Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective:To explore the relationship between fragmented QRS complex and heart rate variability (HRV) and ventricular arrhythmia in patients with old myocardial infarction.Methods:From August 2018 to October 2019, 200 patients with old myocardial infarction were first treated in the Department of cardiac function examination of the First Affiliated Hospital of Hebei North University. The patients were divided into 99 cases of old myocardial infarction with fragmented QRS wave group and 101 cases of old myocardial infarction without fragmented QRS wave group according to the case bank data and conventional 12 lead ECG diagnosis in our hospital for the first time. Then, the 24-h ambulatory ECG reexamined within 1 year after discharge was retrospectively analyzed. The incidence of ventricular arrhythmia was compared between the two groups by χ 2 test. The difference of heart rate variability between the two groups was compared by rank sum test. Multiple logistic regression was used to analyze the value of different indexes of heart rate variability in the evaluation of fragmented QRS complex in old myocardial infarction. Drawing the receiver operating characteristic (ROC), and the area under the curve (AUC) was used to analyze the diagnostic accuracy of different indexes of heart rate variability in the broken QRS complex of old myocardial infarction. Results:According to the Lown classification of ventricular premature contraction, the number of positive ventricular arrhythmias in patients with Grade Ⅰ of ventricular premature contraction and Grade Ⅲ-Ⅴ of ventricular premature contraction in the old myocardial infarction fragmented QRS group was higher than that in the old myocardial infarction non fragmented QRS group (Grade Ⅰ of ventricular premature contraction: 54.5% (54/99)and 39.6%(40/101); χ 2=4.484, P<0.05;Grade Ⅲ-Ⅴ of ventricular premature contraction: 34.3% (34/99) and 9.9%(10/101); χ 2=17.406, P<0.05)). Ventricular premature contraction Grade 0 old myocardial infarction fragmented QRS group was lower than old myocardial infarction non fragmented QRS group (8.1% (8/99) and 48.5% (49/101); χ 2=37.995, P<0.05). The total number of positive cases of ventricular arrhythmia in the old myocardial infarction group with fragmented QRS wave was higher than that in the old myocardial infarction group without fragmented QRS wave (91.9% (91/99) and 51.5%(52/101); χ 2=57.146, P<0.05)). There was no significant difference in the number of positive ventricular arrhythmias between the old myocardial infarction fragmentation QRS group and the old myocardial infarction non fragmentation QRS group ( P>0.05). The standard deviation of NN intervals (SDNN) and the standard deviation of average NN intervals (SDANN) of HRV time domain indexes in the old myocardial infarction fragmented QRS group were higher than those in the old myocardial infarction non fragmented QRS Group (SDNN:143.00(122.00,166.00) vs. 110.00(95.00,130.50), Z=5.780, P<0.05; SDANN:112.00(100.00,136.00) vs. 96.00(76.00,118.50), Z=4.013, P<0.05). Multiple Logistics regression analysis results of HRV domain shows that HRV time domain SDNN and SDANN have diagnositic value in diagnosis fQRS after OMI(SDNN: OR=0.949, 95% CI:0.922-0.977, P<0.001; SDANN: OR=1.036, 95% CI:1.005-1.068, P=0.022). Area under ROC curve of HRV time domain SDNN and SDANN have particular diagnositic accuracy in diagnosis fQRS after OMI(SDNN: AUC 0.737, 95% CI 0.666-0.807, Sensitivity 0.818, Specificity 0.634; SDANN: AUC 0.664, 95% CI 0.587-0.741, Sensitivity 0.737, Specificity 0.673. 0.5

