OBJECTIVE: To analyze the factors associated with mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe aplastic anemia (SAA). METHODS: The clinical data of 90 children with SAA who received allo-HSCT in the Department of Hematology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2016 to July 2023 were collected. The clinical features and causes of death were analyzed retrospectively. Cox proportional hazards model was used to screen the risk factors of death. RESULTS: Only 9 children died with a median time of 6.3(2.6, 8.3) months among the 90 children with SAA after allo-HSCT. Among the 5 deaths due to infection, 3 were pulmonary infection, including 2 cases of cytomegalovirus pneumonia. One case developed septic shock due to gastrointestinal infection. One case experienced graft failure, which was complicated by bloodstream infection, and developed septic shock. Three cases died of transplantation-associated thrombotic microangiopathy (TA-TMA). One case died of gastrointestinal graft-versus-host disease (GVHD). The results of multivariate analysis showed that post-transplant +60 d PLT≤30×10⁹/L (HR=7.478, 95%CI : 1.177-47.527, P =0.033), aGVHD Ⅲ-Ⅳ (HR=7.991, 95%CI : 1.086-58.810, P =0.041), and TA-TMA occurrence (HR=13.699, 95%CI : 2.146-87.457, P =0.006) were independent risk factors for post-transplant mortality. CONCLUSION Allo-HSCT is an effective therapy for SAA in children. Post-transplant +60 d PLT≤30×10⁹/L, aGVHD Ⅲ-Ⅳ, and TA-TMA occurrence are independently associated with post-transplant mortality, which may be helpful for early detection of potential high-risk children and optimization of clinical diagnostic and treatment strategies.
Humans ; Anemia, Aplastic/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Risk Factors ; Retrospective Studies ; Child ; Transplantation, Homologous ; Male ; Female ; Graft vs Host Disease ; Child, Preschool ; Proportional Hazards Models ; Adolescent ; Infant

Acupuncture is an ancient treatment method used in traditional Chinese medicine and has been popularized worldwide. Over the past decade, there has been an increase in the amount of acupuncture research, mostly comprised of randomized controlled trials (RCTs) that aimed to answer the question on the efficacy of acupuncture. However, poor methodology and low replicability in these acupuncture RCTs have resulted in uncertainty about the efficacy of acupuncture. In this review, current advancements and challenges in acupuncture RCTs, regarding the methodological aspects of randomization, blinding, sham acupuncture and quality of reporting, were discussed. While there have been advancements in various aspects, current acupuncture RCTs still face pressing issues such as inadequate randomization and blinding, unviable sham acupuncture controls, and poor reporting quality. Given these limitations, this review seeks to identify the methodological problems that are responsible for these problems and to suggest solutions that could help to overcome them so as to improve the quality of future studies evaluating the efficacy of acupuncture. Please cite this article as: Seetoh WS, Lim RQR, Xu RB, Sun MX, Zhang P, Wang MN. Advancements and challenges of acupuncture randomized controlled trials. J Integr Med. 2025; 23(4): 333-343.
Acupuncture Therapy ; Humans ; Randomized Controlled Trials as Topic/methods* ; Research Design

Objective To investigate the value of procalcitonin-to-albumin ratio(PAR)for predicting 28-day mortality risk in elderly patients with sepsis for optimizing the diagnosis and treatment strategies.Methods The clinical data of 112 elderly patients diagnosed with sepsis in the intensive care unit were retrospectively reviewed and analyzed.Patients were assigned to survivors group or deaths group based on 28-day outcomes.Clinical characteristics and the results of laboratory tests were collected,including procalcitonin(PCT),albumin,and C-reactive protein(CRP).The normally distributed data were compared between groups using t-test.Mann-Whitney U test was adopted for comparing non-normally distributed data.Cox proportional hazards regression model was used to analyze the effects of multiple variables on survival time.Receiver operating characteristic(ROC)curve analysis was performed to determine the sensitivity and specificity of various variables in predicting mortality risk.Results Mechanical ventilation,APACHE Ⅱ scores,and length of hospital stay(all P＜0.05)were significantly different between survivors group and deaths group.Blood culture results showed that Gram-negative bacteria were predominant pathogen(75.9％),especially Escherichia coli(45.5％).Albumin level was significantly lower(P=0.026),while PCT,CRP,and PAR levels were significantly higher(P＜0.05)in the deaths group compared to those in the survivors group.Multivariate Cox regression analysis revealed that PAR was an independent predictor of 28-day mortality(HR=3.72,95％CI:1.98-4.42,P＜0.001).ROC curve analysis showed that the area under the curve(AUC)of PAR was 0.852 in predicting mortality,with a sensitivity of 81.25％and specificity of 87.82％.Conclusions PAR outperformed PCT or albumin alone in predicting 28-day mortality risk in elderly patient with sepsis.For every 0.1 increase in PAR,the risk of mortality increased by 272％.Early monitoring of PAR can assist clinicians in rapidly identifying high-risk patients and optimizing treatment strategies.

