Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*

Objective To explore the evidence,urinary biomarkers,and partial mechanisms of hypercoagulability in the pathogenesis of IgA vasculitis(IgAV).Methods Differential expression of proteins in the urine of 10 healthy children and 10 children with IgAV was screened using high-performance liquid chromatography-tandem mass spectrometry,followed by Reactome pathway analysis.Protein-protein interaction(PPI)network analysis was conducted using STRING and Cytoscape software.In the validation cohort,15 healthy children and 25 children with IgAV were included,and the expression levels of differential urinary proteins were verified using enzyme-linked immunosorbent assay.Results A total of 772 differential proteins were identified between the IgAV group and the control group,with 768 upregulated and 4 downregulated.Reactome pathway enrichment results showed that neutrophil degranulation,platelet activation,and hemostasis pathways were involved in the pathogenesis of IgAV.Among the differential proteins,macrophage migration inhibitory factor(MIF)played a significant role in neutrophil degranulation and hemostasis,while thrombin was a key protein in platelet activation and hemostasis pathways.PPI analysis indicated that thrombin directly interacted with several proteins involved in inflammatory responses,and these interactions involved MIF.Validation results showed that compared to healthy children,children with IgAV had significantly higher urine thrombin/creatinine and urine MIF/creatinine levels(P<0.05).Conclusions Thrombin contributes to the pathogenesis of IgAV through interactions with inflammatory factors.Urinary thrombin and MIF can serve as biomarkers reflecting the hypercoagulable and inflammatory states in children with IgAV.

Objective To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation. Methods A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Results The ALL patients with CREBBP gene mutation accounted for 1.5％ (14/963) among all children diagnosed with ALL during the same period of time,among whom there were 4 boys (29％) and 10 girls (71％),with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS,KRAS,ETV6,FLT3,PAX5,SH2B3,CDKN2A,and CDKN2B,and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen,with a complete remission (CR) rate of 79％ (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone,with a recurrence rate of 21％ (3/14),among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children,1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92％±7％,and the event-free survival rate was 73％±13％. Conclusions ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate,and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.

Objective:To establish a mesenchymal stem cell(MSC)-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease(aGVHD).Methods:Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors,and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients.The recipient mouse received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1× 107/mouse)in 6-8 hours post irradiation to establish a bone marrow transplantation(BMT)mouse model(n=20).In addition,the recipient mice received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1 × 107/mouse)and spleen lymphocytes(2 × 106/mouse)in 6-8 hours post irradiation to establish a mouse aGVHD model(n=20).On the day 7 after modeling,the recipient mice were anesthetized and the blood was harvested post eyeball enucleation.The serum was collected by centrifugation.Mouse MSCs were isolated and cultured with the addition of 2％,5％,and 10％recipient serum from BMT group or aGVHD group respectively.The colony-forming unit-fibroblast(CFU-F)experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC.The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining.In addition,the expression of self-renewal-related genes including Oct-4,Sox-2,and Nanog in MSC was detected by real-time fluorescence quantitative PCR(RT-qPCR).Results:We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD.CFU-F assay showed that,on day 7 after the culture,compared with the BMT group,MSC colony formation ability of aGVHD serum concentrations groups of 2％and 5％was significantly reduced(P＜0.05);after the culture,at day 14,compared with the BMT group,MSC colony formation ability in different aGVHD serum concentration was significantly reduced(P＜0.05).The immunofluorescence staining showed that,compared with the BMT group,the proportion of MSC surface molecules CD29+and CD 105+cells was significantly dereased in the aGVHD serum concentration group(P＜0.05),the most significant difference was at a serum concentration of 10％(P＜0.001,P＜0.01).The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4,Sox-2,and Nanog was decreased,the most significant difference was observed at an aGVHD serum concentration of 10％(P＜0.01,P＜0.001,P＜0.001).Conclusion:By co-culturing different concentrations of mouse aGVHD serum and mouse MSC,we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability,which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

