Research progress and potential medical applications of anaplastic lymphoma kinase in treatment of non-small cell lung cancer / 中国药理学通报

During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.

Executive functions of obese adolescents / 中国学校卫生

Objective@#To explore of executive function in obese adolescents, so as to provide a reference for executive function enhancement intervention in obese adolescents.@*Methods@#A convenience sample of 1 227 adolescents aged 13-18 years was selected from 2 secondary schools in Taiyuan City during March-April 2023. The Flanker task, N-back task and More odd shifting task was used to compare the different subfunctions of executive function (refreshing function, shifting function, inhibiting function) of 61 obese adolescents and 70 normal weight adolescents. Independent samples t-tests was used for between group comparisons and Cohen s d -tests was used to calculate between group differences in executive function between the two groups of adolescents.@*Results@#Compared with the group of normal weight, time responses of the inhibitory function [(29.73±19.55)ms], the refreshing function [1-back: (1 088.75±275.76)ms, 2-back:( 1 285.44± 355.16)ms] and the shifting function [(380.34±153.18) ms] in the obese group were significantly longer than those in the normal weight group [(14.86±20.27, 888.38±286.57, 1 126.20± 287.43 , 323.12±134.71) ms] ( t =4.26, 4.06, 1.92,2.26, P < 0.05 ); inhibitory function (0.91±0.09) and 1-back (0.73±0.24) were also significantly less correct than in the normal weight group (0.94±0.05, 0.83±0.21) ( t =-2.04, -2.04, P <0.05). Obese adolescents showed moderate adverse effect sizes in the inhibition function ( d =0.746,0.712) and the refresh function 1-back, and smaller adverse effect sizes in the refresh function 2-back and the conversion function( d =0.497,0.398).@*Conclusion@#Obese adolescents have significant executive function deficits, but the degree of adverse varies across sub-functions, with inhibitory function being the core deficit component of executive function in obese adolescents.

Improving cardiorespiratory fitness to promote the development of executive function in adolescents / 中国学校卫生

Abstract@#Executive function development is crucial for the overall development of physical and mental health, improvement of mental health literacy, and enhancement of adolescent health and well being in the adolescent population. It is scientific and feasible to promote the development of executive function by improving the cardiorespiratory fitness of adolescents. Therefore, it is important to grasp the "cardiorespiratory fitness improvement" and actively explore ways and methods to improve cardiorespiratory fitness and thus promote the executive function of adolescents, in order to comprehensively strengthen the construction of the adolescent mental health protection mechanism and work system, and to improve the work of students mental health in the new era.

Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this study was to assess the impact of bisphenol A (BPA) and its substitute, bisphenol F (BPF), on the colonic fecal community structure and function of mice.@*METHODS@#We exposed 6-8-week-old male C57BL/6 mice to 5 mg/(kg∙day) and 50 μg/(kg∙day) of BPA or BPF for 14 days. Fecal samples from the colon were analyzed using 16S rRNA sequencing.@*RESULTS@#Gut microbiome community richness and diversity, species composition, and function were significantly altered in mice exposed to BPA or BPF. This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus. Additionally, pathways related to carbohydrate and amino acid metabolism showed substantial enrichment.@*CONCLUSION@#Mice exposed to different BP analogs exhibited distinct gut bacterial community richness, composition, and related metabolic pathways. Considering the essential role of gut bacteria in maintaining intestinal homeostasis, our study highlights the intestinal toxicity of BPs in vertebrates.

