Clinical significance of RNA methylation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a primary liver malignancy with high mortality rates and poor prognosis. Recent advances in high-throughput sequencing and bioinformatic technologies have greatly enhanced the understanding of the genetic and epigenetic changes in liver cancer. Among these changes, RNA methylation, the most prevalent internal RNA modification, has emerged as a significant contributor of the development and progression of HCC. Growing evidence has reported significantly abnormal levels of RNA methylation and dysregulation of RNA-methylation-related enzymes in HCC tissues and cell lines. These alterations in RNA methylation play a crucial role in the regulation of various genes and signaling pathways involved in HCC, thereby promoting tumor progression. Understanding the pathogenesis of RNA methylation in HCC would help in developing prognostic biomarkers and targeted therapies for HCC. Targeting RNA-methylation-related molecules has shown promising potential in the management of HCC, in terms of developing novel prognostic biomarkers and therapies for HCC. Exploring the clinical application of targeted RNA methylation may provide new insights and approaches for the management of HCC. Further research in this field is warranted to fully understand the functional roles and underlying mechanisms of RNA methylation in HCC. In this review, we described the multifaceted functional roles and potential mechanisms of RNA methylation in HCC. Moreover, the prospects of clinical application of targeted RNA methylation for HCC management are discussed, which may provide the basis for subsequent in-depth research on RNA methylation in HCC.

First report of root and crown rot caused by Armillaria gallica on Cannabis sativa in California, U.S.A.

In October 2018, symptoms of leaf necrosis, wilted shoots, and stunted growth were observed on the upper portion of the 7-month-old cannabis (Cannabis sativa L.) plants in Mendocino County, California, U.S.A. Foliar symptoms were followed by a rapid death of the plants within 24 hours. Out of 200 affected plants, 80% (160/200) were symptomatic. All affected plants were grown in non-woven polypropylene containers (Smart pots, Oklahoma, USA) set directly on the ground approximately 3 m apart outdoors, surrounded by native forest (Quercus spp., Pseudotsuga menzeisii). Closer examination of the C. sativa plants revealed diagnostic signs of Armillaria root disease: white mycelial fans at the base of the woody stem (root collar) and abundant rhizomorphs on the roots and root collar (Supplementary Fig 1A). Also, both woody roots and the root collar exhibited severely rotted wood. Rotted wood, mycelial fans, and rhizomorphs (n=20) were surface sterilized with 0.6% sodium hypochlorite, rinsed with sterile water, and plated on PDA amended with tetracycline (1 mg/L). Sixteen cultures with morphological characters of Armillaria sp. (regular colony margin, no spore structures, no clamp connections) were recovered (Baumgartner et al., 2011). Species identity was confirmed by sequencing the internal transcribed spacer (ITS) region of rDNA and the translation elongation factor subunit 1-alpha (TEF1a) loci (White et al. 1990, Baumgartner et al 2010). Sequences (GenBank nos. MT248417 and MT259788) were compared with those in the NCBI GenBank database using a BLAST search, revealing 876/881bp matching with Armillaria gallica ITS sequence, GenBank no KP960553, and 146/150bp matching with TEF1a sequence from a North America A. gallica isolate, GenBank no. JF895844 (Brazee et al., 2011). Pathogenicity tests were conducted twice using two A. gallica isolates (15389-1 and 15389-2) by inoculating sterile, 1-month old, rooted tissue-cultured cannabis plants of 'Wedding Cake' with 7.5 ml of homogenized A. gallica liquid inoculum (Baumgartner et al., 2010), added aseptically to the surface of the vermiculite, near the plant stem (Ford et al., 2017). Eight plants were inoculated and two (using sterile water instead of inoculum) were used as negative controls. Plants were incubated at 21-26 °C under 40 to 80 µmol·m-2·s-1 from full spectrum light source with an 18/6 photoperiod to support vegetative growth. Plants were watered with 25 ml sterile nutrient solution (Cutting Edge Solutions, Santa Rosa, CA, U.S.A.) at 1 to 2-week intervals, according to the plant's need. At eight weeks post inoculation, all eight inoculated plants showed symptoms of yellowing and wilting. Uptake of the nutrient solution and water had also stopped by this time. The two non-inoculated plants, however, remained healthy throughout the 8-week period (Supplementary Fig 1B). At the end of the experiment, samples were taken aseptically from the crowns and roots of each plant and plated on water agar amended with streptomycin (100 µg/ml) and benomyl (4 µg/ml). Hyphae were subcultured to 0.5X PDA to confirm species identity through ITS and TEF1a. A. gallica was reisolated from affected crowns and stems. This is the first report of A. gallica causing root and crown rot of C. sativa. Considering the expanding cultivation area of Cannabis crops due to legalization of the industry in many U.S. states, A. gallica root and crown rot may become a serious issue affecting the industry, even for plants maintained in non-woven polypropylene containers in direct contact with soil.

