The risk factors of reintubation in intensive care unit patients on mechanical ventilation: A systematic review and meta-analysis.

OBJECTIVE: To assess risk factors of reintubation in intensive care unit patients on mechanical ventilation. METHODOLOGY: We conducted a systematic review of literature (inception to May 2022) and a meta-analysis. Data are reported as pooled odds ratios for categorical variables and mean differences for continuous variables. RESULTS: A total of 2459 studies were retrieved of which 38 studies were included in a meta-analysis involving 22,304 patients. Risk factors identified were: older age, higher APACHE II scores, COPD, pneumonia, shock, low SaO2, low PaO2, low PaO2/FiO2, low hemoglobin, low albumin, high brain natriuretic peptide, low pH, high respiratory rate, low tidal volume, a higher rapid shallow breathing index, a lower vital capacity, a higher number of spontaneous breathing trials, prolonged length of mechanical ventilation, weak cough, a reduced patient's cough peak flow and positive cuff leak test. Subgroup analysis showed that risk factors substantially overlap when reintubation was considered within 48 hours or within 72 hours after extubation. CONCLUSIONS: We identified 21 factors associated with increased risk for reintubation. These allow to recognize the patient at high risk for reintubation at an early stage. Future studies may combine these factors to develop comprehensive predictive algorithms allowing appropriate vigilance.

A Metabolism-Related Gene Landscape Predicts Prostate Cancer Recurrence and Treatment Response.

Background: Prostate cancer (PCa) is the most common malignant tumor in men. Although clinical treatments of PCa have made great progress in recent decades, once tolerance to treatments occurs, the disease progresses rapidly after recurrence. PCa exhibits a unique metabolic rewriting that changes from initial neoplasia to advanced neoplasia. However, systematic and comprehensive studies on the relationship of changes in the metabolic landscape of PCa with tumor recurrence and treatment response are lacking. We aimed to construct a metabolism-related gene landscape that predicts PCa recurrence and treatment response. Methods: In the present study, we used differentially expressed gene analysis, protein-protein interaction (PPI) networks, univariate and multivariate Cox regression, and least absolute shrinkage and selection operator (LASSO) regression to construct and verify a metabolism-related risk model (MRM) to predict the disease-free survival (DFS) and response to treatment for PCa patients. Results: The MRM predicted patient survival more accurately than the current clinical prognostic indicators. By using two independent PCa datasets (International Cancer Genome Consortium (ICGC) PCa and Taylor) and actual patients to test the model, we also confirmed that the metabolism-related risk score (MRS) was strongly related to PCa progression. Notably, patients in different MRS subgroups had significant differences in metabolic activity, mutant landscape, immune microenvironment, and drug sensitivity. Patients in the high-MRS group were more sensitive to immunotherapy and endocrine therapy, while patients in the low-MRS group were more sensitive to chemotherapy. Conclusions: We developed an MRM, which might act as a clinical feature to more accurately assess prognosis and guide the selection of appropriate treatment for PCa patients. It is promising for further application in clinical practice.

MLPH Accelerates the Epithelial-Mesenchymal Transition in Prostate Cancer.

INTRODUCTION: Prostate cancer (PC) is the second greatest cause of cancer deaths globally. PC presents a poor prognosis once it metastasizes. There is considerable proof of vital epithelial-mesenchymal transition (EMT) functionality in PC metastasis. Previous studies revealed that melanophilin (MLPH) is associated with PC; however, its role in PC remains poorly understood. METHODS: Bioinformatics analyses were performed. The cellular responses to MLPH knockdown were examined in HCC cell lines via wound healing assay, migration and invasion assay, Western blotting. RESULTS: Analysis of the PROGgeneV2 database revealed that high MLPH expression might indicate poor overall survival. MLPH knockdown reduced PC cell migration, proliferation, and invasion. MLPH downregulation in vivo resulted in a lower growth rate and fewer metastatic nodules in lung tissues. Furthermore, MLPH knockdown recovered downregulated expression of the mesenchymal marker N-cadherin and the epithelial marker E-cadherin following a decrease in ß-catenin. CONCLUSION: These results indicate that progression of PC is stimulated via MLPH-dependent initiation of the EMT.

Icariside II facilitates the differentiation of ADSCs to schwann cells and restores erectile dysfunction through regulation of miR-33/GDNF axis.

