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It is well-known that highly reactive hydroxyl radicals (HOâ¢) can be produced by the classic Fenton system and our recently discovered haloquinone/H2O2 system, but rarely from thiol-derivatives. Here, we found, unexpectedly, that HO⢠can be generated from H2O2 and thiourea dioxide (TUO2), a widely used and environmentally friendly bleaching agent. A carbon-centered radical and sulfite were detected and identified as the transient intermediates, and urea and sulfate as the final products, with the complementary application of electron spin-trapping, oxygen-18 isotope labeling coupled with HPLC/MS analysis. Density functional theory calculations were conducted to further elucidate the detailed pathways for HO⢠production. Taken together, we proposed that the molecular mechanism for HO⢠generation by TUO2/H2O2: TUO2 tautomerizes from sulfinic acid into ketone isomer (TUO2-K) through proton transfer, then a nucleophilic addition of H2O2 on the S atom of TUO2-K, forming a S-hydroperoxide intermediate TUO2-OOH, which dissociates homolytically to produce HOâ¢. Our findings represent the first experimental and computational study on an unprecedented new molecular mechanism of HO⢠production from simple thiol-derived sulfinic acids, which may have broad chemical, environmental, and biomedical significance for future research on the application of the well-known bleaching agent and its analogs.
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We have found recently that two-step intrinsic hydroxyl radical (·OH)-dependent chemiluminescence (CL) could be produced by carcinogenic tetrahaloquinone and H2O2. However, the first-step CL was too fast to clearly detect the stepwise generation of ·OH and CL, and to distinguish the exact dividing point between the first-step and second-step CL. Here we found that, extremely clear two-step intrinsic CL could be produced by the relative slow reaction of tetrabromohydroquinone (TBHQ) with H2O2, which was directly dependent on the two-step ·OH generation. Interestingly, the second-step, but not the first-step CL production of TBHQ/H2O2 (CRET donor) was markedly enhanced by fluorescein (a typical xanthene dye, CRET acceptor) through a unique chemiluminescence resonance energy transfer (CRET) process. The novel CRET system of TBHQ/H2O2/fluorescein was successfully applied for the sensitive detection of TBHQ with the detection limit as low as 2.5 µmol/L. These findings will help to develop more sensitive and highly efficient CL or CRET systems and specific CL sensor to detect the carcinogenic haloquinones, which may have broad environmental applications.
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Carcinógenos , Hidroquinonas , Luminescência , Peróxido de Hidrogênio , FluoresceínasRESUMO
OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.
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Neurodevelopmental disorders (NDDs) in children are a group of chronic developmental brain disorders caused by multiple genetic or acquired causes, including disorders of intellectual development, developmental speech or language disorders, autism spectrum disorders, developmental learning disorders, attention deficit hyperactivity disorder, tic disorders, and other neurodevelopmental disorders. With the improvement in the research level and the diagnosis and treatment techniques of NDDs, great progress has been made in the research on NDDs in children. This article reviews the research advances in NDDs, in order to further improve the breadth and depth of the understanding of NDDs in children among pediatricians.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Humanos , Criança , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/terapia , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/terapiaRESUMO
OBJECTIVES: To study the very-early and early neuroelectrophysiological features of childhood Guillain-Barré syndrome (GBS) and their association with clinical diagnosis. METHODS: A retrospective analysis was performed on the neuroelectrophysiological data of 43 children with GBS. According to the interval from onset to neuroelectrophysiological examination, the children were divided into a very-early examination group with 18 children (an interval from onset to the examination of ≤7 days) and an early examination group with 25 children (an interval from onset to the examination of 7 to ≤14 days). The children with acute flaccid paralysis, matched for the examination time of GBS children, were enrolled as the control group. The abnormal rates of neuroelectrophysiological parameters were compared between the above groups. According to the results of the H reflex test, the GBS children were divided into an abnormal H reflex group and a normal H reflex group, and related clinical data were compared between the two groups. RESULTS: Compared with the control group, the very-early and early examination groups had a significantly higher abnormal rate of H reflex (P<0.05), while there was no significant difference in the abnormal rates of F wave, motor nerve conduction, and sensory nerve conduction (P>0.05). Compared with the normal H reflex group, the abnormal H reflex group had a significantly shorter interval from onset to the time of confirmed diagnosis (P<0.05). CONCLUSIONS: Absence of the H reflex is a valuable parameter of neuroelectrophysiological abnormalities in the early stage of GBS and can help with the diagnosis of GBS.
