Global trends in COVID-19 incidence and case fatality rates (2019-2023): a retrospective analysis.

Objectives: Analyzing and comparing COVID-19 infection and case-fatality rates across different regions can help improve our response to future pandemics. Methods: We used public data from the WHO to calculate and compare the COVID-19 infection and case-fatality rates in different continents and income levels from 2019 to 2023. Results: The Global prevalence of COVID-19 increased from 0.011 to 0.098, while case fatality rates declined from 0.024 to 0.009. Europe reported the highest cumulative infection rate (0.326), with Africa showing the lowest (0.011). Conversely, Africa experienced the highest cumulative case fatality rates (0.020), with Oceania the lowest (0.002). Infection rates in Asia showed a steady increase in contrast to other continents which observed initial rises followed by decreases. A correlation between economic status and infection rates was identified; high-income countries had the highest cumulative infection rate (0.353) and lowest case fatality rate (0.006). Low-income countries showed low cumulative infection rates (0.006) but the highest case fatality rate (0.016). Initially, high and upper-middle-income countries experienced elevated initial infection and case fatality rates, which subsequently underwent significant reductions. Conclusions: COVID-19 rates varied significantly by continent and income level. Europe and the Americas faced surges in infections and low case fatality rates. In contrast, Africa experienced low infection rates and higher case fatality rates, with lower- and middle-income nations exceeding case fatality rates in high-income countries over time.

YOLOX-SwinT algorithm improves the accuracy of AO/OTA classification of intertrochanteric fractures by orthopedic trauma surgeons.

PURPOSE: Intertrochanteric fracture (ITF) classification is crucial for surgical decision-making. However, orthopedic trauma surgeons have shown lower accuracy in ITF classification than expected. The objective of this study was to utilize an artificial intelligence (AI) method to improve the accuracy of ITF classification. METHODS: We trained a network called YOLOX-SwinT, which is based on the You Only Look Once X (YOLOX) object detection network with Swin Transformer (SwinT) as the backbone architecture, using 762 radiographic ITF examinations as the training set. Subsequently, we recruited 5 senior orthopedic trauma surgeons (SOTS) and 5 junior orthopedic trauma surgeons (JOTS) to classify the 85 original images in the test set, as well as the images with the prediction results of the network model in sequence. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) 20.0 (IBM Corp., Armonk, NY, USA) to compare the differences among the SOTS, JOTS, SOTS + AI, JOTS + AI, SOTS + JOTS, and SOTS + JOTS + AI groups. All images were classified according to the AO/OTA 2018 classification system by 2 experienced trauma surgeons and verified by another expert in this field. Based on the actual clinical needs, after discussion, we integrated 8 subgroups into 5 new subgroups, and the dataset was divided into training, validation, and test sets by the ratio of 8:1:1. RESULTS: The mean average precision at the intersection over union (IoU) of 0.5 (mAP50) for subgroup detection reached 90.29%. The classification accuracy values of SOTS, JOTS, SOTS + AI, and JOTS + AI groups were 56.24% ± 4.02%, 35.29% ± 18.07%, 79.53% ± 7.14%, and 71.53% ± 5.22%, respectively. The paired t-test results showed that the difference between the SOTS and SOTS + AI groups was statistically significant, as well as the difference between the JOTS and JOTS + AI groups, and the SOTS + JOTS and SOTS + JOTS + AI groups. Moreover, the difference between the SOTS + JOTS and SOTS + JOTS + AI groups in each subgroup was statistically significant, with all p < 0.05. The independent samples t-test results showed that the difference between the SOTS and JOTS groups was statistically significant, while the difference between the SOTS + AI and JOTS + AI groups was not statistically significant. With the assistance of AI, the subgroup classification accuracy of both SOTS and JOTS was significantly improved, and JOTS achieved the same level as SOTS. CONCLUSION: In conclusion, the YOLOX-SwinT network algorithm enhances the accuracy of AO/OTA subgroups classification of ITF by orthopedic trauma surgeons.

Prognostic and immune infiltration features of disulfidptosis-related subtypes in breast cancer.

