There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Objective To investigate the effects of 16-week Tai Chi exercise on muscle strength,plantar tactile sensation,kinesthesia,and postural control of older adults at different ages.Methods Thirty-nine older adults were divided into 60-75-year-old group(n=24)and the 76-90-year-old group(n=15),and both groups received Tai Chi practice for 16 weeks.The muscle strength,plantar tactile sensation,kinesthesia,and center of pressure root mean square(CoP-RMS)were measured before and after practice.Results After 16 weeks of Tai Chi exercise,the fifth metatarsal head tactile sensation and ankle dorsiflexion/plantarflexion kinesthesia thresholds decreased in the 76-90-year-old group.However,there was no significant change in the 60-75-year-old group.The CoP-RMS in the medial/lateral direction decreased in the 60-75-year-old and 76-90-year-old group.Conclusions After 16 weeks of Tai Chi exercise,muscle strength,plantar tactile sensation,kinesthesia,and postural control were improved.Especially for older adults aged over 75 years,Tai Chi exercise improved their plantar tactile sensation,kinesthesia,and postural control to a greater extent.Tai Chi practice provides a suitable and effective exercise form for older adults over 75 years.

Parkinson's disease(PD)is the second most prevalent neurodegenerative disease and a major cause of movement disorders.Neuroinflammation plays an important role in the pathogenesis of PD.Icilin is a small molecule compound that has been reported to inhibit inflammation.Howev-er,its role in PD has not been reported.This study explored the effects of icilin on motor behavior,nerve damage,microglia activation,and neuroinflammation in MPTP-induced PD Meriones unguic-ulatus by behavioral experiments,immunohistochemistry,Western blot,and fluorescence quantifi-cation.The results showed that Icilin not only ameliorated motor dysfunction and neurological damage in MPTP-induced Meriones unguiculatus,but also inhibited microglia hyperactivation and its mediated neuroinflammation.The present study provides an evidence that icilin attenuates MPTP-induced neurodegenerative lesions in long-pawed gerbils,suggesting that it is a promising candidate for PD.

Objective To analyze the risk factors for chronic mountain sickness(CMS)in young male migrants living in high-altitude areas and to construct a diagnostic model and evaluate its diagnostic efficacy.Methods From June 10 to December 29,2023,a cross-sectional study was conducted on young male migrants subjected with convenience sampling who had been living in high-altitude areas(4 500～5 000 m)for 6 months or longer.Their demographic data were collected and blood samples were collected for laboratory test.According to the Qinghai Score for Chronic Mountain Sickness,they were divided into CMS group and non-CMS group.Then the participants were randomly divided into a training set and a test set in a ratio of 8∶2.Independent risk factors for CMS occurrence were screened out,through random forest variable importance ranking,univariate and multivariable logistic regression analysis,and a diagnostic model was constructed based on these factors.Receiver operating characteristic(ROC)curve analysis,calibration curve analysis,clinical decision curve analysis,and influence curve analysis were used to comprehensively evaluate the diagnostic performance of the model.Results According to the inclusion and exclusion criteria,308 out of 376 participants were finally subjected,and 17.53%of them were diagnosed with CMS.The major clinical symptoms of the CMS patients were dyspnea or palpitations(79.63%)and sleep disorders(85.19%).Further analysis revealed that creatine kinase-MB/creatine kinase(CK-MB/CK,OR=2.17,95%CI:1.43～3.28),high-altitude residence time(OR=2.44,95%CI:1.08～5.54),and body mass index(BMI,OR=1.62,95%CI:1.05～2.50)were 3 major independent risk factors for CMS.The area under the curve(AUC)value of the CMS diagnostic model in the training set and test set was 0.821(95%CI:0.756～0.886)and 0.821(95%CI:0.700～0.944),the specificity was 66.30%and 73.90%,the sensitivity was 89.50%and 81.20%,respectively,indicating good discrimination ability.Hosmer-Lemeshow goodness-of-fit test showed consistency between predicted results and actual observations(χ2=10.029,P=0.263;χ2=4.477,P=0.812).Clinical decision curve analysis demonstrated that within the threshold probability range from 0.1 to 0.7,the net benefit of the model exceeded both full intervention and no intervention strategies.The influence curve analysis showed high consistency between the model predictions and actual incidence when the threshold probability exceeded 0.4.These two analyses together confirmed the clinical application value of the model.Conclusion CK-MB/CK,high-altitude residence time and BMI are independent risk factors for CMS,and their diagnostic model helps identify potential individuals at risk for CMS.Early intervention can prevent the harm of CMS to the health of young men migrating to high-altitude areas.