Objective To investigate the value of procalcitonin-to-albumin ratio(PAR)for predicting 28-day mortality risk in elderly patients with sepsis for optimizing the diagnosis and treatment strategies.Methods The clinical data of 112 elderly patients diagnosed with sepsis in the intensive care unit were retrospectively reviewed and analyzed.Patients were assigned to survivors group or deaths group based on 28-day outcomes.Clinical characteristics and the results of laboratory tests were collected,including procalcitonin(PCT),albumin,and C-reactive protein(CRP).The normally distributed data were compared between groups using t-test.Mann-Whitney U test was adopted for comparing non-normally distributed data.Cox proportional hazards regression model was used to analyze the effects of multiple variables on survival time.Receiver operating characteristic(ROC)curve analysis was performed to determine the sensitivity and specificity of various variables in predicting mortality risk.Results Mechanical ventilation,APACHE Ⅱ scores,and length of hospital stay(all P＜0.05)were significantly different between survivors group and deaths group.Blood culture results showed that Gram-negative bacteria were predominant pathogen(75.9％),especially Escherichia coli(45.5％).Albumin level was significantly lower(P=0.026),while PCT,CRP,and PAR levels were significantly higher(P＜0.05)in the deaths group compared to those in the survivors group.Multivariate Cox regression analysis revealed that PAR was an independent predictor of 28-day mortality(HR=3.72,95％CI:1.98-4.42,P＜0.001).ROC curve analysis showed that the area under the curve(AUC)of PAR was 0.852 in predicting mortality,with a sensitivity of 81.25％and specificity of 87.82％.Conclusions PAR outperformed PCT or albumin alone in predicting 28-day mortality risk in elderly patient with sepsis.For every 0.1 increase in PAR,the risk of mortality increased by 272％.Early monitoring of PAR can assist clinicians in rapidly identifying high-risk patients and optimizing treatment strategies.

Objective To investigate the effect of artesunate(ART)on hypoxia/reoxygenation(H/R)-induced injury of human renal proximal tubular HK-2 cells by regulating the high mobility group protein B1(HMGB1)-receptor of advanced glycation endproduct(RAGE)signaling pathway.Methods HK-2 cells cultured in vitro were stochastically separated into control group,model group,L-ART group(4 μg/ml ART),H-ART group(16 μg/ml ART),H-ART+pcDNA NC group(16 μg/ml ART+transfected pcDNA NC plasmid),and H-ART+pcDNA-HMGB1 group(16 μg/ml ART+transfected pcDNA-HMGB1 plasmid).HK-2 cells in the control group were cultured normally,while the cells in the other groups were induced with hypoxia/reoxygenation(H/R).MTT and plate clone formation experiments were applied to detect the proliferation of cells in each group;ELISA kits were used to measure the expression of interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in various groups;flow cytometry was applied to detect the apoptosis in various groups;Western blot was applied to detect the expression of proliferation related proteins(PCNA),apoptosis related proteins(Bcl-2,Bax),and HMGB1-RAGE signaling pathway related proteins(HMGB1,RAGE)in each group.Results Compared with the control group,the survival rate,clone number,PCNA and Bcl-2 proteins expression of HK-2 cells decreased in the model group,but the apoptosis rate,IL-1β,IL-6,TNF-α,Bax,HMGB1 and RAGE proteins expression increased(P<0.05).Compared with the model group,the survival rate,clone number,PCNA and Bcl-2 proteins expression of HK-2 cells increased in L-ART and H-ART groups,but the apoptosis rate,IL-1β,IL-6,TNF-α,Bax,HMGB1 and RAGE proteins expression decreased(P<0.05).Compared with the H-ART and H-ART+pcDNA NC groups,the survival rate,clone number,PCNA and Bcl-2 proteins expression of HK-2 cells decreased in the H-ART+pcDNA-HMBB1 group,but the apoptosis rate,IL-1β,IL-6,TNF-α,Bax,HMGB1 and RAGE proteins expression increased(P<0.05).Conclusion ART may suppress inflammatory response and cell apoptosis,promote cell proliferation,and alleviate H/R-induced injury of renal proximal tubular HK-2 cells by inhibiting the HMGB1-RAGE signaling pathway.