Breast cancer (BC) is a prominent cause of cancer incidence and mortality around the world. Disulfidptosis, a type of cell death, can induce tumor cell death. The purpose of this study was to analyze the potential impact of disulfidptosis-related genes (DRGs) on the prognosis and immune infiltration features of BC. Based on DRGs, we conducted an unsupervised clustering analysis on gene expression data of BC in TCGA-BRCA dataset and identified two BC subtypes, cluster1 and cluster2, with cluster1 showing a higher likelihood of favorable survival. Through immune analysis, we found that cluster1 had lower proportions of infiltration in immune-related cells, including aDCs, DCs, NK_cells, Th2_cells, and Treg. Based on the immunophenoscore (IPS) results, we inferred that cluster1 might benefit more from immune checkpoint inhibitors targeting CTLA-4 and PD1. Targeted small molecule prediction results showed that patients with cluster2 BC might respond better to antagonistic small molecule compounds, including clofazimine, lenalidomide, and epigallocatechin. Differentially expressed genes between the two subtypes were found to be enriched in signaling pathways related to steroid hormone biosynthesis, ovarian steroidogenesis, and neutrophil extracellular trap formation, according to enrichment analyses. In conclusion, this study identified BC subtypes based on DRGs so as to help predict patient prognosis and provide valuable tools for guiding clinical management and precise treatment of BC patients.

Phonon vortices at heavy impurities in two-dimensional materials.

The advent of monochromated electron energy-loss spectroscopy has enabled atomic-resolution vibrational spectroscopy, which triggered interest in spatially localized or quasi-localized vibrational modes in materials. Here we report the discovery of phonon vortices at heavy impurities in two-dimensional materials. We use density-functional-theory calculations for two configurations of Si impurities in graphene, Si-C3 and Si-C4, to examine atom-projected phonon densities of states and display the atomic-displacement patterns for select modes that are dominated by impurity displacements. The vortices are driven by large displacements of the impurities, and reflect local symmetries. Similar vortices are found at phosphorus impurities in hexagonal boron nitride, suggesting that they may be a feature of heavy impurities in crystalline materials. Phonon vortices at defects are expected to play a role in thermal conductivity and other properties.

An atlas of immune cell transcriptomes in human immunodeficiency virus-infected immunological non-responders identified marker genes that control viral replication.

BACKGROUND: Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness. This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness. METHODS: A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders (IRs) (CD4 + T-cell count >500) and immunological non-responders (INRs) (CD4 + T-cell count <300) was conducted. The transcriptomic profiles were used to identify distinct cell subpopulations, marker genes, and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness. RESULTS: Among the cellular subpopulations analyzed, the ratios of monocytes, CD16 + monocytes, and exhausted B cells demonstrated the most substantial differences between INRs and IRs, with fold changes of 39.79, 11.08, and 2.71, respectively. In contrast, the CD4 + T cell ratio was significantly decreased (0.39-fold change) in INRs compared with that in IRs. Similarly, the ratios of natural killer cells and terminal effector CD8 + T cells were also lower (0.37-fold and 0.27-fold, respectively) in the INRs group. In addition to several well-characterized immune cell-specific markers, we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus (HIV) replication. Notably, ISG15 , IFITM3 , PLSCR1 , HLA-DQB1 , CCL3L1 , and DDX5 , which have been demonstrated to influence HIV replication through their interaction with viral proteins, emerged as significant monocyte marker genes. Furthermore, the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication. CONCLUSIONS: We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs. Host genes associated with HIV replication were identified as markers of, and were found to be differentially expressed in, different types of immune cells.

Expression of RNA-m6A-related genes correlates with the HIV latent reservoir level and the CD4+ and CD8+T cell profiles of patients with AIDS.

