Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Symbiotic microbial communities in various locations of the lung cancer respiratory tract along with potential host immunological processes affected.

Lung cancer has the highest mortality rate among all cancers worldwide. The 5-year overall survival rate for non-small cell lung cancer (NSCLC) is estimated at around 26%, whereas for small cell lung cancer (SCLC), the survival rate is only approximately 7%. This disease places a significant financial and psychological burden on individuals worldwide. The symbiotic microbiota in the human body has been significantly associated with the occurrence, progression, and prognosis of various diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Studies have demonstrated that respiratory symbiotic microorganisms and their metabolites play a crucial role in modulating immune function and contributing to the pathophysiology of lung cancer through their interactions with the host. In this review, we provide a comprehensive overview of the microbial characteristics associated with lung cancer, with a focus on the respiratory tract microbiota from different locations, including saliva, sputum, bronchoalveolar lavage fluid (BALF), bronchial brush samples, and tissue. We describe the respiratory tract microbiota's biodiversity characteristics by anatomical region, elucidating distinct pathological features, staging, metastasis, host chromosomal mutations, immune therapies, and the differentiated symbiotic microbiota under the influence of environmental factors. Our exploration investigates the intrinsic mechanisms linking the microbiota and its host. Furthermore, we have also provided a comprehensive review of the immune mechanisms by which microbiota are implicated in the development of lung cancer. Dysbiosis of the respiratory microbiota can promote or inhibit tumor progression through various mechanisms, including DNA damage and genomic instability, activation and regulation of the innate and adaptive immune systems, and stimulation of epithelial cells leading to the upregulation of carcinogenesis-related pathways.

Screening of Organic Small Molecule Excipients on Ternary Solid Dispersions Based on Miscibility and Hydrogen Bonding Analysis: Experiments and Molecular Simulation.

The preparation of solid dispersions by mixing insoluble drugs with polymers is the main way to improve the aqueous solubility of drugs. The introduction of organic small molecule excipients into binary solid dispersions is expected to further enhance drug solubility by regulating intermolecular hydrogen bonding within the system at the microscopic level. In this study, we used carbamazepine (CBZ) as the target drug and polyvinylpyrrolidone as the solid dispersion matrix and screened the third component from 13 organic small molecules with good miscibility in the solid dispersion based on the principle of similarity of solubility parameters. The hydrogen bonding parameters and dissociation Gibbs free energy of the 13 organic small molecule-CBZ dimer were calculated by quantum mechanical simulation, and the tryptophan (Try) was identified as the optimal third component of organic small molecule. The migration of CBZ in binary and ternary systems was also analyzed by molecular dynamics simulation. On this theoretical basis, the corresponding solid dispersions were prepared, characterized, and tested for solubility analysis, which verified that the drug solubility was stronger for the system with the addition of polar fractions and the Try was indeed the best third component of organic small molecule compound, which was consistent with the simulation predictions. This screening method may provide theoretical guidance for drug modification design and clinical studies.

Role of systemic immune-inflammation index (SII) in assessing clinical efficacy of TNF-α inhibitors for rheumatoid arthritis.

OBJECTIVE: To find out if systemic immune-inflammation index (SII) has the potential to determine the clinical efficacy of TNF-α inhibitors in treating rheumatoid arthritis (RA). METHODS: A retrospective analysis was conducted in 154 RA patients who were treated from January 2021 to January 2023. The patients were grouped, based on their treatment response, into ineffective (32 cases) and effective (122 cases) groups. Univariate analysis was conducted to evaluate the clinical data, test indicators, and functional scores. Lasso regression was employed to identify factors impacting patient outcomes. Predictive utility of these factors was assessed via receiver operating characteristic curves, and differences were evaluated using the DeLong test. RESULTS: No significant difference was identified in age, gender, disease duration, and other clinical parameters between the two groups (P>0.05). The effective group exhibited lower pre-treatment counts of neutrophils, lymphocytes, as well as SII, C-reactive protein (CRP), rheumatoid factor (RF), and erythrocyte sedimentation rate (ESR), but higher platelet count (P<0.01). Lasso regression found that neutrophil count, lymphocyte count, SII, CRP, RF, and ESR were associated with the treatment efficacy (P<0.05). Among these, SII and lymphocytes demonstrated the highest predictive value in the DeLong test. CONCLUSION: SII along with multiple other pre-treatment parameters are significantly associated with the efficacy of TNF-α inhibitors in the treatment of RA. Notably, SII emerges as a crucial tool in evaluating the efficacy of this treatment.

