Metagenomic assessment of gut microbial communities and risk of severe COVID-19.

BACKGROUND: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. METHODS: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. RESULTS: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. CONCLUSIONS: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.

Calycosin protects against oxidative stress-induced cardiomyocyte apoptosis by activating aldehyde dehydrogenase 2.

Myocardial infarction (MI) is the leading cause of death worldwide, and oxidative stress is part of the process that causes MI. Calycosin, a naturally occurring substance with cardioprotective properties, is one of the major active constituents in Radix Astragali. In this study, effect of Calycosin was investigated in vivo and in vitro to determine whether it could alleviate oxidative stress and oxidative stress-induced cardiac apoptosis in neonatal cardiomyocytes (NCMs) via activation of aldehyde dehydrogenase 2 (ALDH2). Calycosin protected against oxidative stress and oxidative stress-induced apoptosis in NCMs. Molecular docking revealed that the ALDH2-Calycosin complex had a binding energy of -9.885 kcal/mol. In addition, molecular docking simulations demonstrated that the ALDH2-Calycosin complex was stable. Using BLI assays, we confirmed that Calycosin could interact with ALDH2 (KD  = 1.9 × 10-4 M). Furthermore, an ALDH2 kinase activity test revealed that Calycosin increased ALDH2 activity, exhibiting an EC50 of 91.79 µM. Pre-incubation with ALDH2 inhibitor (CVT-10216 or disulfiram) reduced the cardio-protective properties Calycosin. In mice with MI, Calycosin therapy substantially reduced myocardial apoptosis, oxidative stress, and activated ALDH2. Collectively, our findings clearly suggest that Calycosin reduces oxidative stress and oxidative stress-induced apoptosis via the regulation of ALDH2 signaling, which supports potential therapeutic use in MI.

Radix Glycyrrhizae extract and licochalcone a exert an anti-inflammatory action by direct suppression of toll like receptor 4.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Glycyrrhizae (GL), a herbal medicine that is widely available, has shown advantages for a variety of inflammatory diseases. Toll like receptor 4 (TLR4) pathway has been shown to play a key role in the progression of inflammation. AIM OF THE STUDY: The purpose of this study was to investigate the involvement of TLR4 in the anti-inflammatory mechanism of GL extract and its active constituent on acute lung injury (ALI). MATERIALS AND METHODS: A model of inflammation produced by lipopolysaccharide (LPS) was established in C57BL/6 mice and macrophages derived from THP-1. To screen the active components of GL, molecular docking was used. Molecular dynamics and surface plasmon resonance imaging (SPRi) were used to study the interaction of a specific drug with the TLR4-MD2 complex. TLR4 was overexpressed by adenovirus to confirm TLR4 involvement in the anti-inflammatory activities of GL and the chosen chemical. RESULTS: We observed that GL extract significantly reduced both LPS-induced ALI and the production of pro-inflammatory factors including TNF-α, IL-6 and IL-1ß. Additionally, GL inhibited the binding of Alexa 488-labeled LPS (LPS-488) to the membrane of THP-1 derived macrophages. GL drastically reduce on the expression of TLR4 and the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-κB). Furthermore, molecular docking revealed that Licochalcone A (LicoA) docked into the LPS binding site of TLR4-MD2 complex. MD2-LicoA binding conformation was found to be stable using molecular dynamic simulations. SPRi indicated that LicoA bound to TLR4-MD2 recombinant protein with a KD of 3.87 × 10-7 M. LicoA dose-dependently reduced LPS-488 binding to the cell membrane. LicoA was found to significantly inhibit LPS-induced lung damage and inflammation. Furthermore, LicoA inhibited TLR4 expression, MAPK and NF-κB activation in a dose-dependent manner. The inhibitory effects of GL and LicoA on LPS-induced inflammation and TLR4 signaling activation were partly eliminated by TLR4 overexpression. CONCLUSION: Our findings imply that GL and LicoA exert inhibitory effects on inflammation by targeting the TLR4 directly.

