Crystal structure and function analysis of 6-phosphogluconate dehydrogenase in Mycobacterium tuberculosis.

6-phosphogluconate dehydrogenase (6PGDH) is an essential enzyme in energy metabolism and redox reactions, and represents a potential drug target for the development of therapies targeting trypanosomes, plasmodium, or other pathogens. Tuberculosis, caused by Mycobacterium tuberculosis, is a contagious disease that severely affects human health, with approximately one-third of the world's population infected. However, the protein structure, exact oligomeric state, and catalytic mechanism of 6PGDH in Mycobacterium tuberculosis (Mt6PGDH) have remained largely unknown. In this study, we successfully purified and determined the structure of Mt6PGDH, revealing its function as a tetramer in both solution and crystal states. Through structural comparisons, we clarified the tetramer formation mechanism and the oligomeric organization of short-chain 6PGDHs. Additionally, we identified key residues for coenzyme recognition and catalytic activity. This work not only deepens our understanding of the enzymatic function of Mt6PGDH but also lays a foundation for the development of drugs targeting this enzyme.

Negative cooperativity between Gemin2 and RNA provides insights into RNA selection and the SMN complex's release in snRNP assembly.

The assembly of snRNP cores, in which seven Sm proteins, D1/D2/F/E/G/D3/B, form a ring around the nonameric Sm site of snRNAs, is the early step of spliceosome formation and essential to eukaryotes. It is mediated by the PMRT5 and SMN complexes sequentially in vivo. SMN deficiency causes neurodegenerative disease spinal muscular atrophy (SMA). How the SMN complex assembles snRNP cores is largely unknown, especially how the SMN complex achieves high RNA assembly specificity and how it is released. Here we show, using crystallographic and biochemical approaches, that Gemin2 of the SMN complex enhances RNA specificity of SmD1/D2/F/E/G via a negative cooperativity between Gemin2 and RNA in binding SmD1/D2/F/E/G. Gemin2, independent of its N-tail, constrains the horseshoe-shaped SmD1/D2/F/E/G from outside in a physiologically relevant, narrow state, enabling high RNA specificity. Moreover, the assembly of RNAs inside widens SmD1/D2/F/E/G, causes the release of Gemin2/SMN allosterically and allows SmD3/B to join. The assembly of SmD3/B further facilitates the release of Gemin2/SMN. This is the first to show negative cooperativity in snRNP assembly, which provides insights into RNA selection and the SMN complex's release. These findings reveal a basic mechanism of snRNP core assembly and facilitate pathogenesis studies of SMA.

PIKE-A Modulates Mitochondrial Metabolism through Increasing SDHA Expression Mediated by STAT3/FTO Axis.

Previous studies have shown that phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A) is involved in the regulation of several biological processes in cancer. In our previous study, we demonstrated a crucial function of PIKE-A in cancer energy metabolism by regulating pentose phosphate pathway (PPP) flux. However, whether PIKE-A regulates energy metabolism through affecting mitochondrial changes are poorly understood. In the present study, we show that PIKE-A promotes mitochondrial membrane potential, leading to increasing proliferation of glioblastoma cell. Mechanistically, PIKE-A affects the expression of respiratory chain complex Ⅱ succinate dehydrogenase A (SDHA), mediated by regulating the axis of STAT3/FTO. Taken together, these results revealed that inhibition of PIKE-A reduced STAT3/FTO/SDHA expression, leading to the suppression of mitochondrial function. Thus, our findings suggest the PIKE-A/STAT3/FTO/SDHA axis as promising anti-cancer treatment targets.

Analgesic Pump Tubing Securement to Prevent Dislodgement of Peripheral Vein Indwelling Catheter.