Non-invasive prenatal testing for the diagnosis of congenital abnormalities: Insights from a large multicenter study in southern China

Although non-invasive prenatal testing (NIPT) is widely used to detect fetal abnormalities, the results of NIPT vary by population, and data for the screening efficiency of NIPT positive predictive value (PPV) from different populations is limited. Herein, we retrospectively analyzed the NIPT results in a large multicenter study involving 52,855 pregnant women. Depending on gestational age, amniotic fluid or umbilical cord blood was extracted for karyotype and/or chromosome microarray analysis (CMA) in NIPT-positive patients, and the PPV and follow-up data were evaluated to determine its clinical value. Among the 52,855 cases, 754 were NIPT-positive, with a positivity rate of 1.4%. Karyotype analysis and/or CMA confirmed 323 chromosomal abnormalities, with a PPV of 45.1%. PPV for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosomal aneuploidies (SCAs), and copy number variations (CNVs) were 78.9, 35.3, 22.2, 36.9, and 32.9%, respectively. The PPVs for T21, T18, and T13 increased with age, whereas the PPVs for SCAs and CNVs had little correlation with age. The PPV was significantly higher in patients with advanced age and abnormal ultrasound. The NIPT results are affected by population characteristics. NIPT had a high PPV for T21 and a low PPV for T13 and T18, and screening for SCAs and CNVs showed clinical significance in southern China.

Clinical features of 23 neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 / 中国当代儿科杂志

OBJECTIVES@#To summarize the clinical features of neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*METHODS@#The medical data of 23 neonates with Omicron variant of SARS-CoV-2 infection admitted to the City North Campus of Urumqi First People's Hospital from October to December 2022 were retrospectively reviewed.@*RESULTS@#All 23 infants had a history of exposure to confirmed caregivers with SARS-CoV-2 infection after birth, and none of them was vertically transmitted. Clinical classification: 5 cases of asymptomatic infection, 18 cases of mild infection, and no cases of moderate, severe, or critically ill. The first symptoms were fever in 13 cases, cough in 3 cases, nasal congestion in 1 case, and diarrhea in 1 case. Blood white blood cell counts decreased in 2 cases, and C-reactive protein increased in 1 case. Seven infants underwent chest X-ray examination due to cough or shortness of breath, and one of which showed focal exudative changes, while the rest showed no abnormal changes. All infants were discharged after symptomatic treatment and the median hospital stay was 6 days. The duration of nucleic acid positivity of SARS-CoV-2 was negatively correlated with N gene Ct values and ORF1ab gene Ct values (rs=-0.719 and -0.699, respectively; P<0.05). One month after discharge, all infants had no symptoms or signs of nucleic acid re-positivity.@*CONCLUSIONS@#The clinical manifestations are usually mild or asymptomatic in neonates infected with SARS-CoV-2 Omicron variant. The lower the Ct values of the N and ORF1ab genes of SARS-CoV-2, the longer the duration of nucleic acid positivity. Neonates infected with SARS-CoV-2 Omicron variant can have a good prognosis after symptomatic treatment.

Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species / 中国中药杂志

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 μL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Correlation analysis of vitamin D level and anti-Müllerian hormone in infertile female and the role in predicting pregnancy outcome / 北京大学学报(医学版)

