Stanniocalcin-1 secreted by human umbilical mesenchymal stem cells regulates interleukin-10 expression via the PI3K/AKT/mTOR pathway in alveolar macrophages.

Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure caused by infection, trauma, shock, aspiration or drug reaction. The pathogenesis of ARDS is characterized as an unregulated inflammatory storm, which causes endothelial and epithelial layer damage, leading to alveolar fluid accumulation and pulmonary edema. Previous studies have shown the potential role of mesenchymal stem cells (MSC) in combating the inflammatory cascade by increasing the anti-inflammatory mediator interleukin-10 (IL-10). However, the involved mechanisms are unclear. Here we investigated whether a key immunomodulatory regulator, stanniocalcin-1 (STC-1), was secreted by MSC to activate phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)/ mammalian target of rapamycin (mTOR) signaling pathway to increase IL-10 expression in alveolar macrophages. Lipopolysaccharide (LPS)-stimulated alveolar macrophages co-cultured with human umbilical mesenchymal stem cells (HUMSC) secreted high levels of IL-10. HUMSC co-cultured with alveolar macrophages expressed high STC-1 levels and increased PI3K, AKT and mTOR phosphorylation after LPS activation in alveolar macrophages. STC-1 knockdown in HUMSC decreased the phosphorylation of PI3K, AKT and mTOR and suppressed IL-10 expression in alveolar macrophages. Rapamycin (an mTOR inhibitor) reduced IL-10 secretion in alveolar macrophages. These results, together with our previous study and others, indicate that the PI3K/AKT/mTOR pathway is involved in the regulation of IL-10 production by STC-1 secreted by HUMSC in alveolar macrophages.

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/ß-catenin signaling.

Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/ß-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/ß-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.

miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1.

BACKGROUND: MicroRNAs (miRNAs) serve as important regulators of the tumorigenesis and progression of many human cancers. Therefore, we evaluated the biological function and underlying mechanism of miR-363 in clear cell renal cell carcinoma (ccRCC). METHODS: The expression of miR-363 in ccRCC tissues compared with adjacent normal renal tissues was detected by quantitative real-time polymerase chain reaction, and the association between miR-363 levels and prognosis of ccRCC patients was analyzed. The candidate target gene of miR-363 was determined by in silico analysis and luciferase reporter assays. The effects of miR-363 on the proliferation, migration and invasion of ccRCC cells in vitro were determined by MTS assay, colony formation assay, Transwell assay and wound healing assay. We also investigated the roles of miR-363 in vivo by a xenograft tumour model. The mechanism of miR-363 on the proliferation, migration and invasion of ccRCC was determined by gain- and loss-of-function analyses. RESULTS: we demonstrated that miR-363 expression was obviously downregulated in ccRCC tissues and that reduced miR-363 expression was correlated with poor disease-free survival (DFS) in ccRCC patients after surgery. S1PR1 expression was inversely correlated with the level of miR-363 in human ccRCC samples. Luciferase reporter assays suggested that S1PR1 was a direct functional target of miR-363. miR-363 downregulated S1PR1 expression and suppressed the proliferation, migration and invasion abilities of ccRCC cells in vitro and suppressed xenograft tumour growth in vivo. Importantly, miR-363 exerted its biological function by inhibiting S1PR1 expression in ccRCC cells, leading to the repression of ERK activation. Moreover, we found that the levels of downstream effectors of ERK, including PDGF-A, PDGF-B, and epithelial-mesenchymal transition (EMT)-related genes, were decreased after miR-363 overexpression. CONCLUSIONS: Our results suggest that miR-363 acts as a tumour suppressor by directly targeting S1PR1 in ccRCC and may be a potential new therapeutic target for ccRCC.

FOXK2 suppresses the malignant phenotype and induces apoptosis through inhibition of EGFR in clear-cell renal cell carcinoma.