The HIV latent reservoir is the main obstacle to the eradication of AIDS. Recent studies have shown that the RNA m6A is involved in the regulation of HIV-1 replication. However, no relevant study has reported the relationship between RNA m6A and HIV latent reservoir. For this purpose, peripheral blood mononuclear cell (PBMC) was collected from 36 HIV-infected patients at 1, 24, and 48 weeks after treatment initiation. The number of CD4+ and CD8+ T cells was detected by flow cytometry. Amount of HIV DNA in the PBMC samples one week after treatment initiation was detected by Q-PCR. The expression levels of 23 RNA-m6A-related genes were detected by Q-PCR and Pearson's correlation analysis was performed. Results showed that there was a negative correlation between HIV DNA concentration and the number of CD4+ T cells (r=-0.32, p=0.05; r=-0.32, p=0.06) and a positive correlation with the number of CD8+ T cells (r=0.48, p=0.003; r=0.37, p=0.03). Furthermore, a negative correlation was observed between HIV DNA concentration and the CD4+/CD8+ T cell ratio (r=-0.53, p=0.001; r=-0.51, p=0.001). RNAm6A related genes which correlated with HIV DNA concentration includedALKBH5 (r=-0.45, p=-0.006), METTL3 (r=0.73, p=2.76e-7), METTL16 (r=0.71, p=1.21e2.76e-06), YTHDF1 (r=0.47, p=0.004). Moreover, they have different degrees of correlation with numbers ofCD4+ and CD8+ T cell subsets, and the CD4+/CD8+T cell ratio. In addition, the expression of RBM15 was not correlated with HIV DNA concentration but was significantly negatively correlated with the number of CD4+T cells (r=-0.40, p=0.02). In conclusion, the expression of ALKBH5, METTL3, and METTL16 is correlated with the HIV DNA level, the levels of CD4+ and CD8+ T cell counts, and the CD4+/CD8+ T cell ratio. RBM15 is independent of HIV DNA level and negatively correlated with the number of CD4+T cells.

In Situ Monitoring of Curing Reaction in Solid Composite Propellant with Fiber-Optic Sensors.

Curing activity in the preparation of solid composite propellants determines the performance of solid rocket motors in operation. Limited by the lack of effective monitoring tools, the complete curing behavior and thermal-induced curing kinetics are rarely disclosed. It is still a challenge to monitor in situ and in real-time the physical and chemical cross-linking reaction during the curing of propellant. Herein, we demonstrate a promising approach based on optical fiber capable of being implanted inside the propellant to monitor the internal stress evolution during the curing process, by taking hydroxyl-terminated polybutadiene propellant as an example. Attributed to the strain and temperature sensitivity of a pair of optical fiber gratings, the thermal-assisted physico-chemical cross-linking states of curing process have been demonstrated in detail. By tracking the stress-induced wavelength shifts of fiber gratings and calculating the curing mechanism function, the complete curing roadmap, including the viscous flow stage, gel stage, hardening stage can be clearly revealed, and the curing completion times are obtained as 154, 81, and 40 h, at the curing temperatures of 60, 70, and 80 °C, respectively. The apparent activation energy of this curing system obtained by calculation is 73.88 kJ/mol. This flexible fiber-based sensor provides an effective tool for unraveling the cure kinetic mechanism, and paves a universal pathway to guide the preparation and applications of versatile composite materials for solid rocket motors.

High exogenous humus inhibits greenhouse gas emissions from steppe lakes.

Although freshwater lakes are considered to be an important source of greenhouse gas (GHG) emissions, the potential driving mechanisms of such emissions are not well understood, especially in steppe lakes. In this study, the GHG emission characteristics in Hulun Lake Basin, including Hulun Lake, Beier Lake, Wulannuoer Lake, and their surrounding watersheds were investigated. The average methane (CH4) and nitrous oxide (N2O) emission fluxes released from rivers were 67.84 ± 20.53 and 0.11 ± 0.04 µg m-2·min-1, which were larger than those of lakes, with values of 28.60 ± 13.02 and 0.06 ± 0.02 µg m-2·min-1, respectively. Conversely, the average carbon dioxide (CO2) emission flux from lakes (1816.58 ± 498.98 µg m-2·min-1) was higher than that of rivers of (1795.41 ± 670.49 µg m-2·min-1). The water in Hulun Lake Basin was rich in organic matter and had a high chemical oxygen demand (COD). Three-dimensional fluorescence combined with a parallel factor analysis (3D-EEM-PARAFAC) demonstrated that the organic matter was composed of four humus types (from Component 1 (C1) to Component 4 (C4)), of which, C1 and C4 were terrestrial humus. The fluorescence index (FI) and humification index (HIX) indicated that the organic matter in the water was mainly imported from exogenous humus. The GHG emission fluxes were negatively correlated with these four components, indicating that GHG emissions were mainly affected by the organic matter source and components, and humus was the most important factor that inhibited GHG emissions in steppe lakes. However, the GHG emission flux was relatively high in some areas of the lake, especially in areas with high nutrient levels or where algal blooms occurred, as evidenced by the significantly positive correlations with total nitrogen (TN), total phosphorous (TP), and chlorophyll-a (chl-a) (p < 0.01). The algae-derived organic matter simulated the decomposition of refractory humus, thus, promoting GHG emissions. These findings are crucial for accurately evaluating the GHG emission fluxes, understanding the carbon cycle, and proposing future management strategies for steppe lakes.

