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Abstract China has implemented the “tiered medical services” policy since 2015, while there is a paucity of data evaluating the the current status of chronic obstructive pulmonary disease (COPD) management under the system. Characteristics and treatments from 11,905 COPD patients in 88 hospitals across different tiers in China were included and analyzed. We assessed the statistical significance of differences by one way analysis of variance (ANOVA) for continuous variables and with the chi-squared test for categorical variables. Patients in primary hospitals (Tier1) exhibited heightened exposure to risk factors including smoking, household biofuel, and family history of respiratory diseases, and displayed elevated COPD assessment test (CAT) and modified Medical Research Council (mMRC) dyspnea scale scores, and worse lung function, in comparison to tertiary (Tier3) hospitals (P

Abstract Adjuvant endocrine therapy (AET) is essential for improving survival and reducing mortality and recurrence rates in breast cancer (BrCa) patients. However, the adherence to AET among BrCa patients is poor, and there is no scale to measure adherence to AET or the reasons for non-adherence among BrCa patients in mainland China. The aim of this study was to assess the psychometric properties of the simple Chinese version of the Medication Adherence Reasons (MAR) scale in BrCa patients undergoing AET. This study utilized a cross-sectional research design with two phases: (1) translation and cross-cultural adaptation of the original English version of the MAR scale into simple Chinese and (2) validation of the simple Chinese version of the MAR scale (s-ChMAR scale) in BrCa patients. Instrument assessments included content validity, face validity, item analysis, construct validity, criterion-related validity and reliability testing. This study recruited participants using convenience sampling to investigate adherence to AET among BrCa patients. Inclusion criteria were: (a) female, (b) aged 18 years or older, (c) diagnosed with Stage I to III BrCa, (d) completed primary treatment for hormone receptor-positive BrCa and had been on AET for more than six months but less than five years, (e) proficient in Mandarin, and (f) provided informed consent. Exclusion criteria included psychiatric illness, cognitive impairment, or a diagnosis of another cancer type. The sample size for exploratory factor analysis (EFA) was determined based on a ratio of five to ten participants per scale item to ensure sufficient statistical power. Data were collected from a sample of 325 participants who received AET for over six months. All the items had a content validity index (CVI) of more than 0.80. Regarding construct validity, the s-ChMAR scale fit a four-dimensional model, the same as the original MAR scale tested in asthma patients. The s-ChMAR scale had good internal reliability (Cronbach’s α = 0.896) and good stability (ICC = 0.837). In terms of quantifying non-adherence, the s-ChMAR scale identified a non-adherent participant rate of over 50%. The study findings support the reliability and validity of the s-ChMAR scale in measuring the non-adherence of Chinese BrCa patients to AET.

There is an abundance of tight gas resources in narrow channel sand-bodies from the Jurassic Shaximiao Formation of the Jinqiu gas field in the central Sichuan Basin of China. The architecture of sand group in the study area is undefined, and the spatial distribution of channel sand-bodies is unclear. The complex and inhomogeneous sandstones have a significant impact on the reservoir’s physical properties and the fluid mobility of the reservoir. In this study, data from drilling cores, logs, seismic, and experiment testing were used to investigate the spatial distribution of sand group architecture and the channel types. There are five channel genetic types, including the multiphase superimposed type, deeply incised type, abandoned type, progradational superimposed type, and normal single genetic type. Based on the channel genetic types, the ratio of sandstone and mudstone, the ratio of width to depth, the connectivity ratio of sand-bodies, and the production dynamic characteristics, the channel sand-body connectivity is defined into three types. The connected sand-bodies occur in the multiphase superimposed and deeply incised types of channels, with an average connectivity ratio of 83%, a ratio of sandstone and mudstone larger than 0.9, and a ratio of width and depth larger than 40. Based on the association of sandstone and mudstone and rhythmic structure, the sand group architecture can be divided into three types, including (A) uniform-grain-sequence pure sandstone architecture, (B) positive-grain-sequence thick sandstone and thin mudstone architecture, and (C) positive-grain-sequence thick mudstone and thin sandstone architecture. There is a high content of natural gas in Types A and B of sandstones, with a daily gas production of 29.16×104–47.6×104 m3/day and pressure coefficients of 0.72–1.08. The sand group architecture of the study area is mainly controlled by the channel sinuosity and the ratio of accommodation and sediment supply, and Types A and B of sand group architectures occur with large channel sinuosity of 1.14–1.36 and a large ratio of accommodation and sediment supply of 0.61–2.92. Based on the connectivity degree of channel sand-bodies, the sand group architectures, and production data, the channels of the study area can be divided into three types. Type I channels mainly occur in Sand Groups 6, 8, and 9, and Type II and Type III channels occur in Sand Groups 6 and 7 in the western and southern parts of the study area. The technology of fine characterization for channel sand-bodies on the basis of human–computer interaction and seismic attributes is proposed, and geological modelling of the spatial distribution of sand group architectures and channel types is established. The research results achieve a theoretical breakthrough in the characterization of the sand-body structure of tight sandstone reservoirs in narrow river channels and assist in the efficient exploration and development of tight sandstone gas.

Hemophagocytic syndrome (HPS) is a rapidly progressive and highly fatal disease, and is even more complex when it occurs during pregnancy. Currently, the HLH-94 protocol is commonly used for treatment for HPS, with ruxolitinib being mostly used for salvage therapy. Here, we report a pregnant woman who presented with fever, thrombocytopenia, splenomegaly, and subsequently developed into severe pneumonia and multiple organ dysfunction(MODS). The patient was diagnosed as HPS based on clinical manifestations, laboratory indexes, and hemophagocytosis observed in bone marrow aspirate smear. After receiving ruxolitinib as induction therapy combined with HLH-94 protocol, the patient significantly improved and eventually cured.

