Development and validation of a nomogram for predicting in-hospital survival rates of patients with COVID-19.

Objective: Our aim was to develop and validate a nomogram for predicting the in-hospital 14-day (14 d) and 28-day (28 d) survival rates of patients with coronavirus disease 2019 (COVID-19). Methods: Clinical data of patients with COVID-19 admitted to the Renmin Hospital of Wuhan University from December 2022 to February 2023 and the north campus of Shanghai Ninth People's Hospital from April 2022 to June 2022 were collected. A total of 408 patients from Renmin Hospital of Wuhan University were selected as the training cohort, and 151 patients from Shanghai Ninth People's Hospital were selected as the verification cohort. Independent variables were screened using Cox regression analysis, and a nomogram was constructed using R software. The prediction accuracy of the nomogram was evaluated using the receiver operating characteristic (ROC) curve, C-index, and calibration curve. Decision curve analysis was used to evaluate the clinical application value of the model. The nomogram was externally validated using a validation cohort. Result: In total, 559 patients with severe/critical COVID-19 were included in this study, of whom 179 (32.02 %) died. Multivariate Cox regression analysis showed that age >80 years [hazard ratio (HR) = 1.539, 95 % confidence interval (CI): 1.027-2.306, P = 0.037], history of diabetes (HR = 1.741, 95 % CI: 1.253-2.420, P = 0.001), high APACHE II score (HR = 1.083, 95 % CI: 1.042-1.126, P < 0.001), sepsis (HR = 2.387, 95 % CI: 1.707-3.338, P < 0.001), high neutrophil-to-lymphocyte ratio (NLR) (HR = 1.010, 95 % CI: 1.003-1.017, P = 0.007), and high D-dimer level (HR = 1.005, 95 % CI: 1.001-1.009, P = 0.028) were independent risk factors for 14 d and 28 d survival rates, whereas COVID-19 vaccination (HR = 0.625, 95 % CI: 0.440-0.886, P = 0.008) was a protective factor affecting prognosis. ROC curve analysis showed that the area under the curve (AUC) of the 14 d and 28 d hospital survival rates in the training cohort was 0.765 (95 % CI: 0.641-0.923) and 0.814 (95 % CI: 0.702-0.938), respectively, and the AUC of the 14 d and 28 d hospital survival rates in the verification cohort was 0.898 (95 % CI: 0.765-0.962) and 0.875 (95 % CI: 0.741-0.945), respectively. The calibration curves of 14 d and 28 d hospital survival showed that the predicted probability of the model agreed well with the actual probability. Decision curve analysis (DCA) showed that the nomogram has high clinical application value. Conclusion: In-hospital survival rates of patients with COVID-19 were predicted using a nomogram, which will help clinicians in make appropriate clinical decisions.

Natural image restoration based on multi-scale group sparsity residual constraints.

The Group Sparse Representation (GSR) model shows excellent potential in various image restoration tasks. In this study, we propose a novel Multi-Scale Group Sparse Residual Constraint Model (MS-GSRC) which can be applied to various inverse problems, including denoising, inpainting, and compressed sensing (CS). Our new method involves the following three steps: (1) finding similar patches with an overlapping scheme for the input degraded image using a multi-scale strategy, (2) performing a group sparse coding on these patches with low-rank constraints to get an initial representation vector, and (3) under the Bayesian maximum a posteriori (MAP) restoration framework, we adopt an alternating minimization scheme to solve the corresponding equation and reconstruct the target image finally. Simulation experiments demonstrate that our proposed model outperforms in terms of both objective image quality and subjective visual quality compared to several state-of-the-art methods.

Combined computational analysis and cytology show limited depth osteogenic effect on bone defects in negative pressure wound therapy.