BACKGROUND: Adipose derived stem cells (ADSCs) have the property to differentiate into neuron-like cells, which may provide a novel insight for the restoration of erectile dysfunction (ED) mainly induced by cavernous nerve injury. Icariside II (ICA II) has been reported to play a key role in the regulation of erectile function via stimulating the differentiation of ADSCs to Schwann Cells (SCs). However, the function and molecular mechanisms of ICA II in ED remains to be further clarified. METHODS: The expression of S100, P75, GDNF and miR-33 was detected by qRT-PCR. And the relative proteins expression was determined by western blot. Cell viability was measured by Cell Counting Kit-8 (CCK-8) assay. Bioinformatics, luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the interaction between miR-33 and GDNF. Intracavernosal pressure (ICP), the ratio of ICP and mean arterial pressure (MAP), as well as nNOS expression were examined to evaluate the erectile function of SD rats with bilateral cavernous nerve injury (BCNI). RESULTS: ICA II and miR-33 respectively promoted and inhibited the differentiation of ADSCs to SCs. MiR-33 could negatively regulate P75 and GDNF expression. ICA II exerted promotion effects on differentiation of ADSCs to SCs via regulating miR-33. GDNF was identified to be a target of miR-33. MiR-33 overexpression abrogated the stimulatory effect of ICA II on ADSCs' differentiation, which was blocked by GDNF overexpression. treated with ICA II recovered the erectile function of BCNI model rats through regulation of miR-33. CONCLUSION: ICA II contributed to the differentiation of ADSCs to SCs viamiR-33/GDNF axis, contributing to the recovery of erectile function in BCNI rats.

[Efficacy and safety of regular use of sildenafil in the treatment of penile erectile dysfunction].

OBJECTIVE: To investigate the efficacy and safety of regular oral use of sildenafil in the treatment of ED. METHODS: We randomly divided 334 ED patients into three groups to be treated orally with sildenafil tablets at 50 mg qd (sildenafil regular), sildenafil tablets at 100 mg 30 minutes before intercourse (sildenafil on-demand), and tadalafil tablets at 10 mg qd (tadalafil regular), all for 3 months. Then we recorded the IIEF-5 score and penile erection hardness score (EHS) and adverse reactions and compared them among the three groups of patients. RESULTS: There were no statistically significant differences among the three groups of patients in age, body mass index, education, ED duration, or baseline IIEF-5 and EHS (P > 0.05). After 3-month medication, both IIEF-5 score and EHS were significantly improved in the three groups of patients as compared with the baseline (P < 0.05), with no statistically significant difference in the IIEF-5 score among the sildenafil regular, sildenafil on-demand and tadalafil regular groups (15.15 ± 2.05 vs 15.55 ± 2.36 vs 15.54 ± 2.27, P > 0.05), but the EHS markedly higher in the sildenafil on-demand than in the sildenafil regular group (3.48 ± 1.80 vs 3.12 ± 1.52, P < 0.05). The effectiveness rates in the sildenafil regular, sildenafil on-demand and tadalafil regular groups were 76.2%, 62.4% and 80.8%, respectively, significantly lower in the sildenafil on-demand than in the other two groups (P < 0.05). Adverse reactions were mild and showed no statistically significant difference in the incidence rate among the three groups (P > 0.05). CONCLUSIONS: Regular use of sildenafil has a therapeutic effect similar to that of tadalafil but better than that of sildenafil on-demand, without more adverse effects.

A Diaphragmatic Hernia and Pericardial Rupture Caused by Blunt Injury of the Chest: A Case Review.

Blunt traumatic diaphragmatic hernias are most commonly seen in combination with other injuries. Right diaphragmatic ruptures with serious pericardium ruptures are relatively rare. The diagnosis of diaphragmatic hernias is not difficult; however, prior to surgery, it is difficult to judge whether pericardium damage has occurred, particularly on the right side. This injury may occur in a critical pathological state in which cardiac tissue is outside the pericardium due to the pericardial defect. Severe hemodynamic disorders or even death may occur if the patient's condition is not diagnosed and treated in a timely manner. The transportation of patients with severe trauma must be performed with extreme caution. It is necessary to weigh a wide range of differential diagnoses in a serious and thorough initial investigation.

Icariside II Promotes the Differentiation of Adipose Tissue-Derived Stem Cells to Schwann Cells to Preserve Erectile Function after Cavernous Nerve Injury.