ABSTRACT Background With the increasing use of lung cancer screening, the detection of ground glass nodules (GGNs) has risen. However, the natural course of GGNs and their relationship to pathologic features remains unclear. Differentiating between invasive and pre‐invasive lesions based on GGN growth may improve clinical intervention timing. Ki‐67, a proliferation marker, holds value in assessing tumor malignancy. This study analyzes the association between GGN growth, pathology, and Ki‐67 expression to provide new insights into early‐stage lung cancer management. Methods We retrospectively evaluated 183 GGNs with at least two preoperative CT scans. Nodule location, type, natural course, and volume doubling time (VDT) were compared between invasive adenocarcinoma (IAC) and pre‐IAC groups. We also assessed differences in Ki‐67 expression and correlated VDT with Ki‐67 levels. Results A total of 183 nodules were finally included; gender, nodule location, smoking history, and duration of follow‐up did not differ between the IAC group and the pre‐IAC group, whereas age was statistically different between the two groups. Of the 183 nodules, 52 showed growth and the predominant pathologic type was IAC, these IACs showed more PSN in nodule type, while the IAC group showed more significant differences in nodule type, nodules growth, and VDT than the pre‐IAC group. There were also differences in pathologic type and VDT between different Ki‐67 expression groups, and Ki‐67 expression gradually increased as VDT decreased. Conclusion Lung adenocarcinoma (LUAD) presenting as GGNs exhibit distinct natural courses among pathologic subtypes. VDT effectively distinguishes these growth characteristics, with IACs showing shorter VDT. The significant correlation between VDT and Ki‐67 expression suggests that combining these parameters may provide valuable insights into the biological behavior and invasiveness of LUAD.

Abstract Benefiting from the outstanding optical, thermal, electrical, and mechanical properties, carbon nanotubes (CNTs) hold significant potential in the fields of materials, physics, chemistry, biology, as well as emerging disciplines such as electronics and optoelectronics. This paper provides a comprehensive review of the latest developments of CNTs optoelectronic devices operating in the terahertz (THz) and infrared (IR) wave range. At the beginning of this review, the unique structural characteristics of CNTs are introduced, overviewing their fundamental electronic structure, and emphasizing their impact on optoelectronics behavior. Further, on various synthesis techniques are discussion employed for the growth of single nanotube and the preparation of CNTs films. The penultimate section, the optical properties of CNTs are analyzed within the THz and IR spectral region and overview the application of THz time‐domain spectroscopy in extracting key material parameters of CNTs, and further discuss the theoretical models describing THz conductivity in CNTs. In the end, the most promising CNTs‐based device concepts are highlighted for sources, detectors, modulators, absorbers, and sensors within in THz and IR frequency band. This comprehensive review provides a valuable insight into the utilization of CNTs across various aspects of THz and IR optoelectronic devices.

Prolonged inhalation of environmental crystalline silica (CS) can cause silicosis, characterized by persistent pulmonary inflammation and irreversible fibrosis, but the mechanism has not been elucidated. To uncover the role and underlying mechanism of glycolytic reprogramming in CS-induced pulmonary inflammation, the mouse silicosis models and glycolysis inhibition models were established in vivo. And the CS-induced macrophage activation models were utilized to further explore the underlying mechanism in vitro. The results showed that CS induced lung inflammation accompanied by glycolytic reprogramming and pyroptosis. The application of glycolysis inhibitor (2-DG) suppressed CS-induced pyroptosis and alleviated lung inflammation. In vitro, 2-DG effectively impeded CS-induced macrophage pyroptosis and inflammatory response. Mechanistically, 2-DG suppressed pyroptosis by inhibiting NLRP3 inflammasome activation both in vivo and in vitro. Furtherly, metabolite lactate facilitated NLRP3-dependent pyroptosis synergistically with CS particles, while blocking the source of lactate largely alleviated NLRP3 inflammasome activation and subsequent pyroptosis triggered by CS. More profoundly, the increment of lactate induced by CS might drive NLRP3-dependent pyroptosis by increasing histone lactylation levels. In conclusion, our findings demonstrated inhibiting glycolytic reprogramming could alleviate CS-induced inflammatory response through suppressing NLRP3 -dependent pyroptosis. Increased glycolytic metabolite lactate and protein lactylation modifications might represent significant mechanisms during CS-induced NLRP3 activation and macrophage pyroptosis.

Background Despite substantial progress in reducing the global burden of chronic obstructive pulmonary disease (COPD), traditional methods to promote understanding and management of COPD are insufficient. We developed an innovative model based on the internet of things (IoT) for screening and management of COPD in primary healthcare (PHC).Methods Electronic questionnaire and IoT-based spirometer were used to screen residents. We defined individuals with a questionnaire score of 16 or higher as high-risk population, COPD was diagnosed according to 2021 Global Initiative for COPD (Global Initiative for Chronic Obstructive Lung Disease) criteria. High-risk individuals and COPD identified through the screening were included in the COPD PHC cohort study, which is a prospective, longitudinal observational study. We provide an overall description of the study’s design framework and baseline data of participants.Results Between November 2021 and March 2023, 162 263 individuals aged over 18 from 18 cities in China were screened, of those 43 279 high-risk individuals and 6902 patients with COPD were enrolled in the cohort study. In the high-risk population, the proportion of smokers was higher than that in the screened population (57.6% vs 31.4%), the proportion of males was higher than females (71.1% vs 28.9%) and in people underweight than normal weight (57.1% vs 32.0%). The number of high-risk individuals increased with age, particularly after 50 years old (χ2=37 239.9, p

Abstract Background Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive. Methods Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed. Results Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized. Conclusions Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN. Video Abstract

BackgroundAeromonas dhakensis is a gram-negative bacterium. In recent years, Aeromonas dhakensis has gradually attracted increasing attention due to its strong virulence and poor prognosis. Clinical reports of pulmonary infection caused by Aeromonas dhakensis are rare.Case presentationA patient with acute T lymphoblastic leukemia experienced myelosuppression after chemotherapy, developed a secondary pulmonary infection with Aeromonas dhakensis and was hospitalized due to fever. The patient underwent testing for inflammatory markers, chest imaging, blood culture, bronchoalveolar lavage, pleural drainage, and metagenomic next-generation sequencing of alveolar lavage fluid and pleural fluid to obtain evidence of Aeromonas dhakensis infection, and was treated with four generations of cephalosporin combined with fluoroquinolone antibiotics. The patient’s condition significantly improved.DiscussionAmong pulmonary infectious pathogens, Aeromonas dhakensis is relatively rare. Once an Aeromonas strain is cultured in the clinical work, pathogenic sequencing should be performed on the detected samples for early accurate diagnosis and effective anti-infection treatment.

In this paper, we study initial boundary value problems for the following fully nonlocal Boussinesq equation $ _0^{C}D_{t}^{\beta}u+(-\Delta)^{\sigma}u+(-\Delta)^{\sigma}{_0^{C}D_{t}^{\beta}}u = -(-\Delta)^{\sigma}f(u) $ with spectral fractional Laplacian operators and Caputo fractional derivatives. To our knowledge, there are few results on fully nonlocal Boussinesq equations. The main difficulty is that each term of this equation has nonlocal effect. First, we obtain explicit expressions and some rigorous estimates of the Green operators for the corresponding linear equation. Further, we get global existence and some decay estimates of weak solutions. Second, we establish new chain and Leibnitz rules concerning $ (-\Delta)^{\sigma} $. Based on these results and small initial conditions, we obtain global existence and long-time behavior of weak solutions under different dimensions $ N $ by Banach fixed point theorem.