Chemoenzymatic Synthesis of Cylindrocyclophanes A and F and Merocyclophanes A and D.

Incorporating enzymatic reactions into natural product synthesis can significantly improve synthetic efficiency and selectivity. In contrast to the increasing applications of biocatalytic functional-group interconversions, the use of enzymatic C-C bond formation reactions in natural product synthesis is underexplored. Herein, we report a concise and efficient approach for the synthesis of [7.7]paracyclophane natural products, a family of polyketides with diverse biological activities. By using enzymatic Friedel-Crafts alkylation, cylindrocyclophanes A and F and merocyclophanes A and D were synthesized in six to eight steps in the longest linear sequence. This study demonstrates the power of combining enzymatic reactions with contemporary synthetic methodologies and provides opportunities for the structure-activity relationship studies of [7.7]paracyclophane natural products.

Thioredoxin facilitates hepatocellular carcinoma stemness and metastasis by increasing BACH1 stability to activate the AKT/mTOR pathway.

Thioredoxin (TXN) is essential for preserving balance and controlling the intracellular redox state. Most studies have focused on the function of TXN in redox reactions, which is critical for tumor progression. Here, we showed that TXN promotes hepatocellular carcinoma (HCC) stemness properties in a non-redox-dependent manner, which has rarely been reported in previous studies. TXN exhibited upregulated expression in human HCC specimens, which was associated with a poor prognosis. Functional studies showed that TXN promoted HCC stemness properties and facilitated HCC metastasis both in vitro and in vivo. Mechanistically, TXN promoted the stemness of HCC cells by interacting with BTB and CNC homology 1 (BACH1) and stabilized BACH1 expression by inhibiting its ubiquitination. BACH1 was positively correlated with TXN expression and was significantly upregulated in HCC. In addition, BACH1 promotes HCC stemness by activating the AKT/mammalian target of rapamycin (mTOR) pathway. Furthermore, we found that the specific inhibition of TXN in combination with lenvatinib in mice significantly improved the treatment of metastatic HCC. In summary, our data demonstrate that TXN plays a crucial role in HCC stemness and BACH1 plays an integral part in regulating this process by activating the AKT/mTOR pathway. Thus, TXN is a promising target for metastatic HCC therapy.

Characteristics of COVID-19 (Delta Variant)/HIV Co-infection: A Cross-sectional Study in Henan Province, China.

Background: Since the end of July 2021, SARS-CoV-2 (Delta variant) invaded Henan Province, China, causing a rapid COVID-19 spread in the province. Among them, the clinical features of COVID-19 (Delta Variant)/HIV co-infection have attracted our attention. Methods: We included 12 COVID-19 patients living with HIV (human immunodeficiency virus) from July 30, 2021 to September 17, 2021 in Henan Province, China. Demographic, clinical, laboratory, and computed tomography (CT) imaging data were dynamically collected from first nucleic acid positive to hospital discharge. Laboratory findings included SARS-CoV-2 viral load, HIV viral load, IgM, IgG, cytokines, lymphocyte subpopulation, ferritin, etc. Statistical analyses were performed using IBM SPSS version 26·0 and GraphPad Prism version 9·0. Results: It was founded that the low Ct value persisted for about 21 days, and the viral shedding time (turn negative time) of the patients was 32·36 ± 2·643 days. Furthermore, chest CT imaging revealed that lesions were obviously and rapidly absorbed. It was surprising that IgM levels were statistically higher in patients taking azvudine or convalescent plasma than in patients not taking these drugs (P < 0·001, P = 0·0002, respectively). IgG levels were significantly higher in patients treated with the combined medication of BRII/196 and BRII/198 than in those not treated with these drugs (P = 0·0029). IgM was significantly higher in those with low HIV viral load than those with high HIV viral load (P < 0·001). In addition, as treatment progressed and patients' condition improved, IL-17a showed a decreasing trend. Conclusions: Based on this study, we found that HIV infection might not exacerbate COVID-19 severity. Supplementary Information: The online version contains supplementary material available at 10.1007/s44231-022-00018-z.

