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Objective:To evaluate the in vitro antifungal activity of berberine against Talaromyces marneffei (TM) in yeast phase. Methods:There were 21 TM strains, including l standard strain (ATCC22019), 10 clinical isolates and 10 isolates from wild bamboo rats. TM strain suspensions at a concentration of (1 - 5) × 10 3 colony-forming units/ml were incubated in microdilution plates containing difierent concentrations of berberine, fluconazole, itraconazole, voriconazole, amphotericin B or caspofungin at 37 ℃ for 48 hours. Meanwhile, the wells containing only culture media and TM strains but without antifungal drugs served as the positive control group, and those containing only culture media served as the negative control group. The minimum inhibitory concentrations (MICs) of antifungal drugs against TM yeasts were determined according to the Clinical and Laboratory Standards Institute (CLSI) broth microdilution susceptibility method (M27-A3 document) . Results:The MICs of the above antifungal drugs were all within the reference ranges for the quality control strain (ATCC22019), and TM strains grew well in the positive control wells. The MIC ranges of berberine, itraconazole, voriconazole, amphotericin B and caspofungin against TM strains were 32 - 64 mg/L, 0.06 - 0.125 mg/L, 0.06 - 0.125 mg/L, 1 - 2 mg/L and 16 - 32 mg/L respectively; the MIC range of fluconazole was 2 - 4 mg/L for non-resistant strains, and 128 mg/L for fluconazole-resistant clinical strains.Conclusion:Berberine exhibits antifungal activity against TM in yeast phase.
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Objective:To establish an in vivo diffusion model of Treponema pallidum (Tp) in New Zealand rabbits. Methods:A standard strain of Tp (Nichols strain) was recovered in the testes of New Zealand rabbits, and isolated and passaged continuously. The suspensions of the second-passage Tp were collected and inoculated onto the dorsal skin of New Zealand rabbits. After 21-day infection, the New Zealand rabbits were anesthetized and sacrificed, blood samples were collected, and skin tissues at the infection site as well as liver, spleen, testes and lymph nodes were aseptically resected. Real-time fluorescence-based quantitative PCR was performed to detect the spread of Tp in different tissues and organs.Results:On day 21 after infection with Tp, skin lesions such as indurations and ulcers were seen at all inoculated sites of New Zealand rabbits. Pathological examination showed a lot of inflammatory cells in the infected lesions, mainly including plasma cells, macrophages and lymphocytes. Real-time fluorescence-based quantitative PCR revealed a large number of Tp in tissues and organs, such as liver, spleen and testes.Conclusion:After inoculation with Tp in the dorsal skin of New Zealand rabbits, Tp could spread to the liver, spleen, testes and other tissues and organs through blood and lymph nodes, and the in vivo diffusion model of Tp strains in New Zealand rabbits was successfully constructed.
