Shared Immune Associations Between COVID-19 and Inflammatory Bowel Disease: A Cross-Sectional Observational Study in Shanghai, China.

Purpose: The rapid global spread of the SARS-CoV-2 Omicron variant introduces a novel complication: the emergence of IBD (inflammatory bowel disease)-like ulcers in certain patients. This research delves into this new challenge by juxtaposing the clinical manifestations and genetic expression patterns of individuals affected by the Omicron variant of COVID-19 with those diagnosed with IBD. It aims to decode the link between these conditions, potentially shedding light on previously unexplored facets of COVID-19 pathophysiology. This investigation emphasizes gene expression analysis as a key tool to identify wider disease correlations and innovative therapeutic avenues. Patients and Methods: From March to December 2022, patients with SARS-CoV-2 Omicron infection and inflammatory bowel disease and healthy controls were recruited in Shanghai East Hospital, Shanghai, China. The epidemiological and clinical characteristics of the patients were compared. Four RNA sequencing datasets (GSE205244, GSE201530, GSE174159, and GSE186507) were extracted from the Gene Expression Omnibus database to detect mutually differentially expressed genes and common pathways in patients with SARS-CoV-2 infection and inflammatory bowel disease. Results: Compared to patients with active inflammatory bowel disease, patients with SARS-CoV-2 infection were more likely to have elevated interferon-α levels and an increased lymphocyte count and less likely to have high interleukin-6, tumor necrosis factor-α, and C-reactive protein levels and an elevated neutrophil count. A total of 51 common differentially expressed genes were identified in the four RNA-sequencing datasets. Enrichment analysis suggested that these genes were related to inflammation and the immune response, especially the innate immune response and nucleotide oligomerization domain-like receptor signaling pathway. Conclusion: The inflammation and immune-response pathways in COVID-19 and inflammatory bowel disease have several similarities and some differences. The study identifies the NLR signaling pathway's key role in both COVID-19 and IBD, suggesting its potential as a target for therapeutic intervention and vaccine development.

Effectiveness of Hypertension Management Strategies in SPRINT-Eligible US Adults: A Simulation Study.

BACKGROUND: Despite reducing cardiovascular disease (CVD) events and death in SPRINT (Systolic Blood Pressure Intervention Trial), intensive systolic blood pressure goals have not been adopted in the United States. This study aimed to simulate the potential long-term impact of 4 hypertension management strategies in SPRINT-eligible US adults. METHODS AND RESULTS: The validated Blood Pressure Control-Cardiovascular Disease Policy Model, a discrete event simulation of hypertension care processes (ie, visit frequency, blood pressure [BP] measurement accuracy, medication intensification, and medication adherence) and CVD outcomes, was populated with 25 000 SPRINT-eligible US adults. Four hypertension management strategies were simulated: (1) usual care targeting BP <140/90 mm Hg (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care), (2) intensive care per the SPRINT protocol targeting BP <120/90 mm Hg (SPRINT intensive), (3) usual care targeting guideline-recommended BP <130/80 mm Hg (American College of Cardiology/American Heart Association usual care), and (4) team-based care added to usual care and targeting BP <130/80 mm Hg. Relative to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, among the 18.1 million SPRINT-eligible US adults, an estimated 138 100 total CVD events could be prevented per year with SPRINT intensive, 33 900 with American College of Cardiology/American Heart Association usual care, and 89 100 with team-based care. Compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, SPRINT intensive care was projected to increase treatment-related serious adverse events by 77 600 per year, American College of Cardiology/American Heart Association usual care by 33 300, and team-based care by 27 200. CONCLUSIONS: As BP control has declined in recent years, health systems must prioritize hypertension management and invest in effective strategies. Adding team-based care to usual care may be a pragmatic way to manage risk in this high-CVD-risk population.

Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China.

