Deep learning-based lung sound analysis for intelligent stethoscope

Auscultation is crucial for the diagnosis of respiratory system diseases.However,traditional stethoscopes have inherent limitations,such as inter-listener variability and subjectivity,and they cannot record respiratory sounds for offline/retrospective diagnosis or remote prescriptions in telemedicine.The emergence of digital stethoscopes has overcome these limitations by allowing physicians to store and share respiratory sounds for consultation and education.On this basis,machine learning,particularly deep learning,enables the fully-automatic analysis of lung sounds that may pave the way for intelligent stethoscopes.This review thus aims to provide a comprehensive overview of deep learning algorithms used for lung sound analysis to emphasize the significance of artificial intelligence(AI)in this field.We focus on each component of deep learning-based lung sound analysis systems,including the task categories,public datasets,denoising methods,and,most importantly,existing deep learning methods,i.e.,the state-of-the-art approaches to convert lung sounds into two-dimensional(2D)spectrograms and use convolutional neural networks for the end-to-end recognition of respiratory diseases or abnormal lung sounds.Additionally,this review highlights current challenges in this field,including the variety of devices,noise sensitivity,and poor interpretability of deep models.To address the poor reproducibility and variety of deep learning in this field,this review also provides a scalable and flexible open-source framework that aims to standardize the algorithmic workflow and provide a solid basis for replication and future extension:https://github.com/contactless-healthcare/Deep-Learning-for-Lung-Sound-Analysis.

Identification of a novel inflammatory-related gene signature to evaluate the prognosis of gastric cancer patients

BACKGROUND Gastric cancer(GC)is a highly aggressive malignancy with a heterogeneous nature,which makes prognosis prediction and treatment determination difficult.Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours.Inflammation also affects the prognosis of GC patients.Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis.However,the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear.AIM To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients.was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database.GC patients from the GSE26253 cohort were used for validation.Univariate and multivariate Cox analyses were used to determine the independent prognostic factors,and a prognostic nomogram was established.The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram.The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram.Gene set enrichment analysis was performed to explore the potential regulatory pathways involved.The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT.Finally,we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents.RESULTS A prognostic model consisting of three inflammatory-related genes(MRPS17,GUF1,and PDK4)was constructed.Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients.According to the risk score,GC patients were stratified into high-and low-risk groups,and patients in the high-risk group had significantly worse prognoses according to age,sex,TNM stage and Lauren type.Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging.Finally,the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group,indicating a link between inflammation-related genes and drug sensitivity.CONCLUSION In conclusion,we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

支气管镜介入技术治疗典型类癌的近期疗效及远期疗效观察

背景与目的支气管镜下的各种介入治疗技术包括圈套、二氧化碳冷冻、氩等离子体凝固(argon plasma coagulation,APC)、激光(Neodymium-dopted Yrium Aluminium Garnet,Nd:YAG)、光动力治疗(photodynamic therapy,PDT),以上治疗技术通常用于治疗气管腔内肿瘤,但用于治疗典型类癌(typical carcinoid,TC)的研究并不普遍。本研究拟探讨支气管镜介入技术治疗典型类癌的近期疗效和远期疗效。方法回顾性分析北京应急总医院2010年12月-2020年12月可消瘤的腔内典型类癌患者的临床资料,采用Wilcoxon秩和检验和卡方检验进行统计分析。结果共纳入32例患者,术前支气管动脉栓塞18例(栓塞率56%,95%CI:31%-79%)。呼吸困难分级评分治疗后较治疗前下降,差异有统计学意义[(1.44±1.03)分vs(0.25±0.58)分,P=0.003];支气管管腔狭窄程度治疗后较治疗前改善,差异有统计学意义[(87.50%±13.90%)vs(17.50%±6.83%),P<0.001];支气管内径治疗后较治疗前扩宽,差异有统计学意义[(0.14±0.18)cm vs(0.84±0.29)cm,P<0.001]。近期有效率为100%。32例患者中24例支气管镜介入治疗能够完全消瘤,完全缓解(complete remission,CR)率为75%。结论支气管镜介入治疗技术治疗典型类癌的近期疗效及远期疗效显著。