CircSCAPER knockdown attenuates IL-1ß-induced chondrocyte injury by miR-127-5p/TLR4 axis in osteoarthritis.

PURPOSE: Osteoarthritis (OA) is a chronic inflammatory degenerative disease characterized by articular cartilage degradation. Circular RNAs have been shown to play significant roles in OA process. Herein, this work aimed to investigate the potential role and mechanism of circSCAPER in OA progression. METHODS: Levels of circSCAPER, miR-127-5p and toll-like receptor 4 (TLR4) were detected by qRT-PCR or western blotting. Cell apoptosis was determined by flow cytometry. The expression of Aggrecan and Matrix metallopeptidase was examined using western blot to assess extracellular matrix (ECM) degradation. Inflammatory response and oxidative stress were determined by measuring the release of inflammatory factors, along with the generation of intracellular reactive oxygen species and malondialdehyde. The interaction between miR-127-5p and circSCAPER or TLR4 was determined by dual-luciferase reporter, RNA immunoprecipitation and pull-down assays. RESULTS: Chondrocytes were treated with interleukin-1ß (IL-1ß) to mimic OA condition in vitro. CircSCAPER was increased in OA cartilages and IL-1ß-induced chondrocytes. Functionally, knockdown of circSCAPER attenuated IL-1ß-evoked apoptosis, ECM degradation, inflammation and oxidative stress in vitro. CircSCAPER up-regulation in OA cartilages was discovered to be accompanied by decreased miR-127-5p and increased TLR4. Mechanistically, circSCAPER acted as a sponge for miR-127-5p to positively regulate TLR4 expression in chondrocytes. IL-1ß treatment reduced miR-127-5p expression but up-regulated TLR4 expression, re-expression of miR-127-5p suppressed IL-1ß-caused chondrocyte injury, which was abolished by TLR4 overexpression. Moreover, miR-127-5p inhibition reversed the protective action of circSCAPER knockdown on chondrocytes under IL-1ß treatment. CONCLUSION: CircSCAPER silencing protected against IL-1ß-induced apoptosis, ECM degradation, inflammation and oxidative stress in chondrocytes via miR-127-5p/TLR4 axis.

Single-cell RNA transcriptomic analysis identifies Creb5 and CD11b-DCs as regulator of asthma exacerbations.

Immune responses that result in asthma exacerbation are associated with allergen or viral exposure. Identification of common immune factors will be beneficial for the development of uniformed targeted therapy. We employed a House Dust Mite (HDM) mouse model of asthma and challenged allergic HDM mice with allergens (HDM, cockroach extract (CRE)) or respiratory syncytial virus (RSV). Purified lung immune cells underwent high-dimensional single-cell RNA deep sequencing (scRNA-seq) to generate an RNA transcriptome. Gene silencing with siRNA was employed to confirm the efficacy of scRNA-seq analysis. scRNA-seq UMAP analysis portrayed an array of cell markers within individual immune clusters. SCENIC R analysis showed an increase in regulon number and activity in CD11b- DC cells. Analysis of conserved regulon factors further identified Creb5 as a shared regulon between the exacerbation groups. Creb5 siRNAs attenuated HDM, CRE or RSV-induced asthma exacerbation. scRNA-seq multidimensional analysis of immune clusters identified gene pathways that were conserved between the exacerbation groups. We propose that these analyses provide a strong framework that could be used to identify specific therapeutic targets in multifaceted pathologies.

CircCAMSAP1 promotes non-small cell lung cancer proliferation and inhibits cell apoptosis by sponging miR-1182 and regulating BIRC5.

