Allergy-related Evidences in Relation to Serum IgE:Data from the China State Key Laboratory of Respiratory Disease,2008-2013

Objective To investigate the serum total IgE （tlgE） and specific IgE （slgE） to common allergens among allergic patients in Guangzhou, China. Methods 7 085 patients were examined for tlgE and slgE to 15 allergens, based on the protocols of reversed enzyme allergosorbent test and the sandwich enzyme-linked immunosorbent assay. Results 3 758 （53.04%） patients tested positive for tlgE, and 4 640 （65.49%） for slgE. Der pteronyssinus, Derfarinae, eggs, and cow＇s milk were the most common allergens leading to higher positive rates of slgE responses. Several peaks of sensitization were： Der pteronyssinus, Derfarinae, and Blomia tropicalis at age 10-12; cow＇s milk at age below 3; eggs at age 4-6. The mean level and positive rate of tlgE tended to increase in subjects sensitized to more allergens. Sensitization to Der pteronyssinus （OR, 1.6; P〈O.05）, Der farinae （OR, 1.5; P〈O.05）, Blomia tropicalis （OR, 1.4; P〈O.05）, Blattella germanica （OR, 1.5; P〈O.05）, cow＇s milk （OR, 1.3; P〈O.05）, and soy beans （OR, 2.0; P〈O.05） were independently correlated with allergy-related conditions in preliminary diagnosis. Conclusion The major allergens in Guangzhou include Derpteronyssinus, Derfarinae, cow＇s milk, and eggs. Sensitization to these allergens appears to be predictors of allergy-related disorder.

Isolated diatomic Zn-Co metal–nitrogen/oxygen sites with synergistic effect on fast catalytic kinetics of sulfur species in Li-S battery

Lithium-sulfur batteries are severely restricted by low electronic conductivity of sulfur and Li_(2)S,shuttle effect,and slow conversion reaction of lithium polysulfides(LiPSs).Herein,we report a facile and highyield strategy for synthesizing dual-core single-atom catalyst(ZnCoN_(4)O_(2)/CN)with atomically dispersed nitrogen/oxygen-coordinated Zn-Co sites on carbon nanosheets.Based on density functional theory(DFT)calculations and LiPSs conversion catalytic ability,ZnCoN_(4)O_(2)/CN provides dual-atom sites of Zn and Co,which could facilitate Li^(+)transport and Li_(2)S diffusion,and catalyze LiPSs conversion more effectively than homonuclear bimetallic single-atom catalysts or their simple mixture and previously reported singleatom catalysts.Li-S cell with ZnCoN_(4)O_(2)/CN modified separator showed excellent rate performance(789.4 mA h g^(-1)at 5 C)and stable long cycle performance(0.05%capacity decay rate at 6C with 1000cycles,outperforming currently reported single atomic catalysts for LiPSs conversion.This work highlights the important role of metal active centers and provides a strategy for producing multifunctional dual-core single atom catalysts for high-performance Li-S cells.

Pharmacodynamic study in multi-animal models on the efficacy and optimal dosage of antiviral oral liquid for children

Antiviral Oral Liquid(AOL)is an adult medicine in the Chinese Pharmacopoeia used to treat upper respiratory infections such as influenza.It has shown promising clinical efficacy in relieving flu-like symptoms such as fever,inflammation,and pharyngalgia both in adults and children.However,the instruction manual does not specify the exact usage and dosage of AOL for children.In this article,we set 6 dosage ranges:0.2,0.5,0.7,0.9,1.1,1.4 mL/kg/d,according to its dosage for adults and the conversion method between adult and children dosage.And six animal models were used to evaluate the effectiveness of AOL in different doses.The results indicated that AOL could reduce the lung index,virus load,and expression of proinflammatory cytokines in the lung.AOL could improve pathological changes and prolong the survival time of mice infected by the Influenza A virus(H1N1)A/PR/8/34 strains at 0.5–0.9 mL/kg/d concentrations in different degrees.The four dose groups of 0.7–1.4 mL/kg/d could significantly inhibit the ear shell swelling caused by xylene and reduce the rabbit body temperature induced by lipopolysaccharide(P<0.01,P<0.05).All the five dosage groups of 0.2–1.1 mL/kg/d could inhibit the increase of peritoneal capillary permeability induced by glacial acetic acid(P<0.01).AOL at 0.7 and 0.9 mL/kg/d reduced the painful writhing times in young mice induced by glacial acetic(P<0.01).These results indicated that the optimal dose of AOL in antiviral,antipyretic,anti-inflammatory,and analgesic effects is 0.7 mL/kg/d.

