BACKGROUND: All-trans retinoic acid (ATRA) is an ideal therapy for acute promyelocytic leukemia, which can induce promyelocytes to differentiate to mature granulocytes. However, differentiation syndrome is still a high risk for the patients undergoing ATRA therapy. Occurrence of this complication is closely related with cellular morphology change and expression and function of cellular adhesion molecules, especially selectin and integrin families. OBJECTIVE: To reveal rolling adhesion behavior and mechanical mechanism of ATRA treated HL-60 cells on the substrate coated with E-selectin under different fluid shear forces. METHODS: Using the equipment of parallel plate flow chamber, untreated and ATRA treated HL-60 cells were driven to roll on E-selectin-coated substrate. The mean rolling velocity and mean stop time were calculated. Here, the HL-60 cells were incubated in the medium containing 1×10-6mol/L ATRA for 0, 48, 72, 96 hours. The substrates were captured with 40 μg/L E-selectin overnight and the shear stresses were set to 0.02, 0.04, 0.06 Pa. RESULTS AND CONCLUSION: The velocity of untreated/treated HL-60 cells decreased firstly and then increased with monotonously increasing shear stress. On the contrary, the mean stop time and factional stop time increased firstly and then decreased. Therefore, we deduced that the flow enhanced rolling adhesion was regulated by the catch bond for the HL-60 cells rolling on E-selectin under flow. On the other side, rolling velocities decreased under the same shear stress even if treated with or without ATRA, and the mean stop time and factional stop time increased inversely, which further illustrate the rolling velocity is mainly regulated by stop time.

OBJECTIVETo study the clinical and pathological features of children with Duchenne muscular dystrophy (DMD), with the aim of increasing the possibility of early diagnosis.

METHODSThe clinical data of 50 children who were definitely diagnosed with DMD, based on clinical manifestations and the results of skeletal muscle biopsies and monoclonal antibody immunohistochemical staining, was reviewed.

RESULTSThe children showed similar clinical manifestations, including running slowly in the toddler period, muscle weakness when climbing stairs and standing up followed by squatting down and walking abnormalities a predominant increase in serum creatine kinase level increased dominantly, and myopathic lesions seen on electromyography. Hematoxylin-eosin staining showed similar pathological presentations in all 50 children, including different-sized muscle fibers with rounding, degeneration and necrosis in various degrees, and proliferation of connective tissues. There was some inflammatory cell infiltration in muscle fibers and interstitial tissues. Dystrophin expression was completely absent at the sarcolemma in all 50 children, and sarcoglycan-α,-β, -',-δ expression was reduced to various degrees in 33 of them.

CONCLUSIONSFor children with the clinical manifestations mentioned above, skeletal muscle biopsies and monoclonal antibody immunohistochemical staining are recommended as these examinations contribute to a definite diagnosis of DMD by demonstrating dystrophin deficiency at the sarcolemma.

Adolescent ; Child ; Child, Preschool ; Dystrophin ; genetics ; Humans ; Immunohistochemistry ; Infant ; Male ; Muscle, Skeletal ; pathology ; Muscular Dystrophy, Duchenne ; complications ; genetics ; pathology ; Retrospective Studies

Objective:To explore the type distribution and severity of central nervous system(CNS) complications in severe hand, foot and mouth disease (HFMD) cases prior to the introduction of human enterovirus A group 71 type (EV-A71) vaccine, and provide scientific data for early clinical intervention.Methods:A total of 3 583 laboratory-confirmed severe HFMD cases in Jiangsu province during 2010-2016 were collected and analyzed retrospectively. Related early warning signs of increased HFMD severity were estimated with logistic regression analyses.Results:The severity-fatality rate, severity-pediatric intensive care unit(PICU) admission rate, and sequelae rate were 8.09‰(29/3 583), 11.75% (421/3 583)and 5.30‰(19/3 583). Of them, 39.02% (1 398/3 583) patients suffered from mild CNS involvement, 59.22% (2 122/3 583) patients suffered from severe CNS involvement, 1.76%(63/3 583) suffered from critical CNS involvement. The rates of the cases whose age of onset was 6-11 months, the rates of cases with atypical rash, respiratory-related signs and symptoms (shortness of breath, slowed breathing, dyspnea, etc), neurological-related signs and symptoms [(hand and foot shaking, convulsions, lethargy(sleepiness), etc], circulatory-related system signs and symptoms (faster heart rate, abnormal skin color, arrhythmia, cold limbs), laboratory-related indicators (increased white blood cell count, increased lymphocyte count, increased platelet count, increased C-reactive protein, etc), clinical auxiliary examination [electroencephalogram(EEG), brain CT, chest X-ray)] were highest in the critical CNS involvement group, and the differences were significant ( P<0.05). Multivariate logistic regression analysis showed that with the increase of proportion of convulsions, slowed breathing, vomiting, meningeal irritation and other 7 variables, the severity of CNS complications increased ( P<0.05). Conclusions:The indicators such as easily startled, slow breathing, vomiting, elevated lymphocytes, abnormal EEG and other indicators have important clinical significance for children with severe HFMD to progress to CNS complications of different severity.