OBJECTIVE@#To investigate the relationship between serum 25(OH)D and anti-Müllerian hormone (AMH) among infertile females and their predictive impacts on in vitro fertilization and embryo transfer pregnancy outcome.@*METHODS@#Totally 756 infertile females treated with assisted reproductive technology were enrolled and divided into three groups according to their vitamin D levels (group A with serum 25(OH)D≤10 μg/L, group B with serum (10-20) μg/L, and group C with serum ≥20 μg/L). The serum AMH levels were detected. The differences among the groups were analyzed, as well as the correlation between vitamin D levels and serum AMH levels in various infertility types (fallopian tube/male factor, polycystic ovary syndrome (PCOS), ovulation disorders excluded PCOS, endometriosis, unexplained infertility, and others). Also, the predictive roles of vitamin D and AMH in pregnancy outcome in all the infertile females were discussed.@*RESULTS@#(1) 87.7% of the enrolled females were insufficient or deficient in vitamin D. (2) The serum AMH levels in the three groups with different vitamin D levels were 1.960 (1.155, 3.655) μg/L, 2.455 (1.370, 4.403) μg/L, 2.360 (1.430, 4.780) μg/L and there was no significant difference in serum AMH levels among the three groups (P>0.05). (3) Serum 25(OH)D and AMH levels presented seasonal variations (P < 0.05). (4) There was no prominent correlation between the serum AMH level and serum 25(OH)D level in females of various infertility types after adjusting potential confounding factors [age, body mass index (BMI), antral follicle count (AFC), vitamin D blood collection season, etc.] by multiple linear regression analysis (P>0.05). (5) After adjusting for confounding factors, such as age, BMI, number of transplanted embryos and AFC, the results of binary Logistics regression model showed that in all the infertile females, the serum AMH level was an independent predictor of biochemical pregnancy outcome (P < 0.05) while the serum 25(OH)D level might not act as a prediction factor alone (P>0.05). In the meanwhile, the serum 25(OH)D level and serum AMH level were synergistic predictors of biochemical or clinical pregnancy outcome (P < 0.05).@*CONCLUSION@#Based on the current diagnostic criteria, most infertile females had vitamin D insufficiency or deficiency, but there was not significant correlation between serum 25(OH)D and ovarian reserve. While vitamin D could not be used as an independent predictor of pregnancy outcome in infertile females, the serum AMH level could predict biochemical pregnancy outcome independently or jointly with vitamin D.

Effect of Recombinant Human Thrombopoietin (rhTPO) on Hematopoietic Reconstitution in Allogeneic Hematopoietic Stem Cell Transplantation Model / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of recombinant human thrombopoietin (rhTPO) on hematopoietic reconstruction in allogeneic hematopoietic stem cell transplantation (allo-HSCT) model.@*METHODS@#The C57BL/6 mice were employed as the donors, and BALB/c mice as recipients. The bone marrow mononuclear cells of the donor mice were extracted and pretreated, which then were injected with 5×106 per mouse through the tail vein of the recipient to establish an allo-HSCT model. The implantation of hematopoietic stem cells in the recipient mice was detected by flow cytometry on the 28th day after transplantation. Next, the successfully modeled recipient mice were randomly divided into experimental group and control group. The rhTPO was injected into mice in the experimental group on the first day after transplantation, while the saline was injected into mice in the control group. Both groups were injected for 14 consecutive days. The peripheral blood and bone marrow hematopoiesis of the two groups were observed on day 1, 3, 7, 14, and 21 after transplantation.@*RESULTS@#The expression rate of H-2Kb in the bone marrow of recipient mice was 43.85% (>20%) on the 28th day after transplantation, which indicated that the recipient mice were successfully chimerized. Meanwhile, counts of PLTs on the day 3, 7, 14, and 21 after transplantation in the experimental group were higher than those in the control group with statistical significances (P<0.05). In addition, hematopoietic function of bone marrow was suppressed in both groups on day 1, 3 and 7 after transplantation, but hematopoietic bone marrow hyperplasia was better in the experimental group than in the control group. On day 14 and 21 after transplantation, the hematopoietic function of bone marrow in the two groups was recovered, and the experimental group showed more obvious than the control group.@*CONCLUSION@#rhTPO can effectively stimulate the production of PLTs and facilitate the recovery of white blood cells and hemoglobin after allo-HSCT, and promote hematopoietic recovery and reconstitution of bone marrow.

Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing / 亚洲男科学杂志(英文版)

Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.

Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia / 北京大学学报(医学版)

OBJECTIVE@#To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer.@*METHODS@#Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve.@*RESULTS@#A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration.@*CONCLUSION@#It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

Investigation of the prevalence of deciduous teeth caries and its correlation with nutritional status among kindergarten children in Zhag yab of Tibet in 2022 / 中国学校卫生

Objective@#To investigate the health of deciduous teeth and the effect of deciduous teeth caries on the nutritional status of Tibetan children in kindergartens in Zhag-yab of Tibet, so as to provide a reference for the prevention and treatment of dental caries in local children.@*Methods@#A cross sectional survey was conducted among all Tibetan children aged 3 to 7 years in kindergartens from 13 districts in Zhag yab of Tibet, a total of 1 263 eligible children were included. Oral examination, height, weight measurement and hemoglobin test were performed. The health status of children was evaluated according to WHO diagnostic criteria of dental caries rate, average of decayed missing filled tooth(DMFT), malnutrition and anemia, and the correlation between deciduous teeth caries and nutritional status of children were analyzed.@*Results@#The overall deciduous teeth caries prevalence rate of Tibetan children in Zhag yab kindergarten was 62.6%, and the mean dmft was (4.0±4.6). Aged 3, 4, 5, 6, 7-year-old children s deciduous teeth caries rate were 31.1%, 55.3%, 63.8%, 70.9%, 76.6%, respectively, mean dmft were (1.1±2.0) (2.9±3.4) ( 3.5± 3.3) (5.4±5.4) (5.9±6.6) respectively. The prevalence of deciduous teeth caries and mean dmft increased with age, and the differences among age groups were statistically significant ( χ 2/F=72.17, 33.47, P <0.05). The overall detection rate of malnutrition( 25.4% ), stunting(12.3%), underweight(12.6%), wasting(10.9%) and anemia(29.6%) in caries children were higher than those in children without caries(19.5%, 8.1%, 6.1%, 6.6%, 15.5%), the differences were statistically significant ( χ 2=5.81, 5.49, 13.61 , 6.52, 32.02, P <0.05). Caries children s overweight rate (3.7%) was higher than that of children without caries (3.4%), obesity rate ( 1.3% ) was lower than that of children without caries(1.9%), there was no statistically significant difference ( χ 2=0.07, 0.82, P >0.05).@*Conclusion@#The problem of deciduous teeth caries in kindergartens in Zhag yab is serious, and it is closely related to the occurrence of malnutrition and anemia. The prevention and intervention of dental caries in local children should be strengthened.

Differentiation Between Amyotrophic Lateral Sclerosis and Mimics Using Quantitative Analysis of Fsciculation with Muscle Ultrasound / 中国医学科学杂志(英文版)

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ2 = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.

Status of anemic among kindergarten children within Suzhou urban area from 2018 to 2022 / 中国学校卫生

Objective@#To understand the current situation and trends of anemia among kindergarten children in urban area of Suzhou from 2018 to 2022, so as to provide a theoretical basis for prevention and intervention in anemia among kindergarten children.@*Methods@#From March 2023, a total of 24 178 person times of children from 59 kindergartens selected by random number table method were enrolled, and their physical examination data from 2018 to 2022 were collected, including hemoglobin (Hb), height, gender, weight. The period of 2018-2019 was defined as before the COVID-19 epidemic, and period of 2020-2022 was defined as the COVID-19 epidemic. Data were analyzed using the Mann Whitney U test, χ 2 test and Spearman s correlation analysis.@*Results@#From 2018 to 2019, the M ( P 25 ， P 75 ) of Hb levels of children in nursery, middle, and senior class were 118 (112, 129), 120 (112, 132) and 122 (113, 134)g/L, respectively, which were higher than that of during 2020-2022 [116(110, 123), 117(111, 124) , 119(112, 126)g/L, Z =-10.7, -12.7, -12.9, P <0.05]. A total of 4 584 person times of children were anemic, with a detection rate of 19.0%. The overall anemia detection rate of kindergarten children during 2018-2019 was lower than that in 2020-2022 (15.3% vs 20.7%, χ 2=100.8, P <0.05). The anemia detection rate of kindergarten children in 2022 (24.5%) was higher than that in 2020 (20.6%) and in 2021 (17.0%) ( χ 2=93.9, P <0.05). The anemia prevalence of children in the nursery, middle, and senior class were 13.9%, 14.7% and 17.1% during 2018-2019, 19.3%, 15.9% and 26.6% during 2020-2022, and 17.6%, 15.5% and 23.6% during 2018-2022, respectively ( χ 2=10.7, 204.6, 186.8, P <0.01). There was no statistically significant correlation between Hb values and body mass index (BMI) in boys and girls with anemia, and all children in kindergarten ( r=0.03, 0.03, 0.09, P ＞0.05).@*Conclusion@#The prevalence of anemia among kindergarten children in the urban area of Suzhou is relatively high. The COVID-19 pandemic may have increased the risk of anemia among children.