Objective:To observe the body fluid and cellular immune function of children with cerebral palsy (CP) in the plateau area, as well as the exchanges of these factors during the comprehensive rehabilitation treatment.Methods:A total number of 144 children admitted to Xining Hospital of Traditional Chinese Medicine from June 2018 to October 2019 were selected as the CP group for comprehensive rehabilitation treatment (consecutive courses). The peripheral blood immunoglobulin/complement (IgA, IgG, lgM, C3, C4) level, T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and neuron-specific enolase (NSE) content was examined in the clinical specimens before and after treatment by using the immunoturbidimetry, flow cytometry, electrochemiluminescence analysis according to the Gross Motor Function Classification System (GMFCS) and Gross Motor Function Test Scale (GMFM-88). Children were divided as the different degrees to evaluate the rehabilitation efficacy. A total number of 50 healthy children taken a health check/physical examinations during the same period were considered as the control group. For statistical Analysis, the χ2 test and independent sample t test were performed. Results:The levels of humoral immune IgG, IgA, IgM, C3 and C4 in CP Group [(6.42±1.05), (0.64±0.13), (0.89±0.13), (0.80±0.08), (0.17±0.03) g/L, respectively] in CP groups′ children were lower than those in the control group [(10.25±0.62), (1.04±0.06), (1.06±0.17), (1.04±0.04), (0.27±0.04) g/L, respectively]. The humoral immune IgG and IgA levels [severe (5.40±0.69) and (0.55±0.09)g/L, moderate (6.63±0.30) and (0.66±0.14)g/L, mild (7.57±0.63) and (0.74±0.09)g/L, P<0.05] were also related to the children with CP of different GMFCS grades. Moreover, the level of T lymphocyte subsets (CD3+,CD4+,CD8+,CD4+/CD8+) in the CP group were not statistically different to that in the control groups children. Receiving the rehabilitation treatment, the levels of serum humoral IgG and IgA in CP Group (7.69±1.14) and (0.79±0.17) g/L were significantly enhanced; whereas the serum NSE (12.82±2.49) μg/L was lower than that before treatment (18.57±3.08) μg/L, and the total score of GMFM-88 (121.35±26.51) was higher than that before treatment (101.04±27.62). The differences were statistically significant ( P<0.05). IgM, C3, C4 and T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) had no significant difference compared with those before treatment ( P>0.05). Conclusions:Children with CP at high altitude have abnormal humoral immune function. IgG and IgA may be related to the severity of CP and neuronal damage. Comprehensive rehabilitation can not only improve the motor function of children with CP, relieve neuronal damage, but also enhance their humoral immunity status.

Objective:To explore the changes of serum neuron-specific enolase (NSE) and myelin basic protein (MBP) in children with cerebral palsy at high altitude during comprehensive rehabilitation and their clinical significance.Methods:A clinical randomized controlled study design was used to select 144 children with cerebral palsy who were diagnosed and treated in the Rehabilitation Center of Xining Traditional Chinese Medicine Hospital of Qinghai Province from June 2018 to October 2019, including 83 males and 61 females, aged 3-5 years old. According to the order of admission, the random number table was used to divide into a conventional treatment group ( n=72, 40 males and 32 females) and a comprehensive treatment group ( n=72, 43 males and 29 females). The conventional treatment group was treated with conventional rehabilitation. The comprehensive treatment group was treated with monosialotetrahexose ganglioside sodium on the basis of conventional rehabilitation. In addition, 30 healthy children aged 3-5 years, 16 males and 14 females, were selected as the control group during the physical examination of the Pediatrics Department of Xining Hospital of Traditional Chinese Medicine, Qinghai Province. The serum levels of NSE and MBP in each group were detected, and the children′s GMFM-88 scores were evaluated before and after treatment. The SPSS19.0 software was used for statistical analysis, the count data was tested by χ 2. Results:The serum NSE and MBP levels of the control group were (5.96±0.80), (0.71±0.15) μg/L. Before treatment, the serum NSE and MBP levels of children with severe, moderate, and mild cerebral palsy were [(21.63±1.92), (3.63±0.49) μg/L], [(17.86±1.43) μg/L, (2.21±0.07) μg/L] and [(15.14±0.95), (1.76±0.30) μg/L], respectively. After treatment, the serum NSE and MBP levels of the conventional treatment group and the comprehensive treatment group were [(13.54±2.41), (2.07±0.85) μg/L] and [(12.09±2.37), (1.81±0.69) μg/L], respectively, and the GMFM-88 score was (116.75±27.41) points and (125.94±24.93) points. The levels of NSE and MBP in the serum of children with cerebral palsy were significantly higher than those of normal children in the control group, and their levels increased with the degree of disease, and the corresponding gross motor function scores were lower. After treatment, the GMFM-88 scale assessment scores of the two groups of children were significantly improved ( t values were 310.97 and 70.86, P values were both<0.05), and serum NSE and MBP levels decreased to varying degrees compared with before treatment. The decline in the comprehensive treatment group was greater than that in the conventional treatment group. Conclusions:Serum NSE and MBP levels in children with cerebral palsy at high altitude are significantly higher than those in healthy children, and their levels are closely related to the degree of impairment and GMFM-88 scores in children with cerebral palsy. Dynamic monitoring of changes in NSE and MBP levels may be responsible for the condition and treatment effects of children with cerebral palsy judgments based.