Background: The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods: Using a Bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL), and disability in 1082 severely and critically ill patients with COVID-19 between 8 December 2022 and 9 February 2023 in Shanghai, China. The final 60-day follow-up was completed on 10 April 2023. Results: Among 1082 patients (mean age, 78.0 years, 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval, 0.24-0.79]), and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 0.44-1.14]) compared with the control. IL-6 receptor antagonist, baricitinib and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR > 0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06-2.50]) and glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71-2.16]). Paxlovid, Azvudine, and therapeutic anticoagulation showed a significant reduction in disability (p < 0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in a resource-limited scenario. Treatment with an IL-6 receptor antagonist, baricitinib, and a-thymosin also had high probabilities of benefit in improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine, and therapeutic anticoagulation could significantly reduce disability at day 60.

Raman spectromics method for fast and label-free genotype screening.

It is now understood that genes and their various mutations are associated with the onset and progression of diseases. However, routine genetic testing techniques are limited by their high cost, time consumption, susceptibility to contamination, complex operation, and data analysis difficulties, rendering them unsuitable for genotype screening in many cases. Therefore, there is an urgent need to develop a rapid, sensitive, user-friendly, and cost-effective method for genotype screening and analysis. In this study, we propose and investigate a Raman spectroscopic method for achieving fast and label-free genotype screening. The method was validated using spontaneous Raman measurements of wild-type Cryptococcus neoformans and its six mutants. An accurate identification of different genotypes was achieved by employing a one-dimensional convolutional neural network (1D-CNN), and significant correlations between metabolic changes and genotypic variations were revealed. Genotype-specific regions of interest were also localized and visualized using a gradient-weighted class activation mapping (Grad-CAM)-based spectral interpretable analysis method. Furthermore, the contribution of each metabolite to the final genotypic decision-making was quantified. The proposed Raman spectroscopic method demonstrated huge potential for fast and label-free genotype screening and analysis of conditioned pathogens.

Mueller matrix imaging of pathological slides with plastic coverslips.

Mueller matrix microscopy is capable of polarization characterization of pathological samples and polarization imaging based digital pathology. In recent years, hospitals are replacing glass coverslips with plastic coverslips for automatic preparations of dry and clean pathological slides with less slide-sticking and air bubbles. However, plastic coverslips are usually birefringent and introduce polarization artifacts in Mueller matrix imaging. In this study, a spatial frequency based calibration method (SFCM) is used to remove such polarization artifacts. The polarization information of the plastic coverslips and the pathological tissues are separated by the spatial frequency analysis, then the Mueller matrix images of pathological tissues are restored by matrix inversions. By cutting two adjacent lung cancer tissue slides, we prepare paired samples of very similar pathological structures but one with a glass coverslip and the other with a plastic coverslip. Comparisons between Mueller matrix images of the paired samples show that SFCM can effectively remove the artifacts due to plastic coverslip.

Multi-threshold splitting tree algorithm to reduce the number of filters in programmable hyperspectral imaging for fast multi-target classification.

Programmable hyperspectral imaging is a promising and efficient technique for fast target classification by coding hyperspectral post-processing algorithms as spectral transmittances, which enables such post-processing to be directly performed by special optical dispersive element during the process of optical imaging. Compared with conventional hyperspectral imaging and post-processing techniques, it shows significant advantages of fast image acquisition, post-processing free, and a much lower load of data transmission and storage. However, when multi-target classification tasks are encountered, the speed would decrease seriously due to the requirement of a large number of filters. In this study, a novel splitting strategy is proposed to reduce the number of filters in programmable hyperspectral imaging for fast multi-target classification while maintaining the classification performance. Numerical simulation experiments were performed on six publicly available hyperspectral data sets. Compared with the conventional splitting strategies, the proposed splitting strategy can reduce the number of filters by 25% to 80% and achieve similar classification performance, which is of great significance to improve the speed of multi-target classification with programmable hyperspectral imaging technique.

Polarization imaging-based radiomics approach for the staging of liver fibrosis.

