Objective To investigate the role of cytochrome P450 2E1 (CYP2E1) in trichloroethylene (TCE)-induced skin sensitization and liver damage in guinea pigs, using diallyl sulfide (DAS), a CYP2E1 inhibitor, as an intervention. Methods Specific pathogen-free female guinea pigs were randomly divided into blank control group, solvent control group, positive control (2,4-dinitrochlorobenzene) group, TCE-exposure group, and DAS-intervention group. Skin sensitization experiments were conducted using the guinea pig TCE maximal dose-skin sensitization test. Urinary trichloroacetic acid levels were determined following TCE induction and challenge. At 48 hours after the final challenge, serum liver function markers and inflammatory cytokines levels were detected. Histopathological examination on skin and liver tissues was performed, and hepatic CYP2E1 protein expression and oxidative stress indicators were assessed. Results The sensitization rates of guinea pigs were 100.0%, 75.0%, and 33.3% in the positive control, TCE-exposure, and DAS-intervention groups, respectively, while the blank control and solvent control groups were both 0.0%. Compared with the guinea pigs in TCE-exposure group, those in the DAS-intervention group had lower urinary trichloroacetic acid levels at intradermal induction, local induction, first challenge, and 24 hours after the final challenge time point (all P<0.05). Histopathology of guinea pigs showed dermal inflammatory infiltration and basal keratinocyte necrosis in the TCE-exposure group, whereas only mild dermal inflammation was observed in the DAS-intervention group. The guinea pigs in TCE-exposure group exhibited diffuse hepatocellular necrosis, while hepatic damage in the DAS-intervention group was alleviated, characterized by only mild hepatocellular steatosis and hepatocyte swelling around the central vein. The skin sensitization rate of guinea pigs in the TCE-exposure group increased (all P<0.01), the serum alanine aminotransferase (ALT )activity, the levels of interleukin (IL)-2, IL-17, and tumor necrosis factor-α (TNF- α) increased (all P<0.05), the relative expression of CYP2E1 protein, the activity of superoxide dismutase (SOD), and the level of malondialdehyde in liver tissue increased (all P<0.05), while the activity of catalase decreased (P<0.05), compared with the blank control and solvent control groups. The serum ALT activity and the levels of IL-2, IL-17, and TNF-α of guinea pigs in DAS-intervention group reduced (all P<0.05), as well as CYP2E1 protein expression, SOD activity, and malondialdehyde level in liver tissue reduced (all P<0.05), compared with the TCE-exposure group. Conclusion TCE can induce hepatic CYP2E1 expression, thereby promoting oxidative stress and inflammatory responses, which contributes to skin sensitization and liver damage. DAS alleviates TCE-induced toxic effects on skin and liver by inhibiting CYP2E1 expression.

Objective : To investigate the mechanisms of bromodomain-containing protein 4(BRD4) in TGF-β1-induced epithelial-mesenchymal transition in alveolar type II epithelial cells. Methods : MLE-12 cells were stimulated with different concentrations(5 ng/ml, 10 ng/ml) of TGF-β1 for 48 h to establish an EMT cell model. The cells were pretreated with 50 nmol/L BRD4 inhibitor JQ-1, 100 μmol/L high mobility group box 1 protein(HMGB1)inhibitor glycyrrhizin acid(GA), and 3 μg/ml rHMGB1. The experimental groups were divided as follows: control group, TGF-β1 group, JQ-1 group, JQ-1+TGF-β1 group, GA group, GA+TGF-β1 group, and JQ-1+TGF-β1+rHMGB1 group. The effect of JQ-1 on cell viability was examined using cell counting kit-8(CCK-8). The protein expression levels of CDH1, ZO-1, Vimentin, α-SMA, BRD4, HMGB1, TGF-β1, Smad2/3 and p-Smad2/3 were detected by Western blot. The cell migration ability was detected by a scratch test. Results : Compared with the control group, the levels of Vimentin and α-SMA in the TGF-β1 group increased, and the levels of CDH1 and ZO-1 protein decreased, suggesting that the EMT model was successfully established. In this model, the expression of BRD4 and HMGB1 significantly increased. Different concentrations of JQ-1 could inhibit the cell viability of MLE-12 in a concentration-dependent manner. Both JQ-1 and GA could effectively alleviate TGF-β1-induced EMT, and reduce the increase in HMGB1 expression and the activation of TGF-β1/Smad2/3 pathway caused by TGF-β1. Moreover, rHMGB1 treatment could reduce the effects of JQ-1 on EMT and the TGF-β1/Smad2/3 pathway. Additionally, both JQ-1 and glycyrrhizin could effectively decrease TGF-β1-induced cell migration, whereas rHMGB1 could alleviate the inhibitory effect of JQ-1 on the rate of cell migration. Conclusion BRD4 can regulate epithelial-mesenchymal transition in alveolar type II epithelial cells via HMGB1/TGF-β1/Smad2/3 signaling cascade, and BRD4 may be a potential target for inhibition of pulmonary fibrosis.