One-year follow-up of chest CT findings in patients after SARS-CoV-2 infection.

BACKGROUND: Knowledge about the 1-year outcome of COVID-19 is limited. The aim of this study was to follow-up and evaluate lung abnormalities on serial computed tomography (CT) scans in patients with COVID-19 after hospital discharge. METHODS: A prospective cohort study of patients with COVID-19 from the First Affiliated Hospital, Zhejiang University School of Medicine was conducted, with assessments of chest CT during hospitalization and at 2 weeks, 1 month, 3 months, 6 months, and 1 year after hospital discharge. Risk factors of residual CT opacities and the influence of residual CT abnormalities on pulmonary functions at 1 year were also evaluated. RESULTS: A total of 41 patients were followed in this study. Gradual recovery after hospital discharge was confirmed by the serial CT scores. Around 47% of the patients showed residual aberration on pulmonary CT with a median CT score of 0 (interquartile range (IQR) of 0-2) at 1 year after discharge, with ground-glass opacity (GGO) with reticular pattern as the major radiologic pattern. Patients with residual radiological abnormalities were older (p = 0.01), with higher rate in current smokers (p = 0.04), higher rate in hypertensives (p = 0.05), lower SaO2 (p = 0.004), and higher prevalence of secondary bacterial infections during acute phase (p = 0.02). Multiple logistic regression analyses indicated that age was a risk factor associated with residual radiological abnormalities (OR 1.08, 95% CI 1.01-1.15, p = 0.02). Pulmonary functions of total lung capacity (p = 0.008) and residual volume (p < 0.001) were reduced in patients with residual CT abnormalities and were negatively correlated with CT scores. CONCLUSION: During 1-year follow-up after discharge, COVID-19 survivors showed continuous improvement on chest CT. However, residual lesions could still be observed and correlated with lung volume parameters. The risk of developing residual CT opacities increases with age.

Recombinant Human Growth Hormone Ameliorates Cognitive Impairment in Stroke Patients.

OBJECTIVE: We aimed to determine the effects of recombinant human growth hormone (rhGH) replacement on cognitive function in subjects with poststroke cognitive impairment using resting-state functional magnetic resonance imaging. METHODS: We included 60 patients with a first-ever stroke for 3 months and a diagnosis of cognitive impairment who were randomized 1:1 to receive either rhGH subcutaneously or placebo injection for 6 months. All subjects were required to receive the same rehabilitative therapy program. Both groups were subjected to pretreatment and posttreatment neuropsychological assessment using the Montreal Cognitive Assessment, serum neurotrophic factors, biomarkers of glucose and lipid metabolism, and functional magnetic resonance imaging during 6 months of the study period. The pattern of brain activity was determined by examining the functional connectivity and amplitude of low-frequency fluctuations (ALFF) of blood oxygen level dependent signal. RESULTS: Forty-three (82.7%) completed the study. Treatment with rhGH reduced levels of triglycerides and low-density lipoprotein cholesterol but did not significantly altered plasma concentrations of glucose and glycated hemoglobin. We found a significant increase in serum insulin-like growth factor 1 levels (32.6%; P < 0.001) in the rhGH-treated group compared with that in the controls. After 6 months of rhGH treatment, mean Montreal Cognitive Assessment score improved from 16.31 (5.32) to 21.19 (6.54) (P < 0.001). The rhGH group showed significant increased area of activation with increased ALFF values in the regions of the frontal lobe, putamen, temporal lobe, and thalamus (P < 0.05), relative to the baseline conditions. The correlation analysis revealed that the ALFF and functional connectivity of default mode network was positively correlated with the ΔMoCA score and ΔIGF-1 levels; that is, the more the scale score increased, the higher the functional connection strength. No undesirable adverse effects were observed. CONCLUSIONS: The rhGH replacement has a significant impact on global and domain cognitive functions in poststroke cognitive impairment.