IntroductionIt is necessary to explore the evidence-based practice of perioperative management of elderly patients undergoing ambulatory surgery, to optimize the clinical workflow and improve the quality of nursing care.MethodsBased on the best evidence obtained from the previous study, the perioperative management model and examination index of elderly patients undergoing day surgery were established, and the evidence of best practice was obtained by using the evidence-based methodology. Then, we integrated evidence into clinical practice and improved the process. We made a comparative analysis of the effect before and after the implementation of the evidence.ResultsThis study summarized 26 pieces of evidence of perioperative management of elderly patients undergoing day surgery and transformed the evidence into 7 items and 11 items of examination index. After the application of the best evidence, knowledge, belief, and practice of perioperative management of nurses for elderly patients in the day operation ward reached 100%, and the rate of reaching the standard of most indicators increased after the application of evidence. The length of waiting for admission and waiting for operation and returning to the ward to discharge of elderly patients decreased significantly, and the difference was statistically significant (All p

IntroductionTumor-associated autoantibodies have been revealed as promising biomarkers for the early detection of lung cancer. This study was designed to develop an autoantibody panel for early detection of lung cancer in the Chinese population.MethodsRecruited prospectively in three clinical centers, the subjects (n = 991) who had a definite diagnosis during follow-up were included in the development of the autoantibody panel. The levels of 14 autoantibody candidates in plasma were detected.ResultsA panel of nine autoantibody markers (named as CN9), namely, P53, SOX2, SSX1, HuD, NY-ESO-1, CAGE, MAGE-A4, P62, and CK20, was preferably selected from 14 candidates. The overall specificity, sensitivity, and AUC were 90.5%, 40.8%, and 0.64, respectively. The CN9 panel demonstrated a reasonable detection rate in lung cancer patients at all stages, histological types, sizes of lesions, and risk levels. Its estimated overall accuracy is 85.5% and 90%, with PPV at 0.32 and 0.04, and NPV at 0.93 and 0.99 in the scenario of pulmonary nodules' characterizing and lung cancer screening, respectively. Two risk models were developed within the subgroups of malignant and benign pulmonary nodules in this study. By adding the CN9 result to the Mayo model indicators, it achieved a sensitivity of 41.3% and an AUC of 0.74 at a specificity of 91.3%. By adding the CN9 result to the Brock model indicators, it achieved a sensitivity of 47.7% and an AUC of 0.78 at a specificity of 91.3%. Both were improved compared with either the standalone Mayo or Brock model.DiscussionThis multi-center prospective study indicates a panel of nine autoantibody markers that can help in the detection of lung cancer and the classification of pulmonary nodules in the Chinese population.

Abstract Background Obesity has been identified as a risk factor for acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the underlying mechanisms remain elusive. This study aimed to investigate the role of fatty acid synthase (FASN) in lipopolysaccharide (LPS)-induced ALI under obesity. Methods A high-fat diet-induced obese (DIO) mouse model was established and lean mice fed with regular chow diet were served as controls. LPS was intratracheally instilled to reproduce ALI in mice. In vitro, primary mouse lung endothelial cells (MLECs), treated by palmitic acid (PA) or co-cultured with 3T3-L1 adipocytes, were exposed to LPS. Chemical inhibitor C75 or shRNA targeting FASN was used for in vivo and in vitro loss-of-function studies for FASN. Results After LPS instillation, the protein levels of FASN in freshly isolated lung endothelial cells from DIO mice were significantly higher than those from lean mice. MLECs undergoing metabolic stress exhibited increased levels of FASN, decreased levels of VE-cadherin with increased p38 MAPK phosphorylation and NLRP3 expression, mitochondrial dysfunction, and impaired endothelial barrier compared with the control MLECs when exposed to LPS. However, these effects were attenuated by FASN inhibition with C75 or corresponding shRNA. In vivo, LPS-induced ALI, C75 pretreatment remarkably alleviated LPS-induced overproduction of lung inflammatory cytokines TNF-α, IL-6, and IL-1β, and lung vascular hyperpermeability in DIO mice as evidenced by increased VE-cadherin expression in lung endothelial cells and decreased lung vascular leakage. Conclusions Taken together, FASN inhibition alleviated the exacerbation of LPS-induced lung injury under obesity via rescuing lung endothelial dysfunction. Therefore, targeting FASN may be a potential therapeutic target for ameliorating LPS-induced ALI in obese individuals.

Background: Recently, Professor Chunxue Bai and colleagues have proposed a definition of the Metaverse in Medicine as the medical Internet of Things (MIoT) facilitated using AR and/or VR glasses. Methods: A multi-disciplinary panel of doctors and IT experts from Asia, the United States, and Europe analyzed published articles regarding expert consensus on the Medical Internet of Things, with reference to study results in the field of metaverse technology. Findings: It is feasible to implement the three basic functions of the MIoT, namely, comprehensive perception, reliable transmission, and intelligent processing, by applying a metaverse platform, which is composed of AR and VR glasses and the MIoT system, and integrated with the technologies of holographic construction, holographic emulation, virtuality-reality integration, and virtuality-reality interconnection. In other words, through interactions between virtual and real cloud experts and terminal doctors, we will be able to carry out medical education, science popularization, consultation, graded diagnosis and treatment, clinical research, and even comprehensive healthcare in the metaverse. The interaction between virtual and real cloud experts and terminal users (including terminal doctors, patients, and even their family members) could also facilitate different medical services, such as disease prevention, healthcare, physical examination, diagnosis and treatment of diseases, rehabilitation, management of chronic diseases, in-home care, first aid, outpatient attendance, consultation, etc. In addition, it is noteworthy that security is a prerequisite for the Metaverse in Medicine, and a reliable security system is the foundation to ensure the normal operation of such a platform. Conclusion: The application of a Cloud Plus Terminal platform could enable interaction between virtual and real cloud experts and terminal doctors, in order to realize medical education, science popularization, consultation, graded diagnosis and treatment, clinical research, and even comprehensive healthcare in the metaverse.

