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.

ObjectiveTo investigate the effects of acupuncture combined with Du-Moxibustion (ADM) on peripheral blood cell count and levels of immune factors in patients with occupational chronic benzene poisoning. Methods A total of 70 patients with occupational chronic benzene poisoning (leukopenia and neutropenia) were selected as the research subjects by judgement sampling method. They were randomly divided into a control group and an ADM group using a random number table method, with 35 cases in each group. Patients in the control group were treated with conventional Western medicine such as leukocyte boosting and symptomatic treatment. While patients in the ADM group were treated with ADM treatment in addition to treatments of the control group, once per week for five consecutive weeks. Peripheral blood samples of patients were collected before and after treatment from both groups, to detect cell counts and serum levels of immune factors. Results The white blood cell count, red blood cell count, absolute lymphocyte count, absolute neutrophil count, platelet count, and levels of hemoglobin, immunoglobulins (Ig) A, IgM, IgG, complement C3 and complement C4 of patients in both groups improved after treatment compared with those before treatment (all P<0.05). The white blood cell count, levels of IgA, IgM, IgG, complement C3 and complement C4 of patients in the ADM group were higher than those in the control group after treatment (all P<0.05). Conclusion ADM treatment can increase peripheral blood white blood cells and serum levels of immune factor in patients with occupational chronic benzene poisoning (leukopenia, neutropenia), which helps improve patient recovery and can be promoted clinically.

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 establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

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 study the genetic profiles and clinical characteristics of neonatal-onset genetic epilepsy.Methods:From July 2016 to May 2021, patients with neonatal-onset genetic epilepsy admitted to our hospital and received second-generation genetic sequencing were enrolled in this study. According to the types of genetic variations, the patients were assigned into ion channel group and non-ion channel group. Clinical characteristics, treatments and prognosis of the two groups were compared.Results:A total of 36 patients with identified genetic variations were enrolled, involving 15 epilepsy-related genes. KCNQ2, SCN2A and STXBP1 were the most common pathogenic genes. 20 cases (55.6%) were in the ion channel group and 16 cases (44.4%) in the non-ion channel group. No significant differences existed in their general status, seizure types, EEG characteristics, treatments and outcomes between the two groups ( P>0.05). Among all 36 cases, the age of onset ranged from 10 min to 24 d after birth and 28 cases (78.8%) developed epilepsy within 1 week after birth. Developmental and epileptic encephalopathies were diagnosed in 20 patients. 7 patients were diagnosed with self-limited neonatal epilepsy, 2 were pyridoxine dependence, 2 were Zellweger syndrome and 1 case of self-limited familial neonatal-infantile epilepsy, Turner type mental retardation with epilepsy, PURA syndrome, Rett syndrome and 22q11.2 deletion syndrome, each. The patients received antiepileptic drugs including phenobarbital, levetiracetam, oxcarbazepine, topiramate, valproic acid, benzodiazepines (nizepam/clonazepam /clobazam/midazolam), lacosamide and lamotrigine. 5 patients died after giving up treatment. 31 patients were followed up for 6 to 50 months. 22 cases (71.0%) were controlled at 1- to 35-month-old including 21 cases (56.7%) with developmental delay. 6 cases (19.4%) had ineffective seizure control and 3 cases (9.7%) showed reduced seizures, all with varying degrees of developmental delay. Conclusions:Neonatal-onset epilepsy is correlated with multiple genes. KCNQ2, SCN2A, STXBP1 are the common pathogenic genes with multiple variants of KCNQ2 gene. Most patients have seizures within 1 week after birth. More than half of patients have ion channel related gene variations. Sodium channel blockers have certain effects as treatment.

Abstract Comprehensive sexuality education is an important part of quality education, primary and secondary schools are the most suitable places for sex education. This paper sorts out the current status of sexuality education for primary and secondary school students in developed countries after presenting the overall significance of school based sexuality education, and further points out the problems and urgency of sexuality education for primary and secondary school students in China. It also put forward the way to new directions for advocacy, including the comphrehensive sexuality education curriculum system, training of sexuality education teachers, the positive and active role of families, as well as social and community support for sexuality education in schools.

