OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

OBJECTIVE: To investigate the effect of Tongmai Hypoglycemic Capsule (THC) on myocardium injury in diabetic cardiomyopathy (DCM) rats. METHODS: A total of 24 Sprague Dawley rats were fed for 4 weeks with high-fat and high-sugar food and then injected with streptozotocin intraperitoneally for the establishment of the DCM model. In addition, 6 rats with normal diets were used as the control group. After modeling, 24 DCM rats were randomly divided into the model, L-THC, M-THC, and H-THC groups by computer generated random numbers, and 0, 0.16, 0.32, 0.64 g/kg of THC were adopted respectively by gavage, with 6 rats in each group. After 12 weeks of THC administration, echocardiography, histopathological staining, biochemical analysis, and Western blot were used to detect the changes in myocardial structure, oxidative stress (OS), biochemical indexes, protein expressions of myocardial fibrosis, and nuclear factor erythroid 2-related faactor 2 (Nrf2) element, respectively. RESULTS: Treatment with THC significantly decreased cardiac markers such as creatine kinase, lactate dehydrogenase, and creatine kinase-MB, etc., (P<0.01); enhanced cardiac function indicators including heart rate, ejection fraction, cardiac output, interventricular septal thickness at diastole, and others (P<0.05 or P<0.01); decreased levels of biochemical indicators such as fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, aspartate transaminase, (P<0.05 or P<0.01); and decreased the levels of myocardial fibrosis markers α-smooth muscle actin (α-SMA), and collagen I (Col-1) protein (P<0.01), improved myocardial morphology and the status of myocardial interstitial fibrosis. THC significantly reduced malondialdehyde levels in model rats (P<0.01), increased levels of catalase, superoxide dismutase, and glutathione (P<0.01), and significantly increased the expression of Nrf2, NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1, and superoxide dismutase 2 proteins in the left ventricle of rats (P<0.01). CONCLUSION THC activates the Nrf2 signaling pathway and plays a protective role in reducing OS injury and cardiac fibrosis in DCM rats.
Animals ; Diabetic Cardiomyopathies/physiopathology* ; Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats, Sprague-Dawley ; Myocardium/metabolism* ; Fibrosis ; Male ; Capsules ; Hypoglycemic Agents/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Rats ; Diabetes Mellitus, Experimental/drug therapy*

Objective:To investigate the effects of different intensities of grip strength training on arteriovenous fistula (AVF) in patients with chronic kidney disease.Methods:Different intensities of grip strength training programs were developed through literature analysis, expert argumentation, and group discussion. From July to November 2024, 90 hospitalized patients with chronic kidney disease and AVF in the Department of Nephrology of the First Affiliated Hospital of Hunan Traditional Chinese Medical College were selected as study subjects using convenience sampling. Using the random number table method, study subjects were divided into group A, group B, and group C, with 30 cases in each group. Group A underwent low-intensity grip strength training, group B underwent moderate-intensity grip strength training, and group C underwent high-intensity grip strength training. The intervention period lasted six weeks. After intervention, the internal diameter of the cephalic vein, anastomotic blood flow, and incidence of complications were compared among three groups of patients with chronic kidney disease.Results:After intervention, the internal diameter of the cephalic vein in group C was larger than that in group A and group B ( P<0.05). The anastomotic blood flow in group B and group C was higher than that in group A ( P<0.05). There was no statistically significant difference in the incidence of complications among the three groups ( P>0.05) . Conclusions:Appropriately increasing the intensity of grip strength training has a positive effect on enlarging the internal diameter of the cephalic vein and enhancing anastomotic blood flow.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

This study aims to investigate the ameliorating effect of Corni Fructus(CF) on the myocardial ischemic injury and the pharmacokinetic properties of characteristic components of CF. The mouse model of isoproterenol-induced myocardial ischemia was established and administrated with the aqueous extract of CF. The general efficacy of CF in ameliorating the myocardial ischemic injury was evaluated based on the cardiac histopathology and the levels of myocardial injury markers: creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTn-I). The metabolomics analysis was carried out for the heart and serum samples of mice to screen the biomarkers of CF in ameliorating the myocardial ischemic injury and then the predicted biomarkers were submitted to metabolic pathway enrichment. The pharmacokinetic analysis was performed for morroniside, loganin, and cornuside Ⅰ in mouse heart and serum samples to obtain the pharmacokinetic parameters of these components. The pharmacokinetic parameters were then integrated on the basis of self-defined weighting coefficients to simulate an integrated pharmacokinetic profile of CF iridoid glycosides in the heart and serum of the mouse model of myocardial ischemia. The results indicated that CF reduced the pathological damage to cardiac cells and tissue(hematoxylin-eosin staining) and lowered the levels of CK-MB and cTn-I in the serum of the mouse model of myocardial ischemia(P<0.01). Metabolomics analysis screed out 31 endogenous metabolites in the heart and 35 in the serum as biomarkers of CF in ameliorating the myocardial ischemic injury. These biomarkers were altered by modeling and restored by CF. Six metabolic pathways in the heart and 5 in the serum were enriched based on these metabolic markers. The main integrated pharmacokinetic parameters of CF iridoid glycosides were T_(max)=1 h, t_(1/2)=(1.52±0.05) h in the heart and T_(max)=1 h, t_(1/2)=(1.56±0.50) h in the serum. Both concentration-time curves showed a double-peak phenomenon. In conclusion, CF demonstrated the cardioprotective effect by regulating metabolic pathways such as taurine and hypotaurine metabolism, and pantothenic acid and coenzyme A biosynthesis. The integrated pharmacokinetics reflect the general pharmacokinetic properties of characteristic components in CF.
Animals ; Cornus/chemistry* ; Mice ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Myocardial Ischemia/metabolism* ; Humans ; Troponin I/metabolism* ; Myocardium/pathology* ; Disease Models, Animal ; Biomarkers/metabolism* ; Creatine Kinase, MB Form/metabolism*