BACKGROUNDFenvalerate (FEN) has been demonstrated to be a reproductive toxicant in humans and rodents. However, little is known about whether short-term exposure to low-dose FEN produces reproductive toxicity.

METHODSWe administered FEN (0.009 375, 0.1875, 3.750, or 45.00 mg×kg(-1)×d(-1) by gavage for 30 days) to male ICR mice and compared reproductive toxicity parameters between groups receiving different concentrations of FEN. Reproductive toxicity was evaluated by computer-assisted semen quality analysis (CASA), chlortetracycline (CTC) assay, and histopathology.

RESULTSThe sperm morphology and testis histology of FEN-exposed mice (all doses) were similar to that in controlling mice. Exposure to FEN at a concentration of 0.1875 mg×kg(-1)×d(-1) decreased sperm path straightness (STR) and linearity (LIN) (both P < 0.05), but had no significant impact on average path velocity (VAP), straight line velocity (VSL), curvilinear velocity (VCL), lateral amplitude (ALH), beat cross frequency (BCF), or progressive motility (MOT). FEN reduced the rate of mouse sperm capacitation in a dose-dependent manner.

CONCLUSIONThe present results demonstrate that exposure to low-dose FEN for 30 days reduces semen quality and sperm capacitation in adult mice.

Animals ; Body Weight ; drug effects ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Nitriles ; pharmacology ; Organ Size ; drug effects ; Pyrethrins ; pharmacology ; Semen ; drug effects ; Semen Analysis ; Sperm Motility ; drug effects ; Testis ; drug effects

Non-progressive congenital myopathy is a group of muscle diseases occurring at birth or during teenage years. A number of new reports of congenital myopathy, such as homogeneous bodies myopathy, muscle quality control myopathy and type 1 fiber predominance have recently been reported, but they lack of sufficient quantity and constant clinico-pathologic manifestations. This paper reports two cases of congenital myopathy with type 1 fiber predominance confirmed by muscle biopsy. The clinical manifestations of the two children (a 4.5-year-old girl and an 11-year-old boy) included non-progressive symptoms of muscle weakness, skeletal deformities and other clinical features of congenital myopathy. The physical examinations showed a long face or figure and funnel chest or kyphosis/scoliosis, high palatal arch and wing-like shoulder. Serum levels of creatine kinase were normal but slightly elevated serum lactate dehydrogenase levels were noted in the two children. The skeletal muscle biopsy by ATPase staining showed that type 1 fibers accounted for more than 90% of the total number of muscle fibers. No other abnormal pathological changes, such as central cores, muscle tube and central nuclei, were found in the two children.
Diagnosis, Differential ; Female ; Humans ; Infant ; Male ; Muscle, Skeletal ; pathology ; Myopathies, Structural, Congenital ; diagnosis ; pathology ; therapy

Objective: To evaluate the pathogenicity of Acinetobacter venetum（Av），which is expected to be used as an environmental remediation agent，using Caenorhabditis elegans（C.elegans）. Methods: The C.elegans were cultured on the media loaded with E.coli OP50 and Av，respectively. The pathogenicity of Av was evaluated by observing the effects of Av on the growth，movement，digestive function，lifespan and reproduction of C.elegans，compared with that of another evaluation system according to NY 1109-2017 General Biosafety Standard for Microbial Fertilizers. Results: By C. elegans system，it was found that the body length，width，head thrash frequency，body bending frequency and average lifespan [（13.5±0.4）d vs.（13.7±0.4）d] of adult nematodes in the Av group were not significantly different from those in the OP50 group（all P>0.05）；while the average time of defecation cycle in the Av group shortened，the total number of progenies in the Av group increased by 18.7%（all P<0.05）. According to NY1109-2017 General Biosafety Standard for Microbial Fertilizers，it was found that the oral LD50 values for both male and female mice were more than 10 g/kgbw，which was practically non-toxic；the pathogenicity test of acute intraperitoneal injection showed that the animals did not have signs of poisoning，deaths or any abnormalities in gross anatomy；Av had no irritation to damaged skin and eyes of rabbits；the hemolysis test was negative；Av was sensitive to seven antibiotics and was medium to one antibiotic. Conclusion Av is not pathogenic. C. elegans can be used in early screening for the pathogenicity of environmental remediation agents.

