Factors Associated with Respiratory Insufficiency in Children with Guillain-Barré Syndrome.

OBJECTIVE: The risk factors for respiratory insufficiency in children with Guillain-Barré syndrome (GBS) are poorly known. This study aimed to investigate the factors associated with respiratory insufficiency in children with GBS. METHODS: This retrospective study included children diagnosed with GBS by pediatric neurologists and admitted at the Wuhan Children's Hospital and other hospitals from January 2013 to October 2022. The patients were divided into the respiratory insufficiency and nonrespiratory insufficiency groups according to whether they received assist breathing during treatment. RESULTS: The median (interquartile range) age of onset of 103 patients were 5 (3.1-8.5) years, 69 (67%) were male, and 64 (62.1%) had a history of precursor infection. Compared with the nonrespiratory insufficiency group, the respiratory insufficiency group showed more facial and/or bulbar weakness (p = 0.002), a higher Hughes Functional Grading Scale (HFGS) at admission (p < 0.001), and a shorter onset-to-admission interval (p = 0.017). Compared with the acute motor axonal neuropathy (AMAN) subtype, the acute inflammatory demyelinating polyneuropathy (AIDP) subtype showed longer days from onset to lumbar (p = 0.000), lower HFGS at admission (p = 0.04), longer onset-to-admission interval (p = 0.001), and more cranial nerve involvement (p = 0.04). The incidence of respiratory insufficiency between AIDP and AMAN showed no statistical difference (p > 0.05). CONCLUSION: In conclusion, facial and/or bulbar weakness, HFGS at admission, and onset-to-admission interval were associated with respiratory insufficiency and might be useful prognostic markers in children with GBS.

Network pharmacology to explore the mechanism of traditional Chinese medicine in the treatment of ground glass nodules.

Background: Ground glass nodules (GGNs) in the lung are considered to be a high-risk factor of lung adenocarcinoma. Immediate surgery is not recommended for GGNs patients, and low-dose computed tomography (CT) is often used for observation and follow-up, which brings high psychological and economic burden to the patient. Methods: Three traditional Chinese medicine (TCM) prescriptions for the treatment of GGNs were found through database including PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI), Scopus and so on. The possible targets of the active ingredients of the TCM preparations and the gene targets of GGNs were screened out from Traditional Chinese Medicine Systems Pharmacology (TCMSP), UniProt and GeneCards. Network visualization was realized via STRING, Cytoscape 3.7.2, Evenn, DAVID and Hiplot. Finally, molecular docking Vina and PyMOL software were performed to further explore the possibility of drug-target interactions using PubChem compounds, protein data bank (PDB) database, Autodocktools and Autodock. Results: Three TCM preparations could target the same 13 potential therapeutic targets in GGNs. From network pharmacology, 14 signaling pathways, the functions of the significant targets, an effective ingredient in TCM prescriptions and its functions were obtained. Conclusions: Chinese herbal formulas containing quercetin could be a potential treatment for GGNs, targeting C-reactive protein (CRP), tumor necrosis factor (TNF), interferon gamma (IFN-γ), intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor A (VEGFA) through the hypoxia-inducible factor 1 (HIF-1) pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and leukocyte transendothelial migration.

Ion-selective detection by plasticized poly(vinyl chloride) membrane in glass nanopipette with alternating voltage modulation.

An alternating current (AC) voltage modulation was applied to ion-selective observations with plasticized poly(vinyl chloride) membranes in glass nanopipettes. The liquid confronting the membranes in the nanopipettes, the conditioning process, and AC voltage modulation play important roles in the ion-selective detection. In the AC detection system developed by us, where distilled water was used as the liquid within the nanopipettes, potassium ions were selectively detected in the sample solution of sodium and potassium ions because sodium ions were captured at the membrane containing bis(12-crown-4) ionophores, before the saturation of the ionophores. The membrane lost the selectivity after the saturation. On using sodium chloride as the liquid within the nanopipette, the membrane selectively detected potassium and sodium ions before and after the saturation of ionophores, respectively. The ion-selective detection of our system can be explained by the ion extraction-diffusion-dissolution mechanism through the bis(12-crown-4) ionophores with AC voltage modulation.

[Cnb1 involved in cytokinesis in Schizosaccharomyces pombe].

