Comparative study of two indoor microbial volatile pollutants, 2-Methyl-1-butanol and 3-Methyl-1-butanol, on growth and antioxidant system of rice (Oryza sativa) seedlings.

2-Methyl-1-butanol (2MB) and 3-Methyl-1-butanol (3MB) are microbial volatile organic compounds (VOCs) and found in indoor air. Here, we applied rice as a bioindicator to investigate the effects of these indoor microbial volatile pollutants. A remarkable decrease in germination percentage, shoot and root elongation, as well as lateral root numbers were observed in 3MB. Furthermore, ROS production increased by 2MB and 3MB, suggesting that pentanol isomers could induce cytotoxicity in rice seedlings. The enhancement of peroxidase (POD) and catalase (CAT) activity provided evidence that pentanol isomers activated the enzymatic antioxidant scavenging systems, with a more significant effect observed in 3MB. Furthermore, 3MB induced higher activity levels of glutathione (GSH), oxidized glutathione (GSSG), and the GSH/GSSG ratio in rice compared to the levels induced by 2MB. Additionally, qRT-PCR analysis showed more up-regulation in the expression of glutaredoxins (GRXs), peroxiredoxins (PRXs), thioredoxins (TRXs), and glutathione S-transferases (GSTUs) genes in 3MB. Taking the impacts of pentanol isomers together, the present study suggests that 3MB exhibits more cytotoxic than 2MB, as such has critical effects on germination and the early seedling stage of rice. Our results provide molecular insights into how isomeric indoor microbial volatile pollutants affect plant growth through airborne signals.

Computational exploration of the significance of COPS6 in cancer: Functional and clinical relevance across tumor types.

BACKGROUND: The COP9 signalosome subunit 6 (COPS6) has been implicated in cancer progression, while its precise role in most types of cancer remains elusive. AIM: To investigate the functional and clinical relevance of COPS6 across various tumor types using publicly available databases. METHODS: We used R software and online analysis databases to analyze the differential expression, prognosis, mutation and related functions of COPS6 in pan-cancer. RESULTS: Differential expression analysis and survival analysis demonstrated that COPS6 was highly expressed and associated with high-risk profiles in the majority of cancer types. Possible associations between COPS6 expression level and prognostic outcomes were found using data from public databases. Mutational analysis revealed that missense mutations were the predominant type of COPS6 mutation. Additionally, positive correlations were identified between COPS6 expression level and tumor mutational burden and microsatellite instability in most types of cancer. Immune infiltration analysis demonstrated a negative correlation between COPS6 expression level and CD8+ T cell infiltration in certain types of cancer. The correlation between COPS6 expression level and cancer-associated fibroblast infiltration exhibited heterogeneity, in which a positive correlation was found in head and neck squamous cell carcinoma and tenosynovial giant cell tumor, and a negative correlation was identified in diffuse large B-cell lymphoma and thymoma. The correlation between COPS6 expression level and macrophage infiltration was closely related to macrophage type. Gene co-expression and enrichment analysis highlighted transcription elongation factor B polypeptide 2 and G protein pathway suppressor 1 were significantly and positively associated with COPS6 expression level. These genes were predominantly involved in processes, such as ubiquitin-mediated proteolysis and human immunodeficiency virus 1 infection. CONCLUSION: In conclusion, this study systematically explored the significance of COPS6 across different tumor types, providing a solid foundation for considering COPS6 as a novel biomarker in cancer research.

Hemorrhagic Bartholin's cyst in a woman using anti-platelet medication: A case report and review of the literature.

BACKGROUND: We report the case of a postmenopausal female with a hemorrhagic Bartholin's cyst who has been using an antiplatelet medication. CASE SUMMARY: A postmenopausal woman, 84 years of age, had a medical history of hypertension, diabetes mellitus, coronary artery disease (three-vessel disease), chronic kidney disease (stage 3), and dementia. The patient has been taking clopidogrel, an antiplatelet medication, for several years. She presented at our outpatient clinic complaining of painful swelling over her left vulva for several days. A Bartholin's cyst over the left vulva was suspected, and the patient underwent marsupialization under local anesthesia, which was well-tolerated. During the incision procedure, bright-red blood with some blood clots was discharged, and a hemorrhagic Bartholin's cyst was observed. There was no recurrence of the hemorrhagic Bartholin's cyst during the 6-mo subsequent follow-up period. CONCLUSION: Hemorrhagic Bartholin's cysts rarely occur. We report the case of a postmenopausal female with a hemorrhagic Bartholin's cyst who had been on antiplatelets and was successfully treated with marsupialization. No recurrence was noted during the 6-mo follow-up period. Older females taking antiplatelets should be cautious of bleeding when presenting with a Bartholin's cyst.

