Objective To investigate the clinical characteristics of antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV)with peripheral neuropathy as the initial symptom and to enhance the understanding of the disease.Methods The clinical data of 6 patients of AAV with peripheral neuropathy as the initial symptom at Xiangya Hospital of Central South University from 2017 to 2021 were collected.Results All 6 cases were middle-aged or elderly males,and the initial symptoms mainly consisted of limb numbness,pain,and weakness.In addition to neurological involvement,some patients had upper respiratory tract,lungs,kidneys,eyes,ears,skin and joints involved.Electromyography showed multiple peripheral nerve damage;Five patients were positive for pANCA and MPO,and one patient was positive for cANCA and PR3.Six patients were all treated with glucocorticoid and cyclophosphamide,and the clinical symptoms and laboratory indexes were improved to different degrees.Conclusions There were no characteristic symptoms in AAV with peripheral neuropathy as the first symptom.Early diagnosis and treatment of AAV can improve the quality of life and prognosis of patients.

Objective:To evaluate the effect of PACS system (picture archiving and communication system) in the standardized residency training of cardiovascular medicine.Methods:Fifty-nine residents taking the standardized residency training of cardiovascular medicine in Changhai Hospital from 2018 to 2019 were randomly divided into PACS teaching group ( n = 30) and traditional teaching group ( n = 29). The research group adopted the PACS system for the teaching of cardiovascular medicine, and the control group took the traditional teaching method. The teaching effect was evaluated by theoretical examination, imaging examination and questionnaire. SPSS 19.0 was used for t test and chi-square test. Results:The theoretical and film reading scores of the PACS teaching group were significantly higher than those of the control group [(87.70 ± 6.52) vs. (80.55 ± 8.63); (86.67 ± 6.33) vs. (77.48 ± 10.29), P < 0.05)]. The results of the questionnaire showed that PACS teaching method was helpful for residents to master cardiovascular knowledge, arouse their learning interest and improve their clinical thinking ability. The satisfaction with the teaching method in the PACS teaching group was significantly higher than that in the traditional teaching group [(9.22 ± 0.44) vs. (8.26 ± 0.72), P < 0.05]. Conclusion:The application of PACS system in the teaching of cardiovascular medicine can significantly improve the teaching effect of residents.

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Liposomes, as one of the most successful nanotherapeutics, have a major impact on many biomedical areas. In this study, we performed laser scanning confocal microscope (LSCM) and immunohistochemistry (IHC) assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptide-conjugated active targeting liposomes (GE11-TLs) in SMMC7721 xenograft model. According to classification of individual cell types in high resolution images, biodistribution of macrophages, tumor cells, cells with high epidermal growth factor receptor (EGFR) expression and interstitial matrix in tumor microenvironment, in addition, their impacts on intra-tumor penetration of GE11-TLs were estimated. Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts. Tumor angiogenesis was of great heterogeneity from the periphery to the center region. However, the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs. We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drug delivery.

Objective To investigate the infection status, serotype distribution, drug sensitivity and molecular characteristics of diarrheagenic Escherichia coli (DEC) in patients with diarrhea in Guangdong Province. Methods Fecal samples were collected, cultured and isolated by traditional methods. Suspected Escherichia coli isolates were confirmed by multiplex PCR used for detecting specific virulence genes and bio-chemical methods. Positive strains were serotyped, characterized for drug sensitivity and analyzed by pulsed-field gel electrophoresis ( PFGE). Results The total positive rate of DEC in patients with diarrhea was 6.26%. The positive rates of enteropathogenic Escherichia coli (EPEC), enterotoxigenic Escherichia coli (ETEC), enterohemorrhagic Escherichia coli (EHEC), enteroadherent Escherichia coli (EAEC) and en-teroinvasive Escherichia coli (EIEC) were 2. 47% , 1. 54% , 1. 32% , 0. 62% and 0. 09% , respectively, with infections primarily in children aged 0-<7 years. The total seropositive rate was 52. 54% , with EHEC accounting for 15. 00% . DEC showed high sensitivity to imipenem, ciprofloxacin, ceftazidime and cefo-taxime. The multidrug resistance rate of DEC was 58. 45% , with EPEC being the most serious for multidrug resistance. PFGE results showed that ETEC, EHEC, EPEC and EAEC had a high degree of polymorphism. Conclusion EPEC is the predominant type of DEC circulating in Guangdong Province. Third-generation cephalosporins are the first drugs of choice for treating infections in children. Ciprofloxacin can be used to treat adults. The problem of multiple drug resistance of DEC is severe and efforts to monitor DEC infections and drug resistance should be strengthened.