Clinical characteristics,management,and prevention of coronavirus disease 2019

Coronavirus disease 2019(COVID-19)is the third severe acute respiratory disease of the 21st century and the most aggressive global pandemic to date.The whole population has been susceptible to the disease,particularly the emerging variants of the virus.The core pathophysiological mechanism is viral sepsis that can lead to the respiratory tract disorders and even systemic disorders such as cytokine release syndrome,thrombosis,abnormal angiogenesis,and multiple organ dysfunction.Despite only few licensed treatments to date,rapid advances have been made in exploring the effectiveness and safety of pharmacological interventions and vaccines.However,three pillars of preventative and control measures-proactive contact tracing,wearing facial masks,and social distancing-are essential to combat the ongoing pandemic.As the number of patients recovering from COVID-19 rapidly increases,the world has entered the era of caring for patients during the convalescence phase.This phase still represents a largely unmet medical need globally.

Effect of early enteral nutrition on postoperative nutritional status and immune function in elderly patients with esophageal cancer or cardiac cancer

To explore the effect of early enteral nutrition （EN） on postoperative nutritional status, intestinal permeability, and immune 6anction in elderly patients with esophageal cancer or cardiac cancer. Methods： A total of 96 patients with esophageal cancer or cardiac cancer who underwent surgical treatment in our hospital from June 2007 to December 2010 were enrolled in this study. They were divided into EN group （n=50） and parenteral nutrition （PN） group （n=46） based on the nutrition support modes. The body weight, time to first flatus/defecation, average hospital stay, complications and mortality after the surgery as well as the liver function indicators were recorded and analyzed. Peripheral blood samples were collected on the days 1, 4 and 7 after surgery. The plasma diamine oxidase （DAO） activity and D-lactate level were determined to assess the intestinal permeability. The plasma endotoxin levels were determined using dynamic turbidimetric assay to assess the protective effect of EN on intestinal mucosal barrier. The postoperative blood levels of inflammatory cytokines and immunoglobulins were determined using enzyme- linked immunosorbent assay （ELISA）. Results： After the surgery, the time to first flatus/defecation, average hospital stay, and complications were significantly less in the EN group than those in the PN group （P〈0.05）, whereas the EN group had significantly higher albumin levels than the PN group （P〈0.05）. On the 7th postoperative day, the DAO activity, D-lactate level and endotoxin contents were significantly lower in the EN group than those in the PN group （all P〈0.05）. In addition, the EN group had significantly higher IgA, IgG, IgM, and CD4 levels than the PN group （P〈0.05） but significantly lower IL-2, IL-6, and TNF-a levels （P〈0.05）. Conclusions： In elderly patients with esophageal cancer or cardiac cancer, early EN after surgery can effectively improve the nutritional status, protect intestinal mucosal barrier （by reducing plasma endoxins）, and enhance the immune function

Respiratory Virus Multiplex RT-PCR Assay Sensitivities and Influence Factors in Hospitalized Children with Lower Respiratory Tract Infections

Multiplex RT-PCR assays have been widely used tools for detection and differentiation of a panel of respiratory viral pathogens. In this study, we evaluated the Qiagen ResPlex II V2.0 kit and explored factors influencing its sensitivity. Nasopharyngeal swab (NPS) specimens were prospectively collected from pediatric inpatients with lower respiratory tract infections at the time of admission in the Shenzhen Children's Hospital from May 2009 to April 2010. Total nucleic acids were extracted using the EZ1 system (Qiagen, Germany) and 17 respiratory viruses and genotypes including influenza A virus (FluA), FluB, parainfluenza virus 1 (PIV1), PIV2, PIV3, PIV4, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), rhinoviruses (RhV), enteroviruses (EnV), human bocaviruses (hBoV), adenoviruses (AdV), four coronaviruses (229E, OC43, NL63 and HKU1), and FluA 2009 pandemic H1N1(H1N1-p) were detected and identified by the ResPlex II kit. In parallel, 16 real-time TaqMan quantitative RT-PCR assays were used to quantitatively detect each virus except for RhV. Influenza and parainfluenza viral cultures were also performed. Among the total 438 NPS specimens collected during the study period, one or more viral pathogens were detected in 274 (62.6%) and 201(45.9%) specimens by monoplex TaqMan RT-PCR and multiplex ResPlex, respectively. When results from monoplex PCR or cell culture were used as the reference standard, the multiplex PCR possessed specificities of 92.9-100.0%. The sensitivity of multiplex PCR for PIV3, hMPV, PIV1 and BoV were 73.1%, 70%, 66.7% and 55.6%, respectively, while low sensitivities (11.1%-40.0%) were observed for FluA, EnV, OC43, RSV and H1N1. Among the seven viruses/genotypes detected with higher frequencies, multiplex PCR sensitivities were correlated significantly with viral loads determined by the TaqMan RT-PCR in FluA, H1N1-p and RSV (p=0.011-0.000). The Qiagen ResPlex II multiplex RT-PCR kit possesses excellent specificity for simultaneous detection of 17 viral pathogens in NPS specimens in pediatric inpatients at the time of admission. The sensitivity of multiplex RT-PCR was influenced by viral loads, specimen process methods, primer and probe design and amplification condition.