Parthenolide Attenuates Sepsis-Induced Acute Kidney Injury in Rats by Reducing Inflammation.

Background: Sepsis is a common complication of severe trauma, burns, infection, or major surgery. This disease-related end-organ dysfunction results from systemic inflammatory response syndrome (SIRS). Acute kidney damage (AKI), also known as acute renal failure, is one of the most frequent and serious sequelae of sepsis. Nuclear transcription factor-κB (NF-κB) regulates the transcription of inflammation-related genes and operates as a mediator in the immune system. While parthenolide (PTL) has been reported to prevent harmful inflammatory reactions, its effects on sepsis-associated AKI are unknown. The current study investigates the effects of PTL in sepsis-associated AKI using cell and cecal ligation and puncture (CLP) models. Methods: Lipopolysaccharide (LPS)-stimulated rat glomerular mesangial cells were treated with 10 µM PTL. Inflammatory mediators, including TNF-α, IL-6, and IL-1ß, in the culture supernatants were measured by ELISA, and NF-κB levels were assessed by qPCR. After the generation of the septic CLP model, rats were intraperitoneally injected with 500 g/kg PTL and were euthanized after 72 h. Serum and kidney samples were analyzed. Results: TNF-α, IL-1ß, and IL-6 levels were elevated after LPS treatment of rat glomerular mesangial cells (p=0.004, p=0.002, and p=0.004, respectively) but were significantly reduced in the PTL treatment group (p ≤ 0.001, p=0.01, and p ≤ 0.001). NF-κB p65 levels were also increased after LPS treatment in this group and were reduced in the PTL treatment group. PTL treatment also reduced kidney damage after CLP induction, as shown by histological analysis and reductions in the levels of BUN, Cre, KIM-1, and NAGL. CLP-induced kidney inflammation together with increased levels of proinflammatory cytokines and inflammatory-related proteins. The elevated levels of renal TNF-α, IL-6, and IL-1ß were downregulated after PTL treatment. The PTL treatment also reduced the CLP-induced activation of NF-κB p65 in the damaged kidneys. Conclusion: PTL reduced inflammation induced by CLP-induced AKI in rat models and LPS-induced damage to glomerular mesangial cells by suppressing NF-κB signaling.

A Poling-Free Supramolecular Crown Ether Compound with Large Piezoelectricity.

Supramolecular host-guest ferroelectrics based on solution processing are highly desirable because they are generally created with intrinsic piezoelectricity/ferroelectricity and do not need further poling. Poly(vinylidene fluoride) (PVDF) in the electric-active beta phase after stretching/annealing still shows no piezoelectric response unless poled. Although many supramolecular host-guest ferroelectrics have been discovered, their piezoelectricity is relatively small. Based on H/F substitution, we reported a supramolecular host-guest compound [(CF3-C6H4-NH3)(18-crown-6)][TFSA] (CF3-C6H4-NH3 = 4-trifluoromethylanilinium, TFSA = bis(trifluoromethanesulfonyl)ammonium) with a remarkable piezoelectric response of 42 pC/N under no poling condition. The introduction of F atoms increases phase transition temperature, polar axes, second harmonic generation (SHG) intensity, and piezoelectric coefficient d33. To our knowledge, such a large piezoelectric performance of [(CF3-C6H4-NH3)(18-crown-6)][TFSA] makes its d33, piezoelectric voltage coefficient g33, and mechanical quality factor Qm the highest among the reported supramolecular host-guest ferroelectric compounds and even larger than the values of PVDF. This work provides inspiration for optimizing piezoelectricity on molecular materials.

Blood monocyte levels predict the risk of acute exacerbations of chronic obstructive pulmonary disease: a retrospective case-control study.

