Epidemiological characteristics, clinical characteristics, and prognostic factors of children with atopy hospitalised with adenovirus pneumonia.

BACKGROUND: Atopy may be associated with disease severity and a poor prognosis of human adenovirus (HAdV) pneumonia in children. Our aim was to observe the clinical characteristics and pulmonary radiological changes in children with atopy and HAdV pneumonia in China. METHODS: Children hospitalised with HAdV pneumonia from June 2018 to December 2019 were analysed. All children were divided into atopic with HAdV, non-atopic with HAdV, and atopic without HAdV infection group. Each group was further divided into the mild and severe pneumonia groups according to disease severity. Standard treatment was initiated after admission, and regular follow-up evaluations were conducted at 1 month after discharge. Baseline and clinical characteristics and pulmonary radiological changes in children with and without atopy were evaluated. Risk factors associated with small airway lesions in patients with HAdV pneumonia were analysed. RESULTS: The eosinophil count in the atopic group was significantly higher than that in the non-atopic group (P < 0.05). Severe coughing, wheezing, and small airway lesions on chest high-resolution computed tomography (HRCT) upon admission, after discharge and 1 month after discharge were significantly higher in the atopic group (with or without HAdV infection) than in the non-atopic group (P < 0.05). There were significant differences in the number of patients with wheezing and small airway lesions during hospitalisation and after discharge among the three groups (P < 0.05). The risks of small airway lesions in children with a family or personal history of asthma, severe infection, atopy, and HAdV infection were 2.1-, 2.7-, 1.9-, 2.1-, and 1.4-times higher than those in children without these characteristics, respectively. CONCLUSIONS: Children with atopy and HAdV pneumonia may experience severe coughing in mild cases and wheezing in mild and severe cases. Children with atopy are more susceptible to the development of small airway lesions, recurrent wheezing after discharge and slower recovery of small airway lesions as observed on pulmonary imaging than non-atopic children after HAdV infection. A family or personal history of asthma, atopy, severe infection, and HAdV infection are independent risk factors associated with the development of small airway lesion as observed on chest HRCT.

Repetitive transcranial magnetic stimulation promotes functional recovery and differentiation of human neural stem cells in rats after ischemic stroke.

Stem cells hold great promise as a regenerative therapy for ischemic stroke by improving functional outcomes in animal models. However, there are some limitations regarding the cell transplantation, including low rate of survival and differentiation. Repetitive transcranial magnetic stimulation (rTMS) has been widely used in clinical trials as post-stroke rehabilitation in ischemic stroke and has shown to alleviate functional deficits following stroke. The present study was designed to evaluate the therapeutic effects and mechanisms of combined human neural stem cells (hNSCs) with rTMS in a middle cerebral artery occlusion (MCAO) rat model. The results showed that human embryonic stem cells (hESCs) were successfully differentiated into forebrain hNSCs for transplantation and hNSCs transplantation combined with rTMS could accelerate the functional recovery after ischemic stroke in rats. Furthermore, this combination not only significantly enhanced neurogenesis and the protein levels of brain-derived neurotrophic factor (BDNF), but also rTMS promoted the neural differentiation of hNSCs. Our findings are presented for the first time to evaluate therapeutic benefits of combined hNSCs and rTMS for functional recovery after ischemic stroke, and indicated that the combination of hNSCs with rTMS might be a potential novel therapeutic target for the treatment of stroke.

Adenosine A2A Receptor Modulates the Activity of Globus Pallidus Neurons in Rats.

The globus pallidus is a central nucleus in the basal ganglia motor control circuit. Morphological studies have revealed the expression of adenosine A2A receptors in the globus pallidus. To determine the modulation of adenosine A2A receptors on the activity of pallidal neurons in both normal and parkinsonian rats, in vivo electrophysiological and behavioral tests were performed in the present study. The extracellular single unit recordings showed that micro-pressure administration of adenosine A2A receptor agonist, CGS21680, regulated the pallidal firing activity. GABAergic neurotransmission was involved in CGS21680-induced modulation of pallidal neurons via a PKA pathway. Furthermore, application of two adenosine A2A receptor antagonists, KW6002 or SCH442416, mainly increased the spontaneous firing of pallidal neurons, suggesting that endogenous adenosine system modulates the activity of pallidal neurons through adenosine A2A receptors. Finally, elevated body swing test (EBST) showed that intrapallidal microinjection of adenosine A2A receptor agonist/antagonist induced ipsilateral/contralateral-biased swing, respectively. In addition, the electrophysiological and behavioral findings also revealed that activation of dopamine D2 receptors by quinpirole strengthened KW6002/SCH442416-induced excitation of pallidal activity. Co-application of quinpirole with KW6002 or SCH442416 alleviated biased swing in hemi-parkinsonian rats. Based on the present findings, we concluded that pallidal adenosine A2A receptors may be potentially useful in the treatment of Parkinson's disease.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate firing of globus pallidus neurons in vivo.

