Non-malignant pathological results from CT-guided biopsy for pulmonary nodules: a predictive model for identifying false-negative results.

BACKGROUND: Computed tomography (CT)-guided biopsy (CTB) procedures are commonly used to aid in the diagnosis of pulmonary nodules (PNs). When CTB findings indicate a non-malignant lesion, it is critical to correctly determine false-negative results. Therefore, the current study was designed to construct a predictive model for predicting false-negative cases among patients receiving CTB for PNs who receive non-malignant results. MATERIALS AND METHODS: From January 2016 to December 2020, consecutive patients from two centers who received CTB-based non-malignant pathology results while undergoing evaluation for PNs were examined retrospectively. A training cohort was used to discover characteristics that predicted false negative results, allowing the development of a predictive model. The remaining patients were used to establish a testing cohort that served to validate predictive model accuracy. RESULTS: The training cohort included 102 patients with PNs who showed non-malignant pathology results based on CTB. Each patient underwent CTB for a single nodule. Among these patients, 85 and 17 patients, respectively, showed true negative and false negative PNs. Through univariate and multivariate analyses, higher standardized maximum uptake values (SUVmax, P = 0.001) and CTB-based findings of suspected malignant cells (P = 0.043) were identified as being predictive of false negative results. Following that, these two predictors were combined to produce a predictive model. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.945. Furthermore, it demonstrated sensitivity and specificity values of 88.2% and 87.1% respectively. The testing cohort included 62 patients, each of whom had a single PN. When the developed model was used to evaluate this testing cohort, this yielded an AUC value of 0.851. CONCLUSIONS: In patients with PNs, the predictive model developed herein demonstrated good diagnostic effectiveness for identifying false-negative CTB-based non-malignant pathology data.

Astrocyte-specific inhibition of sigma-1 receptor leads to depressive-like behaviors in mice via activation of NF-κB-induced neuroinflammation.

Major depressive disorder (MDD) is a global health burden characterized by persistent low mood, deprivation of pleasure, recurrent thoughts of death, and physical and cognitive deficits. The current understanding of the pathophysiology of MDD is lacking, resulting in few rapid and effective antidepressant therapies. Recent studies have pointed to the sigma-1 (σ-1) receptor as a potential rapid antidepressant target; σ-1 agonists have shown promise in a variety of preclinical depression models. Hypidone hydrochloride (YL-0919), an independently developed antidepressant by our institute with faster onset of action and low rate of side effects, has recently emerged as a highly selective σ-1 receptor agonist; however, its underlying astrocyte-specific mechanism is unknown. In this study, we investigated the effect of YL-0919 treatment on gene expression in the prefrontal cortex of depressive-like mice by single-cell RNA sequencing. Furthermore, we knocked down σ-1 receptors on astrocytes in the medial prefrontal cortex of mice to explore the effects of YL-0919 on depressive-like behavior and neuroinflammation in mice. Our results demonstrated that astrocyte-specific knockdown of σ-1 receptor resulted in depressive-like behavior in mice, which was reversed by YL-0919 administration. In addition, astrocytic σ-1 receptor deficiency led to activation of the NF-κB inflammatory pathway, and crosstalk between reactive astrocytes and activated microglia amplified neuroinflammation, exacerbating stress-induced neuronal apoptosis. Furthermore, the depressive-like behavior induced by astrocyte-specific knockdown of the σ-1 receptor was improved by a selective NF-κB inhibitor, JSH-23, in mice. Our study not only reaffirms the σ-1 receptor as a key target of the faster antidepressant effect of YL-0919, but also contributes to the development of astrocytic σ-1 receptor-based novel drugs.

The optimal second-line therapy for older adults with type 2 diabetes mellitus: protocol for a systematic review and network meta-analysis using individual participant data (IPD).

BACKGROUND: Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. METHODS: All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. DISCUSSION: With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272686.