Meta-Analysis of Peripheral Blood Transcriptome Datasets Reveals a Biomarker Panel for Tuberculosis in Patients Infected With HIV.

Biomarkers are critical for rapid diagnosis of tuberculosis (TB) and could benefit patients with AIDS where diagnosis of TB co-infection is challenging. Meta-analysis is an approach to combine the results of the studies with standard statistical method by weighting each study with different sample size. This study aimed to use meta-analysis to integrate transcriptome datasets from different studies and screen for TB biomarkers in patients who were HIV-positive. Five datasets were subjected to meta-analysis on whole-blood transcriptomes from 640 patients infected with HIV. A total of 293 differentially expressed genes (DEGs) were identified as significant (P<0.0001) using the random effective model to integrate the statistical results from each study. DEGs were enriched in biological processes related to TB, such as "Type I interferon signaling" and "stimulatory C-type lectin receptor signaling". Eighteen DEGs had at least a two-fold change in expression between patients infected with HIV who were TB-positive and those who were TB-negative. GBP4, SERPING1, ATF3 and CDKBN3 were selected as a biomarker panel to perform multivariable logistic regression analysis on TB status and relative gene expression levels. The biomarker panel showed excellent accuracy (AUC>0.90 for HIV+TB) in clinical trial and suggests that meta-analysis is an efficient method to integrate transcriptome datasets from different studies.

Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naïve HIV Patients in Southeast China.

BACKGROUND: With the widespread use of integrase strand transfer inhibitors (INSTIs) in the clinical setting, transmission of INSTIs-resistance mutations may increase. Data regarding transmitted drug resistance mutations (TDRM) to INSTIs in Chinese HIV patients are limited. The aim of this study was to summarize the INSTIs TDRM, including the frequency of protease inhibitors (PIs) and reverse transcriptase (RT) inhibitors (RTIs) mutations in treatment-naïve patients in Southeast China. METHODS: HIV-1 positive patients were retrospectively selected between April 2018 and October 2020 from the Mengchao Hepatobiliary Hospital of Fujian Medical University, the largest designated HIV/AIDS care hospital in Southeast China. Individuals who were antiretroviral therapy-naïve and received antiretroviral drug resistance testing at baseline were included. Clinical data including demographic data, CD4 counts, HIV-RNA loads, and drug resistance mutations were collected. RESULTS: A total of 147 patients were enrolled. INSTIs TDRM was rare, with only one primary integrase mutation E138K observed in one sample and one secondary mutation E157Q detected in another sample. The overall prevalence of INSTIs TDRM was 1.36%. A substantial proportion of patients harbored common INSTIs-associated polymorphic variants. Two samples harbored the T215S, M184V and K70E mutations related to nucleoside RTIs (NRTIs). Twelve patients carried nonnucleoside RTIs (NNRTIs)-resistance mutations. Two individuals harbored PIs-resistance mutations: Q58E in one patient and M46I, I54V, V82A, L10F, and Q58E mutations in another patient. The total TDRM rate for RTIs and PIs was 10.20% (15/147), but only 0.68% (1/147) was according to the WHO recommendations on TDRM. CONCLUSION: The rate of INSTIs TDRM was low among therapy-naïve HIV patients in Southeast China. INSTIs as a first-line regimen are suitable for untreated HIV-1 patients in Southeast China. But special attention must be still paid to INSTIs TDRM in clinical practice.

Functional plasticity abnormalities over the lifespan of first-episode patients with major depressive disorder: a resting state fMRI study.

