Apolipoprotein E enhances migration of endometrial cancer cells byactivating the ERK/MMP9 signaling pathway / 南方医科大学学报

OBJECTIVE@#To study the role of apolipoprotein E (APOE) in regulating endometrial cancer metastasis and explore the signaling pathway in the regulatory mechanism.@*METHODS@#Human endometrial cancer cell line HEC-1B was transfected with a control siRNA (siCtrl) or a specific siRNA targeting APOE (siAPOE) or with either pEGFP-N1 plasmid or an APOEoverexpressing plasmid. The changes in migration, proliferation, apoptosis and cell cycle of the transfected cells were examined using wound healing assay, Transwell migration assay, MTT assay, flow cytometry, and Hoechst staining. The activity of the ERK/MMP9 signaling pathway in the transfected cells was assessed using RT-qPCR and Western blotting. The expression level of APOE in clinical specimens of endometrial cancer tissues were detected using immunohistochemistry and its correlation with differentiation of endometrial cancer tissues was analyzed.@*RESULTS@#Wound healing assay and Transwell migration assay showed that compared with those in siCtrl group, HEC-1B cells transfected with siAPOE showed significantly reduced migration ability (P < 0.05), whereas APOE overexpression significantly promoted the migration of the cells (P < 0.05). Neither APOE knockdown nor overexpression produced significant effects on HEC-1B cell proliferation as shown by MTT assay and flow cytometry. Hoechst staining revealed that transfection with siAPOE did not significantly affect apoptosis of HEC-1B cells. APOE knockdown obviously reduced and APOE overexpression enhanced ERK phosphorylation and MMP9 expression in HEC-1B cells (P < 0.05). Treatment with U0126 partially reversed the effects of APOE overexpression on ERK phosphorylation, migration and MMP9 expression in HEC-1B cells (P < 0.05). APOE is highly expressed in clinical samples of endometrial cancer tissues as compared with the adjacent tissues.@*CONCLUSION@#APOE is highly expressed in endometrial cancer tissues to promote cancer cell migration by enhancing ERK phosphorylation and MMP9 expression.

Investigation of medical humanistic practice ability of nurses and factors affecting their practices: a questionnaire-based analysis of 1196 cases in a general hospital in Hunan Province / 南方医科大学学报

OBJECTIVE@#To investigate humanistic practice ability of nurses in a general hospital in Hunan Province and analyze the factors affecting their practices to provide evidence for interventions to improve humanistic practice ability of the nurses.@*METHODS@#A total of 1196 nurses were surveyed using a self-designed questionnaire and a nurse humanistic practice ability assessment scale questionnaire for assessment of their abilities for humanistic care practice, psychological adjustment, interpersonal communication, self-management, ethics and legal practice. Univariate and multivariate analyses were performed for analysis of the factors affecting the practice abilities of the nurses.@*RESULTS@#The total score of humanistic practice ability of the 1196 nurses was 105.69±16.45 (the full score of the scale was 130), and the scores of humanistic care practice ability, psychological adjustment ability, interpersonal communication ability, self-management ability, ethics and legal practice ability were 40.95±6.46, 16.41±2.66, 16.41±2.66, 11.32±2.05 and 12.43±2.00, respectively. Univariate analysis and multiple linear regression analysis showed that gender (P=0.033), age (P < 0.001), department (P=0.015), working years (P < 0.001), professional title (P < 0.001), first academic degree (P < 0.001), highest academic degree (P < 0.001), family location (P=0.010), marital status (P=0.023), number of patients to care for (P=0.022), number of children (P=0.001), previous humanities related training (P < 0.001), training times (P < 0.001), and care received from family members (P < 0.001) and colleagues (P < 0.001) were all the factors affecting humanistic practice ability of the nurses. Among these factors, age, working in department of obstetrics and gynecology and emergency department, professional title, humanities training, and care from family and colleagues explained 20.7% of the variance.@*CONCLUSION@#The humanistic practice ability of nurses in this general hospital is above the average level, but their self-management ability needs to be improved. Intervention measures should be implemented to improve the nurses' humanistic practice ability including more attentions to the key groups and departments, strengthening the training of humanistic practice ability, and improving the promotion assessment system.

