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: 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

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 obtain ancient traditional Chinese medicine（TCM）literatures relating to tumor and visual analysis by an automatic framework tool， in order to systematically sort out the development of ancient Chinese medicine oncology. Method:Based on the database platform of ancient TCM books，names of tumor-related diseases in ancient TCM books were retrieved by Selenium WebDriver， an automation framework tool under Python 3.8. Lxml's etree library was used to parse the data. Statistics was made for "classification"， "authors"， "completion time" and "summary" of relevant ancient books automatically. After the data was checked and processed， Tableau 2019.2 software was used for data visualization analysis. And ancient Chinese medicine literatures relating to tumor were consulted at the database manually，with the dynasties as the clue，and the symptoms，etiology，pathogenesis and prognosis as the emphasis，this paper explores the development process of TCM oncology. Result:A total of 774 349 bytes of text data of 1 128 entries in 242 ancient books were included automatically. According to the findings， there were simple classification and time distribution of tumor diseases in ancient TCM books in the pre-Qin period， with a simple view on the pathogenesis of tumor diseases. From the Han dynasty to the Tang dynasty， the number of relevant literature records and the types and disease names had gradually increased，which further enriched the cognition of tumor nature，signs，classification methods，differential diagnosis；in Song and Ming dynasties，the proportion of Chinese prescription books and surgery books had increased gradually，with the largest number of abdominal organ tumor names among all dynasties；from Qing dynasty to the Republic of China，literatures relating to tumor name and classification were the most improved，and then the TCM tumor syndrome differentiation and treatment system had been formed. Conclusion:It was found that TCM oncology originated in the pre-Qin dynasty，and was improved in the Han and Tang dynasties， mature in the Song and Ming dynasties and completed in the Qing dynasty and the Republic of China. The data visualization method with integrated automation framework and parsing tools is helpful to analyze the subdivision characteristics of ancient TCM literatures，which is convenient，efficient and innovative，in the expectation to provide a classic reference for contemporary TCM 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.

Objective:To investigate the effectiveness of surgical treatment for patients with T 4 stage prostate cancer. Methods:The clinical data and prognosis of 18 patients with T 4 stage prostate cancer treated in Shanghai Tenth People's Hospital from July 2013 to December 2019 were retrospectively analyzed. The average age of these 18 patients was 68.3 (53-81)years. 10 patients were castration resistant prostate cancer (CRPC) and 8 patients were hormone-sensitive prostate cancer (HSPC). 10 CRPC patients were treated with surgical treatment due to bladder clot packing and/or lower urinary tract obstruction. 8 HSPC patients had severe hematuria, severe dysuria and local symptoms. The KPS scores of all patients were ≥80 points with an average score of 84 (80-90). The average QOL score of 18 patients was 28 (21-32). 2 cases in 18 patients underwent total pelvic resection for rectal invasion (one CRPC and one HSPC). 7 cases underwent radical cystoprostatectomy for ureteral invasion (5 cases of CRPC, 2 cases of HSPC), 9 cases underwent bladder preservation surgery for bladder neck invasion (4 cases of CRPC, 5 cases of HSPC), of which 4 cases of enlarged lymph node dissection were all HSPC patients. Results:All cases of T 4 stage prostate cancer patients operation were successfully completed, the average operation time was 256 (219-310)min and the median intraoperative blood loss was about 300 (250-350)ml. Four of them (3 cases of CRPC and 1 case of HSPC) received blood transfusion after operation. The average postoperative hospital stay was 21(11-37) days. All 18 cases were followed up and the median follow-up time was 23.8 months. There was no perioperative death, and no bladder-preserving patients had true urinary incontinence or bladder outlet stenosis.2 CRPC cases died 8 and 15 months after surgery respectively, 7 patients were PSA relapse treated with docetaxel or abiterone therapy, and 1 HSPC patient with rectal invasion was followed up for 58 months after total pelvic resection, the PSA level was still 0.003ng/ml, no distant metastasis was found. 8 cases of hormone-sensitive patients were treated with endocrine therapy, and PSA was less than 0.2 ng/ml. The average QOL of 18 patients 3 months after operation was 37 points (25-45), which was significantly higher than that before operation. The average maximum urine flow rate of patients with bladder preservation was 23(19-25)ml/s. Conclusions:For T 4 stage prostate cancer, surgical treatment is feasible and safe for doctors with extensive surgical experience. For CRPC patients, the surgery can significantly improve short-term symptoms and quality of life, and long-term benefits need to be further evaluated with a large sample. For HSPC patients, it can not only improve clinical symptoms and QOL of patients, but also provide long-term benefits.