Recently, various studies have suggested that circular RNAs (circRNAs) are ubiquitous in various malignant events, including non-small cell lung cancer (NSCLC) and are closely related to cell proliferation and apoptosis. Unfortunately, the molecular functions involved in this action still have little overlap. Therefore, this study aimed to identify a novel circCAMSAP1 role in NSCLC. Overexpression of circCAMSAP1 has been demonstrated in NSCLC lung tissues and cell lines. Sequencing and RNase R experiments were planned to determine whether circCAMSAP1 is looped and exists in NSCLC. We also found that downregulated circCAMSAP1 repressed cell proliferation and increased apoptosis of NSCLC cells in vitro and suppressed xenograft tumor growth in vivo. Furthermore, a luciferase assay revealed that circCAMSAP1 could regulate baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5, also known as survivin) expression by directly binding to miR-1182. However, BIRC5 without 3' untranslated regions (3'UTR) could reverse the influence of downregulated circCAMSAP1 on proliferation and apoptosis in NSCLC. Together, our findings reveal a novel mechanism by which the circCAMSAP1/miR-1182/BIRC5 axis promotes NSCLC progression.

CircTUBGCP3 facilitates the tumorigenesis of lung adenocarcinoma by sponging miR-885-3p.

BACKGROUND: Circular RNAs (circRNAs) act pivotal roles in the progression of multiple malignancies. However, the underlying mechanisms by which hsa_circ_0007031 (circTUBGCP3) contributes to lung adenocarcinoma (LAC) remain largely unknown. METHODS: The association of circTUBGCP3 expression with clinicopathological characteristics and prognosis in patients with LAC was determined by RT-qPCR and fluorescence in situ hybridization. The in vitro functional experiments as well as a subcutaneous tumorigenesis model were executed to estimate the role of circTUBGCP3 in LAC cells. The interaction between circTUBGCP3 and miR-885-3p was confirmed by RNA immunoprecipitation, luciferase gene report and RT-qPCR assays. The effects of circTUBGCP3 on miR-885-3p-mediated Wnt10b/ß-catenin signaling were evaluated by Western blot. RESULTS: The upregulation of circTUBGCP3 or downregulation of miR-885-3p was associated with the pathological stage and poor survival in patients with LAC. Restored expression of circTUBGCP3 facilitated the growth and invasion of LAC cells, but knockdown of circTUBGCP3 harbored the opposite effects. In mechanism, circTUBGCP3 could act as a sponge of miR-885-3p, which suppressed the cell proliferation and colony formation and attenuated the tumor-promoting effects of circTUBGCP3. Wnt10b as a target of miR-885-3p could be upregulated be circTUBGCP3 and indicate poor survival in patient with LAC. CONCLUSIONS: Our findings demonstrated that circTUBGCP3 promoted LAC progression by sponging miR-885-3p, and might represent a prognostic factor for LAC.

The Neutrophil-to-Lymphocyte Ratio (NLR) Predicts the Prognosis of Unresectable Intermediate and Advanced Hepatocellular Carcinoma Treated with Apatinib.

PURPOSE: Patients with hepatocellular carcinoma (HCC) who might benefit most from anti-angiogenesis therapy remain unknown. In recent years, neutrophil-to-lymphocyte ratio (NLR), an indicator of inflammatory response, has received particular attention in HCC. Herein, we explored the prognostic value of pre-treatment NLR in individuals with unresectable intermediate and advanced hepatocellular carcinoma treated with apatinib, a second-line angiogenesis inhibitor. The findings of this study would assist in precision medicine and provide clinical decision support. PATIENTS AND METHODS: This is a retrospective study in which 171 HCC patients attending Tianjin Medical University Cancer Institute and Hospital and treated with apatinib between January 2016 and July 2018 were enrolled. The prognosis of the patients based on NLR signatures was then analyzed. RESULTS: Patients with a low pre-treatment NLR (NLR < 2.49) presented a significantly longer overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P = 0.043). Furthermore, a low pre-treatment NLR level could be used to predict a longer OS in patients with non-macrovascular invasion (P < 0.001). Independent of serum alpha-fetoprotein (AFP) levels, a low NLR level in this cohort of patients is associated with a longer OS. CONCLUSION: Pre-treatment NLR predicts the prognosis of patients with unresectable intermediate and advanced HCC treated with apatinib.