Objective:To explore the diagnostic value of 18F-FDG PET/CT imaging in etiology of patients with hemophagocytic lymphohistiocytosis (HLH). Methods:Retrospective analysis was performed on 49 patients newly diagnosed as HLH (32 males, 17 females; age 19-61 years) who received 18F-FDG PET/CT imaging in Affiliated Hospital of Jining Medical University from January 2017 to January 2023. PET/CT images and clinical parameters were observed and recorded. Based on the pathological examination and clinical follow-up results, diagnostic efficacies for HLH etiology of PET/CT, PET and CT imaging were calculated. χ2 test, independent-sample t test and Mann-Whitney U test were used to compare the differences between hematologic tumors associated HLH and non-hematologic tumor associated HLH. Multivariate logistic regression was used to analyze the predictors of secondary HLH in hematologic tumors. ROC curve analysis was used to calculate AUCs and optimal threshold of lymph node SUV max and soluble CD25 (sCD25) to predict secondary HLH in patients with hematologic tumors. Results:The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET/CT, PET and CT in the etiological diagnosis of HLH were 85.7%(30/35), 8/10, 84.4%(38/45), 93.8%(30/32), 8/13; 77.1%(27/35), 6/10, 73.3%(33/45), 87.1%(27/31), 6/14; 62.9%(22/35), 5/10, 60.0%(27/45), 81.5%(22/27), 5/18, respectively. There were differences in lymph node distribution and boundary, liver and spleen and bone lesions, SUV max of lymph node and liver and spleen and bone, gender, age, WBC, neutrophil (ANC), PLT, lactate dehydrogenase (LDH), total bilirubin (TBIL), C-reactive protein (CRP) and sCD25 between different etiology groups ( χ2 values: 3.91-9.66, t values: 3.75-7.90, z values: 3.82-4.01, all P<0.05). SUV max of lymph nodes and sCD25 were predictive factors for secondary HLH of hematological tumors (odds ratio ( OR): 1.28 (95% CI: 1.09-1.72), 1.56 (95% CI: 1.17-2.49), P values: 0.004, 0.013). The optimal thresholds were 12.6 and 40 028 ng/L, with the AUC of 0.87 and 0.76, with the sensitivity and specificity of 88.6%(31/35) and 8/10, 65.7%(23/35) and 7/10, respectively. The combined AUC was 0.83 and the sensitivity and specificity were 74.3% (26/35) and 9/10. Conclusions:18F-FDG PET/CT imaging is of high value for the diagnosis of the cause of HLH. SUV max of lymph node and sCD25 are predictive factors for secondary HLH of hematologic tumors.

Objective To investigate the effect of artesunate(ART)on hypoxia/reoxygenation(H/R)-induced injury of human renal proximal tubular HK-2 cells by regulating the high mobility group protein B1(HMGB1)-receptor of advanced glycation endproduct(RAGE)signaling pathway.Methods HK-2 cells cultured in vitro were stochastically separated into control group,model group,L-ART group(4 μg/ml ART),H-ART group(16 μg/ml ART),H-ART+pcDNA NC group(16 μg/ml ART+transfected pcDNA NC plasmid),and H-ART+pcDNA-HMGB1 group(16 μg/ml ART+transfected pcDNA-HMGB1 plasmid).HK-2 cells in the control group were cultured normally,while the cells in the other groups were induced with hypoxia/reoxygenation(H/R).MTT and plate clone formation experiments were applied to detect the proliferation of cells in each group;ELISA kits were used to measure the expression of interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in various groups;flow cytometry was applied to detect the apoptosis in various groups;Western blot was applied to detect the expression of proliferation related proteins(PCNA),apoptosis related proteins(Bcl-2,Bax),and HMGB1-RAGE signaling pathway related proteins(HMGB1,RAGE)in each group.Results Compared with the control group,the survival rate,clone number,PCNA and Bcl-2 proteins expression of HK-2 cells decreased in the model group,but the apoptosis rate,IL-1β,IL-6,TNF-α,Bax,HMGB1 and RAGE proteins expression increased(P<0.05).Compared with the model group,the survival rate,clone number,PCNA and Bcl-2 proteins expression of HK-2 cells increased in L-ART and H-ART groups,but the apoptosis rate,IL-1β,IL-6,TNF-α,Bax,HMGB1 and RAGE proteins expression decreased(P<0.05).Compared with the H-ART and H-ART+pcDNA NC groups,the survival rate,clone number,PCNA and Bcl-2 proteins expression of HK-2 cells decreased in the H-ART+pcDNA-HMBB1 group,but the apoptosis rate,IL-1β,IL-6,TNF-α,Bax,HMGB1 and RAGE proteins expression increased(P<0.05).Conclusion ART may suppress inflammatory response and cell apoptosis,promote cell proliferation,and alleviate H/R-induced injury of renal proximal tubular HK-2 cells by inhibiting the HMGB1-RAGE signaling pathway.