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Objective:To investigate the influencing factors for lung metastasis of hepato-cellular carcinoma after liver transplantation and application value of its nomogram prediction model.Methods:The retrospective cohort study was conducted. The clinicopathological data of 339 hepatocellular carcinoma patients with lung metastasis after liver transplantation who were admitted to Zhongshan Hospital of Fudan University from January 2015 to June 2019 were collected. There were 299 males and 40 females, aged from 23 to 73 years, with a median age of 54 years. According to the random numbers showed in the computer, all 339 patients were divided into training dataset consisting of 226 and validation dataset consisting of 113, with a ratio of 2:1. All patients underwent classic orthotopic liver transplantation. Observation indicators: (1) analysis of clinicopathological data of patients in the training dataset and validation dataset; (2) follow-up; (3) analysis of influencing factors for lung metastasis of hepatocellular carcinoma after liver transplanta-tion; (4) construction and evaluation of nomogram prediction model for lung metastasis of hepatocellular carcinoma after liver transplantation. Follow-up was conducted using outpatient examination and telephone interview to detect lung metastasis of patients up to November 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the paired t test. Measurement data with skewed distribution were represented as M( P25, P75) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute number or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate lung metastasis rate and draw lung metastasis curve. The Log-rank test was used for survival analysis. The COX proportional hazard model was used for univariate and multivariate analysis. Based on the results of multivariate analysis, the nomogram prediction model was constructed. The prediction accuracy of the nomogram model was evaluated using C-index and receiver operating characteristic (ROC) curve. The calibration curve was used to evaluate the prediction error of the model. Results:(1) Analysis of clinicopathological data of patients in the training dataset and validation dataset: there was no significant difference in general data between patients in the training dataset and validation dataset ( P>0.05). (2) Follow-up: 226 patients in training dataset and 113 patients in validation dataset were followed up. The follow-up time of training dataset was 5.2 to 69.0 months, with a median follow-up time of 29.3 months, and the follow-up time of validation dataset was 4.3 to 69.0 months, with a median follow-up time of 30.4 months. Up to the last follow-up, 48 cases of the training dataset and 22 cases of the validation dataset had lung metastasis, with the incidence and median time of lung metastasis were 21.24%(48/226), 19.47%(22/113) and 8.5 months, 7.8 months, respectively. There was no significant difference in lung metastasis between patients in the training dataset and validation dataset ( χ2=0.144, P>0.05). (3) Analysis of influencing factors for lung metastasis of hepatocellular carcinoma after liver transplantation: results of univariate analysis showed that age, alpha fetoprotein, tumor diameter, tumor differentiation degree, vascular invasion, systemic immune inflammation index and postoperative treatment were related factors for lung metastasis of hepatocellular carcinoma after liver transplantation ( hazard ratio=0.465, 3.413, 1.140, 3.791, 2.524, 2.053, 1.833, 95% confidence interval as 0.263?0.822, 1.740?6.695, 1.091?1.191, 1.763?8.154, 1.903?3.349, 1.047?4.027, 1.038?3.238, P<0.05) . Results of multivariate analysis showed that age, tumor diameter and vascular invasion were independent influencing factors for lung metastasis of hepatocellular carcinoma after liver transplantation ( hazard ratio=0.462, 1.076, 2.170, 95% confidence interval as 0.253?0.843, 1.013?1.143, 1.545?3.048, P<0.05). (4) Construction and evaluation of nomogram prediction model for lung metastasis of hepatocellular carcinoma after liver transplantation: the C-index was 0.810 (95% confidence interval as 0.758?0.863) and 0.802 (95% confidence interval as 0.723?0.881) of the nomogram prediction model for lung metastasis of hepatocellular carcinoma after liver transplanta-tion in the training dataset and validation dataset, respectively, showing good discrimination ability. The area under ROC of 0.5-, 1- and 2-year nomogram prediction model in the training dataset and the validation dataset were 0.815(95% confidence interval as 0.725?0.905), 0.863(95% confidence interval as 0.809?0.917), 0.835(95% confidence interval as 0.771?0.900)and 0.873(95% confidence interval as 0.801?0.945), 0.858(95% confidence interval as 0.760?0.956), 0.841(95% confidence interval as 0.737?0.945), respectively, which illustrated that the model had good predictive ability. The formula of nomogram prediction model=33.300 06+(?33.300 06)×age(≤50 years=0, >50 years=1)+2.857 14×tumor diameter (cm)+31.585 71×vascular invasion (M0 stage of microvascular invasion staging=0, M1 stage of microvascular invasion staging=1, M2 stage of microvascular invasion staging=2, visible tumor thrombus=3). The optimal threshold of nomogram risk score was 77.5. Patients with risk score ≥77.5 were assigned into high risk group, and patients with risk score <77.5 were assigned into low risk group. The 0.5-,1- and 2-year lung metastasis rate of patients in the high risk group and low risk group of the training dataset were 16.7%, 39.2%, 46.4% and 1.4%, 4.1%, 6.9%, respectively, showing a significant difference between the two groups ( χ2=54.86, P<0.05). The 0.5-,1- and 2-year lung metastasis rate of patients in the high risk group and low risk group of the validation dataset were 17.6%, 29.0%, 39.5% and 0, 3.1%, 4.8%, respectively, showing a significant difference between the two groups ( χ2=25.29, P<0.05). Conclusions:Age, tumor diameter and vascular invasion are independent influencing factors for lung metastasis of hepatocellular carcinoma after liver transplantation. The nomogram prediction model based on age, tumor diameter and vascular invasion can predict risk of lung metastasis for hepatocellular carcinoma patients after liver transplantation accurately.