Background Silicosis is an occupational disease mainly characterized by pulmonary progressive fibrosis induced by the accumulation of free silica (SiO₂) in the lungs due to long-term exposure to SiO₂ dust. It has been shown that neutrophil extracellular traps (NETs) are increased in the lung tissues of silicotic mice after 28 d SiO₂ exposure, but it is unclear how the levels of NETs change throughout entire progression of silicosis in mice. Objective To observe the levels of NETs and pathological changes in the lungs of silicotic mice after different duration of SiO₂ exposure, and to confirm the possible role and significance of NETsin the development of SiO₂-induced pulmonary fibrosis. Methods A total of 28 SPF male C57BL/6J mice were randomly divided into a control group, and a model group, and the model group was subdivided into, a 2 d model group, a 7 d model group, and a 28 d model group, with 7 mice in each group. The mice in the model groups were given intratracheal instillation with 10 mg SiO₂ suspension (50 μL), and the mice in the control group were received same volume of saline. Mice were sacrificed and samples were collected at designed time points. The pathological changes of lung tissues of mice were observed after hematoxylin-eosin (HE) and Van Gieson (VG) staining. Immunofluorescence was used to observe the NETs markers citrullination histone H3 (CitH3) and myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF), and the percentage of NETs-positive cells was calculated. PicoGreen fluorescent dye kit was used to detect the content of extracelluar DNA (ex-DNA) in mouse BALF, and the expression levels of fibrosis-related proteins α-smooth muscle actin (α-SMA) and fibronectin (FN) and NETs marker CitH3 in lung tissues of mice were detected by Western blot (WB). Results Compared with the control group, inflammatory cells accumulation, alveolar wall thickening, and collagen deposition were obviously observed in the lungs of the silicosis model groups, and a large number of silicone nodules were recorded in the lung tissues in the 28 d group. Compared with the control group, the expressions of α-SMA and FN in the lung tissue of the 28 d group were significantly increased (P<0.05). The percentages of NETs in BALF increased significantly in the 2 d and the 7 d model group, then decreased in the 28 d model group (P<0.05). Compared with the control group (7.434±0.258) ng·mL⁻¹, the ex-DNA levels in BALF of mice in the 2 d [(35.110±6.331) ng·mL⁻¹], the 7 d [(39.491±6.948) ng·mL⁻¹], and the 28 d [(23.360±4.809) ng·mL⁻¹] model groups were increased (P<0.05), and the increase of ex-DNA in the 2 d and the 7 d model groups were statistically significant (P<0.05). In comparison with the control group, the protein level of CitH3 was significantly increased in the lung tissues of mice in the 7 d model group (P<0.05). Conclusion The content of NETs increases significantly and reaches a peak in the early inflammatory stage of silicosis, and decreases as the disease progresses to the fibrotic stage, suggesting that NETs may play a role in early stage of silicosis.

