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.

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.

Application of Nanopore Sequencing Technology in the Clinical Diagnosis of Infectious Diseases

Infectious diseases are an enormous public health burden and a growing threat to human health worldwide.Emerging or classic recurrent pathogens,or pathogens with resistant traits,challenge our ability to diagnose and control infectious diseases.Nanopore sequencing technology has the potential to enhance our ability to diagnose,interrogate,and track infectious diseases due to the unrestricted read length and system portability.This review focuses on the application of nanopore sequencing technology in the clinical diagnosis of infectious diseases and includes the following:(i)a brief introduction to nanopore sequencing technology and Oxford Nanopore Technologies(ONT)sequencing platforms;(ii)strategies for nanopore-based sequencing technologies;and(iii)applications of nanopore sequencing technology in monitoring emerging pathogenic microorganisms,molecular detection of clinically relevant drug-resistance genes,and characterization of disease-related microbial communities.Finally,we discuss the current challenges,potential opportunities,and future outlook for applying nanopore sequencing technology in the diagnosis of infectious diseases.

Therapeutic potential of gasotransmitters for cold stress-related cardiovascular disease

Growing evidence has shown that exposure to low ambient temperature poses a huge challenge to human health globally.Actually,cold stress is closely associated with a higher incidence of cardiovascular morbidity and mortality in winter or in cold regions.Cellular and molecular mechanisms underlying cardiovascular complications in response to cold exposure have yet to be fully clarified.Considering that cold exposure is an important risk of cardiovascular complications,it is necessary to clarify the molecular mechanism of cold stress-induced cardiovascular diseases and to develop effective intervention strategies.Hydrogen sulfide(H2S),nitric oxide(NO),and carbon monoxide(CO)are well-known gasotransmitters that are endogenously produced in many biological systems.Accumulating studies have demonstrated that these gasotransmitters play a critical role in a wide spectrum of physiological and/or pathophysiological processes by regulating numerous signaling pathways.These gas signal molecules are emerging as important players in cardiovascular homeostasis,and disruption of these gasotransmitters is critically implicated in cardiovascular anomalies,such as hypertension,atherosclerosis,myocardial ischemia,heart failure,and stroke.Also,evidence is emerging that H2S,NO,and CO may be involved in the pathologies of cold stress-induced cardiovascular ailments.In this review,we aim to highlight and discuss the recent advances towards the development of gasotransmitters-based therapeutics for cold stress-related cardiovascular pathogenesis.We believe that the effects of H2S,NO,and CO on cardiovascular regulation under cold environment will attract tremendous interest in the near future as they serve as novel regulators of cardiovascular biology in cold environment.

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.

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.

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.

Pan-cancer analysis of positive regulatory domain-containing 16 in human tumors

Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multiple types of cancer by pan cancer analyses.Methods:UALCAN and TIMER2 database were utilized to evaluate PRDM16 expression in cancer patients.Gene Expression Profiling Interactive Analysis was employed to analyze the overall survival and disease-free survival across all The Cancer Genome Atlas Program tumors.Using the cBioPortal tool,we analyzed the mutation features of PRDM16 for the The Cancer Genome Atlas Program tumors,then utilized the Encyclopedia of RNA Interactomes database to predict the miRNA-mRNA relationships associated with the PRDM16 for all tumors.Results:The expression level of PRDM16 in the tumor tissues is lower than that in the normal tissues.Interesting,the high expression of PRDM16 has a positive effect on the prognosis of kidney clear cell carcinoma and lung adenocarcinoma,but not conducive to the prognosis of most cancers.In multiple cancer types,the expression of PRDM16 was significantly positively correlated with immune infiltration of cancer-associated fibroblasts.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated that PRDM16 may be related to transcriptional misregulation pathway in cancer.We identified potential miRNAs that play regulatory roles of PRDM16 in kidney clear cell carcinoma and lung adenocarcinoma.Conclusion:PRDM16 is expressed in different cancers,it can be used as a biomarker for prognosis of pan-cancer and is associated with immune infiltration.

Non-invasive estimation of pulmonary hypertension and clinical deterioration risk in pediatric congenital heart disease:Development and validation of predictive tools

To the Editor:Owing to the heterogeneity of congenital heart disease-associated pulmonary hypertension(CHDPH)disease and the development of the pulmonary vascular system in pediatric patients,the management of CHD-PH in children is signicantly different from that in adults.[1]Early identication and intervention of CHD-PH are of great signicance for disease management in children with CHD,and non-invasive,accurate clinical tools are urgently needed to predict PH risk in children with CHD.However,the applicability of the current risk-scoring system to pediatric CHD-PH remains unclear.Furthermore,there are presently no user-friendly,non-invasive online tools available for predicting CHD-PH,and there is a scarcity of related studies in Asian populations.This study aimed to develop and validate the prediction tools for estimating the risk of pulmonary hypertension and clinical deterioration in children with congenital heart disease.