Mueller matrix imaging contains abundant biological microstructure information and has shown promising potential in clinical applications. Compared with the ordinary unpolarized light microscopy that relies on the spatial resolution to reveal detailed histological features, Mueller matrix imaging encodes rich information on the microstructures even at low-resolution and wide-field conditions. Accurate staging of liver fibrosis is essential for the therapeutic diagnosis and prognosis of chronic liver diseases. In the clinic, pathologists commonly use semiquantitative numerical scoring systems to determine the stages of liver fibrosis based on the visualization of stained characteristic morphological changes, which require skilled staining technicians and well-trained pathologists. A polarization imaging based quantitative diagnostic method can help to reduce the time-consuming multiple staining processes and provide quantitative information to facilitate the accurate staging of liver fibrosis. In this study, we report a polarization imaging based radiomics approach to provide quantitative diagnostic features for the staging of liver fibrosis. Comparisons between polarization image features under a 4× objective lens with H&E image features under 4×, 10×, 20×, and 40× objective lenses were performed to highlight the superiority of the high dimensional polarization image features in the characterization of the histological microstructures of liver fibrosis tissues at low-resolution and wide-field conditions.

Accelerating Monte Carlo simulation of light propagation in tissue mimicking turbid medium based on generative adversarial networks.

PURPOSE: Monte Carlo (MC) simulation is the most frequently used method to numerically model the light propagation in biological tissues because of its high flexibility and precision. Although MC simulation is assumed to be capable of achieving any desired precision, larger number of photons are always necessary for more precise simulation, leading to its major limitation of intensive computation. In this work, the authors present a way to adapt generative adversarial networks (GAN) to accelerate MC simulation. METHODS: The pix2pix network, a variant of GAN, was investigated to reconstruct precise MC simulation results from the results roughly modeled by small amount of photons, thus the computation time was expected to be significantly saved. The proposed method was tested on single-layer embedded tumor models to derive the absorption distribution maps. RESULTS: The results demonstrate that the absorption distribution maps reconstructed from the simulation of only 10 000 photons were very similar to those modeled by using 1 000 000 photons, based on the criterion of peak signal to noise ratio (PSNR) and percentage difference of power coupling efficiencies, and the simulation process was proved to be accelerated by approximately 102 times. CONCLUSIONS: For the first time, GAN was adapted to save computation time of MC simulation of light propagation. By achieving MC simulation with acceptable quality, the proposed method can speed up the computation by hundreds of times.

Development and validation of a novel epigenetic-related prognostic signature and candidate drugs for patients with lung adenocarcinoma.

BACKGROUND: Epigenetic dysregulation has been increasingly proposed as a hallmark of cancer. Here, the aim of this study is to establish an epigenetic-related signature for predicting the prognosis of lung adenocarcinoma (LUAD) patients. RESULTS: Five epigenetic-related genes (ERGs) (ARRB1, PARP1, PKM, TFDP1, and YWHAZ) were identified as prognostic hub genes and used to establish a prognostic signature. According our risk score system, LUAD patients were stratified into high and low risk groups, and patients in the high risk group had a worse prognosis. ROC analysis indicated that the signature was precise in predicting the prognosis. A new nomogram was constructed based on the five hub genes, which can predict the OS of every LUAD patients. The calibration curves showed that the nomogram had better accuracy in prediction. Finally, candidate drugs that aimed at hub ERGs were identified, which included 47 compounds. CONCLUSIONS: Our epigenetic-related signature nomogram can effectively and reliably predict OS of LUAD patients, also we provide precise targeted chemotherapeutic drugs. METHODS: The genomic data and clinical data of LUAD cohort were downloaded from the TCGA database and ERGs were obtained from the EpiFactors database. GSE31210 and GSE50081 microarray datasets were included as independent external datasets. Univariate Cox, LASSO regression, and multivariate Cox analyses were applied to construct the epigenetic-related signature.

Establishment and validation of a prognostic signature for lung adenocarcinoma based on metabolism-related genes.