Objective To investigate the effects of long-term exposure to three new types of light emitting diode (LED) sources on the behavior, learning, and memory of rats. Methods A total of 160 specific pathogen-free SD rats were divided into eight groups as followed, trichromatic fluorescent lamps color temperature control group, violet-chip full-spectrum white LED group, blue-chip white LED group, and blue-chip full-spectrum white LED group based on the light sources types, with color temperature of 4 000 K and 6 500 K groups in each group using the 4×2 factorial design. There were 20 rats in each group, with half of the rats were males and half females. Rats were exposed to artificial lighting, and the illumination was set at 750 lx. The rats in each group were exposed to different lighting environments for 12 hours per day for 24 weeks. The open-field and step-down tests were conducted in rats after 24 weeks exposure, followed by sacrifice of rats and measurement of organ coefficients. Differences in body weight, organ coefficients, and neurobehavioral indexes of rats in different groups were compared. Results The spleen coefficient of female rats decreased in blue-chip white LED of 6 500 K color temperature group, and the liver coefficient of male rats decreased in the violet-chip full-spectrum white LED of 4 000 K color temperature, blue-chip full-spectrum white LED of 4 000 K color temperature, and blue-chip full-spectrum white LED of 6 500 K color temperature groups, compared with the same-sex rats in trichromatic fluorescent lamps with same-color temperature control group (all P<0.05). The result of different types of light sources compared in the open-field test showed that the index of total distance and movement speed of female rats in the blue-chip full-spectrum white LED group were lower than those in the other three groups, and the time cost to the central area was longer than that in the blue-chip white LED group and the violet-chip full-spectrum white LED group (all P<0.05). The total distance and movement speed of male rats in the blue-chip full-spectrum white LED group were longer or higher than those in the violet-chip full-spectrum white LED group (all P<0.05). Based on the comparison of color temperature, the time and total distance of male rats in 6 500 K color temperature group were lower than that in the 4 000 K color temperature group (both P<0.05). In the step-down test, both male and female rats in the blue-chip full-spectrum white LED group made more errors compared with other three groups with the same gender (all P<0.05). Conclusion Based on the experimental conditions of this study, the blue-chip full-spectrum white light LED affects behavior, learning and memory of the rats, and trichromatic fluorescent lamp has the lowest effect on neurobehavior. The color temperature also affects behavior of the rats, and high color temperature has higher risk.

Objective:To study the clinical characteristics, diagnostic methods and genotypes of neonatal chronic granulomatous disease(CGD).Methods:From April 2013 to August 2020, neonates admitted to our hospital, diagnosed with neonatal CGD and confirmed using neutrophil respiratory burst test and genetic testing were retrospectively studied. Their clinical characteristics and diagnostic methods were summarized.Results:A total of eleven neonates with CGD were enrolled, including ten males and one female. The age of onset was 3-23 d and the age of admission was 11-28 d. 3 cases had family history. The initial symptoms were fever (10 cases) and coughing (1 case). The accompanying symptoms included coughing (6 cases), dyspnea (4 cases), skin pustules (3 cases), fever (1 case) and diarrhea (1 case). Lung CT showed patchy shadows (6 cases), pulmonary nodules (3 cases), round and irregular high-density shadow (1 case), pulmonary consolidation (1 case), pleural effusion (1 case) and pleural thickening (2 cases). CGD was pathologically diagnosed in one patient. Sputum culture showed Candida albicans (3 cases), Aspergillus fumigatum (2 cases), Aspergillus fumigatum combined with Klebsiella pneumoniae and Escherichia coli (1 case), Aspergillus fumigatum combined with Staphylococcus aureus (1 case). GM tests were positive in two cases and negative in other two cases. Blood and cerebrospinal fluid cultures were negative. White blood cell counts were (10.0-44.0)×10 9/L and C-reactive proteins were (14-165) mg/L. 11 cases had positive neutrophil respiratory burst test. Genetic tests showed CYBB gene mutations (9 cases) , NCF1 gene mutation(1 case) and NCF2 gene mutation (1 case). All cases received antibacterial and antifungal treatments for 2-5 weeks and were discharged with improvement. 8 patients survived, 5 received hematopoietic stem cell transplantation, 4 succeeded and one failed and continued to survive on oral medication. 3 cases took sulfamethoxazole, voriconazole or itraconazole orally for long periods. 3 cases died of severe infections after withdrawal of medication. Conclusions:Neonatal CGD is characterized by lung infections. Pulmonary CT shows mostly nodular or patchy shadows with occasional pulmonary consolidation or pleural effusion. It can be diagnosed by neutrophil respiratory burst test and genetic testing. X-linked CYBB gene mutations are common and autosomal recessive NCF1/NCF2 gene mutations less common.