TIGAR suppresses seizures induced by kainic acid through inhibiting oxidative stress and neuronal apoptosis.

TP53-induced glycolysis and apoptosis regulator (TIGAR) activates the pentose phosphate pathway (PPP), which feeds reduced nicotinamide adenine dinucleotide phosphate (NADPH) to the antioxidant glutathione pathway. Oxidative stress-induced neuronal apoptosis is the pathological basis of several neurological disorders, including epilepsy. To determine the potential anti-epileptic action TIGAR in a rodent kainic acid (KA)-induced seizure model. Seizures were induced by the intra-cerebroventricular injection of KA, followed by injection of empty or TIGAR-expressing lentiviral vectors. Immunofluorescence was used to detect the localization of TIGAR in the cortices and hippocampi, and the expression levels of relevant proteins were determined by Western blotting. Oxidative stress-related markers were detected using commercially available kits. Neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. TIGAR were mainly expressed in the neurons and rarely located in the astrocytes, and increased in the cortices and hippocampi of KA-treated rats in a time-dependent manner. Lentivirus-mediated TIGAR overexpression significantly decreased the oxidative stress and neuronal apoptosis induced by KA, resulting in prolonged seizure latency and lower Racine scores. Our findings indicate that TIGAR has anti-epileptic, anti-oxidant and anti-apoptotic effects, and is therefore a promising therapeutictarget for epilepsy.

Evaluation of Quinoxyfen Resistance of Erysiphe necator (Grape Powdery Mildew) in a Single Virginia Vineyard.

The protectant fungicide quinoxyfen has been used against grape powdery mildew (Erysiphe necator) in the United States since 2003. In 2013, isolates of grape powdery mildew with reduced quinoxyfen sensitivity (here designated as quinoxyfen lab resistance or QLR) were detected in a single vineyard in western Virginia, USA. Field trials were conducted in 2014, 2015, and 2016 at the affected vineyard to determine to what extent quinoxyfen might still contribute to disease control. Powdery mildew control by quinoxyfen was similar to, or only slightly less than, that provided by myclobutanil and boscalid in all three years. In 2016, early- versus late-season applications of quinoxyfen were compared to test the hypothesis that early-season applications were more effective, but differences were small. A treatment with two early quinoxyfen applications, at bloom and 2 weeks later, followed by a myclobutanil-boscalid plus a low dose of sulfur rotation provided slightly better control of foliar disease incidence than treatments containing four quinoxyfen applications or two midseason or two late quinoxyfen applications supplemented by myclobutanil and boscalid applications; severity differences were small and nonsignificant. Metrafenone and benzovindiflupyr generally provided excellent powdery mildew control. The frequency of QLR in vines not treated with quinoxyfen slowly declined from 65% in 2014 to 46% in 2016. Further research is needed to explain how, despite this QLR frequency, quinoxyfen applied to grapes in the field was still able to effectively control powdery mildew.

[Safety of tirofiban in patients with acute cerebral infarct receiving endovascular therapy].