Forkhead box K2 (FOXK2) belongs to the forkhead box transcription factor family. Recent studies have revealed that FOXK2 plays essential roles in cancer cell proliferation and survival. However, the biological function of FOXK2 in renal cell carcinoma remains unexplored. In our study, we demonstrated that FOXK2 mRNA and protein levels were decreased in clear-cell renal cell carcinoma (ccRCC) tissues compared to those in corresponding non-tumor renal tissues, and decreased FOXK2 levels were associated with poor prognosis in ccRCC patients after nephrectomy. FOXK2 suppressed proliferation, migration and invasion capabilities of ccRCC cells and induced cellular apoptosis in vitro. Moreover, we found that FOXK2 overexpression inhibited xenograft tumor growth and promoted apoptosis in vivo. Genome-wide transcriptome profiling using FOXK2 overexpressed 769-P cells revealed that the epidermal growth factor receptor (EGFR) was a potential downstream gene of FOXK2. Overexpression of EGFR is able to rescue the inhibited proliferation capacity and the enhanced apoptosis capacity due to the overexpression of FOXK2 in 769-P cells. Collectively, our results indicate that FOXK2 inhibits the malignant phenotype of ccRCC and acts as a tumor suppressor possibly through the inhibition of EGFR.

Laparoscopic vs robot-assisted partial nephrectomy for renal tumours of >4 cm: a propensity score-based analysis.

OBJECTIVES: To compare perioperative data, functional and oncological outcomes between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) for renal tumours of >4 cm. PATIENTS AND METHODS: We retrospectively reviewed patients who underwent either LPN or RAPN between 2008 and 2015. To adjust for potential baseline confounders, propensity score matching (1:1) was performed. Perioperative data, functional and oncological outcomes were reviewed. Disease-free survival, cancer-specific survival and overall survival were analysed using Kaplan-Meier survival curves with log-rank tests. RESULTS: In all, 197 patients underwent LPN and 96 underwent RAPN during the study period. After matching, there was no significant difference between the groups for baseline characteristics. Within the matched cohort, the LPN group was associated with significantly higher estimated blood loss (150 vs 100 mL; P < 0.001), longer renal artery clamp time (25 vs 20 min; P < 0.001), longer postoperative hospital stay (7 vs 5 days; P < 0.001), and lower rate of Margin, Ischaemia, and Complications (MIC) achievement (30.2% vs 46.9%; P = 0.018). The postoperative percentage of estimated glomerular filtration rate decline was higher in the LPN group (11.3% vs 5.5%; P = 0.018). Complication and surgical conversion outcomes were similar between LPN and RAPN. There was no significant difference in oncological outcomes between the groups. CONCLUSIONS: For patients with renal tumours of >4 cm, RAPN is more favourable than LPN in terms of perioperative outcomes (i.e. estimated blood loss, renal artery clamp time and postoperative hospital stay) and early renal functional preservation.

Robotic versus Open Level I-II Inferior Vena Cava Thrombectomy: A Matched Group Comparative Analysis.

PURPOSE: We compared treatment outcomes of robotic vs open inferior vena cava thrombectomy for renal tumors with level I-II inferior vena cava tumor thrombus. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent robotic or open inferior vena cava thrombectomy between 2006 and 2016. To reduce the inherent biases of a nonrandomized study the robotic and open groups were matched 1:1 based on key variables. Perioperative data and oncologic outcomes were reviewed. Progression-free and overall survival was analyzed using Kaplan-Meier survival curves and compared between groups using the log rank test. RESULTS: A total of 31 and 37 patients underwent robotic and open inferior vena cava thrombectomy, respectively. After matching there were no significant differences in baseline characteristics between the groups. Of the matched cohorts the robotic cohort had significantly shorter median operative time (150 vs 230 minutes, p <0.001), lower median estimated blood loss (250 vs 1,000 ml, p <0.001), a lower rate of blood transfusion (6.5% vs 54.8%, p <0.001), a lower median transfusion requirement (420 vs 790 ml, p = 0.012) and a shorter median postoperative hospital stay (5 vs 9 days, p <0.001). The postoperative complication rate was lower in the robotic group than in the open group (9.7% vs 29.0%, p = 0.070). However, there were no significant differences in oncologic outcomes between the groups. CONCLUSIONS: Robotic inferior vena cava thrombectomy can achieve more favorable perioperative results and similar oncologic outcomes compared with open inferior vena cava thrombectomy. Prospective studies with a larger sample size and longer followup are needed to validate our findings.