Background: The treatment of bone defects remains a clinical challenge. The effect of negative pressure wound therapy (NPWT) on osteogenesis in bone defects has been recognized; however, bone marrow fluid dynamics under negative pressure (NP) remain unknown. In this study, we aimed to examine the marrow fluid mechanics within trabeculae by computational fluid dynamics (CFD), and to verify osteogenic gene expression, osteogenic differentiation to investigate the osteogenic depth under NP. Methods: The human femoral head is scanned using micro-CT to segment the volume of interest (VOI) trabeculae. The VOI trabeculae CFD model simulating the bone marrow cavity is developed by combining the Hypermesh and ANSYS software. The effect of trabecular anisotropy is investigated, and bone regeneration effects are simulated under NP scales of -80, -120, -160, and -200 mmHg. The working distance (WD) is proposed to describe the suction depth of the NP. Finally, gene sequence analysis, cytological experiments including bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation are conducted after the BMSCs are cultured under the same NP scale. Results: The pressure, shear stress on trabeculae, and marrow fluid velocity decrease exponentially with an increase in WD. The hydromechanics of fluid at any WD inside the marrow cavity can be theoretically quantified. The NP scale significantly affects the fluid properties, especially those fluid close to the NP source; however, the effect of the NP scale become marginal as WD deepens. Anisotropy of trabecular structure coupled with the anisotropic hydrodynamic behavior of bone marrow; An NP of -120 mmHg demonstrates the majority of bone formation-related genes, as well as the most effective proliferation and osteogenic differentiation of BMSCs compared to the other NP scales. Conclusion: An NP of -120 mmHg may have the optimal activated ability to promote osteogenesis, but the effective WD may be limited to a certain depth. These findings help improve the understanding of fluid mechanisms behind NPWT in treating bone defects.

Downregulation of phosphoserine phosphatase potentiates tumor immune environments to enhance immune checkpoint blockade therapy.

BACKGROUND: Effects of immune checkpoint blockade (ICB) treatment in hepatocellular carcinoma (HCC) are limited. The current study explored the possibility of exploiting tumor metabolic switches to enhance HCC sensitivity to immune therapies. METHODS: Levels of one-carbon (1C) metabolism and the expression of phosphoserine phosphatase (PSPH), an upstream enzyme of 1C pathway, were evaluated in paired non-tumor and tumor tissues from HCC. Underlying mechanisms mediating the role of PSPH in regulating the infiltration of monocytes/macrophages and CD8+ T lymphocytes were studied through both in vitro and in vivo experiments. RESULTS: PSPH was significantly upregulated in tumor tissues of HCC and its levels were positively correlated with disease progression. PSPH knockdown inhibited tumor growth in immunocompetent mice, but not in those with macrophage or T lymphocyte deficiencies, indicating the pro-tumor effects of PSPH were dependent on both immune components. Mechanistically, PSPH facilitated monocytes/macrophages infiltration by inducing the production of C-C motif chemokine 2 (CCL2), while at the same time reduced CD8+ T lymphocytes recruitment through inhibiting the production of C-X-C Motif Chemokine 10 (CXCL10) in tumor necrosis factor alpha (TNF-α)-conditioned cancer cells. Glutathione and S-adenosyl-methionine were partially involved in regulating the production of CCL2 and CXCL10, respectively. shPSPH (short hairpin RNA) transfection of cancer cells enhanced tumor sensitivity to anti-programmed cell death protein 1 (PD-1) therapy in vivo, and interestingly, metformin could inhibit PSPH expression in cancer cells and mimic the effects of shPSPH in sensitizing tumors to anti-PD-1 treatment. CONCLUSIONS: By tilting the immune balance towards a tumor-friendly composition, PSPH might be useful both as a marker in stratifying patients for ICB therapy, and as an attractive therapeutic target in the treatment of human HCC.

