Metabolomics is an interdisciplinary subject that rose in the post-genomic era, which focuses on quantitative study of the response of living organisms to outside stimulation and pathophysiological changes, as well as multiple dynamic response of the level of in vivo metabolites caused by genetic mutation. It is extensively used in basic research of system biology, materia medica, clinical medicine, etc. In the forensic field, metabolomics mainly focuses on forensic toxicology, but with the generalization of certain techniques, it's foreseeable that metabolomics has a broad research prospect in forensic pathology. This article summarizes the major analysis techniques and methods of metabolomics, describes the research status of metabolomic techniques in the field of forensic pathology application research, including postmortem interval and death cause. Moreover, this article summarizes and discusses the potential applicable areas, in order to provide reference for relative research and application.
Autopsy ; Forensic Pathology/trends* ; Forensic Toxicology ; Humans ; Metabolomics ; Postmortem Changes

OBJECTIVETo explore the development and prognosis of the acute flaccid paralysis (AFP) associated with enterovirus 71 (EV71) infection through clinical follow-up study for clinical and magnetic resonance imaging (MRI) features based on the research progress of virology and pathology.

METHODSixteen children with HFMD associated with AFP in hospital from May 1, 2011 to August 31, 2011 were investigated and the patients received intensive rehabilitation training. The 16 cases were divided into two groups (the recovery or the sequela) by if the muscle strength recovered to level 4 after intensive rehabilitation. The MRI findings of 15 children were analyzed and among them, 6 patients were reexamined after one month. The clinical markers were compared between groups including course of disease, WBC, WBC in cerebrospinal fluid (CSF), ventilator support, therapy, the worst muscle strength, the initial tendon reflex, the muscle atrophy, and multi-limb paralysis. The data were analyzed by t test and χ2 test with SPSS10.0.

RESULTAll the 16 children were infected with enterovirus 71 (EV71). The myodynamia of 7 children were level 0, 4 children had serious upper limbs paralysis. The neck muscle in 3 cases and the brain stem motor ruckus in 4 cases were involved. The ankle clonus of non-completely paralyzed limbs in 14 cases occurred during rehabilitation. Eight children had the better prognosis, the other 8 children had sequela. 0 level muscle strength (0 case vs. 7 cases, χ2=12.4), the initial tendon reflex (2 cases vs. 8 cases, χ2=9.6), obvious muscle atrophy (0 case vs. 8 cases, χ2=16), were significantly different in the children with the recovery when compared to the sequela (P<0.01). The severe upper limbs paralysis had the worse prognosis than the severe lower limbs paralysis. MR imaging showed signs of spinal nerve root inflammation and the bilateral hyperintense lesions, symmetrical in the posterior portions of the medulla, pons, and asymmetrical in the ventral horns of cervical spinal cord. Signal enhancement occurred only in the early MRI examination.

CONCLUSIONIn the evolution of AFP due to EV71 infection, the upper motor neuron damage is common, the prognosis is related with the severity of early paralysis and neuron damage. MR imaging is helpful to understand the pathological mechanism of AFP.

Child, Preschool ; Enterovirus A, Human ; pathogenicity ; Female ; Follow-Up Studies ; Hand, Foot and Mouth Disease ; diagnosis ; pathology ; virology ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Paralysis ; diagnosis ; pathology ; virology ; Prognosis

BACKGROUNDAttention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood, characterized by the core symptoms of hyperactivity, impulsivity and inattention and puts great burden on children themselves, their families and the society. Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH). It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles. The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.

METHODSThis 6-week, multi-center, prospective, open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg, 36 mg or 54 mg) treatment. The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales, physician-rated CGI-I and parent-rated global efficacy assessment scale. Blood pressure, pulse rate measurement, adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.

RESULTSA total of 1447 children with ADHD (mean age (9.52 ± 2.36) years) were enrolled in this trial. Totally 96.8% children received an OROS-MPH modal dose of 18 mg, 3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study. The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P < 0.001) improvement with OROS-MPH (mean: 6.95 ± 2.71) versus the score at baseline (10.45 ± 2.72). The change in the parent IOWA Conners O/D subscale, CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment. Fewer than half of 1447 patients (511(35.3%)) reported AEs, and the majority of the events reported were mild (68.2%). No serious adverse events were reported during the study.