External validation of the Arterial Based Complexity (ABC) scoring system in renal tumors treated by minimally invasive partial nephrectomy.

OBJECTIVE: To assess the role of the Arterial Based Complexity (ABC) scoring system in predicting clinically relevant outcomes of a minimally invasive partial nephrectomy (MIPN). PATIENTS AND METHODS: We retrospectively reviewed 350 consecutive patients who underwent a MIPN between 2013 and 2014. Tumor complexity was evaluated according to the ABC scoring system. Complications, surgical, and renal outcomes were recorded. RESULTS: There were respectively 36 (10.3%), 229 (65.4%), 43 (12.3%), and 42 (12.0%) patients in category 1, 2, 3S, 3H. Multivariate regression showed category assignment was associated with warm ischemia time (P < 0.001), estimated blood loss (P = 0.001), and operative time (P = 0.032). On multivariate analyses, tumor size was the only independent predictor of overall (P = 0.035) and minor (P = 0.032) complications, but ABC category failed to predict complications (P > 0.05 for all). For renal function, ABC category failed to predict postoperative estimated glomerular filtration rate at 1 day and 6 months (P > 0.05 for both). CONCLUSIONS: In MIPN, the ABC scoring system predicted a prolonged warm ischemia time and operative time, and an added estimated blood loss. This scoring system was not a predictor for the occurrence of complications and postoperative renal function.

Identification of a novel sepsis prognosis model : Based on transcriptome and proteome analysis.

ABSTRACT: Sepsis is a highly prevalent and deadly disease. Currently, there is a lack of ideal biomarker prognostis models for sepsis. We attempt to construct a model capable of predicting the prognosis of sepsis patients by integrating transcriptomic and proteomic data. Through analysis of proteomic and transcriptomic data, we identified 25 differentially expressed genes (DEGs). Single-factor Cox-Lasso regression analysis identified 16 DEGs (OS-DEGs) associated with patient prognosis. Through multi-factor Cox-Lasso regression analysis, a prognostic model based on these 16 genes was constructed. Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curve analysis were used to further validate the high stability and good predictive ability of this prognostic model with internal and external data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of OS-DEGs and differentially expressed genes between high and low-risk groups based on the prognostic model revealed significant enrichment in immune-related pathways, particularly those associated with viral regulation.

Diagnostic value of DNA or RNA-based metagenomic next-generation sequencing in lower respiratory tract infections.

Objectives: We aimed to evaluate and compare the diagnostic performance of RNA-mNGS and DNA-mNGS workflow in bacterial pneumonia, fungal pneumonia and tuberculosis. Methods: A total of 134 cases suspected pneumonia undergoing both DNA and RNA based mNGS of bronchoalveolar lavage fluid (BALF) and also traditional etiological examination were evaluated retrospectively.Sensitivity, specificity, PPV, NPV and accuracy rate of DNA and RNA based mNGS were estimated. Results: In the diagnosis performance of bacterial pathogens in LRTIs,the specificity of RNA-mNGS was higher than that of DNA-mNGS(82.3 % vs. 61.9 %, P < 0.01). There was no significant difference of sensitivity between the two process(71.4 % vs. 85.7 %, P = 0.375).In the diagnosis performance of fungal pathogens in LRTIs,the specificity of RNA-mNGS was higher than that of DNA-mNGS (72.3 % vs. 27.3 %,p < 0.001). There was no significant difference of sensitivity between the two process(96.5 % vs. 98.8 %,p = 0.125).In the diagnosis performance of tuberculosis in LRTIs,the sensitivity of DNA-mNGS was higher than that of RNA-mNGS (91.7 % vs. 33.3 %,p = 0.016),the specificity was similar in the two process (100 %). Conclusions: RNA-mNGS may reduced the misdiagnosis rate of bacterial and fungal pathogens in LRTIs.Compared to RNA-mNGS, DNA-mNGS may could improve the diagnostic rate of tuberculosis.

