Early growth response factor 3 regulates coronary atherosclerosis through the NF-κB signaling pathway and VEGF expression.

AIM: The present study was conducted to measure the expression of early growth response factor 3 (Egr3), inflammatory cytokines (IL-1ß, IL-6), vascular endothelial growth factor (VEGF) and NF-κB in patients with coronary artery disease (CAD) to investigate the relationships of these molecules and Egr3 gene expression. METHODS: We recruited 132 CAD patients and 63 healthy individuals. The expression levels of Egr3, VEGF, p50 and p65 were measured by reverse transcription quantitative polymerase chain reaction and the levels of Egr3, IL-1ß and IL-6 in patients serum and in human coronary artery endothelial cells (HCAECs) were measured by enzyme-linked immunosorbent assay (ELISAs) in CAD patients. HCAECs were treated with ox-LDL to establish an in vitro atherosclerosis model. An oil red O staining assay was used to assess the lipid droplet formation. A colloidal external lumen formed by Matrigel was used to test the migration of HCAECs. The expression of Egr3, VEGF and NF-κB was determined by Western blotting. RESULTS: The levels of serum Egr3 and IL-6 in the severe stenosis group were greater than those in the mild stenosis group and controls (p < 0.05). The level of serum IL-1ß in the severe stenosis group was greater than that in the control group (p < 0.05). Moreover, Egr3 expression was positively associated with IL-6 levels (r= 0.55, p < 0.001), IL-1ß levels (r=0.21, p=0.004) and the Gensini score (r=0.20, p=0.02). We also found that Egr3 expression was significantly greater in CAD patients than that in controls. And its expression was highest in the mild patients. The expression of VEGF, P50 and P65 was also greater in CAD patients. In the in vitro experiment, we found that the inhibition of Egr3 expression significantly reduced the expression levels of p50, p65, IL-6 and CRP. Moreover, the inhibition of Egr3 expression significantly reduced the lipid droplet formation and decreased capability of lumen formation. CONCLUSIONS: In the pathogenesis of atherosclerosis, Egr3 gene expression may induce the expression of inflammatory factors and lipid droplet formation and lumen formation, which could promote the atherosclerosis development.

HIV-1 Molecular Networks and Pretreatment Drug Resistance at the Frontier of Yunnan Province, China.

The border areas of Yunnan Province in China are severely affected by human immunodeficiency virus (HIV). To investigate the risk of HIV transmission and assess the prevalence of pretreatment drug resistance (PDR) in the border area, blood samples were collected from individuals with newly reported HIV in 2021 in three border counties (Cangyuan, Gengma, and Zhenkang) in Yunnan Province. Among the 174 samples successfully genotyped, eight circulating recombinant forms (CRFs), two subtypes, and several unique recombinant forms (URFs) were identified. CRF08_BC (56.9%, 99/174), URFs (14.4%, 25/174), CRF01_AE (10.9%, 19/174), and CRF07_BC (8.0%, 14/174) were the main genotypes. CRF08_BC and URFs were detected more frequently in Chinese and Burmese individuals, respectively. CRF07_BC was found more frequently in men who have sex with men. The proportion of individuals detected in HIV-1 networks was only associated with case-reporting counties. When stratified by county, individuals aged ≤40 years in Cangyuan and ≥41 years in Gengma were more likely to be found in these networks. Furthermore, 93.8% (15/16) of the links in Cangyuan and 79.4% (50/63) of those in Gengma were located within their own counties. The prevalence of PDR to any antiretroviral drug, nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 10% (17/170), 0.6% (1/170), and 9.4% (16/170), respectively. The most frequent resistance-associated mutations (RAMs) were V179D/VD/E/T (22.9%, 39/170) and E138A/G/K/R (13.5%, 23/170). In the molecular networks, six clusters shared common RAMs. HIV-1 genetics has become more diverse in border areas. HIV-1 molecular network analysis revealed the different characteristics of the HIV-1 epidemic in the border counties. The prevalence of PDR showed an upward trend, and the PDR to NNRTIs was close to the public response threshold. These findings provide information for the development of AIDS prevention and treatment strategies.

Ag85B with c-di-AMP as mucosal adjuvant showed immunotherapeutic effects on persistent Mycobacterium tuberculosis infection in mice.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

Reconstruction of High Entropy Alloys on a Metal-Organic Framework Approaching Active Oxygen Reduction Electrocatalysts.