The pathogenesis of anti-signal recognition particle necrotizing myopathy: A Review.

Immune-mediated necrotizing myopathy (IMNM) is a class of idiopathic inflammatory myopathies. According to the types of antibodies in serum, IMNM can be divided into three subtypes: anti-signal recognition particle (SRP) necrotizing myopathy, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) necrotizing myopathy, and serum antibody-negative necrotizing myopathy. Different subtypes of IMNM have common characteristics, but the specific pathological mechanisms differ. Anti-SRP necrotizing myopathy is an important type of IMNM. At present, the pathogenesis of the disease is unclear. Most views suggest that the disease is mainly caused by an autoimmune response; therefore, the therapeutic strategy is primarily immune regulation. Recent studies have implicated non-immune mechanisms such as endoplasmic reticulum stress and autophagy in the occurrence and development of the disease. Here, we review what is known about the pathogenesis of anti-SRP necrotizing myopathy and summarize the latest research progress, aiming to better understand the disease and provide new ideas for treatment targets.

Supplemental Oxygen Alters the Airway Microbiome in Cystic Fibrosis.

Features of the airway microbiome in persons with cystic fibrosis (pwCF) are correlated with disease progression. Microbes have traditionally been classified for their ability to tolerate oxygen. It is unknown whether supplemental oxygen, a common medical intervention, affects the airway microbiome of pwCF. We hypothesized that hyperoxia significantly impacts the pulmonary microbiome in cystic fibrosis. In this study, we cultured spontaneously expectorated sputum from pwCF in artificial sputum medium under 21%, 50%, and 100% oxygen conditions using a previously validated model system that recapitulates microbial community composition in uncultured sputum. Culture aliquots taken at 24, 48, and 72 h, along with uncultured sputum, underwent shotgun metagenomic sequencing with absolute abundance values obtained with the use of spike-in bacteria. Raw sequencing files were processed using the bioBakery pipeline to determine changes in taxonomy, predicted function, antimicrobial resistance genes, and mobile genetic elements. Hyperoxia reduced absolute microbial load, species richness, and diversity. Hyperoxia reduced absolute abundance of specific microbes, including facultative anaerobes such as Rothia and some Streptococcus species, with minimal impact on canonical CF pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus. The effect size of hyperoxia on predicted functional pathways was stronger than that on taxonomy. Large changes in microbial cooccurrence networks were noted. Hyperoxia exposure perturbs airway microbial communities in a manner well tolerated by key pathogens. Supplemental oxygen use may enable the growth of lung pathogens and should be further studied in the clinical setting. IMPORTANCE The airway microbiome in persons with cystic fibrosis (pwCF) is correlated with lung function and disease severity. Supplemental oxygen use is common in more advanced CF, yet its role in perturbing airway microbial communities is unknown. By culturing sputum samples from pwCF under normal and elevated oxygen conditions, we found that increased oxygen led to reduced total numbers and diversity of microbes, with relative sparing of common CF pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus. Supplemental oxygen use may enable the growth of lung pathogens and should be further studied in the clinical setting.

Metagenomic assessment of gut microbial communities and risk of severe COVID-19.

The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. We profiled 127 hospitalized patients with COVID-19 (n=79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. 48 species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID", suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with predicting whether stool was obtained from patients with severe vs. moderate COVID-19. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to validate these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.

10-Gingerol, a natural AMPK agonist, suppresses neointimal hyperplasia and inhibits vascular smooth muscle cell proliferation.