Lung cancer is the leading cause of cancer deaths. Although targeted therapies and programmed cell death protein 1 (PD-1) blockade have offered great advances, five-year survival rates remained low. Diagnosis of lung cancer at an earlier stage is the most efficient approach to improve survival. Tumor associated autoantibodies (TAAb) have been proven a promising innovative biomarker of lung cancer. We aimed to comprehensively evaluate the sensitivity, specificity, and accuracy of TAAbs in lung cancer detection, especially in early-stage patients, through a multicenter prospective observational clinical trial, and to screen out the novel combination of TAAbs with the best detection value for Chinese population. We aimed to enroll 1,400 participants from three clinical centers and divide into two cohorts. One cohort is participants with newly pathologically confirmed lung cancer as the case cohort, and the other is participants with benign nodules, matched healthy controls and other benign lung diseases as the control cohort. Cases and controls were randomly distributed into training or validation set. The level of 14 autoantibody candidates in their plasma were detected. A Monte-Carlo Simulated Annealing method was implemented to develop a composite panel of autoantibodies to distinguish between matched lung cancer cases and controls in the training set. The newly developed autoantibody panel was tested in the validation set for sensitivity, specificity and accuracy. This is the first and largest clinical trial designed to develop a novel autoantibody panel for lung cancer detection specifically for Chinese people. We performed a multicenter, prospective, observational study to find a novel panel of autoantibody markers that can help the diagnosis of lung cancer and the characterization of pulmonary nodules in Chinese population. The results may help to provide evidence-based recommendations to clinicians for lung cancer early detection and pulmonary nodule management. This study is registered in the ClinicalTrials.gov (NCT04216511).

The thin but widely distributed sandstones in the shallow-water deltas have the potential to hold large deposits of natural gas. The fluvial sand bodies formed from river channels with different sedimentary facies and sandstone architectures have remarkable heterogeneities. The results of this investigation suggest that the sandstone architectures of river channels have a significant impact on the hydrocarbon accumulation and production of sandstone reservoirs. Information regarding the sandstone origin and architecture of shallow-water deltas, especially of the fingered bar type, is still very limited. This investigation focused on the channel sandstones in the shallow-water delta of the Jurassic Shaximiao Formation on the eastern slope of the western Sichuan Basin in China. Based on data from cores and logs of sandstones, seven types of lithofacies and four sedimentary facies were identified. Sand-rich sedimentary facies, including distributary channels, mouth bars, and overbanks, have merged to form four types of compound sandbodies corresponding to the fourth-order architectural unit in the architectural classification. Four types of compound sand bodies were classified, including CS1 (variable distributary channel sand body), CS2 (diverting channel and residual overbank sand body), CS3 (diverting channel and residual mouth bar sand body), and CS4 (terminal channel and residual mouth bar sand body). Relatively good physical properties occur in the sandstone architectures of types CS3 and CS4, with an average porosity of 11.06% and an average permeability of 0.97 mD. Sandstone architectures from the Jurassic Shaximiao Formation of the study area were controlled by water depth and climate, tectonic subsidence, distance from provenance, erosion effect, and channel sinuosity and discharge. With strong lateral erosion, a shallow-water delta would have more sandstone architectures of types CS3 and CS4 in the high sinuosity of channels far from the provenance. Furthermore, sandstone architectures of types CS3 and CS4 are prone to form in connected channel sandbodies with relatively high contents of natural gas of approximately 4.48 × 104 m3/d. The results of this investigation are beneficial to improve the understanding of the characteristics of sandstone distributions in shallow-water deltas, especially in fingered bar types, and to guide oil and gas explorations in shallow-water delta systems.

Objective: This study aims to develop and test the self-management instrument for breast cancer patients undergoing adjuvant therapy (SMAT-B). Methods: After a qualitative interview with 29 patients and two rounds of Delphi expert consultation with 15 experts, 49 items were initially generated. Before item reduction, another structured interview was conducted for content validity. Item analysis and exploratory factor analysis (n ​= ​377) were used for item reduction. After that, internal consistency, split-half reliability, test-retest reliability (n ​= ​30), measurement error, construct validity, and structural validity (n ​= ​342) were preliminarily evaluated using the COnsesus-based Standards for the selection of health Measurements INstruments guidelines. Results: The final version of SMAT-B includes 7 dimensions and 31 items after item reduction. The testing results suggested that SMAT-B had good internal consistency (Total Cronbach's α ​= ​0.952), good split-half reliability (Spearman-Brown coefficient ​= ​0.904), good stability (Total intraclass correlation coefficient = ​0.797), acceptable measurement error (SEM ​= ​5.28), and acceptable construct validity (Standardized root mean square residual ​= ​0.055). The hypotheses of construct validity were all verified to a certain extent (r ​> ​0.20, P ​

We reported a case of a 60-year-old male with fever, cough, expectoration, and chest distress after right lung transplanted. Blood examination showed elevated C-reaction protein (CRP), white blood cell (WBC), and ammonia. Computed tomography (CT) revealed patchy high-density shadows and few pleural effusions in the transplanted lung. Bronchoscopy illustrated anastomotic fistula, and pseudomembrane and mucus plugs around the right main bronchial anastomosis. Carbapenem-resistant Klebsiella pneumoniae, Ureaplasma urealyticum, and Aspergillus flavus was successively detected by metagenomic next-generation sequencing (mNGS). Targeted anti-microbial agents were administered and patient was successfully discharged. Unfortunately, a year later, patient died of respiratory failure due to recurrent pulmonary infections.

Background: Recurrence and metastasis are the main causes of non-small cell lung cancer (NSCLC)-related death. CD146 has been identified as a potential risk factor for poor prognosis, closely related to the distant metastasis and drug resistance in various cancers. However, the clinical significance of CD146 in NSCLC requires further investigation. Materials and Methods: This study explored the correlation between CD146 expression and clinical variables using tumor tissue samples collected from our hospital. CD146 expression levels in NSCLC cell lines and tissues were assessed and compared using immunohistochemistry, real-time polymerase chain reaction (RT-qPCR), flow cytometry, and western blot analysis. The invasion and migration capabilities of tumor cells were determined using transwell and wound healing assays. The levels of proteins related to epithelial-mesenchymal transition (EMT) as well as the underlying PI3K/Akt signaling pathway was measured by western blotting. Results: We discovered that CD146 expression is significantly associated with the EMT signaling pathway. High CD146 expression predicted lymph node metastasis, metastasis to distant organs, advanced Tumor, Node, Metastasis (TNM) staging, and poor survival in NSCLC patients. Wound healing and transwell assays showed that knocking down CD146 significantly suppressed cell migration along with cell invasion in NSCLC, whereas overexpressing CD146 notably enhanced these processes. Western blot analysis revealed significantly reduced levels of N-cadherin, vimentin, snail, twist, PI3K, and AKT phosphorylation in shCD146 H460 cells compared to vector control cells. Treatment with PI3K inhibitor PI3K-IN-1 increased E-cadherin expression levels but reduced N-cadherin, Twist, Vimentin, PI3K, and AKT phosphorylation levels in pcDNA3.1-CD146 A549 cells compared with the vector control cells. Conclusions: CD146 expression acts as a prognostic risk factor for adverse outcomes in NSCLC, promoting invasion and metastasis by activating the EMT through the PI3K/Akt signaling pathway. These findings underscore the potential therapeutic strategies targeting CD146, offering new treatment options for NSCLC patients, especially those at risk of metastasis.