High-entropy alloys (HEAs) have garnered considerable attention as promising nanocatalysts for effectively utilizing Pt in catalysis toward oxygen reduction reactions due to their unique properties. Nonetheless, there is a relative dearth of attention regarding the structural evolution of HEAs in response to electrochemical conditions. In this work, we propose a thermal reduction method to synthesize high entropy nanoparticles by leveraging the confinement effect and abundant nitrogen-anchored sites provided by pyrolyzed metal-organic frameworks (MOFs). Notably, the prepared catalysts exhibit enhanced activity accompanied by structural reconstruction during electrochemical activation, approaching 1 order of magnitude higher mass activity compared to Pt/C in oxygen reduction. Atomic-scale structural characterization reveals that abundant defects and single atoms are formed during the activation process, contributing to a significant boost in the catalytic performance for oxygen reduction reactions. This study provides deep insights into surface reconstruction engineering during electrochemical operations, with practical implications for fuel cell applications.

Molecular Mechanism of Sevoflurane Affecting Fetal Nervous System's Development Through the GABAAR/Sirt 1 Pathway.

Objective: To investigate the molecular mechanism of sevoflurane affecting the development of the offspring's nervous system through the GABAAR/Sirt 1 pathway. Methods: Pregnant rats were obtained by mating females and males, and were randomly divided into 3 h sevoflurane (2.3% sevoflurane anesthesia for 3 h), 6 h sevoflurane (2.3% sevoflurane anesthesia for 6 h), Sirt-1 activator-SRT1720 (10 mg/kg SRT1720), 6 h sevoflurane+SRT1720 (10 mg/kg SRT1720) and control groups) group and control group, 31-day-old littermates were taken out and their learning and memory functions were examined by the water maze experiment; the heads were severed to remove the brains, and the kits were used to detect the levels of 5-HT and Ach in the brain tissue; the hippocampal tissues of the littermates were isolated, and neuronal damage in the hippocampal tissues was assessed by Nissen staining; neuronal apoptosis in the hippocampal tissues was detected by TUNEL staining; and GABAAR in the hippocampal tissues was detected by Western blot. GABAAR, Sirt-1, and apoptosis-related proteins (Caspase-3, BCL-2, BAX) in hippocampal tissue. Results: Compared with the control group, the 3 h sevoflurane group and the 6 h sevoflurane group neurons were arranged sparsely, the cells appeared to be swollen, the evasion latency, the apoptosis rate of neurons, the expression of Caspase-3, and BAX increased significantly, and the number of crossing the plateau, the level of 5-HT and Ach in the brain tissues, and the expression of GABAAR, Sirt-1, and BCL-2 were decreased significantly, and the differences existed between the groups (P < .5); compared with the 6 h sevoflurane group, neuronal morphological changes in the hippocampal tissue of the 6 h sevoflurane+SRT1720 group were improved, with a significant decrease in the evasion latency, neuronal apoptosis rate, expression of Caspase-3 and BAX, and a significant increase in the number of traversing platforms, brain tissue 5-HT, Ach level, GABAAR, Sirt-1, and BCL-2 expression (P < .5); compared with the SRT1720 group, the neurons in the 6 h sevoflurane + SRT1720 group were sparsely arranged, with a significant increase in evasion latency, neuronal apoptosis rate, caspase-3, BAX expression, and a significant decrease in the number of traversing platforms, brain tissue 5-HT, Ach level, GABAAR, Sirt-1, and BCL-2 expression (P < .5 ). Conclusion: Sevoflurane can affect the neurological development of rat offspring, which may be related to the inhibition of Sirt-1 expression.

Design optimization of groundwater circulation well based on numerical simulation and machine learning.

The optimal design of groundwater circulation wells (GCWs) is challenging. The key to purifying groundwater using this technique is its proficiency and productivity. However, traditional numerical simulation methods are limited by long modeling times, random optimization schemes, and optimization results that are not comprehensive. To address these issues, this study introduced an innovative approach for the optimal design of a GCW using machine learning methods. The FloPy package was used to create and implement the MODFLOW and MODPATH models. Subsequently, the formulated models were employed to calculate the characteristic indicators of the effectiveness of the GCW operation, including the radius of influence (R) and the ratio of particle recovery (Pr). A detailed collection of 3000 datasets, including measures of operational efficiency and key elements in machine learning, was meticulously compiled into documents through model execution. The optimization models were trained and evaluated using multiple linear regression (MLR), artificial neural networks (ANN), and support vector machines (SVM). The models produced by the three approaches exhibited notable correlations between anticipated outcomes and datasets. For the optimal design of circulating well parameters, machine learning methods not only improve the optimization speed, but also expand the scope of parameter optimization. Consequently, these models were applied to optimize the configuration of the GCW at a site in Xi'an. The optimal scheme for R (Q = 293.17 m3/d, a = 6.09 m, L = 7.28 m) and optimal scheme for Pr (Q = 300 m3/d, a = 3.64 m, L = 1 m) were obtained. The combination of numerical simulations and machine learning is an effective tool for optimizing and predicting the GCW remediation effect.