Mechanism of famous classical formula Huaihua Powder in treatment of ulcerative colitis based on metabonomics / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1β in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.

Awareness of HPV and HPV vaccine and willingness to be vaccinated among parents of children aged 9-14 / 公共卫生与预防医学

Objective To investigate the HPV vaccination status of children aged 9-14 years, parents’ vaccine-related cognition, willingness to vaccinate children and their influencing factors. Methods From January to April 2021, the convenience sampling method was used to collect data based on the online platform and the Department of Pediatrics and Adolescent Gynecology of the Children's Hospital of Zhejiang University School of Medicine. The data were analyzed by descriptive analysis, Chi-square test, and logistic regression. Results A total of 864 questionnaires were collected, and 846 valid questionnaires were obtained after screening, with an effective rate of 97.9%. 13.57% of mothers and 3.09% of girls were vaccinated, and the vaccine awareness rate was 68.43%. 87.22% of parents were willing to bring their children for vaccination. Risk perception (OR=4.79, 95% CI: 2.22-10.35), willingness to vaccinate themselves (OR =29.01, 95% CI: 12.62-66.69), awareness of sex education (OR =3.73, 95% CI: 1.08-12.83) and whether the vaccines were free (P<0.001) were related to whether parents were willing to vaccinate their children. Conclusion Parents of children aged 9-14 have high awareness of HPV and HPV vaccine and are willing to vaccinate their children with HPV vaccine , but the vaccination rate in children is low. Disease perception, willingness to vaccinate, awareness of sex education, and whether vaccines are free are all the factors influencing parents' willingness to vaccinate children.

Effect of acid sphingomyelinase on nonalcoholic fatty liver disease via PPARα- PGC-1α pathway / 中国药理学通报

Aim To investigate the effects of acid sphingomyelinase(ASMase)on high-fat induced nonalcoholic fatty liver disease in mice and its regulation of PPARα- PGC-1α pathway. Methods ASMase knockout mice based on C57BL/6 background were constructed. Closed group heterozygotes were obtained through hybridized with wild-type mice(ASMase+/-),together with the littermate WT mice were prepared for NAFLD model in this study. The experiment was divided into four groups:WT+Chow:the WT mice were fed with normal diet for 12 weeks; WT+HFD:the WT mice were fed with high-fat diet for 12 weeks; ASMase+/-+Chow:the ASMase+/- mice were fed with normal diet for 12 weeks; ASMase+/- +HFD:the ASMase+/- mice were fed with high fat diet for 12 weeks. Biochemical method was used to detect serum TC,TG and liver TC,TG contents and liver function such as ALT and AST. Oil red staining,HE staining,Masson staining and Sirius red staining were performed to detect liver lipid accumulation,hepatocyte morphology and liver fibrosis. AmplexTM red sphingomyelinase kit was applied to detect ASMase activity. Western blot was performed to detect protein expressions of ASMase,PPARα,PGC-1α and CPT1. Results WT+HFD group displayed hypercholesterolemia and liver dysfunction. Levels of liver triglyceride(TG)were significantly higher than those in WT+Chow group(P<0.05 or P<0.01). Meanwhile,the hepatocytes showed marked steatosis,balloon-like changes,and fibrosis. Protein expression and activity of ASMase in liver increased significantly(P<0.01 or P<0.001),whereas CPT1,PPARα and PGC-1α expressions were not statistically significant compared with matched control group. Heterozygously ASMase-deficient mice reduced the elevated liver TG induced by HFD,as well as improving balloon-like changes and liver fibrosis. Furthermore,the expressions of PPARα,PGC-1α and CPT1 were up-regulated in ASMase+/- +HFD mice compared with WT+Chow group.Conclusions ASMase promotes hepatic steatosis and fibrosis,which may be related to its inhibition of PPARα-PGC-1α pathway.

