DNA methylation heterogeneity attributable to a complex tumor immune microenvironment prompts prognostic risk in glioma.

Gliomas are malignant tumours of the human nervous system with different World Health Organization (WHO) classifications, glioblastoma (GBM) with higher grade and are more malignant than lower-grade glioma (LGG). To dissect how the DNA methylation heterogeneity in gliomas is influenced by the complex cellular composition of the tumour immune microenvironment, we first compared the DNA methylation profiles of purified human immune cells and bulk glioma tissue, stratifying three tumour immune microenvironmental subtypes for GBM and LGG samples from The Cancer Genome Atlas (TCGA). We found that more intermediate methylation sites were enriched in glioma tumour tissues, and used the Proportion of sites with Intermediate Methylation (PIM) to compare intertumoral DNA methylation heterogeneity. A larger PIM score reflected stronger DNA methylation heterogeneity. Enhanced DNA methylation heterogeneity was associated with stronger immune cell infiltration, better survival rates, and slower tumour progression in glioma patients. We then created a Cell-type-associated DNA Methylation Heterogeneity Contribution (CMHC) score to explore the impact of different immune cell types on heterogeneous CpG site (CpGct) in glioma tissues. We identified eight prognosis-related CpGct to construct a risk score: the Cell-type-associated DNA Methylation Heterogeneity Risk (CMHR) score. CMHR was positively correlated with cytotoxic T-lymphocyte infiltration (CTL), and showed better predictive performance for IDH status (AUC = 0.96) and glioma histological phenotype (AUC = 0.81). Furthermore, DNA methylation alterations of eight CpGct might be related to drug treatments of gliomas. In conclusion, we indicated that DNA methylation heterogeneity is associated with a complex tumour immune microenvironment, glioma phenotype, and patient's prognosis.

Development of a novel dynamic nosocomial infection risk management method for COVID-19 in outpatient settings.

BACKGROUND: Application of accumulated experience and management measures in the prevention and control of coronavirus disease 2019 (COVID-19) has generally depended on the subjective judgment of epidemic intensity, with the quality of prevention and control management being uneven. The present study was designed to develop a novel risk management system for COVID-19 infection in outpatients, with the ability to provide accurate and hierarchical control based on estimated risk of infection. METHODS: Infection risk was estimated using an auto regressive integrated moving average model (ARIMA). Weekly surveillance data on influenza-like-illness (ILI) among outpatients at Xuanwu Hospital Capital Medical University and Baidu search data downloaded from the Baidu Index in 2021 and 22 were used to fit the ARIMA model. The ability of this model to estimate infection risk was evaluated by determining the mean absolute percentage error (MAPE), with a Delphi process used to build consensus on hierarchical infection control measures. COVID-19 control measures were selected by reviewing published regulations, papers and guidelines. Recommendations for surface sterilization and personal protection were determined for low and high risk periods, with these recommendations implemented based on predicted results. RESULTS: The ARIMA model produced exact estimates for both the ILI and search engine data. The MAPEs of 20-week rolling forecasts for these datasets were 13.65% and 8.04%, respectively. Based on these two risk levels, the hierarchical infection prevention methods provided guidelines for personal protection and disinfection. Criteria were also established for upgrading or downgrading infection prevention strategies based on ARIMA results. CONCLUSION: These innovative methods, along with the ARIMA model, showed efficient infection protection for healthcare workers in close contact with COVID-19 infected patients, saving nearly 41% of the cost of maintaining high-level infection prevention measures and enhancing control of respiratory infections.

CRF07_BC is associated with slow HIV disease progression in Chinese patients.

HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count < 200 cells/µL) in patients with HIV subtype B, CRF01_AE, and CRF07_BC. Of the 20,663 sequences, 9,156 (44.3%) were CRF01_AE. CRF07_BC was responsible for 28.3% of infections, followed by B (13.9%). In multivariable analysis, the risk of AIDSAD differed significantly according to HIV subtype (OR for CRF07_BC vs. B: 0.46, 95% CI 0.39─0.53), age (OR for ≥ 65 years vs. < 18 years: 4.3 95% CI 1.81─11.8), and transmission risk groups (OR for men who have sex with men vs. heterosexuals: 0.67 95% CI 0.6─0.75). These findings suggest that HIV diversity in China is constantly evolving and gaining in complexity. CRF07_BC is less pathogenic than subtype B, while CRF01_AE is as pathogenic as B.