Objective To investigate the effects of fasting serum triglycerides (TG) levels at different baseline on the risk of new-onset acute pancreatitis (AP) in in-service and retired employees of Kailuan Group.Methods A total of 125 178 in-service and retired employees of Kailuan Group who received health check-ups from 2006 to 2009 and had no AP history but had complete TG data were prospectively enrolled.According to quantile level,the baseline serum fasting TG level of study subjects were divided into ＜1.01 mmol/L group (n=42 128),1.01 to 1.64 mmol/L group (n=41 711) and ＞ 1.64 mmol/L group (n=41 339).The incidence of new-onset AP of these three groups was analyzed.The survival curve was plotted by Kaplan-Meier method.The cumulative incidence rate was calculated and tested by log-rank method.And multivariate Cox proportional hazards regression model was performed to calculate hazard ratios (HR) of baseline fasting serum TG level for AP.Results After followed up for (7.36±1.23) years,a total of 193 cases of AP occurred.The incidences of AP in ＜1.01 mmol/L group,1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group were 1.43 events/10 000 person-years,2.37 events/10 000 person-years and 2.49 events/10 000 person-years,respectively.The cumulative incidence rates of AP in ＜1.01 mmol/L group,1.01 to 1.64 mmol/L group and ＞1.64 mmol/L group were 0.10％ (44/42 128),0.18％ (73/41 711) and 0.18％ (76/41 339),respectively,and the difference was statistically significant (x2 =9.998,P=0.007).The results of multivariate Cox proportional hazards regression model analysis indicated that the risk of AP increased in 1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group compared with that of ＜1.01 mmol/L group,HR and 95％ confidence interval (CI) were 1.56 (1.07 to 2.29) and 1.57 (1.06 to 2.32),respectively.After excluded onset AP within one year,with a control group of ＜1.01 mmol/L group,the results of multivariate Cox proportional hazards regression model analysis indicated that the HR and 95％CI for AP of 1.01 to 1.64 mmol/L group and ＞ 1.64 mmol/L group were 1.70 (1.11 to 2.58) and 1.69 (1.10 to 2.60),respectively.Conclusion Baseline fasting serum TG levels over 1.01 mmol/L may increase the risk of AP.

Objective To analyze the serotype distribution and antibiotic resistance characteristics of Salmonella strains isolated in Guangdong province for better understanding the condition of Salmonella infection in patients with diarrhea.Methods Fecal samples collected from patients with diarrhea in Guangdong province were used to isolate Salmonella strains.Biochemical analysis was performed to identify these isolated strains.Serotyping and antimicrobial susceptibility testing were carried out for further analysis of the isolated Salmonella strains.Results The rate of Salmonella infection was 7.64％in 2015, and the male to female patient ratio was 1.52∶1.A total of 2 377 patients of all age groups were positive for Salmonella infection and the patients aged 0-6 years accounted for 81.74％.The isolation rate of Salmonella strains in the summer and autumn was higher than that in the winter and spring (10.73％ vs 4.24％;X2=463.77, P<0.01).The Salmonella isolation rates in different areas were as follows: 16.82％ in Zhuhai, 15.85％ in Heyuan, 11.81％ in Yangjiang, 10.68％ in Jiangmen, 8.49％ in Zhongshan, 8.07％ in Maoming, 8.05％ in Jieyang, 7.35％ in Shaoguan, 6.97％ in Foshan, 6.03％ in Dongguan, 5.48％ in Guangzhou and 0.00％ in Zhanjiang.And the differences between different regions were statistically significant (X2=367.67, P<0.01).The 2 377 isolated Salmonella strains were classified into 108 serotypes except for oneSalmonella strain that could not be classified.The top four predominant serotypes were 4,5,12:i:-, Salmonella enteritidis,Salmonella stanley and Salmonella typhimurium.Most Salmonella strains were sensitive to imipenem, azithromycin, ceftazidime, cefotaxime and trimethoprim/sulfamethoxazole, but multidrug resistance was common among those strains.Conclusion Salmonella serotypes of 4,5,12:i:-and Salmonella enteritidis are the predominant pathogens causing human Salmonella infections in Guangdong province.Ceftazidime and cefotaximeare are preferred in the treatment of Salmonella infections.Surveillance for drug resistance in Salmonella should be strengthened as multidrug resistant strains have become a serious problem in Guangdong province.