The globus pallidus plays a significant role in motor control under both health and pathological states. Recent studies have revealed that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels occupy a critical position in globus pallidus pacemaking activity. Morphological studies have shown the expression of HCN channels in the globus pallidus. To investigate the in vivo effects of HCN channels in the globus pallidus, extracellular recordings and behavioral tests were performed in the present study. In normal rats, micro-pressure ejection of 0.05mM ZD7288, the selective HCN channel blocker, decreased the frequency of spontaneous firing in 21 out of the 40 pallidal neurons. The average decrease was 50.4±5.4%. Interestingly, in another 18 out of the 40 pallidal neurons, ZD7288 increased the firing rate by 137.1±27.6%. Similar bidirectional modulation on the firing rate was observed by a higher concentration of ZD7288 (0.5mM) as well as another HCN channel blocker, CsCl. Furthermore, activation of HCN channels by 8-Br-cAMP increased the firing rate by 63.0±9.3% in 15 out of the 25 pallidal neurons and decreased the firing rate by 46.9±9.4% in another 8 out of the 25 pallidal neurons. Further experiments revealed that modulation of glutamatergic but not GABAergic transmission may be involved in ZD7288-induced increase in firing rate. Consistent with electrophysiological results, further studies revealed that modulation of HCN channels also had bidirectional effects on behavior. Taken together, the present studies suggest that HCN channels may modulate the activity of pallidal neurons by different pathways in vivo.

7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cell death through modulating PI3K/Akt and JNK pathways.

We have recently shown that 7,8-dihydroxyflavone (7,8-DHF) protects PC12 cells against 6-OHDA-induced cytotoxicity through its antioxidant activity. In the present study, we investigated the molecular mechanisms underlying the neuronal protective activity of 7,8-DHF. Western blot analysis showed that 6-OHDA (100µM, 24h) enhanced the phosphorylation of JNK and ERK1/2, but it markedly suppressed the expression of p-Akt, implying that 6-OHDA induces PC12 cell death through activating the pro-apoptotic MAPKs pathway but suppressing the survival PI3K/Akt pathway. More importantly, addition of 7,8-DHF fully prevented the activation of JNK and suppression of Akt induced by 6-OHDA. Interestingly, pretreatment with the PI3K-specific inhibitor LY294002 largely blocked 7,8-DHF function in protecting PC12 cells from 6-OHDA-induced cell death. In contrast, the MEK inhibitor PD98059 showed little effect on the protective activity of 7,8-DHF. These results suggest that 7,8-DHF might protect PC12 cells from 6-OHDA-induced cell death through activating PI3K/Akt pathway and inhibiting JNK pathway.

Clinical characteristics and genetic profiles of 44 patients with severe combined immunodeficiency (SCID): report from Shanghai, China (2004-2011).

Severe combined immunodeficiency (SCID), a rare type of genetic associated immune disorder, is poorly characterized in mainland China. We retrospectively reviewed 44 patients with SCID who received treatment from 2004 to 2011 in Shanghai, China, and herein summarize their clinical manifestations and immunological and preliminary genetic features. The male-to-female ratio was 10:1. Twenty five patients presented with X-SCID symptoms. Only one patient was diagnosed before the onset of symptoms due to positive family history. The mean time of delay in the diagnosis of X-SCID was 2.69 months (range, 0.5-8.67). Thirty-seven of the 44 patients died by the end of 2011 with the mean age of death being 7.87 months (range, 1.33-31). Six patients received hematopoietic stem cell transplantation (HSCT); only one of them survived, who was transplanted twice. The time between onset and death was shorter in the HSCT-treated group compared with the untreated group (2.87 ± 1.28 and 3.34 ± 0.59 months, respectively), probably due to active infections during transplantation. Bacillus Calmette-Guérin (BCG) complications occurred in 14 of the 34 patients who received BCG vaccination. Transfusion-induced graft-versus-host disease occurred in 5 patients. Total 20 mutations in interleukin-2 receptor subunit gamma (IL2RG) were identified in 22 patients, including 11 novel mutations. Most patients were misdiagnosed before referred to our SCID Center. Therefore, establishing more diagnostic centers dedicated to the care of PID and accessible by primary immunodeficiency patients will facilitate early, correct diagnosis and better care of SCID in China.