Acute gastroenteritis outbreak caused by a GII.6 norovirus

AIM:To report an acute gastroenteritis outbreak caused by a genogroup 2 genotype 6(GII.6) strain norovirus in Shanghai,China.METHODS:Noroviruses are responsible for approximately half of all reported gastroenteritis outbreaks in many countries.Genogroup 2 genotype 4 strains are the most prevalent.Rare outbreaks caused by GII.6 strains have been reported.An acute gastroenteritis outbreak occurred in an elementary school in Shanghai in December of 2013.Field and molecular epidemiologic investigations were conducted.RESULTS:The outbreak was limited to one class in an elementary school located in southwest Shanghai.The age of the students ranged from 9 to 10 years.The first case emerged on December 10,2013,and the last case emerged on December 14,2013.The cases peaked on December 11,2013,with 21 new cases.Of 45 students in the class,32 were affected.The main symptom was gastroenteritis,and 15.6%(5/32) of the cases exhibited a fever.A field epidemiologic investigation showed the pathogen may have been transmitted to the elementary school from employees in a delicatessen via the first case student,who had eaten food from the delicatessen one day before the gastroenteritis episodes began.A molecular epidemiologic investigation identified the cause of the gastroenteritis as norovirus strain GII.6;the viral sequence of the student cases showed 100% homology with that of the shop employees.Genetic relatedness analyses showed that the new viral strain is closely related to previously reported GII.6 sequences,especially to a strain reported in Japan.CONCLUSION:This is the first report to show that norovirus strain GII.6 can cause a gastroenteritis outbreak.Thus,the prevalence of GII.6 noroviruses requires attention.

Purification,structural elucidation,and in vitro antitumor effects of novel polysaccharides from Bangia fuscopurpurea

A water-soluble polysaccharide,designated BFP-3,was isolated from Bangia fuscopurpurea by hot water extraction,anion-exchange,and size-exclusion chromatography and tested to determine its antitumor activity.The structural characteristics of BFP-3 were investigated by chemical and spectroscopic methods,including partial acid hydrolysis,methylation analysis,one-and two-dimensional nuclear magnetic resonance,and gas chromatography-mass spectrometry.The results showed that BFP-3 was mainly comprised of rhamnose,arabinose,mannose,glucose,and galactose.Moreover,the weight-average molecular weight of BFP-3 was estimated to be approximately 333 kDa.The backbone of BFP-3 was primarily composed of repeating 5-α-l-Araf-1→(4-α-d-Glcp-1)_(4)→4,6-β-d-Manp-1 units,and the side chains consisted of repeatingβ-d-Galp-1→(4-β-d-Galp-1)_(4)→4,6-β-d-Galp-1→3,4-α-l-Rhap,β-l-Arap-1→(3-β-d-Galp-1)_(3),andβ-l-Arap-1 units.Counting Kit-8 assays revealed that BFP-3 significantly inhibited the proliferation of A2780,COC1,SKOV3,HO-8910,and OVCAR3 ovarian cancer cells in vitro,indicating that BFP-3 could have potential applications in the treatment of ovarian cancer.

Integration of multiple climate models to predict range shifts and identify management priorities of the endangered Taxus wallichiana in the Himalaya–Hengduan Mountain region

Taxus wallichiana Zucc.(Himalayan yew)is subject to international and national conservation measures because of its over-exploitation and decline over the last 30 years.Predicting the impact of climate change on T.wallichiana’s distribution might help protect the wild populations and plan effective ex situ measures or cultivate successfully.Considering the complexity of climates and the uncertainty inherent in climate modeling for mountainous regions,we integrated three Representative Concentration Pathways(RCPs)(i.e.,RCP2.6,RCP4.5,RCP8.5)based on datasets from 14 Global Climate Models of Coupled Model Intercomparison Project,Phase 5 to:(1)predict the potential distribution of T.wallichiana under recent past(1960–1990,hereafter‘‘current’’)and future(2050s and 2070s)scenarios with the species distribution model MaxEnt.;and(2)quantify the climatic factors influencing the distribution.In respond to the future warming climate scenarios,(1)highly suitable areas for T.wallichiana would decrease by 31–55%at a rate of 3–7%/10a;(2)moderately suitable areas would decrease by 20–30%at a rate of 2–4%/10a;(3)the average elevation of potential suitable sites for T.wallichiana would shift upslope by 390 m(15%)to 948 m(36%)at a rate of 42–100 m/10a.Average annual temperature(contribution rate ca.61%),isothermality and temperature seasonality(20%),and annual precipitation(17%)were the main climatic variables affecting T.wallichiana habitats.Prior protected areas and suitable planting areas must be delimited from the future potential distributions,especially the intersection areas at different suitability levels.It is helpful to promote the sustainable utilization of this precious resource by prohibiting exploitation and ex situ restoring wild resources,as well as artificially planting considering climate suitability.