OBJECTIVE: To investigate the effect of tirofiban on hemorrhagic transformation and neurological outcome in patients with acute cerebral infarct treated with endovascular therapy. METHODS: One hundred and fifteen patients with acute cerebral infarct who received endovascular stent mechanical thrombectomy in the Second Affiliated Hospital, Zhejiang University School of Medicine during October 2013 and April 2017 were included in the study. Among 115 patients, 30 received tirofiban treatment. Hemorrhagic transformation and neurological outcomes were assessed using the ECASS Ⅱ criteria and modified Rankin scale (mRS), respectively. Unfavorable outcome was defined as mRS>2. Binary logistic regression model was used to analyze the independent predictors of hemorrhagic transformation and neurological outcome. RESULTS: Binary logistic regression analysis showed that tirofiban treatment did not increase the risk of hemorrhagic transformation (OR=0.437, 95% CI:0.168-1.132, P>0.05); baseline NIHSS (OR=1.136, 95% CI:1.014-1.273, P<0.05), recanalization (OR=0.060, 95% CI:0.010-0.365, P<0.01), hypertension (OR=4.233, 95% CI:1.320-13.570, P<0.05) and onset to treatment time(OR=1.006, 95% CI:1.001-1.011, P<0.05) were independently associated with unfavorable outcome, while such association was not observed in tirofiban treatment (OR=1.923, 95% CI:0.536-6.568, P>0.05). CONCLUSIONS: Tirofiban appears to be safe for patients with acute cerebral infarct receiving endovascular therapy.

Bloodstream infection, peritonitis, and pneumonia caused by Pasteurella multocida in a patient with liver cirrhosis despite no animal contact: case report and literature review.

Pasteurella multocida is an opportunistic pathogen. Previously reported infections associated with P. multocida have often been linked to contact with cats, dogs, and other animals. Cases of systemic multiple-site infections following P. multocida infection are rare. This case study presents a 49-year-old middle-aged man with post-hepatitis B cirrhosis and no history of animal contact. The patient was admitted with symptoms of fever accompanied by diarrhea, abdominal distension, and cough. Blood tests showed elevated levels of CRP, PCT, and IL-6, and blood culture revealed the growth of P. multocida. CT scans revealed a large amount of abdominal effusion, a small amount of pleural effusion, and pulmonary infection foci. The patient's condition improved after successive administration of ceftriaxone and levofloxacin to fight the infection, and abdominal puncture and drainage. Multiple-site infections caused by P. multocida are rarely encountered in patients with liver cirrhosis but without animal contact, which could be regarded as serious conditions warranting careful attention in terms of clinical diagnosis and treatment.

Randomized control study of the use of faropenem for treating patients with pulmonary tuberculosis.

OBJECTIVES: Faropenem has antituberculosis activity in vitro but its utility in treating patients with tuberculosis (TB) is unclear. METHODS: We conducted an open-label, randomized trial in China, involving newly diagnosed, drug-susceptible pulmonary TB. The control group was treated with the standard 6-month regimen. The experimental group replaced ethambutol with faropenem for 2 months. The primary outcome was the treatment success rate after 6 months of treatment. Noninferiority was confirmed if the lower limit of a 95% one-sided confidence interval (CI) of the difference was greater than -10%. RESULTS: A total of 227 patients eligible for the study were enrolled in the trial group and the control group in a ratio of 1:1. Baseline characteristics of participants were similar in both groups. In the modified intention-to-treat population, 88.18% of patients in the faropenem group achieved treatment success, and 85.98% of those in the control group were successfully treated, with a difference of 2.2% (95% CI, -6.73-11.13). In the per-protocol population, treatment success was 96.04% in the faropenem group and 95.83% in the control group, with a difference of 2.1% (95% CI, -5.31-5.72). The faropenem group showed noninferiority to the control group in the 6-month treatment success rates. The faropenem group had significantly fewer adverse events (P <0.01). CONCLUSIONS: Our study proved that oral faropenem regimen can be used for the treatment of TB, with fewer adverse events. (Chinese Clinical Trial Registry, ChiCTR1800015959).

Predictive Analysis of Serum NO, PGI2, and Ox-LDL Levels on Disease Progression in Patients with Lacunar Cerebral Infarction.