Genome-wide association studies identified OsTMF as a gene regulating rice seed germination under salt stress.

Introduction: Salt tolerance during seed germination is an important trait for direct seeding and low-cost rice production. Nevertheless, it is still not clear how seed germination under salt stress is regulated genetically. Methods: In this study, genome-wide association studies (GWAS) were performed to decipher the genetic basis of seed germination under salt stress using 541 rice varieties collected worldwide. Results and discussion: Three quantitative trait loci (QTLs) were identified including qGRG3-1 on chromosome 3, qGRG3-2 on chromosome 5, and qGRG4 on chromosome 4. Assessment of candidate genes in these loci for their responses to salt stress identified a TATA modulatory factor (OsTMF) in qGRG3-2. The expression of OsTMF was up-regulated in both roots and shoots after exposure to salt stress, and OsTMF knockout mutants exhibited delayed seed germination under salt stress. Haplotype analysis showed that rice varieties carrying OsTMF-Hap2 displayed elevated salt tolerance during seed germination. These results provide important knowledge and resources to improve rice seed germination under salt stress in the future.

Evaluation of antisense oligonucleotide therapy targeting Hsd17b13 in a fibrosis mice model.

Human genetic evidence suggests a protective role of loss-of-function variants in 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) for liver fibrotic diseases. Although there is limited preclinical experimental data on Hsd17b13 antisense oligonucleotide (ASO) or siRNA in a fibrosis model, several ASO and siRNA approaches are being tested clinically as potential therapies for nonalcoholic steatohepatitis (NASH). The aim of this study was to assess the therapeutic potential of Hsd17b13 ASO in a preclinical advanced NASH-like hepatic fibrosis in vivo model. In vitro testing on primary hepatocytes demonstrated that Hsd17b13 ASO exhibited strong efficacy and specificity for knockdown of the Hsd17b13 gene. In choline-deficient, L-amino acid-defined, HFD (CDAHFD)-induced steatotic and fibrotic mice, therapeutic administration of Hsd17b13 ASO resulted in a significant and dose-dependent reduction of hepatic Hsd17b13 gene expression. The CDAHFD group exhibited considerably elevated liver enzyme levels, hepatic steatosis score, hepatic fibrosis, and increased fibrotic and inflammatory gene expression, indicating an advanced NASH-like hepatic fibrosis phenotype. Although Hsd17b13 ASO therapy significantly affected hepatic steatosis, it had no effect on hepatic fibrosis. Our findings demonstrate, for the first time, that Hsd17b13 ASO effectively suppressed Hsd17b13 gene expression both in vitro and in vivo, and had a modulatory effect on hepatic steatosis in mice, but did not affect fibrosis in the CDAHFD mouse model of NASH.

Intratumoural microbiota: a new frontier in cancer development and therapy.

Human microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological and pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms, which have been confirmed to be closely related to oncogenesis. The concept of intratumoural microbiota was subsequently proposed. Microbiota could colonise tumour tissues through mucosal destruction, adjacent tissue migration, and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment. Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune destruction, regulating metabolism, and activating invasion and metastasis. Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging, new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination. In addition, interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy, especially immunotherapy, although there are some inevitable challenges. Here, we aim to provide an extensive review of the concept, development history, potential sources, heterogeneity, and carcinogenic mechanisms of intratumoural microorganisms, explore the potential role of microorganisms in tumour prognosis, and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.

CoreSNP: an efficient pipeline for core marker profile selection from genome-wide SNP datasets in crops.