Monocytes were critical cells in the innate immune system. Monocyte recruitment to the lungs is a crucial process of pathophysiology in chronic obstructive pulmonary disease (COPD). Current evidence on the association between the occurrence of acute exacerbations of COPD (AECOPD) and monocytes was unclear. This study aimed to examine whether blood monocytes are associated with the occurrence of AECOPD and to determine the specific blood monocyte level to predict AECOPD. A retrospective case-control study was conducted at Changhua Christian Hospital. A total of 444 eligible patients with COPD were included between January 2017 and December 2019. Restricted cubic splines were used to analyze the nonlinear relationships between continuous white blood cell values and the occurrence of AECOPD. The association between monocytes and the occurrence of AECOPD was assessed using the logistic, lasso, and ridge regression models. Restricted cubic splines revealed nonlinear associations among the monocyte level, the continuous value of the eosinophil-to-lymphocyte ratio, and the occurrence of AECOPD. The lowest risk of occurrence of AECOPD ranged from 7.4 to 10%; < 7.4% with an absolute count < 0.62 or > 10% indicated significant risk. No significant association was noted between the eosinophil-to-lymphocyte ratio categories in the tertiles (< 0.049, 0.049 to < 0.122, and ≥ 0.122) and the risk of AECOPD. A significantly higher risk was noted in the association of the occurrence of AECOPD with the CAT score; mMRC score; wheezing cough; preexisting chronic pulmonary disease; hypertension and malignancy; use of dual- and triple, and oral long-acting bronchodilators for COPD treatment; and WBC count. We reported a nonlinear relationship between monocytes and the occurrence of AECOPD. Patients with monocyte percentage of > 10% or < 7.4% with an absolute count < 0.62 had higher risk of occurrence of AECOPD. Overall, our study demonstrated the specific value of monocytes in identifying high risks of the occurrence of AECOPD; this value is an easy-to-obtain, inexpensive biomarker in patients with AECOPD and should be further investigated in future prospective clinical studies.

Prognostic Value of Systemic Immune-Inflammation Index (SII) in Patients with Glioblastoma: A Comprehensive Study Based on Meta-Analysis and Retrospective Single-Center Analysis.

Inflammation is related to cancer. The systemic immune-inflammation index (SII) has been linked to the prognosis of many types of cancer. The present study aimed to determine the prognostic value of the SII in glioblastoma (GBM) patients based on meta-analysis and single-center retrospective analysis. Relevant publications published before 1 October 2022 were identified by searching PubMed, EMBASE, Cochrane Library databases, and Web of Science. Moreover, 208 GBM patients from Zhongnan Hospital were incorporated. Kaplan−Meier and Cox regression analyses determined the prognostic significance of inflammatory markers. By combining these indicators, we developed scoring systems. Nomograms were also built by incorporating independent variables. The accuracies of nomograms were evaluated by Harrell's concordance index (c-index) and the calibration curve. According to meta-analysis, an elevated SII predicted the worst overall survival (OS) (Hazard ratio [HR] = 1.87, p < 0.001). Furthermore, a higher SII (>510.8) (HR = 1.782, p = 0.007) also predicted a poorer outcome in a retrospective cohort. The scoring systems of SII-NLR (neutrophil-to-lymphocyte ratio) showed the best predictive power for OS. The nomogram without MGMT (c-index = 0.843) exhibited a similar accuracy to that with MGMT (c-index = 0.848). A pre-treatment SII is independently associated with OS in GBM. A nomogram integrating the SII-NLR score may facilitate a comprehensive survival evaluation independent of molecular tests in GBM.

Assistive Mobility Control of a Robotic Hip-Knee Exoskeleton for Gait Training.

In this paper, we present an assistive mobility control for a robotic hip-knee exoskeleton intended for gait training. The robotic hip-knee exoskeleton is designed with an active flexion/extension and a passive abduction/adduction at each hip joint and an active flexion/extension at each knee joint to comply with the movement of lower limbs. While facilitating walking with the robotic exoskeleton, model-free linear extended state observer (LESO)-based controllers are proposed for gait control, in which the LESO is used to deal with each user's different lower limb parameters and unknown exerted torques. Walking and ascending experiments were conducted to evaluate the performance of the proposed methods, and the results are shown with respect to walking parameters. Moreover, a preliminary study for an extended application to the recovery of normal gaits that relieves the freezing of gait (FOG) in Parkinson's disease (PD) patients is also investigated in the paper.

The Mediating Effect of Cytokines on the Association between Fungal Sensitization and Poor Clinical Outcome in Asthma.