PURPOSE: This study aims to compare the incidence of complications when using a new approach to secure an indwelling peripheral venous catheter (PVC), involving tying of the tube with a surgical knot at two places and several layers of elastic adhesive bandage, with a standard approach using sterile, transparent, and protective film. METHODS: This study enrolled 311 consecutive adults undergoing thoracoscopic lobectomy under general anesthesia at Taizhou Hospital of Zhejiang Province between October 2017 and May 2018. Patients were randomized to experimental and control groups and were followed for up to 72 hours. The primary endpoint was dislodgement of the PVC. Secondary endpoints were blood in the catheter; analgesia pump obstruction alarm; time taken and cost of PVC replacement; replacement of securing materials and analgesia pump line; and time and cost of replacing them. All adverse events were recorded. FINDINGS: Final analysis included 248 patients (experimental group: n = 126; control group: n = 122). PVC dislodgement was less frequent in the experimental group than in the control group. In the control group, 78.7% of patients required replacement of securing materials (costing 37 cents each time) and 13.1% required PVC replacement (costing 3.6 dollars each time), necessitating additional nursing time. No patients in the experimental group required replacement of the PVC or securing materials. Blisters were less common in the experimental group than in the control group (0% vs 9.84%, P < .001). No patients had limb edema. CONCLUSIONS: This new method of securing an analgesia pump line can reduce traction on the indwelling PVC, lowering the dislodgement rate.

Path Planning of Pattern Transfer Based on Dual-Operator and a Dual-Population Ant Colony Algorithm for Digital Mask Projection Lithography.

In the process of digital micromirror device (DMD) digital mask projection lithography, the lithography efficiency will be enhanced greatly by path planning of pattern transfer. This paper proposes a new dual operator and dual population ant colony (DODPACO) algorithm. Firstly, load operators and feedback operators are used to update the local and global pheromones in the white ant colony, and the feedback operator is used in the yellow ant colony. The concept of information entropy is used to regulate the number of yellow and white ant colonies adaptively. Secondly, take eight groups of large-scale data in TSPLIB as examples to compare with two classical ACO and six improved ACO algorithms; the results show that the DODPACO algorithm is superior in solving large-scale events in terms of solution quality and convergence speed. Thirdly, take PCB production as an example to verify the time saved after path planning; the DODPACO algorithm is used for path planning, which saves 34.3% of time compared with no path planning, and is about 1% shorter than the suboptimal algorithm. The DODPACO algorithm is applicable to the path planning of pattern transfer in DMD digital mask projection lithography and other digital mask lithography.

Novel circular RNA expression profile of uveal melanoma revealed by microarray.

OBJECTIVE: The present study aimed to investigate circular RNA (circRNA) expression in uveal melanoma (UM). METHODS: First, we used microarray to compare the expression profiles of circRNA in five UM samples and five normal uvea tissues. Next, bioinformatics analyses, including gene ontology (GO) analysis and pathway analysis, were applied to study these differentially expressed circRNAs to predict pathogenic pathways that may be involved. Quantitative real-time polymerase chain reaction (qRT-PCR) in 20 UM samples and 20 normal uvea samples was used to confirm the circRNA expression profiles obtained from the microarray data. Finally, we analyzed the interaction between validated circRNAs and their potential cancer-associated miRNA targets. RESULTS: In total, 50,579 circRNAs [fold change (FC) ≥2.0; P<0.05], including 20,654 up-regulated and 29,925 down-regulated circRNAs, were identified as differentially expressed between UM tissues and normal uvea tissues. We used qRT-PCR to verify seven dysregulated circRNAs indicated by the microarray data, including hsa_circ_0119873, hsa_circ_0128533, hsa_circ_0047924, hsa_circ_0103232, hsa-circRNA10628-6, hsa_circ_0032148 and hsa_circ_0133460, which may be promising candidates to study future molecular mechanisms. CONCLUSIONS: This study explored, for the first time, the abnormal expression of circRNAs in UM and described the expression profile of circRNAs, providing a new potential target for the mechanism of UM and future treatment of UM.