Treatment plan complexity quantification for predicting gamma passing rates in patient-specific quality assurance for stereotactic volumetric modulated arc therapy.

PURPOSE: To investigate the beam complexity of stereotactic Volumetric Modulated Arc Therapy (VMAT) plans quantitively and predict gamma passing rates (GPRs) using machine learning. METHODS: The entire dataset is exclusively made of stereotactic VMAT plans (301 plans with 594 beams) from Varian Edge LINAC. The GPRs were analyzed using Varian's portal dosimetry with 2%/2 mm criteria. A total of 27 metrics were calculated to investigate the correlation between metrics and GPRs. Random forest and gradient boosting models were developed and trained to predict the GPRs based on the extracted complexity features. The threshold values of complexity metric were obtained to predict a given beam to pass or fail from ROC curve analysis. RESULTS: The three moderately significant values of Spearman's rank correlation to GPRs were 0.508 (p < 0.001), 0.445 (p < 0.001), and -0.416 (p < 0.001) for proposed metric LAAM, the ratio of the average aperture area over jaw area (AAJA) and index of modulation, respectively. The random forest method achieved 98.74% prediction accuracy with mean absolute error of 1.23% using five-fold cross-validation, and 98.71% with 1.25% for gradient boosting regressor method, respectively. LAAM, leaf travelling distance (LT), AAJA, LT modulation complexity score (LTMCS) and index of modulation, were the top five most important complexity features. The LAAM metric showed the best performance with AUC value of 0.801, and threshold value of 0.365. CONCLUSIONS: The calculated metrics were effective in quantifying the complexity of stereotactic VMAT plans. We have demonstrated that the GPRs could be accurately predicted using machine learning methods based on extracted complexity metrics. The quantification of complexity and machine learning methods have the potential to improve stereotactic treatment planning and identify the failure of QA results promptly.

Revolutionizing Neurocare: Biomimetic Nanodelivery Via Cell Membranes.

Brain disorders represent a significant challenge in medical science due to the formidable blood-brain barrier (BBB), which severely limits the penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into the innovative realm of biomimetic nanodelivery systems, including stem cell-derived nanoghosts, tumor cell membrane-coated nanoparticles, and erythrocyte membrane-based carriers, highlighting their potential to circumvent the BBB's restrictions. By mimicking native cell properties, these nanocarriers emerge as a promising solution for enhancing drug delivery to the brain, offering a strategic advantage in overcoming the barrier's selective permeability. The unique benefits of leveraging cell membranes from various sources is evaluated and advanced technologies for fabricating cell membrane-encapsulated nanoparticles capable of masquerading as endogenous cells are examined. This enables the targeted delivery of a broad spectrum of therapeutic agents, ranging from small molecule drugs to proteins, thereby providing an innovative approach to neurocare. Further, the review contrasts the capabilities and limitations of these biomimetic nanocarriers with traditional delivery methods, underlining their potential to enable targeted, sustained, and minimally invasive treatment modalities. This review is concluded with a perspective on the clinical translation of these biomimetic systems, underscoring their transformative impact on the therapeutic landscape for intractable brain diseases.

Bone marrow stromal cells dictate lanosterol biosynthesis and ferroptosis of multiple myeloma.

Ferroptosis has been demonstrated a promising way to counteract chemoresistance of multiple myeloma (MM), however, roles and mechanism of bone marrow stromal cells (BMSCs) in regulating ferroptosis of MM cells remain elusive. Here, we uncovered that MM cells were more susceptible to ferroptotic induction under the interaction of BMSCs using in vitro and in vivo models. Mechanistically, BMSCs elevated the iron level in MM cells, thereby activating the steroid biosynthesis pathway, especially the production of lanosterol, a major source of reactive oxygen species (ROS) in MM cells. We discovered that direct coupling of CD40 ligand and CD40 receptor constituted the key signaling pathway governing lanosterol biosynthesis, and disruption of CD40/CD40L interaction using an anti-CD40 neutralizing antibody or conditional depletion of Cd40l in BMSCs successfully eliminated the iron level and lanosterol production of MM cells localized in the Vk*MYC Vk12653 or NSG mouse models. Our study deciphers the mechanism of BMSCs dictating ferroptosis of MM cells and highlights the therapeutic potential of non-apoptosis strategies for managing refractory or relapsed MM patients.