CONCLUSIONThis open-label, naturalistic study provides further evidence of effectiveness and safety of OROS-MPH in school-aged children under routine practice.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; drug therapy ; Child ; Delayed-Action Preparations ; Female ; Humans ; Male ; Methylphenidate ; administration & dosage ; adverse effects ; therapeutic use ; Prospective Studies ; Treatment Outcome

Child ; Humans ; Motor Skills Disorders ; diagnosis ; therapy

OBJECTIVETo study the features of interictal epileptiform discharges (IED) during sleep and wakefulness in children with epilepsy.

METHODSThe polysomnography, active EEG and video EEG were performed on 48 children with epilepsy during the whole night, and wakefulness of pre- and post-sleep. The epileptiform sharp/spike discharge indexes during sleep and wakefulness were recorded. The positive rate of IED in focal and generalized epilepsy was compared.

RESULTSOf the 48 patients, 25 showed IED, including 9 cases (36.0%) in the generalized seizure group and 16 cases (64.0%) in the focal seizure group (P<0.05). The epileptiform sharp/spike discharge indexes in the whole non-rapid eye movement (NREM) sleep stage (stages S1-S4: 21.13+/-19.96, 19.59+/-17.76, 22.85+/-18.99, and 20.37+/-16.63) were significantly higher than that in the wakefulness stage (8.20+/-6.21) (P<0.05). The discharge index in the S3 stage during NREM sleep was higher than that during the rapid eye movement (REM) sleep (22.85+/-18.99 vs 12.91+/-10.95; P<0.05).

CONCLUSIONSThe positive rate of IED in the focal seizure group was higher than that in the generalized seizure group. Sleep, especially NREM sleep, facilitates IED in children with epilepsy.

Child ; Child, Preschool ; Electroencephalography ; Epilepsy ; physiopathology ; Humans ; Polysomnography ; Sleep ; physiology ; Wakefulness ; physiology

Objective To explore the feasibility of in vitro magnetic resonance imaging on Fe2O3-arginine labeled heNOS gene modified endothelial progenitor cells(EPCs). Methods Fe2O3 was incubated with arginine to form Fe2O3-arginine complex. Rabbit peripheral blood mononuclear cells (MNCs)were isolated and EPCs were isolated by adherence method, expanded and modified with heNOS gene using Lipofectamine<'TM2000. After 48 hours, genetically modified EPCs were incubated with Fe2O3-arginine for 24 hours. Intracellular iron was detected by Prussian blue stain. The expression of heNOS gene was detected by Western blot. MTT assay was used to evaluate cell survival and proliferation of Fe2O3-arginine labeled heNOS-EPCs. Flow cytometry was used to measure cell apoptosis. The cells underwent in vitro MR imaging with various sequences. Results Iron-containing intracytoplasmatic vesicles could be clearly observed with Prussian blue staining, and the labeling rate of labeled heNOS-EPCs were similar to that of labeled EPCs (around 100% ). Survival and apoptosis rates obtained by MTT and flow cytometry analysis were similar among labeled heNOS-EPCs, labeled EPCs and unlabeled EPCs with Fe2O3-arginine. The signal intensity on MRI was equally decreased in labeled heNOS-EPCs and labeled EPCs compared with that in unlabeled cells. The percentage change in signal intensity (ASI) was most significant on T2 * WI and △SI was significantly lower in cells labeled for 7 days than that labeled for 1 days. Conclusions The beNOS gene can be successfully transfected into rabbit peripheral blood EPCs using LipofectamineTM2000. The heNOS-EPCs can be labeled with Fe2O3-arginine without significant change in viability and proliferation capacity. The labeled heNOS-EPCs can be imaged with standard 1.5 T MR equipment. The degree of MR signal intensity may indirectly reflect the cell count, growth and division status.

OBJECTIVETo evaluate the effect of epilepsy on sleep in children.