Up-regulation of carcinoembryonic antigen-related cell adhesion molecule 1 in gastrointestinal cancer and its clinical relevance.

Serum carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is dysregulated in various malignant tumors and has been associated with tumor progression. However, the expression and regulatory mechanisms of serum CEACAM1 in gastrointestinal cancer are still unclear. The expression ratio of the CEACAM1-L and CEACAM1-S isoforms has seldom been investigated in gastrointestinal cancer. In this study, we intended to explore the expression and diagnostic value of CEACAM1 in gastrointestinal cancer. Serum CEACAM1 levels were measured by enzyme-linked immunosorbent assay. The protein expression and distribution of CEACAM1 in tumors were examined by immunohistochemical staining. The expression patterns and ratio of CEACAM1-L/S were analyzed by reverse transcription-polymerase chain reaction. The results showed that serum CEACAM1 levels were significantly higher in cancer patients than in healthy controls. CEACAM1 was found in secreted forms within the neoplastic glands, and its expression was more intense at the tumor invasion front. The CEACAM1-L/S (L:S) ratios were up-regulated during tumorigenesis. Our data suggest that the serum level of CEACAM1 may be used to discriminate gastrointestinal cancer patients from health controls.

Two proteins of Cucurbit chlorotic yellows virus, P59 and P9, are self-interacting.

The yeast two-hybrid (Y2H) assay, a powerful tool for identifying protein-protein interactions, has been widely used to study viral protein interactions and to elucidate the functions of viral proteins. In this study, Cucurbit chlorotic yellows virus-encoded proteins were investigated by Y2H assays in all possible pairwise combinations, and the self-interactions of P59 and P9 were detected. The interacting domains of P59 and P9 were identified using vectors carrying an activation domain fused to a truncated version of P59 or P9. We found that the middle region (amino acids 173-344) of P59 was necessary for this self-interaction, while three different truncated versions of P9 showed no interaction with full-length P9. This is the first report of the self-interaction of P59 in the genus Crinivirus.

LDCT image denoising algorithm based on two-dimensional variational mode decomposition and dictionary learning.

Low-dose X-CT scanning method effectively reduces radiation hazards, however, reducing the radiation dose will introduce noise and artifacts during the projection process, resulting in a decrease in the quality of the reconstructed image. To address this problem, we combined 2D variational modal decomposition and dictionary learning. We proposed a low-dose CT (LDCT) image denoising algorithm based on an improved K-SVD algorithm with image decomposition. The dictionary obtained by K-SVD training lacks consideration of image structure information. To address this problem, we employ the two-dimensional variational mode decomposition (2D-VMD) method to decompose the image into distinct modal components. Through the adaptive learning of dictionaries based on the characteristics of each modal component, independent denoising processing is applied to each component, avoiding the loss of structural and detailed information in the image. In addition, we introduce the regularized orthogonal matching pursuit algorithm (ROMP) and dictionary atom optimization method to improve the sparse representation ability of the dictionary and reduce the impact of noise atoms on denoising performance. The experiments show that the proposed method outperforms other denoising methods regarding peak signal-to-noise ratio and structural similarity. The proposed method maintains the denoised image details and structural information while removing LDCT image noise and artifacts. The image quality after denoising is significantly improved and facilitates more accurate detection and analysis of lesion areas.

Fast high quality computational ghost imaging based on saliency variable sampling detection.

Fast computational ghost imaging with high quality and ultra-high-definition resolution reconstructed images has important application potential in target tracking, biological imaging and other fields. However, as far as we know, the resolution (pixels) of the reconstructed image is related to the number of measurements. And the limited resolution of reconstructed images at low measurement times hinders the application of computational ghost imaging. Therefore, in this work, a new computational ghost imaging method based on saliency variable sampling detection is proposed to achieve high-quality imaging at low measurement times. This method physically variable samples the salient features and realizes compressed detection of computational ghost imaging based on the salient periodic features of the bucket detection signal. Numerical simulation and experimental results show that the reconstructed image quality of our method is similar to the compressed sensing method at low measurement times. Even at 500 (sampling rate 0.76 % ) measurement times, the reconstructed image of the method still has the target features. Moreover, the 2160 × 4096 (4K) pixels ultra-high-definition resolution reconstructed images can be obtained at only a sampling rate of 0.11 % . This method has great potential value in real-time detection and tracking, biological imaging and other fields.