Background: Abnormal proliferation of vascular smooth muscle cells (VSMCs) in the intimal region is a key event in the development of neointimal hyperplasia. 10-G, a bioactive compound found in ginger, exerted inhibitory effects on the proliferation of several cancer cells. However, the effect and mechanism of 10-G on neointimal hyperplasia are not clear. Purpose: To explore the suppressive effects of 10-G on the proliferation and migration of VSMCs, and investigate the underlying mechanisms. Methods: In vivo, a left common carotid artery ligation mouse model was used to observe the effects of neointimal formation through immunohistochemistry and hematoxylin-eosin staining. In vitro, the cell proliferation and migration of HASMCs and A7r5 cells were detected by MTS assay, EdU staining, wound healing assay, Transwell assay, and western blotting as well. Molecular docking, molecular dynamics simulations and surface plasmon resonance imaging were collectively used to evaluate the interaction of 10-G with AMP-activated protein kinase (AMPK). Compound C and si-AMPK were used to inhibit the expression of AMPK. Results: Treatment with 10-G significantly reduced neointimal hyperplasia in the left common carotid artery ligation mouse model. MST and EdU staining showed that 10-G inhibited the proliferation of VSMC cells A7r5 and HASMC. We also found that 10-G altered the expression of proliferation-related proteins, including CyclinD1, CyclinD2, CyclinD3, and CDK4. Molecular docking revealed that the binding energy between AMPK and 10-G is -7.4 kcal mol-1. Molecular simulations suggested that the binding between 10-G and AMPK is stable. Surface plasmon resonance imaging analysis also showed that 10-G has a strong binding affinity to AMPK (KD = 6.81 × 10-8 M). 10-G promoted AMPKα phosphorylation both in vivo and in vitro. Blocking AMPK by an siRNA or AMPK inhibitor pathway partly abolished the anti-proliferation effects of 10-G on VSMCs. Conclusion: These data showed that 10-G might inhibit neointimal hyperplasia and suppress VSMC proliferation by the activation of AMPK as a natural AMPK agonist.

Dihydrotanshinone I inhibits the growth of hepatoma cells by direct inhibition of Src.

BACKGROUND: Liver cancer is one of the leading causes of cancer-related death worldwide. Dihydrotanshinone I (DHI) was shown to inhibit the growth of several types of cancer. However, research related to hepatoma treatment using DHI is limited. PURPOSE: Here, we explored the inhibitory effect of DHI on the growth of hepatoma cells, and investigated the underlying molecular mechanisms. METHODS: The proliferation of Hep3B, SMCC-7721 and SK-Hep1 hepatoma cells was evaluated using the MTS and Edu staining assay. Hepatoma cell death was analyzed with a LIVE/DEAD Cell Imaging Kit. The relative expression and phosphorylation of proto-oncogene tyrosine-protein kinase Src (Src) and signal transducer and activator of transcription-3 (STAT3) proteins in hepatoma cells, as well as the expression of other protein components, were measured by western blotting. The structural interaction of DHI with Src proteins was evaluated by molecular docking, molecular dynamics simulation, surface plasmon resonance imaging and Src kinase inhibition assay. Src overexpression was achieved by infection with an adenovirus vector encoding human Src. Subsequently, the effects of DHI on tumor growth inhibition were further validated using mouse xenograft models of hepatoma. RESULTS: In vitro studies showed that treatment with DHI inhibited the proliferation and promoted cell death of Hep3B, SMCC-7721 and SK-Hep1 hepatoma cells. We further identified and verified Src as a direct target of DHI by using molecular stimulation, surface plasmon resonance image and Src kinase inhibition assay. Treatment with DHI reduced the in vitro phosphorylation levels of Src and STAT3, a transcription factor regulated by Src. In the xenograft mouse models, DHI dose-dependently suppressed tumor growth and Src and STAT3 phosphorylation. Moreover, Src overexpression partly abrogated the inhibitory effects of DHI on the proliferation and cell death in hepatoma cells. CONCLUSION: Our results suggest that DHI inhibits the growth of hepatoma cells by direct inhibition of Src.

Design and Development of a Model to Study the Effect of Supplemental Oxygen on the Cystic Fibrosis Airway Microbiome.

