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.

Primary hepatic angiosarcoma: a clinicopathological analysis of nine cases / 中华病理学杂志

Objective: To investigate the clinical manifestations, histomorphology, and differential diagnosis of primary hepatic angiosarcoma. Methods: Nine cases of primary hepatic angiosarcoma diagnosed in the Department of Pathology, the First Affiliated Hospital of Nanjing Medical University from January 2014 to December 2021 were collected, including biopsy and surgical specimens. The histomorphology, clinical, and radiologic findings were analyzed. The relevant literature was also reviewed. Results: There were six males and three females, aged 30 to 73 years (mean 57 years). Grossly, the growth pattern of the tumor was classified as either mass formation or non-mass formation (sinusoidal). Microscopically, the mass-forming primary hepatic angiosarcoma were further subdivided into vasoformative or non-vasoformative growth patterns; and those non-vasoformative tumors had either epithelioid, spindled, or undifferentiated sarcomatoid features. Sinusoidal primary hepatic angiosarcoma on the other hand presented with markedly dilated and congested blood vessels of varying sizes, with mild to moderately atypical endothelial cells. Follow-up in all nine cases revealed 8 mortality ranging from 1 to 18 months (mean 5 months) from initial diagnosis. One patient was alive with disease within a period of 48 months. Conclusions: Primary hepatic angiosarcoma is a rare entity with a wide spectrum of histomorphology, and often misdiagnosed. It should be considered when there are dilated and congested sinusoids, with overt nuclear atypia. The overall biological behavior is aggressive, and the prognosis is worse.

Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation / 中华病理学杂志

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

Performance of the Ebel standard-setting method for the spring 2019 Royal College of Physicians and Surgeons of Canada internal medicine certification examination consisting of multiple-choice questions / 보건의료교육평가

Purpose@#This study aimed to assess the performance of the Ebel standard-setting method for the spring 2019 Royal College of Physicians and Surgeons of Canada internal medicine certification examination consisting of multiple-choice questions. Specifically, the following parameters were evaluated: inter-rater agreement, the correlations between Ebel scores and item facility indices, the impact of raters’ knowledge of correct answers on the Ebel score, and the effects of raters’ specialty on inter-rater agreement and Ebel scores. @*Methods@#Data were drawn from a Royal College of Physicians and Surgeons of Canada certification exam. The Ebel method was applied to 203 multiple-choice questions by 49 raters. Facility indices came from 194 candidates. We computed the Fleiss kappa and the Pearson correlations between Ebel scores and item facility indices. We investigated differences in the Ebel score according to whether correct answers were provided or not and differences between internists and other specialists using the t-test. @*Results@#The Fleiss kappa was below 0.15 for both facility and relevance. The correlation between Ebel scores and facility indices was low when correct answers were provided and negligible when they were not. The Ebel score was the same whether the correct answers were provided or not. Inter-rater agreement and Ebel scores were not significantly different between internists and other specialists. @*Conclusion@#Inter-rater agreement and correlations between item Ebel scores and facility indices were consistently low; furthermore, raters’ knowledge of the correct answers and raters’ specialty had no effect on Ebel scores in the present setting.

Cost-effectiveness of lung cancer screening worldwide: a systematic review / 中华流行病学杂志

Objective: From the economic point of view, this study was to systematically assess the status quo on lung cancer screening in the world and to provide reference for further research and implementation of the programs, in China. Methods: PubMed, EMbase, The Cochrane Library,CNKI and Wanfang Data were searched to gather papers on studies related to economic evaluation regarding lung cancer screening worldwide, from the inception of studies to June 30(th), 2018. Basic characteristics, methods and main results were extracted. Quality of studies was assessed. Cost were converted to Chinese Yuan under the exchange rates from the World Bank. The ratio of incremental cost-effectiveness ratio (ICER) to local GDP per capita were calculated. Results: A total of 23 studies (only 1 randomized controlled trial) were included and the overall quality was accepted. 22 studies were from the developed countries. Nearly half of the studies (11 studies) took 55 years old as the starting age of the screening program. Smoking history was widely applied for the selection of criteria on target populations (18). Low-dose computed tomography (LDCT) was involved in every study used to evaluate the economic effectiveness. Annual (17) and once-life time (7) screening were more common frequencies. 22 studies reported ICERs for LDCT screening, compared to no screening, of which 17 were less than 3 times local GDP per capita, and were considered as cost-effectiveness, according to the WHO's recommendation. 15 and 7 studies reported ICERs for annual and once-life time screening, of which 12 and 7 studies were in favor the results of their cost-effectiveness, respectively. Additionally, the cost-effectiveness of once-lifetime screening was likely to be superior to the annual screening. Differences of cost-effectiveness among the subgroups, by starting age or by the smoking history, might exist. Conclusions: Based on the studies, evidence from the developed countries demonstrated that LDCT screening programs on lung cancer, implemented among populations selected by age and smoking history, generally appeared more cost-effective. Combined with the local situation of health resource, the findings could provide direction for less developed regions/countries lacking of local evidence. Low frequency of LDCT screening for lung cancer could be adopted when budget was limited. Data on starting ages, smoking history and other important components related to the strategy of screening programs, needs to be precisely evaluated under the situation of local population.