Discovery of a Long Half-Life AURKA Inhibitor to Treat MYC-Amplified Solid Tumors as a Monotherapy and in Combination with Everolimus.

Aurora kinase inhibitors, such as alisertib, can destabilize MYC-family oncoproteins and have demonstrated compelling antitumor efficacy. In this study, we report 6K465, a novel pyrimidine-based Aurora A inhibitor, that reduces levels of c-MYC and N-MYC oncoproteins more potently than alisertib. In an analysis of the antiproliferative effect of 6K465, the sensitivities of small cell lung cancer (SCLC) and breast cancer cell lines to 6K465 were strongly associated with the protein levels of c-MYC and/or N-MYC. We also report DBPR728, an acyl-based prodrug of 6K465 bearing fewer hydrogen-bond donors, that exhibited 10-fold improved oral bioavailability. DBPR728 induced durable tumor regression of c-MYC- and/or N-MYC-overexpressing xenografts including SCLC, triple-negative breast cancer, hepatocellular carcinoma, and medulloblastoma using a 5-on-2-off or once-a-week dosing regimen on a 21-day cycle. A single oral dose of DBPR728 at 300 mg/kg induced c-MYC reduction and cell apoptosis in the tumor xenografts for more than 7 days. The inhibitory effect of DBPR728 at a reduced dosing frequency was attributed to its uniquely high tumor/plasma ratio (3.6-fold within 7 days) and the long tumor half-life of active moiety 6K465. Furthermore, DBPR728 was found to synergize with the mTOR inhibitor everolimus to suppress c-MYC- or N-MYC-driven SCLC. Collectively, these results suggest DBPR728 has the potential to treat cancers overexpressing c-MYC and/or N-MYC.

High Manganese Content of Lipid NanoMn (LNM) by Microfluidic Technology for Enhancing Anti-Tumor Immunity.

Immunotherapy is a clinically effective method for treating tumors. Manganese can activate the cGAS-STING signaling pathway and induce an anti-tumor immune response. However, its efficacy is hindered by non-specific distribution and low uptake rates. In this study, we employed microfluidic technology to design and develop an innovative preparation process, resulting in the creation of a novel manganese lipid nanoparticle (LNM). The lipid manganese nanoparticle produced in this process boasts a high manganese payload, excellent stability, the capacity for large-scale production, and high batch repeatability. LNM has effectively demonstrated the ability to activate the cGAS-STING signaling pathway, induce the production of pro-inflammatory cytokines, and inhibit tumor development. Notably, LNM does not require combination chemotherapy drugs or other immune activators. Therefore, LNM presents a safe, straightforward, and efficient strategy for anti-tumor immune activation, with the potential for scalable production.

In vivo absorption, in vitro simulated digestion and fecal fermentation properties of polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine and their effects on human gut microbiota.

Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine (PPA) have various biological activities, but their properties after oral administration are not clear. In this study, the absorption, digestion and fermentation properties of PPA were studied using in vivo fluorescence tracking, in vitro simulated digestion and fecal fermentation experiments. The absorption experiment showed that fluorescence was only observed in the gastrointestinal system, indicating that PPA could not be absorbed. Simulated digestion results showed that there were no significant changes in the molecular weight, Fourier transform infrared spectroscopy (FT-IR) spectrum, monosaccharides and reducing sugar of PPA during the digestion process, showing that the overall structure of PPA was not damaged. However, the carbohydrate gel electrophoresis bands of PPA enzymatic hydrolysates after simulated digestion were significantly changed, indicating that simulated digestion might impact the configuration of PPA. In vitro fermentation showed that PPA could be degraded by microorganisms to produce short chain fatty acids, leading to a decrease in pH value. PPA can promote the proliferation of Bacteroideaceae, Megasphaera, Bacteroideaceae, and Bifidobacteriaceae, and inhibit the growth of Desulfobacteriota and Enterobacteriaceae. The results indicated that PPA could treat diseases by regulating gut microbiota, providing a scientific basis for the application and development of PPA.