Sensitization to fungal allergens is one of the proposed phenotypes in asthma. An association between fungal sensitization and worse clinical outcomes is apparent. Moreover, fungal sensitization in asthma that is associated with different type of immunological mechanism has been reported. How the role of cytokines mediates the association between fungal sensitization and poorer asthmatic outcomes remains unclear. We aimed to determine role of cytokines in the relationship between fungal sensitization and worse clinical outcomes in asthma. METHOD: We conducted a prospective study to recruit adult patients with asthma. Data including age, sex, height, weight, smoking history, medication, emergency visit and admission, pulmonary function testing result, and Asthma Control Test (ACT) scores were collected. We used the automated BioIC method to measure fungal allergen sIgE in sera. Serum levels of Interleukin (IL) -4, IL-13, IL-6, IL-9, IL-10, IL-17 A, IL-22, Interferon (IFN) -γ, Immunoglobulin E (IgE), Tumor necrosis factor-α (TNF-α), and Transforming growth factor-ß (TGF-ß) were measured using ELISA. RESULT: IL-6 and IL-17A had a significant positive correlation between sensitization and most fungi species compared to IgE. Sensitization to Candida albicans had strongly positive association both with IL-6 and IL-17A. However, only IL-17A had significant relationship with ED visit times. The mediation analysis result indicates that IL-17A had a significant positively mediating effect (ME) on the association between Candida albicans and ED visit times. CONCLUSION: IL-17A is a potential mediator to link Candida albicans sensitization and ED visits for asthma. We suggest that patients with fungal sensitization, such as Candida albicans, have poorer outcomes associated with Th17-mediated immune response rather than Th2.

Cumulative Scoring Systems and Nomograms for Predicating Survival in Patients With Glioblastomas: A Study Based on Peripheral Inflammatory Markers.

Inflammation is a hallmark of cancers. The purpose of the present study was to evaluate the prognostic potential of hematological inflammatory markers in glioblastoma multiforme (GBM) patients. The clinical data of 99 patients with lower-grade gliomas and 88 patients with GBMs were retrospectively analyzed. The optimal cutoff values for peripheral markers were determined by X-tile. Kaplan-Meier and Cox proportional hazard regression analyses were performed to identify markers with prognostic significance. Several scoring systems were constructed by combining these prognostic markers. The predictive accuracies of nomograms incorporating these scoring systems were evaluated by Harrell's concordance index and receiver operating characteristic curve analysis. GBM patients exhibited higher neutrophil counts (p=0.001), neutrophil-to-lymphocyte ratio (NLR) (p<0.001), and platelet-to-lymphocyte ratio (PLR) (p=0.001), as well as lower lymphocyte counts (p=0.023), lymphocyte-to-monocyte ratio (LMR) (p=0.015), and albumin-to-globulin ratio (AGR) (p=0.003) than those with lower-grade gliomas. Multivariate analysis indicated that a high NLR (> 2.0) (Hazard ratio[HR]=2.519, 95% confidence interval (CI): 1.220-5.204, p=0.013), low LMR (< 2.3) (HR=2.268, 95%CI: 1.172-4.386, p=0.015), or low AGR (< 1.7) (HR=2.924, 95%CI: 1.389-6.135, p=0.005) were associated with poor overall survival in GBM patients. The scoring systems of AGR-NLR, AGR-LMR, and LMR-NLR were associated with GBM survival. The nomogram integrating AGR-NLR score had the best efficacy in predicting GBM survival (c-index=0.874). Pretreatment scores of AGR-NLR, AGR-LMR, and LMR-NLR may serve as prognostic factors for GBM patients, and a nomogram integrating AGR-NLR may provide a reliable tool to facilitate personalized preoperative evaluations.