Owing to its high ornamental, medicinal and horticultural values, herbaceous peony (Paeonia lactiflora Pall.) has been widely used as a landscaping and economical plant around the world. However, the lack of an efficient and stable regeneration system in P. lactiflora restricts its rapid propagation and large-scale production. By testing the key factors affecting callus formation, proliferation, adventitious bud induction and rooting, here, we developed an in vitro system for callus induction and regeneration in P. lactiflora. Our results show that callus formation was affected by explant types, culture environment, basal medium and plant growth regulators. Using cotyledons as explants, we established good conditions for P. lactiflora callus induction and callus proliferation. We effectively obtained adventitious buds differentiated from callus in Murashige and Skoog (MS) medium containing kinetin (KT) and thidiazuron (TDZ). Adventitious bud growth can be further promoted by adding gibberellin 3 (GA3), 1-naphthaleneacetic acid (NAA) and 6-benzyleaminopurine (6-BA) into the MS medium. A high percentage of rooting can be achieved by adding indolebutyric acid (IBA) and activated carbon (AC) to ½ MS medium. Overall, our system promotes callus induction and adventitious bud regeneration for P. lactiflora through improved culture conditions and plant growth regulators in the culture media, and lays a foundation for subsequent genetic engineering research.

Objective: To standardize the distress management of gastric cancer patients receiving chemotherapy, the adapted Cancer-related Distress Management Guidelines were implemented in nursing practice among gastric cancer patients receiving chemotherapy based on A Guideline Adaptation and Implementation Planning Resource (CAN-IMPLEMENT). Methods: Based on the theoretical framework of CAN-IMPLEMENT, A multidisciplinary team was established, barriers and facilitators obstacles of guidelines implementation in medical oncology units were assessed, corresponding solutions were formulated, the guidelines implementation process was monitored, and implementation results were evaluated. Results: The multidisciplinary team developed review criteria, standardized work paths, assessment tools, training manuals for healthcare professionals, education manuals for patients and their caregivers. After guidelines implementation, the completion rate of the distress management record came up to 97.9% (189/193). From September 2017 to December 2018, the compliance of medical staff on most items in the audit checklist was improved, ranging from 57.1% (100/175) to 100.0% (193/193). The positive distress rate of gastric cancer patients receiving chemotherapy was decreased from 22.7% (32/141) to 9.3% (18/193) (P

RNA folding free energy nearest neighbor parameters were determined for sequences with the nucleotide m6A. The RNAstructure software package can accommodate modified nucleotides, enabling secondary structure prediction of sequences with m6A.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

Abstract Emerging evidence reveals that amino acid metabolism plays an important role in ferroptotic cell death. The conversion of methionine to cysteine is well known to protect tumour cells from ferroptosis upon cysteine starvation through transamination. However, whether amino acids‐produced metabolites participate in ferroptosis independent of the cysteine pathway is largely unknown. Here, the authors show that the tryptophan metabolites serotonin (5‐HT) and 3‐hydroxyanthranilic acid (3‐HA) remarkably facilitate tumour cells to escape from ferroptosis distinct from cysteine‐mediated ferroptosis inhibition. Mechanistically, both 5‐HT and 3‐HA act as potent radical trapping antioxidants (RTA) to eliminate lipid peroxidation, thereby inhibiting ferroptotic cell death. Monoamine oxidase A (MAOA) markedly abrogates the protective effect of 5‐HT via degrading 5‐HT. Deficiency of MAOA renders cancer cells resistant to ferroptosis upon 5‐HT treatment. Kynureninase (KYNU), which is essential for 3‐HA production, confers cells resistant to ferroptotic cell death, whereas 3‐hydroxyanthranilate 3,4‐dioxygenase (HAAO) significantly blocks 3‐HA mediated ferroptosis inhibition by consuming 3‐HA. In addition, the expression level of HAAO is positively correlated with lipid peroxidation and clinical outcome. Together, the findings demonstrate that tryptophan metabolism works as a new anti‐ferroptotic pathway to promote tumour growth, and targeting this pathway will be a promising therapeutic approach for cancer treatment.

BackgroundAlthough the status of universal upregulation for the Hyaluronan-Mediated Motility Receptor (HMMR) in pan-cancer is still unknown, HMMR is upregulated and associated with poor prognosis for some tumors.MethodsExploring HMMR expression in different tumor types using The Cancer Genome Atlas (TCGA) or other public databases for a pan-cancer analysis, exploring the relationship between HMMR and tumor prognosis, and exploring the role of HMMR in tumor immunity.ResultsNo matter the pairing or unpairing of data, HMMR expression generally increased compared to corresponding normal tissue. Based on a CCLE study, our results indicated that HMMR is widely expressed in various tumor cells. For most tumor types, high HMMR expression was associated with reduced Overall Survival (OS), Return to Functional Status (RFS), and Platinum Free Interval (PFI). ROC curves indicated that HMMR displays high prediction potential for most tumor types. In pan-cancer, HMMR is correlated with some clinical staging, immune cells, and immune checkpoints for some tumors. The GO/KEGG enrichment analysis results for proteins most closely related to HMMR indicate that the most highly enriched pathways are all related to tumor development.ConclusionsOur pan-cancer analysis of HMMR suggests that HMMR can be used as a potential diagnostic and prognostic indicator of pan-cancer and that HMMR may be involved in tumor development.

A sideways problem of the time-fractional diffusion equation is investigated. The solution of this problem does not depend on the given data. In view of this, this article uses a Tikhonov-type regularized method to construct an approximate solution and overcome the ill-posedness of considered problem. The a-posteriori convergence estimates of logarithmic and double logarithmic types for the regularized method are derived. Finally, for smooth and non-smooth cases we respectively verify the effectiveness of proposed method by doing the coresponding numerical experiments.