A Semi-Quantitative Risk Assessment and Management Strategies on COVID-19 Infection to Outpatient Health Care Workers in the Post-Pandemic Period.

BACKGROUND: In the pandemic of COVID-19, due to asymptomatic patients and high personnel fluidity in outpatient clinics, health care workers (HCWs) in outpatients were facing severe threat from infection. There is an urgent need for a risk assessment to recognize and prevent infection risks. PURPOSE: To establish a semi-quantitative risk assessment model on COVID-19 infections for HCWs in outpatient departments, and apply it to practices. Further to provide infection risk management strategies to reduce infection threats in the post-pandemic of COVID-19. METHODS: We used the method of Brainstorm, Literature study and Analytic Hierarchy Process (AHP) for risk factors selection and model construction, we also created corresponding indicators for each risk factors, in order to collect data in assessment practice. RESULTS: Eighteen risk factors were recognized and selected for model construction, by scatter plot, these risk factors had been classified into four parts, spanned the scopes of diagnosis and treatment, environment, personal protection and emergency handling, with specific management suggestions provided. In the practice, outpatient clinics were divided into three risk levels, 5 clinics in high risk level, 9 in medium risk level and 11 in low risk level. CONCLUSION: A proper comprehensive risk assessment model for COVID-19 infections has been successfully established. With the model, the ability to COVID-19 prevention in outpatients can be easily evaluated. The strategies on disinfection, surveillance and personal protection were also valuable references in the post-pandemic of COVID-19.

Transcriptomic and Functional Evidence Show Similarities between Human Amniotic Epithelial Stem Cells and Keratinocytes.

Amniotic epithelial stem cells (AESCs) are considered as potential alternatives to keratinocytes (KCs) in tissue-engineered skin substitutes used for treating skin damage. However, their clinical application is limited since similarities and distinctions between AESCs and KCs remain unclear. Herein, a transcriptomics analysis and functional evaluation were used to understand the commonalities and differences between AESCs and KCs. RNA-sequencing revealed that AESCs are involved in multiple epidermis-associated biological processes shared by KCs and show more similarity to early stage immature KCs than to adult KCs. However, AESCs were observed to be heterogeneous, and some possessed hybrid mesenchymal and epithelial features distinct from KCs. A functional evaluation revealed that AESCs can phagocytose melanosomes transported by melanocytes in both 2D and 3D co-culture systems similar to KCs, which may help reconstitute pigmented skin. The overexpression of TP63 and activation of NOTCH signaling could promote AESC stemness and improve their differentiation features, respectively, bridging the gap between AESCs and KCs. These changes induced the convergence of AESC cell fate with KCs. In future, modified reprogramming strategies, such as the use of small molecules, may facilitate the further modulation human AESCs for use in skin regeneration.

Characterization of subtypes and transmitted drug resistance strains of HIV among Beijing residents between 2001-2016.