Association of elastic power in mechanical ventilation with the severity of acute respiratory distress syndrome: a retrospective study.

BACKGROUND: Mechanical power (MP) is the total energy released into the entire respiratory system per minute which mainly comprises three components: elastic static power, Elastic dynamic power and resistive power. However, the energy to overcome resistance to the gas flow is not the key factor in causing lung injury, but the elastic power (EP) which generates the baseline stretch of the lung fibers and overcomes respiratory system elastance may be closely related to the ARDS severity. Thus, this study aimed to investigate whether EP is superior to other ventilator variables for predicting the severity of lung injury in ARDS patients. METHODS: We retrieved patient data from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The retrieved data involved adults (≥ 18 years) diagnosed with ARDS and subjected to invasive mechanical ventilation for ≥ 48 h. We employed univariate and multivariate logistic regression analyses to investigate the correlation between EP and development of moderate-severe ARDS. Furthermore, we utilized restricted cubic spline models to assess whether there is a linear association between EP and incidence of moderate-severe ARDS. In addition, we employed a stratified linear regression model and likelihood ratio test in subgroups to identify potential modifications and interactions. RESULTS: Moderate-severe ARDS occurred in 73.4% (296/403) of the patients analyzed. EP and MP were significantly associated with moderate-severe ARDS (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.15-1.28, p < 0.001; and OR 1.15, 95%CI 1.11-1.20, p < 0.001; respectively), but EP showed a higher area-under-curve (95%CI 0.72-0.82, p < 0.001) than plateau pressure, driving pressure, and static lung compliance in predicting ARDS severity. The optimal cutoff value for EP was 14.6 J/min with a sensitivity of 75% and specificity of 66%. Quartile analysis revealed that the relationship between EP and ARDS severity remained robust and reliable in subgroup analysis. CONCLUSION: EP is a good ventilator variable associated with ARDS severity and can be used for grading ARDS severity. Close monitoring of EP is advised in patients undergoing mechanical ventilation. Additional experimental trials are needed to investigate whether adjusting ventilator variables according to EP can yield significant improvements in clinical outcomes.

The association between blood eosinophils and clinical outcome of acute exacerbations of chronic obstructive pulmonary disease: A systematic review and meta-analysis.

OBJECTIVES: Studies have shown an association between eosinophilia and clinical outcomes in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, contradictory findings exist. Our study aims to systematically evaluate the association between elevated peripheral blood eosinophils and clinical outcome of patients with AECOPD. METHODS: An electronic search was conducted for relevant studies published from database inception to February 28, 2023, on PubMed, EMBASE, Cochrane Library, and Web of Science. The analysis covered studies on the correlation between EOS AECOPD and mortality, hospital stay duration, readmission and hospitalization rates, and invasive mechanical ventilation. Where applicable, relative risk (RR) and weighted mean difference (WMD) were extracted, pooled, and assessed using meta-analysis. Sensitivity analysis was performed to explore the source of heterogeneity. RESULTS: Fifteen high-quality studies including 14 cohort studies and one case-control study were included in the meta-analysis. Compared with non-eosinophilic AECOPD patients, those with eosinophilic AECOPD had a lower risk of mortality (RR = 0.65, 95 % confidence interval [CI] 0.54, 0.77, P < 0.001), shorter length of hospital stay (WMD = -1.56, 95%CI -2.16, -0.96, P < 0.001), and higher readmission rate (RR = 1.07, 95%CI 1.01,1.13, P = 0.029). No difference was found concerning the rate of hospitalization and invasive mechanical ventilation between the two groups. CONCLUSION: Individuals diagnosed with eosinophilic AECOPD had a reduced mortality rate, a truncated period of hospitalization, and an insubstantial increase in the probability of readmission relative to their non-eosinophilic AECOPD counterparts. The level of eosinophils in blood has been shown to serve as a potential predictive biomarker for AECOPD patients.