The mechanism underlying the effects of the cell surface ATP synthase on the regulation of intracellular acidification during acidosis.

The F1F0 ATP synthase has recently become the focus of anti-cancer research. It was once thought that ATP synthases were located strictly on the inner mitochondrial membrane; however, in 1994, it was found that some ATP synthases localized to the cell surface. The cell surface ATP synthases are involved in angiogenesis, lipoprotein metabolism, innate immunity, hypertension, the regulation of food intake, and other processes. Inhibitors of this synthase have been reported to be cytotoxic and to induce intracellular acidification. However, the mechanisms by which these effects are mediated and the molecular pathways that are involved remain unclear. In this study, we aimed to determine whether the inhibition of cell proliferation and the induction of cell apoptosis that are induced by inhibitors of the cell surface ATP synthase are associated with intracellular acidification and to investigate the mechanism that underlines the effects of this inhibition, particularly in an acidic tumor environment. We demonstrated that intracellular acidification contributes to the cell proliferation inhibition that is mediated by cell surface ATP synthase inhibitors, but not to the induction of apoptosis. Intracellular acidification is only one of the mechanisms of ecto-ATP synthase-targeted antitumor drugs. We propose that intracellular acidification in combination with the inhibition of cell surface ATP generation induce cell apoptosis after cell surface ATP synthase blocked by its inhibitors. A better understanding of the mechanisms activated by ecto-ATP synthase-targeted cancer therapies may facilitate the development of potent anti-tumor therapies, which target this enzyme and do not exhibit clinical limitations.

Clinical and experimental studies regarding the expression and diagnostic value of carcinoembryonic antigen-related cell adhesion molecule 1 in non-small-cell lung cancer.

BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in non-small-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC. METHODS: The expression of the serum CEACAM1 was determined by enzyme-linked immunosorbent assay. The protein expression and the location of CEACAM1 in tumours were observed by immunohistochemical staining. The CEACAM1 mRNA levels in tumour and normal adjacent tissues were measured using quantitative real-time PCR, and the expression patterns and the rate of CEACAM1-S and CEACAM1-L were analysed by reverse transcription-PCR. RESULTS: Serum CEACAM1 levels were significantly higher in NSCLC patients compared with that from normal healthy controls (P <0.0001). 17 patients (81%) among 21 showed high expression of CEACAM1 by immunohistochemical staining. Although no significant differences were found between tumour and normal tissues on mRNA expression levels of CEACAM1 (P >0.05), the CEACAM1-S and the CEACAM1-S/L (S: L) ratios were significantly higher in tumour than normal tissues (P <0.05). CONCLUSIONS: Our data indicated that the serum levels of CEACAM1 could discriminate lung cancer patients from health donors and that CEACAM1 might be a useful marker in early diagnosis of NSCLC. Moreover, our results showed that the expression patterns of CEACAM1 isoforms could be changed during oncogenesis, even when total CEACAM1 in tumour tissues did not show significant changes. Our study suggested that the expression ratios of CEACAM1-S/CEACAM1-L might be a better diagnostic indicator in NSCLC than the quantitative changes of CEACAM1.

[The cause and efficacy of benign tracheal stenosis].