Objective To evaluate the clinical efficacy of electroacupuncture at acupoints distributed on conception vessel(CV)and governor vessel(GV)in treating ischemic stroke(AIS)complicated with dysphagia and explore its potential mechanism.Methods A total of 120 patients diagnosed with AIS complicated with dysphagia at Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from December 2020 to December 2023 were enrolled and randomly divided into an observation group and a control group,with 60 patients per group.The control group received conventional swallowing training,while the observation group received additional electroacupuncture at acupoints distributed on CV and GV.The treatment lasted for 4 weeks.After 1 month of treatment,clinical efficacy was assessed,and the changes in Standardized Swallowing Assessment(SSA)scores,National Institutes of Health Stroke Scale(NIHSS)scores,hyolaryngeal mobility(thyroid cartilage anterior/superior displacement,hyoid bone anterior/superior displacement),and KubotaWater Swallowing Test scores were observed.Cerebral microcirculation parameters and the Chinese version of the Eating/Drinking Quality of Life(EDQoL)questionnaire were also compared.Safety and adverse events were evaluated.Results(1)The total effective rate in the observation group was 95.00%(57/60),compared to 76.67%(46/60)in the control group,demonstrating statistically superior therapeutic efficacy in the observation group(P＜0.05).(2)After treatment,both groups showed significant improvements in SSA scores and NIHSS scores(P＜0.05),with the observation group exhibiting markedly better enhancement in both SSA and NIHSS scores compared to the control group,showing statistically significant differences(P＜0.05).(3)After intervention,significant improvements were observed in anterior displacement of thyroid cartilage,superior displacement of thyroid cartilage,anterior displacement of hyoid bone,and superior displacement of hyoid bone in both groups(P＜0.05).The observation group outperformed the control group in all these laryngeal kinematic parameters with statistically significant differences(P＜0.05).(4)Both groups demonstrated significant improvement in Kubota Water Swallowing Test scores after treatment(P＜0.05),with the observation group displaying statistically greater improvement than the control group(P＜0.05).(5)Cerebral arterial parameters including peak systolic velocity(Vs),mean velocity(Vm),and resistance index(RI)were significantly improved in both groups after treatment(P＜0.05).The observation group showed superior enhancement in these cerebrovascular hemodynamic indices compared to the control group(P＜0.05).(6)Significant improvements in EDQoL scores were observed in both groups after treatment(P＜0.05),with the observation group achieving statistically greater improvement than the control group(P＜0.05).(7)The total incidence of adverse reactions was 1.67%(1/60)in the observation group versus 11.67%(7/60)in the control group,indicating a statistically significant lower adverse event rate in the observation group(P＜0.05).Conclusion Electroacupuncture at acupoints distributed on CV and GV effectively alleviates dysphagia and neurological impairment,improves hyolaryngeal mobility and cerebral microcirculation,enhances quality of life,and reduces adverse events such as aspiration pneumonia in AIS patients complicated with dysphagia.

Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.

Objective:To investigate the effects of different intensities of grip strength training on arteriovenous fistula (AVF) in patients with chronic kidney disease.Methods:Different intensities of grip strength training programs were developed through literature analysis, expert argumentation, and group discussion. From July to November 2024, 90 hospitalized patients with chronic kidney disease and AVF in the Department of Nephrology of the First Affiliated Hospital of Hunan Traditional Chinese Medical College were selected as study subjects using convenience sampling. Using the random number table method, study subjects were divided into group A, group B, and group C, with 30 cases in each group. Group A underwent low-intensity grip strength training, group B underwent moderate-intensity grip strength training, and group C underwent high-intensity grip strength training. The intervention period lasted six weeks. After intervention, the internal diameter of the cephalic vein, anastomotic blood flow, and incidence of complications were compared among three groups of patients with chronic kidney disease.Results:After intervention, the internal diameter of the cephalic vein in group C was larger than that in group A and group B ( P<0.05). The anastomotic blood flow in group B and group C was higher than that in group A ( P<0.05). There was no statistically significant difference in the incidence of complications among the three groups ( P>0.05) . Conclusions:Appropriately increasing the intensity of grip strength training has a positive effect on enlarging the internal diameter of the cephalic vein and enhancing anastomotic blood flow.

Transfer-RNA derived small RNA(tsRNA),a re-cently discovered class of non-coding RNA,is produced by ma-ture tRNA or tRNA precursor through the mediation of specific endonucleases.By regulating gene expression at the transcrip-tional and post transcriptional levels and acting as an epigenetic regulator,tsRNA plays an important role in the physiological and pathological processes of many organisms.Therefore,it has gradually become a research hotspot in biomedicine and attracted widespread attention.Moreover,there is increasing evidence that tsRNA is involved in the occurrence and development of many neuropsychiatric diseases through participating in stress re-sponse,cell proliferation and apoptosis,neural development,synaptic plasticity,neuroinflammation and immune regulation,epigenetic regulation,RNA processing,and protein translation regulation.This article mainly discusses the generation,classifi-cation and biological functions of tsRNA,and elaborates on the role and possible mechanisms of tsRNA in neurodevelopment and neuropsychiatric disorders,thereby further revealing the poten-tial of tsRNA as a reliable biomarker and therapeutic target for neuropsychiatric disorders.