Humans ; Child ; Executive Function

The UHPLC-LTQ-orbitrap-MS metabolomics technique was used to determine the effect of deapio-platycodin D (DPD) on endogenous metabolites in lung tissues of mice with ammonia-induced cough, and to identify the metabolic regulatory pathways of DPD in its antitussive and expectorant activities. This work was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (Approval No. JZLLSC-20190235). Metabolites were identified by UHPLC-LTQ-orbitrap-MS method and the metabolic pathways related to differentially-expressed metabolites were analyzed by the MetaboAnalyst platform. DPD significantly prolonged (P < 0.05) cough latency, reduced the number of coughs, and significantly increased (P < 0.05) phenol red excretion in ammonia-induced cough mice. Twenty-five metabolites related to cough and 38 metabolites related to sputum excretion were identified by UHPLC-LTQ-orbitrap-MS. Changes in the metabolism of linoleic acid, arachidonic acid, glycerophospholipid, alanine, aspartic acid and glutamic acid, pentose and glucuronate interconversions, and lysine degradation were evident with DPD treatment of ammonia-induced cough mice. Changes in the metabolism of linoleic acid, taurine and hypotaurine, glycerophospholipid, purines and pyrimidines, arachidonic acid and the biosynthesis of unsaturated fatty acids after DPD treatment were related to phenol red excretion. Linoleic acid metabolism, arachidonic acid metabolism and glycerophospholipid metabolism are common regulatory pathways by which DPD appears to exert its antitussive and expectorant activity. These metabolic pathways are closely related to anti-inflammatory pathways, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and apoptosis. This study clarifies the antitussive and expectorant activity and mechanism of DPD.

Humans ; Magnetic Resonance Imaging ; Nocturnal Enuresis/diagnostic imaging*

Objective: To explore the possibility that the intestinal flora profile in complex anal fistula patients is different to that of healthy controls. This was assessed by sequencing of 16S rDNA in fecal samples from cohorts representing these populations. Methods: Fecal samples were collected from 30 complex anal fistula patients and 30 matched healthy controls. Patients were included if they met the diagnostic criteria of cryptoglandular anal fistula and had exhibited symptoms for more than 3 months. Complex anal fistula is diagnosed under the following circumstances: if the fistula in question spans 2/3 or more of the diameter of the anal sphincter; if there are more than two external orifices or fistula tracks; or if recurrence is observed after previous anal fistula surgery. Patients were excluded if there were comorbities including inflammatory bowel disease (as assessed by colonoscopy), chronic diarrhea, chronic constipation, diabetes, gastrointestinal malignancies, liver/ kidney dysfunction, or cognitive impairment. Patients whose anal fistulas were caused by Crohn's disease, trauma, special infections (such as actinomycosis and tuberculosis) were also excluded, as were those who had used antibiotics, prebiotics, or probiotics that may affect intestinal microecology in the month prior to the study. Total bacterial genomic DNA was extracted by PCR amplification of the V4 hypervariable region of the 16S rRNA sequences. High-throughput sequencing and data analysis were performed on the Illumina Miseq platform. Finally, operational taxonomic unit (OTU) clustering, alpha diversity and LEfSE data analysis were carried out. The larger the Chao or ACE index is, the higher the species abundance of the microflora is expected to be. Similarly, a smaller value for the Simpson index or a larger value for the Shannon index indicates greater microflora diversity. There was no statistically significant difference in gender, age, body mass index (BMI), drinking history, or smoking history between the two groups (P>0.05), indicating that they were comparable. Results: The α-diversity analysis including ACE, Chao, Shannon and Simpson indexes indicated a richer diversity of intestinal microflora in complex anal fistula patients than in healthy controls. In both patients and controls, OUT cluster analysis demonstrated that 93.4%±32.0% and 87.4%±41.2% of sequences were from Firmicutes and Bacteroidetes spp., respectively. On a genus level, samples from anal fistula patients showed a greater abundance of Prevotella spp. (4.9%±7.4% vs. 0.1%±1.1%, P<0.001), Megamonas (3.9%±8.2% vs. 0.5%±4.2%, P<0.05) and Lachnospira (2.6%±5.7% vs. 0.1%±3.4%, P<0.05), while showing a lesser abundance of Proteobacteria spp. (0.02%±4.2% vs. 9.3%±14.4%, P<0.01), Enterococcus (0.02%±2.3% vs. 9.3%±19.6%, P<0.05), Bacteroides (24.7%±9.9% vs. 29.8%±9.1%, P<0.05) and Klebsiella (0.4%±4.2% vs. 3.9%±7.3%, P<0.05) compared with healthy controls. Intestinal flora diversity in the complex anal fistula group was richer than in controls, as indicated by a higher ACE index (293.30±44.00 vs. 218.75±33.83, t=102.069, P<0.001), a higher Chao index (318.40±41.99 vs. 250.00±46.38, t=77.818, P=0.028), a higher Shannon index (3.36±0.29 vs. 2.43±0.34, t=9.657, P=0.001), and a lower Simpson index (0.103±0.013 vs. 0.131±0.013, t=5.551, P=0.046). LDA effect size analysis suggests that the main strains of Veillonellaceae, Selenemondales and Negativicutes, which all belong to the phylum Firmicutes, have the greatest influence on the above difference (LDA>4). Conclusions: The diversity of intestinal flora in patients with complex anal fistula is greater than in healthy controls, suggesting that these bacteria or their metabolites may be involved in the occurrence and development of anal fistulas.
Anti-Bacterial Agents ; Bacteria/genetics* ; DNA, Ribosomal ; Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics* ; Rectal Fistula/surgery*

OBJECTIVETo analyze the clinical effect of spinal cord decompression and lavage therapy on chronic cervical spinal cord injury and explore the possible mechanism.