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Síndrome de Guillain-Barré , Criança , Síndrome de Guillain-Barré/diagnóstico , Humanos , Condução Nervosa/fisiologia , Estudos RetrospectivosRESUMO
Pyridinium aldoximes are best-known therapeutic antidotes used for clinical treatment of poisonings by organophosphorus nerve-agents and pesticides. Recently, we found that pralidoxime (2-PAM, a currently clinically used nerve-agent antidote) could also detoxify tetrachloro-1,4-benzoquinone (TCBQ), which is a carcinogenic quinoid metabolite of the widely used wood preservative pentachlorophenol under normal physiological conditions, via an unusually mild and facile Beckmann fragmentation mechanism accompanied by radical homolysis. However, it is not clear whether the less-chlorinated benzoquinones (CnBQs, n ≤ 3) act similarly; if so, what is the structure-activity relationship? In this study, we found that (1) The stability of reaction intermediates produced by different CnBQs and 2-PAM was dependent not only on the position but also the degree of Cl-substitution on CnBQs, which can be divided into TCBQ- and DCBQ (dichloro-1,4-benzoquinone)-subgroup; (2) The pKa value of hydroxlated quinones (Cn-1BQ-OHs, the hydrolysis products of CnBQs), determined the stability of corresponding intermediates, that is, the decomposition rate of the intermediates depended on the acidity of Cn-1BQ-OHs; (3) The pKa value of the corresponding Cn-1BQ-OHs could also determine the reaction ratio of Beckmann fragmentation to radical homolysis in CnBQs/2-PAM. These new findings on the structure-activity relationship of the halogenated quinoid carcinogens detoxified by pyridinium aldoxime therapeutic agents via Beckmann fragmentation and radical homolysis reaction may have broad implications on future biomedical and environmental research.
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Benzoquinonas/química , Carcinógenos/química , Agentes Neurotóxicos/química , Oximas/química , Halogenação , Concentração de Íons de Hidrogênio , Hidrólise , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To study the association of motor nerve conduction block (CB) with different subtypes of childhood Guillain-Barré syndrome (GBS). METHODS: A retrospective analysis was performed on the clinical and nerve electrophysiological data of 50 children with GBS. According to the results of nerve electrophysiology, the children were divided into an acute inflammatory demyelinating polyneuropathy (AIDP) group with 29 children and an acute motor axonal neuropathy (AMAN) group with 21 children. According to the presence or absence of motor nerve CB, the children with AMAN or AIDP were further divided into subgroups: group AMAN with or without motor nerve CB (n=10 and 11 respectively) and group AIDP with or without motor nerve CB group (n=19 and 10 respectively). The subgroups were compared in terms of age of onset, sex, Hughes Functional Grading Scale (HFGS) at nadir for the most severe involvement of motor function, and short-term prognosis based on HFGS score at 1 month after disease onset. RESULTS: Motor nerve CB was reversible in children with AMAN. AMAN children with motor nerve CB had a significantly lower HFGS score than those without motor nerve CB at 1 month after onset (P<0.05). AIDP children with motor nerve CB had a significantly higher HFGS score than those with motor nerve CB at 1 month after onset (P<0.05). CONCLUSIONS: AMAN with reversible motor nerve CB suggests mild nerve fiber lesion and has better recovery than AMAN and AIDP without motor nerve CB in short term.