OBJECTIVE: To analysis the causes of benign tracheal stenosis and evaluate the curative effect of intraluminal bronchoscopic treatment. METHODS: 158 patients with benign tracheal stenosis in our hospital from September 2005 to September 2012 were collected to retrospectively analysis the causes and clinic features of tracheal stenosis. Interventional treatments through bronchoscopy were used to treat the benign tracheal stenosis and the curative effects were evaluated. RESULTS: 158 cases of benign tracheal stenosis were recruited to our study, 69.6% of them were young and middle-aged. The main causes of benign tracheal stenosis were as follows: secondary to postintubation or tracheotomy in 61.4% (97/158), tuberculosis in 16% (26/158), benign tumor in 5.1% (8/158) and other 27 cases. 94.3% patients improved in symptoms with alleviation immediately after bronchoscopic treatment, the average tracheal diameter increased form (4.22 ± 2.06) mm to (10.16 ± 2.99) mm (t = 21.48, P < 0.01), dyspnea index decreased from 2.29 ± 0.75 to 0.63 ± 0.67 (t = 19.85, P < 0.01). The recurrence rate in 1 and 3 month after interventional treatment were 38.3% and 26.8%, respectively. CONCLUSION: The cases of benign tracheal stenosis were increasing year by year. The most common cause of benign tracheal stenosis was postintubation and tracheotomy. Interventional treatments through bronchoscopy is effective in treating benign tracheal stenosis, but repeated interventional procedures may be required to maintain the favorable long-term effects.

Increasing the Light Extraction Efficiency of Organic Light-Emitting Devices by Electrochemically Corroded Patterned Substrates.

A substrate with microstructure can increase the light extraction efficiency of OLEDs. However, the present preparation methods for micro- and nanostructures are not suited for broad-area manufacturing. In this research, we suggested an electrochemical etching approach to patterning Si substrates and effectively generated a vast area of micro-/nanostructures on the surface of Si. We created OLEDs using this patterned substrate. It was discovered through this study that when the current density is 100 mA/cm2, the brightness increases by 1.67 times and the efficiency increases by 1.43 times, over a planar equivalent. In the future, this electrochemical etching process for patterned silicon substrates might give rise to a new approach to the large-scale manufacture of microstructured silicon substrates.

GATR: A Road Network Traffic Violation Prediction Method Based on Graph Attention Network.

Prediction of traffic violations plays a key role in transportation safety. Combining with deep learning to predict traffic violations has become a new development trend. However, existing methods are based on regular spatial grids which leads to a fuzzy spatial expression and ignores the strong correlation between traffic violations and road network. A spatial topological graph can express the spatiotemporal correlation more accurately and then improve the accuracy of traffic violation prediction. Therefore, we propose a GATR (graph attention network based on road network) model to predict the spatiotemporal distribution of traffic violations, which adopts a graph attention network model combined with historical traffic violation features, external environmental features, and urban functional features. Experiments show that the GATR model can express the spatiotemporal distribution pattern of traffic violations more clearly and has higher prediction accuracy (RMSE = 1.7078) than Conv-LSTM (RMSE = 1.9180). The verification of the GATR model based on GNN Explainer shows the subgraph of the road network and the influence degree of features, which proves GATR is reasonable. GATR can provide an important reference for prevention and control of traffic violations and improve traffic safety.

Effects and Mechanisms of Cu Species in Fe-MOFs on Fenton-Like Catalytic Activity and Stability.