BACKGROUND: Beijing is a national and international hub potentially containing a broad diversity of HIV variants. Previous studies on molecular epidemiology of HIV in Beijing pooled together samples from residents and non-residents. Pooling residents and non-residents has potentially introduced bias and undermined a good assessment and the intervention among the autochthonous population. Here, we aimed to define HIV subtype diversity and investigate the TDR in Beijing residents exclusively. METHODS: We analyzed the demographic, clinical, and virological data collected between 2001 and 2016 from residents in Beijing. A population-based sequencing of the HIV pol gene was carried out using plasma specimens. Phylogenetic analysis was performed in order to classify sequences into their corresponding subtypes using an automated subtyping tool, the Context-Based Modeling for Expeditious Typing (COMET). Furthermore, the drug resistance mutations were determined using the World Health Organization list for surveillance of TDR mutations. RESULTS: Data on TDR were available for 92% of 2,315 individuals with HIV infection, of whom 7.1% were women. The bioinformatic analysis of HIV strains from this study revealed that a combined 17 subtypes were circulating in Beijing, China between 2001 and 2016. The most common ones were CRF01_AE, CRF07_BC, and subtype B in Beijing during this period. The overall prevalence of TDR was 4.5% (95% confidence intervals[CI]: 3.6%-5.4%), with a declining trend over the period of spanning 2001 through 2016. In-depth class-specific analysis revealed that the prevalence of TDR for the nucleoside reverse-transcriptase inhibitors (NRTIs) was 1.0% (95% CI: 0.6-1.5), 0.9% (95% CI:0.6-1.4) for non-NRTIs and 2.8% (95% CI:2.1-3.5) for protease inhibitors. The prevalence of TDR was lower in individuals infected with the CRF07_BC HIV strain than those infected with CRF01_AE. CONCLUSIONS: Our data showed that the HIV epidemic in Beijing displayed a high genetic heterogeneity and a low and declining prevalence of TDR. In sharp contrast to Europe and North America, the declining trend of TDR between 2001 through 2016 was noticed while there was a widespread distribution of antiretroviral treatment in Beijing, China.

Transmitted HIV drug resistance among individuals with newly diagnosed HIV infection: a multicenter observational study.

OBJECTIVES: Fifteen years after the roll-out of antiretroviral treatment (ART) in China, there is limited information available on transmitted HIV drug resistance (TDR). This study aimed to characterize the epidemiology of TDR in China. DESIGN: We conducted a prospective cross-sectional observational study. METHODS: We analyzed the demographic, clinical, and virological data of individuals with newly diagnosed HIV infection using data from the Beijing HIV laboratory network collected between 2001 and 2017. We did population-based sequencing of the pol gene on plasma specimens and identified TDR mutations using the WHO list for surveillance of TDR mutations. RESULTS: Data on TDR were available for 91% of the 10 115 individuals with newly diagnosed HIV infection tested, of whom 19.2% were from rural areas. The overall prevalence of TDR was 4.1% [95% confidence interval (CI): 3.7-4.5%], with a declining trend over the period 2001-2017. In the multivariable analysis, the risk of TDR differed significantly according to sex [odds ratio (OR) for women vs. men: 0.41, 95% CI: 0.22-0.69, P = 0.002]; infection type (OR for CRF07_BC vs. CRF01_AE: 0.24, 95% CI: 0.16-0.36, P < 0.001); and sampling period (OR for 2009-2012 vs. 2001-2008: 0.57, 95% CI: 0.41-0.79; P = 0.01), and was significantly higher among individuals from Hebei province than in those from Beijing (OR: 1.43, 95% CI: 1.05-1.96; P = 0.02). CONCLUSION: In China, the prevalence of TDR among individuals with newly diagnosed HIV infection is relatively low. Trends in TDR should be assessed in other countries with a high TDR burden.

[Rupture of Coronary Artery Aneurysm with Coronary Artery to Pulmonary Artery Fistula;Report of a Case].

We report a rare case of ruptured coronary artery aneurysm. A 58-year-old woman experienced a sudden chest pain. Coronary arteriography( CAG) and computed tomography(CT) showed pericardial effusion and 2 saccular coronary artery aneurysms connected by a communicating artery. The 1st one was originated from the right coronary artery and flowed to the communicating artery. The 2nd one was originated from both the diagonal branch and the communicating artery, and flowed to the main pulmonary artery, forming a fistula. Since the 1st one was larger, it was suspected to be the rupture site. Emergency operation was performed and the aneurysms were directly closed under cardiopulmonary bypass. The postoperative course was uneventful.

Co-evolution of compensatory mutation K43E with mutation M41L in long-term HIV antiretroviral treatment.