Objective: To evaluate the efficacy and prognosis of loop cutaneous ureterostomy (LCU) in the treatment of primary obstructive megaureter (POM) with severe hydroureteronephrosis (HUN) in infants under 1 year of age，so as to provide reference for infants unsuitable for stage-Ⅰ ureteral reimplantation. Methods: A retrospective analysis was conducted on 12 infants with POM and severe HUN treated with LCU in our hospital during Jan.2019 and Dec.2023.The clinical characteristics，surgical techniques，indications，postoperative complications，stage-Ⅱ surgical approaches，and follow-up outcomes were summarized. Results: All operations were successful，with an average operation time of (37.08±7.53) min (6 left-sided LCU and 6 right-sided LCU).During the mean follow-up of (10.12±2.70) months，all infants showed clinical improvement，with complete resolution or significant alleviation of hydronephrosis，reduced ureteral diameter，and increased renal cortical thickness.Complications included asymptomatic bacteriuria in 3 cases (25%) and urinary tract infection (UTI) in 1 case，all resolved with oral antibiotics.Four cases developed peristomal rashes，which improved with topical treatment.Eleven infants underwent stage-Ⅱ Cohen ureterovesical reimplantation at a mean age of (15.20±2.07) months.Notably，27.3%(3/11) required ureteral tailoring or plication during reimplantation，which reduced the risk of ischemic necrosis from excessive trimming.During the follow-up of (22.17±13.93) months，hydronephrosis and renal function improved，and no febrile UTI or bladder dysfunction occurred. Conclusion: LCU is a safe and effective method，which can provide adequate urinary drainage，relieve obstruction，stabilize renal function，and allow time for ureteral maturation and renal parenchymal recovery.LCU also facilitates subsequent stage-Ⅱ surgery by reducing ureteral dilation.

Objective:To investigate the staging of cardiovascular-kidney-metabolic (CKM) syndrome before onset, and to analyze its impact on short-term prognosis in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 993 patients with AMI from January 2017 to December 2023 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The basic information, baseline data, in-hospital data, cardiac-related examination results, CKM syndrome staging and in-hospital outcomes were recorded.Results:Among the 2 993 patients with AMI, the CKM syndrome stage 0 was in 23 cases (0.77%), stage 1 in 35 cases (1.17%), stage 2 in 2 015 cases (67.32%), stage 3 to 4 in 920 cases (30.74%). The male proportion, high density lipoprotein-cholesterol (HDL-C) and neutrophil-to-lymphocyte ratio in patients with CKM syndrome stage 0 and 1 were significantly higher than those in patients with CKM syndrome stage 2 and 3 to 4, the hypertension proportion, diabetes proportion, chronic kidney disease proportion, triglyceride (TG), glycated hemoglobin (HbA 1c) and creatinine were significantly lower than those in patients with CKM syndrome 2 stage 3 to 4, and there were statistical differences ( P<0.05); the body mass index (BMI) and non-ST-elevation myocardial infarction (NSTEMI) proportion in patients with CKM syndrome stage 0 were significantly lower than those in patients with CKM syndrome stage 1, 2 and 3 to 4, and there were statistical differences ( P<0.05); the cerebrovascular diseases proportion, Killip stage ≥3 proportion, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left main coronary artery lesions proportion in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4, and there were statistical differences ( P<0.05); the global registry of acute coronary events score (GRACE score) in patients with CKM syndrome stage 0 was significantly lower than that in patients with CKM syndrome stage 3 to 4, and there was statistical difference ( P<0.05). Although there were statistical differences in low density lipoprotein-cholesterol (LDL-C) and number of blood vessels involved among the four groups ( P<0.05), but pairwise comparisons showed no statistically significant differences ( P>0.05). There were no statistical differences in age, smoking history, hyperlipidemia, high-sensitivity C-reactive protein, uric acid, cardiac troponin I (cTnI) peak, left ventricular ejection fraction and left ventricular end-diastolic diameter among the four groups ( P>0.05). The incidence of in-hospital major adverse coronary events (MACE) was 