[Protective effect of melatonin on myocardial injury in severely- burned rats].

OBJECTIVE: To investigate the protective effect of melatonin (MLT) on myocardial injury in severely-burned rats and its mechanism. METHODS: A total of 30 Sprague-Dawley (SD) rats were randomly assigned to three groups: sham group, burn group and MLT group, each n=10. The dorsal skin of animal was immersed into boiling water for 15 seconds to induce 30% total body surface area (TBSA) full-thickness burn, or immersed into 37 centigrade water for sham operation. Immediately after burn, the animals in burn group and MLT group were given intraperitoneally vehicle (1% alcohol in normal saline) or MLT (10 mg/kg) respectively. Six hours postburn, the blood from tail vessel was collected for serum preparation. After sacrificed, the myocardial tissues of rats were collected for the determination of malondialdehyde (MDA) and reduced glutathione (GSH) as well as glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO) activities. Serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) were also estimated. RESULTS: Compared with the sham control, burn injury increased MDA by 66.7% (1.55±0.17 nmol/mg vs. 0.93±0.05 nmol/mg) and decreased GSH by 27.8% (13.58±0.33 nmol/mg vs. 18.82±0.55 nmol/mg, both P<0.01) in myocardial tissues, GSH-Px activity was also slightly inhibited (74.04±3.42 nmol×min(-1)×mg(-1) vs. 93.79±3.76 nmol×min(-1)×mg(-1), P<0.05), but MPO level was found to increase to 2.8 folds (9.43±1.15 U/g vs. 3.41±0.27 U/g, P<0.01). These changes indicated the occurrence of oxidative stress in myocardial tissues after severe burn. MLT treatment relieved most of the abnormality with significant statistical significances (MDA: 0.89±0.08 nmol/mg vs. 1.55±0.17 nmol/mg, GSH: 17.23±0.54 nmol/mg vs. 13.58±0.33 nmol/mg, MPO: 6.91±0.51 U/g vs. 9.43±1.15 U/g, P<0.05 or P<0.01). In addition, the serum levels of CK and LDH in burn group increased to 37.8 folds and 7.4 folds respectively (both P<0.01). MLT treatment reduced CK by 32.9% and reduced LDH by 21.2% (P<0.05 and P<0.01). CONCLUSION: MLT treatment exerts the protective effect on myocardial injury in severely-burned rats, which is attributed predominantly to its inhibition on burn-induced oxidative stress injury.

[Protective effect of melatonin against renal dysfunction following severe burn in rats].

OBJECTIVE: To explore the protective effect of melatonin (MLT) against renal dysfunction in the early stage of burn in rats. METHODS: Seventy SD rats were randomly assigned to three groups: sham control (n=10), burn control (n=30) and MLT group (n=30). The 30% total body surface area (TBSA) full-thickness burn was induced by immersing the dorsal skin into boiling water for 30 seconds, while MLT (10 mg/kg, i.p.) was given immediately postburn, and the same dose was repeated once after 12 hours. The contents of malondialdehyde (MDA) and reduced glutathione (GSH) in renal tissue, as well as plasma creatinine (BCr) and urea nitrogen (BUN) levels were measured at 6, 24 and 72 hours postburn, while the activities of glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO) of renal tissue were measured only at 6 hours postburn. RESULTS: MDA content was significantly increased and GSH content was decreased in renal tissue after a 30 % TBSA full-thickness burn at all time points. Plasma BCr and BUN levels were elevated within 24 hours postburn. All these changes peaked at 6 hours postburn (all P<0.01). Single injection of MLT decreased MDA by 27.8% (P<0.01) but increased GSH by 44.4% (P<0.05). It also inhibited the rise in plasma BCr and BUN levels (P<0.05 and P<0.01). However, repeated MLT injection did not show additional effect on these parameters as single injection of MLT. In addition, single dose of MLT also lowered the MPO level by 30.2% (P<0.05), but did not improve the GSH-Px activity at 6 hours postburn. CONCLUSION: Severe burn may result in obvious oxidative stress (within 72 hours postburn) in the kidney with acute renal dysfunction (within 24 hours postburn). Single injection of MLT partially counteracted these changes, due to its high free radical scavenging capacity as well as its inhibitory effect on neutrophil-mediated tissue injury.