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.

Objective: To establish a UPLC-MS/MS analysis method for determination of baicalin, geniposide, chlorogenic acid, cholic acid and hyodeoxycholic acid in Qingkailing (lyophilized) for injection in rat plasma, and to investigate the pharmacokinetic behavior of this preparation in normal and cerebral ischemic rats. Method: Rats were randomly divided into normal group and cerebral ischemia model group. The rat model of cerebral ischemia was established by suture embolization. The rats were given by intraperitoneal injection, and normal saline was used as the solvent. Blood samples were taken at the corresponding time points. After treatment, UPLC-MS/MS was used to determine the blood concentration of five components. The main detection conditions were mobile phase of 0.1%formic acid aqueous solution-acetonitrile for gradient elution (0-0.25 min, 90%A; 0.25-1 min, 90%-75%A; 1-2 min, 75%-50%A; 2-2.6 min, 50%-45%A; 2.6-2.65 min, 45%-90%A; 2.65-4.0 min, 90%A), the flow rate of 0.4 mL·min^-1, the column temperature at 40℃, electrospray ionization under negative ion mode. The pharmacokinetic parameters were fitted and the bioavailability was calculated, the differences of treatment process of five components from Qingkailing (lyophilized) for injection in normal and cerebral ischemic rats were analyzed. Result: Compared with the normal group, the area under the curve (AUC_0-t) of geniposide in rats from cerebral ischemia model group decreased significantly after intraperitoneal injection of Qingkailing (lyophilized) for injection (P<0.05), and the time to peak (T_max) of chlorogenic acid in rats from cerebral ischemia model group was significantly earlier than that in the normal group (P<0.01). Pharmacokinetic parameters of baicalin, cholic acid and hyodeoxycholic acid had no significant difference between these 2 groups. Conclusion: Qingkailing (lyophilized) for injection has a certain difference in the treatment process between normal and cerebral ischemic rats, which has certain guiding significance for the clinical treatment of cerebral ischemic diseases with this preparation.

OBJECTIVE: To investigate the incidence of neonatal asphyxia and possible contributing factors for the development of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture, China. METHODS: A total of 16 hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture were selected as research centers. A retrospective analysis was performed for the clinical data of 22 294 live births in these 16 hospitals from January to December, 2016 to investigate the incidence rate of neonatal asphyxia and possible contributing factors for the development of severe asphyxia. RESULTS: Of the 22 294 neonates born alive, 733 (3.29%) were diagnosed with neonatal asphyxia, among whom 627 had mild asphyxia and 106 had severe asphyxia. The neonates with low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight had a higher incidence of severe asphyxia (P<0.05). CONCLUSIONS The incidence rate of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture is higher. Low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight may be related to the development of severe neonatal asphyxia.
Asphyxia Neonatorum ; epidemiology ; China ; Humans ; Incidence ; Infant, Newborn ; Retrospective Studies

OBJECTIVE: To investigate the gene mutation types and spectrum of α, β-thalassemia in Fuzhou area of China. METHODS: Thalassemia gene screening was performed in the women receiving physical, prenatal, and pre-pregnancy examination, and the patients with suspected thalassemia in our hospital from July 2013 to March 2018.Genotypes of thalassem were detected by Gap-PCR and RDB-PCR. RESULTS: 1042 were positive among 2074 suspected cases with a positive rate of 50.24%; 618 cases were confirmed to be α-thalassemia and with a positive rate of 29.8%; 409 cases were confirmed to be β-thalassemia with a positive rate of 19.72%. 15 cases were confirmed to be α-β complex thalassemia with a positive rate of 0.72%. the --/αα(76.54%) was the most common genotype among α-thalassemia, -α/αα(10.03%) and -α/αα(2.91%) in hot pursuit. In addition, IVS-II-55 (T->G) and IVS-II-119 (-G, +CTCGGCCC) were newly found alpha mutations; the IVS-2-654 (C→T) (40.83%) was the most common genotype among β-thalassemia, CD41-42 (-TCTT) (35.94%) and CD17 (A→T) (9.78%) in hot pursuit. CONCLUSION The genotype of thalassemia in Fuzhou area is highly heterogenic, --/αα is the most common genotype among α-thalassemia, IVS-2-654 (C→T) is the most common genotype among β-thalassemia, Meanwhile, two α-mutation sites are found in this study which were not reported in the Database of Human Hemoglobin Variants and Thalassemias.
China ; Female ; Genotype ; Humans ; Mutation ; Pregnancy ; alpha-Thalassemia ; beta-Thalassemia