Effects of paroxetine on the safety of mothers and infants in the second and third trimesters of pregnancy：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the safety of paroxetine in the treatment of pregnant patients with depression in the second and third trimesters of pregnancy， and provide reference for rational clinical use of it. METHODS Retrieved from Cochrane Library， PubMed， Embase， VIP， CNKI， Wanfang database and SinoMed database， by manual search， randomized controlled studies or observational studies were collected on depression patients who were given paroxetine vs. selective serotonin reuptake inhibitor （SSRI） in the second and third trimesters of pregnancy during the inception to Aug. 2022. Methodological qualities of the included studies were assessed by Cochrane Handbook 5.1.0 or Newcastle-Ottawa Scale （NOS）. Meta-analysis was performed with RevMan 5.4.1 software. RESULTS Finally， 9 observational studies were included， and all included studies were of high quality in NOS scale. Meta-analysis was performed on 8 cohort studies. Meta-analysis showed that the total incidence of adverse pregnancy outcomes of mothers and infants [RR＝0.99， 95%CI（0.89，1.10），P＝0.87]， total incidence of maternal adverse pregnancy outcomes [RR＝0.98， 95%CI （0.87，1.10）， P＝0.69] and premature birth [RR＝0.89， 95%CI （0.43， 1.83）， P＝0.75] in the second and third trimesters of pregnancy were lower than that with other SSRI， without statistical significance. The incidence of neonatal complications with paroxetine in the second and third trimesters of pregnancy was higher than that with other SSRI， but the difference was not statistically significant [RR＝1.02， 95%CI （0.82，1.29）， P＝0.84]. One study reported that the incidence of neonatal pulmonary hypertension in paroxetine group was higher than that in other SSRI group （0.4% vs. 0.3%）. CONCLUSIONS The safety of peroxetine in the second and third trimesters of pregnancy is comparable with that of other SSRI， but it is necessary to be alert to the occurrence of neonatal pulmonary hypertension.

Case analysis of a patient with osimertinib-induced interstitial pneumonia who re-used EGFR-TKI therapy / 中国药房

OBJECTIVE To explore the way to re-use epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKI） in patients with EGFR-TKI-induced interstitial pneumonia （IP）， using osimertinib as an example. METHODS The IP treatment regimen and re-use of EGFR-TKI regimen in a patient who developed IP after the use of osimertinib were analyzed. And a literature review was made by combining the characteristics of the cases which reported in the literature and the characteristics of this case. RESULTS The patient’s IP symptoms due to treatment with osimertinib had resolved after treatment. The patient’s IP symptoms also did not worsen after using almonertinib in combination with hormones as re-use of EGFR-TKI regimen. However， almonertinib was discontinued as the patient experienced disease progression. The adverse reactions of IP needed to be dealt with in time， the EGFR-TKI should be discontinued and symptomatic treatment should be given. CONCLUSIONS EGFR-TKI targeted therapy could be re-selected by replacing EGFR-TKI， adjusting the dose of EGFR-TKI， and using hormones in combination. EGFR-TKI-induced adverse drug reactions of IP are rare， but need to be observed closely. If other EGFR-TKI is used， close monitoring of adverse reactions and curative effects are also required in order to adjust the patient’s treatment plan in time.

Construction and Validation of Mortality Risk Nomograph Model for Severe/Critical Patients with COVID-19.

Objective: A nomograph model of mortality risk for patients with coronavirus disease 2019 (COVID-19) was established and validated. Methods: We collected the clinical medical records of patients with severe/critical COVID-19 admitted to the eastern campus of Renmin Hospital of Wuhan University from January 2020 to May 2020 and to the north campus of Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, from April 2022 to June 2022. We assigned 254 patients to the former group, which served as the training set, and 113 patients were assigned to the latter group, which served as the validation set. The least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression were used to select the variables and build the mortality risk prediction model. Results: The nomogram model was constructed with four risk factors for patient mortality following severe/critical COVID-19 (≥3 basic diseases, APACHE II score, urea nitrogen (Urea), and lactic acid (Lac)) and two protective factors (percentage of lymphocyte (L%) and neutrophil-to-platelets ratio (NPR)). The area under the curve (AUC) of the training set was 0.880 (95% confidence interval (95%CI), 0.837~0.923) and the AUC of the validation set was 0.814 (95%CI, 0.705~0.923). The decision curve analysis (DCA) showed that the nomogram model had high clinical value. Conclusion: The nomogram model for predicting the death risk of patients with severe/critical COVID-19 showed good prediction performance, and may be helpful in making appropriate clinical decisions for high-risk patients.

Carbonic anhydrase XII mediates the survival and prometastatic functions of macrophages in human hepatocellular carcinoma.