Objective To prepare simulated stool specimens for proficiency testing ( PT) by mix-ing lentils with Salmonella, Shigella and Escherichia coli strains and to establish an assessment scheme for the detection of Salmonella and Shigella in clinical samples. Methods Salmonella, Shigella and Escherich-ia coli strains were respectively spiked to lentils in Cary-Blair transport medium to create simulated stool specimens. Various ratios of Escherichia coli to Salmonella strains were spiked to lentils to prepare mixed simulated stool specimens. The accuracy and stability of prepared stool samples for PT were tested in-house. Results of sample detection were collected from participating laboratories for further external quality assess-ment. Results The Escherichia coli and Salmonella strains mixed at ratios of 100 ∶ 1 to 106 ∶ 1 could be ef-ficiently isolated from the media. Enrichment was needed in order to effectively isolate Salmonella strains from the media when the ratios of Escherichia coli to Salmonella strains were 104 ∶ 1 to 106 ∶ 1. Of the16 participating laboratories, 14 laboratories (87. 5%) received a grade of“satisfactory” and the other 2 labo-ratories (12. 5%) received a grade of “mainly satisfactory”. Conclusion The simulated stool specimens and the PT procedures designed in this study were suitable for proficiency testing program on the detection of Salmonella, Shigella and other similar microbes.

Objective To understand the effect ofserotyping on Salmonella isolates,by use of Microsphere-based Liquid Array method,among diarrhea patients,in Guangdong.Methods Salmonella isolated from humans in Guangdong province were serotyped on the Microsphere-based Liquid Array platform with SSA kit.Results A total of 4 942 Salmonella strains with 189 serotypes,were identified in Guangdong province in 2010-2014.The top 100 serotypes accounted for 98.08％ (4 847/4 942) of all the strains.98％ of the top 100 species serotypes could completely be serotyped with SSA kit.In order to detect O antigen among 198 isolates with SSA kit,181 strains were carrying the O antigen,with the coincidence rate as 100％.However,under the SSA,98.32％ (528/537) of the H antigen could be detected and were consistent with the traditional serum agglutination test.The coincidence rate of fljB gene was 93.09％ (175/188),with false negative rate and false positive rate of fljB gene as 7.35％ (9/134) and 7.41％ (4/54) respectively.The coincidence rate of sdf gene and Vi gene were 100％.11 out of the 12 Salmonella strains could not be serotyped under the traditional methods but were successfully serotyped by the molecular serotyping method.Conclusions Using the SSA kit,more than 96％ of the anthropogenic Salmonella strains could be serotyped in Guangdong province.Comparing with the traditional methods,the coincidence rate of serotyping appeared over 98％.Under the Microsphere-based Liquid Array techniques,the molecular serotyping method appeared faster and more accurate on Salmonella serotyping than those traditional methods.

OBJECTIVETo investigate the effect of body mass index (BMI) on new-onset non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).

METHODSSubjects with T2DM were recruited from the population of individuals attending the Affiliated General Hospital of North China University for routine health examination between 2006 and 2007 and offered participation in this community-based prospective cohort study. Enrollees were categorized into groups according to weight assessed by baseline BMI (underweight, normal, overweight, and obese groups). Cumulative incidence of NAFLD was compared between each group and the effect of baseline BMI on new-onset NAFLD was assessed by Cox regression analysis.

RESULTSThe cumulative incidence of NAFLD increased in conjunction with increases in weight (low weight: 69%, normal weight: 73%, overweight: 90%, obese: 97%; P<0.01). Subjects in the overweight and obese groups showed an increased risk of NAFLD (relative risk (RR)=2.00, 95% CI: 1.76-2.29 and =2.87, 95% CI: 2.42-3.40; P<0.01), compared to those in the normal weight group. Moreover, after adjustment for baseline factors (e.g.age, sex) risk of NAFLD remained higher for the overweight and obese subjects (RR=1.73, 95% CI: 1.49-2.00 and =2.12, 95% CI: 1.73-2.60; P<0.01).

CONCLUSIONRisk of NAFLD in T2DM patients increases in parallel to increase in weight assessed by BMI. BMI appeared to be an independent risk factor for NAFLD.

Body Mass Index ; China ; Cohort Studies ; Diabetes Mellitus, Type 2 ; Humans ; Incidence ; Non-alcoholic Fatty Liver Disease ; Obesity ; Prospective Studies ; Risk Factors