BACKGROUND: Given that dysregulated metabolism has been recently identified as a hallmark of cancer biology, this study aims to establish and validate a prognostic signature of lung adenocarcinoma (LUAD) based on metabolism-related genes (MRGs). METHODS: The gene sequencing data of LUAD samples with clinical information and the metabolism-related gene set were obtained from The Cancer Genome Atlas (TCGA) and Molecular Signatures Database (MSigDB), respectively. The differentially expressed MRGs were identified by Wilcoxon rank sum test. Then, univariate cox regression analysis was performed to identify MRGs that related to overall survival (OS). A prognostic signature was developed by multivariate Cox regression analysis. Furthermore, the signature was validated in the GSE31210 dataset. In addition, a nomogram that combined the prognostic signature was created for predicting the 1-, 3- and 5-year OS of LUAD. The accuracy of the nomogram prediction was evaluated using a calibration plot. Finally, cox regression analysis was applied to identify the prognostic value and clinical relationship of the signature in LUAD. RESULTS: A total of 116 differentially expressed MRGs were detected in the TCGA dataset. We found that 12 MRGs were most significantly associated with OS by using the univariate regression analysis in LUAD. Then, multivariate Cox regression analyses were applied to construct the prognostic signature, which consisted of six MRGs-aldolase A (ALDOA), catalase (CAT), ectonucleoside triphosphate diphosphohydrolase-2 (ENTPD2), glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1), lactate dehydrogenase A (LDHA), and thymidylate synthetase (TYMS). The prognostic value of this signature was further successfully validated in the GSE31210 dataset. Furthermore, the calibration curve of the prognostic nomogram demonstrated good agreement between the predicted and observed survival rates for each of OS. Further analysis indicated that this signature could be an independent prognostic indicator after adjusting to other clinical factors. The high-risk group patients have higher levels of immune checkpoint molecules and are therefore more sensitive to immunotherapy. Finally, we confirmed six MRGs protein and mRNA expression in six lung cancer cell lines and firstly found that ENTPD2 might played an important role on LUAD cells colon formation and migration. CONCLUSIONS: We established a prognostic signature based on MRGs for LUAD and validated the performance of the model, which may provide a promising tool for the diagnosis, individualized immuno-/chemotherapeutic strategies and prognosis in patients with LUAD.

A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular Carcinoma.

PURPOSE: Given that metabolic reprogramming has been recognized as an essential hallmark of cancer cells, this study sought to investigate the potential prognostic values of metabolism-related genes (MRGs) for the diagnosis and treatment of hepatocellular carcinoma (HCC). METHODS: In total, 2752 metabolism-related gene sequencing data of HCC samples with clinical information were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). One hundred and seventy-eight the differentially expressed MRGs were identified from the ICGC cohort and TCGA cohort. Then, univariate Cox regression analysis was performed to identify these genes that were related to overall survival (OS). A novel metabolism-related prognostic signature was developed using the least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analyses in the ICGC dataset. The Broad Institute's Connectivity Map (CMap) was used in predicting which compounds on the basis of the prognostic MRGs. Furthermore, the signature was validated in the TCGA dataset. Finally, the expression levels of hub genes were validated in HCC cell lines by Western blotting (WB) and quantitative real-time PCR (qRT-PCR). RESULTS: We found that 17 MRGs were most significantly associated with OS in HCC. Then, the Lasso and multivariate Cox regression analyses were applied to construct the novel metabolism-relevant prognostic signature, which consisted of six MRGs. The prognostic value of this prognostic model was further successfully validated in the TCGA dataset. Further analysis indicated that this particular signature could be an independent prognostic indicator after adjusting to other clinical factors. Six MRGs (FLVCR1, MOGAT2, SLC5A11, RRM2, COX7B2, and SCN4A) showed high prognostic performance in predicting HCC outcomes. Candidate drugs that aimed at hub ERGs were identified. Finally, hub genes were chosen for validation and the protein, mRNA expression of FLVCR1, SLC5A11, and RRM2 were significantly increased in human HCC cell lines compared to normal human hepatic cell lines, which were in agreement with the results of differential expression analysis. CONCLUSION: Our data provided evidence that the metabolism-related signature could serve as a reliable prognostic and predictive tool for OS in patients with HCC.