Erucic acid from Isatis indigotica Fort. suppresses influenza A virus replication and inflammation in vitro and in vivo through modulation of NF-kB and p38 MAPK pathway

Isatis indigotica Fort.(Ban-Lan-Gen)is an herbal medicine prescribed for influenza treatment.However,its active components and mode of action remain mostly unknown.In the present study,erucic acid was isolated from Isatis indigotica Fort.,and subsequently its underlying mechanism against influenza A virus(IAV)infection was investigated in vitro and in vivo.Our results demonstrated that erucic acid exhibited broad-spectrum antiviral activity against IAV resulting from reduction of viral polymerase transcription activity.Erucic acid was found to exert inhibitory effects on IAV or viral(v)RNA-induced pro-inflam-matory mediators as well as interferons(IFNs).The molecular mechanism by which erucic acid with antiviral and anti-inflammatory properties was attributed to inactivation of NF-kB and p38 MAPK signaling.Furthermore,the NF-kB and p38 MAPK inhibitory effect of erucic acid led to diminishing the transcriptional activity of interferon-stimulated gene factor 3(ISGF-3),and thereby reducing IAV-triggered pro-inflammatory response amplification in IFN-β-sensitized cells.Additionally,IAV-or vRNA-triggered apoptosis of alveolar epithelial A549 cells was prevented by erucic acid.In vivo,erucic acid administration consistently displayed decreased lung viral load and viral antigens expression.Meanwhile,erucic acid markedly reduced CD8+cytotoxic T lymphocyte(CTL)recruitment,pro-apoptotic signaling,hyperactivity of multiple signaling pathways,and exacerbated immune inflammation in the lung,which resulted in decreased lung injury and mortality in mice with a mouse-adapted A/FM/1/47-MA(H1N1)strain infection.Our findings provided a mechanistic basis for the action of erucic acid against IAV-mediated inflammation and injury,suggesting that erucic acid may have a therapeutic potential in the treatment of influenza.

The Effects of Secondary Pneumonia on the Curative Efficacy of Multidrug-resistant Tuberculosis: A Retrospective Cohort Study

Tuberculosis(TB)is a formidable global health problem and ranks above HIV as the leading cause of death world wide.In2017,a total number of 10.0 million cases of TB were reported, which resulted in1.3 million TB deaths. Resistance to standard anti-TB

Strategies for Antiviral Screening Targeting Early Steps of Virus Infection

Viral infection begins with the entry of the virus into the host target cell and initiates replication. For this reason, the virus entry machinery is an excellent target for antiviral therapeutics. In general, a virus life cycle includes several major steps: cell-surface attachment, entry, replication, assembly, and egress, while some viruses involve another stage called latency. The early steps of the virus life cycle include virus attachment, receptor binding, and entry. These steps involve the initial interactions between a virus and the host cell and thus are major determinants of the tropism of the virus infection, the nature of the virus replication, and the diseases resulting from the infection. Owing to the pathological importance of these early steps in the progress of viral infectious diseases, the development of inhibitors against these steps has been the focus of the pharmaceutical industry. In this review, Herpes Simplex Virus (HSV), Hepatitis C Virus (HCV), and Human Enterovirus 71 (EV71) were used as representatives of enveloped DNA, enveloped RNA, and non-enveloped viruses, respectively. The current mechanistic understanding of their attachment and entry, and the strategies for antagonist screenings are summarized herein.