Serine/Threonine-specific calcineurin (CN) is highly conserved in eukaryotes, which plays an important role in transcriptional regulation. In Schizosaccharomyces pombe, CN exists as a heterodimer composed by catalytic subunit Ppb1 and regulatory subunit Cnb1. Deletion of cnb1+ reduced the growth rate of cells, and caused a chained phenotype, and had delay in cytokinesis. In cytokinesis, Cnb1 could form CN complex with Ppb1 and could colocalize and constrict with the contractile ring at division plane. Tubulin could cross the septum in cnb1Δ strain, suggesting that the septum is not fully matured. These results suggest Cnb1 might be involved in maturation of septum. The signals of septins in cnb1Δ strain were also analyzed. Septins include Spn1, Spn2, Spn3, and Spn4. Septins help to guide hydrolytic enzymes for septum degrada-tion. Eighty percent of cnb1Δ cells lacked the signals of Spn2 or Spn3 at septum, and twenty percent of cnb1Δ cells lacked the signals of Spn1 or Spn4 at septum. The reduction of the septin signals was not due to impaired transcription of septins, since the protein levels of septins in the cnb1Δ cells were not decreased. These results imply that Cnb1 might regulate the stability of septin ring in a transcription-independent manner. In general, our study showed that Cnb1 contributes to the maturation of septum and the stability of septin ring and is important in the cytokinesis.

Genome-Wide Transcriptome Analysis in Type 2 Diabetes Patients Treated by Sitagliptin.

Objective: In this study, transcriptome sequencing was performed on patients with type 2 diabetes mellitus treated with different prognosis to explore the differential level genes of different hypoglycemic effects of sitagliptin. Methods: Patients with newly diagnosed T2DM (within six months of diagnosis) were selected as the study subjects. Patients were given sitagliptin 100 mg once a day orally. After 12 weeks of regular drug therapy, the reduction in glycated hemoglobin was compared before and after drug administration. The patients were then divided into two groups: the significantly effective group (M) and the less effective group (N). High-throughput sequencing of the transcriptome was conducted to detect the differential expression levels of genes in peripheral blood mononuclear cells. Expanded sample size validation of the candidate differential genes was conducted using reverse transcription-polymerase chain reaction (RT-PCR). Results: After 12 weeks of treatment with sitagliptin, high-throughput sequencing of the transcriptome found that expression of the following genes was different when comparing the significantly effective group (M) and the less effective group (N): ghrelin (GHRL), insulin-like growth factor-1 receptor (IGF1R), mitogen-activated protein kinase-3 (MAPK3), phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit delta (PIK3CD), and the suppressor of cytokine signaling-3 (SOCS3). The validation results of RT-PCR showed that, in the significantly effective group (M), the expression of IGF1R was significantly increased (P = 0.034), the expression of MAPK3 was significantly reduced (P = 0.002), and the expression of SOCS3 was also significantly reduced (P < 0.001). Conclusion: There was a significant difference in gene level between patients with significant hypoglycemic effect and patients with poor hypoglycemic effect, and the expression of IGF1R increased and the expression of MAPK3 and SOCS3 decreased.

[Effects of edaravone on glial fibrillary acidic protein and interleukin-lß expression and neuronal apoptosis in juvenile rat hippocampus after status convulsion].

OBJECTIVE: To study the effects of edaravone on glial fibrillary acidic protein (GFAP) and interleukin-1ß (IL-lß) expression and neuronal apoptosis in the juvenile rat hippocampus after status convulsion (SC). METHODS: One hundred and ninety-five juvenile male Sprague-Dawley (SD) rats were randomly divided into 3 groups: normal saline control and SC with and without edaravone treatment. Each of the 3 groups was further subdivided into subgroups sacrificed at 4, 12, 24, 48 and 72 hrs after SC (n=15). The SC model was prepared using lithium-pilocarpine. The expression of GFAP and IL-lß protein was detected with immunohistochemistry methods. The neuronal apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL). The hippocampal GFAP mRNA expression was detected by RT-PCR. RESULTS: The value of IOD of GFAP and IL-lß positive cells measured by immunohistochemistry in the untreated SC group increased compared with the control group. Expression of GFAP and IL-lß protein was significantly reduced in the edaravone treated SC group compared with the untreated SC group. RT-PCR showed the expression trend of GFAP mRNA was similar to that of protein. The TUNEL positive cells in the hippocampus CA1 in the untreated SC group increased significantly 12 hrs after SC and reached a peak at 48 hrs compared with the control group. The intervention with edaravone decreased significantly TUNEL positive cells between 12-48 hrs after SC, but the number of TUNEL positive cells in the intervention group remained significantly greater than in the control group. CONCLUSIONS: The expression of GFAP and IL-lß in the hippocampus increases after SC in rats. Edaravone may decrease the expression of GFAP and IL-1ß and reduce the number of neuronal apoptosis. These results suggest that edaravone may have protective effects against brain damage caused by SC.