Ocular biometry in the adult population in rural central China: a population-based, cross-sectional study

·AIM: To describe the distribution and determinants of ocular biometric parameters and to ascertain the relative importance of these determinants in a large population of adults in rural central China.·METHODS: A population-based, cross-sectional study performed in rural central China included 1721 participants aged 40 or more years. Ocular biometrical parameters including axial length(AL), anterior chamber depth(ACD), radius of corneal curvature(K) and horizontal corneal diameter [white-to-white(WTW)distance] were measured using non-contact partial coherence interferometry [intraocular lens(IOL)-Master].·RESULTS: Ocular biometric data on 1721 participants with a average age of 57.0 ±8.7y were analyzed at last.The general mean AL, ACD, mean corneal curvature radius(MCR), WTW were 22.80±1.12, 2.96±0.36, 7.56±0.26 and 11.75 ±0.40 mm, respectively. The mean values of each parameter in 40 to 49, 50 to 59, 60 to 69, and 70 to91 years age groups were as follows: AL, 22.77 ±0.87,22.76 ±1.06, 22.89 ±1.41, 22.92 ±0.80 mm; ACD, 3.10 ±0.32,2.98 ±0.34, 2.86 ±0.36, 2.77 ±0.35 mm; MCR, 7.58 ±0.25,7.54 ±0.26, 7.55 ±0.26, 7.49 ±0.28 mm; WTW, 11.79 ±0.38,11.75 ±0.40, 11.72 ±0.41, 11.67 ±0.41 mm. The AL, ACD,MCR and WTW were correlated with age and the AL was correlated with height and weight.·CONCLUSION: Our findings can serve as an important normative reference for multiple purposes and may help to improve the quality of rural eye care.

An In Vitro and In Vivo Study of Thyroid Disruption of 1,2-Bis(2,4,6-tribromophenoxy)ethane(BTBPE)�A Novel Brominated Flame Retardant

The novel brominated flame retardant,1,2-bis-(2,4,6-tribromophenoxy)ethane(BTBPE),is an emerging environ-mental pollutant with undetermined toxicity.We investigated how BTBPE causes thyroid endocrine disruption with integrated in silico,in vitro,and in vivo assays.In yeast two-hybrid and T-Screen assays,BTBPE interacted with zebrafish thyroid hormone receptors with binding energies weaker than the TR agonist-3,3′,5-Triiodo-L-thyronine(T3),and disrupted thyroid function as a thyroid receptor(TR)agonist.We examined the bioconcentra-tion,developmental toxicity,and thyroid endocrine disruption in zebrafish after a 14-day exposure to BTBPE(1,3,10μg/L).Thyroxine(T4)was lower in BTBPE-treated larvae,whereas corticotropin-releasing hormone(CRH)and thyroid-stimulating hormone(TSH)were higher.The gene transcription alterations along the hypothalamic-pituitary-thyroid(HPT)axis were observed.Furthermore,reduced locomotion suggested that BTBPE imparts developmental neurotoxicity at zebrafish early developmental stage.Establishing that BTBPE has thyroid endocrine-disrupting effects is an important step for understanding and managing BTBPE toxicity.

Cross-Sectional Online Survey on Depression and Anxiety Among the Population Infected or Non-Infected with COVID-19——China,December 2022

Summary What is already known about this topic?The psychological impact of the large-scale infection of the population resulting from the end of lockdown measures in China during the coronavirus disease 2019(COVID-19)pandemic is unknown.What is added by this report?Among all participants,55.7%had depression symptoms,with a significant difference between the infected and non-infected groups,and 30.1%had anxiety.Those who were young,unvaccinated,had lower incomes,and experienced chronic diseases were more likely to experience negative emotions.What are the implications for public health practice?Government officials should take into account the effect of policies on public sentiment during similar public health events and implement tailored community interventions to address any negative sentiment.