BACKGROUND: Neurodevelopmental and neurodegenerative theories of depression suggest that patients with major depressive disorder (MDD) may follow abnormal developmental, maturational, and aging processes. However, a lack of lifespan studies has precluded verification of these theories. Herein, we analyzed functional magnetic resonance imaging (fMRI) data to comprehensively characterize age-related functional trajectories, as measured by the fractional amplitude of low frequency fluctuations (fALFF), over the course of MDD. METHODS: In total, 235 MDD patients with age-differentiated onsets and 235 age- and sex-matched healthy controls (HC) were included in this study. We determined the pattern of age-related fALFF changes by cross-sectionally establishing the general linear model (GLM) between fALFF and age over a lifespan. Furthermore, the subjects were divided into four age groups to assess age-related neural changes in detail. Inter-group fALFF comparison (MDD vs. HC) was conducted in each age group and Granger causal analysis (GCA) was applied to investigate effective connectivity between regions. RESULTS: Compared with the HC, no significant quadratic or linear age effects were found in MDD over the entire lifespan, suggesting that depression affects the normal developmental, maturational, and degenerative process. Inter-group differences in fALFF values varied significantly at different ages of onset. This implies that MDD may impact brain functions in a highly dynamic way, with different patterns of alterations at different stages of life. Moreover, the GCA analysis results indicated that MDD followed a distinct pattern of effective connectivity relative to HC, and this may be the neural basis of MDD with age-differentiated onsets. CONCLUSIONS: Our findings provide evidence that normal developmental, maturational, and ageing processes were affected by MDD. Most strikingly, functional plasticity changes in MDD with different ages of onset involved dynamic interactions between neuropathological processes in a tract-specific manner.

Automatic identification of compressions and ventilations during CPR based on the fuzzy c-means clustering and deep belief network.

BACKGROUND: A transthoracic impedance (TTI) signal is an important indicator of the quality of chest compressions (CCs) during cardiopulmonary resuscitation (CPR). We proposed an automatic detection algorithm including the wavelet decomposition, fuzzy c-means (FCM) clustering, and deep belief network (DBN) to identify the compression and ventilation waveforms for evaluating the quality of CPR. METHODS: TTI signals were collected from a cardiac arrest model that electrically induced cardiac arrest in pigs. All signals were denoised using the wavelet and morphology method. The potential compression and ventilation waveforms were marked using an algorithm with a multi-resolution window. The compressions and ventilations in these waveforms were identified and classified using the FCM clustering and DBN methods. RESULTS: Using the FCM clustering method, the positive predictive values (PPVs) for compressions and ventilations were 99.7% and 95.7%, respectively. The sensitivities of recognition were 99.8% for compressions and 95.1% for ventilations. The DBN approach exhibited similar PPV and sensitivity results to the FCM clustering method. The time cost was satisfactory using either of these techniques. CONCLUSIONS: Our findings suggest that FCM clustering and DBN can be utilized to effectively and accurately evaluate CPR quality, and provide information for improving the success rate of CPR. Our real-time algorithms using FCM clustering and DBN eliminated most distortions and noises effectively, and correctly identified the compression and ventilation waveforms with a low time cost.

Correction to: Organic Matter Pollution During the Spring Thaw in Hulun Lake Basin: Contribution of Multiform Human Activities.

In the original publication of the article, there was an error in the name of institution. The incorrect name of institution "Nanjing Institute of Environmental Sciences, Ministry of Environmental Protection, 8, Jiangwangmiao Road, XuanWu District, 210042 Nanjing, People's Republic of China" should be revised to "Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environmental, 8, Jiangwangmiao Road, XuanWu District, 210042 Nanjing, People's Republic of China". The institution was still the same, but the name of the institution was changed.

Organic Matter Pollution During the Spring Thaw in Hulun Lake Basin: Contribution of Multiform Human Activities.

It has recently been reported that plateau lakes have been seriously polluted by organic matter, however, the sources of this organic matter and their relative contributions remain unknown. In this study, to determine the sources and composition of the organic matter in the Hulun Lake basin during the spring-thaw period, a total of twenty-three sampling sites were investigated. Results showed high levels of organic matter pollution in the surface water of Hulun Lake, with an average COD values of 119.35 mg L-1. Organic matter came from natural sources as well as a variety of anthropogenic activities. The direct sources included urbanization, industrial and residential wastewater discharge, and emission from burning fossile fuels. A large indirect source was organic matter from tumbleweed decomposition, which had increased due to desertification caused by overgrazing. The principal component analysis showed that organic matter from Hulun lake shared composition and sources with the upstream sections of the natural tributaries and the downstream section of the artificial tributary. The artificial inflow river contributed more organic matter than the other tributaries. Notably, a large portion of organic matter in Hulun Lake came from decomposing tumbleweed concentrated in the downstream section of one of the natural rivers. New indirect consequences of human activities must be factored into the rule and regulations that protect plateau lake ecosystems alongside the direct effects of established human activities.