BACKGROUND: DNA marker profiles play a crucial role in the identification and registration of germplasm, as well as in the distinctness, uniformity, and stability (DUS) testing of new plant variety protection. However, selecting minimal marker sets from large-scale SNP dataset can be challenging to distinguish a maximum number of samples. RESULTS: Here, we developed the CoreSNP pipeline using a "divide and conquer" strategy and a "greedy" algorithm. The pipeline offers adjustable parameters to guarantee the distinction of each sample pair with at least two markers. Additionally, it allows datasets with missing loci as input. The pipeline was tested in barley, soybean, wheat, rice and maize. A few dozen of core SNPs were efficiently selected in different crops with SNP array, GBS, and WGS dataset, which can differentiate thousands of individual samples. The core SNPs were distributed across all chromosomes, exhibiting lower pairwise linkage disequilibrium (LD) and higher polymorphism information content (PIC) and minor allele frequencies (MAF). It was shown that both the genetic diversity of the population and the characteristics of the original dataset can significantly influence the number of core markers. In addition, the core SNPs capture a certain level of the original population structure. CONCLUSIONS: CoreSNP is an efficiency way of core marker sets selection based on Genome-wide SNP datasets of crops. Combined with low-density SNP chip or genotyping technologies, it can be a cost-effective way to simplify and expedite the evaluation of genetic resources and differentiate different crop varieties. This tool is expected to have great application prospects in the rapid comparison of germplasm and intellectual property protection of new varieties.

Preliminary study of donor volume changes after dual-graft liver transplantation in rats.

Dual-graft liver transplantation (DGLT) expands the pool of donors, ensures the safety of the donors, and treats a potential small for size syndrome (SFSS). However, some of the recipient graft showed atrophy. The cause and mechanism of the unbalanced proliferation and atrophy of dual grafts after clinical DGLT have not been clarified. We established and optimized the rat model of DGLT to explore the causes of growth unbalance. Continuously and dynamically observed bilateral graft volume and portal vein blood flow change by magnetic resonance imaging (MRI) and ultrasound (US). We detected liver function indexes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL). Liver samples from receptors were obtained for morphology, and apoptosis was measured by RT-PCR and western blot. Optimization of the model improved the 7-day survival rate from former 58.3% to 87.5%, and the 30-day survival rate was 68.8%. The volume of the right graft gradually increased, and the left graft atrophied during the 30-day observation period. The portal blood flow of the left graft gradually decreased until the 30th day (0.13 ± 0.01 ml/s) compared with the sham group (0.63 ± 0.05 ml/s), and the right graft significantly increased on the 30th day (0.75 ± 0.11ml/s). The liver function initially increased and then recovered. The total volume (12.52 ± 1.60 ml vs 4.47 ± 0.08 ml) and weight (12.09 ± 1 g vs 4.91 ± 0.18 g) of the graft increased significantly compared to pre-transplantation and reached the level of the sham operation group on the 30th day. The volume and weight of the right graft increased more than those of the left graft (P < 0.05). There was more inflammatory cell infiltration in the left graft, and the right graft had obvious proliferation of hepatocytes and mature bile duct cells. Left grafts were more prone to apoptosis than right grafts (P < 0.05). In conclusion, growth of the right graft is superior to the left; after double liver transplantation, perfusion blood flow and apoptosis may be the reason contributing to the volume differences in dual grafts.

Characterization and genome analysis of Neobacillus mesonae NS-6, a ureolysis-driven strain inducing calcium carbonate precipitation.

In this study, a highly promising bacterium was isolated from sandstone oil in the Ordos Basin, named strain NS-6 which exhibited exceptional urease production ability and demonstrated superior efficiency in inducing the deposition of calcium carbonate (CaCO3). Through morphological and physiochemical characteristics analysis, as well as 16S rRNA sequencing, strain NS-6 was identified as Neobacillus mesonae. The activity of urease and the formation of CaCO3 increased over time, reaching a maximum of 7.9 mmol/L/min and 184 mg (4.60 mg/mL) respectively at 32 h of incubation. Scanning Electron Microscopy (SEM) revealed CaCO3 crystals ranging in size from 5 to 6 µm, and Energy Dispersive X-ray (EDX) analysis verified the presence of calcium, carbon, and oxygen within the crystals. X-ray Diffraction (XRD) analysis further confirmed the composition of these CaCO3 crystals as calcite and vaterite. Furthermore, the maximum deposition of CaCO3 by strain NS-6 was achieved using response surface methodology (RSM), amounting to 193.8 mg (4.845 mg/mL) when the concentration of calcium ions was 0.5 mmol/L supplemented with 0.9 mmol/L of urea at pH 8.0. Genome-wide analysis revealed that strain NS-6 possesses a chromosome of 5,736,360 base pairs, containing 5,442 predicted genes, including 3,966 predicted functional genes and 1,476 functionally unknown genes. Genes like ureA, ureB, and ureC related to urea catabolism were identified by gene annotation, indicating that strain NS-6 is a typical urease-producing bacterium and possesses a serial of genes involved in metabolic pathways that mediated the deposition of CaCO3 at genetic level.