METHODSWhole night polysomnography was performed in 48 epileptic children and 12 healthy controls. The 48 epileptic children were divided into focal seizure and generalized seizure groups and into waking seizure and sleeping seizure groups according to the time of occurrence of the seizures. Various parameters of sleep structure were analyzed.

RESULTSThe sleep efficiency of epileptic children was significantly lower than that of the healthy controls (85.4 +/- 8.6% vs 90.9 +/- 5.8%; P < 0.05). The total recording time (TRT) of sleep was significantly longer and the sleep efficiency was significantly lower in the focal seizure group compared to the control group (P < 0.05). The percentage of stage 1 non-rapid-eye-movement sleep (S1 sleep) increased and the percentage of rapid-eye-movement (REM) sleep decreased in the generalized seizure group compared to the control group (P < 0.05). The percentage of S1 sleep increased and both the percentage of REM sleep and the sleep efficiency decreased in the sleeping seizure group as compared with the control group (P < 0.05). There were no significant differences in the parameters of sleep structure between the waking seizure and the control group. Among the sleeping seizure group, the children with generalized seizure showed significantly lower REM sleep percentage and sleep efficiency, and those with focal seizure had significantly longer TRT and higher S1 sleep percentage as compared with the controls.

CONCLUSIONSEpilepsy affects sleep structure of patients, and different types of seizure have different influences on sleep structure. Children with generalized seizure have prolonged light sleep and shortened REM sleep. When generalized seizures occur during waking, the increase of light sleep is more pronounced. While generalized seizures occur during sleeping, REM sleep reduction is more prominent. Children with focal seizures have decreased sleep efficiency. When focal seizures occur during waking, the sleep structure of patients is normal. However, when seizures occur during sleeping light sleep increases and sleep efficiency decreases.

Adolescent ; Child ; Child, Preschool ; Epilepsy ; physiopathology ; Female ; Humans ; Infant ; Male ; Polysomnography ; Sleep Stages ; physiology

OBJECTIVETo investigate the effects of transcutaneous electrical nerve stimulation (TENS) on motor function in children with spastic cerebral palsy (CP).

METHODSAfter signing the informed consent, 78 children with CP, aged 45.6 +/- 8.5 months (36 to 58 months), were randomly divided into a TENS group (n = 40) and a control group (n = 38). All the subjects received standardized functional exercise program. In TENS group, 2 TENS devices were used and the surface electrodes were applied on the spastic musculotendinous and antagonist muscles in the affected lower extremity. TENS lasted for 20 min per session, 5 days weekly for 6 weeks. After 6 weeks, the functional exercise program was applied by the caregivers. Demographic data were recorded, including age, gender, number of the hemiplegic and diplegic CP, level of gross motor function classification system (GMFCS). Clinical assessments included the composite spasticity scale (CSS), D and E dimensions of the Gross Motor Function Measure (GMFM), and walking velocity was determined before treatment and at 6, 12 and 24 weeks after treatment.

RESULTSNo statistically significant differences were found in age, gender, number of the hemiplegic and diplegic CP, level of GMFCS, as well as clinical assessments (CSS, GMFM and walking velocity) before treatment between the 2 groups (P > 0.05). All the children showed a reduction of spasticity (CSS) after 6, 12 and 24 weeks of treatment (P < 0.05). When compared with the results obtained before treatment, the improvement of standing and walking (GMFM), walking velocity was statistically significant after 6, 12 and 24 weeks of treatment (P < 0.05). Furthermore, the differences of CSS, GMFM and walking velocity between the two groups at 6, 12 and 24 weeks examination were also statistically significant (after 24 weeks of treatment: t value was 8.96, 3.14 and 2.35, P < 0.05, respectively).

CONCLUSIONWhen compared with the control group, 6 weeks of TENS treatment on the affected lower extremity was more effective in terms of reducing spasticity and improving functional performance in standing, walking, and walking velocity in ambulant children with the spastic CP.