Contemporary strategies and approaches for characterizing composition and enhancing biofilm penetration targeting bacterial extracellular polymeric substances.

Extracellular polymeric substances (EPS) constitutes crucial elements within bacterial biofilms, facilitating accelerated antimicrobial resistance and conferring defense against the host's immune cells. Developing precise and effective antibiofilm approaches and strategies, tailored to the specific characteristics of EPS composition, can offer valuable insights for the creation of novel antimicrobial drugs. This, in turn, holds the potential to mitigate the alarming issue of bacterial drug resistance. Current analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias, which is likely due to the selection of a standard compound and the cross-interference of various EPS compounds. Considering the pivotal role of EPS in biofilm functionality, it is imperative for EPS research to delve deeper into the analysis of intricate compositions, moving beyond the current focus on polymeric materials. This necessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical approaches. In this study, we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS compositions. Additionally, novel strategies aimed at targeting EPS to enhance biofilm penetration were explored, with a specific focus on highlighting the limitations associated with colorimetric methods. Furthermore, we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these challenges. This review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS, thereby inhibiting biofilm formation. This insight opens up a new avenue for exploration within this research domain.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

Study on the material source and enrichment mechanism of REE-rich phosphorite in Zhijin, Guizhou.

Rare earth element (REE)-rich phosphorite in the Guizhou region mainly exists in the Doushantuo Formation and Gezhongwu Formation in early Cambrian strata, which are some of the important strata containing phosphorite resources in China. The early Cambrian Zhijin phosphorite in Guizhou Province, China, has high rare earth element and yttrium (REY) contents of up to 2500 ppm, with heavy REY (HREY) contents accounting for ~ 30% of the total REY contents. However, the specific controlling source and environment of phosphorite (especially the REEs in Zhijin phosphorite) are still unsolved. Through field geological investigations; mineralogical, geochemical, Sr-Nd isotope analyses; and tectonic characteristics, the material source, sedimentary environment and seawater dynamics of REEs in phosphorite are studied. It is considered that the REEs enriched in the Zhijin phosphorite are mainly affected by precipitation from hydrothermal fluid. Moreover, from the late Ediacaran to the early Cambrian, the depositional environment from the bottom to the top of the water tended to be hypoxic, and the activity of hot water fluid tended to be strong. The change in redox conditions is closely related to the rise and fall of sea level. Combined with the tectonic background, these results show that the weakly oxidized environment may be an important factor controlling the enrichment of REEs. The enrichment of REEs may be closely related to volcanic hydrothermal activity, later diagenesis and seawater dynamics.