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Síndrome de Guillain-Barré , Criança , Humanos , Condução Nervosa , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To study the clinical features of asymptomatic or subclinical coronavirus disease 2019 (COVID-19) in children. METHODS: A retrospective analysis was performed for the clinical data of 53 children who were confirmed with asymptomatic or subclinical COVID-19, including epidemiological history, clinical typing, co-infection, time to clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid in nasopharyngeal swabs, laboratory examination results, length of hospital stay, and treatment outcome. RESULTS: The children with asymptomatic or subclinical COVID-19 accounted for 30.5% (53/174) in children with COVID-19 hospitalized in the COVID-19 ward of Wuhan Children's Hospital. All cases occurred with familial aggregation. Among the 53 children, 35 (66%) had asymptomatic infection and 18 (34%) had subclinical infection. Mycoplasma infection was found in 17 children (32%). For the 53 children, the mean time to clearance of SARS-CoV-2 nucleic acid in nasopharyngeal swabs was 9±4 days. Most laboratory markers were maintained within the normal range. The mean hospital stay was 11±4 days. Lung CT of 18 children with subclinical COVID-19 showed ground-glass opacities, linear opacities, and patchy opacities, with relatively limited lesions. CONCLUSIONS: There is a high proportion of children with asymptomatic or subclinical COVID-19 among the children with COVID-19 hospitalized in the COVID-19 ward. The transmission risk of asymptomatic or subclinical COVID-19 should be taken seriously.
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Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , COVID-19 , Criança , Humanos , Estudos Retrospectivos , SARS-CoV-2RESUMO
An atmosphere-pressure Dielectric Barrier Discharge in Ar/NH3 mixtures between cylinder electrodes is studied by Optical Emission Spectroscopy and the main particles of atmosphere-pressure Ar/NH3 DBD plasma are NH, N, N+, N2, Ar, H(α) and OH. NH is decomposition products of NH3, and NH(c 1π) and NH(A 3π) are two kinds of excited-state neutral particles and produced by penning ionization of Ar* and NH3. The nitrogen active atom is detected at 674.5 nm which may provide the experimental foundation for the synthesis of ε-Fe3N ferroparticles by the atmosphere-pressure Ar/NH3 DBD plasma. The intensities of main particles are analyzed at different NH3 flow rate and applied voltage peak-peak value. The results show that the spectral line intensities of various particles increase with the rise of the applied voltage peak-peak value at the same NH3 flow rate, and first increase and then decrease with the increase of the NH3 flow rate at the same applied voltage peak-peak value. The applied voltage peak-peak value being kept constant, the spectral line intensity of nitrogen active atom first increases and then decreases with the increase of the NH3 flow rate. When NH3 flow rate is 20 mL x min(-1), the spectral line intensity of nitrogen active atom reaches a maximum at the same applied voltage peak-peak value. The spectral line intensity of nitrogen active atom decreases gradually with increasing the applied voltage peak-peak value at the same NH3 flow rate and it is mainly because of the translation of discharge mode from multi-pulse APGD to filamentary discharge in the atmosphere-pressure Ar/NH3 DBD. The microdischarge channels overlap and the microdischarges affect each other in multi-pulse APGD; hence the increasing rate of the spectral line intensity is quicker in multi-pulse APGD than in filamentary discharge with increasing the applied voltage peak-peak value. When the applied voltage peak-peak value is up from 4 600 to 6 400 V, the single-pulse and two-pulse APGD mode which are two kinds of homogeneous DBD mode are found in the atmosphere-pressure Ar/NH3 DBD and the increasing rate of the spectral line intensity is quicker in multi-pulse APGD than in filamentary discharge which is beneficial to synthesize ε-Fe3N ferroparticles.