In vitro fungistatic activity of 36 traditional oriental medicines and their synergistic effect against Trichophyton rubrume

Objective:To investigate the fungistatic activity and synergistic effects of natural products and their constituents, including traditional oriental medicines (TOMs).Methods:Fungistatic activities of TOMs prepared by hot-water (115 °C) or ethanol (70%; 40 °C) extraction were determined by their minimum inhibitory concentration. To assess possible synergistic effects, minimum inhibitory concentrations of various combinations were evaluated.Results:By evaluating antifungal susceptibility of Trichophyton rubrum, which is a major causative fungus for several types of dermatophytosis, we confirmed that ethanol extracts were more active than hot-water extracts in 25 of the 36 TOMs, suggesting that the constituents with high hydrophobicity tend to contribute significantly to fungistatic activity. We selected four TOMs with high fungistatic activity, including Aucklandiae radix, Gentianae macrophyllae radix, Scutellariae radix, and Galla rhois, and their synergistic effects were investigated through the combination studies between TOMs or TOM-conventional drug terbinafine. In combinations between four TOMs, partial synergistic effects were observed in Aucklandiae radix–Galla rhois and Gentianae macrophyllae radix–Galla rhois combinations, as supported by the lowest fractional inhibitory concentration index value of 0.66 for both combinations. Furthermore, Galla rhois showed the strongest synergistic effect on growth inhibition of Trichophyton rubrum with a fractional inhibitory concentration index value of 0.50 in combination with terbinafine.Conclusions:Our findings indicate that the combination of TOMs and TOM-terbinafine may be effective on treatment for chronic and recurrent dermatophytosis by improving fungistatic activity and led to decrease systemic toxicity in clinical practice.

Willingness and influencing factors related to "centralized slaughtering, fresh poultry listing and marketing" strategy among the household chefs in Guangzhou / 中华流行病学杂志

Objective: To study the willingness and influence factors related to "centralized slaughtering, fresh poultry listing and marketing" strategy, among the household chefs, and provide reference for government to adjust and optimize the strategy on avian influenza prevention. Methods: According to the geographical characteristics and regional functions, 6 'monitoring stations' were selected from 12 residential districts of Guangzhou, respectively. Another 21 meat markets which selling live poultry, were selected in each station and 5 household chefs of each market were invited to attend a face to face interview. Basic information, personal cognitive, willingness and influencing factors to the policy were under study. Univariate and multivariate logistic regression methods were used. Results: A total of 664 household chefs underwent the survey and results showed that the rate of support to the "centralized slaughtering, fresh poultry listing and marketing" strategy was 44.6% (296/664). Results from the multi-factor logistic regression showed that those household chefs who were males (OR=1.618, 95% CI: 1.156-2.264, P=0.005), having received higher education (OR=1.814, 95% CI: 1.296-2.539, P=0.001), or believing that the existence of live poultry stalls was related to the transmission of avian influenza (OR=1.918, 95% CI: 1.341-2.743, P<0.001) were factors at higher risk. These household chefs also intended to avoid the use of live poultry stalls (OR=1.666, 95%CI: 1.203-2.309, P=0.002) and accept the "centralized slaughtering, fresh poultry listing and marketing" strategy. Conclusion: Detailed study on this subject and, setting up pilot project in some areas as well as prioritizing the education programs for household chefs seemed helpful to the implementation of the 'freezing-fresh poultry' policy.