Quantification of preexisting lung ground glass opacities on CT for predicting checkpoint inhibitor pneumonitis in advanced non-small cell lung cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can lead to life-threatening pneumonitis, and pre-existing interstitial lung abnormalities (ILAs) are a risk factor for checkpoint inhibitor pneumonitis (CIP). However, the subjective assessment of ILA and the lack of standardized methods restrict its clinical utility as a predictive factor. This study aims to identify non-small cell lung cancer (NSCLC) patients at high risk of CIP using quantitative imaging. METHODS: This cohort study involved 206 cases in the training set and 111 cases in the validation set. It included locally advanced or metastatic NSCLC patients who underwent ICI therapy. A deep learning algorithm labeled the interstitial lesions and computed their volume. Two predictive models were developed to predict the probability of grade ≥ 2 CIP or severe CIP (grade ≥ 3). Cox proportional hazard models were employed to analyze predictors of progression-free survival (PFS). RESULTS: In a training cohort of 206 patients, 21.4% experienced CIP. Two models were developed to predict the probability of CIP based on different predictors. Model 1 utilized age, histology, and preexisting ground glass opacity (GGO) percentage of the whole lung to predict grade ≥ 2 CIP, while Model 2 used histology and GGO percentage in the right lower lung to predict grade ≥ 3 CIP. These models were validated, and their accuracy was assessed. In another exploratory analysis, the presence of GGOs involving more than one lobe on pretreatment CT scans was identified as a risk factor for progression-free survival. CONCLUSIONS: The assessment of GGO volume and distribution on pre-treatment CT scans could assist in monitoring and manage the risk of CIP in NSCLC patients receiving ICI therapy. CLINICAL RELEVANCE STATEMENT: This study's quantitative imaging and computational analysis can help identify NSCLC patients at high risk of CIP, allowing for better risk management and potentially improved outcomes in those receivingICI treatment.

Characterization of a membrane Fcγ receptor in largemouth bass (Micropterus saloumoides) and its response to bacterial challenge.

Fc receptors (FcRs), specific to the Fc portion of immunoglobulin (Ig), are required to regulate immune responses against pathogenic infections. However, FcγR is a member of FcRs family, whose structure and function remains to be elucidated in teleost fish. In this study, the FcγRII, from largemouth bass (Micropterus saloumoides), named membrane MsFcγRII (mMsFcγRII), was cloned and identified. The opening reading frame (ORF) of mMsFcγRII was 750 bp, encoding 249 amino acids with a predicted molecular mass of 27 kDa. The mMsFcγRII contained a signal peptide, two Ig domains, a transmembrane domain, and an intracellular region, which was highly homology with FcγR from other teleost fish. The mRNA expression analysis showed that mMsFcγRII was widely distributed in all tested tissues and with the highest expression level in spleen. After bacterial challenge, the expression of mMsFcγRII was significantly upregulated in vivo (spleen and head kidney), as well as in vitro (leukocytes from head kidney). The subcellular localization assay revealed that mMsFcγRII was mostly observed on the membrane of HEK293T cells which were transfected with mMsFcγRII overexpression plasmid. Flow cytometric analysis showed that natural mMsFcγRII protein was highly expressed in head kidney lymphocytes. Moreover, indirect immunofluorescence assay and pull-down assay indicated that mMsFcγRII could bind to IgM purified from largemouth bass serum. These results suggested that mMsFcγRII was likely to play an influential role in the immune response against pathogens and provided valuable insights for studying the function of FcRs in teleost.

PD-L1 Expression Is Increased in LPS-Induced Acute Respiratory Distress Syndrome by PI3K-AKT-Egr-1/C/EBPδ Signaling Pathway.

The role of programmed death ligand 1 (PD-L1) has been extensively investigated in adaptive immune system. However, increasing data show that innate immune responses are also affected by the immune checkpoint molecule. It has been demonstrated that regulation of PD-L1 signaling in macrophages may be a potential therapeutic method for acute respiratory distress syndrome (ARDS). However, the PD-L1 expression pattern in local macrophages and whole lung tissues remains mysterious, hindering optimization of the potential treatment program. Therefore, we aim to determine the PD-L1 expression pattern during ARDS. Our findings show that PD-L1 levels are markedly increased in lipopolysaccharide (LPS)-stimulated lung tissues, which might be attributable to an increase in the gene expression by immune cells, including macrophages and neutrophils. In vitro experiments are performed to explore the mechanism involved in LPS-induced PD-L1 production. We find that PD-L1 generation is controlled by transcription factors early growth response 1 (Egr-1) and CCAAT/enhancer binding protein delta (C/EBPδ). Strikingly, PD-L1 production is enhanced by phosphoinositide-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway via up-regulation of Egr-1 and C/EBPδ expressions. Additionally, we observe that expressions of Egr-1 and C/EBPδ mutually reinforce each other. Moreover, we observe that PD-L1 is protective for ARDS due to its regulatory role in macrophage-associated inflammatory response. In summary, during LPS-induced ARDS, PD-L1 expression, which is beneficial for the disease, is increased via the PI3K-AKT1-Egr-1/C/EBPδ signaling pathway, providing theoretical basis for application of methods controlling PD-L1 signaling in macrophages for ARDS treatment in clinic.