Clinical and etiological characteristics of infectious vulvovaginitis in children in Zhejiang province from 2009 to 2019 / 中华儿科杂志

Objective: To explore the clinical characteristics, common pathogens in children with vulvovaginitis. Methods: This was a retrospective cases study. A total of 3 268 children with vulvovaginitis were enrolled, who visited the Department of Pediatric and Adolescent Gynecology, Children's Hospital, Zhejiang University School of Medicine from January 2009 to December 2019. Patients were divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Patients were also divided in to 4 groups according to the season of first visit. The pathogen distribution characteristics of infective vulvovaginitis were compared between the groups. Their clinical data were collected and then analyzed by χ2 test. Results: The were 3 268 girls aged (6.2±2.5) years. There were 1 728 cases (52.9%) aged <7 years, 875 cases (26.8%) aged 7-<10 years, and 665 cases (20.3%) aged 10-18 years. Of these cases, 2 253 cases (68.9%) were bacterial vulvovaginitis, 715 cases (21.9%) were fungal vulvovaginitis and 300 cases (9.2%) were vulvovaginitis infected with other pathogens. Bacterial culture of vaginal secretions was performed in 2 287 cases, and 2 287 strains (70.0%) of pathogens were detected, of which the top 5 pathogens were Streptococcus pyogenes (745 strains, 32.6%), Haemophilus influenzae (717 strains, 31.4%), Escherichia coli (292 strains, 12.8%), Staphylococcus aureus (222 strains, 9.7%) and Klebsiella pneumoniae (67 strains, 2.9%). Regarding different age groups, H.influenzae was the most common in children under 7 years of age (40.3%, 509/1 263), S.pyogenes (41.9%, 356/849) was predominantly in children aged 7 to 10 years, and E.coli was predominant in children aged 10 to 18 years (26.3%, 46/175). Susceptibility results showed that S.pyogenes was susceptible to penicillin G (610/610, 100.0%), ceftriaxone (525/525, 100.0%), and vancomycin (610/610, 100.0%); the resistance rates to erythromycin and clindamycin were 91.9% (501/545)and 90.7% (495/546), respectively. For H.influenzae, 32.5% (161/496) produced β-elactamase, and all strains were sensitive to meropenem (489/489, 100.0%) and levofloxacin (388/388, 100.0%), while 40.5% (202/499) were resistant to ampicillin. Among E.coli, all strains were sensitive to imipenem(100%, 175/175). The resistance rates of E.coli to levofloxacin and ceftriaxone were 29.1% (43/148) and 35.1% (59/168), respectively. A total of 48 strains of methicillin-resistant Staphylococcus aureus (MRSA) were isolated with a proportion of 28.3% (45/159) in 3 268 patients. The results of drug susceptibility test showed that all MRSA strains were sensitive to linezolid 100.0% (40/40), vancomycin (45/45, 100.0%), and tigecycline (36/36, 100.0%); the resistance rates of MRSA to penicillin G, erythromycin and clindamycin were 100% (45/45), 95.6% (43/45) and 88.9% (40/45), respectively. All methicillin-sensitive Staphylococcus aureus (MSSA) strains were sensitive to oxacillin (114/114, 100.0%), linezolid (94/94, 100.0%), vancomycin (114/114, 100.0%), and tigecycline (84/84, 100.0%); it's resistance rates to penicillin G, erythromycin and clindamycin were 78.1% (89/114), 59.7% (68/114) and 46.5% (53/114), respectively. The drug resistance rate of MSSA to penicillin G, erythromycin and clindamycin were lower than those of MRSA (χ²=11.71,19.74,23.95, respectively, all P<0.001). Conclusions: The age of consultation for pediatric infectious vulvovaginitis is mainly around 6 years. The most common pathogens are S.pyogenes, H.influenzae and Escherichia coli. Third generation cephalosporins can be used as the first choice of empirical anti-infection drugs. However, the results of drug susceptibility should be considered for targeted treatment.