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The Corona Virus Disease 2019 (COVID-19) that occurred December of 2019 has a wide range of impacts, and its epidemic situation is grim. China has a large population of liver cancer, accounting for 50% of new cases of liver cancer worldwide. How to ensure the diagnosis, treatment and rehabilitation of liver cancer patients while preventing and controlling the epidemic situation is an issue that urgently need specialists pay attention to. The authors propose an overall management model for patients with liver cancer, combined with their own experience, in order to guide specialists to safely and effectively carry out clinical diagnosis and treatment of liver cancer during the prevention and control of epidemics, and to help liver cancer patients receive treatment.
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Although the epidemic situation of Corona Virus Disease 2019 (COVID-19) has been controlled, the epidemic situation remains grim. The COVID-19 is highly infectious, with various clinical manifestations including liver injury. The authors make a preliminary investigation on the mechanisms of liver injury related to COVID-19, and put forward correspon-ding control measures for reference.
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Objective To explore the application of projection pursuit model in anti-assessment on peer reviewer of scientific research project,discussing the rational of this application.Methods Establishing the projection pursuit model of anti-assessment on peer reviewer,with the best projection direction as a weight,making an evaluation on the peer reviewer,and sequencing experts by projection value.Results The projection pursuit model is stable and scientific,the importance of index ranking as correlation coefficient＞ dispersion＞ hit rate＞ synthetic dispersion＞ self dispersion ratio.Conclusions The application of projection pursuit model in anti-assessment on peer reviewer of scientific research project,is reasonable and practicable.
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Peer review anti assessment includes the evaluation of expert and index system in two parts.The current status of anti-assessment study mainly focused on expert,much of the index system anti-assessment study reports.As can be seen from the status,the anti-assessment system not yet formed and the application is rare.In urgent need of further research to improve our peer-reviewed scientific research.
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It is imperative to apply information technology in the area of management of clinical research so as to ensure the quality of clinical trials and to improve management efficiency.In this study,the based analysis method was the quality function deployment (QFD).This methodology is used to analysis the clinical trials management information system on a hospital directly under the Ministry of Health.It ensured user participation,lay a solid foundation for software engineers on system design.
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Objective To investigate the phenotype,number and distribution of inflammatory cells in early and late stages of spontaneous regression of halo nevi,and to elucidate the immunological mechanisms for spontaneous regression of these nevi.Methods Halo nevi,their surrounding non-lesional skin,and normal control skin were examined by immunohistochemical staining with monoclonal antibodies to CD3,CD4,CD8,CD20,CD1a,CD56 and CD68.Staining results were observed and analyzed by the computer image analysis system,image-pro plus 6.0.Results The number of CD4+,CD8+,CD20+,CD1a+cells,along with the diameter of CD1a+and CD68+ cells was significantly increased in the lesions of early and late stage of spontaneous regression of halo nevi than in non-lesional skin and normal control skin(both P＜0.01).The ratio of CD8+/CD4+ cells in the lesions of late stage of spontaneous regression was also higher than that in the lesions of early stage (2.05∶1 VS 1.82∶1).A massive infiltrate of CD8+ cells was observed in the nests of nevus cells.ConclusionsCD4,CD8,CD20,CD1a,CD56 and CD68 positive cells are all involved in the spontaneous regression of halo nevi,and CD8+ cells may play a predominant role in this process.