Exploration on multifunctional linkage and scientific use of medical colleges psychological experimental teaching center based on the network background / 中华医学教育探索杂志

The experimental teaching of psychology is not only an important course in the undergraduate and graduate education of applied psychology, but also can assist the practical teaching of quite a few other subjects. It clearly divides three basic functions of experimental psychology teaching center: teaching, scientific research and service, which play an important role in facilitating teachers and students to understand corresponding courses. At the same time, it is discussed and proposed to strengthen the internal and external scientific linkage of the experimental center under the network background, and put forward the use of Internet technology, in order to improve the scientific use of the experimental teaching center, and reflect its maximum value, thereby achieving the purpose of university laboratory joint construction and serve the university to cultivate innovative and compound personnels.

The effects of natural polysaccharide supramolecular hydrogel on bacteriostatic activity and biofilm clearance of berberine / 药学学报

Taking berberine (BBR) as an example, to study whether the supramolecular hydrogel formed by berberine and lotus root starch (Nelumbo nucifera Gaertn; LRS), a natural polysaccharide, affects the inhibition to Staphylococcus aureus and the ability of biofilm clearance. The chemical structure and rheological properties of BBR@LRS gel were characterized by infrared spectroscopy and rheometer. The in vitro release of supramolecular hydrogel was observed at pH = 1.2 and pH = 7.4. Broth dilution method and biofilm clearence experiment were used to observe the bacteriostasis and biofilm clearance respectively. Cytotoxicity test and in vitro hemolysis test were used to evaluate the biosafety preliminarily. The results showed that the LRS polysaccharide hydrogel could encapsulate BBR, and there was an interaction between them. The BBR@LRS gel had good rheological properties and biosafety, and played a role in solubility enhancement and slow release of BBR, which was stronger than BBR in inhibiting the growth of Staphylococcus aureus and clearing biofilm. This study provides reference for the effect of natural polysaccharide supramolecular hydrogels on biological functions of active components of traditional Chinese medicine.

Characteristics of kidney diseases in children aged 0-3 years old / 中华肾脏病杂志

Objective:To investigate the characteristics of renal disease spectrum in children aged 0-3 years old, and to evaluate the clinical value of renal biopsy in children aged 0-3 years old with renal diseases.Methods:It was a retrospective analysis study. The children aged 0-3 years old with kidney diseases receiving renal biopsy and having complete clinical data in Shanghai Children's Hospital from January 1, 2009 to December 31, 2020 were enrolled. The clinical and pathological data of the children were collected. The spectrum of renal diseases, clinical phenotype, renal pathology, and the relationship between renal pathology/genotype and clinical phenotype were analyzed.Results:A total of 117 children aged 0-3 years old with kidney diseases were enrolled in the study, accounting for 6.5% (117/1 790) of all children (0-18 years old) with renal biopsies during the same period. There were 77 males and 40 females. The age was (2.20±0.51) years old (5-35 months). All cases of renal biopsies in children aged 0-3 years old were successful without serious complications. Nephrotic syndrome was the common clinical phenotype of kidney diseases in children aged 0-3 years old (59.0%, 69/117), followed by hematuria and proteinuria (29.1%, 34/117). Primary glomerular disease (69.2%, 81/117) was the major clinical type of renal diseases, followed by hereditary kidney diseases (29.1%, 34/117), in which Alport syndrome was the main hereditary kidney disease (79.4%, 27/34). Renal pathological types of children aged 0-3 years old were mainly distributed in minimal change disease (30.8%, 36/117), followed by glomerular minor lesion (26.5%, 31/117), mesangial proliferative glomerulonephritis (15.4%, 18/117), and focal segmental glomerulosclerosis (10.3%, 12/117). Among 40 children aged 0-3 years old with hematuria with/without proteinuria, 25 cases were diagnosed as Alport syndrome by abnormal immunofluorescence of type IV collagen in renal tissues. Among the 28 children with kidney diseases who underwent genetic testing, 23 cases had gene mutations, mainly in COL4A5 gene (60.9%, 14/23), among which 4 children had gene mutations in 8 children with refractory nephrotic syndrome. Among the children aged 0-3 years old with clinical manifestations of hematuria, the proportion of gross hematuria in children diagnosed with Alport syndrome (59.3%, 16/27) was significantly higher than that in children without Alport syndrome (20.0%, 3/15, χ2=5.999, P=0.014). Conclusions:Primary glomerular disease is the principal type of kidney diseases in children aged 0-3 years old, followed by hereditary kidney disease. Attention should be paid to children aged 0-3 years old with gross hematuria. Renal biopsy in children aged 0-3 years old is safe and reliable, and it is an essential means for the diagnosis of renal diseases. Renal biopsy combined with gene testing can better understand the etiology of kidney diseases and guide treatment in children aged 0-3 years old.