MicroRNA-16 regulates lipopolysaccharide-induced inflammatory factor expression by targeting TLR4 in normal human bronchial epithelial cells.

Acute lung injury (ALI) is mainly caused by inflammation and is associated with high mortality rates. Emerging evidence has suggested that microRNAs (miRNAs or miRs) serve a significant function in ALI. However, the fundamental mechanism underlying ALI remain to be fully elucidated. Although miR-16 has been reported to be involved in the occurrence and development of a number of diseases its association with ALI has not been previously investigated. Therefore, the present study aimed to explore the role of miR-16 in the lipopolysaccharide (LPS)-induced ALI model. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß and IL-6 were measured by ELISA in the blood samples of rats with ALI and in the normal human bronchial epithelial (NHBE) cell line. The role of miR-16 in inflammation was evaluated using gene overexpression and silencing experiments in NHBE cells by reverse transcription-quantitative PCR. In addition, the expression levels of inflammatory factors TNF-α, IL-1ß and IL-6 were also determined using ELISA. The potential interaction between miR-16 and TLR4 was assessed using bioinformatics analysis by the TargetScan database and then verified in 293T cells using luciferase reporter assay. The expression of miR-16 was notably decreased in the lung tissues of rats with LPS-induced ALI compared with the PBS treated-group. Additionally, the levels of the proinflammatory cytokines TNF-α, IL-1ß and IL-6 were reduced following transfection of NHBE cells with miR-16 mimics compared with those in the miR-negative control group. Western blot analysis revealed that miR-16 overexpression could downregulate TLR4 expression in NHBE cells compared with that in the miR-NC group. Luciferase reporter assay confirmed that TLR4 may be directly targeted by miR-16. The effect of miR-16 on TLR4 was rescued in NHBE cells following treatment with LPS. Overall, these aforementioned findings suggest that miR-16 may serve a protective role against LPS-mediated inflammatory responses in NHBE cells by regulating TLR4, where this mechanism may be considered to be a novel approach for treating ALI in the future.

Combination therapy for advanced hepatocellular carcinoma: do we see the light at the end of the tunnel?

IMPORTANCE: Combination therapies of anti-PD-1 and anti-angiogenesis regimens are emerging rapidly and exhibit more promising anti-tumor efficacy for advanced hepatocellular carcinoma (HCC), and consistently it is the hotspot in clinical studies. OBJECTIVE: To elaborate several issues which are warranted further consideration as more regimens are being investigated in combination therapies. EVIDENCE REVIEW: We searched PubMed, MEDLINE, Cochrane Library and Google Scholar by 2021 February for publications on combination therapies for HCC. FINDINGS: Several clinical issues are worth reconsidering, such as the evaluation on appropriate primary endpoints in phase III clinical trials as for different practical problems, the translation of surrogate endpoint objective response rate (ORR) benefits into overall survival (OS) benefits, and whether conversion surgery contributes to initial expectations of long-term survival or not. New concepts in novel immunotherapy and targeted therapy in combination with loco-regional therapies may improve overall survival for HCC. CONCLUSIONS AND RELEVANCE FOR REVIEWS: Comprehensive understanding of the mechanism of immunotherapy and targeted therapy contributes to better prognosis of advanced HCC and more explorative combination therapies are needed.

Increased Drought Resistance 1 Mutation Increases Drought Tolerance of Upland Rice by Altering Physiological and Morphological Traits and Limiting ROS Levels.

