricular fractional shortening,and CD31 positive cell rate increased(P<0.05),and the myocardial infarct size,collagen volume fraction,and cardiomyocyte apoptosis rate decreased(P<0.05)in the stem cell therapy,exercise preconditioning,and combined intervention groups.Compared with the stem cell therapy group,exercise performance,left ventricular ejection fraction,left ventricular shortening fraction,and CD31 positive cell rate increased(P<0.05),myocardial infarct size,collagen volume fraction,and myocardial cell apoptosis rate decreased(P<0.05)in the combined intervention group.(2)Protein expression:Compared with the sham operation group,the expression of tumor necrosis factor-α increased(P<0.05),while interleukin-10 and vascular endothelial growth factor expression decreased(P<0.05)in the model group.Compared with the model group,the expression of CXC chemokine receptor protein 4 increased(P<0.05)in the stem cell therapy group and combined intervention group,and the expression of tumor necrosis factor-α decreased(P<0.05)while interleukin-10 and vascular endothelial growth factor increased(P<0.05)in the stem cell therapy group,exercise preconditioning group,and combined intervention group.Compared with the stem cell therapy group,the expression of tumor necrosis factor-α decreased(P<0.05),while CXC chemokine receptor protein 4,interleukin-10,and vascular endothelial growth factor increased(P<0.05)in the combined intervention group.To conclude,exercise preconditioning can enhance the therapeutic effect of bone marrow mesenchymal stem cells in rats with acute myocardial infarction,which can inhibit cardiac remodeling,improve cardiac function,and delay the progress of heart failure.Its mechanism is related to the promotion of stem cell homing,inhibition of inflammatory response,and promotion of angiogenesis.

BACKGROUND:Exercise training is an important non-drug rehabilitation method for many heart diseases,and it can also enhance the heart's tolerance to adverse stressors(such as myocardial ischemia),that is,exercise preconditioning.Granulocyte colony-stimulating factor can effectively mobilize stem cell homing and differentiation and promote the repair of damaged myocardium.However,the effect of the combination of the two treatments is not yet clear. OBJECTIVE:To explore the effect of granulocyte colony-stimulating factor supplementation combined with high-intensity intermittent exercise preconditioning on cardiac remodeling in rats with acute myocardial infarction and investigate its possible mechanism. METHODS:Totally 58 male Wistar rats were divided into sham group(n=10),model group(n=12),model drug group(n=12),model exercise group(n=12)and model combined treatment group(n=12).The myocardial infarction rat model was made by coronary artery ligation.The model exercise group and the model combined treatment group were pretreated with 8 weeks of high-intensity intermittent exercise on an electric treadmill before modeling.The model drug group and the model combined treatment group were subcutaneously injected with human recombinant granulocyte colony-stimulating factor 3 hours after modeling for 5 days(10 μg/kg per day).At 8 weeks after administration,echocardiography was used to detect heart structure and function;heart was stained with 2,3,5-triphenyltetrazolium chloride and Masson staining to obtain myocardial infarct area and collagen volume fraction,respectively.Vessel density and cell apoptosis rate were detected by immunofluorescence.Real-time fluorescent quantitative PCR was utilized to detect the mRNA expression of embryonic genes(brain natriuretic peptide,β-myosin heavy chain)and myocardial contraction regulatory factors(α-myosin heavy chain,sarcoplasmic reticulum Ca2+-ATPase).Western blot assay was used to detect the protein expression of cardiac stromal cell-derived factor 1,CXC chemokine receptor protein 4,Janus kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3),Bcl2,Bax,and cleaved caspase-3. RESULTS AND CONCLUSION:(1)Compared with sham group,myocardial infarct size,collagen volume fraction,and apoptosis rate increased(P<0.05);vessel density,left ventricular fractional shortening,and left ventricular ejection fraction decreased(P<0.05);brain natriuretic peptide and β-myosin heavy chain mRNA increased(P<0.05),α-myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase mRNA and α-myosin heavy chain/β-myosin heavy chain ratio decreased(P<0.05);stromal cell-derived factor 1,CXC chemokine receptor protein 4,Bax,cleaved caspase-3 protein expression increased(P<0.05);p-JAK2,p-STAT3,and Bcl-2 protein expression decreased(P<0.05)in the model group.(2)Compared with the model group,the above indexes in the model drug and model exercise groups were significantly improved(P<0.05).Compared with the model drug and model exercise groups,the above parameters were further ameliorated(P<0.05)in the model combined treatment group.(3)The results showed that supplementation of granulocyte colony-stimulating factor or high-intensity intermittent exercise preconditioning alone can improve cardiac remodeling in rats with acute myocardial infarction,and the combined therapy has a better effect,which may be related to the induction of stem cell homing and the activation of JAK2/STAT3 signaling pathway to inhibit cardiomyocyte apoptosis.