Airway microbial communities are thought to play an important role in the progression of cystic fibrosis (CF) and other chronic pulmonary diseases. Microbes have traditionally been classified based on their ability to use or tolerate oxygen. Supplemental oxygen is a common medical therapy administered to people with cystic fibrosis (pwCF); however, existing studies on oxygen and the airway microbiome have focused on how hypoxia (low oxygen) rather than hyperoxia (high oxygen) affects the predominantly aerobic and facultative anaerobic lung microbial communities. To address this critical knowledge gap, this protocol was developed using an artificial sputum medium that mimics the composition of sputum from pwCF. The use of filter sterilization, which yields a transparent medium, allows optical methods to follow the growth of single-celled microbes in suspension cultures. To create hyperoxic conditions, this model system takes advantage of established anaerobic culturing techniques to study hyperoxic conditions; instead of removing oxygen, oxygen is added to cultures by daily sparging of serum bottles with a mixture of compressed oxygen and air. Sputum from 50 pwCF underwent daily sparging for a 72-h period to verify the ability of this model to maintain differential oxygen conditions. Shotgun metagenomic sequencing was performed on cultured and uncultured sputum samples from 11 pwCF to verify the ability of this medium to support the growth of commensal and pathogenic microbes commonly found in cystic fibrosis sputum. Growth curves were obtained from 112 isolates obtained from pwCF to verify the ability of this artificial sputum medium to support the growth of common cystic fibrosis pathogens. We find that this model can culture a wide variety of pathogens and commensals in CF sputum, recovers a community highly similar to uncultured sputum under normoxic conditions, and creates different culture phenotypes under varying oxygen conditions. This new approach might lead to a better understanding of unanticipated effects induced by the use of oxygen in pwCF on airway microbial communities and common respiratory pathogens.

Dauricine inhibits proliferation and promotes death of melanoma cells via inhibition of Src/STAT3 signaling.

Melanoma is the most common type of skin cancer. Signal transducer and activator of transcription 3 (STAT3) signaling has been demonstrated to be a therapeutic target for melanoma. Dauricine (Dau), an alkaloid compound isolated from the root of Menispermum dauricum DC., has shown tumor-suppressing effects in multiple human cancers, but its potential in melanoma remains unexplored. In this study, we demonstrated that Dau significantly inhibited the viability and proliferation of A375 and A2058 melanoma cells. Death of melanoma cells was also markedly promoted by Dau. Moreover, Dau inhibited phosphorylation-mediated activation of STAT3 and Src in a dose-dependent manner. Notably, constitutive activation of Src partially abolished the antiproliferative and cytotoxic activities of Dau on melanoma cells. Molecular docking showed that Dau could dock on the kinase domain of Src with a binding energy of -10.42 kcal/mol. Molecular dynamics simulations showed that Src-Dau binding was stable. Surface plasmon resonance imaging analysis also showed that Dau has a strong binding affinity to Src. In addition, Dau suppressed the growth of melanoma cells and downregulated the activation of Src/STAT3 in a xenograft model in vivo. These data demonstrated that Dau inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways.

Impact of DNA Extraction Method on Variation in Human and Built Environment Microbial Community and Functional Profiles Assessed by Shotgun Metagenomics Sequencing.

Both the host microbiome and the microbiome of the built environment can have profound impacts on human health. While prior studies have suggested that the variability introduced by DNA extraction method is less than typical biologic variation, most studies have focused on 16S rRNA amplicon sequencing or on high biomass fecal samples. Shotgun metagenomic sequencing provides advantages over amplicon sequencing for surveying the microbiome, but is a challenge to perform in lower microbial biomass samples with high human DNA content such as sputum or vacuumed dust. Here we systematically evaluate the impact of four different extraction methods (phenol:choloroform, and three high-throughput kit-based approaches, the Promega Maxwell gDNA, Qiagen MagAttract PowerSoil DNA, and ZymoBIOMICS 96 MagBead). We report the variation in microbial community structure and predicted microbial function assessed by shotgun metagenomics sequencing in human stool, sputum, and vacuumed dust obtained from ongoing cohort studies or clinical trials. The same beadbeating protocol was used for all samples to focus our evaluation on the impact of kit chemistries on sequencing results. DNA yield was overall highest in the phenol:choloroform and Promega approaches. Only the phenol:choloroform approach showed evidence of contamination in negative controls. Bias was evaluated using mock community controls, and was noted across all extraction methods, although Promega exhibited the least amount of bias. The extraction method did not impact the proportion of human reads, although stool had the lowest proportion of human reads (0.1%) as compared to dust (44.1%) and sputum (80%). We calculated Bray-Curtis dissimilarity and Aitchison distances to evaluate the impact of extraction method on microbial community structure by sample type. Extraction method had the lowest impact in stool (extraction method responsible for 3.0-3.9% of the variability), the most impact in vacuumed dust (12-16% of the variability) and intermediate values for sputum (9.2-12% variability). Similar differences were noted when evaluating microbial community function. Our results will inform investigators planning microbiome studies using diverse sample types in large clinical studies. A consistent DNA extraction approach across all sample types is recommended, particularly with lower microbial biomass samples that are more heavily influenced by extraction method.

