OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Objective To explore the neuroprotective effects and mechanisms of the sesquiterpene lactone compound ACT001 on rotenone(ROT)-induced Parkinson's disease(PD)model mouse.Methods SPF C57BL/6 mice were randomly divided into 6 groups,including control group,solvent control group,ROT model group,ACT001 5 mg/kg group(ROT+ACT001-5),ACT001 20 mg/kg group(ROT+ACT001-20),and levodopa(L-dopa)positive control group(ROT+L-dopa),with 9 mice in each group.The control group received an equivalent amount of intraperitoneal injection of saline,the solvent control group received an equivalent amount of rotenone solvent without rotenone,the remaining groups of mice were used to establish a PD mouse model by intraperitoneal injection of rotenone.Mice in different ACT001 dosage groups received intraperitoneal injections of high and low doses of ACT001,while the positive control group received levodopa intraperitoneally for 15 consecutive days.Behavioral changes in mice were assessed using open field,rotarod,pole-climbing,and balance beam tests.Immunofluorescence(IF)assay to detect the expression of tyrosine hydroxylase(TH)neurons,content of TH-positive fibers in the striatum and to detect the activation status of nigrostriatal microglia in the mouse midbrain;Real-time PCR was employed to measure the levels of interleukin(IL)-6,IL-1β,and tumor necrosis factor-α(TNF-α)in the substantia nigra of the mouse brain.Western blotting was used to measure the protein levels of TH,nuclear factor-κB(NF-κB)p65,NF-κB inhibitor α(IκBα),and phosphorylated IκBα(p-IκBα)in the substantia nigra of the mouse brain.Results Compared to the control group and the solvent control group,the rotenone-induced PD model group exhibited motor impairments in behavioral tests,a decrease in the number of TH positive neurons in the substantia nigra(P＜0.0001),decreased levels of TH-positive fibers in the striatum,activation of midbrain substantia microglia,and elevated levels of IL-6,IL-1β,TNF-α,p-IκBα,and NF-κB p65 expression.ACT001 significantly improved the behavioral impairments and substantia nigra damage in PD mice,increased the number of TH-positive neurons in the substantia nigra,increased levels of TH-positive fibers in the striatum,inhibition of microglial cell activation in the midbrain substantia nigra,and elevated the protein expression levels of IκBα while reducing the levels of IL-6,IL-1β,TNF-α,p-IκBα,and NF-κB p65 in the substantia nigra(P＜0.05).At a dose of 5 mg/kg,ACT001 significantly improved behavioral impairments in rotenone-induced PD mice,reduced the loss of dopaminergic neurons,and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the suppression of inflammation.In summary,the intervention of ACT001 in the rotenone-induced PD mouse model inhibited the inflammatory response in the midbrain,increased the number of TH-positive neurons,and augmented the population of dopaminergic neurons in the substantia nigra,exerting a protective effect on neurons.Conclusion ACT001 significantly improves behavioral deficits in ROT-induced PD mice,ameliorates of dopaminergic neuron loss from the midbrain substantia nigra and striatum,inhibits the activation of nigrostriatal microglia in the midbrain,and suppresses inflammatory responses by inhibiting the activation of the NF-κB signaling pathway.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

[Purpose]To analyze the causes of death and potential life loss of malignant tumors in Sichuan Province from 2017 to 2022.[Methods]Data were collected from the death information registration and management system of China Disease Prevention and Control Information System,and national cause of death monitoring sites in Sichuan Province from 2017 to 2022.SAS 9.4 and Joinpoint 4.9.1.0 software were used to calculate crude cancer mortality rate,age-standardized mortality rate by Chinese standerd population(ASMRC),annual percentage change and potential years of life lost(PYLL)and potential years of life lost rate(PYLLR).[Results]From 2017 to 2022,the crude cancer mortality rate in Sichuan Province was 169.32/105,and the ASMRC was 111.26/105.The cancer mortality rate in the general population and that stratified by sex showed an increasing trend(all P＜0.05).The top 5 causes of cancer death were lung cancer,liver cancer,esophageal cancer,gastric cancer and colorectum cancer.The mortality rates of lung cancer,colorectum can-cer,female breast cancer,pancreatic cancer,lip,oral and pharyngeal malignancies all increased(all P＜0.05).From 2017 to 2022,the PYLL caused by malignant tumors in Sichuan Province was 1 520 175.00 person-year,the PYLLR was 13.98‰.[Conclusion]In Sichuan Province,the mortali-ty rate of malignant tumors is on the rise.Lung cancer and gastrointestinal cancers are the main malignancies causing life loss.Early diagnosis and treatment of key cancers should be strengthened to reduce cancer mortality.