OBJECTIVE: To study the association between maternal reduced folate carrier ( METHODS: A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that maternal CONCLUSIONS Maternal
Case-Control Studies ; Child ; Female ; Genetic Predisposition to Disease ; Genotype ; Heart Defects, Congenital/genetics* ; Humans ; Infant ; Polymorphism, Single Nucleotide ; Reduced Folate Carrier Protein/genetics* ; Risk Factors

Remitting seronegative symmetrical synovitis with pitting edema(RS3PE),the inflammatory arthritis attacking mainly elderly males,is characterized by symmetrical synovitis with pitting edema of the dorsum of hands and feet and the absence of rheumatoid factor.RS3PE commonly accompanies malignant tumor,infections and other diseases.Here we report a case of RS3PE associated with lung malignancy and review other six cases to summarize the clinical features,treatment and prognosis.
Aged ; Edema/etiology* ; Humans ; Lung Neoplasms/complications* ; Male ; Syndrome ; Synovitis/drug therapy*

Objective To investigate the trend and risk factors of leukemia disease burden in Chinese population from 1990 to 2019, and to provide new ideas for leukemia prevention. Methods The Global Burden of Disease (GBD) study data in 2019 were used for regression analysis through Joinpoint Regression Program. The leukemia incidence, mortality, disability adjusted life year (DALY), years of life lost (YLL), years lived with disability (YLD) and their corresponding age standardized rates were calculated and compared with global level and all Socio–Demographic Index (SDI) countries. Average annual percentage of change (AAPC) was calculated to reflect the trend of disease burden. The changes in disease burden attributable to each risk factor were calculated. Results From 1990 to 2019, the incidence of leukemia in China decreased from 12.06/100 000 to 10.87/100 000, the mortality decreased from 5.65/100 000 to 4.25/100 000 , and the DALY rate decreased from 328.95/100 000 to 162.36/100 000. The standardized incidence, standardized mortality and standardized DALY rates all decreased year by year, with AAPC being 0.6%, 1.8%, and 2.4%, respectively. In 2019, the disease burden of leukemia in China was higher than the global average, and the standardized DALY rate and standardized YLL rate were the highest among all SDI countries. Adolescents and children had the greatest decline in the disease burden index. Smoking was the main risk factor among the four risk factors collected, and the increase of body mass index (BMI) was also one of the important risk factors. Conclusion From 1990 to 2019, the disease burden of leukemia in China generally showed a downward trend. Smoking is the main risk factor of leukemia. At present, the disease burden of leukemia in China is still at a high level, and intervention should be strengthened for key populations.

Cyclophosphamide (CPA) is one of the most commonly used alkylating agents in the treatment of malignant cancer. CPA is metabolized by cytochrome P450 enzymes into 4-hydroxycyclophosphamide in vivo which can exhibit anti-tumor activity. Metabolic activation of CPA can cause adverse reactions such as myelosuppression, cystitis, and liver injury. The aim of this study was to evaluate the dynamic changes of hepatic injury induced by CPA in mice. Male BALB/c mice were injected CPA (200 mg·kg^-1) intraperitoneally. Both serum and liver samples were collected at 0, 2, 6, 12 and 24 hours after dosing. The animal experiment protocol was approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University. The results showed that hepatotoxicity was observed at 2 hours after CPA dosing, and the most serious liver injury was measured at 12 hours. The level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) was significantly increased, glutathione (GSH) level was significantly decreased, hepatocyte edema and vacuolar degeneration were widely observed in liver tissue, and began to recover 24 hours after dosing. In addition, due to oxidative stress damage caused by CPA, nuclear factor-erythroid 2-related factor 2 (NRF2) signaling pathway was activated and the mRNA and protein expression of its downstream targets such as quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate cysteine modifier subunit (GCLM) were up-regulated, which alleviated oxidative stress injury. In a summary, this study demonstrate the dynamic change of CPA-induced liver injury and the NRF2-mediated protective mechanisms, providing new insights into the CPA-induced liver injury.