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OBJECTIVE: To study the association between two single nucleotide polymorphisms (SNP), rs2295080 and rs2536, in mammalian target of rapamycin (mTOR) gene and the susceptibility to pediatric epilepsy. METHODS: A case- control study was performed on 480 children with epilepsy (116 cases of refractory epilepsy) and 503 healthy children. SNP rs2295080 and rs2536 in the mTOR gene were detected by polymerase chain reaction restriction and fragment length polymorphisms (PCR-RFLP). Genotype and allele frequencies of SNP rs2295080 and rs2536 were compared between the children with epilepsy and healthy controls. RESULTS: There were no significant differences in the genotype and allele frequencies of SNP rs2295080 between the children with epilepsy and healthy controls. There were no significant differences in the genotype frequencies of SNP rs2536 between the two groups either, but the frequency of G allele of SNP rs2536 was higher in children with epilepsy than that in healthy controls (P=0.042, OR=1.344, 95%CI: 1.010-1.789). CONCLUSIONS: SNP rs2536 of mTOR gene may be associated with the risk of pediatric epilepsy.
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Epilepsia/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Serina-Treonina Quinases TOR/genética , Epilepsia/etiologia , Frequência do Gene , Genótipo , Humanos , RiscoRESUMO
OBJECTIVE: This study was to establish the population pharmacokinetic (PPK) model of pharmacologically active metabolite of oxcarbazepine (OXC) and to estimate PPK parameters for the optimal individuation administration of OXC in Chinese children with epilepsy. METHODS: The pharmacologically active metabolite, 10-monohydroxy derivative of OXC (MHD)was used as the analytical target for monitoring therapy of OXC. A total of 840 MHD serum samples from 466 children with epilepsy were analyzed using high-performance liquid chromatography with UV detection. Patients' clinical data were retrospectively collected. Population pharmacokinetics analysis was performed using a non-linear mixed-effect model with Phoenix NLME 1.2. Pharmacokinetic parameters were estimated according to a one-compartment model with first-order absorption and elimination. Effects of age,gender, total body weight (TBW), daily doseper weight (DDPW) and use of concomitant antiepileptic drugs (AEDs) were analyzed.Bootstrap and predictive check were used simultaneously to validate the final population pharmacokinetics models. RESULTS: The final PPK model of MHD was: Ka = 0.645 h⻹, V(L) = (11.3 + (age - 90.5) x 0.0282 + (TBW - 25.0) x 0.402) x e(0.0689), CL (L/h) = (0.557 + (DDPW - 20.8) x 0.00367 + (gender) x (-0.0636)) x e(0.120). The final PPK model was demonstrated to be suitable and effective by the bootstrap and predictive check. CONCLUSIONS: A PPK model of MHD in Chinese children with epilepsy was successfully established. PPK parameters of MHD could be predicted accurately by this model. This model may be very useful for establishing individual dosage guidelines of OXC in Chinese children with epilepsy.
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Anticonvulsivantes/farmacocinética , Carbamazepina/análogos & derivados , Epilepsia/tratamento farmacológico , Modelos Biológicos , Adolescente , Anticonvulsivantes/uso terapêutico , Povo Asiático , Carbamazepina/farmacocinética , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Humanos , Lactente , Masculino , Dinâmica não Linear , Oxcarbazepina , Estudos RetrospectivosRESUMO
Previous studies have demonstrated a strong association between carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) and HLA-B*1502 in Han Chinese. Here, we extended the study of HLA-B*1502 susceptibility to two different antiepileptic drugs, oxcarbazepine (OXC) and phenobarbital (PB). In addition, we genotyped HLA-B*1511 in a case of CBZ-induced SJS with genotype negative for HLA-B*1502. The presence of HLA-B*1502 was determined using polymerase chain reaction with sequence-specific primers (PCR-SSP). Moreover, we genotyped HLA-B*1502 in 17 cases of antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs), in comparison with AEDs-tolerant (n=32) and normal controls (n=38) in the central region of China. The data showed that HLA-B*1502 was positive in 5 of 6 cases of AEDs-induced SJS (4 CBZ, 1 OXC and 1 PB), which was significantly more frequent than AEDs-tolerant (2/32, 18 CBZ, 6 PB and 8 OXC) and normal controls (3/38). Compared with AEDs-tolerant and normal controls, the OR for patients carrying the HLA-B*1502 with AEDs-induced SJS was 6.25 (95% CI: 1.06-36.74) and 4.86 (95% CI: 1.01-23.47). The sensitivity and specificity of HLA-B*1502 for prediction of AEDs-induced SJS were 71.4%. The sensitivity and specificity of HLA-B*1502 for prediction of CBZ-induced SJS were 60% and 94%. HLA-B*1502 was not found in 11 children with maculopapular exanthema (MPE) (n=9) and hypersensitivity syndrome (HSS) (n=2). However, we also found one case of CBZ-induced SJS who was negative for HLA-B*1502 but carried HLA-B*1511. It was suggested that the association between the CBZ-induced SJS and HLA-B*1502 allele in Han Chinese children can extend to other aromatic AEDs including OXC and PB related SJS. HLA-B*1511 may be a risk factor for some patients with CBZ-induced SJS negative for HLA-B*1502.