Objective:To summarize the clinical features and prognosis of neonates with congenital fissure of larynx due to choking, and improve the diagnosis and treatment of congenital fissure of larynx by neonatal medical professionals.Methods:This study was a single-center retrospective case series report.With "choking" as the key word, combined with the information from the first page of the medical record, we searched in the electronic medical record system, and summarized the clinical characteristics and prognosis of neonates diagnosed as congenital fissure of larynx.The study period was from January 2017 to February 2021.Results:A total of seven cases were diagnosed as congenital fissure of larynx, accounting for 2.2% of the total number of hospitalized children due to choking during the same period.Among them, six cases were male, gestational age was 38 (36, 39) weeks, birth weight was 2 820 (2 255, 3 420) g, admission age was 18(5, 20) days and hospitalization duration was 26 (6, 45) days.The common clinical symptoms were choking (7/7) and cyanosis (5/7). Six of the seven children with fissure of larynx were clearly classified as type Ⅰ(two cases), type Ⅲ(three cases), and type Ⅳ(one case). All the seven cases were accompanied by other site/tracheal malformations or congenital abnormalities, among which four (4/7) cases had VACTERL syndrome.A total of three children (two cases of type Ⅲ and one case of type Ⅳ) underwent laryngeal cleft repair operation, and all died shortly after surgery.Four cases didn′t receive laryngeal cleft repair operation (two cases of type Ⅰ, one case of type Ⅲ, one case of parting was unknown), one case with type Ⅰ fissure of larynx accepted the tracheoesophageal fistula repair operation only, who was followed up until the age of two years and six months, and he could have normal diet, one case of typeⅠfissure of larynx with gastric tube discharge, who was followed up to one year and eight months old, could be normal diet too, the two cases of children with no difference between the growth with their peers; one case with type Ⅲ fissure of larynx was lost to follow-up; One case, whose classification was unknown, was followed up until he was 40 days old, and still could be fed orally.The physical development of the child was significantly behind that of the same age.Conclusion:Congenital fissure of larynx is rare, with choking as its main symptom and other malformations.Diagnosis and classification require fiberlaryngoscope and bolting laryngoscope under general anesthesia combined with bronchoscopy, which is difficult to treat.Type Ⅰ has a good prognosis, while type Ⅲ and Ⅳ have poor prognosis.

Objective:Objective To explore the special role of nutrition specialists in the one-day-care clinic of gestational diabetes mellitus (GDM), and provide a basis for strengthening the standardized construction of one-day-care clinic.Methods:It was a retrospective observation study that the pregnant women who participated in the one-day-care clinic of GDM in our hospital without nutrition specialists in November and December 2017 were divided into control group (177 cases), and who participated in the one-day-care clinic of GDM in our hospital with nutrition specialists in January and February 2018 were divided into observation group (307 cases). The differences of pregnancy outcomes between the two groups were compared after the propensity score matching.Results:176 pairs of patients were successfully matched with a 1:1 propensity score. The incidence of macrosomia in pregnant women with GDM in the observation group (2.8%) was significantly lower than that in the control group (8.5%) ( P=0.036). There were no significant differences in the weight gain during pregnancy, the gestational week of delivery and the incidences of insulin use, hypertension during pregnancy, preeclampsia, cesarean section, premature infants, premature rupture of membranes, umbilical cord around the neck, and fetal distress between the two groups ( P>0.05). Conclusion:Nutrition specialists are indispensable in the multidisciplinary cooperation of one-day-care clinic of GDM, and they play a key role in considerably lowering the prevalence of macrosomia in GDM pregnant women.