Quercetin pretreatment enhances the radiosensitivity of colon cancer cells by targeting Notch-1 pathway.

Cancer stem-like cells are rare immortal cells within tumor, which are thought to play important roles in ionizing radiation (IR) therapy-resistance. Quercetin is a natural flavonoid with potential anti-cancer properties without significant cytotoxicity in normal tissues. In this study, we demonstrated that quercetin-IR combination treatment exhibited more dramatic anti-cancer effect than either quercetin or IR treatment alone via targeting colon cancer stem cells (CSCs) and inhibiting the Notch-1 signaling. These effects were further verified by in vivo studies which showed remarkable decrease of the CSCs markers and the expression of Notch-1 signaling proteins in human colon cancer xenografts in nude mice. Co-treatment with quercetin and low dose of radiation significantly reduced the expressions of all five proteins of γ-secretase complex in HT-29 and DLD-1 cells. In addition, ectopic expression of the Notch intracellular domain (NICD) partly reversed the inhibition effects by the combination therapy. In conclusion, our results indicated that the combination of quercetin (20 µM) and IR (5Gy) might be a promising therapeutic strategy for colon cancer treatment by targeting colon cancer stem-like cells and inhibiting the Notch-1 signaling. In future studies, we intend to further explore the potential therapeutic efficacy of the quercetin-radiation combination treatment in clinical trials.

The efficacy of PD-1/PD-L1 inhibitors in advanced squamous-cell lung cancer: a meta-analysis of 3112 patients.

Aim: We performed a meta-analysis to explore the efficacy of immunotherapy for patients with squamous non-small-cell lung cancer (NSCLC). Materials & methods: Randomized clinical trials comparing immunotherapy with chemotherapy for advanced NSCLC patients were included. Results: A total of 11 trials (3112 patients) were included. PD-1/PD-L1 inhibitors demonstrated significant superiority to chemotherapy in overall survival (OS) (hazard ratio [HR]: 0.74; p < 0.001) and progression-free survival (PFS) (HR: 0.66; p < 0.001) for squamous NSCLC. The OS and PFS benefits of PD-1/PD-L1 inhibitors for squamous NSCLC were similar in subgroup analyses of line settings, PD-L1 expression and different study methodologies. No advantage in OS was found in advanced squamous NSCLC patients treated with atezolizumab (HR: 0.87; p = 0.087). Conclusion: PD-1/PD-L1 inhibitors significantly improved OS and PFS in advanced squamous NSCLC patients when compared with chemotherapy.

Menstrual Disturbances in Premenopausal Women with End-Stage Renal Disease: A Cross-Sectional Study.