Fe-based MOFs (Fe-MOFs) are deemed promising Fenton-like catalysts due to their well-developed pores and accessible active sites. However, their inferior catalytic activity, iron leaching, and low H2O2 utilization always hinder their application as Fe-based MOF catalysts. In this work, we manipulated the structure of Fe-oxo nodes in MIL-88B(Fe) via a CuI species substitution method, affording a mixed-valence (Cu-incorporated Fe-MOFs) with highly improved Fenton-like performance. It is found that the CuI serves as a shuttle to promote transfer between FeII/FeIII, inducing the formation of a larger amount of stable FeII sites, which was proven by experimental and DFT calculation results. A linear relationship was observed for the Fenton-like performance and the amount of CuI species for the catalysts. The corresponding value of the •OH formation is 2.17 eV for Cu-incorporated MIL-88B(Fe), which is significantly lower than that of MIL-88B(Fe) (2.69 eV). Meanwhile, the enriched CuI species suppress Fe species leaching during the catalytic reaction. The Fe-ion leakage of 0.4Cu@MIL-88B is very tiny (0.01-0.03 mg/L), significantly less than that of MIL-88B (2.00-3.02 mg/L). At the same time, H2O2 utilization for 0.4Cu@ MIL-88B(Fe) is 88%, which is almost 4.4 times that of pure MIL-88B(Fe). This work provides insights into the rational design of Fe-MOFs as promising Fenton-like catalysts for wastewater treatment.

Mechanism of assembly of snRNP cores assisted by ICln and the SMN complex in fission yeast.

The spliceosomal snRNP cores, each comprised of a snRNA and a seven-membered Sm ring (D1/D2/F/E/G/D3/B), are assembled by twelve chaperoning proteins in human. However, only six assembly-assisting proteins, ICln and the SMN complex (SMN/Gemin2/Gemin6-8), have been found in Schizosaccharomyces pombe (Sp). Here, we used recombinant proteins to reconstitute the chaperone machinery and investigated the roles of these proteins systematically. We found that, like the human system, the assembly in S. pombe requires ICln and the SMN complex sequentially. However, there are several significant differences. For instance, h_F/E/G forms heterohexamers and heterotrimers, while Sp_F/E/G only forms heterohexamers; h_Gemin2 alone can bind D1/D2/F/E/G, but Sp_Gemin2 cannot. Moreover, we found that Sp_Gemin2 is essential using genetic approaches. These mechanistic studies reveal that these six proteins are necessary and sufficient for Sm core assembly at the molecular level, and enrich our understanding of the chaperone systems in species variation and evolution.

The accuracy of simplified calculation of mechanical power: a simulation study.

Background: Mechanical ventilation (MV) is an important life-saving method in the intensive care unit (ICU). A lower mechanical power (MP) is associated with a better MV strategy. However, traditional MP calculating methods are complicated, and algebraic formulas seem to be rather practical. The aim of the present study was to compare the accuracy and application of different algebraic formulas calculating MP. Methods: A lung simulator, TestChest, was used to simulate pulmonary compliance variations. Using the TestChest system software, the parameters, including compliance and airway resistance, were set to simulate various acute respiratory distress syndrome (ARDS) lungs. Ventilator was also set to volume- and pressure-controlled modes with various parameter values (respiratory rate, RR, time of inspiration, Tinsp, positive end-expiratory pressure, PEEP) to ventilate the simulated lung of ARDS (with various respiratory system compliance, Crs). For the lung simulator, resistance of airway (Raw) was fixed to 5 cmH2O/L/s. Crs below lower inflation point (LIP) or above upper inflation point (UIP) was set to 10 mL/cmH2O. The reference standard geometric method was calculated offline with a customized software. Three algebraic formulas for volume-controlled and three for pressure-controlled were used to calculate MP. Results: The performances of the formulas were different, although the derived MP were significantly correlated with that derived from the reference method (R2>0.80, P<0.001). Under volume-controlled ventilation, medians of MP calculated with one equation was significantly lower than that with the reference method (P<0.001). Under pressure-controlled ventilation, median of MP calculated with two equations were significantly higher (P<0.001). The maximum difference was over 70% of the MP value calculated with the reference method. Conclusions: The algebraic formulas may introduce considerably large bias under the presented lung conditions, especially in moderate to severe ARDS. Cautious is required when selecting adequate algebraic formulas to calculate MP based on the formula's premises, ventilation mode, and patients' status. In clinical practice, the trend rather than the value of MP calculated by formulas should require more attention.

Physiological and transcriptomic analyses reveal that phytohormone pathways and glutathione metabolism are involved in the arsenite toxicity response in tomatoes.