Objective:To analyze the coupling coordination relationship and spatial correlation among the service demand,resource allocation and utilization efficiency of Traditional Chinese Medicine(TCM),aiming to provide theoretical support and optimization strategies for achieving the coordinated operation of the TCM systems in various provinces and promoting the coordinated development of TCM in different provinces.Methods:The data were collected from the China Health and Family Planning Statistical Yearbook(2013-2017)and the China Health Statistics Yearbook(2018-2023),the entropy method was employed to determine the weight of each evaluation index within the subsystems.A coupling coordination degree model and spatial econometric model were applied to assess the coupling coordination values and spatial correlations of the TCM system across various provinces in China.Results:In 2022,the national average coupling coordination degree was 0.603,with values of 0.648,0.577,and 0.563 for the eastern,central,and western regions,respectively.The western region had the highest number of provinces classified as"disordered type".A spatial clustering effect of the coupling coordination degree across 30 provinces.Conclusions:While the allocation of TCM resources has shown steady improvement,the demand for TCM services and utilization efficiency have exhibited a declining trend.The coupling coordination degree follows a decreasing gradient from east to west and exhibits significant spatial effects,a regional collaborative development mechanism for TCM should be established.

Objective:To investigate the effect of baicalin on Th17/Treg cell balance in autoimmune myocarditis(AM)rats and its possible mechanism.Methods:AM rats were grouped into control group,model group,low-dose baicalin group[20 mg/(kg·d)],high-dose baicalin group[100 mg/(kg·d)],and high mobility group B1(HMGB1)inhibitor group;the cardiac ultrasound diagnostic instrument was applied to detect the cardiac function of rats in each group,the cardiac mass index,hematoxylin eosin(HE)staining was applied to detect myocardial pathology,ELISA was applied to detect serum levels of cytokines such as IFN-γ,IL-4,IL-17 and TGF-β,Western blot was applied to detect the expression levels of myocardial HMGB1 and receptor for advanced glycation end product(RAGE)proteins,flow cytometry was applied to detect the proportions of Th17 and Treg cells in the spleen.Results:Com-pared with the control group,the rats in the model group showed myocarditis symptoms and diffuse inflammatory cell infiltration under the endocardium,the left ventricular end diastolic diameter(LVEDd),left ventricular end systolic diameter(LVEDs),IFN-γ,IL-4,IL-17,TGF-β,the proportion of Th17 cells and the expression levels of HMGB1 and RAGE proteins increased,the left ventricular short axis shortening fraction(FS%),ejection fraction(LVEF%),cardiac mass index,and the proportion of Treg cell decreased(P<0.05);compared with the model group,the myocardial interstitial edema and inflammatory cell infiltration were reduced in the ba-icalin low and high dose groups and HMGB1 inhibitor groups,and the proportion of LVEDd,LVEDs,serum IFN-γ and IL-17,spleen Th17 cells and the expression levels of myocardial HMGB1 and RAGE protein were decreased.FS%,LVEF%,heart mass index,IL-4,TGF-β,Treg cell proportion increased;compared with the low-dose baicalin group,the symptoms of myocarditis in the high-dose baicalin group and the HMGB1 inhibitor group were obviously improved,the LVEDd,LVEDs,IFN-γ,IL-17,the proportion of Th17 cells,and the expression levels of HMGB1 and RAGE proteins decreased,the FS%,LVEF%,cardiac mass index,IL-4,TGF-β,and the proportion of Treg cells increased(P<0.05);there was no statistically obvious difference in each index between the high-dose baicalin group and the HMGB1 inhibitor group(P>0.05).Conclusion:The protective effect of baicalin on AM rats is related to the inhibition of HMGB1/RAGE axis activation.