Objective: To analyze and predict the progress of patients with lacunar infarction by analyzing the levels of serum NO, PGI2, and Ox-LDL produced by endothelial cells. Methods: 138 patients with lacunar infarction and 34 healthy people were selected. The selected samples were divided into progressive group, nonprogressive group, and control group for biochemical test and endothelial function test. The levels of serum NO, PGI2, and Ox-LDL were obtained. The observation indexes of different groups were compared for statistical analysis and multivariate logistic regression analysis. Results: The indexes of LI patients in the nonprogression group were different from those in the control group. The content of Ox-LDL in the nonprogression group was higher than that in the control group, while the indexes of serum NO and PGI2 were lower than that in the control group. The level of Ox-LDL in LI patients in the progressive group was much higher than that in healthy people in the control group seven days after admission, while the levels of serum NO and PGI2 were lower, and the difference of serum on was more obvious. The level of Ox-LDL in the progressive group was much higher than that in the nonprogressive group, while the levels of serum NO and PGI2 in the progressive group were lower, and the level of serum NO was significantly different from that in the nonprogressive group. Ox - LDL > 76.48 U/L, NO > 55.24 ummol/L, and PGI2 > 29.78 ng/L were independent risk factors for the progression of lacunar infarction. Conclusion: Because the patients with lacunar infarction have endothelium-dependent relaxation disorder, the changes of serum NO, PGI2, and Ox-LDL can be used as the evaluation index of the disease progress of patients with lacunar infarction and can be widely used in clinical detection.

Epidemic Trends in High Tuberculosis Burden Countries During the Last Three Decades and Feasibility of Achieving the Global Targets at the Country Level.

Objective: To estimate the epidemic trends of tuberculosis (TB) in 30 high burden countries (HBCs) over the past 30 years, which is crucial for tracking the status of disease control, especially at the country level. Methods: Annual data on incidence and mortality of TB in these 30 HBCs were extracted from the Global Burden of Disease database. The average annual percent change (AAPC) was used to evaluate the trends of incidence and mortality. The trajectory analysis was used to identify different trends among the subgroup countries. The predicted incidence and mortality rates in 2025, 2030, and 2035 were also calculated. Results: The incidence and mortality decreased in most of the HBCs. The AAPCs of incidence ranged between -4.0 (Indonesia) and -0.2% (DR Congo) (all p < 0.05). The incidence trends in Lesotho (AAPC: 0%, 95% CI: -0.4, 0.3, p = 0.8) and South Africa (AAPC: -0.2%, 95% CI: -0.5, 0, p = 0.1) were stable, and increased in Kenya with AAPC of 0.1% (95% CI: 0.1, 0.2, p < 0.05). The AAPCs for mortality ranged between -5.8 (Ethiopia) and -0.6% (Central African Republic) (all p < 0.05). The mortality trends in DPR Korea (AAPC: 0.1%, 95% CI: -0.3, 0.4, p = 0.6) and Russian Federation (AAPC: -0.5%, 95% CI: -1.9, 0.9, p = 0.5) were stable, and increased in Lesotho and Zimbabwe with AAPC of 1.3% (95% CI: 1.1, 1.4, p < 0.05) and 1.6% (95% CI: 1.0, 2.2, p < 0.05), respectively. Trajectory analysis showed that the Central African Republic, Lesotho, Cambodia, Namibia, and South Africa had higher incidences, and the Central African Republic had higher mortality. Brazil and China had relatively lower rates of incidence and mortality. Predictions showed that reduction rates of incidence and mortality could hardly be reached compared with those set for the global targets for the majority HBCs. Conclusions: The disease burden of TB has been reduced among the majority HBCs over the last three decades. According to the current control levels, achieving the ambitious global targets at the country level for these 30 HBCs is challenging.

Aortic Involvement in Disseminated Tuberculosis - Challenges Beyond the Diagnosis.