Development and validation of a CT-based deep learning radiomics nomogram to predict muscle invasion in bladder cancer.

Objective: This study aimed to develop a nomogram combining CT-based handcrafted radiomics and deep learning (DL) features to preoperatively predict muscle invasion in bladder cancer (BCa) with multi-center validation. Methods: In this retrospective study, 323 patients underwent radical cystectomy with pathologically confirmed BCa were enrolled and randomly divided into the training cohort (n = 226) and internal validation cohort (n = 97). And fifty-two patients from another independent medical center were enrolled as an independent external validation cohort. Handcrafted radiomics and DL features were constructed from preoperative nephrographic phase CT images. Least absolute shrinkage and selection operator (LASSO) regression was used to identify the most discriminative features in train cohort. Multivariate logistic regression was used to develop the predictive model and a deep learning radiomics nomogram (DLRN) was constructed. The predictive performance of models was evaluated by area under the curves (AUC) in the three cohorts. The calibration and clinical usefulness of DLRN were estimated by calibration curve and decision curve analysis. Results: The nomogram that incorporated radiomics signature and DL signature demonstrated satisfactory predictive performance for differentiating non-muscle invasive bladder cancer (NMIBC) from muscle invasive bladder cancer (MIBC), with an AUC of 0.884 (95 % CI: 0.813-0.953) in internal validation cohort and 0.862 (95 % CI: 0.756-0.968) in external validation cohort, respectively. Decision curve analysis confirmed the clinical usefulness of the nomogram. Conclusions: A CT-based deep learning radiomics nomogram exhibited a promising performance for preoperative prediction of muscle invasion in bladder cancer, and may be helpful in the clinical decision-making process.

A CT-based deep learning model predicts overall survival in patients with muscle invasive bladder cancer after radical cystectomy: a multicenter retrospective cohort study.

BACKGROUND: Muscle invasive bladder cancer (MIBC) has a poor prognosis even after radical cystectomy (RC). Postoperative survival stratification based on radiomics and deep learning (DL) algorithms may be useful for treatment decision-making and follow-up management. This study was aimed to develop and validate a DL model based on preoperative computed tomography (CT) for predicting postcystectomy overall survival (OS) in patients with MIBC. METHODS: MIBC patients who underwent RC were retrospectively included from four centers, and divided into the training, internal validation, and external validation sets. A DL model incorporated the convolutional block attention module (CBAM) was built for predicting OS using preoperative CT images. The authors assessed the prognostic accuracy of the DL model and compared it with classic handcrafted radiomics model and clinical model. Then, a deep learning radiomics nomogram (DLRN) was developed by combining clinicopathological factors, radiomics score (Rad-score) and deep learning score (DL-score). Model performance was assessed by C-index, KM curve, and time-dependent ROC curve. RESULTS: A total of 405 patients with MIBC were included in this study. The DL-score achieved a much higher C-index than Rad-score and clinical model (0.690 vs. 0.652 vs. 0.618 in the internal validation set, and 0.658 vs. 0.601 vs. 0.610 in the external validation set). After adjusting for clinicopathologic variables, the DL-score was identified as a significantly independent risk factor for OS by the multivariate Cox regression analysis in all sets (all P <0.01). The DLRN further improved the performance, with a C-index of 0.713 (95% CI: 0.627-0.798) in the internal validation set and 0.685 (95% CI: 0.586-0.765) in external validation set, respectively. CONCLUSIONS: A DL model based on preoperative CT can predict survival outcome of patients with MIBC, which may help in risk stratification and guide treatment decision-making and follow-up management.

Serum Mrp 8/14 as a Potential Biomarker for Predicting the Occurrence of Acute Respiratory Distress Syndrome Induced by Sepsis: A Retrospective Controlled Study.