Objective:To explore the impact of early and late antibody-mediated rejection (AMR) on treatment options and allograft outcomes after kidney transplantation (KT).Methods:From January 2013 to December 2022, the study retrospectively enrolled 141 KT allograft recipients receiving allograft biopsy and diagnosed as AMR according to the Banff 2019 criteria. Recipients with a diagnosis of AMR within 30 days post-KT were classified into early AMR group (n=19) while the remainders assigned as late AMR group (n=122). The outcome endpoints included recipient survival rate, death-censored graft survival rate, follow-up estimated glomerular filtration rate (eGFR) and immunodominant donor-specific antibody (DSA) intensity. Wilcoxon's test was utilized for assessing the differences in eGFR and DSA intensity while Kaplan-Meier curve and Log-rank test were employed for evaluating graft survival impact. Treatment regimens for AMR were collected and categorized.Results:The median follow-up duration was 2.6(1.2, 5.2) year. No graft failure was noted in early AMR group while 44 recipients in late AMR group experienced graft failure, with 34 cases (77.2%) due to AMR progression. The 5-year death-censored graft survival rate was significantly better in early AMR group than that in late AMR group [100% vs 60.1%(50.5%, 71.6%), P=0.002]. The one-year change in eGFR for early AMR group was significantly superior to that of late AMR group [19.3(-2.6, 38.1) vs -3.3(-14.0, 5.4), P=0.001]. One-year mean fluorescent intensity (MFI) of early AMR group was 1 158(401.5, 3 126.5). It was significantly lower than that when diagnosed with early AMR [3 120.5(2 392.8, 9 340.0)] and one-year MFI of late AMR group [8 094(2 251.5, 13 560.5)] ( P=0.005, P<0.001). Early AMR group primarily received standard treatment (3/19, 15.8%) and regimens centered on rituximab and/or bortezomib (7/19, 43.8%). Late AMR group mainly received standard (16/122, 13.1%) or intensified regimens (9/122, 7.4%) and regimens focused upon rituximab and/or bortezomib (32/122, 26.2%) and MP monotherapy (21/122, 17.2%). Conclusion:The outcome for early AMR is significantly better than that for late AMR. For early AMR, early and robust immunosuppression is recommended. For late AMR, early detection and timely treatment are crucial and individualized strategies should be implemented.

Objective:To explore the morbidity features and therapeutic outcomes of rejections in pediatric kidney transplantation (KT) recipients.Methods:Between January 2013 and June 2022, 360 children undergoing KT were recruited.The relevant clinical data were collected for examining the morbidity features and therapeutic outcomes of rejections.The serum levels of creatinine were compared among groups by non-parametric rank test.And Kaplan-Meier and Log-rank methods were employed for examining the incidence of rejection and comparing mortality-censored graft survival rates among patients with different times of rejection.Results:A total of 58 recipients had 82 incidents of rejection with a cumulative incidence of 6.3%, 9.2% and 11.3% at 3/6/12 months respectively.Among 50 incidents of biopsy-proved rejections, the types were T cell-mediated rejection [TCMR, 42.0%(21/50)], antibody-mediated rejection [20.0%(10/50), ABMR] and mixed rejection [38.0%(19/50)].Among 58 incidents of initial rejection, 69% had maintained graft function (MGF) and 31% impaired graft function (IGF) after anti-rejection regimens.Among 80.8%, 85.7% and 75% of recipients with clinical rejection, ABMR or borderline rejection while 36.4% in TCMR patients had MGF.Fifteen kidney allografts lost function in 58 recipients with rejection.Five-year death-censored graft survival was significantly lower in patients with two or more incidents of rejection (30.5%, 95% CI: 12.3%-75.4%) than in those without rejection (92.9%, 95% CI: 89.3%-96.6%) ( P<0.000 1) or with only one rejection (82.9%, 95% CI: 65.9%-100%)( P<0.001). Conclusions:The rejection rate remains high in KT children and it affects graft survival.And TCMR is more likely to cause impaired graft function.Recurrent rejections have a more pronounced impact upon graft survival.

This report describs 2 domestic cases of tacrolimus poisoning in kidney transplant recipients due to overexposure of tacrolimus caused by nirmatrelvir/ritonavir for SARS-CoV-2 infection.Phenytoin sodium is prescribed for inducing CYP3A enzyme.It is intended for providing references for formulating and adjusting treatment protocols for tacrolimus overexposure and related toxicity in kidney transplant recipients caused by nirmatrelvir/ritonavir.

Objective:To explore the diagnosis and treatment of transplanted renal artery stenosis(TRAS)in children.Methods:From January 2016 to August 2021, clinical data of 7 TRAS patients were collected.A definite diagnosis was confirmed by Doppler ultrasound and computed tomography angiography.Results:Patient age was significantly higher than donor age(11.9±3.7 vs 1.0±0.5 years, P<0.001); 5 patients had a widened diameter at stenotic grafted renal artery after intervention(1.98±0.47 vs 4.64±1.19 mm, P=0.002). A reduction in peak systolic flow velocity in stenotic segment of artery(463.3±90.6 vs 183.6±58.9 cm/s, P<0.001)and lower systolic blood pressure(137.2±15.5 vs 129.7±12.3 mmHg, P=0.029)were observed.Resistance index rose(0.38±0.22 vs 0.60±0.03, P=0.063). Significant difference of estimated glomerular filtration rate was observed at Week 4 post-operation as compared with pre-intervention.Two patients developed complications after intervention, including perirenal hematoma and stent-attached thrombus.Two patients were treated conservatively with a gradual increase in blood pressure and three antihypertensive drugs prescribed. Conclusions:Doppler ultrasound should be performed regularly after renal transplantation for detecting TRAS at an early stage in children.Interventional treatment is ideal for severe TRAS to improve perfusion and renal function.Clinicians should pay more attention to complications.