Macrophages constitute a major immune component in tumor tissues, but how these cells adapt to and survive in the nutrient-depleted and lactic acid-induced acidic tumor microenvironments is not yet fully understood. Here, we found that levels of carbonic anhydrase XII (CA12) expression were significantly and selectively upregulated on macrophages in human hepatocellular carcinoma (HCC). Transient glycolytic activation of peritumoral monocytes induced sustained expression of CA12 on tumor-infiltrating macrophages via autocrine cytokines and HIF1α pathways. On the one hand, CA12 mediated the survival of macrophages in relatively acidic tumor microenvironments, while on the other hand, it induced macrophage production of large amounts of C-C motif chemokine ligand 8 (CCL8), which enhanced cancer cell epithelial-mesenchymal transition (EMT) and facilitated tumor metastasis. Consistently, the accumulation of CA12+ macrophages in tumor tissues was associated with increased tumor metastatic potential and reduced survival of patients with HCC. Selective targeting of tumor-infiltrating macrophages with a CA12 inhibitor reduced tumor growth in mice and was sufficient to synergistically enhance the therapeutic efficacy of immune-checkpoint blockade. We suggest that CA12 activity is a previously unappreciated mechanism regulating the accumulation and functions of macrophages in tumor microenvironments and therefore represents a selective vulnerability that could be exploited in future designs for antitumor immunotherapeutic strategies.

Neutrophil extracellular traps induce tumor metastasis through dual effects on cancer and endothelial cells.

Neutrophils constitute a major component in human hepatocellular carcinoma (HCC) and can facilitate disease progression via poorly understood mechanisms. Here, we show that neutrophil extracellular traps (NETs) formation was increased in human HCC tumor tissues than in paired non-tumor liver tissues. Mechanism study revealed that tumor-induced metabolic switch toward glycolysis and pentose phosphate pathway in tumor infiltrating neutrophils promoted NETs formation in a reactive oxygen species dependent-manner. NETs subsequently induced the migration of cancer cells and down-regulation of tight junction molecules on adjacent endothelial cells, thus facilitating tumor intravasation and metastasis. Accordingly, NETs depletion could inhibit tumor metastasis in mice in vivo, and the infiltration levels of NETs-releasing neutrophils were negatively associated with patient survival and positively correlated with tumor metastasis potential of HCC patients. Our results unveiled a pro-metastatic role of NETs in the milieu of human HCC, and pointed to the importance of metabolic reprogramming in shaping their characteristics, thus providing an applicable efficient target for anti-cancer therapies.

Celastrol targets adenylyl cyclase-associated protein 1 to reduce macrophages-mediated inflammation and ameliorates high fat diet-induced metabolic syndrome in mice

Metabolic syndrome is a clustering of metabolic disorder with unclear molecular mechanism. Increasing studies have found that the pathogenesis and progression of metabolic syndrome are closely related to inflammation. Here, we report celastrol, a traditional Chinese medicine, can improve high fat diet-induced metabolic syndrome through suppressing resistin-induced inflammation. Mechanistically, celastrol binds to adenylyl cyclase associated protein 1 (CAP1) and inhibits the interaction between CAP1 and resistin, which restrains the cyclic adenylate monophosphate (cAMP)-protein kinase A (PKA)-nuclear factor kappa-B (NF-

Glycolytic activation of monocytes regulates the accumulation and function of neutrophils in human hepatocellular carcinoma.

BACKGROUND & AIMS: Neutrophils are one of the most abundant components in human hepatocellular carcinoma (HCC) and have been shown to play important roles in regulating disease progression. However, neutrophils are very short-lived cells in circulation, and mechanisms regulating their accumulation and functions in HCC are not yet fully understood. METHODS: Monocytes were purified from non-tumor or paired tumor tissues of patients with HCC, and their production of neutrophil-attracting chemokines was evaluated. Mechanisms regulating the expression of CXCL2/8 by tumor monocytes, and the role of tumor monocyte-derived chemokines and cytokines in modulating neutrophil accumulation and functions were studied with both ex vivo analyses and in vitro experiments. RESULTS: Monocyte-derived CXCL2 and CXCL8 were major factors in regulating the recruitment of neutrophils into tumor milieus. These chemokines, in addition to tumor-derived soluble factors, could inhibit apoptosis and sustain survival of neutrophils, thus leading to neutrophil accumulation in tumor tissues. Moreover, monocyte-derived TNF-α acted synergistically with tumor-derived soluble factors to induce the production of the pro-metastasis factor OSM by neutrophils. Further, the glycolytic switch in tumor-infiltrating monocytes mediated their production of CXCL2 and CXCL8 via the PFKFB3-NF-κB signaling pathway. Accordingly, levels of PFKFB3, CXCL2/CXCL8 production in monocytes and infiltration of OSM-producing neutrophils were positively correlated in human HCC tissues. CONCLUSIONS: Our results unveiled a previously unappreciated link between monocytes and neutrophils in human HCC, identifying possible targets that could be therapeutically exploited in the future. LAY SUMMARY: Neutrophils constitute a major but poorly understood component of human hepatocellular carcinoma (HCC). Herein, we unveil a novel mechanism by which metabolic switching in monocytes promotes the accumulation of neutrophils in the tumors of patients with HCC. Both monocyte-produced chemokines and signals from the tumor microenvironment promote the production of the pro-metastatic factor OSM by neutrophils. These data identify potential targets for immune-based anticancer therapies for HCC.