10.76% (322/2 993). Among them, the incidence of MACE, all-cause mortality and longer length of stay in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4: 4.35% (1/23), 8.57% (3/35) and 8.59% (173/2 015) vs. 15.76% (145/920), 0, 2.86% (1/35) and 2.38% (48/2 015) vs. 4.78% (44/920), (8.17 ± 3.87), (8.15 ± 5.32) and (8.89 ± 6.42) d vs. (9.81 ± 9.29) d, and there were statistical differences ( P<0.05); the incidences of acute kidney injury and atrial fibrillation in patients with CKM syndrome stage 0 and 1 were significantly lower than those in patients with CKM syndrome stage 2 and 3 to 4: 8.70% (2/23) and 8.57% (3/35) vs. 24.17% (487/2 015) and 34.35% (316/920), 0 and 0 vs. 3.52% (71/2 015) and 10.00% (92/920), and there were statistical differences ( P<0.05); there were no statistical differences in the incidences of ventricular tachycardia/ventricular fibrillation, cardiac arrest, mechanical complications and mechanical circulatory support among the four groups ( P>0.05). Conclusions:The severity of CKM syndrome is closely related to the occurrence of AMI. CKM patients with higher CKM stages have more severe AMI and poorer in-hospital prognosis. CKM syndrome staging can serve as a potential prognostic indicator for AMI patients.

BACKGROUND:It has been proved that induced pluripotent stem cells can differentiate into cardiomyocytes,but there are few reports on the maturity of differentiated cardiomyocytes.OBJECTIVE:To explore the effect of prolonging the induced differentiation time on the morphology,sarcomere length,binuclear cell content,cardiac gene expression,cardiac protein expression,and mitochondrial function of cardiomyocytes derived from induced pluripotent stem cells.METHODS:Bone morphogenetic protein 4,CH IR 99021,and IWR1 were used to induce pluripotent stem cells to differentiate into cardiomyocytes,and differentiated cardiomyocytes were collected on days 20 and 40 respectively.The expression levels of cardiac genes and proteins in differentiated cardiomyocytes were detected by RT-PCR and immunofluorescence,respectively.LAS X image analysis software was used to analyze the morphology and sarcomere length of differentiated cardiomyocytes.MitoTracker Green FM mitochondrial staining was used to detect total mitochondria.JC-1 mitochondrial staining was used to detect mitochondrial membrane potential.RESULTS AND CONCLUSION:Differentiated card io myocytes on day 40 had longer cell circumference and sarcomere length,and larger cell area than those on day 20(P＜0.05).The proportion of multinucleated cells rose sharply from about 16％on day 20 to about 29％on day 40(P＜0.05).Differentiated cardiomyocytes on day 40 had gene expression levels that were more similar to those of the primary cardiomyocytes,and the expression levels of SERCA2A,Cx-43,and α-MHC genes were significantly higher than on day 20(P＜0.05).Compared with the differentiated cardiomyocytes on day 20,the expression density of TNNT2 and α-MHC protein was relatively higher,the distribution density of mitochondria was larger,and the number of functional mitochondria was greater on day 40(P＜0.05).The results show that prolonging the induced differentiation time can increase the maturity of differentiated cardiomyocytes by increasing the length of sarcomere and the number of functional mitochondria,as well as improving the expression levels of cardiac genes and proteins.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Parkinson's disease(PD)is the second most prevalent neurodegenerative disease and a major cause of movement disorders.Neuroinflammation plays an important role in the pathogenesis of PD.Icilin is a small molecule compound that has been reported to inhibit inflammation.Howev-er,its role in PD has not been reported.This study explored the effects of icilin on motor behavior,nerve damage,microglia activation,and neuroinflammation in MPTP-induced PD Meriones unguic-ulatus by behavioral experiments,immunohistochemistry,Western blot,and fluorescence quantifi-cation.The results showed that Icilin not only ameliorated motor dysfunction and neurological damage in MPTP-induced Meriones unguiculatus,but also inhibited microglia hyperactivation and its mediated neuroinflammation.The present study provides an evidence that icilin attenuates MPTP-induced neurodegenerative lesions in long-pawed gerbils,suggesting that it is a promising candidate for PD.