Effectiveness of Nationwide COPD Pay-for-Performance Program on COPD Exacerbations in Taiwan.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has also imposed a substantial economic and social burden on the health care system. In Taiwan, a nationwide COPD pay-for-performance (P4P) program was designed to improve the quality of COPD-related care by introducing financial incentives for health care providers and employing a multidisciplinary team to deliver guideline-based, integrated care for patients with COPD, reducing adverse outcomes, especially COPD exacerbation. However, the results of a survey of the effectiveness of the pay-for-performance program in COPD management were inconclusive. To address this knowledge gap, this study evaluated the effectiveness of the COPD P4P program in Taiwan. METHODS: This retrospective cohort study used data from Taiwan's National Health Insurance claims database and nationwide COPD P4P enrollment program records from June 2016 to December 2018. Patients with COPD were classified into P4P and non-P4P groups. Patients in the P4P group were matched at a ratio of 1:1 based on age, gender, region, accreditation level, Charlson Comorbidity Index (CCI), and inhaled medication prescription type to create the non-P4P group. A difference-in-difference analysis was used to evaluate the influence of the P4P program on the likelihood of COPD exacerbation, namely COPD-related emergency department (ED) visit, intensive care unit (ICU) admission, or hospitalization. RESULTS: The final sample of 14,288 patients comprised 7144 in each of the P4P and non-P4P groups. The prevalence of COPD-related ED visits, ICU admissions, and hospitalizations was higher in the P4P group than in the non-P4P group 1 year before enrollment. After enrollment, the P4P group exhibited a greater decrease in the prevalence of COPD-related ED visits and hospitalizations than the non-P4P group (ED visit: -2.98%, p<0.05, 95% confidence interval [CI]: -0.277 to -0.086; hospitalization: -1.62%, p<0.05, 95% CI: -0.232 to -0.020), whereas no significant difference was observed between the groups in terms of the changes in the prevalence of COPD-related ICU admissions. CONCLUSION: The COPD P4P program exerted a positive net effect on reducing the likelihood of COPD exacerbation, namely COPD-related ED visits and hospitalizations. Future studies should examine the long-term cost-effectiveness of the COPD P4P program.

Temozolomide-Induced Changes in Gut Microbial Composition in a Mouse Model of Brain Glioma.

BACKGROUND: Gut microbiota is associated with the progression of brain tumors. However, the alterations in gut microbiota observed during glioma growth and temozolomide (TMZ) therapy remain poorly understood. METHODS: C57BL/6 male mice were implanted with GL261 glioma cells. TMZ/sodium carboxymethyl cellulose (SCC) was administered through gavage for five consecutive days (from 8 to 12 days after implantation). Fecal samples were collected before (T0) and on days 7 (T1), 14 (T2), and 28 (T3) after implantation. The gut microbiota was analyzed using 16S ribosomal DNA sequencing followed by absolute and relative quantitation analyses. RESULTS: Nineteen genera were altered during glioma progression with the most dramatic changes in Firmicutes and Bacteroidetes phyla. During glioma growth, Lactobacillus abundance decreased in the early stage (T1) and then gradually increased (T2, T3); Intestinimonas abundance exhibited a persistent increase; Anaerotruncus showed a transient increase (T2) and then a subsequent decrease (T3). Similar longitudinal changes in Intestinimonas and Anaerotruncus abundance were observed in TMZ-treated mice, but the decrease of Anaerotruncus at T3 in the TMZ-treated group was less than that in the vehicle-treated group. No significant change in Lactobacillus was observed after TMZ treatment. Additionally, compared to vehicle control, TMZ treatment led to an enrichment in Akkermansia and Bifidobacterium. CONCLUSION: Glioma development and progression altered the composition of gut microbiota. Induction of Akkermansia and Bifidobacterium as well as the prevention of the reduction in Anaerotruncus may contribute to the anti-tumor effect of TMZ. This study helps to reveal the association between levels of specific microbial species in the gut and the anti-tumor effect of TMZ.

Aqueous Extract of Kan-Lu-Hsiao-Tu-Tan Ameliorates Collagen-Induced Arthritis in Mice by Inhibiting Oxidative Stress and Inflammatory Responses.