Body weight change and metabolic index control in patients with type 2 diabetes mellitus under standardized metabolic disease management model / 中华内分泌代谢杂志

Objective:To explore the relationship between weight change and metabolic control of type 2 diabetic patients after 1 year treatment under the standardized metabolic disease management model.Methods:From November 2017 to November 2021, 950 patients with T2DM in the Standardized Metabolic Management Center of Suzhou Municipal Hospital were recruited in this research, who were divided into normal(BMI 18.5-23.9 kg/m 2), overweight(BMI 24.0-27.9 kg/m 2), and obese(BMI≥28 kg/m 2)groups according to baseline BMI. The metabolic indicators and control rates were compared. The overweight and obese 599 patients were divided into weight reduction(<-3 kg), maintenance(-3-1 kg) and gain(>1 kg)groups according to weight changes by one year, and metabolic indicators and control rates were compared to analyze the influence of weight change on metabolic control of overweight and obese patients. Results:(1) The overweight and obese groups had worse metabolic control at baseline and the obese group was younger. After 1 year, the metabolic indicators of three groups were significantly improved. (2) After 1 year, the metabolic control was better in weight reduction group and worse in weight gain group. The control rates were increased in weight reduction and maintenance groups. (3) For every 1 kg reduction in body weight of overweight and obese patients, blood glucose, blood lipids, blood pressure and comprehensive control rate increased by 1.206, 1.046, 1.069 and 1.107 times, respectively. There was a positive linear relationship between weight reduction and metabolic improvement.Conclusion:Standardized metabolic disease management model promotes metabolic control in type 2 diabetic patients, especially in overweight and obese patients who actively lose weight. In the future we should strengthen the management of overweight and obese patients, enhance self-management ability, and manage body weight scientifically and effectively.

Urine virology and clinical characteristics of female patients with overactive bladder / 中华泌尿外科杂志

Objective:To investigate the urinary virology and clinical characteristics of female overactive bladder (OAB) patients.Methods:Catheterized urine samples were collected from 55 women with OAB and 18 control individuals between January 2021 and August 2021. Inclusion criteria were: female with age>18, diagnosed as OAB, OABSS total score≥3 and item Urgency score≥2, informed consent signed. Exclusion criteria were: Urine culture positive, urinary catheter indwelling status, antibiotic usage in recent 30 days, other disease leading to OAB-like symptoms, pelvic organ prolapse and current pregnancy, immunosuppressive therapy or status. Clinical characteristic and history were collected. OAB symptoms were assessed via both OABSS (overactive bladder symptom score) and OAB-V8 (8-item overactive bladder questionnaire). The urine specimens were analyzed using mNGS for identifying viral infections. The correlation between the disease and JC virus infection was analyzed by t test, chi-square test, binary logistic regression analysis and Spearman correlation matrix, and the Nomogram map for predicting the risk of viral infection was constructed. Results:In total, 55 women with OAB and 18 healthy controls were recruited in the study. There are significant difference in terms of UTI history, pelvic surgery history and the habit of holding urine [60.0%(n=33)to 16.7%(n=3), P=0.002; 43.6%(n=24)to 0.0%(n=0), P<0.01; 36.4%( n=20)to 5.6%( n=1), P=0.015]. Based on mNGS results, OAB patients were identified with more positive viral infection [47.3%(n=26)to 33.3%(n=6)] and more JC virus infection. In the OAB group, subtype 7B of JCV ( n=8) was identified, while in the control group, subtype 7A(n=2) was identified. Pairwise Spearman correlation analysis indicated high correlations between viral infection and OABSS ( r=0.58), age and pausimenia ( r=0.68), hypertension and age ( r=0.53), respectively. Estimates from binary logistic regression model indicated risk factors for virus infection in OAB patients including age ( OR=1.99, 95% CI 0.02-2.61), holding urine habit( OR=2.16, 95% CI 0.18-3.85) and pelvic surgery ( OR=2.53, 95% CI 0.54-4.27). Conclusions:Urinary viral infections appear to be associated with more severe OAB symptoms and JC virus may be a potential therapeutic target for OAB.