Icariside II (ICA II) is used in erectile dysfunction treatment. Adipose tissue-derived stem cells (ADSCs) are efficient at improving erectile function. This study aimed to explore the action mechanism of ADSCs in improving erectile function. ADSCs were isolated from the adipose tissues of rats. Cell proliferation was determined using the Cell Counting Kit-8 (CCK-8) assay. The expressions of mRNA and protein were determined separately through qRT-PCR and western blot. The endogenous expressions of related genes were regulated using recombinant plasmids and cell transfection. A Dual-Luciferase Reporter Assay was performed to determine the interaction between miR-34a and STAT3. Rat models with bilateral cavernous nerve injuries (BCNIs) were used to assess erectile function through the detection of mean arterial pressure (MAP) and intracavernosal pressure (ICP). ICA II promoted ADSCs' proliferation and differentiation to Schwann cells (SCs) through the inhibition of miR-34a. Suppressed miR-34a promoted the differentiation of ADSCs to SCs by upregulating STAT3. ICA II promoted the differentiation of ADSCs to SCs through the miR-34a/STAT3 pathway. The combination of ICA II and ADSCs preserved the erectile function of the BCNI model rats. ADSCs treated with ICA II markedly preserved the erectile function of the BCNI model rats, which was reversed through miR-34a overexpression. ICA II promotes the differentiation of ADSCs to SCs through the miR-34a/STAT3 pathway, contributing to erectile function preservation after the occurrence of a cavernous nerve injury.

Genipin inhibits the growth of human bladder cancer cells via inactivation of PI3K/Akt signaling.

Genipin, a natural compound derived from the fruit of Gardenia jasminoides, possesses numerous biological properties. The aim of the present study was to investigate the anticancer effects of genipin in human bladder cancer. T24 and 5637 bladder cancer cells were treated with different concentrations of genipin (0-200 µM) and tested for cell viability, colony formation, cell cycle progression and apoptosis. A xenograft model of bladder cancer was established to determine the anticancer effect of genipin in vivo. The involvement of the phosphoinositide-3 kinase (PI3K)/Akt pathway in the action of genipin was examined. Genipin treatment significantly inhibited the viability and clonogenic growth of bladder cancer cells and inhibited the growth of T24 xenograft tumors, compared with vehicle controls (P<0.05). Genipin-treated cells exhibited a cell cycle arrest at the G0/G1-phase, which was accompanied by a deregulation of numerous cell cycle regulators. Genipin-treated cells demonstrated a significant increase in the percentage of apoptotic cells, loss of mitochondrial membrane potential, Bax translocation to the mitochondria and the release of cytochrome c to the cytosol. Additionally, genipin treatment significantly (P<0.05) reduced the phosphorylation levels of PI3K and Akt in bladder cancer cells. Importantly, genipin-mediated anticancer effects were reversed by the overexpression of constitutively active Akt. In conclusion, to the best of our knowledge, the present study demonstrates for the first time the growth inhibitory effects of genipin in bladder cancer cells, and indicates its potential as a natural anticancer agent for bladder cancer.

Low concentration of BPA induces mice spermatocytes apoptosis via GPR30.

Bisphenol A (BPA) acts as xenoestrogen and has a great impact on disorders of human reproductive system. However, the mechanism through which BPA can affect human testicular function remains to be identified. GPR30 is a novel membrane estrogen receptor with high-affinity and low-capacity binding to estrogens. We demonstrated that estrogen receptor α (ERα), estrogen receptor ß (ERß) as well as GPR30 are expressed in mouse spermatocyte-derived GC-2 cells using Real-time PCR. We treated the cells with different doses of BPA and found that even low doses of BPA can inhibit GC-2 cell growth using MTT assay. To make sure which receptor is responsible for the biological function of BPA, we used ER down-regulator ICI and indicated that BPA could bind to GPR30. We also observed that BPA was able to induce Erk1/2 phosphorylation in GC-2 cells and proved that this process was mediated by GPR30-related EGFR-MAPK pathway using western blot. By Real-time PCR, we found that the expression of c-Fos was up-regulated and Cyclin D1 gene was down-regulated, in the presence of BPA and ICI. The results of MTT assay, comet assay and flow cytometry indicated that the activation of GPR30 induced by BPA inhibited the cell growth and induced cell apoptosis and ICI, GPR30 siRNA, EGFR inhibitor (AG), and MAPK (PD) inhibitor could partially reverse this effect. Immunohistochemistry on the testis of BPA -damaged mice showed that BPA induced spermatocyte apoptosis without affecting the seminiferous tubules and spermatocyte. In conclusion, BPA triggered spermatocyte apoptosis via GPR30.