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Anticonvulsivantes/efeitos adversos , Predisposição Genética para Doença/genética , Antígeno HLA-B15/genética , Síndrome de Stevens-Johnson/genética , Adolescente , Alelos , Povo Asiático/genética , Carbamazepina/efeitos adversos , Carbamazepina/análogos & derivados , Criança , Pré-Escolar , China , Feminino , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Lactente , Masculino , Oxcarbazepina , Fenobarbital/efeitos adversos , Reação em Cadeia da Polimerase , Síndrome de Stevens-Johnson/etnologia , Síndrome de Stevens-Johnson/etiologiaRESUMO
OBJECTIVE: To study the clinical features and mutations in methyl-CpG-binding protein 2 (MECP2) gene among children with classical Rett syndrome in China. METHODS: PCR and direct sequencing were employed to analyze the three exons of MECP2 gene in 9 children recently diagnosed with Rett syndrome and their parents. RESULTS: Heterozygous mutations were identified in 5 out of 9 patients, with a mutation rate of over 50%; there was one case of insert mutation (c.913insT) and 4 cases of missense mutation (exon 3: c.316C>T (R106W); exon 4: c.502C>T (R168X), c.808C>T (R270X), and c.1126C>T (P376S). A new mutation (c.913insT) was found. No mutations were detected in their parents. Two patients had MECP2 mutations in the transcriptional repression domain (TRD). They had almost lost language functions and were found to have significantly delayed development compared with other patients. CONCLUSIONS: Mutations in MECP2 gene were detected in 5 confirmed cases of Rett syndrome, and most of them were on exon 4. Mutations in the TRD of MECP2 protein may affect the language ability and development in children with Rett syndrome.
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Proteína 2 de Ligação a Metil-CpG/genética , Mutação , Síndrome de Rett/genética , Pré-Escolar , Feminino , Humanos , Lactente , Desenvolvimento da Linguagem , Síndrome de Rett/psicologiaRESUMO
BACKGROUND: Laparoscopic low anterior resection (LLAR) has become a mainstream surgical method for the treatment of colorectal cancer, which has shown many advantages in the aspects of surgical trauma and postoperative rehabilitation. However, the effect of surgery on patients' left coronary artery and its vascular reconstruction have not been deeply discussed. With the development of medical imaging technology, 3D vascular reconstruction has become an effective means to evaluate the curative effect of surgery. AIM: To investigate the clinical value of preoperative 3D vascular reconstruction in LLAR of rectal cancer with the left colic artery (LCA) preserved. METHODS: A retrospective cohort study was performed to analyze the clinical data of 146 patients who underwent LLAR for rectal cancer with LCA preservation from January to December 2023 in our hospital. All patients underwent LLAR of rectal cancer with the LCA preserved, and the intraoperative and postoperative data were complete. The patients were divided into a reconstruction group (72 patients) and a nonreconstruction group (74 patients) according to whether 3D vascular reconstruction was performed before surgery. The clinical features, operation conditions, complications, pathological results and postoperative recovery of the two groups were collected and compared. RESULTS: A total of 146 patients with rectal cancer were included in the study, including 72 patients in the reconstruction group and 74 patients in the nonreconstruction group. There were 47 males and 25 females in the reconstruction group, aged (59.75 ± 6.2) years, with a body mass index (BMI) (24.1 ± 2.2) kg/m2, and 51 males and 23 females in the nonreconstruction group, aged (58.77 ± 6.1) years, with a BMI (23.6 ± 2.7) kg/m2. There was no significant difference in the baseline data between the two groups (P > 0.05). In the submesenteric artery reconstruction group, 35 patients were type I, 25 patients were type II, 11 patients were type III, and 1 patient was type IV. There were 37 type I patients, 24 type II patients, 12 type III patients, and 1 type IV patient