Background: To date, there are no studies regarding the Mrp 8/14 in predicting the occurrence of acute respiratory distress syndrome (ARDS) induced by sepsis. Thus, the objective of this study was to investigate the expression of Myeloid-related proteins 8 and 14 (Mrp 8/14) and its role in ARDS induced by sepsis. Methods: A total of 168 septic patients were enrolled in the observational study. The baseline information and clinical outcomes were obtained retrospectively. Serum Mrp 8/14 level was determined by enzyme linked immunosorbent assay (ELISA). The patients were categorized into sepsis and ARDS group based on whether they developed ARDS during the intensive care unit (ICU) hospitalization. Results: There was significant difference in the level of Mrp 8/14 between the sepsis group and ARDS groups (P < 0.05). Mrp 8/14 correlated positively with procalcitonin (PCT), interleukin-6 (IL-6), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score on day 1, mechanical ventilation time, length of ICU stay and hospitalization expenses in ICU (all P < 0.05). Logistic regression analysis showed Mrp 8/14 was the independent factor for forecasting the occurrence of sepsis- induced ARDS (P < 0.05). The areas under receiver operating characteristic curves for Mrp 8/14 were higher than that of PCT, APACHE II score and SOFA score on day 1 (P < 0.05). Conclusion: The serum Mrp 8/14 level at admission may be a potential marker for predicting the occurrence of ARDS induced by sepsis. Early detection of serum Mrp 8/14 could help clinicians to identify and evaluate the severity of ARDS induced by sepsis.

[Based on the Hippo signaling pathway to explore the mechanism of autophagy in lung injury of acute respiratory distress syndrome induced by sepsis].

The systemic inflammatory response caused by various pathogenic factors is a key stage in the development of acute respiratory distress syndrome (ARDS). At present, suppression of the inflammatory response and symptomatic support are main methods for the treatment of ARDS. Alveolar epithelial autophagy has an important role in the regulation of the inflammatory response in ARDS. Autophagy is a normal immune mechanism in the body, and it is a metabolic process by which phagocytes degrade intracellular components with the help of lysosomes to maintain intracellular homeostasis. Current studies have shown that pathogenic factors both inside and outside the lung can cause alveolar epithelial cells to form an unfavorable internal environment of hypoxia, starvation, infection, and even apoptosis by triggering inflammatory responses, leading to autophagy dysfunction. Excessive autophagy activation can continue to aggravate inflammatory responses. Autophagy related proteins such as Beclin1, microtubule-associated protein 1 light chain 3 (LC3), mammalian target of rapamycin (mTOR), and p62 are common autophagic markers in current research, which play a crucial role in regulating the autophagic process and the development of lung injury. Therefore, the expression of cellular autophagy genes can be used as early markers and important mechanisms of lung injury in septic ARDS. The Hippo signaling pathway is derived from the protein kinase Hippo in Drosophila, and the Hippo and autophagy are two conserved pathways that are essential for the protection of homeostasis in vivo. The mutual regulation of Hippo signaling pathway and autophagy is currently a hot topic in the academic community. This paper reviews the relevant literature to explore whether the Hippo signaling pathway can regulate cellular autophagy to alleviate the inflammatory response in septic ARDS, so as to provide further research directions for the treatment of ARDS.

Paraneoplastic syndrome in malignant lymphoma: A case report.

Hypercalcaemia associated with malignancy is a complication of advanced tumors. Lactic acidosis is also an extremely rare paraneoplastic syndrome of malignancy, and the presence of both usually indicates an extremely poor prognosis for the tumour. Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma and is also a common aggressive lymphoma. It is extremely rare for patients with diffuse large B-cell lymphoma to develop both hypercalcaemia and severe lactic acidosis. In this article, we report a case of CD5 positive diffuse large B-cell lymphoma with hypercalcaemic crisis and persistent lactic acidosis, in which calcium was rapidly reduced to normal after rehydration, diuresis, calcitonin and zoledronate, and continuous renal replacement therapy (CRRT). After correction of acidosis with sodium bicarbonate, diuresis, vitamin B1 and CRRT, the patient's lactate remained at a high level. The aim of this article is to analyse the experience of the combination of hypercalcaemia and intractable lactic acidosis, which should be considered as a serious electrolyte disorder possibly associated with abnormal metabolism of malignant tumors, and to identify and treat the primary lesion as early as possible.