AIM To investigate the effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in isoproterenol(ISO)-induced rat heart tissue and primary myocardial cells of neonatal rats.METHODS The SD rats were randomly divided into the normal group,the model group,the Xinyue Capsules intervention group and Xinyue Capsules control group,with 8 rats in each group.The rat model of cardiac hypertrophy was established by 14 days consecutive intraperitoneal injection of ISO(30 mg/kg).Prior to the modeling,once daily administration of 0.393 g/kg Xinyue Capsules was given by gavage from 3 days in advance to the end of the experiment.After the last administration,the procurement of blood from abdominal aorta,the left and right ventricles were processed.And the rats had their indices levels of the heart,the left ventricle and the right ventricle measured;their pathomorphological changes of myocardial tissue observed using HE staining;their expressions of cardiac hypertrophy-related myocardial embryonic genes ANP,β-MHC and α-SKA mRNA detected using RT-qPCR method;and their serum TC,TG,LDL-C and HDL-C levels detected by biochemical method.In in vitro experiment,the neonatal rat model of myocardial hypertrophy was induced by exposure to ISO 1 μmol/L for 24 h.The investigation of the effect of Xinyue Capsules 12.5 μg/mL on ISO-induced myocardial hypertrophy was conducted by detection of myocardial cell area,embryo genes related to cardiac hypertrophy and myocardial cells protein cuntent.The further anti-cardiac hypertrophy mechanism of Xinyue Capsules research was conducted using RT-qPCR and Western blot to detect the gene and protein expressions of phospholipase A2(PLA2G6),phospholipase A1 member A(PLA1A)and lecithin cholesterol acyltransferase(LCAT)in left ventricle tissue and myocardial cells of each group.RESULTS The in vivo experimental result showed that compared with the normal group,the model group displayed increased indices levels of the heart,the left ventricle and the right ventricle and cross-sectional area of left ventricular myocytes(P＜0.05);and up-regulated expressions of ANP,β-MHC,α-SKA mRNA and PLA2G6,PLA1A and LCAT mRNA and proteins in the left ventricle(P＜0.05);and increased levels of serum TC,TG and LDL-C(P＜0.05);and decreased HDL-C level(P＜0.05).However,the intervention of Xinyue Capsules inhibited the changes of the aforementioned indices(P＜0.05).The in vitro experimental result revealed that Xinyue Capsules inhibited the ISO-induced increases of myocardial cell surface area and myocardial cell protein level,the up-regulation of ANP,β-MHC,α-SKA mRNA expressions and the PLA2G6,PLA1A,LCAT mRNA and protein expressions as well(P＜0.05).CONCLUSION Xinyue Capsules can improve the ISO-induced cardiac hypertrophy in rats,and its mechanism may be associated with its regulation upon the expressions of glycerophospholipid metabolism-related enzymes PLA2G6,PLA1A and LCAT.

Objective:To summarize the clinical manifestations, experiences in diagnosis and treatment of arrhythmogenic cardiomyopathy (ACM) in children.Methods:A retrospective analysis of the clinical manifestations, laboratory tests, radiological features, treatment and follow-up results was conducted in 11 children diagnosed with ACM at the center of congenital heart disease, Beijing anzhen hospital from May 2010 to March 2022.Results:A total of 11 patients aged 2 to 16 years, including 5 males and 6 females were diagnosed with ACM. The clinical manifestations included decreased activity tolerance (7 patients), heart failure (4 patients), syncope or sudden death (3 patients), palpitation (3 patients), and chest tightness and pain (3 patients). Electrocardiogram showed right bundle branch block in 9 cases, paroxysmal ventricular tachycardia in 4 cases, frequent premature ventricular contraction in 4 cases, ventricular pre-excitation in 1 case, left bundle branch block in 1 case, and first degree atrioventricular block in 2 cases. Echocardiography showed enlargement of the right heart, widening of the right ventricular outflow tract, and thinning and bulging of the local wall of the right ventricle with reduced pulsation. Ventricular thrombosis was found in 2 cases. Six children underwent cardiac magnetic resonance imaging, which mainly showed severe enlargement of the right heart, thin free wall of the right ventricle, decreased right heart function, enhanced right ventricular myocardium, and formation of right ventricular aneurysm. Two children underwent myocardial biopsy examination and presented with typical pathological changes of ACM. Genetic tests in five patients revealed DSG2 gene mutation in 2 cases, PKP2 gene mutation in 2 cases, and MYH6 gene mutation in 1 case. All patients received anti heart failure treatment and antiarrhythmic drugs. Two children received anticoagulant treatment due to ventricular thrombosis. Radiofrequency ablation was performed in 2 patients. Glenn procedure was performed in 4 patients, and heart transplantation was performed in 1 patient due to progressive heart failure. The follow-up period ranged from 6 months to 12 years. Two cases died of right heart failure, 6 cases had different degrees of heart failure, 1 case had intermittent chest tightness and pain, and 2 cases were stable.Conclusions:ACM is a progressive genetic cardiomyopathy characterized by decreased activity tolerance, cardiac failure and arrhythmia in pediatric patients. The diagnosis is mainly based on clinical manifestations, electrocardiogram, cardiac imaging changes, and genetic testing. Early detection, diagnosis, and personalized treatment can improve the prognosis.