Prognostic value of primary tumor surgery in seminoma patients with distant metastasis at diagnosis: a population-based study / 亚洲男科学杂志(英文版)

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

Three-Dimensional Graphene-Based Composite Hydrogel Materials for Flexible Supercapacitor Electrodes.

Three-dimensional (3D) graphene-based hydrogels have attracted great interest for applying in supercapcacitors electrodes, owing to their intriguing properties that combine the structural interconnectivities and the outstanding properties of graphene. However, the pristine graphene hydrogel can not satisfy the high-performance demands, especial in high specific capacitance. Consequently, novel graphene-based composite hydrogels with increased electrochemical properties have been developed. In this mini review, a brief summary of recent progress in the research of the three-dimensional graphene-based composite hydrogel for flexible supercapacitors electrodes materials is presented. The latest progress in the graphene-based composite hydrogel consisting of graphene/metal, graphene/polymer, and atoms doped graphene is discussed. Furthermore, future perspectives and challenges in graphene-based composite hydrogel for supercapacitor electrodes are also expressed.

Fumigaclavine C attenuates adipogenesis in 3T3-L1 adipocytes and ameliorates lipid accumulation in high-fat diet-induced obese mice.

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

Glycolytic activation of peritumoral monocytes fosters immune privilege via the PFKFB3-PD-L1 axis in human hepatocellular carcinoma.

BACKGROUND & AIMS: Programmed cell death 1 ligand 1 (PD-L1) expression on antigen-presenting cells is essential for T cell impairment, and PD-L1-expressing macrophages may mechanistically shape and therapeutically predict the clinical efficacy of PD-L1 or programmed cell death 1 blockade. We aimed to elucidate the mechanisms underlying PD-L1 upregulation in human tumor microenvironments, which remain poorly understood despite the clinical success of immune checkpoint inhibitors. METHODS: Monocytes/macrophages were purified from peripheral blood, non-tumor, or paired tumor tissues of patients with hepatocellular carcinoma (HCC), and their possible glycolytic switch was evaluated. The underlying regulatory mechanisms and clinical significance of metabolic switching were studied with both ex vivo analyses and in vitro experiments. RESULTS: We found that monocytes significantly enhanced the levels of glycolysis at the peritumoral region of human HCC. The activation of glycolysis induced PD-L1 expression on these cells and subsequently attenuated cytotoxic T lymphocyte responses in tumor tissues. Mechanistically, tumor-derived soluble factors, including hyaluronan fragments, induced the upregulation of a key glycolytic enzyme, PFKFB3, in tumor-associated monocytes. This enzyme not only modulated the cellular metabolic switch but also mediated the increased expression of PD-L1 by activating the nuclear factor kappa B signaling pathway in these cells. Consistently, the levels of PFKFB3+CD68+ cell infiltration in peritumoral tissues were negatively correlated with overall survival and could serve as an independent prognostic factor for survival in patients with HCC. CONCLUSIONS: Our results reveal a mechanism by which the cellular metabolic switch regulates the pro-tumor functions of monocytes in a specific human tumor microenvironment. PFKFB3 in both cancer cells and tumor-associated monocytes is a potential therapeutic target in human HCC. LAY SUMMARY: Programmed cell death 1 ligand 1 (PD-L1) expressed on antigen-presenting cells, rather than tumor cells, has been reported to play an essential role in checkpoint blockade therapy. A fundamental understanding of mechanisms that regulate the expression of PD-L1 on tumor-infiltrating monocytes/macrophages will undoubtedly lead to the possibility of developing novel PD-L1 blockade strategies with high specificity and efficiency. The current study unveils a novel mechanism by which metabolic switching links immune activation responses to immune tolerance in the tumor milieu, identifying potential targets for future immune-based anti-cancer therapies.