METHODSFifty-seven patients with chronic cervical spinal cord injury treated in our hospital from January, 2008 to January, 2015 were enrolled, including 17 with multilevel cervical disc herniation, 25 with long segmental ossification of the posterior longitudinal ligament, 13 with hypertrophy or calcification of neck ligamentum flavum, and 2 with old cervical fractures. Open-door spinal canal laminoplasty via a posterior approach and decompression in simple extramedullary decompression was performed in 31 cases (group A), and open-door spinal cord incision decompression via a posterior approach, saline irrigation, and spinal canal laminoplasty in intramedullary decompression was performed in 26 cases (group B). The pre-operative cerebrospinal fluid in group B patients was collected to examine the inflammatory factors. All the patients were followed up and evaluated for pre- and postoperative JOA scores to calculate the improvement rate with regular examinations by X-ray, CT or MRI.

RESULTSImaging examinations 2 weeks after the operation showed obvious relief of the primary lesion in both groups, and the improvement of high signals was better in group B than in group A. The mean improvement rate at 12 months after the operation was 52.33% in group A and 61.52% in group B (P<0.05), and the mean JOA score was significantly higher in group B than in group A (14.80∓1.51 vs 13.58∓0.56; P<0.05). Cerebrospinal fluid leakage occurred in 3 cases, epidural hematoma in 2 cases, internal fixation loosening in 1 case in group A; portal shaft fracture and internal fixation loosening occurred in 1 case in group B. Postoperative recovery time was shorter in group B and entered the platform phase in 3 months. The inflammatory factors IFN-γ, IL-17F, IL-6 and sCD40L were all significantly higher than the normal levels after spinal cord injury, and the increment of IL-6 was the most conspicuous (P<0.05).

CONCLUSIONIntramedullary and extramedullary decompression can achieve better outcomes than extramedullary decompression in patients with chronic cervical cord injury. This may be related not only to relieving adhesions and secondary compression by cutting the dura under the microscope, but also to removal of local inflammatory factors.

OBJECTIVETo investigate the effects of miR-181b on the migration and invasion of osteosarcoma cells.

METHODSThree cultured osteosarcoma cell lines and MG-63 cells transfected with miR-181b inhibitor were examined for miR-181b expression using qRT-PCR analysis. The cell migration and invasion of the transfected cells were assessed with Transwell assay. The targets of miR-181b were predicted using a miRNA target prediction software and the results were verified with luciferase reporter assay. The target protein expression in osteosarcoma cells lines was determined by Western blotting, and the cell migration and invasion changes following inhibition of miR-181b or its target protein were assessed using Transwell assay.

RESULTSAll the 3 osteosarcoma cells lines showed significantly up-regulated miR-181b expression. Inhibition of miR-181b expression obviously suppressed the migration and invasion of MG-63 cells. Based on luciferase reporter assay, N-myc downstream regulated gene 2 (NDRG2) was identified as the direct target gene of miR-181b, and inhibition of NDRG2 expression significantly reversed the effect of miR-181b on cell migration and invasion in MG-63 cells.

CONCLUSIONmiR-181b is over-expressed in osteosarcoma cells, and inhibition of miR-181b, which directly targets NDRG2, can suppress the migration and invasion of osteosarcoma cells.

Bone Neoplasms ; genetics ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs ; genetics ; metabolism ; Neoplasm Invasiveness ; Osteosarcoma ; genetics ; pathology ; Tumor Suppressor Proteins ; genetics ; metabolism

Antiviral Agents ; adverse effects ; therapeutic use ; Female ; Hepatitis C, Chronic ; complications ; drug therapy ; psychology ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Mental Disorders ; complications ; Middle Aged

OBJECTIVETo explore the level of serum uric acid (UA) in children with obstructive sleep apnea/hypopnea syndrome (OSAHS).

METHODBetween Sep. 2008 and Mar. 2010, 138 children with OSAHS were enrolled in study group. Sixty-five children with accessory auricle or ptosis of upper lid were enrolled into the control group. Furthermore, according to apnea/hypopnea index (AHI) or obstructive apnea index (OAI) the study group was further divided into three subgroups (mild, moderate and severe group). At last, the study group and control group were divided into two groups according to the body mass index (BMI), separately. The fasting serum UA level was compared among the different groups. Then the correlation between the serum UA level and AHI, BMI, oxygen desaturation index, least arterial oxygen saturation (LSaO(2)) and the percentage of total sleep time with arterial oxygen saturation < 0.92 was also analyzed in OSAHS children with or without overweight and obesity respectively.