SnRNA-Seq analysis reveals ten hub genes associated with alveolar epithelial cell injury during pulmonary acute respiratory distress syndrome.

Background: Alveolar epithelial cell injury is a key factor in the occurrence and development of pulmonary acute respiratory distress syndrome (ARDSp). Yet the gene expression profile of alveolar epithelial cells of patients with ARDSp remains unclear. Methods: We analyzed single nuclear RNA sequencing (snRNA-Seq) data from autopsy lung tissues of both ARDSp patients and healthy donors. Sequence data for type 2 alveolar epithelizal cells (AT2) were extracted by the Seurat package. Differentially expressed genes (DEGs) in AT2 were identified by the criteria |log2FC| ≥ 0.25 and P < 0.05 with DESeq2. A protein interaction network was constructed using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software to identify hub genes. We then constructed an ARDSp rat model through induction by lipopolysaccharide (LPS) airway instillation. Left lung RNA was extracted and sequenced via Illumina Hiseq platforms. Analysis of the rat RNA sequencing data was then used to verify hub genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the identified hub genes. Results: In AT2, a total of 289 genes were identified as differentially expressed between those from ARDSp patients and healthy donors, and these included 190 upregulated and 99 downregulated genes. Ten hub genes were further identified (RPS27A, ACTG1, CAV1, HSP90AA1, HSPA5, CCND1, ITGA3, B2M, NEDD4L, and SEMA5A). There was a similar expression trend of HSPA5 between rat RNA and snRNA sequencing data. Discussion: ARDSp altered the gene expression profile of AT2. The identified hub genes were enriched in biological processes mainly involved in cell growth and transformation. Relatedly, ferroptosis and autophagy are possibly involved in AT2 injury during ARDSp. These novel insights into ARDSp may aid the discovery of potential targets for the diagnosis and treatment of ARDSp.

Effects of early standardized enteral nutrition on preventing acute muscle loss in the acute exacerbation of chronic obstructive pulmonary disease patients with mechanical ventilation.

BACKGROUND: To investigate the effects of early standardized enteral nutrition (EN) on the cross-sectional area of erector spine muscle (ESMcsa), plasma growth differentiation factor-15 (GDF-15), and 28-day mortality of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with invasive mechanical ventilation (MV). METHODS: A total of 97 AECOPD patients with invasive MV were screened in the ICUs of the First People's Hospital of Lianyungang. The conventional EN group (stage I) and early standardized EN group (stage II) included 46 and 51 patients, respectively. ESMcsa loss and GDF-15 levels on days 1 and 7 of ICU admission and 28-day survival rates were analyzed. RESULTS: On day 7, the ESMcsa of the early standardized EN group was significantly higher than that of the conventional EN group, while the plasma GDF-15 levels were significantly lower than those in the conventional EN group (ESMcsa: 28.426±6.130 cm2 vs. 25.205±6.127 cm2; GDF-15: 1661.608±558.820 pg/mL vs. 2541.000±634.845 pg/mL; all P<0.001]. The 28-day survival rates of the patients in the early standardized EN group and conventional EN group were 80.40% and 73.90%, respectively (P=0.406). CONCLUSION: ESMcsa loss in AECOPD patients with MV was correlated with GDF-15 levels, both of which indicated acute muscular atrophy and skeletal muscle dysfunction. Early standardized EN may prevent acute muscle loss and intensive care unit-acquired weakness (ICU-AW) in AECOPD patients.

Elastic power, a novel predictor of the severity and prognosis of ARDS.