Evoking robust immunogenic cell death by synergistic sonodynamic therapy and glucose depletion using Au clusters/single atoms modified TiO_(2)nanosheets

Facilitated by reactive oxygen species(ROS)-involved therapies,tumor cells undergo immunogenic cell death(ICD)to stimulate long-term immunity response.However,it is hard to trigger abundant and large-scale ICD for satisfactory cancer immunotherapy.Herein,a multifunctional sonosensitizer that consists of Au single atoms and clusters anchored on TiO_(2)nanosheets(named Au_(S/C)-TiO_(2))is reported for augmented sonodynamic therapy(SDT)and glucose depletion,which ultimately induce robust ICD due to the improved ROS generation and strong endoplasmic reticulum(ER)stress.The synergy effect between Au cluster/single atom with TiO_(2)nanosheets intensifies apoptosis and ICD pathways to inhibit 80%of tumor cells through in vivo analyses.Furthermore,immune cells in vivo analyses verify the effectiveness of Au_(S/C)-TiO_(2)sonosensitizer towards the induction of antitumor immunity.This study thus reveals that simultaneous presence of ROS generation and strong ER stress can efficiently evoke a strong ICD-mediated immune response.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis

Background:Critical patients with the coronavirus disease 2019(COVID-19),even those whose nucleic acid test results had turned negative and those receiving maximal medical support,have been noted to progress to irreversible fatal respiratory failure.Lung transplantation(LT)as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.Methods:From February 10 to March 10,2020,three male patients were urgently assessed and listed for transplantation.After conducting a full ethical review and after obtaining assent from the family of the patients,we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.Results:Two of the three recipients survived post-LT and started participating in a rehabilitation program.Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved.The pathological results of the explanted lungs were concordant with the critical clinical manifestation,and provided insight towards better understanding of the disease.Government health affair systems,virology detection tools,and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.Conclusions:LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis.If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT,LT provided the final option for these patients to avoid certain death,with proper protection of transplant surgeons and medical staffs.By ensuring instant seamless care for both patients and medical teams,the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Reversing cold tumors to hot: An immunoadjuvant-functionalized metalorganic framework for multimodal imaging-guided synergistic photoimmunotherapy

Immunotherapy assays using immunoadjuvants and tumor antigens could greatly increase the survival rates of patients with malignant tumors.As effective carriers,metal-organic frameworks(MOFs)have been widely utilized in cancer therapy due to their remarkable histocompatibility and low toxicity.Herein,we constructed a multimodal imaging-guided synergistic cancer photoimmunotherapy by employing a specific MOF(MIL101-NH2)as the core carrier;the MOF was dual-dressed with photoacoustic and fluorescent signal donors(indocyanine green,ICG)and immune adjuvants(cytosine-phosphate-guanine sequence,CpG)and named ICGCpG@MOF.This nanocarrier could passively target the tumor site through the EPR effect and achieve multimodal imaging(fluorescence,photoacoustic,photothermal and magnetic resonance imaging)of the tumor.Synergistic cancer photoimmunotherapy was achieved via simultaneous photodynamic and photothermal methods with 808 nm laser irradiation.ICG-CpG@MOF achieved the GSH-controlled release of immunoadjuvant into the tumor microenvironment.Furthermore,the released tumor-associated antigen along with CpG could induce the transformation of tumor cells from cold to hot by activating the immune system,which significantly enhanced tumor cytotoxicity and achieved high cure rates with minimal side-effects.This strategy utilizing multimodal imaging and synergistic cancer photoimmunotherapy provides a promising approach for the diagnosis and treatment of cancer.

Regulatory science for hernia mesh: Current status and future perspectives

Regulatory science for medical devices aims to develop new tools,standards and approaches to assess the safety,effectiveness,quality and performance of medical devices.In the field of biomaterials,hernia mesh is a class of implants that have been successfully translated to clinical applications.With a focus on hernia mesh and its regulatory science system,this paper collected and reviewed information on hernia mesh products and biomaterials in both Chinese and American markets.The current development of regulatory science for hernia mesh,including its regulations,standards,guidance documents and classification,and the scientific evaluation of its safety and effectiveness was first reported.Then the research prospect of regulatory science for hernia mesh was discussed.New methods for the preclinical animal study and new tools for the evaluation of the safety and effectiveness of hernia mesh,such as computational modeling,big data platform and evidence-based research,were assessed.By taking the regulatory science of hernia mesh as a case study,this review provided a research basis for developing a regulatory science system of implantable medical devices,furthering the systematic evaluation of the safety and effectiveness of medical devices for better regulatory decision-making.This was the first article reviewing the regulatory science of hernia mesh and biomaterial-based implants.It also proposed and explained the concepts of evidence-based regulatory science and technical review for the first time.