Prevalence of myopia and consistency evaluation of three myopia assessment methods among children and adolescents / 中国学校卫生

Objective@#To evaluate the prevalence and consistency of screening myopia, non-cycloplegic myopia and cycloplegic myopia in children and adolescents, and to provide references for exploring the factors affecting the consistency of different definition methods.@*Methods@#A total of 3 868 children and adolescents aged 6 to 17 years from seven schools were included in a school based cross sectional study in Shandong Province in September 2020. The prevalence of screening myopia, non cycloplegic refraction, and cycloplegic refraction at different ages and all children and adolescents were analyzed. With cycloplegic spherical equivalent ≤-0.50 D as the gold standard for myopia, and Kappa test and area under the ROC curve were used to evaluate the consistency.@*Results@#The prevalence of cycloplegic myopia and screening myopia were 36.7% and 38.3% among children and adolescents. The prevalence of non cycloplegic myopia was 62.4%, which was significantly higher than screening myopia and cycloplegic myopia two methods in primary and junior high schools. Among 3 868 subjects, there were 3 628 (93.8%) subjects with screening myopia and 2 862 (74.0%) subjects with non cycloplegic myopia who were consistent with the gold standard for myopia. The Kappa values of screening myopia and non cycloplegic myopia were 0.87 and 0.51, and the area under the ROC curve was 0.94 (95% CI =0.93-0.95) and 0.79 (95% CI =0.78-0.81). Compared with other groups, children and adolescents aged 8 to 17 years, in junior or high school, urban residence, better presenting distance visual acuity, and astigmatism ≤1.50 D had a higher consistency in the application of screening myopia ( P <0.05).@*Conclusion@#The consistency between screening myopia and cycloplegic myopia is high, and the consistency between non cycloplegic objective myopia is low.

Mass spectrometry-guided study on cyclic peptides from sponge Reniochalina sp / 药学实践杂志

Objective To study the cyclic peptides from sponge Reniochalina sp. under the guidance of mass spectrometry. Methods Mass spectrometry-guided procedural separation methods were used to track and isolate the cyclic peptides from the sponge genus Reniochalina. The structures of compounds were elucidated by the determination of physicochemical parameters and comparison of spectroscopic data. The preliminary cytotoxic activity of compounds was assessed by the Cell Counting Kit-8 (CCK-8) method. Results Three cyclic peptides were isolated from the sponge Reniochalina sp. and identified as stylopeptide 1 (1), hymenamide D (2) and axinastatin 2 (3). Compound 1 exhibited cytotoxicity against six human cancer cell lines with IC50 values ranging from 6.09 to 17.26 μmol/L. Conclusion Compound 1 - 3 were isolated from Reniochalina sp. for the first time, and compound 1 was a cytotoxic cyclic heptapeptide.