Objective:To explore the changes of serum neuron-specific enolase (NSE) and myelin basic protein (MBP) in children with cerebral palsy at high altitude during comprehensive rehabilitation and their clinical significance.Methods:A clinical randomized controlled study design was used to select 144 children with cerebral palsy who were diagnosed and treated in the Rehabilitation Center of Xining Traditional Chinese Medicine Hospital of Qinghai Province from June 2018 to October 2019, including 83 males and 61 females, aged 3-5 years old. According to the order of admission, the random number table was used to divide into a conventional treatment group ( n=72, 40 males and 32 females) and a comprehensive treatment group ( n=72, 43 males and 29 females). The conventional treatment group was treated with conventional rehabilitation. The comprehensive treatment group was treated with monosialotetrahexose ganglioside sodium on the basis of conventional rehabilitation. In addition, 30 healthy children aged 3-5 years, 16 males and 14 females, were selected as the control group during the physical examination of the Pediatrics Department of Xining Hospital of Traditional Chinese Medicine, Qinghai Province. The serum levels of NSE and MBP in each group were detected, and the children′s GMFM-88 scores were evaluated before and after treatment. The SPSS19.0 software was used for statistical analysis, the count data was tested by χ 2. Results:The serum NSE and MBP levels of the control group were (5.96±0.80), (0.71±0.15) μg/L. Before treatment, the serum NSE and MBP levels of children with severe, moderate, and mild cerebral palsy were [(21.63±1.92), (3.63±0.49) μg/L], [(17.86±1.43) μg/L, (2.21±0.07) μg/L] and [(15.14±0.95), (1.76±0.30) μg/L], respectively. After treatment, the serum NSE and MBP levels of the conventional treatment group and the comprehensive treatment group were [(13.54±2.41), (2.07±0.85) μg/L] and [(12.09±2.37), (1.81±0.69) μg/L], respectively, and the GMFM-88 score was (116.75±27.41) points and (125.94±24.93) points. The levels of NSE and MBP in the serum of children with cerebral palsy were significantly higher than those of normal children in the control group, and their levels increased with the degree of disease, and the corresponding gross motor function scores were lower. After treatment, the GMFM-88 scale assessment scores of the two groups of children were significantly improved ( t values were 310.97 and 70.86, P values were both<0.05), and serum NSE and MBP levels decreased to varying degrees compared with before treatment. The decline in the comprehensive treatment group was greater than that in the conventional treatment group. Conclusions:Serum NSE and MBP levels in children with cerebral palsy at high altitude are significantly higher than those in healthy children, and their levels are closely related to the degree of impairment and GMFM-88 scores in children with cerebral palsy. Dynamic monitoring of changes in NSE and MBP levels may be responsible for the condition and treatment effects of children with cerebral palsy judgments based.

Pharmaceutical cocrystals are a promising technology that can be used to improve the solubility of poor aqueous compounds. The objective of this study was to systematically investigate the solubility of myricetin (MYR) cocrystals, including their kinetic solubility, thermodynamic solubility, and intrinsic dissolution rate (IDR). The effects of pH, surfactant, ion concentration, and coformers on the cocrystal solubility were evaluated. Furthermore, single crystal structures of MYR, myricetin-isonicotinamide (MYR-INM) and myricetin-caffeine (MYR-CAF) cocrystals were analyzed to discuss the possible reasons for the enhancement of cocrystal solubility from the perspective of the spatial structure. The results indicated that the kinetic solubility of MYR cocrystals was modulated by pH and cocrystal coformer (CCF) ionization in buffer solution, while it primarily depended on the CCF solubility in pure water. In addition, the solubility of MYR cocrystals was increased in a concentration dependent fashion by the surfactant or ion concentration. The thermodynamic solubility of MYR-INM (1:3) cocrystals decreased with the increases of the pH value of the dissolution media. The IDR of MYR cocrystals was faster than that of MYR in the same medium and extremely fast in pH 4.5 buffer. The improved solubility of MYR cocrystals was probably related to the alternate arrangements of MYR and INM/CAF molecules and increased intermolecular distance. The present study provides some references to investigate the solubility behavior of pharmaceutical cocrystals.

Objective To evaluate the effect of propofol on high-mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4) signaling pathway during hepatic ischemia-reperfusion (I/R) injury in rats.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 3 months,weighing 250 -300 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),hepatic I/R group (group I/R) and propofol group (group P).Hepatic I/R injury was induced by occluding the portal vein and hepatic artery supplying the left and middle lobes of the liver for 1 h followed by 6-h reperfusion in anesthetized rats.Propofol was infused via the tail vein at a rate of 12 mg ·kg-1 · h-1 starting from 20 min before ischemia until 6 h of reperfusion in group P.The rats were sacrificed at 6 h of reperfusion,and the left lobe of the liver was removed for microscopic examination of the pathological changes which were scored and for determination of the expression of HMGB1,TLR4,tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-6) in liver tissues (by Western blot).Results Compared with group S,pathological scores of liver tissues were significantly increased,and the expression of HMGB1,TLR4,TNF-α and IL-6 was up-regulated in I/R and P groups (P＜0.05).Compared with group I/R,pathological scores of liver tissues were significantly decreased,and the expression of HMGB1,TLR4,TNF-α and IL-6 was down-regulated in group P (P＜ 0.05).Conclusion The mechanism by which propofol reduces liver I/R injury is associated with blocking HMGB-1/TLR4 signaling pathway and inhibiting inflammatory responses in rats.