Reprogramming of phytopathogen transcriptome by a non-bactericidal pesticide residue alleviates its virulence in rice

Bacteria equipped with virulence systems based on highly bioactive small molecules can circumvent their host's defense mechanisms.Pathogens employing this strategy are currently threatening global rice production.In the present study,variations in the virulence of the highly destructive Barkholderiaplantarii were observed in different rice-producing regions.The environment-linked variation was not attributable to any known host-related or external factors.Co-occurrence analyses indicated a connection between reduced virulence and 5-Amino-l,3,4-thiadiazole-2-thiol(ATT),a non-bactericidal organic compound.ATT,which accumulates in rice plants during metabolization of specific agrochemicals,was found to reduce virulence factor secretion by B.plantarii up to 88.8%and inhibit pathogen virulence by hijacking an upstream signaling cascade.Detailed assessment of the newly discovered virulence inhibitor resulted in mechanistic insights into positive effects of ATT accumulation in plant tissues.Mechanisms of virulence alleviation were deciphered by integrating high-throughput data,gene knockout mutants,and molecular interaction assays.TroK,a histidine protein kinase in a two-component system that regulates virulence factor secretion,is likely the molecular target antagonized by ATT.Our findings provide novel insights into virulence modulation in an important plant-pathogen system that relies on the host's metabolic activity and subsequent signaling interference.

A self-crosslinking,double-functional group modified bacterial cellulose gel used for antibacterial and healing of infected wound

Cellulose/chitosan composite,as a mature commercial antibacterial dressing,is an important type of wound repair material.However,how to achieve the perfect compound of two components and improve antibacterial activity is a major,lingering issue.In this study,a bifunctional group modified bacterial cellulose(DCBC)was prepared by carboxymethylation and selective oxidation.Further,the chitosan(CS)was compounded in the network of DCBC by self-crosslinking to form dialdehyde carboxymethyl bacterial cellulose/chitosan composites(S-DCBC/CS).The aldehyde group can react with amino of CS by Schiff base reaction.The carboxyl group of DCBC and the amorphous distribution of CS molecular chains increase the antimicrobial properties of com-posites.The bacteriostatic rate of composites could be higher than 95%.Bacteria can be attracted onto the surface of composites,what we call it“directional adhesion antibacterial effects”.In particular,a kind of large animal wound model,deep II degree infected scald of Bama miniature pig,was used to research the antimicrobial and healing properties of materials.The S-DCBC/CS can effectively inhibit bacterial proliferation of wound and kill the bacteria.The wound healing rate of S-DCBC/CS was up to 80%after three weeks.The composites show better antibacterial and promoting concrescence effects than traditional chitosan dressings.

Comparative transcriptome analysis of Phascolosoma esculenta under different salinities

Salinity is an important parameter that influences the developmental progress of aquatic organisms.The larvae of Phascolosoma esculenta developed into the early stage trochosphere,the late stage trochosphere and the early stage pelagosphere in the low-salinity group(15),the middle group(22.5)and the high-salinity group(30),respectively,after being incubated for 50 h,according to morphological observation.The results showed that high salinity could accelerate the cellular development of P.esculenta.To elucidate the molecular mechanism of larval development of P.esculenta under different salinities,we performed transcriptome analysis of the larvae in P.esculenta.Nine transcriptome libraries of P.esculenta larvae were constructed,i.e.,the low-salinity group(A1,A2 and A3),the middle group(B1,B2 and B3)and the high-salinity group(C1,C2 and C3),and each group with three repeats.These nine paired-end libraries were sequenced using the Illumina HiSeq 2500 platform.In total,57.63 Gb clean data were obtained and de novo assembled into 320,527 unigenes with mean lengths of 482.62 bp and N50 of 529 bp.A total of 249,162 unigenes were significantly matched to known unique proteins.The gene ontology(GO)annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to determine the regulation pathways and candidate genes that are associated with the process of larval development.A total number of 12,811,16,991 and 1735 transcripts were identified as differentially expressed genes(DEGs)from the comparison of A vs.B,A vs.C,and B vs.C,respectively.Of these differentially expressed genes,many DEGs that were upregulated in the high-salinity group were involved in the function that controls the larval development of P.esculenta,such as the neuroactive ligand-receptor interaction and ECM-receptor interaction.In addition,the results of the transcriptome analysis were verified by quantitative real-time PCR(qRT-PCR).After morphological observation and transcriptome analysis,we think high salinity(30)is more suitable than medium(22.5)or low(15)salinity for the development of P.esculenta larvae.This information provides guidance for artificial breeding and paves the way to the further research on the individual development of P.esculenta under different salinities.