To discover new mutants conferring enhanced tolerance to drought stress, we screened a mutagenized upland rice (Oryza sativa) population (cv. IAPAR9) and identified a mutant, named idr1-1 (increased drought resistance 1-1), with obviously increased drought tolerance under upland field conditions. The idr1-1 mutant possessed a significantly enhanced ability to tolerate high-drought stresses. Map-based cloning revealed that the gene LOC_Os05g26890, residing in the mapping region of IDR1 locus, carried a single-base deletion in the idr1-1 mutant. IDR1 encodes the Gα subunit of the heterotrimeric G protein (also known as RGA1), and this protein was localized in nucleus and to plasma membrane or cell periphery. Further investigations indicated that the significantly increased drought tolerance in idr1-1 mutants stemmed from a range of physiological and morphological changes, including greater leaf potentials, increased proline contents, heightened leaf thickness and upregulation of antioxidant-synthesizing and drought-induced genes, under drought-stressed conditions. Especially, reactive oxygen species (ROS) production might be remarkably impaired, while ROS-scavenging ability appeared to be markedly enhanced due to significantly elevated expression of ROS-scavenging enzyme genes in idr1-1 mutants under drought-stressed conditions. In addition, idr1-1 mutants showed reduced expression of OsBRD1. Altogether, these results suggest that mutation of IDR1 leads to alterations in multiple layers of regulations, which ultimately leads to changes in the physiological and morphological traits and limiting of ROS levels, and thereby confers obviously increased drought tolerance to the idr1-1 mutant.

Silencing SIX1 by miR-7160 inhibits non-small cell lung cancer cell growth.

The homeoprotein SIX1 is upregulated in non-small cell lung cancer (NSCLC) and associated with NSCLC tumorigenesis and progression. We identified microRNA-7160 (miR-7160) as a SIX1-targeting miRNA. RNA immunoprecipitation results confirmed a direct binding between miR-7160 and SIX1 mRNA in NSCLC cells. In the primary and established NSCLC cells, forced overexpression of miR-7160 downregulated SIX1 and inhibited cancer cell growth, proliferation, migration and invasion. Furthermore, miR-7160 overexpression induced apoptosis activation in NSCLC cells. Conversely, miR-7160 inhibition elevated SIX1 expression and enhanced NSCLC cell progression in vitro. Restoring SIX1 expression, by an untranslated region-depleted SIX1 expression construct, reversed miR-7160-induced anti-NSCLC cell activity. CRISPR/Cas9-inudced knockout of SIX1 mimicked miR-7160-induced actions and produced anti-NSCLC cell activity. In vivo, intratumoral injection of miR-7160-expressing lentivirus downregulated SIX1 mRNA and inhibited NSCLC xenograft growth in severe combined immunodeficient mice. Significantly, miR-7160 expression is downregulated in human NSCLC tissues and is correlated with SIX1 mRNA upregulation. Collectively, miR-7160 silenced SIX1 and inhibited NSCLC cell growth in vitro and in vivo.

Clinical Characteristics and Prognosis of Patients With Pulmonary Mucoepidermoid Carcinoma: A SEER-Based Analysis.

BACKGROUND: Primary pulmonary mucoepidermoid carcinoma (PMEC) is an extremely rare malignancy. Its clinical characteristics and prognosis are not fully understood. This study evaluated clinical characteristics and prognostic factors of PMEC and established a nomogram to predict its 1-, 3-, 5- and 10-year cancer-specific survival (CSS) rates. METHODS: In the Surveillance, Epidemiology, and End Results database from January 1, 2016 to December 31, 2016, patients pathologically diagnosed with PMEC were identified. Kaplan-Meier analysis and Cox regression were performed to evaluate the CSS stratified by different covariates. A predictive nomogram model was built and validated by the concordance index (C-index) and calibration curves. RESULTS: A total of 585 PMEC patients were identified. A total of 408 (70%) of patients were placed into the training cohort, and 177 (30%) patients were placed into the validation cohort. The 5- and 10-year CSS rates of stage I-II PMEC patients were 91.4 and 88.9, respectively. The 1-, 3- and 5-year CSS rates of stage III-IV PMEC were 56.5, 39.45, and 32.1%, respectively. Survival curves showed that older age, large tumor size, poor differentiation, and high TNM stage were associated with a significantly worse prognosis. CSS outcomes were significantly better in patients who received surgical treatments (surgical alone, surgery plus radiation and/or chemotherapy). Patients who received radiation and/or chemotherapy had the worst prognosis. Multivariate Cox results revealed that covariates, including age, tumor laterality, tumor sizes, pathological differentiation, lymph node metastasis, distant metastasis, TNM stage and therapy, were independent prognostic factors for PMEC. These factors were used to construct a nomogram. The C-index of the nomogram was 0.921. The calibration curve presented favorable consistency between the predicted CSS and actual observations. This nomogram was validated by the validation cohort. The C-index of the validation cohort was 0.968. CONCLUSION: Age, bilateral tumors, tumor size, pathological differentiation grade, lymph node metastasis, distant metastasis, TNM stage and therapy were independent prognostic factors of PMEC patients. The first nomogram for predicting the CSS of PMEC was built and validated, showing its potential value in practice.