Influencing factors of adherence to clinical decision support system which based on clinical practice guideline / 中国实用护理杂志

The clinical decision support system can provide medical staff with targeted patient diagnosis, treatment and care plan according to the recommendations of the guidelines, and assist medical staff to make clinical decisions. However, the adherence to clinical decision support system which based on guidelines was poor in clinical practice. Therefore, this article reviewed the influence factors of adherence to clinical decision support system which based on guideline from four aspects: system factors, individual factors, organizational factors and environmental factors, so as to improve the hindering factors and promote the application of clinical decision support system which based on guideline in future research and clinical practice.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

Exposure level of neonicotinoid pesticides and their metabolites in pregnant women in the suburb of Shanghai / 中华预防医学杂志

In 2021, a total of 151 pregnant women were selected from the suburb of Shanghai. A questionnaire survey was conducted to obtain data about maternal age, gestational week, total annual household income, education level and passive smoking among pregnant women and one spot urine was collected. The concentrations of eight neonicotinoid pesticides and four metabolites in urine were measured by ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. The differences in detection frequencies and concentrations of neonicotinoid pesticides and their metabolites among pregnant women with different characteristics were compared, and the influencing factors of the detection of neonicotinoid pesticides in urine were analyzed. The results showed that at least one neonicotinoid pesticide was detected in 93.4% (141 samples) of urine samples. The detection frequencies of N-desmethyl-acetamiprid, clothianidin, thiamethoxam, and N-desmethyl-clothianidin were high, about 78.1% (118 samples), 75.5% (114 samples), 68.9% (104 samples), and 44.4% (67 samples), respectively. The median concentration of the sum of all neonicotinoid pesticides was 2.66 μg/g. N-desmethyl-acetamiprid had the highest detection concentration with a median concentration of 1.04 μg/g. A lower urinary detection frequency of imidacloprid and its metabolites was seen in pregnant women aged 30-44 years [OR (95%CI): 0.23 (0.07-0.77)]. A higher detection frequency of clothianidin and its metabolites was seen in pregnant women with per capita annual household income≥100 000 yuan [OR (95%CI): 6.15 (1.56-24.28)]. There was widespread exposure to neonicotinoid pesticides and their metabolites in pregnant women from the suburb of Shanghai, which might pose potential health risks to pregnant women, and maternal age and household income were potential influencing factors of the exposure to neonicotinoid pesticides.

Single base editing system mediates site-directed mutagenesis of genes GDF9 and FecB in Ouler Tibetan sheep / 生物工程学报

In this study, a single base editing system was used to edit the FecB and GDF9 gene to achieve a targeted site mutation from A to G and from C to T in Ouler Tibetan sheep fibroblasts, and to test its editing efficiency. Firstly, we designed and synthesized sgRNA sequences targeting FecB and GDF9 genes of Ouler Tibetan sheep, followed by connection to epi-ABEmax and epi-BE4max plasmids to construct vectors and electrotransfer into Ouler Tibetan sheep fibroblasts. Finally, Sanger sequencing was performed to identify the target point mutation of FecB and GDF9 genes positive cells. T-A cloning was used to estimate the editing efficiency of the single base editing system. We obtained gRNA targeting FecB and GDF9 genes and constructed the vector aiming at mutating single base of FecB and GDF9 genes in Ouler Tibetan sheep. The editing efficiency for the target site of FecB gene was 39.13%, whereas the editing efficiency for the target sites (G260, G721 and G1184) of GDF9 gene were 10.52%, 26.67% and 8.00%, respectively. Achieving single base mutation in FecB and GDF9 genes may facilitate improving the reproduction traits of Ouler Tibetan sheep with multifetal lambs.

Principle and development of single base editing technology and its application in livestock breeding / 生物工程学报

CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein) is widely used in the field of livestock breeding. However, its low efficiency, untargeted cutting and low safety have greatly hampered its use for introducing single base mutations in livestock breeding. Single base editing, as a new gene editing tool, can directly replace bases without introducing double strand breaks. Single base editing shows high efficiency and strong specificity, and provides a simpler and more effective method for precise gene modification in livestock breeding. This paper introduces the principle and development of single base editing technology and its application in livestock breeding.