in the nonreconstruction group. There was no significant difference in arterial typing between the two groups (P > 0.05). The operation time of the reconstruction group was 162.2 ± 10.8 min, and that of the nonreconstruction group was 197.9 ± 19.1 min. Compared with that of the reconstruction group, the operation time of the two groups was shorter, and the difference was statistically significant (t = 13.840, P < 0.05). The amount of intraoperative blood loss was 30.4 ± 20.0 mL in the reconstruction group and 61.2 ± 26.4 mL in the nonreconstruction group. The amount of blood loss in the reconstruction group was less than that in the control group, and the difference was statistically significant (t = -7.930, P < 0.05). The rates of anastomotic leakage (1.4% vs 1.4%, P = 0.984), anastomotic hemorrhage (2.8% vs 4.1%, P = 0.672), and postoperative hospital stay (6.8 ± 0.7 d vs 7.0 ± 0.7 d, P = 0.141) were not significantly different between the two groups. CONCLUSION: Preoperative 3D vascular reconstruction technology can shorten the operation time and reduce the amount of intraoperative blood loss. Preoperative 3D vascular reconstruction is recommended to provide an intraoperative reference for laparoscopic low anterior resection with LCA preservation.
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Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment, and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.
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Mpox , Humanos , Criança , Mpox/diagnóstico , Mpox/epidemiologia , Mpox/prevenção & controle , Saúde Pública , Diagnóstico Diferencial , Vacinação , China/epidemiologiaRESUMO
OBJECTIVE: To establish an in vitro model of perineural invasion (PNI) with co-culture of human pancreatic cancer cells and rat root ganglion, to observe the neurite outgrowth and pancreatic cancer cell proliferation and migration, and to explore the molecular basis of perineural invasion (PNI) of pancreatic cancer. METHODS: Human pancreatic cancer cell line (MIA PaCa-2) and rat dorsal root ganglion (DRG) were co-cultured in Matrigel matrix to generate the PNI model. The neurite outgrowth, pancreatic cancer cell colony formation, neurite-colony contact and retrograde migration were observed under an inverted microscope. The data were analyzed with the Image-Pro Plus 5.0 system. The proliferative index (PI) was measured by immunohistochemical staining with the Ki-67 antibody. In order to determine the absorbance (A) of the pancreatic cancer cells, MTT assay was used. The apoptotic index (AI) was evaluated by flow cytometry. RESULTS: Neurite outgrowth was stimulated in the presence of pancreatic cancer cells. After 72 hours of the co-culture, MIA PaCa colonies co-cultured with DRG exhibited a significantly larger colony area (242.83 ± 4.92) than that of the control (182.50 ± 5.39, P < 0.001). In the MIA PaCa-2/DRG co-culture system, the neurites exhibited a trend of growing towards the pancreatic cancer cell colony. However, the pancreatic cancer cells showed a trend of retrogradely migrating to the DRG along the neurite outgrowth, when MIA PaCa-2 colonies touched the DRG. The positive rate of Ki-67 nuclear antigen was significantly higher than in the co-culture group. The PI value was higher in the experimental group (12.80%) than that in the control group (6.81%, P < 0.01). The MTT assay showed that proliferation of the pancreatic cancer cells was more active than that in the control group. Flow cytometry analysis showed that the apoptosis rate of the pancreatic cancer cell was 2.46%, significantly lower than that of the control group (4.89%, P < 0.001). CONCLUSIONS: An in vitro co-culture model of rat dorsal root ganglion and human pancreatic cancer cell line is successfully established in this study. This MIA PaCa-2/DRG co-culture system demonstrates that the neural-pancreatic carcinoma cell interaction is a mutually beneficial process for the growth of neurites and pancreatic carcinoma cells. The pancreatic cancer cells show a trend of migrating to the DRG along the neurite outgrowth.