BACKGROUND: Compensatory mutations have been observed to emerge with drug resistance (DR) mutations, but their effects on virological response to treatment have not been fully examined. In this study, we characterized the emergence and depletion dynamics of a compensatory mutation K43E that correlated with primary nucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations in Chinese HIV patients on antiretroviral treatment. METHOD: Single Genome Amplification (SGA) was used to obtain the HIV-1 pol gene quasispecies in three patients over 6 years of Antiretroviral Therapy (ART) treatment. SGA sequences were analyzed by Markov Chain Monte Carlo (MCMC) phylogenetic trees with molecular clock to identify and track compensatory mutation K43E correlated with primary DR mutation M41L. We evaluated the relationship between potential compensatory mutation and DR mutations through Ka/Ks ratio, Jaccard similarity coefficient, and compared these with concurrent viral load data. CONCLUSION: We determined that a known compensatory mutation, K43E, frequently co-occurs with the drug resistance mutation M41L and may offer a significant advantage in the long-term survival of such drug resistant strains.

The development of drug resistance mutations K103N Y181C and G190A in long term Nevirapine-containing antiviral therapy.

OBJECTIVE: We built a cohort study of HIV patients taking long-term first-line Antiretroviral Therapy in 2003. In this assay, we focused on the development of primary drug resistance mutations against Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), K103N, Y181C and G190A. METHOD: The cohort study was built in Henan province, China. We used Single Genome Amplification (SGA) to analyze the frequency of K103N, Y181C and G190A in serial plasma samples of three individual patients. We also performed standard genotype HIV drug resistance assay in 204 patients of this cohort study to analyze the frequency of these mutations. RESULT: In the SGA sequences, the K103N decreased and vanished, while the frequency of Y181C and G190A increased in individual patient receiving long-term Antiretroviral Therapy (ART). In the sequences of standard genotype HIV drug resistance assay, the frequency of K103N, Y181C and G190A had the similar pattern with that in SGA sequences. Among these patients, the viral suppression were still sufficient after receiving ART for 72 months, and 78.6% (160/204) patients could have their CD4 count over than 200cells/ul. CONCLUSION: In some patients, first-line ART had the possibility to provide sufficient treatment effect for over than 72 months, but in long-term treatment, the dominant NNRTI drug resistance mutation K103N could reduced, while the proportion of variants with mutation Y181C or G190A may increased. This result was not similar with that in vitro study, which state that variant with K103N or Y181C had an equal viral fitness with wild type.

Aortic valve replacement in a porcelain aorta using endo balloon occlusion.

Aortic valve surgery carries increased risks in patients with an extensively calcified aorta. We describe a technique in which we maintain systemic perfusion via bilateral axillary artery perfusion in conjunction with endoaortic balloon occlusion, and limit the circulatory arrest time.

[The study of an in-house method for drug resistance genotyping testing on HIV-1 strains prevailing in China].

OBJECTIVE: To evaluate the amplification rate and the lowestlower detection limit of an in-house HIV-1 Drug resistant (HIVDR) genotyping test. METHODS: A total of 30 plasma samples were selected, which covered all major HIV-1 subtypes predominating prevailing in China (B', CRF07_BC, CRF01 _AE). The viral loads of the 30 selected samples were detected in triplicate by Easy Q method and the average values were taken as the viral loads of the samples. Each sample was diluted to the concentration of > 1000 copies/ml, 401-1000 copies/ml, 101-400 copies/ml, 50-100 copies/ml and < 50 copies/ml with HIV-negative plasma. After extraction of nucleic acids, RT-PCR and nested PCR amplification were performed, the efficiency of amplification of each subtype and the minimum detection limit were determined statistically based on the PCR results. RESULTS: The viral loads of the selected samples ranged from 2.03 x 10(2)-5.92 x 10(4) copies/ml. The sample of 50-1000 copies/ml have a high amplification rate (86%). CONCLUSION: The In-house method for HIV-1 drug resistance genotyping has a high sensitivity with a high successful amplification rate, especially in the samples with low viral load. This method can be used to the detection of drug-resistant virus and to provide scientific data to treatment options for patients.