PURPOSE: To explore the predictive value of the new comprehensive respiratory mechanics parameters elastic power (EP) and elastic power normalized to the compliance (Cst-EP) in the evaluation of the severity and 28-day prognosis of ARDS patients. METHODS: The MIMIC-III database was used to identify ARDS patients under invasive mechanical ventilation for at least 48 h. Their baseline data and ventilatory variables were collected. EP, elastic energy, driving pressure and mechanical power were calculated according to the corresponding formulas. Their value in assessing the severity of ARDS was evaluated. The correlation between Cst-EP and 28-day prognosis of ARDS patients was analyzed. RESULTS: EP was independently associated with the severity of the ARDS and the odds ratio (OR) was 1.301 [95% CI (1.190-1.423), p < 0.001]. It has higher accuracy for the severity of ARDS, with an optimal cut-off value of 14.6 J/min. The Cst-EP was significantly associated with increased risk of death and the hazard ratio (HR) per 100 J/min × cmH2O/ml × 10-3 was 1.169 [95% CI (1.093-1.250), p < 0.001]. In addition, the 28-day cumulative survival rate of the high Cst-EP group was significantly lower than that of the low Cst-EP group. CONCLUSION: EP can be used to predict the severity of ARDS, and Cst-EP is associated with mortality during controlled mechanical ventilation in ARDS.

[Development and validation of a mechanical power-oriented nomogram model for predicting the risk of weaning failure in mechanically ventilated patients: an analysis using the data from MIMIC-IV].

OBJECTIVE: To develop and validate a mechanical power (MP)-oriented nomogram prediction model of weaning failure in mechanically ventilated patients. METHODS: Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and were weaned using a T-tube ventilation strategy were collected from the Medical Information Mart for Intensive Care-IV v1.0 (MIMIC-IV v1.0) database. Demographic information and comorbidities, respiratory mechanics parameters 4 hours before the first spontaneous breathing trial (SBT), laboratory parameters preceding the SBT, vital signs and blood gas analysis during SBT, length of intensive care unit (ICU) stay and IMV duration were collected and all eligible patients were enrolled into the model group. Lasso method was used to screen the risk factors affecting weaning outcomes, which were included in the multivariate Logistic regression analysis. R software was used to construct the nomogram prediction model and build the dynamic web page nomogram. The discrimination and accuracy of the nomogram were assessed by receiver operator characteristic curve (ROC curve) and calibration curves, and the clinical validity was assessed by decision curve analysis (DCA). The data of patients undergoing mechanical ventilation hospitalized in ICU of the First People's Hospital of Lianyungang City and the Second People's Hospital of Lianyungang City from November 2021 to October 2022 were prospectively collected to externally validate the model. RESULTS: A total of 3 695 mechanically ventilated patients were included in the model group, and the weaning failure rate was 38.5% (1 421/3 695). Lasso regression analysis finally screened out six variables, including positive end-expiratory pressure (PEEP), MP, dynamic lung compliance (Cdyn), inspired oxygen concentration (FiO2), length of ICU stay and IMV duration, with coefficients of 0.144, 0.047, -0.032, 0.027, 0.090 and 0.098, respectively. Logistic regression analysis showed that the six variables were all independent risk factors for predicting weaning failure risk [odds ratio (OR) and 95% confidence interval (95%CI) were 1.155 (1.111-1.200), 1.048 (1.031-1.066), 0.968 (0.963-0.974), 1.028 (1.017-1.038), 1.095 (1.076-1.113), and 1.103 (1.070-1.137), all P < 0.01]. The MP-oriented nomogram prediction model of weaning failure in mechanically ventilated patients showed accurate discrimination both in the model group and external validation group, with area under the ROC curve (AUC) and 95%CI of 0.832 (0.819-0.845) and 0.879 (0.833-0.925), respectively. Furthermore, its predictive accuracy was significantly higher than that of individual indicators such as MP, Cdyn, and PEEP. Calibration curves showed good correlation between predicted and observed outcomes. DCA indicated that the nomogram model had high net benefits, and was clinically beneficial. CONCLUSIONS: The MP-oriented nomogram prediction model of weaning failure accurately predicts the risk of weaning failure in mechanical ventilation patients and provides valuable information for clinicians making decisions on weaning.