Identification of seven long noncoding RNAs signature for prediction of biochemical recurrence in prostate cancer / 亚洲男科学杂志(英文版)

Accumulating evidence suggested that long noncoding RNAs (lncRNAs) possess a potential role in prostate cancer (PCa) diagnosis and prognosis. Rapid biochemical recurrence (BCR) is considered as a sign for clinical recurrence metastasis and PCa-specific mortality. Hence, the aim of the present study was to identify a lncRNA signature that can predict BCR of PCa accurately. Bioinformatics analysis, Kaplan-Meier analyses, Cox regression analyses, and Gene Set Enrichment Analysis (GSEA) were performed in a publicly available database with 499 PCa tissues and 52 matched normal tissues. A signature was identified. All these lncRNAs were differentially expressed between tumor and normal tissues and differentially expressed between high Gleason score and low Gleason score tissues. Furthermore, we developed a seven lncRNAs signature that can predict PCa BCR. Patients classified into low-risk group showed better BCR survival significantly than the patients in the high-risk group (hazard ratio = 0.32, 95% CI: 0.20-0.52, concordance index = 0.63). The area under the curve was 0.68 for BCR. The signature also had good discrimination for BCR in men with Gleason 7 PCa. In conclusion, our results suggest that the seven lncRNAs signature is a new biomarker of BCR and high risk in PCa. In addition, the individual lncRNA warrants further study to uncover the associated mechanisms of PCa progression and the signature could be used to design direct clinical trials for adjuvant therapy.

Peritumoral monocytes induce cancer cell autophagy to facilitate the progression of human hepatocellular carcinoma.

Macroautophagy/autophagy is an important catabolic process mediating cellular homeostasis and plays critical roles in cancer development. Whereas autophagy has been widely studied in various pathological models, little is known about the distribution, clinical significance and regulatory mechanism of this process in human hepatocellular carcinoma (HCC). In the present study, we found that tumor tissues exhibited significantly increased levels of autophagy compared with non-tumor tissues, and cancer cells with higher levels of autophagy were predominantly enriched in the invading edge regions of human HCC. Increased MAP1LC3B/LC3B expression in the invading edge regions was significantly correlated with a higher density of closely located monocytes, and TNF and IL1B derived from tumor-activated monocytes synergistically induced cancer cell autophagy in the invading edge regions of HCC. Monocyte-elicited autophagy induced the epithelial-mesenchymal transition (EMT) of cancer cells and promoted tumor metastasis by activating the NFKB-SNAI1 signaling pathway. Moreover, the increase of LC3B+ cancer cells in the invading edge areas was associated with high mortality and reduced survival of patients with HCC. These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction.

Effect of metabolites of Clostridium butyricum, butyric acid and hydro-gen, on acute gastric mucosal lesion / 中国病理生理杂志

