OBJECTIVES: To explore the factors related to prognosis and treatment failure in children with acute lymphoblastic leukemia (ALL). METHODS: A retrospective study was conducted to collect and analyze clinical data of ALL children admitted to the Department of Pediatric Hematology at Tongji Hospital, Huazhong University of Science and Technology, from January 2012 to December 2019, with follow-up until June 2024. RESULTS: A total of 341 children with ALL were included. Among the 69 children with treatment failure, 55 (80%) experienced relapse, while 14 (20%) had non-relapse-related deaths, and no secondary tumors were observed. Initial WBC count ≥50×10⁹/L, positive minimal residual disease, and severe adverse events were identified as independent risk factors for treatment failure (P<0.05). Among the 55 relapsed patients, early relapses were predominant (36%), and the primary site of relapse was the bone marrow (56%). Immunophenotyping (P=0.009), initial WBC count (P=0.011), and fusion genes (P=0.040) were associated with the timing of relapse. High-risk status, T-cell ALL, relapse, and severe adverse events were independent risk factors affecting long-term survival (P<0.05). CONCLUSIONS The prognosis of children with ALL is related to risk stratification, immunophenotyping, relapse status, and occurrence of severe adverse events. Among these factors, relapse is the primary cause of treatment failure. Actively preventing relapse may reduce the treatment failure rate and improve long-term survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Prognosis ; Treatment Failure ; Adolescent ; Infant ; Risk Factors

OBJECTIVES: To study the effects of early respiratory training combined with swallowing function training on physical development and neurodevelopment at a corrected gestational age of 6 months in infants with bronchopulmonary dysplasia (BPD). METHODS: A total of 69 BPD infants who could not be fed completely orally were prospectively selected from the Department of Neonatology of Hunan Children's Hospital between January 2018 and January 2021. Based on a random number table, the infants were divided into a conventional group (35 cases) and a training group (34 cases) (with 8 cases lost to follow-up; the final follow-up included 31 cases in the training group and 30 cases in the conventional group). Both groups received routine clinical treatment and care, while the training group additionally received respiratory and swallowing function training until the infants could independently feed orally. The weight, length, Gesell Developmental Schedule (GDS) results, readmission rate, and multiple readmission rate (two or more admissions) were compared between the two groups at a corrected age of 6 months. RESULTS: At corrected gestational age of 6 months, the training group had higher weight, length, and GDS scores in personal-social, language, gross motor, fine motor, and adaptive development compared to the conventional group (P<0.05). The readmission rate and multiple readmission rate were lower in the training group compared to the conventional group (P<0.05). CONCLUSIONS Early respiratory training combined with swallowing function training for BPD infants in a neonatal intensive care unit setting helps improve physical and neurological development and reduces the readmission rate.
Humans ; Bronchopulmonary Dysplasia/physiopathology* ; Prospective Studies ; Male ; Female ; Infant ; Deglutition/physiology* ; Gestational Age ; Infant, Newborn ; Breathing Exercises ; Child Development

A retrospective analysis was conducted on the clinical course of two children with PICALM-MLLT10-positive acute leukemia treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between July 2021 and July 2023. The patients were diagnosed with acute T-lymphoblastic leukemia with central nervous system involvement and high-risk acute myeloid leukemia, respectively. Both achieved bone marrow complete remission after conventional chemotherapy combined with venetoclax. Following conversion to molecular negativity, they underwent sequential allogeneic hematopoietic stem cell transplantation. At the latest follow-up, both patients were alive and in good clinical condition. These observations suggest that proceeding to hematopoietic stem cell transplantation after venetoclax-based chemotherapy may improve the long-term survival of children with PICALM-MLLT10-positive leukemia.
Humans ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child, Preschool ; Transplantation, Homologous ; Child ; Leukemia, Myeloid, Acute/genetics* ; Oncogene Proteins, Fusion/genetics*