Classification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas

The limited molecular classifications and disease signatures of osteoarthritis(OA)impede the development of prediagnosis and targeted therapeutics for OA patients.To classify and understand the subtypes of OA,we collected three types of tissue including cartilage,subchondral bone,and synovium from multiple clinical centers and constructed an extensive transcriptome atlas of OA patients.By applying unsupervised clustering analysis to the cartilage transcriptome,OA patients were classified into four subtypes with distinct molecular signatures:a glycosaminoglycan metabolic disorder subtype(C1),a collagen metabolic disorder subtype(C2),an activated sensory neuron subtype(C3),and an inflammation subtype(C4).Through ligand-receptor crosstalk analysis of the three knee tissue types,we linked molecular functions with the clinical symptoms of different OA subtypes.For example,the Gene Ontology functional term of vasculature development was enriched in the subchondral bone-cartilage crosstalk of C2 and the cartilage-subchondral bone crosstalk of C4,which might lead to severe osteophytes in C2 patients and apparent joint space narrowing in C4 patients.Based on the marker genes of the four OA subtypes identified in this study,we modeled OA subtypes with two independent published RNA-seq datasets through random forest classification.The findings of this work contradicted traditional OA diagnosis by medical imaging and revealed distinct molecular subtypes in knee OA patients,which may allow for precise diagnosis and treatment of OA.

Efficacy of third-line pemetrexed monotherapy versus pemetrexed combination with bevacizumab in patients with advanced EGFR mutation-positive lung adenocarcinoma

Objective： The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor（EGFR） mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.Patients and methods： One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin（GP） chemotherapy and second-line EGFR tyrosine kinase inhibitor（TKI） or with first-line EGFR-TKI and second-line GP chemotherapy.Results： The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups（P=0.04）. Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups（P=0.001）. Among 61 cases with thirdline pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different（P=0.001）.Conclusions： Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.

The efficacy of the inhalation of an aerosolized Group A streptococcal preparation in the treatment of lung cancer

Objective： To observe the efficacy of the inhalation of an aerosonzeo group ~ sueloto^u v / preparation in treating orthotopic lung cancer in mouse models and assess the feasibility, safety, and effectiveness of this administration mode for lung cancer. Methods： Lewis lung carcinoma （LLC） cell strains were administered via intrathoracic injection to establish orthotopic lung cancer mouse models. After the tumor-bearing models were successfully established, as confirmed by computed tomography, the mice were administered by inhalation with an aerosolized GAS preparation （GAS group） or aerosolized normal saline （control group）. The anti-tumor effect of the aerosolized GAS preparation was evaluated histologically; meanwhile, the survival and quality of life were compared between these two groups. Results： The aerosolized GAS preparation showed remarkably anti-tumor effect, causing the necrosis of the orthotopic lung cancer cells in tumor-bearing mice. Furthermore, mice in the GAS group had significantly better qualitT of life and longer survival than those in control group. Conclusions： The inhalation of aerosolized GAS preparation may be a feasible, safe and effective solution for lung cancer

The Influence of Pyrazinamide Monoresistance on Treatment Outcomes in Tuberculosis Patients from Southern China

This study aimed to explore the influence of pyrazinamide (PZA) monoresistance on the treatment outcome of otherwise drug susceptible tuberculosis (TB). A cohort of 194 TB patients that were infected with strains susceptible to isoniazid (INH), rifampin (RIF) and ethambutol (EMB) were included in a retrospective study at the Guangzhou Chest Hospital. We reported 148 (76.3%) PZA- susceptible TB cases and 46 (23.7%) PZA-monoresistance TB cases identified by the BACTEC MGIT 960 system. All patients were treated with the standard 6 months WHO recommended regimen, which included 2 months of INH + RIF + EMB + PZA in the intensive-phase, and the subsequent 4 months of INH + RIF during continuation-phase. Bacterial burden in the lungs was estimated using sputum smear acid-fast bacillary count while the lung lesions and cavitations were examined by X-ray at the end of first 2 months of chemotherapy. After intensive-phase treatment, there were 164 (84.5%) cases of smear-negative conversion and 151 (77.9%) cases of total or partial lesion elimination. The rates of smear-negative conversion (78.3%) and lesion elimination (39.1%) of the PZA-monoresistant patients were similar with the PZA-sensitive group (P > 0.05). However, lung cavitation was more likely to be resolved in PZA-sensitive patients than in the PZA-patients (X2 = 9.623, P = 0.002). The smear-negative conversion rates were 95.9% for the PZA-sensitive patients and 87.0% for the PZA-monoresistant patients after 6 months of treatment (X2 = 3.461, P = 0.063). Together, our data suggest that PZA-monoresistance contributes to the delay of resolution of the lung cavitations in the Southern China population without affecting the sputum conversion and lesion elimination rates.