Abstract Coronavirus disease 2019 (COVID‐19) continually poses a significant threat to the human race, and prophylactic vaccination is the most potent approach to end this pandemic. Nanotechnology is widely adopted during COVID‐19 vaccine development, and the engineering of nanostructured materials such as nanoparticles has opened new possibilities in innovative vaccine development by improving the design and accelerating the development process. This review aims to comprehensively understand the current situation and prospects of nanotechnology‐enabled vaccine development against the COVID‐19 pandemic, with an emphasis on the interplay between nanotechnology and the host immune system.

The genus Salicornia (Amaranthaceae) was established by Linnaeus (1753). Commonly known as ‘glassworts’, the species of the genus are articulated succulent herbs with cortical palisade, opposite decussate scale-leaves, thyrsoid cymes, flowers packed in cauline depressions and the diaspore composed of l-seeded utricle. Therefore, due to the importance of the plant species, we performed a combination of morphological and molecular data analyses on this species. A total of 72 randomly collected plants from 8 natural populations in 2 provinces were evaluated using ISSR markers and morphological traits. Analysis of molecular variance (AMOVA) test revealed significant genetic difference among the studied populations, and also showed that 45% of total genetic variability was due to the diversity within the population, while 55% was due to the genetic differentiation among populations. A total number of 158 bands were detected by ISSR primers, of which 144 (89%) bands with an average of 14.4 bands per primer were polymorphic. The Percentage of Polymorphic Bands (PPB) ranged from 70% (ISSR-7) to 100% (ISSR-1, ISSR-4 and ISSR-5). The average Polymorphic Information Content (PIC), Shannon's Information index (I), and Number of effective alleles (Ne) were 0.49, 0.28, and 1.09, respectively.

Owing to the unique electromagnetic response ability, electromagnetic metasurface have potential applications in medical, imaging, sensing, and other fields. In this paper, a graphene-based THz metasurface sensor with an air spacer layer is designed by combining the advantages of the air spacer structure and the dynamic tunability of graphene materials. The proposed metasurface sensor consists of six layers, which are silicon dioxide (SiO2) substrate, metal reflector, air layer, graphene metasurface etched with microstructure, ion-gel layer and silicon dioxide dielectric layer from bottom to top. A comprehensive study of the absorption properties and sensing performance are carried out which is simulated and analyzed with the help of CST Microwave Studio software. The calculation results show that the two obvious resonance absorption peaks located at 0.95 THz and 1.53 THz with absorption of 94.9% and 79%, respectively, and there is a good linear relationship between the absorption peak and dielectric parameters of analyte. The frequency shift sensitivity of the two resonance peaks M1 and M2 can reach 450 GHz/RIU and 717 GHz/RIU, respectively. By changing the thickness of the air layer, when the two resonance peaks M1 and M2 reach the maximum absorption at h2=140 μm and h2=280 μm, respectively, the frequency shift sensitivity is still as high as close to 450 GHz/RIU. The influence of structure parameters and incident angle on the absorption spectrum shows that the proposed structure has good stability and reliability. The proposed graphene-based absorption sensor has good biocompatibility, broadening the application range of terahertz functional devices.

Abstract Background Calotropis procera leaf is one of the plants commonly utilized in phytomedicine in Nigeria. The present investigation explored the use of the extracts on cell viability and apoptosis respectively. In this study, the expression of the Cluster of differentiation 146 (CD146) in the blood of lung cancer patients on regulatory T cells (Tregs) was determined. The antioxidant and anti-proliferative effects of methanol extracts of Caloropis procera leaf on lung cancer cell H1299 were investigated. Methods From the flow cytometry, the expression of the CD146+ in the T cells were evaluated using the healthy patient, adenocarcinoma, squamous, and small cell lung cancer respectively. The apoptosis of granulocytes, monocytes, lymphocytes, CD4+, and Treg were determined by 7-amino-actinomycin D/Annexin V-Allophycocyanin (APC) staining during the resting stage and after 24 h respectively. Immunofluorescence was conducted. Cell viability assay, hydroxyl (OH), hydrogen peroxide (H2O2) and nitric oxide (NO) scavenging radicals were conducted. Reducing power and flavonoid content of Calotropis procera were investigated. The effect of the Calotropis procera at different concentrations at 24hrs was determined. Results From the flow cytometry, the expression of the CD146+ on the T cells includes 4.60 % in healthy patients, 10.10, 12.20, 9.80 % in adenocarcinoma, squamous and small cell lung cancer. The apoptosis of granulocytes, monocytes, lymphocytes, CD4+ and Treg were determined by 7-amino-actinomycin D/Annexin V-APC staining during the resting stage and after 24 h which indicate that apoptosis also occurred on Treg. Immunofluorescence shows the presence of CD146 in lung cancer patient’s tissues. The methanol extracts of Calotropis procera leaf have antioxidant and anti-proliferative effects. Methanol extract of Calotropis procera leaf reduced CD146 expression on blood cells at 24 h. Conclusion Increased CD146 expression in the Treg of lung cancer patients indicates that it may be a possible target for the treatment of lung cancer by utilizing potent immunotherapy or natural products such as methanol extract of Calotropis procera leaf which may ameliorate the expression of CD146. Calotropis procera has antioxidant, inhibitory capacity on H1299 lung cancer cells, and the ability to scavenge OH, H2O2, and NO radicals. Hence, this investigation strengthens the phyto-medicinal properties of Calotropis procera.

Abstract SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing the COVID-19 pandemic in 2020. High adaptive plasticity on the spike protein of SASR-CoV-2 enables it to transmit across different host species. In the present study, we collected 2092 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny. We also analyzed the polymorphic interaction between spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 suggests that SARS-CoV-2 is probably originated from a recombination event on the spike protein between a bat coronavirus and a pangolin coronavirus that endows it humans infectivity. Compared with other regions in the S gene of SARS-CoV-2, the direct-binding sites of the receptor-binding domain (RBD) is more conserved. We focused on 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 and simulated their differential stability and binding affinity to hACE2 (S19-D615). The results indicate no preference for SARS-CoV-2 infectivity on people of different ethnic groups. The variants in the spike protein of SARS-CoV-2 may also be a good indicator demonstrating the transmission route of SARS-CoV-2 from its natural reservoir to human hosts.