A case of human infection with highly pathogenic avian influenza A (H7N9) virus through poultry processing without protection measure / 中华流行病学杂志

Objective: To investigate the infection pattern and etiological characteristics of a case of human infection with highly pathogenic avian influenza A (H7N9) virus and provide evidence for the prevention and control of human infection with highly pathogenic avian influenza virus. Methods: Epidemiological investigation was conducted to explore the case's exposure history, infection route and disease progression. Samples collected from the patient, environments and poultry were tested by using real time reverse transcriptase-polymerase chain reaction (RT-PCR). Virus isolation, genome sequencing and phylogenetic analysis were conducted for positive samples. Results: The case had no live poultry contact history, but had a history of pulled chicken processing without taking protection measure in an unventilated kitchen before the onset. Samples collected from the patient's lower respiratory tract, the remaining frozen chicken meat and the live poultry market were all influenza A (H7N9) virus positive. The isolated viruses from these positive samples were highly homogenous. An insertion which lead to the addition of multiple basic amino acid residues (PEVPKRKRTAR/GL) was found at the HA cleavage site, suggesting that this virus might be highly pathogenic. Conclusions: Live poultry processing without protection measure is an important infection mode of "poultry to human" transmission of avian influenza viruses. Due to the limitation of protection measures in live poultry markets in Guangzhou, it is necessary to promote the standardized large scale poultry farming, the complete restriction of live poultry sales and centralized poultry slaughtering as well as ice fresh sale.

Influenza vaccination and its influencing factors among clinical staff of the hospitals in 2016-2017 season, Xining, Qinghai province, China / 中华流行病学杂志

Objective: To investigate the influenza vaccination and its influencing factors among the clinical staff in Xining, Qinghai province, in the 2016-2017 influenza season, and to explore the promoting strategies to encourage the target population for influenza vaccination. Methods: Four sample hospitals were randomly selected from the total 11 tertiary hospitals in Xining city. Clinical staff that worked in the four hospitals and agreed to participate were recruited for investigation via a self-administered questionnaire. Results: During the 2016-2017 influenza season, the coverage rate of influenza vaccines among the clinical staff was 5.14% (95%CI: 4.80%-5.49%). Multivariate logistic regression showed that knowing the priority of vaccination, the frequency of vaccination, effect of vaccination, and possessing higher professional qualifications were major influencing factors for influenza vaccination. The intention on recommendation of seasonal influenza vaccine was higher in vaccinated group than that in the unvaccinated group (χ(2)=99.57, P<0.001). Conclusion: The lower coverage rate was primarily associated with the lack of knowledge about influenza vaccine among the clinical staff of the hospital. Tailored information should be provided to the clinical staff through effective methods to improve vaccination and the recommendation of influenza vaccine.

Epidemiologic survey on the prevalence and distribution of infants' common gastrointestinal symptoms in 7 cities in China: a population-based study / 中华流行病学杂志

Objective: Regurgitation, infantile colic, and functional constipation are common gastrointestinal symptoms in childhood, the aim of this study was to explore the prevalence and distribution of these symptoms in China. Methods: A screening program in infants aged 0 to 3 years selected through stratified cluster random sampling was carried out in 7 cities in China. Questionnaires were filled, and then diagnosis were made according to Rome Ⅳ criteria. Areas, (urban-rural), age and gender distribution of prevalence of childhood common gastrointestinal symptoms were analyzed. Results: Totally, 20 932 effective questionnaires were returned. The total number of infants aged 0 to 1 years was 10 193. Regurgitation was diagnosed in 1 960 infants, with the prevalence of 19.2%, among infants aged 0 to 3 months that had highest prevalence (29.8%). The prevalence decreased with age, and differences among different age groups showed significant. For infantile colic, 4 470 infants aged 0 to 5 months were analyzed and the prevalence of infantile colic was 7.3%. The prevalence of infantile colic was the highest in infants aged 1 to 2 months (10.0%). Age specific difference was significant. Of all the infants, functional constipation was diagnosed in 1 755 infants with the prevalence of 8.4%, and the lowest prevalence was found in infants aged 0 to 3 months (6.2%), and the highest prevalence was in infants aged 30 to 36 months (10.0%). The differences in different age group were significant. Conclusion: Symptoms of regurgitation, infantile colic, and functional constipation are common in infants in China, with age specific difference in prevalence of the symptoms.

Current status of national free antiretroviral therapy in interprovincial migrating people living with HIV/AIDS and influencing factors, China, 2011-2015 / 中华流行病学杂志