Objective:To investigate the staging of cardiovascular-kidney-metabolic (CKM) syndrome before onset, and to analyze its impact on short-term prognosis in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 993 patients with AMI from January 2017 to December 2023 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The basic information, baseline data, in-hospital data, cardiac-related examination results, CKM syndrome staging and in-hospital outcomes were recorded.Results:Among the 2 993 patients with AMI, the CKM syndrome stage 0 was in 23 cases (0.77%), stage 1 in 35 cases (1.17%), stage 2 in 2 015 cases (67.32%), stage 3 to 4 in 920 cases (30.74%). The male proportion, high density lipoprotein-cholesterol (HDL-C) and neutrophil-to-lymphocyte ratio in patients with CKM syndrome stage 0 and 1 were significantly higher than those in patients with CKM syndrome stage 2 and 3 to 4, the hypertension proportion, diabetes proportion, chronic kidney disease proportion, triglyceride (TG), glycated hemoglobin (HbA 1c) and creatinine were significantly lower than those in patients with CKM syndrome 2 stage 3 to 4, and there were statistical differences ( P<0.05); the body mass index (BMI) and non-ST-elevation myocardial infarction (NSTEMI) proportion in patients with CKM syndrome stage 0 were significantly lower than those in patients with CKM syndrome stage 1, 2 and 3 to 4, and there were statistical differences ( P<0.05); the cerebrovascular diseases proportion, Killip stage ≥3 proportion, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left main coronary artery lesions proportion in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4, and there were statistical differences ( P<0.05); the global registry of acute coronary events score (GRACE score) in patients with CKM syndrome stage 0 was significantly lower than that in patients with CKM syndrome stage 3 to 4, and there was statistical difference ( P<0.05). Although there were statistical differences in low density lipoprotein-cholesterol (LDL-C) and number of blood vessels involved among the four groups ( P<0.05), but pairwise comparisons showed no statistically significant differences ( P>0.05). There were no statistical differences in age, smoking history, hyperlipidemia, high-sensitivity C-reactive protein, uric acid, cardiac troponin I (cTnI) peak, left ventricular ejection fraction and left ventricular end-diastolic diameter among the four groups ( P>0.05). The incidence of in-hospital major adverse coronary events (MACE) was 10.76% (322/2 993). Among them, the incidence of MACE, all-cause mortality and longer length of stay in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4: 4.35% (1/23), 8.57% (3/35) and 8.59% (173/2 015) vs. 15.76% (145/920), 0, 2.86% (1/35) and 2.38% (48/2 015) vs. 4.78% (44/920), (8.17 ± 3.87), (8.15 ± 5.32) and (8.89 ± 6.42) d vs. (9.81 ± 9.29) d, and there were statistical differences ( P<0.05); the incidences of acute kidney injury and atrial fibrillation in patients with CKM syndrome stage 0 and 1 were significantly lower than those in patients with CKM syndrome stage 2 and 3 to 4: 8.70% (2/23) and 8.57% (3/35) vs. 24.17% (487/2 015) and 34.35% (316/920), 0 and 0 vs. 3.52% (71/2 015) and 10.00% (92/920), and there were statistical differences ( P<0.05); there were no statistical differences in the incidences of ventricular tachycardia/ventricular fibrillation, cardiac arrest, mechanical complications and mechanical circulatory support among the four groups ( P>0.05). Conclusions:The severity of CKM syndrome is closely related to the occurrence of AMI. CKM patients with higher CKM stages have more severe AMI and poorer in-hospital prognosis. CKM syndrome staging can serve as a potential prognostic indicator for AMI patients.