Tuberculous aortitis (TA) is a rare disease with a high mortality rate. Aortic pseudoaneurysm is the most common vascular pattern of TA, and isolated arterial wall thickening and arterial stenosis can also be seen in TA. We report two cases of disseminated tuberculosis involving the aorta with clinical improvement after treatment. One patient who had an aortic ulcer and intermural hematoma received anti-tuberculosis along with steroids therapy. The other patient, who developed a tubercular abdominal aortic pseudoaneurysm during anti-tuberculosis therapy, successfully received endovascular stent implantation. Clinicians should be aware that TA should be considered in patients with aortitis and active tuberculosis.

The Application of Whole-Exome Sequencing in Patients With FUO.

BACKGROUND: Fever of unknown origin (FUO) is still a challenge for clinicians. Next-generation sequencing technologies, such as whole exome sequencing (WES), can be used to identify genetic defects in patients and assist in diagnosis. In this study, we investigated the application of WES in individuals with FUO. METHODS: We performed whole-exome sequencing on 15 FUO patients. Clinical information was extracted from the hospital information system. RESULTS: In 7/15 samples, we found positive results, including potentially causative mutations across eight different genes: CFTR, CD209, IRF2BP2, ADGRV 1, TYK2, MEFV, THBD and GATA2. CONCLUSIONS: Our results show that whole-exome sequencing can promote the genetic diagnosis and treatment of patients with FUO.

Risk factors for negative T-SPOT.TB assay results in patients with confirmed active tuberculosis: A retrospective study.

INTRODUCTION: The interferon-γ release assays as potent adjunct tools for the quick detection of TB in high burden countries is feasible. In this retrospective study, we aimed to identify the risk factors for negative T-SPOT results in confirmed active tuberculosis. METHODOLOGY: We consecutively enrolled 1,021 patients who were positive for acid-fast bacilli smear staining or culture-confirmed mycobacterial infection and simultaneously tested with the T-SPOT.TB assay. All of the included specimens were used to discriminate the Mycobacterium species using the biochip assay. We collected basic clinical characteristics and laboratory results for further analysis. RESULTS: Of the 1,021 patients enrolled in the study, 89 patients were identified as having nontuberculous mycobacteria (NTM). Ninety-nine patients were excluded from the analysis because of indeterminate T-SPOT.TB results, while the remaining 833 patients were identified as having Mycobacterium tuberculosis infection. In total, 159 patients had false-negative T-SPOT.TB results (19.1% of 833). The concordance rate between the T-SPOT.TB results and final diagnoses in females was always lower than that in males. Multivariate logistic regression analysis showed that female sex (OR 1.81; 95% CI 1.19, 2.7; p = 0.006), age (OR 1.02; 95% CI 1.01, 1.03; p = 0.003), acid-fast bacilli (AFB) smear-negative (OR 5.45; 95% CI 3.62, 8.19; p < 0.001), HIV coinfection (OR 6.83; 95% CI 2.73, 17.10; p < 0.001) were associated with negative T-SPOT.TB result. CONCLUSIONS: Female is another independent risk factor of negative T-SPOT.TB results, besides to elder, HIV co-infection, acid-fast bacilli (AFB) smear-negative who are suspected of having active TB infection.

Mycobacterium Intracellulare Infection Associated with TYK2 Deficiency: A Case Report and Review of the Literature.

Individuals with genetic defects show an increased susceptibility to poorly pathogenic mycobacteria including nontuberculous mycobacteria and Bacillus Calmette-Guerin (BCG). In previous studies, defects in multiple genes were identified to be associated with mycobacterium infection including tyrosine kinase 2 (TYK2). The mutations lead to insufficient production of interferon (IFN)-γ or an insufficient response to IFN-α/ß, interleukin (IL)-6, IL-10, IL-12 and IL-23. Herein, we describe a case of Mycobacterium intracellulare infection in a male with abdominal pain and diarrhea. Whole exome sequencing of the genomes revealed a compound heterozygous mutation (c.3083A>G/c.2590C>T, p.N1028S/p.R864C) in the TYK2 gene. The patient recovered after two years of anti-mycobacterial treatment and no relapse was observed so far. We also reviewed 24 cases of mycobacterial infection associated with TYK2 deficiency which provides evidence of how personalised genomics can improve outcomes.