Objective:To evaluate the initial clinical outcome of applying a comprehensive debulking procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle to reconstruct the hypertrophic toes and forefoots in one-stage surgery in multiple toes macrodactyly in children.Methods:The clinical data of children with macrodactyly deformity treated by the Department of Burn and Plastic Surgery in Children’s Hospital of Chongqing Medical University from January 2022 to October 2023 were retrospectively analyzed. Design toe and plantar arbitrary flaps with a few vascular perforating branches which pedicle at the comparatively healthy proximal side and resect all tissues beyond the normal length. In severe toe, a composite tissue nail-flap with the artery was dissected to reconstruct the toenail. Fat debulking on the surface of deep plantar fascia as well as within the osseofascial sheath, resecting partially of the fatty infiltrated nerve, transverse and longitudinal osteotomy to shorten and narrowed phalanxes without epiphyseal block, arthroplasty and flexor tendon tightening were performed. Finally, toes shaped by wrapping toe flaps, and pelmas restored by plantar flaps which both with comparatively healthy proximal pedicle. The operation time, healing time, and whether the toes and toenails are preserved were all recorded. The maximum circumference of both foot, the difference in shoe size, the presence of skin ulcers, wound scars, toe webbing morphology, the presence of basic sensation, and the satisfaction of parents were followed-up after surgery. The modified follow-up questionnaire was used to evaluate the surgical effect, the total score is 0-12 points, and the higher the score, the better the surgical outcome. Descriptive methods was used for statistical analysis, and the measurement data conforming to normal distribution were expressed as Mean±SD.Results:A total of 15 patients were enrolled, including 11 males and 4 females. The median age at the time of operation was 2.75 years (0.9-10.8 years). There were 11 cases with 2 toes and 4 cases with 3 toes, a total of 34 toes involved. The average surgical duration was 4.13 hours (3.25 hours for 2 toes and 5.00 hours for 3 toes). Only one severe case with 3 toes involved was amputated the biggest toe ray and totally 2 toe nail flaps were harvested unsuccessfully intraoperative. Except 3 toes had distal skin partially necrosis and 2 nail flaps were completely necrotic which healed after dressing changes, the rest of the toes were healing well after operation. The average follow-up time was 4.8 months (3-11 months), the difference of circumference was less than 1.5 cm, as well as in length was less than 0.5 cm between feet and all children were able to wear the appropriate shoes with same size. A total of 4 toes failed to retain toenails, and 1 had a very thin toenail. Except for one case with insufficient web depth, the other toe webs were close to normal. There was no skin ulcer occurred, the basic sensation of the feet was present, and wound scars were inconspicuous. The score of the modified questionnaire was 10.54±0.88, all parents were satisfied with the results.Conclusion:Comprehensive procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle for debulking multiple toes macrodactyly in children could completely excise distal hypertrophic tissues in a single operation, and the size of the affected feet and toes can be greatly reduced to wearing shoes of the same size, and have a high success rate in preserving the toes, as well as nails. The reconstructed feet, toes and toe webbing have near-normal morphology, hidden scar, no ulcers after walked and achieve a good initial effect.

Objective:To evaluate the initial clinical outcome of applying a comprehensive debulking procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle to reconstruct the hypertrophic toes and forefoots in one-stage surgery in multiple toes macrodactyly in children.Methods:The clinical data of children with macrodactyly deformity treated by the Department of Burn and Plastic Surgery in Children’s Hospital of Chongqing Medical University from January 2022 to October 2023 were retrospectively analyzed. Design toe and plantar arbitrary flaps with a few vascular perforating branches which pedicle at the comparatively healthy proximal side and resect all tissues beyond the normal length. In severe toe, a composite tissue nail-flap with the artery was dissected to reconstruct the toenail. Fat debulking on the surface of deep plantar fascia as well as within the osseofascial sheath, resecting partially of the fatty infiltrated nerve, transverse and longitudinal osteotomy to shorten and narrowed phalanxes without epiphyseal block, arthroplasty and flexor tendon tightening were performed. Finally, toes shaped by wrapping toe flaps, and pelmas restored by plantar flaps which both with comparatively healthy proximal pedicle. The operation time, healing time, and whether the toes and toenails are preserved were all recorded. The maximum circumference of both foot, the difference in shoe size, the presence of skin ulcers, wound scars, toe webbing morphology, the presence of basic sensation, and the satisfaction of parents were followed-up after surgery. The modified follow-up questionnaire was used to evaluate the surgical effect, the total score is 0-12 points, and the higher the score, the better the surgical outcome. Descriptive methods was used for statistical analysis, and the measurement data conforming to normal distribution were expressed as Mean±SD.Results:A total of 15 patients were enrolled, including 11 males and 4 females. The median age at the time of operation was 2.75 years (0.9-10.8 years). There were 11 cases with 2 toes and 4 cases with 3 toes, a total of 34 toes involved. The average surgical duration was 4.13 hours (3.25 hours for 2 toes and 5.00 hours for 3 toes). Only one severe case with 3 toes involved was amputated the biggest toe ray and totally 2 toe nail flaps were harvested unsuccessfully intraoperative. Except 3 toes had distal skin partially necrosis and 2 nail flaps were completely necrotic which healed after dressing changes, the rest of the toes were healing well after operation. The average follow-up time was 4.8 months (3-11 months), the difference of circumference was less than 1.5 cm, as well as in length was less than 0.5 cm between feet and all children were able to wear the appropriate shoes with same size. A total of 4 toes failed to retain toenails, and 1 had a very thin toenail. Except for one case with insufficient web depth, the other toe webs were close to normal. There was no skin ulcer occurred, the basic sensation of the feet was present, and wound scars were inconspicuous. The score of the modified questionnaire was 10.54±0.88, all parents were satisfied with the results.Conclusion:Comprehensive procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle for debulking multiple toes macrodactyly in children could completely excise distal hypertrophic tissues in a single operation, and the size of the affected feet and toes can be greatly reduced to wearing shoes of the same size, and have a high success rate in preserving the toes, as well as nails. The reconstructed feet, toes and toe webbing have near-normal morphology, hidden scar, no ulcers after walked and achieve a good initial effect.

Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.