A family with early onset myopathy caused by MEGF10 gene defect and literature review / 中华儿科杂志

Objective: To summarize the genetic and clinical phenotypic characteristics of patients with early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) caused by multiple epidermal growth factor 10 (MEGF10) gene defect. Methods: The clinical data of 3 infants in 1 family with EMARDD caused by MEGF10 gene defect diagnosed in the Department of Neonatology, Xiamen Children's Hospital in April 2022 were analyzed retrospectively. Using "multiple epidermal growth factor 10" "myopathy" or "MEGF10" "myopathy" as the key words, and searching the relevant literature reports of CNKI, Wanfang Database and PubMed Database from the establishment of the database to September 2022. Combined with this family, the main clinical information and genotype characteristics of EMARDD patients caused by MEGF10 gene defect were summarized. Results: The proband, male, first infant of monozygotic twins, was admitted to hospital 7 days after birth "due to intermittent cyanosis with weak sucking". The infant had dysphagia accompanied with cyanosis of lips during feeding and crying after birth. Physical examination on admission revealed reduced muscle tone of the extremities, flexion of the second to fifth fingers of both hands with limited passive extension of proximal interphalangeal joints, and limited abduction of both hips. He was diagnosed as dysphagia of newborn, congenital dactyly. After admission, he was given limb and oral rehabilitation training, breathing gradually became stable and oral feeding fully allowed, and discharged along with improvement. The younger brother of the proband was admitted to the hospital at the same time, and his clinical manifestations, diagnosis and treatment process were the same as those of the proband. The elder brother of the proband died at the age of 8 months due to the delayed growth and development, severe malnutrition, hypotonia, single palmoclal crease and weak crying. A whole exon sequencing of the family was done, and found that the 3 children were all compound heterozygous variations at the same site of MEGF10 gene, with 2 splicing variants (c.218+1G>A, c.2362+1G>A), which came from the father and mother respectively, and the new variation was consistent with the autosomal recessive inheritance model. Three children were finally diagnosed as EMARDD caused by MEGF10 gene defect. There are 0 Chinese literature and 18 English literature that met the search conditions. Totally 17 families including 28 patients were reported. There were 31 EMARDD patients including 3 infants from this family. Among them, there were 13 males and 18 females. The reported age of onset ranged from 0 to 61 years. Except for 5 patients with incomplete clinical data, 26 patients were included in the analysis of phenotypic and genotypic characteristics. The clinical features were mainly dyspnea (25 cases), scoliosis (22 cases), feeding difficulties (21 cases), myasthenia (20 cases), and other features including areflexia (16 cases) and cleft palate or high palatal arch(15 cases). Muscle biopsy showed non-specific changes, with histological characteristics ranging from slight muscle fiber size variation to minicores change which was seen in all 5 patients with at least 1 missense mutation of allele. In addition, the adult onset was found in patients with at least 1 missense variant of MEGF10 gene. Conclusions: MEGF10 gene defect related EMARDD can occur in the neonatal period, and the main clinical features are muscle weakness, breathing and feeding difficulties. Patients with myopathy who have at least 1 missense mutation and muscle biopsy indicating minicores change may be relatively mild.

Progress in omics research and preclinical models of gallbladder cancer / 中华外科杂志

Gallbladder cancer(GBC)is one common type of bile tract cancers with poor prognosis. This review summarizes the recent development of studies about somatic mutation, molecular subtype, microenvironment heterogeneity, organoid, orthotopic model, patient-derived xenograft and clinical translation on GBC in aspects of genomic,transcriptome,single cell omics and clinical translation. We expect this review will provide new ideas on dissecting molecular mechanisms underlying the development and emerging chemoresistance of GBC following therapy and promote GBC precision medicine.