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective To determine the effective dose of dexmedetomidine administered intranasally combined with oral midazolam sedation before pediatric magnetic resonance image(MRI).Methods This is a prospective modified sequential study.Children scheduled for MRI at the Children's Hospital of Zhejiang University School of Medicine from February to March 2023,aged 1 month to 6 years old,with a weight of 6.0-23.5 kg,were enrolled in this study.All children received 0.5 mg/kg oral midazolam,followed by intranasal dexmedetomidine.The initial dose of dexmedetomidine was 0.5 μg/kg,and the intranasal dose of dexmedetomidine was determined using the modified Dixon's up-and-down method with increments or decrements of 0.1 μg/kg.Probit analysis was used for calculating the half effective dose(ED50),95%effective dose(ED95)and the corresponding 95%confidence interval(CI)of intranasal dexmedetomidine combined with oral midazolam for pediatric sedation during MRI.The sedation onset time,wake-up time,vital signs and adverse reactions were recorded.Results Among all the children,the sedation onset time of successful sedation children was(31.21±7.47)min,and the wake-up time was(81.21±26.04)min.The ED50 for effective sedation with intranasal dexmedetomidine combined with oral medication at a dose of 0.5 mg/kg was calculated to be 0.392 μg/kg,with a 95%CI of 0.302-0.461 μg/kg;the ED95 was 0.549 μg/kg,with a 95%CI of 0.473-0.996 μg/kg.There was a statistically significant difference(P<0.05)in heart rate and diastolic blood pressure after sedation compared to the baseline before medication.Two cases of restlessness during the awakening period were observed,but no other adverse reactions occurred.Conclusions The sedation regimen of intranasal dexmedetomidine combined with oral midazolam is non-invasive,easy to implement,safe,and effective.It can be widely used in pediatric MRI.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

AIM To establish a two reference substances for determination of multiple components(TRSDMC)method for the simultaneous content determination of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid,luteolin-7-O-glucuronide,isochlorogenic acid B,isochlorogenic acid A,isochlorogenic acid C,deoxyelephantopin,isodeoxyelephantopin,isoscabertopin and scabertopin in Elephantopus scabre L..METHODS The analysis was performed on a 35℃thermostatic Waters Symmetry C18,Phenomenex C18,Agilent ZORBAX Eclipse Plus C18 columns(4.6 mm×250 mm,5.0 μm),with the mobile phase comprising of acetonitrile and 0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,326 nm.Chlorogenic acid was used as an internal standard to calculate the relative correction factors of neochlorogenic acid,cryptochlorogenic acid,luteolin-7-O-glucuronide,isochlorogenic acid B,isochlorogenic acid A and isochlorogenic acid C,while isodeoxyelephantopin was used as an internal standard to calculate the relative correction factors of deoxyelephantopin,scabertopin and isoscabertopin,after which the content determination was made.Subsequently,cluster analysis,principal component analysis and orthogonal partial least squares-discriminant analysis were conducted.RESULTS Eleven constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 95.3%-103.4%with the RSDs of 0.32%-3.45%.The result obtained by TRSDMC approximated those obtained by external standard method.Isochlorogenic acid A,isochlorogenic acid C,isochlorogenic acid B,chlorogenic acid,luteolin-7-O-glucuronide and cryptochlorogenic acid were taken as quality differential constituents.CONCLUSION This reliable and stable method can be used for the quality control of E.scabre.