Safety and Effectiveness of Oral Methylprednisolone Therapy in Comparison With Intramuscular Adrenocorticotropic Hormone and Oral Prednisolone in Children With Infantile Spasms.

Background and Purpose: To assess the safety and effectiveness of oral methylprednisolone (oMP) in comparison with intramuscular adrenocorticotropic hormone (imACTH) and oral prednisolone (oP) therapies in children with infantile spasms (IS). Methods: In this prospective, open-label, non-blinded, uncontrolled observational study, children (aged 2-24 months) with newly diagnosed IS presenting with hypsarrhythmia or its variants on electroencephalogram (EEG) were included. It was followed by imACTH, oP, or oMP (32-48 mg/day for 2 weeks followed by tapering) treatments. Electroclinical remission/spasm control, relapse, and adverse effects were evaluated in the short-term (days 14 and 42) and intermediary-term (3, 6, and 12 months) intervals. Results: A total of 320 pediatric patients were enrolled: 108, 107, and 105 in the imACTH, oMP, and oP groups, respectively. The proportion of children achieving electroclinical remission on days 14 and 42 was similar among the three groups (day 14: 53.70 vs. 60.75 vs. 51.43%, p = 0.362; day 42: 57.55 vs. 63.46 vs. 55.34%, p = 0.470). The time to response was significantly faster in the oMP group (6.5 [3.00, 10.00] days vs. 8.00 [5.00, 11.00] days for imACTH and 8.00 [5.00, 13.00] days for oP, p = 0.025). Spasm control at 3, 6, and 12 months was also similar in the three groups (P = 0.775, 0.667, and 0.779). The relapse rate in the imACTH group (24.10%) was lower than oMP (30.77%) and oP groups (33.33%), and the time taken for relapse in the imACTH group (79.00 [56.50, 152.00] days) was longer than oMP (62.50 [38.00, 121.75] days) and oP groups (71.50 [40.00, 99.75] days), but the differences were not statistically significant (p = 0.539 and 0.530, respectively). The occurrence of adverse effects was similar among the three groups. Conclusions: The short and intermediary-term efficacy and recurrence rates of oMP are not inferior to those of imACTH and oP for the treatment of IS. Significantly, the time to achieve electroclinical remission with oMP was quicker than that with imACTH and oP. Considering its convenience, affordability, and the absence of irreversible side effects, oMP can serve as a form of first-line treatment for newly diagnosed IS.

[Effects of edaravone on IRE1 mRNA expression and neuronal apoptosis in the hippocampus of rats with status convulsivus].

OBJECTIVE: To investigate the expression of the key marker of endoplasmic reticulum stress (ERS) IRE1 mRNA and neuronal apoptosis in the rat hippocampus after status convulsivus (SC), and the intervention effects of edaravone, a novel free radical scavenger. METHODS: Sprague-Dawley (SD) rats aged 19-21 days were randomly assigned to three groups: normal control, SC and edaravone-treated SC. SC was induced in the later two groups. The two groups were subdivided into 5 groups sacrificed at 4, 12, 24, 48, and 72 hrs after SC induction. IRE1 mRNA expression in the hippocampus was detected by RT-PCR. Neuronal apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL). The ultramicrostructural changes of neuron were observed by electron microscopy. RESULTS: IRE1 mRNA expression was obviously up-regulated 4 and 12 hrs after SC compared with the normal control group (P<0.01). IRE1 mRNA expression in the edaravone-treated SC group was notably higher than the untreated SC group 4, 12 and 24 hrs after SC and the normal control group (P<0.01). TUNEL positive cells in the hippocampus in the untreated SC group were significantly more than those in the normal control group (P<0.01). The number of TUNEL positive cells increased with the prolonged convulsion time. TUNEL positive cells in the edaravone-treated SC group were significantly reduced compared with those in the untreated SC group 12, 24, 48 and 72 hrs after SC (P<0.05 or P<0.01), but remained higher than the normal control group (P<0.05 or P<0.01). The peri-nucleus cell organ injuries were observed 4 hrs after SC and karyopycnosis and cytoplasm condensation were observed 12 hrs after SC in the SC and the edaravone-treated SC groups. The edaravone-treated SC group demonstrated less severe apoptosis than the untreated SC group. CONCLUSIONS: Edaravone may have neuroprotections against SC by an up-regulation of IRE1 expression. It might serve as an effective agent for reducing ERS in vivo.