Cerebral Palsy ; therapy ; Child ; Electric Stimulation Therapy ; methods ; Female ; Gait Disorders, Neurologic ; therapy ; Hemiplegia ; therapy ; Humans ; Male ; Muscle Spasticity ; therapy ; Transcutaneous Electric Nerve Stimulation ; methods ; Treatment Outcome

OBJECTIVETo compare the effects of botulinum toxin A (BTX-A) injection guided by electric stimulation combined with physiotherapy, with physiotherapy only on the spasticity of the ankle plantar flexor in children with cerebral palsy (CP).

METHODSAfter signing the informed consent, 43 children with CP, aged 52.4 +/- 13.2 months (35 to 82 months), were randomly assigned into 2 groups, (1) BTX-A group (n = 23) treated with BTX-A injection guided by electric stimulation and (2) physiotherapy alone group (n = 20). Children in BTX-A group received injection of HengLi BTX-A in the ankle plantar flexors. A maximum dose of 12 units of BTX-A per kilogram body weight and maximumly 10 units of BTX-A per site were administered. Localization technique was the use of electrical stimulation guidance. Physiotherapy and ankle-foot orthosis were applied to children at 72 hours after injection in BTX-A group and at the time of being recruited into physiotherapy group. Ten days after entering into the study, the program was applied by the parents. Demographic data, including age, gender, number of the spastic lower limbs, affected side (left or right) were recorded. Clinical assessments included the range of passive movement (PROM) measured by goniometer while children maintained the knee extended, modified Ashworth scale (MAS), composite spasticity scale (CSS), D and E dimensions of the Gross Motor Function Measure (GMFM), and walking velocity (WV) was determined before treatment and at 2 weeks, 1, 2, and 3 months after treatment.

RESULTSNo statistically significant differences were found in age, gender, number of the spastic lower limbs, affected side, as well as clinical assessments (PROM, MAS, CSS, GMFM and WV) before treatment between the 2 groups (P > 0.05). All the children showed a reduction of spasticity (PROM, MAS and CSS) after 2 weeks, 1, 2, and 3 months of treatment (P < 0.05). When compared with the baseline findings, the improvement of standing and walking (GMFM), walking velocity were statistically significant after 2 weeks, 1, 2, and 3 months of treatment (P < 0.05). Furthermore, the differences of PROM, MAS and CSS between the 2 groups at 2 weeks, 1, 2, and 3 months examination were also statistically significant (after 3 months of treatment: t(PROM) = 6.48, t(MAS) = 9.74, t(CSS) = 9.59; P < 0.05). The difference in GMFM between the 2 groups was statistically significant (t(1M) = 2.20, t(2M) = 3.26, t(3M) = 4.13; P < 0.05) at 1, 2, and 3 months after treatment. The difference of WV between the 2 groups was statistically significant (t(2M) = 2.12, t(3M) = 2.57; P < 0.05) at 2 and 3 months after treatment.

CONCLUSIONBTX-A injection guided by electrical stimulation in combination with physiotherapy was more effective than physiotherapy alone in terms of reducing spasticity and improving functional performance in standing, walking, walking pattern and velocity on spasticity in ankle plantar flexors of ambulant children with CP.

Ankle Joint ; physiopathology ; Botulinum Toxins, Type A ; administration & dosage ; therapeutic use ; Cerebral Palsy ; drug therapy ; therapy ; Child ; Child, Preschool ; Electric Stimulation Therapy ; Female ; Gait ; Humans ; Male ; Muscle Spasticity ; drug therapy ; therapy

ObjectiveTo explore the effect and safety of intravenous sodium valproate in treatment of pediatric patients with status epilepticus (SE).MethodsTwenty-five children suffering from convulsive SE were treated with intravenous sodium valproate after failure of the conventional treatment, in a dose of tolerability 15 mg/kg and 1～2 mg/kg daily.ResultsIn 25 cases, there were 23 cases (92%) with ≥50% seizure reduction and 11 cases (44%) with complete cessation. Except for winking in 7 cases (28%), no other adverse effects had been found.ConclusionIntravenous sodium valproate is effective and safe on pediatric patients with SE who are resistant to conventional drugs.