Objective : To investigate the combined effects of triclosan（TCS）and PCB153 on the activity of superoxide dismutase（SOD）and the concentration of malondialdehyde（MDA）in zebrafish liver. Methods : Adult zebrafish were exposed to a series of concentrations of TCS,and the mortality in each group was observed and recorded during the acute toxicity test process. The concentrations in subsequent combined exposure experiments were arranged on the basis of the 96 h-LC50. The factorial design was used to determine the concentrations of combined exposure groups between TCS（0,0.125,0.5 μmol/L）and PCB153（0,0.05,0.2 μmol/L）. After 5,10 and 14 days of exposure,the zebrafish livers were dissected and frozen in each group. The potential interactions of these two compounds were analyzed according to the results of the SOD and MDA. Results : The 96 h-LC50 of TCS exposed to adult zebrafish was 2.64 μmol/L（95%CI：2.37-2.89 μmol/L）. After 5 days of exposure,combined exposure to 0.5 μmol/L TCS+0.2 μmol/L PCB153 caused lower liver SOD activities than single exposure groups and the control group（P<0.05）. After 10 days of exposure,combined exposure to 0.125 μmol/L TCS+0.05 μmol/L PCB153,0.5 μmol/L TCS+0.05 μmol/L PCB153 caused lower liver SOD activities than single exposure groups and the control group（P<0.05）. After 14 days of exposure,combined exposure to 0.5 μmol/L TCS+0.05 μmol/L PCB153,0.5 μmol/L TCS+0.2 μmol/L PCB153 caused higher liver SOD activities than single exposure groups and the control group（P<0.05）. There was an interactive effect between TCS and PCB153 on the liver SOD activity in zebrafish（P<0.05）. There was no significant effect of MDA content in each group. Conclusion Combined exposure to TCS and PCB153 could enhance （inhibit first） the liver SOD activities in zebrafish,and the interaction was synergistic.

Clinical phenotype and gene characteristics of a patient diagnosed with Imerslund-Gr?sbeck syndrome (IGS) in Department of Neurology, Children′s Hospital of Soochow University in December 2018 were analyzed retrospectively, and literature review was conducted.The 16 years and 5 months old boy was admitted to the hospital with symptoms of weakness of lower limbs for 2 weeks.He had a history of megaloblastic anemia and isolated proteinuria.Genetic metabolism of hematuria showed methylmalonic academia.Genetic analysis revealed a compound heterozygous AMN gene mutation[c.742C>T(p.Q248 *) and c. 761G>A(p.G254E)]. These two mutations were derived from his parents respectively, which had been reported before.Symptoms of the patient improved after intramuscular administration of hydroxycobalamin and oral betaine.Review of the literature indicated that the clinical manifestations of AMN gene-related IGS were mostly megaloblastic anemia and isolated proteinuria, and the older children might suffer from neurological symptoms such as movement disorders, dementia, delirium or psychosis.The clinical phenotype of this disease was variable, which might easily lead to misdiagnosis.The patient presented with a special phenotype of mild reversible peripheral neuropathy, which expanded the clinical phenotype of pathogenic genes of AMN gene.In addition, peripheral neuropathy caused by vitamin B 12 metabolic disorders is reversible, and it is suggested to measure vitamin B 12, test related genes and treatment with vitamin B 12 in peripheral neuropathy of unknown etiology.

Background:The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear.This study aimed to evaluate the effects of KA supplementation on nutritional status,inflammatory markers,and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patents with MHD without malnutrition.Methods:This was a prospective,randomized,controlled,single-center clinical study conducted in 2011 till 2014.Twenty-nine patients with MHD were randomly assigned to a control (n =14) or a KA (n =15) group.The control group maintained a dietary protein intake of 0.9 g/kg/day.The KA group received additional KA supplement (0.1 g/kg/day).BIA was used to determine the lean tissue mass,adipose tissue mass,and body cell mass.The patients' nutritional status,dialysis adequacy,and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test.Results:The daily total energy intake for both groups was about 28 kcal/kg/day.After 6 months,the Kt/V (where K is the dialyzer clearance of urea,t is the dialysis time,and V is the volume of the distribution of urea) was 1.33 ± 0.25 in KA group,and 1.34 ± 0.25in the control group.The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group.In addition,the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group.There were no significant differences between the groups with respect to the anthropometry parameters,dialysis adequacy,serum calcium and phosphorus levels,inflammatory markers,and amino-acid profiles,or in relation to the parameters determined by BIA.Both groups achieved dialysis adequacy and maintained nutritional status during the study.Conclusions:In this cohort of Chinese patients with MHD,the patients in the control group whose dietary protein intake was 0.9 g/ kg/day and total energy intake was 28 kcal/kg/day,maintained well nutritional status during study period.The KA supplement (0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio,nor did it change the patients' mineral metabolism,inflammatory parameters,or body compositions.

To investigate the anti-hepatoma mechanism of α-pinene, HepG2 cell was treated with α-pinene and the change of cell cycle was examined by flow cytometry. The expression of miR-221, which was related the regulation of G₂/M phase, was detected by quantitative Real-time PCR. Meanwhile, TargetScan and other online bioinformatics methods were used to analyze and predict the target genes of miR-221, then the expression level of related target genes were detected by quantitative Real-time PCR. The results showed that α-pinene inhibited the proliferation of HepG2 cells in dose-dependent manner. It was also proved that HepG2 cells were arrested at G₂/M phase by α-pinene (P<0.05). The expression of miR-221 was down-regulated in α-pinene treated HepG2 cell. The bioinformatics analysis showed that CDKN1B/P27 and CDKN1C/P57 may be the protential targets of miR-221 and both of them were significantly up-regulated（P<0.001,P<0.05）by α-pinene treatment. According to these results, it was believed that α-pinene may inhibit the proliferation of hepatocellular carcinoma cells through arrest the cell at G₂/M phase, which may be associated with the down-regulate of the miR-221 expression and up-regulate of the CDKN1B/P27 and CDKN1C/P57 expression.