Clinico-pathologic determinants of non-e-curative outcome following en-bloc endoscopic submucosal dissection in patients with early gastric neoplasia.

BACKGROUND: Endoscopic submucosal dissection (ESD) is gaining enormous popularity in the treatment of early gastric cancers (EGCs) in many institutions across the world. However, appropriate selection of candidates for endoscopic resection is crucial to sufficiently mitigate non-e-curative (NEC) resection. This study aims at identifying the various clinico-pathologic factors that independently predict the NEC outcome and depth of submucosal invasion following ESD procedure in patients with EGC. METHODS: Multiple logistic regression analysis was applied to investigate factors that independently predict both non-curability phenomenon and the level of submucosal invasion in patients with early gastric neoplasia. Statistical Packages for the Social Sciences version 23 was used for analysis. RESULTS: A total of 153 patients (162 EGC lesions) underwent en-bloc ESD after which the rate of complete resection and non-e-curative outcome were 95% and 22.2%, correspondingly. Multivariate analysis depicted that tumor location in the upper two third of stomach (odds ratio [OR], 5.46; 95% confidence interval [95% CI], 1.65-18.12; p = 0.006), tumor size > 2 cm (OR, 7.63; 95% CI, 2.29-25.42; p = 0.001), histologically undifferentiated tumor (OR, 15.54; 95% CI, 1.65-146.22; p = 0.001), and tumors with 0-IIa/0-IIc or their mixed variants with predominant 0-IIa/0-IIc (OR, 9.77; 95% CI, 1.23-77.65; p = 0.031) were all independent predictors of NEC resection for early gastric tumors. Additionally, location in the upper two third of the stomach (OR, 8.88; 95% CI, 2.90-27.17; p < 0.001), ulcerated lesions (OR, 3.70; 95% CI, 1.15-11.90; p = 0.028), lesions with > 2 cm (OR, 2.94; 95% CI, 1.08-8.02; p = 0.036) and those with poor differentiation (OR, 6.51; 95% CI, 2.23-18.98; p = 0.001) were found to have significant association with submucosal invasion. CONCLUSIONS: Tumors located in the upper two third of the stomach having a larger size (> 2 cm), poor histo-differentiation and a gross type of 0-IIa/0-IIc or their mixed variants with predominant 0-IIa/0-IIc were significantly associated with a risk of NEC after ESD procedure. Thus, early gastric tumors displaying these features need to be handled carefully during endoscopic resection. Our findings may shed light on the pre-procedural detection of clinicopathologic factors that determine non-e-curability in patients with EGC.

Changes in intestinal microbiota in HIV-1-infected subjects following cART initiation: influence of CD4+ T cell count.

The roles of immunodeficiency and combined antiretroviral therapy (cART) in shaping the gut microbiota in HIV-1-infected subjects (HISs) have not been described thoroughly by time-series investigations. In this study, 36 antiretroviral-naïve HISs were enrolled to prospectively assess alterations in the fecal microbiota and plasma markers of microbial translocation and inflammation with cART. At baseline, the species α-diversity of the fecal microbiota was significantly lower in HISs with a CD4+ T cell count <300/mm3 than in HISs with a CD4+ T cell count >300/mm3 (Shannon index: Median 2.557 vs. 2.981, P = 0.006; Simpson index: Median 0.168 vs. 0.096, P = 0.004). Additionally, the baseline α-diversity indices correlated with CD4+ T cell counts (Shannon index: r = 0.474, P = 0.004; Simpson index: r = -0.467, P = 0.004) and the specific plasma biomarkers for microbial translocation and inflammation. After cART introduction, the species α-diversity of fecal microbiota in HISs with CD4+ T cell counts <300/mm3 was significantly restored (Shannon index: Median 2.557 vs. 2.791, P = 0.007; Simpson index: Median 0.168 vs. 0.112, P = 0.004), while the variances were insignificant among HISs with CD4+ T cell counts >300/mm3 (Shannon index: Median 2.981 vs. 2.934, P = 0.179; Simpson index: Median 0.096 vs. 0.119, P = 0.082). Meanwhile, with cART introduction, alterations in the gut microbial composition were more significant in the subgroup with CD4+ T cell counts >300/mm3, corresponding to increases in the specific plasma inflammatory markers. These findings implicated the interactive roles of immunodeficiency and cART for affecting gut microbiota in HIV-1-infected individuals, providing new insights into intestinal microbiome dysbiosis related to HIV-1 infection.