Objective: To understand the current status of national free antiretroviral therapy in interprovincial migrating people living with HIV/AIDS (PLWHA) and influencing factors in China. Methods: Descriptive and trend test analyses were performed to evaluate the historical characteristics and trends of main descriptive indicators on national free antiretroviral therapy for the interprovincial migrating PLWHA by using the data collected from National Comprehensive HIV/AIDS Information System from 2011 to 2015. Logistic regression model was used to explore the main factors that influencing the coverage of national free antiretroviral therapy among the interprovincial migrating PLWHA in China. Results: The proportion of interprovincial migrating PLWHA gradually increased in last 5 years from 7.1% (17 784/250 645) in 2011 to 10.3% (54 596/528 226) in 2015 (Z=51.38, P<0.000 1) in China. The coverage rate of free antiretroviral therapy in interprovincial migrating PLWHA increased from 37.3% (6 641/17 784) in 2011 to 71.0% (38 783/54 596) in 2015, showing a significant rising tendency (Z=96.23, P<0.000 1), but it was slightly lower than that in non-interprovincial migrating PLWHA in 2015 (71.5%, 338 654/473 630). Multivariate logistic regression analysis showed that the PLWHA who were females, aged ≥50 years, of Han ethnic group, married or had spouse, had the educational level of high school or above, infected through homosexual intercourse, with CD(4)(+)T cells counts ≤500 cells/μl at the first visit, identified to be infected with HIV in medical setting, living in urban areas et al, were more likely to receive free antiretroviral therapy. Conclusions: The coverage rate of free antiretroviral therapy varied among the interprovincial migrating PLWHA with different characteristics. It is still necessary to take effective measures to further increase the coverage of free antiretroviral therapy in interprovincial migrating PLWHA and to include the free antiretroviral therapy in interprovincial migrating PLWHA into standardized management system as soon as possible.

Series study on the relationship between air quality index and tuberculosis incidence in Beijing / 中华流行病学杂志

Objective: To analyze the effect of air quality index (AQI) on the incidence of tuberculosis (TB) in Beijing, and to provide evidence for setting up a better program regarding prevention and control of tuberculosis. Methods: Generalized additive model (GAM) was used to analyze the association between AQI and the incidence of tuberculosis in Beijing, from January 1, 2014 to November 9, 2016. Confounding factors as meteorological conditions and time trends were under control. Results: In Beijing, a total of 14 533 TB cases with definite dates of onset were collected during the study period, with 36 children excluded from the study. Finally, 14 497 cases were included in the study, including 9 513 men and 4 984 women, with 11 290 adults (15-59 years old) and 3 207 elderly (≥60 years old). Data from the optimal single-day lag effect of GAM showed that,with every 10 increase of AQI, the percent of increase on the onsets of overall, male, female and adult; tuberculosis cases were 0.85% (95%CI: 0.26%-1.44%), 0.83% (95%CI: 0.24%-1.42%), 0.93% (95%CI: 0.24%-1.62%) and 0.88% (95%CI: 0.29%-1.46%), respectively. The optimal lag time of the single-day effects were 15 days (lag15), but 16 days (lag16) for male. The optimal cumulative lag effect showed that with every 10 AQI increase, the percent of increase on the onsets of overall, male, female and adult tuberculosis cases were 1.92% (95%CI: 0.23%-3.16%), 1.94% (95%CI:0.15%-3.72%), 2.04% (95%CI: 0.10%-3.97%) and 2.00% (95%CI: 0.30%-3.69%), respectively, with the optimal lag time of cumulative delayed effects as 17 days (lag0_17), 18 days (lag0_18), 16 days (lag0_16) and 17 days (lag0_17), respectively. However, there were no statistical significances noticed in the elderly cases. Conclusion: There was a positive correlation between AQI and the number of TB cases in Beijing, and the effects of AQI on the number of TB cases in different genders and age groups were different.

Exposure to Cerium Oxide Nanoparticles Is Associated With Activation of Mitogen-activated Protein Kinases Signaling and Apoptosis in Rat Lungs / 예방의학회지

OBJECTIVES: With recent advances in nanoparticle manufacturing and applications, potential exposure to nanoparticles in various settings is becoming increasing likely. No investigation has yet been performed to assess whether respiratory tract exposure to cerium oxide (CeO2) nanoparticles is associated with alterations in protein signaling, inflammation, and apoptosis in rat lungs. METHODS: Specific-pathogen-free male Sprague-Dawley rats were instilled with either vehicle (saline) or CeO2 nanoparticles at a dosage of 7.0 mg/kg and euthanized 1, 3, 14, 28, 56, or 90 days after exposure. Lung tissues were collected and evaluated for the expression of proteins associated with inflammation and cellular apoptosis. RESULTS: No change in lung weight was detected over the course of the study; however, cerium accumulation in the lungs, gross histological changes, an increased Bax to Bcl-2 ratio, elevated cleaved caspase-3 protein levels, increased phosphorylation of p38 MAPK, and diminished phosphorylation of ERK-1/2-MAPK were detected after CeO2 instillation (p<0.05). CONCLUSIONS: Taken together, these data suggest that high-dose respiratory exposure to CeO2 nanoparticles is associated with lung inflammation, the activation of signaling protein kinases, and cellular apoptosis, which may be indicative of a long-term localized inflammatory response.