Profiling the mRNA and miRNA in Peripheral Blood Mononuclear Cells in Subjects with Active Tuberculosis.

PURPOSE: To identify candidate hub genes and miRNAs associated with active tuberculosis (ATB) and reveal the potential molecular mechanisms of disease progression. PATIENTS AND METHODS: The expression of mRNA and miRNA was evaluated in peripheral blood mononuclear cells (PBMC) from 4 ATB patients and 4 healthy donors (HD) using high throughput sequencing (HTS) and bioinformatics analysis. Moreover, differentially expressed miRNAs were validated with 35 ATB patients and 35 HDs using reverse transcription quantitative real-time PCR (RT-qPCR). RESULTS: A total of 2658 significantly differentially expressed genes (DEG) including 1415 up-regulated genes and 1243 down-regulated genes were identified in the ATB group compared with HDs, and the DEGs enriched in immune-related pathways, especially in TNF signaling pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase (MAPK) signaling pathways and tuberculosis. Additionally, 10 hub genes were acquired according to protein-protein interaction (PPI) analysis of DEGs. Moreover, 26 differentially expressed miRNAs were found in ATB group compared with HDs. Furthermore, RT-qPCR results showed that hsa-miR-23a-5p (P=0.0106), hsa-miR-183-5p (P=0.0027), hsa-miR-193a-5p (P=0.0021) and hsa-miR-941(P=0.0001) were significantly increased in the ATB patients compared with HD group, and the hsa-miR-16-1-3p was significantly decreased (P=0.0032). CONCLUSION: Our research provided a characteristic profile of mRNAs and miRNAs expressed in ATB subjects, and 10 hub genes related with ATB were found, which will contribute to explore the role of miRNAs and hub genes in the pathogenesis of ATB, and improve the ability of differential diagnosis and treatment for the disease.

Epidemic Trends of Tuberculosis in China from 1990 to 2017: Evidence from the Global Burden of Disease Study.

PURPOSE: Tuberculosis remains a major public health problem globally, especially in undeveloped countries. This study aimed to evaluate and review the long-term epidemic trends of tuberculosis in China. METHODS: Data were extracted from the Global Health Data Exchange. Metrics (prevalence, incidence and mortality) and Joinpoint regression were used to identify the epidemic trends. RESULTS: From 1990 to 2017, decreasing trends in prevalence (average annual percent change, AAPC: -0.5%, 95% CI: -0.6% to -0.5%), incidence (-3.2%, 95% CI: -3.5% to -2.9%), and mortality (-5.7%, 95% CI: -6.2% to -5.3%) of tuberculosis were observed. The incidence and mortality of multidrug-resistant tuberculosis (MDR-TB) decreased with AAPC of -2.3% (-3.1% to -1.4%) and -4.9% (-5.4% to -4.5%), respectively, while the prevalence increased with an AAPC of 1.2% (0.3% to 2.0%). The burden of extensively drug-resistant tuberculosis (XDR-TB) increased with an AAPC of 12.5% (11.9% to 13.2%) in prevalence, 7.6% (6.5% to 8.7%) in incidence, and 4.5% (3.6% to 5.4%) in mortality. The disease burden of tuberculosis increased with age and peaked among those aged over 70. CONCLUSION: The epidemic of tuberculosis decreased in China, while the disease burden was still challenging to control. MDR-TB and XDR-TB should be emphasized along with the epidemic. It will certainly be a difficult task to achieve the post-2015 global targets by 2025 and 2035.

Protective Effect of Paeoniflorin on Acute Cerebral Infarction in Rats.