Based on the anticancer mechanism of biological alkylating agent, we designed and synthesized two alpha pinene derivatives:(1R,5S)-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)methyl benzenesulfonate and (1R,5S)-(6,6-dimethylbicyclo[3,1,1]hept-2-en-2-yl)methyl 4-methylbenzenesulfonate, of which structures were confirmed by ¹H-NMR, HPLC and MS date. These two compounds showed a good inhibition of tumor cells' proliferation. Further, the computer siuulation of molecular docking and metabolic kinetics indicated that these two copounds may have stable molecular complexation with protein CDK2, which closely related to the cell cycle.

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min^-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min^-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL^-1 and 9-150 ng·mL^-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL^-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L^-1 ammonium formate (D), with a flow rate of 0.2 mL·min^-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI⁺), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL^-1, 3-100 ng·mL^-1 and 0.9-30 ng·mL^-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL^-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

Objective:To study the efficacy of integrative medicine on congenital muscular torticollis. Methods:From October, 2017 to September, 2019, 80 children with congenital muscular torticollis were divided into group 1 (n = 40) and group 2 (n = 40) according to different treatment schemes. Group 1 received comprehensive physiotherapy, including passive stretching, head control training, posture correction and family rehabilitation. Group 2 received Tuina in addition. Before and six months after treatment, the root mean square (RMS) of surface electromyography of bilateral sternocleidomastoid muscles in supine neutral position, neck rotation and stretch, and the range of motion of passive neck rotation and lateral flexion, and the angle of head deviation from the midline to the affected side were compared. Results:Before treatment, the RMS of sternocleidomastoid muscle in each position was lower in the affected side than in the healthy side (P < 0.01), and the range of motion of neck when lateral flexion to the healthy side and rotation to the affected side was less than that of the other side (P < 0.01) in both groups; however, no significant difference was found between two groups (P > 0.05). After treatment, the RMS of EMG of sternocleidomastoid muscle in each position, and the range of motion of neck when lateral flexion to the healthy side and rotation to the affected side improved (|t| > 3.290, P < 0.01) in both groups, and were better in group 2 than in group 1 (t > 2.401, P < 0.05); the angle of head deviation from the midline to the affected side significantly decreaed (t > 15.075, P < 0.001) in both groups, and was significantly less in group 2 than in group 1 (t = -4.971, P < 0.001). Conclusion:Integrative medicine is effective on infant with congenital muscular torticollis, which is superior to comprehensive physiotherapy only.

Objective: To evaluate the auditory efficacy and subjective satisfaction of adhesive bone conduction hearing aid in children with unilateral congenital aural atresia (UCAA). Methods: Ten subjects (5 males and 5 females) diagnosed with UCAA with an average age of 8.3 years old (ranged from 5 to 15) were included in Beijing Tongren Hospital, Capital Medical University from January to August 2019. The free sound field hearing threshold, word recognition score in quiet, speech reception threshold in noise and sound localization ability (results were measured by RMS error) tests were performed in unaided and aided situation, respectively. Subjective satisfaction questionnaires were also distributed to subjects. Paired t test and Wilcoxon signed rank test were used as statistical analysis methods. Results: The average hearing threshold in aided condition was improved by (21.9±4.4) dB (t=15.8，P<0.05). Speech recognition abilities were generally improved both under quiet and noise (P<0.05);however, when the binaural summation, squelch and head shadow effects were analyzed respectively, the binaural squelch effect was not statistically improved (P>0.05), while the other effects were improved in aided condition (P<0.05). In sound localization test, there was no significant difference of the RMS error value between the unaided and aided situation (P>0.05). The subjects got high satisfaction rates in three subjective questionnaires. Conclusion: The adhesive bone conduction hearing aid can provide significant audiological benefit for children with UCAA as well as raising the quality of their life.
Adhesives ; Adolescent ; Bone Conduction ; Child ; Child, Preschool ; Female ; Hearing Aids ; Hearing Loss, Conductive ; Humans ; Male ; Speech Perception ; Treatment Outcome

OBJECTIVE: Late 2019 witnessed the outbreak and widespread transmission of coronavirus disease 2019 (COVID-19), a new, highly contagious disease caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Consequently, considerable attention has been paid to the development of new diagnostic tools for the early detection of SARS-CoV-2. METHODS: In this study, a new poly-N-isopropylacrylamide microgel-based electrochemical sensor was explored to detect the SARS-CoV-2 spike protein (S protein) in human saliva. The microgel was composed of a copolymer of N-isopropylacrylamide and acrylic acid, and gold nanoparticles were encapsulated within the microgel through facile and economical fabrication. The electrochemical performance of the sensor was evaluated through differential pulse voltammetry. RESULTS: Under optimal experimental conditions, the linear range of the sensor was 10 ^-13-10 ^-9 mg/mL, whereas the detection limit was 9.55 fg/mL. Furthermore, the S protein was instilled in artificial saliva as the infected human saliva model, and the sensing platform showed satisfactory detection capability. CONCLUSION The sensing platform exhibited excellent specificity and sensitivity in detecting spike protein, indicating its potential application for the time-saving and inexpensive detection of SARS-CoV-2.
Humans ; Microgels ; Spike Glycoprotein, Coronavirus ; COVID-19/diagnosis* ; Gold ; Metal Nanoparticles ; SARS-CoV-2