Short article: A randomized-controlled study of sitagliptin for treating diabetes mellitus complicated by nonalcoholic fatty liver disease.

BACKGROUND: This study aimed to evaluate the efficacy and safety of sitagliptin for treating Chinese patients with type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). METHODS: In total, 72 Chinese T2DM patients with NAFLD were divided randomly into two groups of 36 patients each group. All 72 patients were assigned to receive either sitagliptin or diet and exercise for 52 weeks between January 2013 and December 2015. The outcomes' measurements included serum levels of hemoglobin A1c, fasting plasma glucose, aspartate aminotransferase, and alanine aminotransferase. RESULTS: Seventy patients completed the study. Sitagliptin showed greater efficacy than the diet and exercise in decreasing the hemoglobin A1c and fasting plasma glucose levels at weeks 13, 26, 39, and 52. In addition, no significant changes in the average aspartate aminotransferase and alanine aminotransferase levels were found during the 52-week follow-up in both the sitagliptin and the control groups. CONCLUSION: The results of this study indicate that sitagliptin is an effective and safe treatment for patients with T2DM and NAFLD.

Effect of colchicine in prevention of pericardial effusion and atrial fibrillation: a meta-analysis.

Randomized, controlled trials (RCTs) have assessed the effect of colchicine therapy in prevention of pericardial effusion (PE) and atrial fibrillation (AF). However, the effects are still inconclusive. PubMed, Cochrane Library, Google Scholar, and EMBASE database were searched. Primary outcome was the risk of PE and AF. Ten RCTs with 1981 patients and a mean follow-up of 12.6 months were included. Colchicine therapy was not associated with a significantly lower risk of post-operative PE (RR, 0.89; 95 % CI 0.70-1.13; p = 0.33, I (2) = 72.8 %) and AF (RR, 0.77; 95 % CI 0.52-1.13; p = 0.18, I (2) = 47.3 %). However, rates of pericarditis recurrence, symptoms persistence, and pericarditis-related hospitalization were significantly decreased with colchicine treatment. In addition, cardiac tamponade occurrence was similar between groups, and adverse events were significantly higher in the colchicine group. Colchicine may not significantly decrease the post-operative risk of PE and AF. However, only limited studies about patients undergoing cardiac surgery provide data about PE and AF.

Effect of concentration gradient on ionic current rectification in polyethyleneimine modified glass nano-pipettes.

Ion current rectification dependent on the concentration gradient of KCl solutions was systematically investigated in polyethyleneimine modified glass nano-pipettes with inner diameter of 105 nm. Peak shape dependence of the rectification factor on outer KCl solution concentration was observed when inner KCl solution with concentration from 1 mM to 500 mM was used. The peak shape dependence was also observed when the concentrations of the inner and outer KCl solutions were identically controlled. The peak shape in the ion current rectification could be explained by the ion conductance changes through the conical nano-pipette, which result from modulation of ion concentration.

Improved ion-selective detection method using nanopipette with poly(vinyl chloride)-based membrane.

Ion-selective electrodes (ISEs) are widely used to detect targeted ions in solution selectively. Application of an ISE to a small area detection system with a nanopipette requires a special measurement method in order to avoid the enhanced background signal problem caused by a cation-rich layer near the charged inner surface of the nanopipette and the selectivity change problem due to relatively fast saturation of the ISE inside the nanopipette. We developed a novel ion-selective detection system using a nanopipette that measures an alternating current (AC) signal mediated by saturated ionophores in a poly(vinyl chloride) (PVC) membrane located at the conical shank of the nanopipette to solve the above problems. Small but reliable K(+) and Na(+) ionic current passing through a PVC membrane containing saturated bis(benzo-15-crown-5) and bis(12-crown-4) ionophore, respectively, could be selectively detected using the AC signal measurement system equipped with a lock-in amplifier.

Confining grains of textured Cu2O films to single-crystal nanowires and resultant change in resistive switching characteristics.