Role of lateral amygdala calstabin2 in regulation of fear memory.

Calstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, an intracellular calcium channel. Studies from our and other's lab have shown that hippocampal calstabin2 regulates spatial memory. Calstabin2 and RyR2 are widely distributed in the brain, including the amygdala, a key brain area involved in the regulation of emotion including fear. Little is known about the role of calstabin2 in fear memory. Here, we found that genetic deletion of calstabin2 impaired long-term memory in cued fear conditioning test. Knockdown calstabin2 in the lateral amygdala (LA) by viral vector also impaired long-term cued fear memory expression. Furthermore, calstabin2 knockout reduced long-term potentiation (LTP) at both cortical and thalamic inputs to the LA. In conclusion, our present data indicate that calstabin2 in the LA plays a crucial role in the regulating of emotional memory.

Nociceptin impairs acquisition of novel object recognition memory in perirhinal cortex.

Nociceptin/Orphanin FQ (N/OFQ) plays an important role in the regulation of spatial, fear and recognition memories. N/OFQ receptors are highly distributed in the perirhinal cortex, which is a key brain area involved in modulating novel object recognition (NOR) memory. However, the role of N/OFQ in NOR memory in the perirhinal cortex was still unknown. Moreover, the effects of N/OFQ on different stages of NOR memory were still unclear. In NOR task, we found that pre-training intracerebroventricular (icv) injection of N/OFQ (0.3 and 1 nmol) impaired long-term memory in a dose-dependent manner. However, icv infusion of N/OFQ immediately after training did not affect NOR memory consolidation even at a high dose of 3 nmol. Pre-test icv injection of N/OFQ (1 nmol) also did not influence NOR memory retrieval. These data indicate that N/OFQ negatively modulates long-term NOR memory during the acquisition phase. Furthermore, the amnesia effect of N/OFQ (1 nmol, icv) could be antagonist by pre-treatment with the selective N/OFQ receptor antagonist [Nphe1]N/OFQ(1-13)NH2 (10 nmol, icv), indicating pharmacological specificity. Then, we found that pre-training infusion of N/OFQ (0.1 and 0.3 nmol/side) into the bilateral perirhinal cortex impaired long-term NOR memory, suggesting the perirhinal cortex is a critical brain structure in mediating the amnesic effect of N/OFQ in NOR task. In conclusion, our data, for the first time, indicate that N/OFQ in the perirhinal cortex impairs NOR memory acquisition through the NOP receptors.

Colony stimulating factor-1 receptor promotes proliferation, migration and invasion in the human nasopharyngeal carcinoma 6-10B cell line via the phosphoinositide 3-kinase/Akt pathway.

The present study aimed to investigate the effects of colony-stimulating factor-1 receptor (CSF-1R) on proliferation, migration and invasion in the human nasopharyngeal carcinoma (NPC) 6-10B cell line, and to investigate the possible underlying mechanisms. Using a lentiviral transfection method, a virus carrying the CSF-1R gene was transfected into 6-10B cells. The expression of CSF-1R was then detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis, and was revealed to be markedly enhanced in 6-10B cells. Subsequently, an MTT assay was performed to assess cell proliferative ability, and flow cytometric analysis was utilized to measure the apoptotic rate of the cells. Wound healing and Transwell assays were also performed to observe cell migration and invasion capabilities. Additionally, western blot analysis was used to detect the protein expression of the proliferation and apoptosis signaling factors cyclin D1, B-cell lymphoma 2, Bcl-2-associated X protein, and phosphorylated and total extracellular protein kinase B (Akt/PKB) in 6-10B cells. The results showed that CSF-1R overexpression promoted the proliferation, migration and invasion of the 6-10B cells. The corresponding mechanism may be associated with activation of the phosphoinositide 3-kinase/Akt pathway, which promotes cell survival and proliferation. These results indicated a potential molecular target for the treatment of NPC.

Proteomic analysis of serum proteins from HIV/AIDS patients with Talaromyces marneffei infection by TMT labeling-based quantitative proteomics.