Clinical feature difference between juvenile amyotrophic lateral sclerosis with SPTLC1 and FUS mutations / 中华医学杂志(英文版)

BACKGROUND@#Juvenile amyotrophic lateral sclerosis (JALS) is an uncommon form of amyotrophic lateral sclerosis whose age at onset (AAO) is defined as prior to 25 years. FUS mutations are the most common cause of JALS. SPTLC1 was recently identified as a disease-causative gene for JALS, which has rarely been reported in Asian populations. Little is known regarding the difference in clinical features between JALS patients carrying FUS and SPTLC1 mutations. This study aimed to screen mutations in JALS patients and to compare the clinical features between JALS patients with FUS and SPTLC1 mutations.@*METHODS@#Sixteen JALS patients were enrolled, including three newly recruited patients between July 2015 and August 2018 from the Second Affiliated Hospital, Zhejiang University School of Medicine. Mutations were screened by whole-exome sequencing. In addition, clinical features such as AAO, onset site and disease duration were extracted and compared between JALS patients carrying FUS and SPTLC1 mutations through a literature review.@*RESULTS@#A novel and de novo SPTLC1 mutation (c.58G>A, p.A20T) was identified in a sporadic patient. Among 16 JALS patients, 7/16 carried FUS mutations and 5/16 carried respective SPTLC1 , SETX , NEFH , DCTN1 , and TARDBP mutations. Compared with FUS mutation patients, those with SPTLC1 mutations had an earlier AAO (7.9 ± 4.6 years vs. 18.1 ± 3.9 years, P  < 0.01), much longer disease duration (512.0 [416.7-607.3] months vs. 33.4 [21.6-45.1] months, P  < 0.01), and no onset of bulbar.@*CONCLUSION@#Our findings expand the genetic and phenotypic spectrum of JALS and help to better understand the genotype-phenotype correlation of JALS.

Evaluation of subjective scale in allergen nasal provocation test / 临床耳鼻咽喉头颈外科杂志

Objective:To compare the clinical value of visual analogue scale （VAS）, Lebel scale and total nasal symptom scores （TNSS） in evaluating nasal allergen provocation test （NAPT）. Methods:A total of 151 patients suspected of allergic rhinitis admitted to the Department of Otolaryngology-Head and Neck Surgery of our hospital from April 2020 to September 2020 were included, of which 76 were positive for house dust mites and 75 were negative for allergens. Nasal airway resistance（NAR） was measured by active anterior nasal manometry. Nasal symptoms were evaluated by VAS, Lebel and TNSS. House dust mite allergen was used for NAPT by spray method. An increase≥40% in NAR was used as the gold standard for objective evaluation of NAPT. ROC curves of VAS, Lebel and TNSS were drawn to compare the evaluation effectiveness of different subjective evaluation methods, and the optimal critical point of each ROC curve was obtained. Results:With NAR increased by ≥40% as the gold standard, the area under ROC curve of VAS was 0.884, and the sensitivity and specificity were 97.75% and 80.65%, respectively. The area under ROC curve of Lebel was 0.773, and the sensitivity and specificity were 68.54% and 75.81%, respectively. The area under ROC curve of TNSS was 0.792, and the sensitivity and specificity were 68.54% and 79.03%, respectively. There was no significant difference between Lebel and TNSS（P>0.05）. The VAS differed significantly from Lebel and TNSS（P<0.05）. The Kappa values of VAS, Lebel, TNSS and NAR were 0.803, 0.432 and 0.459, respectively. Conclusion:The VAS, Lebel, TNSS subjective scale and NAR are consistent in evaluating the efficacy of NAPT, with the VAS assessment showing highest consistency with NAR. As objective assessment instruments are not widely used in China, subjective assessment method could be adopted to evaluate the efficacy of NAPT in clinical practice, and VAS scale is recommended as a priority.

Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study / 中国当代儿科杂志

OBJECTIVES@#To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia.@*METHODS@#A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively.@*RESULTS@#Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia.@*CONCLUSIONS@#The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

Clinical Analysis of Bloodstream Infection after Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT).@*METHODS@#The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed.@*RESULTS@#Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G-) bacteria (62.8%), 40 Gram-positive (G+) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G+ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001).@*CONCLUSION@#The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;