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:To study the clinical features and prognosis of infantile hepatic hemangioendothelioma-arteriovenous fistula (IHHE-AVF) complicated with heart failure in neonates.Method:From May 2016 to June 2020, neonates with IHHE-AVF complicated with heart failure admitted were retrospectively studied. The clinical presentation, treatment and outcomes were analyzed.Result:A total of 11 cases of IHHE-AVF complicated with heart failure were enrolled (male 5, female 6). The onset age of heart failure was 12.0 (0.0, 17.0) d. 6 cases showed IHHE on fetal ultrasound. All patients had significantly enlarged heart on chest X-ray. All patients had decreased left ventricular systolic function and pulmonary hypertension on echocardiography. All patients required respiratory support and 6 of them were intubated. 3 cases received conservative treatment (all dead). 1 case received surgery (dead). 7 cases received interventional therapy at the age of (25.6±18.5) d. 1 case was dead, and the other 6 cases were improved and discharged. All the 6 cases were followed up to 3~18 months. None of them had heart failure again. The IHHE were shrunk or completely disappeared. Coagulation function and platelet count were normal.Conclusion:The fatality rate of neonatal-onset IHHE-AVF complicated with heart failure is extremely high. Interventional therapy may be more effective than conservative therapy and surgery.

Objective:To explore the effects of maternal pre-pregnancy body mass index (BMI) and gestational weight gain and its subtypes on the risk of preeclampsia.Methods:Pregnant women delivered in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016 were selected as the research subjects. According to the inclusion and exclusion criteria, 9 274 pregnant women were included. 901 preeclampsia pregnant women were selected as the case group, and 8 373 non-preeclampsia pregnant women were selected as the control group. General demographic characteristics, pre-pregnancy weight, height, lifestyle during pregnancy, reproductive history, and disease history of pregnant women were collected, and pre-pregnancy BMI and gestational weight gain were calculated. Unconditional logistic regression was used to analyze the relationship between pre-pregnancy BMI and weight gain during pregnancy and PE and its clinical subtypes.Results:Among the 901 preeclampsia after inclusion and exclusion, 401 cases were diagnosed as early-onset PE (EOPE), 500 cases were late-onset PE (LOPE), 178 cases were Mild PE (MPE), and 723 cases were severe PE (SPE). There were statistically significant differences between PE and non-PE pregnant women in terms of maternal age, residence, parity, family history of gestational diabetes and hypertension ( P<0.05). After adjusting for the above factors, the logistic regression analysis results showed that pre-pregnancy BMI<18.5 kg/m 2 and inadequate gestational weight gain were protective factors for PE ( OR=0.74, 95% CI: 0.56-0.98; OR=0.78, 95% CI: 0.62-0.99), while pre-pregnancy BMI≥24.0 kg/m 2 and excessive gestational weight gain were risk factors for PE ( OR=1.82, 95% CI: 1.54-2.14; OR=1.82, 95% CI: 1.54-2.15). After subtype analysis on PE, the results showed that pre-pregnancy BMI<18.5 kg/m 2 was a protective factor for EOPE and MPE ( OR=0.52, 95% CI: 0.32-0.83; OR=0.47, 95% CI: 0.23-0.97), while pre-pregnancy BMI≥24.0 kg/m 2 and excessive gestational weight gain were risk factors for clinical subtypes of PE. After stratification according to pre-pregnancy BMI, excessive gestational weight gain was the risk factor for PE ( OR=1.86, 95% CI: 1.51-2.30; OR=1.90, 95% CI: 1.39-2.60) in pregnant women 18.5 kg/m 2≤BMI<24.0 kg/m 2 and ≥24.0 kg/m 2. Inadequate gestational weight gain ( OR=0.55, 95% CI: 0.34-0.89) was a protective factor for PE in pregnant women with pre-pregnancy BMI≥24.0 kg/m 2. Excessive gestational weight gain ( OR=4.05, 95% CI: 1.20-13.69) was a risk factor for EOPE in pregnant women with pre-pregnancy BMI<18.5 kg/m 2. Excessive gestational weight gain was a risk factor for the clinical subtype of PE in pregnant women 18.5 kg/m 2≤BMI<24.0 kg/m 2 before pregnancy. Inadequate gestational weight gain was a protective factor for EOPE and MPE ( OR=0.39, 95% CI: 0.19-0.80; OR=0.29, 95% CI: 0.11-0.77) in pregnant women with pre-pregnancy BMI≥24.0 kg/m 2. Excessive weight gain was a risk factor for EOPE, LOPE and SPE ( OR=1.60, 95% CI: 1.06-2.42; OR=2.20, 95% CI: 1.44-3.37; OR=2.28, 95% CI: 1.58-3.29). Conclusions:Pre-pregnancy BMI and gestational weight gain affect the risk of preeclampsia and its clinical subtypes. In contrast, the influence of gestational weight gain on preeclampsia varies among different pre-pregnancy BMI groups. Therefore, it is recommended to pay attention to the changes in pre-pregnancy BMI and gestational weight gain simultaneously to reduce preeclampsia.