BACKGROUND: Talaromyces marneffei (TM) is an emerging pathogenic fungus that can cause a fatal systemic mycosis in patients infected with human immunodeficiency virus (HIV). Although global awareness regarding HIV/TM coinfection is increasing little is known about the mechanism that mediates the rapid progression to HIV/AIDS disease in coinfected individuals. The aim of this study was to analyze the serum proteome of HIV/TM coinfected patients and to identify the associated protein biomarkers for TM in patients with HIV/AIDS. METHODS: We systematically used multiplexed isobaric tandem mass tag labeling combined with liquid chromatography mass spectrometry (LC-MS/MS) to screen for differentially expressed proteins in the serum samples from HIV/TM-coinfected patients. RESULTS: Of a total data set that included 1099 identified proteins, approximately 86% of the identified proteins were quantified. Among them, 123 proteins were at least 1.5-fold up-or downregulated in the serum between HIV/TM-coinfected and HIV-mono-infected patients. Furthermore, our results indicate that two selected proteins (IL1RL1 and THBS1) are potential biomarkers for distinguishing HIV/TM-coinfected patients. CONCLUSIONS: This is the first report to provide a global proteomic profile of serum samples from HIV/TM-coinfected patients. Our data provide insights into the proteins that are involved as host response factors during infection. These data shed new light on the molecular mechanisms that are dysregulated and contribute to the pathogenesis of HIV/TM coinfection. IL1RL1 and THBS1 are promising diagnostic markers for HIV/TM-coinfected patients although further large-scale studies are needed. Thus, quantitative proteomic analysis revealed molecular differences between the HIV/TM-coinfected and HIV-mono-infected individuals, and might provide fundamental information for further detailed investigations.

Overexpression of CSF-1R in nasopharyngeal carcinoma.

BACKGROUND: Tumor-associated macrophages play a significant role in tumor progression. CSF-1/CSF-1R is one of the most primary regulators of macrophage physiology in immune system. The expression of CSF-1/CSF-1R in nasopharyngeal carcinoma is unclear. OBJECTIVES: The aim of this study was to compare the expression of CSF-1R in nasopharyngeal carcinoma to nasopharyngitis for assessing the role CSF-1/CSF-1R in nasopharyngeal carcinoma. MATERIALS AND METHODS: Diagnostic tissues from 56 nasopharyngeal carcinoma patients and 32 nasopharyngitis patients were evaluated retrospectively by immunohistochemical analysis for the expression of CSF-1R. RESULTS: Significant differences of CSF-1R expression exists between nasopharyngeal carcinoma patients and nasopharyngitis patients (p<0.001). However, there is no relevance between CSF-1R and worse survival.

Baseline prognostic factors and statistic model to predict early virological response in telbivudine-treated patients with chronic hepatitis B.

BACKGROUND: Hepatitis B virus (HBV) infection is still a worldwide disease, which may cause liver cirrhosis or even hepatocellular carcinoma. Telbivudine is a potent nucleoside analogue used in the treatment of chronic hepatitis B (CHB); however, drug resistance has remained a challenge. As early virological response can predict long-term efficacy of nucleotide analogue treatment, numerous studies have been conducted in this area. OBJECTIVES: The aim of this study was to establish baseline prognostic factors and a statistical model to predict early virological response in telbivudine-treated CHB patients. PATIENTS AND METHODS: One hundred and eight CHB patients without any experience of nucleotide analogue therapy were assigned to receive telbivudine (600 mg, once daily) for at least 24 weeks, and then were followed up every two weeks. Cox proportional hazard regression model analyses were employed to evaluate baseline variables, and further developing a statistical model to predict early virological response. RESULTS: Negative family history of HBV infection (P = 0.000235), baseline higher serum TBIL (P = 0.038714) and AST (P = 0.020684) concentrations, and lower level of HBV-DNA (P = 0.0034784) were identified to be associated with higher possibility of early virological response. A model was established based on these variables to calculate the risk scores (R) for CHB patients. R > -0.38 suggested early virological response to telbivudine. The model was validated among an independent set of 20 patients. CONCLUSIONS: Family history as well as baseline bilirubin, AST and HBV DNA levels can predict early virological response. The model provides a better tool for response prediction based on the four prognostic factors.