OBJECTIVE: To investigate the chronic toxicity and carcinogenicity of kresoxim-methyl in rats. METHODS: Specific pathogen free SD rats were randomly divided into control group and low-, medium-and high-dose groups according to the body weight of rats, 120 rats in each group with half male and half female rats. The chronic toxicity and carcinogenesis was induced in rats for 104 weeks by oral feeding. The dose of kresoxim-methyl in feed of male and female rats was 0, 75, 300 and 1 200 mg/kg. During the process of experiment, the body weight of rats was weighed. The blood biochemistry, organ coefficient and histopathology were examined at the end of the exposure, and the tumor incidence was calculated. RESULTS: There was no significant difference in mortality of the female or male rats in the four groups(P>0.05). At the 32 nd, 48 th and 56 th week after exposure, the body mass of female rats in the high dose group was lower than that in control group(P<0.05); at the 8 th, 16 th, 24 th and 32 nd week, the body mass of male rats in the high dose group was lower than that in the control group(P<0.05). The organ coefficients of heart and adrenal gland of female rats in the high dose group were higher than those in the control group and the low dose group(P<0.05). The organ coefficient of liver of male rats in the high dose group was lower than that in the control group(P<0.05). The alkaline phosphatase of male rats in the three dose groups was lower than that in the control group(P<0.05). The blood glucose of male rats in the high dose group was higher than that in the control group(P<0.05). The aspartate aminotransferase of male rats in the high dose group was lower than that in the control group(P<0.05). There was no significant difference among the three indexes in female rats(P>0.05). The tumor incidence of the control group and the low, medium and high dose groups were 68.3%, 75.0%, 75.0% and 78.8%, respectively, with no significant difference(P>0.05). The tumor incidence of the female rats was higher than that of the male rats(87.0% vs 61.5%,P<0.01).The tumor multiplicity of the above four groups were 38.3%, 35.8%, 35.0%, 39.8%, respectively, with no significant difference(P>0.05). The tumor multiplicity in female rats was higher than that in male rats(56.9% vs 17.6%,P<0.01). CONCLUSION: The no observed adverse effect level of kresoxim-methyl to female and male SD rats was 24.726 and 20.002 mg/(kg·d), respectively. No carcinogenicity of kresoxim-methyl to SD rats was observed.