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Objective: To study the effects of Nintedanib associated with Shenfu Injection on lung injury induced by paraquat (PQ) intoxication. Methods: In September 2021, a total of 90 SD rats were divided into 5 groups in random, namely control group, PQ poisoning group, Shenfu Injection group, Nintedanib group and associated group, 18 rats in each group. Normal saline was given by gavage route to rats of control group, 20% PQ (80 mg/kg) was administered by gavage route to rats of other four groups. 6 hours after PQ gavage, Shenfu Injection group (12 ml/kg Shenfu Injection), Nintedanib group (60 mg/kg Nintedanib) and associated group (12 ml/kg Shenfu Injection and 60 mg/kg Nintedanib) were administered with medicine once a day. The levels of serum transforming growth factor beta1 (TGF-β1), interleukin-1 beta (IL-1β) were determined at 1, 3 and 7 d, respectively. The pathological changes of lung tissue, the ratio of wet weight and dry weight (W/D) of lung tissue, the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were observed and determined after 7 d. Western blot was used to analyse the expression levels of fibroblast growth factor receptor 1 (FGFR1), platelet derivation growth factor receptor alpha (PDGFRα), vascular endothelial growth factor receptor 2 (VEGFR2) in lung tissue after 7 d. Results: The levels of TGF-β1, IL-1β in all poisoning groups went up first and then went down. The levels of TGF-β1, IL-1β in associated group at 1, 3, 7 d were lower than that of PQ poisoning group, Shenfu Injection group and Nintedanib group at the same point (P<0.05). Pathological changes of lung tissue under the light microscopes showed that the degrees of hemorrhage, effusion and infiltration of inflammatory cells inside the alveolar space of Shenfu Injection group, Nintedanib group and associated group were milder than that of PQ poisoning group, and the midest in associated group. Compared with control group, the W/D of lung tissue was higher, the level of MDA in lung tissue was higher, while the level of SOD was lower, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were higher in PQ poisoning group (P<0.05). Compared with PQ poisoning group, Shenfu Injection group and Nintedanib group, the W/D of lung tissue was lower, the level of MDA in lung tissue was lower, while the level of SOD was higher, the expressions of FGFR1, PDGFRα and VEGFR2 in lung tissue were lower in associated group (P<0.05) . Conclusion: Nintedanib associated with Shenfu Injection can relieve lung injury of rats induced by PQ, which may be related to Nintedanib associated with Shenfu Injection can inhibit the activation of TGF-β1 and the expressions of FGFR1, PDGFRα, VEGFR2 in lung tissue of rats.
Animals ; Rats ; Rats, Sprague-Dawley ; Paraquat ; Transforming Growth Factor beta1 ; Receptor, Platelet-Derived Growth Factor alpha ; Vascular Endothelial Growth Factor A ; Acute Lung Injury/drug therapy*

OBJECTIVE: To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance. METHODS: Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL. RESULTS: 227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ²= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×10⁹/L vs 8.23×10⁹/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037). CONCLUSION Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.
Child ; Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Cell Cycle Proteins/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Retrospective Studies ; Ubiquitin-Protein Ligases/genetics* ; Prognosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Mutation ; Lymphocytes