Early screening of lung cancers:an effort arduous but worthwhile

Cancers are a concerning health catastrophe worldwide that may become the end of lifetime for many of us--they overwhelmingly exhaust medical resources, lead to huge economic burdens, and separate people from their beloved ones. Fewer and fewer insurance agencies are willing to include primary cancers on their general health insurance plan, just because cancers have been so flummoxingly usual in our daily life that many primary cancer claims would give rise to much less profits.

XRCC1 Arg194Trp Polymorphism and Risk of Chronic Obstructive Pulmonary Disease

The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease （COPD）. However, just 20%-30% smokers develop COPD, which suggests that different degrees of DNA repair cause different outcomes in smokers. X-ray repair cross-complementing group 1 （XRCC 1）, a base excision repair protein, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks. The present study investigated the association between polymorphism in XRCC1 （Arg399Gln） and susceptibility of COPD. A total of 201 COPD cases and 309 controls were recruited and frequency-matched on age and sex. XRCC1 genotype was determined by PCR-restriction fragment length polymorphism analysis. Overall, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD had no significant difference among individuals with Trp/Trp genotype. However, after stratifying by smoking status, in former smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Trp/Trp genotype （adjusted OR=0.22, 95% CI 0.06-0.85, P=0.028）; after stratifying by smoking exposure, in light smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Arg/Trp genotype and Trp/Trp genotype （adjusted OR=0.39, 95% CI 0.16=0.94, P=0.036; 0.24, 95% CI 0.07-0.79, P=0.019, respectively）. In conclusion, XRCC1 Arg194Trp genotype is associated with a reduced risk of developing COPD among former and light smokers.

Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice

COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection,the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits.We recently demonstrated that mast cells(MCs)are an essential mediator of SARS-CoV-2-initiated hyperinflammation.We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury.In this study,we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions in vivo,and demonstrated the benefits of co-administration of antihistamines and antiviral drug remdesivir in SARS-CoV-2-infected mice.Specifically,SARSCoV-2 spike protein-induced MC degranulation resulted in alveolar-capillary injury,while pretreatment of pulmonary microvascular endothelial cells with antihistamines prevented adhesion junction disruption;predictably,the combination of antiviral drug remdesivir with the antihistamine loratadine,a histamine receptor 1(HR1)antagonist,dampened viral replication and inflammation,thereby greatly reducing lung injury.Our findings emphasize the crucial role of MCs in SARS-CoV-2-induced inflammation and lung injury and provide a feasible combination antiviral and anti-inflammatory therapy for COVID-19 treatment.

Identification of a 10-pseudogenes signature as a novel prognosis biomarker for ovarian cancer

The outcomes of ovarian cancer are complicated and usually unfavorable due to their diagnoses at a late stage.Identifying the efficient prognostic biomarkers to improve the survival of ovarian cancer is urgently warranted.The survival-related pseudogenes retrieved from the Cancer Genome Atlas database were screened by univariate Cox regression analysis and further assessed by least absolute shrinkage and selection operator(LASSO)method.A risk score model based on the prognostic pseudogenes was also constructed.The pseudogene-mRNA regulatory networks were established using correlation analysis,and their potent roles in the ovarian cancer progression were uncovered by functional enrichment analysis.Lastly,ssGSEA and ESTIMATE algorithms was used to evaluate the levels of immune cell infiltrations in cancer tissues and explore their relationship with risk signature.A prediction model of 10-pseudogenes including RPL10P6,AC026688.1,FAR2P4,AL391840.2,AC068647.2,FAM35BP,GBP1P1,ARL4AP5,RPS3AP2,and AMD1P1 was established.The 10-pseudogenes signature was demonstrated to be an independent prognostic factor in patient with ovarian cancer in the random set(hazard ratio[HR]=2.512,95%confidence interval[CI]=2.03–3.11,P<0.001)and total set(HR=1.71,95%CI=1.472–1.988,P<0.001).When models integrating with age,grade,stage,and risk signature,the Area Under Curve(AUC)of the 1-year,3-year,5-year and 10-year Receiver Operating Characteristic curve in the random set and total set were 0.854,0.824,0.855,0.805 and 0.679,0.697,0.739,0.790,respectively.The results of functional enrichment analysis indicated that the underlying mechanisms by which these pseudogenes influence cancer prognosis may involve the immune-related biological processes and signaling pathways.Correlation analysis showed that risk signature was significantly correlated with immune cell infiltration and immune score.We identified a novel 10-pseudogenes signature to predict the survival of patients with ovarian cancer,and that may serve as novel possible prognostic biomarkers and therapeutic targets for ovarian cancer.