Objective:To investigate the effect of baicalin on Th17/Treg cell balance in autoimmune myocarditis(AM)rats and its possible mechanism.Methods:AM rats were grouped into control group,model group,low-dose baicalin group[20 mg/(kg·d)],high-dose baicalin group[100 mg/(kg·d)],and high mobility group B1(HMGB1)inhibitor group;the cardiac ultrasound diagnostic instrument was applied to detect the cardiac function of rats in each group,the cardiac mass index,hematoxylin eosin(HE)staining was applied to detect myocardial pathology,ELISA was applied to detect serum levels of cytokines such as IFN-γ,IL-4,IL-17 and TGF-β,Western blot was applied to detect the expression levels of myocardial HMGB1 and receptor for advanced glycation end product(RAGE)proteins,flow cytometry was applied to detect the proportions of Th17 and Treg cells in the spleen.Results:Com-pared with the control group,the rats in the model group showed myocarditis symptoms and diffuse inflammatory cell infiltration under the endocardium,the left ventricular end diastolic diameter(LVEDd),left ventricular end systolic diameter(LVEDs),IFN-γ,IL-4,IL-17,TGF-β,the proportion of Th17 cells and the expression levels of HMGB1 and RAGE proteins increased,the left ventricular short axis shortening fraction(FS%),ejection fraction(LVEF%),cardiac mass index,and the proportion of Treg cell decreased(P<0.05);compared with the model group,the myocardial interstitial edema and inflammatory cell infiltration were reduced in the ba-icalin low and high dose groups and HMGB1 inhibitor groups,and the proportion of LVEDd,LVEDs,serum IFN-γ and IL-17,spleen Th17 cells and the expression levels of myocardial HMGB1 and RAGE protein were decreased.FS%,LVEF%,heart mass index,IL-4,TGF-β,Treg cell proportion increased;compared with the low-dose baicalin group,the symptoms of myocarditis in the high-dose baicalin group and the HMGB1 inhibitor group were obviously improved,the LVEDd,LVEDs,IFN-γ,IL-17,the proportion of Th17 cells,and the expression levels of HMGB1 and RAGE proteins decreased,the FS%,LVEF%,cardiac mass index,IL-4,TGF-β,and the proportion of Treg cells increased(P<0.05);there was no statistically obvious difference in each index between the high-dose baicalin group and the HMGB1 inhibitor group(P>0.05).Conclusion:The protective effect of baicalin on AM rats is related to the inhibition of HMGB1/RAGE axis activation.

Objective:To analyze the coupling coordination relationship and spatial correlation among the service demand,resource allocation and utilization efficiency of Traditional Chinese Medicine(TCM),aiming to provide theoretical support and optimization strategies for achieving the coordinated operation of the TCM systems in various provinces and promoting the coordinated development of TCM in different provinces.Methods:The data were collected from the China Health and Family Planning Statistical Yearbook(2013-2017)and the China Health Statistics Yearbook(2018-2023),the entropy method was employed to determine the weight of each evaluation index within the subsystems.A coupling coordination degree model and spatial econometric model were applied to assess the coupling coordination values and spatial correlations of the TCM system across various provinces in China.Results:In 2022,the national average coupling coordination degree was 0.603,with values of 0.648,0.577,and 0.563 for the eastern,central,and western regions,respectively.The western region had the highest number of provinces classified as"disordered type".A spatial clustering effect of the coupling coordination degree across 30 provinces.Conclusions:While the allocation of TCM resources has shown steady improvement,the demand for TCM services and utilization efficiency have exhibited a declining trend.The coupling coordination degree follows a decreasing gradient from east to west and exhibits significant spatial effects,a regional collaborative development mechanism for TCM should be established.