Objective To evaluate the efficacy of Disposcope endoscope(DE)-guided nasotrache-al intubation in patients with difficult airway by comparing with fiberoptic bronchoscope(FOB). Methods One hundred and twenty American Society of Anesthesiologists physical statusⅠ-Ⅲ patients of both se-xes, with body mass index<25 kg∕m2, aged 18-64 yr, with mouth opening<3 cm, of Mallampati classifi-cation Ⅲ or Ⅳ, undergoing maxillofacial surgery requiring nasotracheal intubation were divided into DE group(n=60)and FOB group(n=60)using a random number table.Nasotracheal intubation was per-formed under the guidance of DE or FOB after induction of anesthesia.Glottis exposure was evaluated using Cormack-Lehane grade.Epistaxis during intubation, successful intubation, time and degree of glottis expo-sure, intubation time and development of tachycardia and hypertension and requirement for assisted ventila-tion with face mask during intubation were recorded.The patients were followed up postoperatively, and the development of intubation-related complications was also recorded.Results Compared with group FOB, glottis exposure time and incubation time were significantly shortened(P<0.05), and no significant change was found in Cormack-Lehane grade, rate of successful incubation, rate of successful intubation at first attempt or intubation-related complications in group DE(P>0.05). Hypertension and tachycardia were not found and no patients required assisted ventilation with face mask during intubation in the two groups.Conclusion DE-guided nasotracheal intubation provides similar efficacy to that of FOB with shorter time and is an optimal selection for the patients with difficult airway.

Objective To conduct nutrition risk screening on newborns with modified screening tool for the assessment of malnutrition in pediatrics (STAMP), and to analyze the correlation between nutritional risk of newborns and diseases. Methods A total of 2 300 newborns treated in Neonatal Center (NICU, Department of Neonatology and Department of Neonatal Surgery) in Children's Hospital of Shanxi from February to December 2015 were screened by modified scale STAMP about their nutritional risks, with the data collected and analyzed. Results Top five high risks concerning disease and nutrition among newborns were: hyaline membrane, volvulus, hematochezia of unknown origin, premature infants, and abdominal distension of unknown origin. Differences of malnutrition conditions and nutrition intake among newborns from different departments were statistically significant (χ2=31.74, 177.00; P<0.005). Majority of newborns in NICU and Department of Neonatal Surgery were without any nutrition intake at all, while majority of newborns in Department of Internal Medicine were with only half or less nutrition intake. Differences of high malnutrition risks and insufficient nutrition intake among premature and term infants from different departments were statistically significant (χ2=72.70, 53.95; P<0.001). Differences of weight growth conditions among newborns from different departments were statistically significant (χ2=13.57, P=0.002). Conclusions By using modified STAMP, it can be identified that factors causing high risks of neonatal nutrition include diseases, gestational age, nutritional intake, growth and development. Individualized nutritional support program should be implemented according to results of the screening, so that status quo of extrauterine growth restriction can be improved.

Objective To examine the anticancer effect of a novel histone deacetylase inhibitor (HDACi), JZ004, on colon cancer cells HCT-8 and HT-29, and to investigate the molecular mechanisms of proliferation inhibition and apoptosis induction of cancer cells treated by JZ 004.Methods Colon cancer cells were treated with a series of concentrations of JZ004 .MTT assay was used to detect the proliferation of cancer cells .The cell cycle distribution and apoptosis were deter-mined by flow cytometry .Rhodamine 123 and DCFH-DA were applied to detect the mitochondrial membrane potential (ΔΨm) and reactive oxygen species ( ROS) production.The protein expressions of acetyl-histone H3, p21, cyclin-dependent kinase(CDK)4, Bcl-2, Mcl-1 and Bax were assayed by Western blotting .Results JZ004 was found to inhibit proliferation and induce apoptosis of colon cancer cells in a time-and dose-dependent manner , accompanied by a dose-dependent hyperacetylation of histone H3.JZ004 induced the cancer cell arrest in G 0/G1 phase by increasing the expres-sion level of p21 while CDK4 was downregulated .JZ004 also increased cellular ROS production and reduced ΔΨm by regu-lating the expressions of Bcl-2 family proteins .Conclusion As a novel HDACi , JZ004 effectively inhibits proliferation and increases ROS production to induce apoptosis of colon cancer cells .The results indicate that JZ004 is a potential compound to be developed as an anti-colon cancer agent for clinic application .