Gut Microbiota Dysbiosis Is Not Independently Associated With Neurocognitive Impairment in People Living With HIV.

Gut microbiota dysbiosis, which has been linked to many neurological diseases, is common in HIV infection. However, its role in the pathogenesis of neurocognitive impairment is still not established. In this study, a total of 85 HIV infected subjects, naïve to antiretroviral therapy, were classified into two groups-those with HIV-associated neurological diseases (HAND) and those without, using the Montreal Cognitive Assessment (MoCA) test. Fecal samples were collected from all subjects and microbiota were analyzed by 16S rRNA amplicon sequencing. Subjects with HAND were older (P < 0.001), with lower levels of education (P = 0.002), lower CD4 T-cell counts (P = 0.032), and greater heterosexual preference (P < 0.001), than those without HAND. Gut microbiota from subjects with HAND showed significantly lower α-diversity compared to gut microbiota from subjects without HAND (Shannon index, P = 0.003). To exclude confounding bias, 25 subjects from each group, with comparable age, gender, CD4 T-cell count, educational level and sexual preference were further analyzed. The two groups showed comparable α-diversity (for SOB index, Shannon index, Simpson index, ACE index, and Chao index, all with P-value > 0.05) and ß-diversity (ANOSIM statistic = 0.010, P = 0.231). There were no significant differences in microbiota composition between the two groups after the correction for a false discovery rate. Consistently, microbiota from the two groups presented similar predictive functional profiles. Gut microbiota dysbiosis is not independently associated with neurocognitive impairment in people living with HIV.

An analysis of drug resistance among people living with HIV/AIDS in Shanghai, China.

BACKGROUND: Understanding the mechanisms of drug resistance can facilitate better management of antiretroviral therapy, helping to prevent transmission and decrease the morbidity and mortality of people living with HIV/AIDS. However, there is little data about transmitted drug resistance and acquired drug resistance for HIV/AIDS patients in Shanghai. METHODS: A retrospective cohort study of HIV-infected patients who visited the Department of Infectious Disease from June 2008 to June 2015 was conducted in Shanghai, China. Logistic regression analysis was performed to analyze risk factors for drug resistance among HIV-infected people with virological failure. The related collected factors included patient age, gender, marital status, infection route, baseline CD4 count, antiretroviral therapy regimens, time between HIV diagnosis and initiating antiretroviral therapy. Factors with p<0.1 in the univariate logistic regression test were analyzed by multivariate logistic regression test. RESULTS: There were 575 subjects selected for this study and 369 participated in this research. For the antiretroviral therapy drugs, the rates of transmitted drug resistance and acquired drug resistance were significantly different. The non-nucleoside reverse transcriptase inhibitor (NNRTI) had the highest drug resistance rate (transmitted drug resistance, 10.9%; acquired drug resistance, 53.3%) and protease inhibitors (PIs) had the lowest drug resistance rate (transmitted drug resistance, 1.7%; acquired drug resistance, 2.7%). Logistic regression analysis found no factors that were related to drug resistance except marital status (married status for tenofovir: odds ratio = 6.345, 95% confidence interval = 1.553-25.921, P = 0.010) and the time span between HIV diagnosis and initiating antiretroviral therapy (≤6M for stavudine: odds ratio = 0.271, 95% confidence interval = 0.086-0.850, P = 0.025; ≤6M for didanosine: odds ratio = 0.284, 95% confidence interval = 0.096-0.842, P = 0.023; ≤6M for tenofovir: odds ratio = 0.079, 95% confidence interval = 0.018-0.350,P<0.001). CONCLUSION: NNRTI had a higher DR rate compared with nucleoside reverse transcriptase inhibitor (NRTI) and PIs, consequently, LPV/r was a reasonable choice for patients with NNRTI drugs resistance in China. Only married status and a time span≤6 month between the HIV confirmed date and the time initiating antiretroviral therapy were risk factors for TDF drug resistance. Both baseline HIV-RNA load and resistance test is crucial for TDR diagnosis, and frequent monitoring of HIV-RNA load is crucial for ADR identification and intervention. Treatment adherence still plays a positive role on the outcome of ART.