OBJECTIVE: To evaluate menstrual disturbances and sex hormonal status in premenopausal women with end-stage renal disease (ESRD). SUBJECTS AND METHODS: The study consisted of 184 patients with ESRD treated with one of four treatment modalities (46/modality): conventional hemodialysis (CHD), continuous ambulatory peritoneal dialysis (CAPD), nocturnal hemodialysis (NHD) and renal transplantation (RT). Blood samples were collected to determine sex hormone levels. Sociodemographic and clinical data were collected from medical records. A questionnaire was administered to analyze menstrual patterns, and the final analysis included 46, 43, 40 and 36 patients in the CHD, CAPD, NHD and RT groups, respectively. RESULTS: The overall prevalence of menstrual disturbances was 64.2% for all four treatment modalities (RT: 50%; NHD: 55%; CAPD: 72.1%, and CHD: 76.1%). Serum prolactin levels were significantly lower (p < 0.01) in the NHD (25.1 ± 10.9 ng/ml) and RT (13.4 ± 5.1 ng/ml) groups than in the CHD group (55.2 ± 10.8 ng/ml). Serum progesterone levels were significantly higher (p < 0.01) in the NHD (25.7 ± 8.3 nmol/l) and RT (30.1 ± 5.9 nmol/l) groups than in the CHD group (17.7 ± 7.3 nmol/l). Moreover, the hormonal status (follicle-stimulating hormone, luteinizing hormone and testosterone) was much closer to normal in the NHD and RT groups compared to the other two groups. CONCLUSIONS: In this study, successful transplantation and NHD partially improved the symptoms of menstrual disturbances. Therefore, we recommend that further studies are necessary to confirm our finding in ESRD patients.

[Diagnosing radiation-induced liver injury in rabbit using 3.0 Tesla magnetic resonance diffusion-weighted imaging].

OBJECTIVE: To evaluate the clinical value of magnetic resonance (MR) diffusion-weighted imaging (DWI) for diagnosing radiation-induced liver injury (RILI) and detecting changes in hepatic pathology at different post-irradiation times. METHODS: Male New Zealand white rabbits received no irradiation (C0, control group; n = 10) or irradiation of 50 Gy/10F once every other day by virtual three dimensional conformal radiotherapy (3D-CRT) for one day (C1; n = 10), three days (C2; n = 10), two weeks (C3; n = 10), one month (C4; n = 10) or two months (C5; n = 10). One member of all groups were sacrificed for DWI examination and pathologic study on post-irradiation day 1, day 3, week 2, month 1 and month 2. The apparent diffusion coefficient (ADC) values were measured using a range of b values (50, 300, 600, 800 and 1000 s/mm2). RESULTS: Hematoxylin-eosin (H-E) staining showed that livers of rabbits in the C3, C4 and C5 groups had the characteristic features of veno-occlusive disease. DWI examination showed that the irradiated livers of rabbits in C2, C3, C4 and C5 groups had significantly lower ADC values than the livers of the non-irradiated rabbits at b values of 300, 600, 800 and 1000 s/mm2 (P less than 0.05). When the b value was 600 s/mm2, the best negative correlation between ADC values and pathological stage was seen for the irradiated livers (Spearman's rank, r = -0.459, P less than 0.01). The threshold ADC value to distinguish the normal group (C0) from an irradiated group (more than or equal toC1) was 1.955 * 10-3 mm2/s at 600 s/mm2 b value. When the b value was 1000 s/mm2, the threshold ADC value to predict an irradiated group with normal H-E staining (C1) from an irradiated group with abnormal H-E staining (more than or equal toC2) was 1.5250 * 10-3 mm2/s; the ADC threshold value was 1.5150 * 10-3 mm2/s to predict groups C0-2 and groups C3-5. CONCLUSION: DWI has high sensitivity for detecting RILI at three days after irradiation with proper b values. Use of the ADC value is feasible for estimating the evolutionary process of pathological features of RILI damage. DWI may represent an important clinical tool for detection of early pathological changes in RILI.