Objective:To explore the clinical characteristics of neonatal ureaplasma meningitis.Methods:A retrospective analysis was conducted on the clinical manifestations, diagnosis, treatment, and follow-up of a case of ureaplasma parvum (UP) meningitis in a neonate with persistent cerebrospinal fluid (CSF) abnormalities, admitted to the Neonatology Department of the Children's Hospital of Chongqing Medical University on September 2021. Literature was searched using the keywords "neonate", "ureaplasma", and "meningitis" in databases including CNKI, Wanfang Medical Database, Yiigle, VIP Database, SinoMed, and Chinese Medical Care Repository, as well as PubMed, Embase, and Web of Science, from their inception to December 2023. The clinical characteristics of the cases obtained were analyzed in conjunction with the present case. Descriptive statistical analysis and Chi-square test (or Fisher's exact test) were used for data analysis. Results:(1) Case report: The patient was a female neonate, born at 30 +2 gestational weeks, who experienced severe asphyxia at birth and was transferred to the neonatal intensive care unit of our hospital after resuscitation involving mechanical ventilation and chest compressions at an external hospital. On the 7th day of birth, the patient developed seizures, and CSF examination indicated meningitis. Blood and CSF cultures were negative, and empirical anti-infective treatment for one month showed no significant improvement. On the 39th day of birth, metagenomics next generation sequencing (mNGS) of the CSF indicated UP positivity, confirming UP meningitis. The patient received ten weeks of quinolone antibiotics. During hospitalization, a ventriculoperitoneal shunt was performed due to hydrocephalus, and the patient was discharged after improvement. At 2 years and 1 month of follow-up, the patient had cerebral palsy (hemiplegic type) and was undergoing rehabilitation therapy. (2) Literature review: A total of 31 articles were retrieved, encompassing 46 cases, plus the present case, making a total of 47 cases. Among these, 57% (27/47) were preterm infants, 54% (22/41) were low birth weight infants (some articles did not report this item, hence the denominator is less than 47), and 76% (28/37) were born via vaginal delivery. Cases who developed symptoms within the first week accounted for 71% (24/34), and 74% (26/35) had mothers with ureaplasma infection or high-risk factors during pregnancy. The main clinical manifestations included fever [63% (20/32)], seizures or apnea/respiratory distress [each 44% (14/32)]. CSF examination mainly showed significantly elevated white blood cells [287×10 6/L (69×10 6/L-1 176×10 6/L)], decreased glucose [0.79 mmol/L (0.10-1.17 mmol/L)], and elevated protein [3.01 g/L (1.80-8.14 g/L)], with negative general bacterial cultures. CSF mNGS [30% (14/47)], CSF polymerase chain reaction [17% (8/47)], and CSF culture [66% (31/47)] were the main methods for detecting ureaplasma. Treatment primarily involved macrolide antibiotics alone [46% (16/35)] or in combination with other antibiotics [29% (10/35)]. The duration of anti-ureaplasma treatment ranged from 2 to 10 weeks. Intracranial hemorrhage and hydrocephalus were the most common neurological complications [66% (25/38) and 61% (23/38), respectively]. Among the 47 cases, 31 were infected with ureaplasma urealyticum (UU) and 15 with UP (one case was not typed). There were no significant differences in epidemiology, clinical manifestations, neurological complications, and prognosis between UP and UU meningitis. Compared to UU meningitis, a higher proportion of UP meningitis cases were treated with macrolide antibiotics [13/15 vs. 52% (14/27), χ2=5.09, P=0.024]. Among the 43 reported cases of ureaplasma meningitis with outcomes, 44% (19/43) experienced developmental delays or death. The case fatality rate of UU meningitis was higher than that of UP meningitis [39% (11/28) vs. 0/14, Fisher's exact test, P=0.007]. Conclusions:Neonatal ureaplasma meningitis lacks specific clinical manifestations and has a variable prognosis. When empirical anti-infective treatment is ineffective in infants with purulent changes in CSF, intracranial ureaplasma infection should be considered. Macrolide antibiotics alone or in combination with other antibiotics can be the first-choice treatment for ureaplasma infection.

Establish a production line with controllable process and high intelligence, contribute to improve the quality and production efficiency of aconite processed by microwave, and promote the transformation and application of aconite processed by microwave. According to the principle of aconite detoxification and the characteristics of industrial microwave equipment, an industrial production line of aconite processed by microwave was established with diester alkaloids and monoester alkaloids as indicators, and pilot production was carried out. At the same time, the content of active constituents and efficacy were compared with that of the main processed products, such as Shengfupian, Baifupian and Heishunpian. The results showed that the industrial production of aconite processed by microwave can be divided into two stages: "Liquid seal to detoxification - drying and puffing". The content of monoester alkaloids in 10 batches of aconite processed by microwave was 0.071%-0.166% and the content of diester alkaloids was 0.004%-0.016%, which met the relevant requirements of the Chinese Pharmacopoeia in 2020. Compared with Heishunpian and Baifupian, the retention rate of the effective components of aconite processed by microwave was higher. Pharmacological experiments showed that aconite processed by microwave not only retained the anti-inflammatory and analgesic activities of Heishunpian and Baifupian, but also significantly increased the levels of leukocytes and lymphocytes in mice with liver cancer chemotherapy, enhanced the CD4/CD8 ratio in spleen cells of mice (P < 0.05), thus regulating the body's immunity. However, this effect of Baifupian was weak, while Heishunpian and Shengfupian had no such effect. Through the above research, this study established microwave processing line with controllable process and high intelligence, as well produced the aconite processed by microwave with low toxicity and stable quality. It laid a foundation for the industrialized continuous production and clinical positioning of aconite by microwave processed, and provided scientific support for the development and application of microwave technology in the field of traditional Chinese medicine. All animal experiments in this study were reviewed and approved by the Experimental Animal Ethics Committee of Chengdu University of Traditional Chinese Medicine before being carried out (Approval No. 2020-28).