Objective:To study the role of serum E-selectin and P-selectin in pathogenesis of severe Mycoplasma pneumonia pneumonia(MPP), and to evaluate their value in early clinical recognition of severe MPP.Methods:The clinical data of 87 MPP patients in the Respiratory Ward of Capital Institute of Pediatrics Children′s Hospital between December 2017 and October 2018 were collected.Children were divided into the mild group(37 cases)and the severe group (50 cases) according to the severity of the disease.There were 20 males and 17 females in the mild group, with the age of (7.62±2.02) years.There were 17 males and 33 females in the severe group, with the of (6.97±2.41) years.Serum E-selectin, P-selectin and related inflammatory indicators were measured and compared between the two groups, and their correlation with severe MPP was analyzed.The receiver operating characteristic curve (ROC) analysis was also conducted.Results:The length of stay [(8.46±2.53) d vs.(5.19±1.20) d, P<0.001], C-reactive protein(CRP)[(23.05±37.05) mg/L vs.(15.06±13.79) mg/L, P=0.001], lactate dehydrogenase(LDH)[(342.50±186.00) U/L vs.(284.44±64.82) U/L, P<0.001], procalcitonin(PCT)[(0.19±0.26) μg/L vs.(0.15±0.14) μg/L, P=0.012], serum ferritin(SF)[(197.33±429.43) μg/L vs.(124.60±66.30) μg/L, P<0.001], D-Dimer [(539.00±576.00) μg/L vs.(226.00±170.50) μg/L, P<0.001], E-selectin [(2.36±4.22) μg/L vs.(0.86±0.20) μg/L, P<0.001] and P-selectin [(4.15±4.40)μg/L vs.(1.72±1.22) μg/L, P<0.001] in the severe group were significantly higher than those in the mild group.There was no statistical difference in the white blood cell (WBC) and erythrocyte sedimentation rate(ESR). CRP, LDH, SF, D-Dimer, E-selectin and P-selectin were statistically correlated with severe MPP(all P<0.05), while WBC, PCT and ESR were not statistically correlated with severe MPP.The areas under ROC of CRP, LDH, SF, D-Dimer, E-selectin and P-selectin were all greater than 0.5, and the area under ROC of E-selectin was the largest, followed by that of P-selectin(both>0.8). Conclusions:Severe MPP may lead to excessive inflammatory reactions in the body.E-selectin and P-selectin possibly play an important role in this process, and can act as good indicators for early recognition of severe MPP.

Objective To study the etiology and clinical features of arrhythmia in neonates with cardiac cardiomegaly.Method A retrospective study was conducted on newborns with arrhythmia hospitalized in the neonatal intensive care unit of our Hospiatal from January 2016 to May 2018.The eases were assigned into arrhythmia with cardiac enlargement group and non-benign arrhythmia without cardiac enlargement group cardiomegaly.The etiology,clinical features and prognosis of newborns with arrhythmia and cardiac enlargement were analyzed.Result There were 15 newborns with arrhythmia accompanied with cardiac enlargement,all of them were non-benign arrhythmias,which accounted for 26.8％ (15/56) of all non-benign arrhythmias in the same period.The causes included infections viral myocarditis,pneumonia and digestive tract infection,electrolytes and acid-base imbalance hypocalcemia,hyperkalemia and metabolic acidosis,structural cardiac abnormalities,metabolic cardiomyopathy,nodular sclerosis and indwelling central venous catheter.The median age of onset was 9 (0,19) days,and the median medical history was 2 (1,7) days,the significance of which were not different from those of non-benign arrhythmias without cardiac enlargement group (41 cases).The rate of cesarean section and ventricular rate＞160 bpm at admission were higher than those in the non-benign arrhythmias without cardiac enlargement group.12 of 15 cases began with weak responses,poor appetite and dyspnea.The common arrhythmia types were paroxysmal supraventricular tachycardia (6 cases),atrial tachycardia (4 cases) and atrial flutter (4 cases).The proportion of atrial flutter was higher than that of the non-benign arrhythmias without cardiac enlargement group.8 cases received respiratory support.The average length of stay was (18.4±8.6) days.The mortality rate during hospitalization was 6.7％.The echocardiographic results showed that left atrioventricular enlargement and ejection fraction of left ventricle less than 60％ during arrhythmic episode.The cardiac size and systolic functions of left ventricle reverting to normal after improvement.During the follow-up period,1 case died and 2 cases lost to follow-up,all of them were discharged against medical advice.The median follow-up time of other cases was 1.6 (1.3,2.2) years.All of them recovered well without abnormalities in cardiac size or cardiac function by echocardiography.Conclusion Most newborns with arrhythmia accompanied by cardiac enlargement had insidious onset.Tachyarrhythmia was common and infection was the main cause.Attention should be paid to screening of rare causes in clinical practice.Non-benign arrhythmias with or without cardiac enlargement have no significant difference in the overall prognosis by active treatment.