Diagnosing radiation-induced liver injury in rabbit using 3.0 Tesla magnetic resonance diffusion-weighted imaging / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the clinical value of magnetic resonance (MR) diffusion-weighted imaging (DWI) for diagnosing radiation-induced liver injury (RILI) and detecting changes in hepatic pathology at different post-irradiation times.</p><p><b>METHODS</b>Male New Zealand white rabbits received no irradiation (C0, control group; n = 10) or irradiation of 50 Gy/10F once every other day by virtual three dimensional conformal radiotherapy (3D-CRT) for one day (C1; n = 10), three days (C2; n = 10), two weeks (C3; n = 10), one month (C4; n = 10) or two months (C5; n = 10). One member of all groups were sacrificed for DWI examination and pathologic study on post-irradiation day 1, day 3, week 2, month 1 and month 2. The apparent diffusion coefficient (ADC) values were measured using a range of b values (50, 300, 600, 800 and 1000 s/mm2).</p><p><b>RESULTS</b>Hematoxylin-eosin (H-E) staining showed that livers of rabbits in the C3, C4 and C5 groups had the characteristic features of veno-occlusive disease. DWI examination showed that the irradiated livers of rabbits in C2, C3, C4 and C5 groups had significantly lower ADC values than the livers of the non-irradiated rabbits at b values of 300, 600, 800 and 1000 s/mm2 (P less than 0.05). When the b value was 600 s/mm2, the best negative correlation between ADC values and pathological stage was seen for the irradiated livers (Spearman's rank, r = -0.459, P less than 0.01). The threshold ADC value to distinguish the normal group (C0) from an irradiated group (more than or equal toC1) was 1.955 * 10-3 mm2/s at 600 s/mm2 b value. When the b value was 1000 s/mm2, the threshold ADC value to predict an irradiated group with normal H-E staining (C1) from an irradiated group with abnormal H-E staining (more than or equal toC2) was 1.5250 * 10-3 mm2/s; the ADC threshold value was 1.5150 * 10-3 mm2/s to predict groups C0-2 and groups C3-5.</p><p><b>CONCLUSION</b>DWI has high sensitivity for detecting RILI at three days after irradiation with proper b values. Use of the ADC value is feasible for estimating the evolutionary process of pathological features of RILI damage. DWI may represent an important clinical tool for detection of early pathological changes in RILI.</p>

Characterization, risk stratification and the hypertension control rate at hospital-based clinics: a survey of 25,336 hypertensives in Beijing, Shanghai and Guangzhou.

OBJECTIVE: To characterize hypertensive patients living in metropolitan cities in China. METHODS: This was a cross-sectional survey conducted in Beijing, Shanghai and Guangzhou. The eligibility criteria included outpatients 35-85 years of age with a systolic blood pressure (SBP) of ≥140 mmHg or a diastolic blood pressure (DBP) of ≥90 mmHg or both and/or patients receiving antihypertensive medications. The patients' demographic characteristics, medical history and findings of physical examinations, laboratory tests and cardiovascular imaging (i.e., ultrasonic cardiogram) were included in the survey. Risk stratification and the rate of hypertension control were evaluated. RESULTS: A total of 25,336 individuals were surveyed, of which 79.1% were from cardiology clinics and 51.8% were male hypertensives. The average SBP/DBP was 139.3±18.6/82.3±12.0 mmHg. The mean age was 63.6±11.5 years. The mean BMI was 25.1±3.8 kg/m(2). Among the men, 55.9% had a waist circumference of >90 cm. Among the women, 50.9% had a waist circumference of >85 cm. The percentages of patients with diabetes mellitus, heart disease and cerebral vascular disease were 20.3%, 39.2% and 10.4%, respectively. The smoking rate was 17.6%. Overall, 60.9% of the patients were in the very high risk group. While 97.7% of the patients were receiving antihypertensive drug therapy, only 40.2% had controlled SBP/DBP (i.e., under 140/90 mmHg). The control rate was statistically higher in Beijing and Shanghai than in Guangzhou and among older patients than among younger patients (43% among the patients >75 years of age vs. 28.1% among the patients 35-45 years of age). CONCLUSION: In Beijing, Shanghai and Guangzhou, most hypertensive patients have various cardiovascular risk factors and cardiovascular diseases. High blood pressure is not under appropriate control in all cases, especially among young hypertensives and patients living in Guangzhou city. Approaches designed to target multiple risk factors and concomitant cardiovascular diseases and boost the hypertension control rate are warranted.