Bilirubin inhibits the anticancer activity of sorafenib by blocking MCL-1 degradation in hepatocellular carcinoma cells

Objective:Sorafenib is a first-line drug for advanced hepatocellular carcinoma(HCC).Unfortunately,most patients with HCC do not respond to sorafenib,mainly because of the frequent development of drug resistance.Bilirubin is an end metabolite of heme catabolism and an indicator of liver function,but its direct role in regulating the anticancer activity of sorafenib in HCC cells is unclear.In the current study,we aimed to investigate the mechanism of action of bilirubin in sorafenib-mediated tumor suppression in HCC.Methods:A retrospective observational cohort of 100 patients receiving sorafenib was conducted to evaluate the potential role of bilirubin in predicting the prognosis of patients with HCC.Human HCC cell lines were treated with sorafenib in the absence or presence of bilirubin,and cell proliferation,apoptosis,and signaling pathways were assayed.The antagonistic effect of bilirubin toward sorafenib was assessed in nude mice bearing HCC xenografts.Results:Serum levels of bilirubin(including total,direct,and indirect bilirubin)negatively correlated with the overall survival of patients with HCC treated with sorafenib(P<0.05).Both in vitro and in vivo analyses demonstrated that bilirubin significantly abrogated sorafenib-mediated proliferation inhibition and apoptosis induction in HCC cells(P<0.05).Mechanically,bilirubin inhibited sorafenib-induced activation of GSK-3βand subsequent downstream MCL-1 degradation.Conclusions:Our study provides experimental evidence of the antagonistic effect of bilirubin toward sorafenib-mediated anticancer activity in HCC,and it suggests that bilirubin could be used to predict the efficacy of sorafenib treatment.

Rapid diagnosis of disseminated Mycobacterium mucogenicum infection in formalin-fixed, paraffin-embedded specimen using nextgeneration sequencing: A case report

BACKGROUND Mycobacterium mucogenicum(M.mucogenicum)belongs to the group of rapidly growing Nontuberculous mycobacteria.This microorganism is associated with a wide spectrum of infectious diseases.Due to a low detection rate or the time required for conventional culture methodology,a rapid and broad-spectrum method is necessary to identify rare pathogens.CASE SUMMARY A 12-year-old immunocompetent girl presented with painful masses for five months.The first mass was found in the right upper quadrant of the abdomen,and was about 1 cm×1.5 cm in size,tough but pliable in texture,with an irregular margin and tenderness.An abscess gradually formed and ulcerated with suppuration of the mass.Three new masses appeared on the back one by one.Chest computed tomography showed patchy and streaky cloudy opacities in both lungs.Needle aspiration of the abscess was performed,but the smear and conventional culture were negative,and the pathological examination showed no pathogens.We then performed next-generation sequencing using a formalinfixed,paraffin-embedded specimen to identify the pathogen.A significantly high abundance of M.mucogenicum was detected.The patient’s abscesses gradually decreased in size,while inflammation in both lungs improved following 12-wk of treatment.No recurrence was observed four months after the end of the one-year treatment period.CONCLUSION Next-generation sequencing is a promising tool for the rapid and accurate diagnosis of rare pathogens,even when using a formalin-fixed,paraffin-embedded specimen.

Unexpectedly Strong Diamagnetism of Self-Assembled Aromatic Peptides

There is a considerable amount of work that shows the biomagnetism of organic components without ferromagnetic components at the molecular level,but it is of great challenge to cover the giant gap of biomagnetism between their experimental and theoretical results.Here we show that the diamagnetism of aromatic peptides is greatly enhanced for about 11 times by self-assembling,reaching two orders of magnitude higher than the mass susceptibility of pure water.The self-assembly of aromatic rings in the peptide molecules plays the key role in such a strong diamagnetism.