Clinicopathological analysis of benign mammary ductal cystic papillomatosis with loss of myoepithelial cells / 中华病理学杂志

Objective: To investigate the histopathological and immunohistochemical characteristics of benign apocrine cystic papillary hyperplasia of the breast with loss of myoepithelial cell layer. Methods: The clinical data, histopathological features and immunohistochemical profile of patients with benign apocrine cystic papillary hyperplasia of breast with loss of myoepithelial cell layer from January 2016 to December 2021 were examined, in which six patients were identified. Results: All six patients were female, aged 36-61 years (median 46 years), who presented with a breast mass; three cases were from the left breast and three cases were from the right breast. Microscopic examination of all cases showed breast hyperplasia with apocrine cysts, accompanied by different degrees of micropapillary and papillary hyperplasia of apocrine cells. One case was associated with lobular carcinoma in situ, and one case was associated with apocrine ductal carcinoma in situ with intraductal dissemination in adenosis. Immunohistochemical staining of CK5/6, p63, SMA, SMMHC, Calponin and CD10 showed complete absence of myoepithelial cell layer surrounding ducts in apocrine cystic papillary hyperplasia. Conclusions: The myoepithelial cells of apocrine cystic papillary hyperplasia of the breast may undergo abnormal changes and may even be completely lost. The diagnosis should be comprehensively considered along with cytomorphological and histological features to avoid overdiagnosis.

Utilizing ultra-small volume graft in auxiliary liver transplantation for portal hypertension / 中华外科杂志

Objective: To examine the clinical effect of auxiliary liver transplantation with ultra-small volume graft in the treatment of portal hypertension. Methods: Twelve cases of portal hypertension treated by auxiliary liver transplantation with small volume graft at Liver Transplantation Center,Beijing Friendship Hospital, Capital Medical University between December 2014 and March 2022 were studied retrospectively. There were 8 males and 4 females,aged 14 to 66 years. Model for end-stage liver disease scores were 1 to 15 points and Child scores were 6 to 11 points. The grafts was derived from living donors in 9 cases,from split cadaveric donors in 2 cases,from whole cadaveric liver of child in 1 case. The graft recipient body weight ratios of 3 cadaveric donor livers were 0.79% to 0.90%, and of 9 living donor livers were 0.31% to 0.55%.In these cases, ultra-small volume grafts were implanted. The survivals of patient and graft, complications, portal vein blood flow of residual liver and graft, abdominal drainage and biochemical indexes of liver function were observed. Results: All the grafts and patients survived. Complications included outflow tract torsion in 2 cases, acute rejection in 1 case, bile leakage in 1 case, and thyroid cancer at the later stage of follow-up in 1 case, all of which were cured. The torsion of outflow tract was attributed to the change of anastomotic angle after the growth of donor liver. After the improvement of anastomotic method, the complication did not recur in the later stage. There was no complication of portal hypertension. The measurement of ultrasonic portal vein blood flow velocity showed that the blood flow of residual liver decreased significantly in the early stage after operation, and maintained a very low blood flow velocity or occlusion in the long term after operation, and the blood flow of transplanted liver was stable. Conclusions: Auxiliary liver transplantation can implant ultra-small donor liver through compensation of residual liver. This method may promote the development of living donor left lobe donation and split liver transplantation. However, the auxiliary liver transplantation is complex, and it is difficult to control the complications. Therefore, this method is currently limited to centers that are skilled in living related liver transplantation and that have complete ability to monitor and deal with complications.