Abstract The article investigates a Riesz–Feller space-fractional backward diffusion problem. We develop a generalized Tikhonov regularization method to overcome the ill-posedness of this problem, and then based on the result of conditional stability, we derive the convergence estimates of logarithmic and double logarithmic types for the regularized method by adopting a-posteriori choice rules of regularization parameter. Finally, by using the finite difference method, we solve a direct problem to construct the data, and some corresponding results of numerical simulations are presented to verify the convergence and stability for this method.

Lung cancer is the leading cause of cancer-related deaths worldwide and in China. Screening for lung cancer by low dose computed tomography (LDCT) can reduce mortality but has resulted in a dramatic rise in the incidence of indeterminate pulmonary nodules, which presents a major diagnostic challenge for clinicians regarding their underlying pathology and can lead to overdiagnosis. To address the significant gap in evaluating pulmonary nodules, we conducted a prospective study to develop a prediction model for individuals at intermediate to high risk of developing lung cancer. Univariate and multivariate logistic analyses were applied to the training cohort (n = 560) to develop an early lung cancer prediction model. The results indicated that a model integrating clinical characteristics (age and smoking history), radiological characteristics of pulmonary nodules (nodule diameter, nodule count, upper lobe location, malignant sign at the nodule edge, subsolid status), artificial intelligence analysis of LDCT data, and liquid biopsy achieved the best diagnostic performance in the training cohort (sensitivity 89.53%, specificity 81.31%, area under the curve [AUC] = 0.880). In the independent validation cohort (n = 168), this model had an AUC of 0.895, which was greater than that of the Mayo Clinic Model (AUC = 0.772) and Veterans’ Affairs Model (AUC = 0.740). These results were significantly better for predicting the presence of cancer than radiological features and artificial intelligence risk scores alone. Applying this classifier prospectively may lead to improved early lung cancer diagnosis and early treatment for patients with malignant nodules while sparing patients with benign entities from unnecessary and potentially harmful surgery.Clinical Trial Registration NumberChiCTR1900026233, URL: http://www.chictr.org.cn/showproj.aspx?proj=43370.

This paper deals with n-players fuzzy cooperative continuous static games (FCCSGs). The cost function coefficients are characterized by piecewise quadratic fuzzy numbers. One of the best approximate intervals, namely, the inexact interval of the piecewise quadratic fuzzy number is used. Furthermore, we proposed a new methodology based on the weighted Tchebycheff method to solve CCSG with n-players. The advantages of the approach are the ability to enable the decision-maker to have satisfactory solution and applied for different real-world problems with various types of fuzzy numbers. There is also a stability set of the first kind without differentiability for the optimal compromise solution that was found. In the future, the proposed methodology could be used in different types of real-world problems and multiple decision-makers. This proposed work can also be extended to hypersoft set, fuzzy hypersoft sets, intuitionistic hypersoft sets, bipolar hypersoft sets, and pythagorean hypersoft sets. At the end, a numerical example is given to demonstrate the computational efficiency of the proposed method.

The generalization of Godunova–Levin interval-valued functions has been drastically studied in last few decades, as it has a remarkable applications in both pure and applied mathematics. The goal of this study is to introduce the notion of h-Godunova–Levin interval-valued functions. We establish Hermite–Hadamard and Jensen-type inequalities via Riemann integral operator.

Background: Carbapenemase-producing Klebsiella pneumoniae (CpKP) has been implicated as an increasing threat to public health. CpKP is a ubiquitous, opportunistic pathogen that causes both hospital and community acquired infections. This organism hydrolyzes carbapenems and other β-lactams and thus, leading to multiple resistance to these antibiotics. Despite the difficult to treat nature of infections caused by CpKP, little has been discussed on the mortality, clinical response and microbiological success rates associated with various antibiotic regimen against CpKP. This meta-analysis was designed to fill the paucity of information on the clinical impact of various antibiotic therapeutic regimens among patients infected with CpKP.Materials and Methods: Literature in most English databases such as Medline through PubMed, Google Scholar, Web of Science, Cochrane Library and EMBASE, were searched for most studies published between the years 2015–2020. Data were analyzed using the R studio 2.15.2 statistical software program (metaphor and meta Package, Version 2) by random-effects (DerSimonian and Laird) model.Results: Twenty-one (21) studies including 2841 patients who had been infected with CpKP were analysed. The overall mortality rate was 32.2% (95%CI = 26.23–38.87; I2 = 89%; p-value ≤ 0.01, Number of patients = 2716). Pooled clinical and microbiological success rates were 67.6% (95%CI = 58.35–75.64, I2 = 22%, p-value = 0.25, Number of patients = 171) and 74.9% (95%CI = 59.02–86.09, I2 = 53%, p-value = 0.05, Number of patients = 121), respectively. CpKP infected patients treated with combination therapy are less likely to die as compared to those treated with monotherapy (OR = 0.55, 95%CI = 0.35–0.87, p-value = 0.01, Number of patients = 1,475). No significant difference existed between the mortality rate among 60years and above patients vs below 60years (OR = 0.84, 95%CI = 0.28–2.57, p-value = 0.76, 6 studies, Number of patients = 1,688), and among patients treated with triple therapy vs. double therapy (OR = 0.50, 95%CI = 0.21–1.22, p-value = 0.13, 2 studies, Number of patients = 102). When compared with aminoglycoside-sparing therapies, aminoglycoside-containing therapies had positive significant outcomes on both mortality and microbiological success rates.Conclusion: New effective therapies are urgently needed to help fight infections caused by this organism. The effective use of various therapeutic options and the strict implementation of infection control measures are of utmost importance in order to prevent infections caused by CpKP. Strict national or international implementation of infection control measures and treatment guidelines will help improve healthcare, and equip governments and communities to respond to and prevent the spread of infectious diseases caused by CpKP.

Carbon-based metamaterials are expected to lead to biological and chemical sensing because of their fast electron transfer rate, good biocompatibility, and high absorption ratios. In this work, we integrate carbon nanotubes metasurface (CM) and microfluidic channel (MC) for a composite terahertz (THz) metasurface (CMMC). The absorption properties and sensing performance of the proposed composite metasurface have been studied. It is observed that the absorption is nearly 71.8% at 0.96 THz and 92.4% at 1.65 THz, respectively. The variation of response with refractive index of the analytes for the proposed CMMC is investigated and it is found that the frequency and intensity of the resonance absorption peak at 0.96 THz f1 decrease obviously with the increase of the refractive index of the analytes. Owing to the coupling of the CM and MC in the microfluidic channel, the interaction between the incident THz wave and analytes has been enhanced, and the frequency and intensity sensitivities has achieved 254 GHz/RIU and 314/RIU, respectively. In addition, the influence of the structural parameters of the proposed CMMC on the absorption characteristics is also studied in detail. The results shown that the absorption properties of the CMMC can be adjusted by changing the structural parameters, which will provide a guideline for design. The proposed CMMC will facilitate the realization of carbon nanotube metamaterials sensing applications, and, when combined with microfluidic channel, will lead to large-area THz biological and chemical sensing.