BACKGROUND: Kan-Lu-Hsiao-Tu-Tan (KLHTT) exhibits anti-psoriatic effects through anti-inflammatory activity in mice. However, the therapeutic effects of KLHTT on rheumatoid arthritis (RA), another significant autoimmune inflammatory disorder, have not been elucidated. Herein, we explored the anti-arthritic effects of KLHTT on collagen-induced arthritis (CIA) in mice. METHODS: KLHTT was extracted by boiling water and subjected to spectroscopic analysis. Chicken collagen type II (CII) with complete Freund's adjuvant was intradermally injected to induce CIA in DBA/1J mice. Anti-CII antibody, cytokines, malondialdehyde (MDA), and hydrogen peroxide (H2O2) were measured using ELISA, thiobarbituric acid reactive substances, and a hydrogen peroxide assay kit. Splenocyte proliferation was tested using thymidine incorporation. Th1 and Th17 cells were analyzed by flow cytometry. RESULTS: Oral KLHTT treatment (50 and 100 mg/kg) ameliorated mouse CIA by decreasing the levels of interleukin (IL)-1ß, IL-6, IL-17A, and tumour necrosis factor-α in the paw homogenates and serum. KLHTT also suppressed anti-CII antibody formation, splenocyte proliferation, and splenic Th1 and Th17 cell numbers. Additionally, KLHTT showed antioxidant activity by reducing the concentrations of MDA and H2O2 in paw tissues. CONCLUSIONS: The therapeutic effects of KLHTT in CIA mice were through regulating oxidative stress and inflammatory responses. Our results suggest that KLHTT has potential to treat RA.

Tiotropium/Olodaterol treatment reduces cigarette smoke extract-induced cell death in BEAS-2B bronchial epithelial cells.

BACKGROUND: Cigarette smoking is a critical risk factor for the destruction of lung parenchyma or the development of emphysema, which is characteristic of COPD. Disruption of epithelial layer integrity may contribute to lung injury following cigarette smoke extract (CSE) exposure. Tiotropium/olodaterol acts as a bronchodilator for COPD treatment; however, the effect of dual bronchodilators on epithelial cell injury and its underlying mechanism remain unclear. In this study, we evaluated the effect of tiotropium/olodaterol on CSE-mediated cell death and the underlying mechanisms. METHODS: Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis, necrosis, and autophagy were evaluated using flow cytometry. Autophagy-related protein, phosphorylated ERK, expression was determined using Western blotting. RESULTS: Tiotropium/olodaterol significantly inhibited CSE-induced cell death, mitochondria dysfunction, and autophagy, which had no significant effect on apoptosis or necrosis in BEAS-2B human bronchial epithelial cells. Moreover, tiotropium/olodaterol attenuated CSE-induced upregulation of JNK. CONCLUSIONS: CSE induced cell death and caused consistent patterns of autophagy and JNK activation in BEAS-2B human bronchial epithelial cells. Tiotropium/olodaterol treatment protected bronchial epithelial cells from CSE-induced injury and inhibited activation of autophagy and upregulation of JNK phosphorylation. These results indicate that tiotropium/olodaterol may protect epithelial cells from the deleterious effects of CSE exposure, which is associated with the regulation of autophagy and JNK activation.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Antihelminthic Niclosamide Induces Autophagy and Delayed Apoptosis in Human Non-small Lung Cancer Cells In Vitro and In Vivo.

BACKGROUND/AIM: Niclosamide is an antihe-minthic drug that has shown cytotoxic effects on non-small cell lung carcinoma (NSCLC) cells. However, the exact mechanisms underlying the anti-tumour activity of niclosamide in NSCLC cancer cells remains to be defined. The aim of this study was to evaluate the antitumor activity of niclosamide in human A549 and CL1-5 non-small cell lung cancer cells using in vitro and in vivo. MATERIALS AND METHODS: We investigated the effects of niclosamide on cell viability, apoptosis, the mitochondrial membrane potential (MMP; Δϕm), and autophagy and apoptosis-related protein expression in human A549 and CL1-5 non-small cell lung cancer cells. RESULTS: Niclosamide induced mainly caspase-independent apoptosis through apoptosis-inducible factor (AIF) translocation to the nucleus upon mitochondria damage. Moreover, niclosamide-induced autophagy may act as adaptive response against apoptosis. AMPK/AKT/mTOR pathway were involved in niclosamide-induced cell death and autophagy in response to ATP depletion. Furthermore, niclosamide efficiently suppressed tumor growth and induce autophagy in vivo. CONCLUSION: Niclosamide induced apoptosis by activating the intrinsic and caspase-independent pathway in human A549 and CL1-5 non-small cell lung cancer cells. Therefore, niclosamide is a potential candidate for anti-NSCLC therapy.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

[The third-generation sequencing combined with targeted capture technology for high-resolution HLA typing and MHC region haplotype identification].

