Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45⁺ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3⁺ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.
Humans ; Animals ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Heterografts ; Bone Marrow ; Disease Models, Animal ; T-Lymphocytes ; Mice, SCID

Abstract: Objective　To explore the spatial epidemiological characteristics of severe cases hand, foot and mouth disease (HFMD) in Guangxi, China, from 2014 to 2018, and to provide a basis for identifying the high-risk regions as well as the prevention and control of severe cases of HFMD in Guangxi. Methods　Spatial-temporal scanning analysis, global and local spatial autocorrelation analysis were used to analyze the spatial clustering of HFMD. The trend surface analysis was used to evaluate the spatial distribution trend of HFMD. Results　From 2014 to 2018, the incidence and severe case fatality rates of HFMD were 3.89/100 000 and 4.23%, respectively. Monte Carlo scanning analysis showed that the first cluster region was Cenxi City, the second cluster was mainly concentrated in northwest of Guangxi, and the aggregation time was mainly concentrated in April to May and August to October. The global spatial autocorrelation analysis showed that the severe HFMD was significant clustering distribution, and the Moran's I coefficients of the sever cases, severe morbidity and severe case fatality rate were 0.088, 0.118, 0.197, respectively (P<0.05). Local spatial autocorrelation analysis showed that hotspots of severe HFMD cases were concentrated in the southern Guangxi, mainly in Lingshan County. Anselin local Moran's I clustering and outlier analysis indicated that 5 high-high (H-H) clustering regions for fatality were Lingshan, Pubei, Zhongshan, Zhaoping and Pinggui County. There were 6 high-high (H-H) clustering regions for severe incidence rate, namely Lingshan, Qinnan, Lingyun, Youjiang, Bama Yao Autonomous and Pinggui County, and 1 high-low (H-L) clustering region, Cenxi County. The trend surface analysis showed that the overall number of severe cases of death decreased from east or west to the middle, and increased from north to middle, and then decreased to south. Conclusions　Severe HFMD cases in Guangxi have obvious spatial-temporal clustering, and the hop spots are mainly concentrated in southern Guangxi. The prevention and control of HFMD in areas with high incidence of severe cases should be strengthened to reduce the burden of HFMD cases.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

OBJECTIVE: To systematically evaluate the efficacy and safety of conventional therapy combined with moxibustion in the treatment of chronic obstructive pulmonary disease (COPD) in stable phase based on Meta-analysis medicine. METHODS: The randomized controlled trials (RCTs) of moxibustion as adjuvant therapy for COPD were retrieved from the databases of CNKI, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library and Ebsco. RevMan5.3 software was used for Meta analysis, and the quality of evidence was evaluated according to GRADE standards. RESULTS: A total of 16 RCTs were included, involving 1425 patients. The results of Meta-analysis showed that: compared with the conventional treatment, ①the adjuvant therapy with moxibustion had advantages in reducing the number of acute exacerbations [ CONCLUSION The efficacy of moxibustion as adjuvant therapy for COPD in stable phase is better than that of simple conventional therapy. Due to insufficient clinical evidence and the limitations of this study, clinical safety is unclear and further evidence is needed to support the results.
Humans ; Lung ; Moxibustion ; Pulmonary Disease, Chronic Obstructive/therapy* ; Treatment Outcome

Although there is guidance from different regulatory agencies, there are opportunities to bring greater consistency and stronger applicability to address the practical issues of establishing and operating a data monitoring committee (DMC) for clinical studies of Chinese medicine. We names it as a Chinese Medicine Data Monitoring Committee (CMDMC). A panel composed of clinical and statistical experts shared their experience and thoughts on the important aspects of CMDMCs. Subsequently, a community standard on CMDMCs (T/CACM 1323-2019) was issued by the China Association of Chinese Medicine on September 12, 2019. This paper summarizes the key content of this standard to help the sponsors of clinical studies establish and operate CMDMCs, which will further develop the scientific integrity and quality of clinical studies.

OBJECTIVE: To study the clinical features of children with Guillain-Barré syndrome (GBS) and the significance of Brighton criteria in childhood GBS. METHODS: A retrospective analysis was performed on the medical data of 72 children with GBS. Brighton criteria were used for the grading of diagnostic certainty (level 1 as the highest level, and level 4 as the lowest level). A Spearman's rank correlation analysis was used to evaluate the correlation of auxiliary examinations with the level of diagnostic certainty of Brighton criteria. RESULTS: A total of 72 children with GBS were enrolled, with a mean age of onset of (98±32) months. All children (100%, 72/72) had weakness of bilateral limbs and disappearance or reduction of tendon reflex, and limb weakness reached the highest level of severity within 4 weeks. Of all the 72 children, 68 (94%) had positive results of neural electrophysiological examination and 51 (71%) had positive results of cerebrospinal fluid (CSF) examination, and the positive rate of neural electrophysiological examination was significantly higher than that of CSF examination ( CONCLUSIONS Most of the children with GBS meet Brighton criteria level 1, and the positive results of CSF examination and neural electrophysiological examination play an important role in improving the level of diagnostic certainty of Brighton criteria. Neural electrophysiological examination has a higher positive rate than CSF examination in the early stage of the disease.
Child ; Child, Preschool ; Extremities ; Guillain-Barre Syndrome/diagnosis* ; Humans ; Muscle Weakness ; Physical Examination ; Retrospective Studies