The main forms of inorganic arsenic (As) in soil are arsenate [As(V)] and arsenite [As(III)]. Both forms inhibit plant growth. Here, we investigate the effects of As(III) toxicity on the growth of tomatoes by integrating physiological and transcriptomic analyses. As(III) toxicity induces oxidative damage, inhibits photosynthetic efficiency, and reduces soluble sugar levels. As(III) toxicity leads to reductions in auxin, cytokinin and jasmonic acid contents by 29 %, 39 % and 55 %, respectively, but leads to increases in the ethylene precursor 1-amino-cyclopropane carboxylic acid, abscisic acid and salicylic acid contents in roots, by 116 %, 79 % and 39 %, respectively, thereby altering phytohormone signalling pathways. The total glutathione, reduced glutathione (GSH) and oxidized glutathione (GSSG) contents are reduced by 59 %, 49 % and 94 % in roots; moreover, a high GSH/GSSG ratio is maintained through increased glutathione reductase activity (increased by 214 %) and decreased glutathione peroxidase activity (decreased by 40 %) in the roots of As(III)-treated tomato seedlings. In addition, As(III) toxicity affects the expression of genes related to the endoplasmic reticulum stress response. The altered expression of aquaporins and ABCC transporters changes the level of As(III) accumulation in plants. A set of hub genes involved in modulating As(III) toxicity responses in tomatoes was identified via a weighted gene coexpression network analysis. Taken together, these results elucidate the physiological and molecular regulatory mechanism underlying As(III) toxicity and provide a theoretical basis for selecting and breeding tomato varieties with low As(III) accumulation. Therefore, these findings are expected to be helpful in improving food safety and to developing sustainable agricultural.

An investigation on the respiratory mechanics of mechanically ventilated patients during spontaneous breathing trials with enhanced low-level pressure support ventilation.

INTRODUCTION: Low-level pressure support ventilation (PSV) is most commonly adopted in spontaneous breathing trials (SBTs), and some have proposed setting the positive end-expiratory pressure (PEEP) to 0 cmH2 O in order to shorten the observation time of SBTs. This study aims to investigate the effects of two PSV protocols on the patients' respiratory mechanics. MATERIAL AND METHOD: A prospective randomized self-controlled crossover design was adopted in this study, which involved enrolling 30 difficult-to-wean patients who were admitted to the intensive care unit of the First Affiliated Hospital of Guangzhou Medical University between July 2019 and September 2021. Patients were subjected to the S group (pressure support: 8 cmH2 O, PEEP: 5 cmH2 O) and S1 group (PS: 8 cmH2 O, PEEP: 0 cmH2 O) for 30 min in a random order, and respiratory mechanics indices were dynamically monitored via a four-lumen multi-functional catheter with an integrated gastric tube. Among the 30 enrolled patients, 27 were successfully weaned. RESULT: The S group showed higher airway pressure (Paw), intragastric pressure (Pga) and airway pressure-time product (PTP) than the S1 group. The S group also showed a shorter inspiratory trigger delay, (93.80 ± 47.85) versus (137.33 ± 85.66) ms (P = 0.004); and fewer abnormal triggers, (0.97 ± 2.65) versus (2.67 ± 4.48) (P = 0.042) compared with the S1 group. Stratification based on the causes of mechanical ventilation revealed that under the S1 protocol, patients with chronic obstructive pulmonary disease (COPD) had a longer inspiratory trigger delay compared to both post-thoracic surgery (PTS) patients and patients with acute respiratory distress syndrome. Despite providing greater respiratory support, S group led to significant reductions in inspiratory trigger delay and less abnormal triggers compared to S1 group, especially among patients with chronic obstructive pulmonary disease. CONCLUSION: These findings suggest that the zero PEEP group was more likely to induce a higher number of patient-ventilator asynchronies in difficult-to-wean patients.