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Comunicação Celular , Gânglios Espinais/citologia , Neuritos/fisiologia , Neoplasias Pancreáticas/patologia , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Técnicas de Cocultura , Gânglios Espinais/metabolismo , Humanos , Invasividade Neoplásica , Ratos , Ratos WistarRESUMO
BACKGROUND: Tic disorders (TDs), including Tourette syndrome, are childhood-onset neuropsychiatric disorders characterized by motor and/or vocal tics that commonly affect children's physical and mental health. The pathogenesis of TDs may be related to abnormal neurotransmitters in the cortico-striatal-thalamo-cortical circuitry, especially dopaminergic, glutamatergic, and serotonergic neurotransmitters. The purpose of this study was to preliminarily investigate the differences in the three types of neurotransmitters in plasma and urine between children with TD and healthy children. METHODS: We collected 94 samples of plasma and 69 samples of urine from 3-12-year-old Chinese Han children with TD before treatment. The plasma and urine of the same number of healthy Chinese Han children, matched for age and sex, participating in a physical examination, were collected. Ultra-performance liquid chromatography-tandem mass spectrometry was used to detect the three types of neurotransmitters in the above samples. RESULTS: The plasma levels of norepinephrine, glutamic acid, and γ-aminobutyric acid, and the urine levels of normetanephrine and 5-hydroxyindoleacetic acid were higher in the TD children than in healthy children. The area under the curve (AUC) values of the above neurotransmitters in plasma and urine analyzed by receiver operating characteristic curve analysis were all higher than 0.6, with significant differences. Among them, the combined AUC of dopamine, norepinephrine, normetanephrine, glutamic acid, and γ-aminobutyric acid in the 8-12-year-old subgroup was 0.930, and the sensitivity and specificity for TD were 0.821 and 0.974, respectively (p = 0.000). CONCLUSIONS: There are differences in plasma and urine neurotransmitters between TD children and healthy children, which lays a foundation for further research on the pathogenesis of TD.
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BACKGROUND: Trauma experience increases the risk of suicidal ideation, but little is known about potentially psychological mechanisms underlying this relationship. This study aims to examine the relationship between coronavirus disease 2019 (COVID-19)-related traumatic event (CTE) exposure and suicidal ideation among hospital workers, and identify mediating roles of sleep disturbances in this relationship. METHODS: Workers in seven designated hospitals in Wuhan, China, were invited to participate in an online survey from May 27, 2020, to July 31, 2020. Participants completed a self-report questionnaire to evaluate demographic characteristics, level of CTE exposures, nightmare frequency, insomnia severity, symptoms of depression and anxiety, and suicidal ideation. A series of correlation analyses were performed, and a mediation model was generated to examine correlations between CTE exposure, sleep disturbances, and suicidal ideation. RESULTS: A total of 16,220 hospital workers were included in the final analysis, 13.3% of them reported suicidal ideation in the past month. CTE exposure was significantly associated with insomnia severity, nightmare frequency, and suicidal ideation. After controlling potential confounders, nightmares but not insomnia, depression, or anxiety were shown to be independent risk factors for suicidal ideation. Pathway analyses showed that the relationship between CTE exposure and suicidal ideation was fully mediated by nightmares (proportion mediated 66.4%) after adjusting for demographic characteristics and psychological confounders. LIMITATIONS: Cross-sectional design precluded the investigation of causal relationships. CONCLUSIONS: CTE exposure increases risk of hospital workers' suicidal ideation that is mediated by nightmares, suggesting nightmares intervention might be considered as a component when developing suicide prevention strategies.