By confining columnar grains of textured oxide film using anodized aluminum oxide template, we could obtain a grain-boundary-free (GB-free) cuprous oxide (Cu(2)O) nanowire arrays with a narrow diameter distribution and a high density under the same electrochemical deposition condition. A two-terminal device fabricated using an individual GB-free nanowire and Au/Cr electrodes exhibits bipolar resistive switching contrary to the unipolar one of a textured film, and Schottky-like conduction. On the other hand, a nanowire device with Pt electrodes reveals non-switching behavior and Ohmic conduction. Thus, we can propose that the bipolar switching of a nanowire device with Au/Cr electrodes may result from the modulation of Schottky barrier at the interface by migration of oxygen vacancies while the unipolar one of a textured film may be defined as the bulky filamentary switching along the GBs in the GB-embedded texture films.

[Effects of edaravone on the expression of interleukin-1beta, nuclear factor-kappaB and neuron apoptosis in juvenile rat hippocampus after status convulsion].

OBJECTIVE: To investigate the effect of edaravone on expression of interleukin-1beta (IL-1beta), nuclear factor-kappaB (NF-kappaB) and neuron apoptosis in the juvenile rat hippocampus after status convulsion (SC). METHODS: One hundred and ninety-five juvenile male Sprague-Dawley (SD) rats were randomly divided into normal saline (NS) control group, status convulsive group and edaravone treatment group. Each group was further divided into five subgroups for different time points. The rats in status convulsive group were kindled into epilepsy by lithium-pilocarpine chemical method. Expressions of IL-1beta and NF-kappaB proteins were detected with immunohistochemistry methods. Expression of NF-kappaB mRNA was detected with reverse transcription-polymerase chain reaction (RT-PCR). The neuron apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: (1) Measured by immunohistochemistry the value of IOD of IL-1beta (30.83 +/- 3.81, 41.00 +/- 5.61, 36.32 +/- 6.78 and 28.48 +/- 4.61, respectively, 12-72 h points) and NF-kappaB (67.60 +/- 5.81, 74.61 +/- 7.94, 82.43 +/- 10.67, 70.70 +/- 5.85 and 68.22 +/- 9.67, respectively, 4-72 h points) positive cells in the SC group increased,there was significant difference compared with NS group (IL-1beta: 11.74 +/- 2.32, 12.93 +/- 2.49, 13.02 +/- 2.83 and 12.98 +/- 5.29, respectively, 12-72 h points. NF-kappaB: 48.67 +/- 16.14, 44.62 +/- 7.82, 53.16 +/- 114.45, 54.27 +/- 5.25 and 55.56 +/- 7.56, respectively, 4-72 h points) (P < 0.01, or P < 0.05). By ED intervention in IL-1beta (22.01 +/- 4.45, 28.28 +/- 4.50 and 26.00 +/- 5.34, respectively, 12-48 h points) and NF-kappaB (58.56 +/- 6.37, 59. 86 +/- 6.73, 70.00 +/- 10.09, 64.78 +/- 7.56 and 64.45 +/- 6.51, respectively, 4-72 h points) positive cells value of the IOD decreased as compared with SC group (P < 0.01, or P < 0.05). (2) Measured by RT-PCR, the expression of NF-KB mRNA and protein trend was similar. (3)The TUNEL positive cells in hippocampus, CA1 of SC group (11.41 +/- 2.37) were more than that of NS group 12 h after the SC (P < 0.01), reached its highest level at48 h (28.78 +/- 5.11), after the intervention with edaravone (8.98 +/- 2.22, 13.09 +/- 2.54 and 20. 57 +/- 4.89, respectively, 12-48 h points) ,TUNEL positive cells showed a significant drop in SC group at 12-48 h time points (P < 0.01, or P < 0.05), but still significantly higher than that of the NS group (6.22 +/- 1.50, 6.57 +/- 1.61 and 6.72 +/- 1.14, respectively) (P < 0.01, or P < 0.05), at the 4 h time point(NS group 6.29 +/- 1.49, SC group 6.61 +/- 1.71, ED group 5.75 +/- 1.41) among the three groups, no significant difference in TUNEL positive cells was found (P = 0.759). CONCLUSIONS: Edaravone inhibited expression of IL-1beta and NF-kappaB in pilocarpine-induced seizures in rat hippocampus, reduced the number of neuronal apoptosis. These results suggest that edaravone may have protective effect against the damage caused by status convulsion.