Asian,regional,and national burdens of respiratory tract cancers and associated risk factors from 1990 to 2019:A systematic analysis for the global burden of disease study 2019

Background:Respiratory cancer is the leading cause of cancer-related deaths worldwide,but its statistics vary between the East and West.This study aimed to estimate the burdens of tracheal,bronchus,and lung(TBL)cancer and larynx cancer and their attributable risks from 1990 to 2019 in Asia,and at regional and national levels.Methods:This research evaluated the incidence,mortality,years lived with disability,years of life lost,and disability-adjusted life years(DALYs)for respiratory tract cancers using the Global Burden of Diseases,Injuries,and Risk Factors Study(GBD)2019 database.Age-standardized rates were calculated for TBL cancer from 1990 to 2019,adjusted for smoking and socio-demographic index(SDI).Deaths from TBL cancer and larynx cancer attributable to each risk factor were estimated for 33 Asian countries.Results:The age-standardized incidence and death rates for TBL cancer in Asia declined from 2010 to 2019,while the incidence rate of larynx cancer increased.Smoking was the leading specific risk factor for deaths from both TBL and larynx cancers.The burden of TBL cancer in Asian countries was influenced by SDI and smoking,particularly among males in Central Asia.Deaths,DALYs,and incidences of larynx cancer in East Asia had not changed significantly over the past 30 years,but showed slight downward trends in males and both sexes combined,and an upward trend in females in recent years.Conclusions:The past decade saw increases in numbers of incident cases and deaths from TBL cancer and larynx cancer in Asia.SDI and smoking were the main factors influencing the disease burden of TBL cancer in Asian countries.This study highlights the need for tailored cancer control programs to address the burden of respiratory tract cancers in different Asian countries.

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.

Clinical Characteristics of Hereditary Multiple Exostoses: A Retrospective Study of Mainland Chinese Cases in Recent 23 Years

Hereditary multiple exostoses（HME） are an autosomal dominant skeletal disease with wide variations in clinical manifestations among different ethnic groups. This study investigated the epidemiology, clinical presentations, pathogenetic features and treatment strategies of HME in China's Mainland. We searched and reviewed the related cases published since 1990 by searching electronic databases, namely SinoMed database, Wanfang database, CNKI, Web of Science and PubMed as well as Google search engines. A total of 1051 cases of HME（male-to-female ratio 1.5：1） were investigated and the diagnosis was made in 83% before the age of 10 years. Approximately 96% patients had a family history. Long bones, ribs, scapula and pelvis were the frequently affected sites. Most patients were asymptomatic with multiple palpable masses. Common complications included angular deformities, impingement on neighbouring tissues and impaired articular function. Chondrosarcomas transformation occurred in 2% Chinese cases. Among the cases examined, about 18% had mutations in EXT1 and 28% in EXT2. Frameshift, nonsense and missense mutations represented the majority of HME-causing mutations. Diagnosis of HME was made based on the clinical presentations and radiological documentations. Most patients needed no treatment. Surgical treatment was often directed to remove symptomatic exostoses, particularly those of suspected malignancy degeneration, and correction of skeletal deformities. This study shows some variance from current literature regarding other ethnic populations and may provide valuable baseline assessment of the natural history of HME in China's Mainland.

The Alteration and Significance of Surfactant Protein A in Rats Chronically Exposed to Cigarette Smoke

In order to confirm the alteration and significance of cigarette smoke exposure on SP-A in rats, 20 Wistar rats were assigned randomly to two groups： an N group （n=10）, and an S group （n=10）. The ultra-structural change was observed by electron microscopy. The number of cells positive for SPA was by immunohistochemically measured. The mRNA expression in the lung tissues was determined by reverse transcription polymerase chain reaction （RT-PCR）. The number of cells positive for SPA of the S group （0.52±0.05） was lower than that of the N group （0.72±0.06） （P〈0.05）. The levels of mRNA of SPA in the lung tissues of the S group （0.3522±0.0512） was significantly lower than that of the N group （0.4432± 0.05628） （P〈0.05）. It is concluded that cigarette smoke alone decreased the level of SP-A and that might have an important effect on surfactant metabolism and the host defense functions of surfactant in the peripheral airways, which might play a crucial role in the development of chronic obstructive lung disease.

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

Effect of NADPH Oxidase Inhibitor Apocynin on the Expression of Hypoxia-induced Factor-1α and Endothelin-1 in Rat Carotid Body Exposed to Chronic Intermittent Hypoxia

The effects of nicotinamide adenine dinucleotide phosphate （NADPH） oxidase inhibitor apocynin on the enhanced hypoxia induced factor-let （HIF-lct） and endothelin-1 （ET-1） expression, elevated systolic blood pressure under chronic intermittent hypoxia （CIH） condition and its action mechanism were investigated. Thirty healthy 8-week old Sprague-Dawley （SD） male rats were randomly divided into three groups （n=10 each）： sham group, CIH group, and apocynin-treated CIH group. Tail artery systolic blood pressure was measured by tail-cuff method. Real-time fluorescence quantitative polymerase chain reaction （PCR） was used to detect the mRNA expression of HIF-lu and ET-1 in the carotid body, and the HIF-1a protein expression was examined by using Western blotting. The levels of malondialdehyde （MDA） and superoxide dismutase （SOD） were determined by using colorimetric method. In addition, the plasma ET-1 and HIF-1a levels were measured by using enzyme-linked immunosorbent assay. It was found that CIH exposure was associated with increased MDA levels, and apo- cynin-treated CIH animals showed reduction in MDA levels. Apocynin treatment prevented CIH-induced hypertension as well as CIH-induced decrease in SOD. The increases of HIF-1a and ET-1 mRNA along with HIF-la protein expression in the carotid body, and elevated circulating HIF-1a and ET-1 levels were observed in CIH-exposed animals. Treatment with apocynin significantly decreased the ET-1 mRNA, HIF-lct protein expression and circulating HIF-la level in CIH-exposed animals, and there was no statistically significant difference in the HIF-lu mRNA expression between CIH group and apo- cynin-treated group. These results indicated that apocynin alleviated CIH-induced hypertension by inhibiting NADPH oxidase, further leading to the reduced vasoconstrictor ET-1 level and oxidative stress. HIF-1a/ET-1 system signal pathway may interact with CIH-induced NADPH oxidase-dependent oxidative stress. Inhibition of NADPH oxidase activity may hopefully serve as a useful strategy for prevention and treatment of obstructive sleep apnea hypopnea syndrome-induced hypertension.

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.