The efficacy of probiotics in patients with severe COVID-19.

BACKGROUND: To examine the incidence of diarrhea in severe and critical coronavirus disease 2019 (COVID-19) patients, and to observe the efficacy and prognosis of probiotic use in such patients. METHODS: A retrospective study was conducted to investigate the symptoms and incidence of diarrhea in 156 cases of COVID-19 confirmed by the First Affiliated Hospital of Zhengzhou University and the Xinyang Fifth People's Hospital, China. A total of 58 cases of severe and critical COVID-19 were identified and divided into the treatment group or the control group. The control group was given standard treatment according to the Protocols for Diagnosis and Treatment of COVID-19: Prevention, Control, Diagnosis and Management. Patients in the treatment group were administered oral probiotics as well as the standard treatment. The 2 groups were compared in terms of nutritional status (serum albumin), improvement of diarrhea symptoms, changes in inflammatory condition [procalcitonin (PCT) and C-reactive protein (CRP)], the time taken to register a negative result for respiratory tract pathogens on the nucleic acid test, and changes to white blood cell and lymphocyte cell counts. RESULTS: In this study cohort, diarrhea was detected in 15.38% (24/156) of COVID-19 patients. The incidence of diarrhea in patients with mild and moderate COVID-19 was approximately 8.16% (8/98), and the incidence of diarrhea in severe and critically ill patients was approximately 27.59% (16/58). In patients with severe and critical COVID-19, probiotic treatment obviously shortened the duration of diarrhea. Furthermore, compared with the control group, patients treated with probiotics showed a significantly reduced time to achieving a negative nucleic acid test and the inflammation indexes including PCT and CRP were significantly reduced (P<0.05). CONCLUSIONS: The incidence of diarrhea in severe and critically ill COVID-19 patients was significantly higher than that in patients with mild and moderate COVID-19. Probiotics may have a good supporting role in the treatment of patients with COVID-19 and its early application is recommended.

Single-cell transcriptomic analysis reveals key immune cell phenotypes in the lungs of patients with asthma exacerbation.

BACKGROUND: Asthma exacerbations are associated with heightened asthma symptoms, which can result in hospitalization in severe cases. However, the molecular immunologic processes that determine the course of an exacerbation remain poorly understood, impeding the progression of development of effective therapies. OBJECTIVE: Our aim was to identify candidate genes that are strongly associated with asthma exacerbation at a cellular level. METHODS: Subjects with asthma exacerbation and healthy control subjects were recruited, and bronchoalveolar lavage fluid was isolated from these subjects via bronchoscopy. Cells were isolated through fluorescence-activated cell sorting, and single-cell RNA sequencing was performed on enriched cell populations. RESULTS: We showed that the levels of monocytes, CD8+ T cells, and macrophages are significantly elevated in the bronchoalveolar lavage fluid of patients. A set of cytokines and intracellular transduction regulators are associated with asthma exacerbations and are shared across multiple cell clusters, forming a complicated molecular framework. An additional group of core exacerbation-associated modules is activated, including eukaryotic initiation factor 2 signaling, ephrin receptor signaling, and C-X-C chemokine receptor type 4 signaling in the subpopulations of CD8+ T cells (C1-a) and monocyte clusters (C7 clusters), which are associated with infection. CONCLUSION: Our study identified a significant number of severe asthma-associated genes that are differentially expressed by multiple cell clusters.