OBJECTIVE Right ventricular (RV) remodeling is one of the essential pathological features in pulmonary arterial hypertension (PAH). RV hypertrophy or fibrosis are the leading causes of RV remodeling. Magnolol is a com?pound isolated from Magnolia officinalis. It possesses multiple pharmacological activities, such as anti-oxidation and anti-inflammation. This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH. METHODS ① Male SD rats (220 g) were randomly divided into 5 groups (n=10): the normoxia group, the hypoxia group, the hypoxia plus Magnolol (10 and 20 mg·kg-1·d-1) group, and the vehicle group. Rats in the normoxia group were kept in a normoxia environment for 4 weeks, while rats in the hypoxia group were kept in a hypoxic chamber (10％ O2). The rats in the hypoxia plus magnolol groups were administered with magnolol at 10 or 20 mg·kg-1 (ip) once a day for 4 weeks. At the end of 4 weeks, the heart function was assessed by Doppler echocardiography, and then the rats were anesthetized with sodium pentobarbital (30 mg·kg-1, ip). The RVSP was measured by the right heart catheterization method. The heart tissues were collected and dissected to calculate the index of RV remodeling (RV/LV+IVS, RV/tibial length, or RV/body weight). Part of the RV samples was fixed with 4％paraformaldehyde for morphological analysis, while other samples were frozen at-80℃for molecular studies (measurements of ANP, BNP,α-SMA, and col?lagen Ⅰ/Ⅲ mRNA expression as well as p-JAK2/JAK2 and p-STAT3/STAT3 protein levels). ② To evaluate the effect of magnolol on hypoxia-induced myocardial hypertrophy and fibrosis, H9c2 or cardiac fibroblasts were divided into 7 groups: the control group, cells were cultured under normal conditions; the hypoxia group, cells were cultured under hypoxic condition (3％ O2);the hypoxia plus magnolol 10 mg·kg-1 group, magnolol10μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus magnolol 30 mg·kg-1 group, magnolol 20μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus TG-101348 group, TG-101348 (a specific inhibitor of JAK2) 1μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus JSI-124 group, JSI-124 (a specific inhibitor of JAK2) 1μmol·L-1 was added to the culture medium before the hypoxia treatment;and the hypoxia plus vehicle group, an equal volume of vehicle (DMSO) was added to the culture medium before the hypoxia treatment. At the end of the experiments, the cells were collected for morphological and molecular analysis. RESULTS In vivo, male Sprang-Daley rats were exposed to 10％ O2 for 4 weeks to establish an RV remodeling model, which showed hypertrophic and fibrotic features (increases of RV remodeling index, cellular size, hypertrophic and fibrotic marker expression), accompanied by an elevation in phosphorylation levels of JAK2 and STAT3;these changes were attenuated by treating rats with magnolol. In vitro, the cultured H9c2 cells or cardiac fibroblasts were exposed to 3％ O2 for 48 h to induce hypertrophy or fibrosis, which showed hypertrophic (increases in cellular size as well as the expression of ANP and BNP) or fibrotic features (increases in the expression of collagenⅠ, collagenⅢandα-SMA). Administration of mag?nolol and TG-101348 or JSI-124 (JAK2 selective inhibitors) could prevent the process of myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. CONCLUSION Magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway.

BACKGROUND: MAVERIC (Mitral Valve Repair Clinical Trial) validates the safety and efficacy of the ARTO system. We here report the first two successful cases of utilizing the ARTO system in patients with symptomatic heart failure (HF) with functional mitral regurgitation (FMR) in Asia. METHODS: Two patients, aged 70 and 63, had severe HF with FMR. Transesophageal echocardiography confirmed that the left ventricular ejection fractions were less than 50% with severe mitral regurgitation (MR) in both patients. Optimizing drug treatment could not mitigate their symptoms. Therefore, we used the ARTO system to repair the mitral valve for these patients on March 5 and 6, 2019, respectively. RESULTS: Mitral valve repairs using the ARTO system were successfully performed under general anaesthesia for these two patients. MR was decreased immediately after the procedures in both patients. The 30-day and 3-month transthoracic echocardiography (TTE) revealed a moderate to severe MR in both patients, and the New York Heart Association (NYHA) scales were also partially improved. CONCLUSION The first two cases in Asia indicate that the ARTO system is feasible for patients with heart failure with FMR, and the patient selection appears to be crucial.

Objective: To investigate the clinical outcomes of selective major aortopulmonary collaterals(MAPCAs) unifocalization and report histopathological findings in patients with pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals(PA/VSD/ MAPCAs). Methods: The study enrolled 6 MAPCAs/VSD/PA patients with age ranged from 6 to 96 months and body weight ranged from 5.0 to 23.0 kg. These patients underwent selective MAPCAs unifocalization and primary repairs. Preoperative cardiac catheter, selective arteriography, cardiac CTA and intraoperative pathology were performed to identify different function, anatomic distribution and histopathology of MAPCAs. Results: 6 MAPCAs/VSD/PA patients underwent selective MAPCAs unifocalization and primary repair. No death occurred after operation and at follow-up which lasted for 1 to 20 months. Preoperative cardiac catheter, selective arteriography and intraoperative histopathology demonstrated distribution of functional MAPCAs similar to native pulmonary artery arborization and participating in arterial gas exchange. Functional MAPCAs were classified into elastic arteries according to histopathology. Conclusion There are two histological type of MAPCAs which play different roles. Selective unifocalization to functional MAPCAs which are classified into elastic arteries like native pulmonary artery is a safe and effective treatment approach for PA/VSD/MAPCAs.