Socioeconomic Deprivation and the Risk of Sight-Threatening Diabetic Retinopathy: A Population-Based Cohort Study in the U.K.

OBJECTIVE: To evaluate the associations between socioeconomic deprivation and sight-threatening diabetic retinopathy (STDR) in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Data from 175,628 individuals with diabetes in the Health Improvement Network were used to assess the risk of STDR across Townsend Deprivation Index quantiles using Cox proportional hazard regression. RESULTS: Among individuals with T1D, the risk of STDR was three times higher (adjusted hazard ratio [aHR] 2.67, 95% CI 1.05-7.78) in the most deprived quintile compared with the least deprived quintile. In T2D, the most deprived quintile had a 28% higher risk (aHR 1.28; 95% CI 1.15-1.43) than the least deprived quintile. CONCLUSIONS: Increasing socioeconomic deprivation is associated with a higher risk of developing STDR in people with diabetes. This underscores persistent health disparities linked to poverty, even within a country offering free universal health care. Further research is needed to address health equity concerns in socioeconomically deprived regions.

The great potential of polysaccharides from natural resources in the treatment of asthma: A review.

Despite significant progress in diagnosis and treatment, asthma remains a serious public health challenge. The conventional therapeutic drugs for asthma often have side effects and unsatisfactory clinical efficacy. Therefore, it is very urgent to develop new drugs to overcome the shortcomings of conventional drugs. Natural polysaccharides provide enormous resources for the development of drugs or health products, and they are receiving a lot of attention from scientists around the world due to their safety, effective anti-inflammatory and immune regulatory properties. Increasing evidence shows that polysaccharides have favorable biological activities in the respiratory disease, including asthma. This review provides an overview of primary literature on the recent advances of polysaccharides from natural resources in the treatment of asthma. The mechanisms and practicability of polysaccharides, including polysaccharides from plants, fungus, bacteria, alga, animals and others are reviewed. Finally, the further research of polysaccharides in the treatment of asthma are discussed. This review can provide a basis for further study of polysaccharides in the treatment of asthma and provides guidance for the development and clinical application of novel asthma treatment drugs.

Investigating alcohol consumption in China via wastewater-based epidemiology.

Alcohol abuse and addiction is a public health issue of global concern. Wastewater-based epidemiology (WBE) is a forceful and effective complementary tool for investigating chemical consumption. This study examined alcohol consumption in major cities of China via WBE and compared WBE estimates with other data sources. A simple and valid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of two alcohol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS) in wastewater. The optimized method was applied to 62 sewage samples collected from wastewater treatment plants (WWTPs) in 31 provincial capital cities across China in the fourth quarter of 2020. The methodology established in this study was validated with the lower limit of quantification (LLOQ) up to 0.1 µg/L, good linearity in the range of 0.1-50 µg/L, intra-day and inter-day precision less than 5.58% and 5.55%, respectively, and the recoveries of the extracts were higher than 97.14%. The consumption range of alcohol estimated via WBE was 6.09 ± 4.56 ethanol/person/day (EPD) in the capital cities of China. Alcohol consumption varies significantly between cities in China, with WBE estimating lower alcohol consumption than WHO and lower than foreign countries. Investing in alcohol consumption based on WBE has great potential to accurately and efficiently estimate alcohol consumption.