A promising magnetic SERS immunosensor for sensitive detection of avian influenza virus.

Avian influenza viruses infect a great number of global populations every year and can lead to severe epidemics with high morbidity and mortality. Facile, rapid and sensitive detection of viruses is very crucial to control the viral spread at its early stage. In this work, we developed a novel magnetic immunosensor based on surface enhanced Raman scattering (SERS) spectroscopy to detect intact but inactivated influenza virus H3N2 (A/Shanghai/4084T/2012) by constructing a sandwich complex consisting of SERS tags, target influenza viruses and highly SERS-active magnetic supporting substrates. The procedure of sample pretreatment could be significantly simplified since the magnetic supporting substrates allowed the enrichment and separation of viruses from a complex matrix. With a portable Raman spectrometer, the immunosensor could detect H3N2 down to 102TCID50/mL (TCID50 refers to tissue culture infection dose at 50% end point), with a good linear relationship from 102 to 5×103 TCID50/mL. Considering its time efficiency, portability and sensitivity, the proposed SERS-based magnetic immunoassay is very promising for a point-of-care (POC) test in clinical and diagnostic praxis.

The risk factors for suboptimal CD4 recovery in HIV infected population: an observational and retrospective study in Shanghai, China.

Although the initiation of antiretroviral therapy (ART) has promoted the reconstitution of CD4+ T-cell count in the HIV infected population, not all patients can achieve the normalization of their immunologic functions. We analysed the variables associated with immunologic recovery, which is commonly regarded as the increase of CD4 to 350 cell/µL after a year of ART. We collected data from 3,485 patients attending a university-based HIV clinic from June 2005 to July 2014 in Shanghai, China. Logistic regression test was performed to analyse the risk factors for suboptimal CD4+ recovery following yearlong ART. The CD4+ T-cell of 723 participants (41.5% of the 1744 subjects) showed more than 350 cell/µL after one year of ART. Compared with baseline CD4 > 350 cell/µL, patients with baseline CD4 ≤ 200 cell/µL or 200 < CD4 ≤ 350 cell/µL were 42.6, 4.5 times more likely to be incomplete CD4 recovery, respectively. The risk of suboptimal immunologic recovery among patients with regimen including AZT or d4T were 2.1, 2.4 times higher compared with TDF, respectively. In our study, between optimal CD4 recovery group and suboptimal recovery group, there were no significant differences in age, gender, marital status, transmission routes, WHO stage, and CD4 recovery rates. As for the dynamic CD4 change, we found the CD4 recovery rates were 49.9% and 61.8% in the second and third year of ART, respectively. Patients who had a low level of CD4+ T-cell count (< 200 cell/µL) during the initiation of ART exhibited more difficulties recovering to a normal level. Furthermore, the regimen, including AZT or d4T, was not beneficial to CD4 recovery. So, more efforts should be made to guarantee the early diagnosis and timely treatment for HIV/AIDS patients, and simultaneously optimize antiretroviral therapy.