RESULTThe difference of serum UA level between the study group and control group (z = -0.443), and the difference among the three groups (χ(2) = 1.241) was not significant(P > 0.05). The serum UA level in overweight and obese children [study group, 273.0 (238.3 - 357.3); control group, 298.0 (253.0 - 336.0)] was significantly higher than that in children with normal BMI [study group, 246.5(215.8 - 300.0); control group, 266.0 (224.0 - 303.3)] (z = -2.084, -2.214, P < 0.05). That serum UA level did not correlate with the above index of OSAHS was observed in children with or without overweight and obesity in study group (P > 0.05).

CONCLUSIONFindings of higher serum UA level were not observed in children with OSAHS. There was no correlation between serum UA level and the above indices of OSAHS. The serum UA level in overweight and obese children was significantly higher than that in children with normal BMI.

Case-Control Studies ; Child ; Child, Preschool ; Humans ; Sleep Apnea, Obstructive ; blood ; Uric Acid ; blood

OBJECTIVETo study the changes of MAPK and Akt signaling pathways in hearts and placentas of aborted fetuses with congenital heart disease (CHD), and investigate their roles in the pathogenesis of CHD.

METHODSTen aborted fetuses with severe CHD (CHD group) and 7 gestational age-matched non-cardiac malformation aborted fetuses (control group) were enrolled. Western blot analysis was undertaken to assess the expression of p38, p38alpha, p-p38, MEF2, ERK, p-ERK, Akt, p-Akt(Ser473) and p-Akt(Thr308) in left ventricles and placentas of the fetuses, while semi-quantitative reverse transcription polymerase chain reaction analysis was used to detect the expression of p38alpha isoforms mRNA in hearts.

RESULTSCompared with the heart samples of the control group, the protein expression levels of p38 and its alpha isoform in 4 cases, p-p38 in 6 cases, MEF2 in 2 cases, p-ERK in 8 cases, Akt in 4 cases, p-Akt(Ser473) and p-Akt(Thr308) in 8 cases decreased, while the protein expression levels of p-p38 in 2 cases and p-Akt(Thr308) in 1 case increased. P-p38 protein level in 3 cases and p-ERK protein level in 2 cases decreased in placentas compared with the control group. The changes of protein expression of MAPK and Akt signaling pathway in hearts were not consistent with those in placentas in the CHD group. The expression of p38alpha isoform2 mRNA showed descent tendency in 4 heart samples with CHD, while the expression of other three p38alpha isoforms mRNA was reduced in only 1 sample compared with the control group.

CONCLUSIONSDysfunction of MAPK and Akt signaling pathways is tissue-specific in aborted fetuses with CHD. The perturbed two signaling pathways in hearts may contribute to the pathogenesis of human CHD.

Female ; Fetus ; metabolism ; Heart Defects, Congenital ; metabolism ; Humans ; MAP Kinase Signaling System ; physiology ; Myocardium ; metabolism ; Phosphatidylinositol 3-Kinases ; physiology ; Placenta ; metabolism ; Pregnancy ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction ; physiology ; p38 Mitogen-Activated Protein Kinases ; physiology

OBJECTIVETo summarize the clinical experience of trastuzumab treatment in neoadjuvant, adjuvant, metastatic setting of Chinese patients with Her-2 positive breast cancer and evaluate the efficacy of trastuzumab in combination with chemotherapy.

METHODSFrom January 2004 to December 2008, 141 outpatients with breast cancer treated with trastuzumab were investigated retrospectively. The follow-up time ranged from 3 to 319 months. The disease free survival time (DFS) of metastatic setting was calculated. The overall survival time (OS), time to treatment failure (TTF) and clinical response rate (CRR, including complete response, partial response and stable disease) of adjuvant, first-line, second-line therapy were analyzed statistically.

RESULTSIn the neoadjuvant regimen, paclitaxel plus carboplatin in combination with trastuzumab accounted for 66.7%, which achieved pathological complete response in 10 of 16 patients. In the adjuvant regimen, anthracycline or anthracycline followed by taxane accounted for 53.9%. The median DFS of 57 cases with metastatic diseases was 17 months. The CRR of first-line trastuzumab use in metastatic setting was 84.5%, compared with 44.4% of second-line use. The median TTF of first-line treatment was 24 months compared with 5 months of second-line treatment. Statistically significant differences were observed.

CONCLUSIONThe regimen of paclitaxel plus carboplatin in combination with trastuzumab deserves wide clinical use. In metastatic setting, first-line treatment of trastuzumab plus chemotherapy can achieve a higher response rate than second-line treatment. Continued trastuzumab therapy combined with different chemotherapy treatment after disease progression may obtain additive clinical advantage.

Adult ; Anthracyclines ; administration & dosage ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Bridged-Ring Compounds ; administration & dosage ; Carboplatin ; administration & dosage ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Paclitaxel ; administration & dosage ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; Survival Rate ; Taxoids ; administration & dosage ; Trastuzumab ; Treatment Failure