OBJECTIVE: The purpose of this paper was to study the protective effect of paeoniflorin on acute cerebral ischemia. The animal model of cerebral infarction induced by Middle Cerebral Artery Occlusion (MCAO) was blocked by the suture method. Sixty SD rats were randomly divided into the shame group, MCAO group, paeoniflorin (60, 120, 240 mg/kg, respectively) and Nimodipine (NMDP) group (n = 10 per group). METHODS: The rats were intragastrically administered immediately after the operation. After 7 days of gavage, the brains were decapitated at 24 h. Hematoxylin and Eosin (HE) staining was used to observe the degree of cell damage in the cerebral cortex of rats. Immunohistochemistry was used to detect silver plating and to observe changes in nerve cells. Rats in the model group showed obvious symptoms of neurological deficits, such as the ischemic morphological changed, the Malondialdehyde (MDA), Lactate Dehydrogenase (LD) content and lactate dehydrogenase (LDH) activity were significantly increased in the ischemic brain tissue, while the Superoxide Dismutase (SOD) activity was decreased. RESULTS: The decrease in Na+-K+-ATPase activity was significantly lower than that in the sham group. The neurological symptoms and signs of MCAO in the different doses of paeoniflorin group were improved, and the neuronal edema in the cortical area was alleviated. The activities of SOD, LDH and Na+-K+-ATPase were significantly increased, and the contents of MDA and LD were decreased. CONCLUSION: Therefore, paeoniflorin could alleviate the degree of tissue damage in rats with acute cerebral infarction, inhabit the formation of free radicals in the brain tissue after ischemia, and reduce the degree of lipid peroxidation. Thus, the degree of cell damage was reduced greatly and a protective effect was showed on cerebral ischemia.

Effect of Corticosteroid Therapy on the Duration of SARS-CoV-2 Clearance in Patients with Mild COVID-19: A Retrospective Cohort Study.

INTRODUCTION: In December, 2019, an outbreak of the coronavirus disease 2019 (COVID-19), which was caused by a novel coronavirus, started in Wuhan, China. So far, there is limited clinical evidence on the effect of corticosteroid therapy for this disease. This study aims to investigate the association between corticosteroid therapy and the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance among patients with mild COVID-19. METHODS: Patients with mild COVID-19 were enrolled from two medical centers in China between January 13, 2020 and February 29, 2020. Baseline characteristics and durations of RNA clearance were compared between the corticosteroid and non-corticosteroid therapy groups. The independent effects of corticosteroid therapy on the duration of RNA clearance were estimated by generalized linear models. RESULTS: Of 82 patients with a mild infection, 40 patients were male (48.8%), with a median age of 49 years (interquartile range, IQR 36-61). Among those patients, 36 patients (43.9%) received corticosteroid therapy. The adjusted multivariate models showed that the effects of corticosteroids were non-significant on the durations of onset to first RNA clearance [ß 2.48, 95% CI (95% confidence interval) - 0.42 to 5.38, P = 0.0926] and to persistent RNA clearance (ß 1.54, 95% CI - 1.41 to 4.48, P = 0.3016), and durations of therapy to first RNA clearance (ß 2.16, 95% CI - 0.56 to 4.89, P = 0.1184) and to persistent RNA clearance (ß 1.22, 95% CI - 1.52 to 3.95, P = 0.3787). CONCLUSIONS: Corticosteroid therapy in patients with mild COVID-19 was not associated with the duration of SARS-CoV-2 clearance, suggesting that the use of corticosteroids may not be beneficial for patients with mild COVID-19 and should be prudently recommended in clinical practice. However, further studies are needed to verify the findings.

Dependence of Membrane Tether Strength on Substrate Rigidity Probed by Single-Cell Force Spectroscopy.

Substrate rigidity modulates cell mechanics, which affect cell migration and proliferation. Quantifying the effects of substrate rigidity on cancer cell mechanics requires a quantifiable parameter that can be measured for individual cells, as well as a substrate platform with rigidity being the only variable. Here we used single-cell force spectroscopy to pull cancer cells on substrates varying only in rigidity, and extracted a parameter from the force-distance curves to be used to quantify the properties of membrane tethers. Our results showed that tether force increases with substrate rigidity until it reaches its asymptotic limit. The variations are similar for all three cancer cell lines studied, and the largest change occurs in the rigidity regions of softer tissues, indicating a universal response of cancer cell elasticity to substrate rigidity.