The high-resolution and accurate typing of human leukocyte antigen (HLA) is of great significance for the study of tissue matching in organ transplantation and the correlation between HLA and disease. In this study, the peripheral blood of 12 patients with primary hepatocellular carcinoma was used to compare the advantages and disadvantages of the next- and third-generation sequencing technology for high-resolution HLA typing. In addition, probe capture technology was used to capture the MHC region of YH and HeLa standard cell lines, and a primary hepatocellular carcinoma patient. The captured products were sequenced using PacBio platform to assess the potential of ultra-long reads sequencing technology for analysis of the entire MHC region. Our results showed that: (1) the next- and third-generation sequencing technology can both achieve 6-8 digit high resolution in HLA typing. However, the coverage of the third-generation is significantly better than the next-generation sequencing technology. (2) The ultra-long reads of the third generation sequencing can directly span the entire amplicon region, which has obvious advantages for haplotype phasing, with 92.79% of the HLA genes having accurate phasing results, which is much higher than the 75.65% from the next-generation data. (3) The long-reads from the third generating sequencing can not only be used to assemble the MHC region but also the ability to phase the entire MHC region of 3.6 Mb, thereby helping to clarify the localization information of the mutation sites, alleles and non-coding regions on each MHC haplotype, and providing a theoretical basis for the study of immune and other related diseases.

TGF-ß1 and TNF-α synergistically induce epithelial to mesenchymal transition of breast cancer cells by enhancing TAK1 activation.

TGF-ß1 is a main inducer of epithelial to mesenchymal transition (EMT). However, many breast cancer cells are not sensitive to the EMT induction by TGF-ß1 alone. So far, the mechanisms underlying the induction of TGF-ß1-insensitive breast cancer cells remains unclear. Here we report that TNF-α can induce EMT and invasiveness of breast cancer cells which are insensitive to TGF-ß1. Intriguingly, TGF-ß1 could cooperate with TNF-α to promote the EMT and invasiveness of breast cancer cells. The prolonged co-stimulation with TGF-ß1 and TNF-α could enhance the sustained activation of Smad2/3, p38 MAPK, ERK, JNK and NF-κB pathways by enhancing the activation of TAK1, which was mediated by the gradually up-regulated TßRs. Except for JNK, all of these pathways were required for the effects of TGF-ß1 and TNF-α. Importantly, the activation of p38 MAPK and ERK pathways resulted in a positive feed-back effect on TAK1 activation by up-regulating the expression of TßRs, favoring the activation of multiple signaling pathways. Moreover, SLUG was up-regulated and required for the TGF-ß1/TNF-α-induced EMT and invasiveness. In addition, SLUG could also enhance the activation of signaling pathways by promoting TßRII expression. These findings suggest that the up-regulation of TßRs contributes to the sustained activation of TAK1 induced by TGF-ß1/TNF-α and the following activation of multiple signaling pathways, resulting in EMT and invasiveness of breast cancer cells.

Synergistic Anticancer Effect of a Combination of Paclitaxel and 5-Demethylnobiletin Against Lung Cancer Cell Line In Vitro and In Vivo.

Lung cancer remains a highly prevalent disease and a leading cause of cancer-related deaths worldwide. Currently, exploring antitumor drugs derived from herbs used in traditional Chinese medicine is increasingly becoming an attractive area of research. Paclitaxel (PTX), a highly effective chemotherapeutic drug, is widely used for treating different cancers; however, the clinical use of PTX is dose limited because of its adverse side effects. Chemotherapeutic agents are being developed to enhance the anticancer activity of PTX, particularly for use in combination therapy. 5-Demethylnobiletin (5-DMN), a natural, active compound isolated from orange peel, has been reported to induce apoptosis in several cancer cell lines. In this study, we tested the synergistic anticancer antiproliferative effects of combinations of PTX and 5-DMN on CL1-5 lung cancer cells through the MTT and propidium iodide assays. After low-dose combination treatments (PTX and 5-DMN), a reduction in cell viability and a concomitant increase in apoptosis were observed in the CL1-5 cells. We propose that 5-DMN cooperates with PTX to induce apoptosis via the caspase pathway (by modulating caspase-3, caspase-8, and caspase-9 activities). Furthermore, we observed that the combination treatment significantly suppressed tumor growth in the nude mouse xenograft model. The results suggest that the synergistic effects of PTX and 5-DMN in lung cancer cells deserve particular attention and indicate the possibility of developing additional new strategies for treating lung cancer.