Assuntos
COVID-19 , Distúrbios do Início e da Manutenção do Sono , Estudos Transversais , Sonhos/psicologia , Humanos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Ideação SuicidaRESUMO
OBJECTIVE: To study the effects of TNF-α on ICAM-1 and LFA-1 expression in peripheral blood mononuclear cells (PBMC) of children with febrile seizures (FS). METHODS: Sixteen children with FS and 16 age- and gender-matched healthy children were enrolled. The samples of PBMC from FS children were randomized into two groups with or without TNF-α treatment (TNF-α concentration 1.0 ng/mL). PBMC were purified and cultured with a conventional method in vitro. The expression of ICAM-1 and LFA-1 in PBMC was determined by flow cytometry (FCM). RESULTS: ICAM-1ï¼»(20±9)% vs (14±7)%)ï¼½and LFA-1ï¼»(43±16)% vs (30±16)%ï¼½expression in PBMC in the untreated FS group was significantly higher than that in the normal control group (P<0.05). Compared with the untreated FS group, the treatment with TNF-α remarkably increased the ICAM-1 expressionï¼»(27±11)%ï¼½(P<0.05). PBMC LFA-1 expressionï¼»(52±21)%ï¼½in the TNF-α-treated group was higher than that in the untreated FS group, although there were no statistical differences between the two groups. CONCLUSIONS: TNF-α treatment may increase LFA-1 and ICAM-1 expression in PBMC of children with FS.
Assuntos
Molécula 1 de Adesão Intercelular/sangue , Leucócitos Mononucleares/química , Antígeno-1 Associado à Função Linfocitária/sangue , Convulsões Febris/imunologia , Fator de Necrose Tumoral alfa/farmacologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucócitos Mononucleares/efeitos dos fármacos , MasculinoRESUMO
Background: Acute necrotizing encephalopathy of childhood (ANE) is a rare but rapidly progressing encephalopathy. Importantly, the exact pathogenesis and evidence-based treatment is scarce. Thus, we aimed to identify the clinical, imaging, and therapeutic characteristics that associated with prognosis of pediatric ANE patients. Methods: A retrospective study was conducted on pediatric patients with ANE who were admitted to Wuhan Children's Hospital between January 2014 and September 2019. All cases met the diagnostic criteria for ANE proposed by Mizuguchi in 1997. The clinical information and follow-up data were collected. The prognostic factors were analyzed by trend chi-square test and Goodman-Kruskal gamma test. Results: A total of 41 ANE patients ranging in age from 8.9 to 142 months were included in this study. Seven cases (17%) died, and the other 34 survivors had different degrees of neurological sequelae. Factors tested to be significantly correlated with the severity of neurological sequelae were the intervals from prodromal infection to acute encephalopathy (G = -0.553), conscious disturbance (r = 0.58), endotracheal intubation (r = 0.423), elevation of alanine aminotransferase (r = 0.345), aspartate aminotransferase (r = 0.393), and cerebrospinal fluid protein (r = 0.490). In addition, dynamic magnetic resonance imaging (MRI) evaluation on follow-up revealed that the total numbers of brain lesion location (χ2 = 6.29, P < 0.05), hemorrhage (r = 0.580), cavitation (r = 0.410), and atrophy (r = 0.602) status were significantly correlated with the severity of neurological sequelae, while early steroid therapy (r = -0.127 and 0.212, respectively) and intravenous immunoglobulin (IVIG) (r = 0.111 and -0.023, respectively) within 24 h or within 72 h after onset showed no association. Conclusions: Intervals from prodromal infection to acute encephalopathy (≤1 day), total numbers of brain lesion location (≥3), the recovery duration of hemorrhage and atrophy (>3 months), and the presence of cavitation predict severe neurological sequelae in pediatric patients with ANE. Early treatments, including steroid therapy and IVIG, had no correlation with better outcomes. Further studies are needed to establish a consensus guideline for the management of ANE.