Rapid recruitment of neutrophils to an inflamed site is one of the hallmarks of an effective host defense mechanism. The main pathway through which this happens is by the innate immune response. Neutrophils, which play an important part in innate immune defense, migrate into lungs through the modulation actions of chemokines to execute a variety of pro-inflammatory functions. Despite the importance of chemokines in host immunity, little has been discussed on their roles in host immunity. A holistic understanding of neutrophil recruitment, pattern recognition pathways, the roles of chemokines and the pathophysiological roles of neutrophils in host immunity may allow for new approaches in the treatment of infectious and inflammatory disease of the lung. Herein, this review aims at highlighting some of the developments in lung neutrophil-immunity by focusing on the functions and roles of CXC/CC chemokines and pattern recognition receptors in neutrophil immunity during pulmonary inflammations. The pathophysiological roles of neutrophils in COVID-19 and thromboembolism have also been summarized. We finally summarized various neutrophil biomarkers that can be utilized as prognostic molecules in pulmonary inflammations and discussed various neutrophil-targeted therapies for neutrophil-driven pulmonary inflammatory diseases.

Central nervous system (CNS) disorders feature the progressive and selective loss of normal brain functions. CNS disorders often include an irreversible physiological and anatomical loss of neurons that can lead to dysfunction in various parts of the brain and eventually death. Glioblastoma multiforme (GBM) and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are hard to be diagnosed at an early stage for the prevention of disease propagation. Such diagnosis is vital for the timely commencement of actual treatments. Nanotechnology brings new diagnosis hope for CNS disorders as it provides ultrasensitive detection for more specific biomarkers. Herein, the recent progress in techniques development for detecting pathological biomarkers for GBM, AD, and PD is summarized, in particular, the principles that govern the design of these sensors, blood–brain barrier (BBB) dysfunction, and its integrity during disease development. Finally, a perspective on future directions to further advance and improve the early‐stage diagnosis of CNS disorders is presented.

Surfactant protein D (SP-D) plays an important role in innate and adaptive immune responses. In this study, we found that the expression of total and de-oligomerized SP-D was significantly elevated in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI). To investigate the role of the lower oligomeric form of SP-D in the pathogenesis of ALI, we treated bone marrow-derived macrophages (BMDMs) with ALI-derived bronchoalveolar lavage (BAL) and found that SP-D in ALI BAL predominantly bound to calreticulin (CALR) on macrophages, subsequently increasing the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and expression of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, IL-10, and CD80. However, anti-SP-D (aSP-D) and anti-calreticulin (aCALR) pretreatment reversed the SP-D binding and activation of macrophages induced by ALI BAL or de-oligomerized recombinant murine SP-D (rSP-D). Lack of signal transducer and activator of transcription (STAT)6 in STAT6-/- macrophages resulted in resistance to suppression by aCALR. Further studies in an ALI mouse model showed that blockade of pulmonary SP-D by intratracheal (i.t.), but not intraperitoneal (i.p.), administration of aSP-D attenuated the severity of ALI, accompanied by lower neutrophil infiltrates and expression of IL-1beta and IL-6. Furthermore, i.t. administration of de-oligomerized rSP-D exacerbated the severity of ALI in association with more pro-inflammatory CD45+Siglec-F(-) M1 subtype macrophages and production of IL-6, TNF-alpha, IL-1beta, and IL-18. The results indicated that SP-D in the lungs of murine ALI was de-oligomerized and participated in the pathogenesis of ALI by predominantly binding to CALR on macrophages and subsequently activating the pro-inflammatory downstream signaling pathway. Targeting de-oligomerized SP-D is a promising therapeutic strategy for the treatment of ALI and acute respiratory distress syndrome (ARDS).

The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

Abstract CD146 alternatively called melanoma cell adhesion molecule (MCAM), is a biomarker and therapeutic target of clinical significance. It is found on different cells including the endothelial cells and lymphocytes which participate in heterotypic and homotypic ligand-receptor. This review concentrated on the CD146 expression T cells (or lymphocytes) centering on Treg in lung cancer. Here, we have also considered the vigorous investigation of CD146 mainly acknowledged new roles, essential mechanisms and clinical implications of CD146 in cancer. CD146 has progressively become a significant molecule, particularly recognized as a novel biomarker, prognosis and therapy for cancer. Hence, targeting CD146 expression by utilization of methanol extracts of Calotropis procera leaf may be useful for the treatment of carcinogenesis.

Objective To evaluate the efficacy of the Archimedes Navigation System (Broncus Medical, San Jose, CA, USA) for guidance during transbronchial cryobiopsy and the incidence of complications in patients with diffuse lung disease. Methods High-resolution computed tomography and transbronchial cryobiopsy were used to evaluate eight patients with diffuse lung disease. The Archimedes Navigation System was used before cryobiopsy to obtain the best path with which to avoid large vessels. Three to five cryobiopsy specimens were taken from each sampled segment. Results Preoperative planning using the Archimedes Navigation System was successfully performed on all eight patients. The probe-to-pleura distance was approximately 10 mm. No cases of pneumothorax occurred, one patient developed moderate bleeding, two developed minor bleeding, and five developed minimal bleeding that stopped spontaneously. A final diagnosis was obtained for seven patients, and ongoing follow-up was being conducted for the last patient at the time of this writing. Conclusions This is the first report of combining navigation technology with cryobiopsy to diagnose diffuse lung disease. The Archimedes Navigation System, which provides real-time guidance, is helpful in pre-cryobiopsy planning and diagnosis of diffuse lung disease. Moreover, this system can reduce the pneumothorax rate and bleeding risk by avoiding large vessels.

Background and aims: Asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO) is poorly recognized in China. Our study determined the distribution of ACO and its clinical characteristics among patients (aged ⩾40 years) with airflow limitation at Chinese tertiary hospitals. Methods: This cross-sectional, non-interventional study (NCT02600221), conducted between December 2015 and October 2016 in 20 Tier-3 Chinese hospitals, included patients aged ⩾40 years with post-bronchodilator (BD) FEV 1 /FVC