Delayed traumatic parasternal hernia causes jejunal necrosis: A case report.

Diaphragmatic injury is a common clinical condition, and it may be difficult to avoid diaphragmatic hernia if detection and treatment is not timely. Parasternal hernia is mostly congenital. It is relatively rare in adults, and intestinal obstruction as a complication of intrathoracic intestinal herniation occurs only rarely. We treated a patient in whom parasternal hernia occurred 2 years after thoracic injuries. We present the plain radiography and computed tomography findings of this adult patient with acute abdomen symptoms caused by parasternal hernia.

Interfacial assembly of lipopeptide surfactants on octyltrimethoxysilane-modified silica surface.

The adsorption of a series of cationic lipopeptide surfactants, C14Kn (where C14 denotes the myristic acyl chain and Kn represents n number of lysine residues) at the hydrophobic solid/water interface has been studied using spectroscopic ellipsometry (SE) and neutron reflection (NR). The hydrophobic C8 surface was prepared by grafting a monolayer of octyltrimethoxysilane on the silicon surface. SE was used to follow the dynamic adsorption from these lipopeptide surfactants and the amount was found to undergo a fast increase within the first 2-3 min, followed by a much slower process tending to equilibration in the subsequent 15-20 min. Lipopetide surfactants with n = 1-4 showed similar dynamic features, indicating that the interaction between the acyl chain and the C8 surface is the main driving force for adsorption. The saturation adsorption amount of C14Kn at the C8/water interface was found to be inversely related to the increasing number of Lys residues in the head group due to the increase of steric hindrance and electrostatic repulsion between the head groups. Solution concentration had a significant effect on the initial adsorption rate, similar to the feature observed from nonionic surfactants CmEn. The structure of the adsorbed layers was studied by NR in conjunction with isotopic contrasts. The layer formed by the head groups of C14K1 was 10 Å thick, and those formed by C14K2, C14K3 and C14K4 head groups were all about 13 Å thick. In contrast, the thicknesses of the layers formed by hydrophobic tails of C14K1, C14K2 C14K3, and C14K4 were found to be 17, 13, 10, and 10 Å, respectively, resulting in the steady increase of area per molecule at the interface from 29 ± 2 Å(2) for C14K1 to 65 ± 2 Å(2) for C14K4. Thus, with an increase in the head group length, the molecules in the adsorbed layer tended to lie down upon adsorption.

Dynamic adsorption and structure of interfacial bilayers adsorbed from lipopeptide surfactants at the hydrophilic silicon/water interface: effect of the headgroup length.

Lipopeptides are an important group of biosurfactants expressed by microorganisms. Because they are well-known for being biocompatible, biodegradable, and highly surface active, they are attractive for a wide range of applications. Natural lipopeptide surfactants are however impure; it is hence difficult to use them for exploring the structure-function relation. In this work, a series of cationic lipopeptide surfactants, C(14)K(n) (n = 1-4), where C denotes the myristic acyl chain and K denotes lysine (Lys), have been synthesized, and their interfacial behavior has been characterized by studying their adsorption at the silicon/water interface (bearing a thin native oxide layer) using spectroscopic ellipsometry and neutron reflection (NR). The dynamic adsorption was marked by an initial fast step within the first 2-3 min followed by a slow molecular relaxation process over the subsequent 20-30 min. The initial rate of time-dependent adsorption and the equilibrated adsorbed amount showed a steady decrease with increasing n, indicating the impact of the molecular size, structure, and charge. NR revealed the formation of sandwiched bilayers from C(14)K(n), similar to conventional surfactants such as nonionic C(12)E(6) and cationic C(16)TAB. However, the electrostatic attraction between K and the silica surface caused confinement of the K groups, forcing the head segments into a predominantly flat-on conformation. This characteristic structural feature was confirmed by the almost constant thickness of the headgroup regions ranging from 8 to 11 Å as determined from NR combined with partial deuterium labeling to the acyl tail. An increase in area per molecular pair with n resulted directly from increasing the footprint. As a result, the hydrophobic back-to-back tail mixing and acyl chain tilting rose with n. The extent of chain-head intermixing became so intensified that the C(14)K(4) bilayer could be approximated to a uniform layer distribution.