AIM:To observe the antiulcer effect of butyric acid and hydrogen , the main metabolites of Clos-tridium butyricum (C.butyricum), and to explore the underlying mechanism .METHODS: The mouse model of acute gastric mucosal lesion was prepared by gavage with ethanol .The mice were randomly divided into 4 groups:normal group , model group , butyric acid group and hydrogen group .The mice in butyric acid group and hydrogen group were given buty-rate and hydrogen prior to model establishment , respectively .Macroscopic observation of the pathological changes in gastric tissues was performed to evaluate the effect of the 2 metabolites of C.butyricum.Meanwhile, the mRNA expression levels of inflammatory factors, such as IL-12, RAN1 and MCP-1, were determined by RT-qPCR.The expression levels of apopto-sis-related proteins Bcl-2 and Bax were detected by immunohistochemical staining .RESULTS:The macroscopic observa-tion found that butyrate , not hydrogen , protected gastric mucosa .HE staining also showed that butyrate significantly attenu-ated the pathological damage of the gastric mucosa induced by ethanol .Compared with model group , the mRNA levels of inflammatory factors IL-12, RAN1 and MCP-1 in butyrate group significantly decreased (P<0.01).In butyrate group, the protein level of Bax was obviously decreased compared with model group (P<0.01), while the protein level of Bcl-2 was significantly increased ( P<0.01 ) .CONCLUSION: The gastric mucosa protective metabolite of C.butyricum may be butyric acid , not hydrogen .Butyric acid protects the gastric mucosa against ethanol-induced lesion by inhibiting the inflam- mation and reducing the expression ratio of Bax/Bcl-2.

Effect of metabolites of Clostridium butyricum, butyric acid and hydro-gen, on acute gastric mucosal lesion / 中国病理生理杂志

AIM:To observe the antiulcer effect of butyric acid and hydrogen , the main metabolites of Clos-tridium butyricum (C.butyricum), and to explore the underlying mechanism .METHODS: The mouse model of acute gastric mucosal lesion was prepared by gavage with ethanol .The mice were randomly divided into 4 groups:normal group , model group , butyric acid group and hydrogen group .The mice in butyric acid group and hydrogen group were given buty-rate and hydrogen prior to model establishment , respectively .Macroscopic observation of the pathological changes in gastric tissues was performed to evaluate the effect of the 2 metabolites of C.butyricum.Meanwhile, the mRNA expression levels of inflammatory factors, such as IL-12, RAN1 and MCP-1, were determined by RT-qPCR.The expression levels of apopto-sis-related proteins Bcl-2 and Bax were detected by immunohistochemical staining .RESULTS:The macroscopic observa-tion found that butyrate , not hydrogen , protected gastric mucosa .HE staining also showed that butyrate significantly attenu-ated the pathological damage of the gastric mucosa induced by ethanol .Compared with model group , the mRNA levels of inflammatory factors IL-12, RAN1 and MCP-1 in butyrate group significantly decreased (P<0.01).In butyrate group, the protein level of Bax was obviously decreased compared with model group (P<0.01), while the protein level of Bcl-2 was significantly increased ( P<0.01 ) .CONCLUSION: The gastric mucosa protective metabolite of C.butyricum may be butyric acid , not hydrogen .Butyric acid protects the gastric mucosa against ethanol-induced lesion by inhibiting the inflam- mation and reducing the expression ratio of Bax/Bcl-2.

Risk factors for allergic diseases in children aged 0-24 months in the Wuhu urban area, Anhui Province, China / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of allergic diseases in children aged 0-24 months in the Wuhu urban area of Anhui Province and risk factors for allergic diseases.</p><p><b>METHODS</b>Cluster random sampling was performed to select 600 children aged 0-24 months and their mothers from the Wuhu urban area, and a questionnaire survey was conducted to collect the data of disease history, family history, mothers' conditions during pregnancy, and child-rearing situation. Univariate analysis and multivariate logistic regression analysis were performed for such data.</p><p><b>RESULTS</b>Among the 597 children included in the analysis, 56 (9.4%) were diagnosed with allergic diseases in the past. The univariate analysis showed that the age, use of antipyretic and analgesic drugs, a history of allergy in the father or grandparents, and the consumption of fish, shrimps, crabs, and shellfish during pregnancy were significantly associated with past allergic diseases (P<0.05). The multivariate logistic regression analysis showed that the age and a history of allergy in the father or grandparents were positively associated with past allergic diseases (OR=4.0-4.9, 2.7, and 2.4 respectively; P<0.05), while frequent consumption of fish, shrimps, crabs, and shellfish during pregnancy was negatively associated with past allergic diseases (OR=0.3; P<0.05).</p><p><b>CONCLUSIONS</b>A family history of allergy is an independent risk factor for allergic diseases in children aged 0-24 months in the Wuhu urban area of Anhui Province, while frequent consumption of fish, shrimps, crabs, and shellfish during pregnancy is a protective factor.</p>