Lipid metabolism of plasma-derived small extracellular vesicles in COVID-19 convalescent patients.

The coronavirus disease 2019 (COVID-19), which affects multiple organs, is causing an unprecedented global public health crisis. Most COVID-19 patients recover gradually upon appropriate interventions. Viruses were reported to utilize the small extracellular vesicles (sEVs), containing a cell-specific cargo of proteins, lipids, and nucleic acids, to escape the attack from the host's immune system. This study aimed to examine the sEVs lipid profile of plasma of recovered COVID-19 patients (RCs). Plasma sEVs were separated from 83 RCs 3 months after discharge without underlying diseases, including 18 recovered asymptomatic patients (RAs), 32 recovered moderate patients (RMs), and 33 recovered severe and critical patients (RSs), and 19 healthy controls (HCs) by Total Exosome Isolation Kit. Lipids were extracted from sEVs and then subjected to targeted liquid chromatography-mass spectrometry. The size, concentration, and distribution of sEVs did not differ in RCs and HCs as validated by transmission electron microscopy, nanoparticle tracking analysis, and immunoblot analysis. Fifteen subclasses of 508 lipids were detected in plasma sEVs from HCs, RAs, RMs, and RSs, such as phosphatidylcholines (PCs) and diacylglycerols (DAGs), etc. Total lipid intensity displayed downregulation in RCs compared with HCs. The relative abundance of DAGs gradually dropped, whereas PCs, lysophosphatidylcholines, and sphingomyelins were higher in RCs relative to HCs, especially in RSs. 88 lipids out of 241 in sEVs of RCs were significantly different and a conspicuous increase was revealed with disease status. The sEVs lipids alternations were found to be significantly correlated with the clinical indices in RCs and HCs, suggesting that the impact of COVID-19 on lipid metabolism lingered for a long time. The lipid abnormalities bore an intimate link with glycerophospholipid metabolism and glycosylphosphatidylinositol anchor biosynthesis. Furthermore, the lipidomic analysis showed that RCs were at higher risk of developing diabetes and sustaining hepatic impairment. The abnormality of immunomodulation in RCs might still exist. The study may offer new insights into the mechanism of organ dysfunction and help identify novel therapeutic targets in the RCs.

Using molecular network analysis to understand current HIV-1 transmission characteristics in an inland area of Yunnan, China.

HIV-1 molecular surveillance provides a new approach to explore transmission risks and targeted interventions. From January to June 2021, 663 newly reported HIV-1 cases were recruited in Zhaotong City, Yunnan Province, China. The distribution characteristics of HIV-1 subtypes and HIV-1 molecular network were analysed. Of 542 successfully subtyped samples, 12 HIV-1 strains were identified. The main strains were CRF08_BC (47.0%, 255/542), CRF01_AE (17.0%, 92/542), CRF07_BC (17.0%, 92/542), URFs (8.7%, 47/542), and CRF85_BC (6.5%, 35/542). CRF08_BC was commonly detected among Zhaotong natives, illiterates, and non-farmers and was mostly detected in Zhaoyang County. CRF01_AE was frequently detected among married and homosexual individuals and mostly detected in Weixin and Zhenxiong counties. Among the 516 pol sequences, 187 (36.2%) were clustered. Zhaotong natives, individuals aged ≥60 years, and illiterate individuals were more likely to be found in the network. Assortativity analysis showed that individuals were more likely to be genetically associated when stratified by age, education level, occupation, and reporting area. The genetic diversity of HIV-1 reflects the complexity of local HIV epidemics. Molecular network analyses revealed the subpopulations to focus on and the characteristics of the risk networks. The results will help optimise local prevention and control strategies.

Effect of Ultrasound-guided Erector Spinae Plane Block on Recovery After Laparoscopic Sleeve Gastrectomy in Patients With Obesity: A Randomized Controlled Trial.

PURPOSE: Previous research has not evaluated the potential effect of erector spinae plane block (ESPB) on quality of recovery (QoR) after laparoscopic sleeve gastrectomy. Therefore, we investigated the effect of an ultrasound-guided ESPB performed on patients with obesity who have undergone laparoscopic sleeve gastrectomy, measured using the 15-item QoR (QoR-15) scale. METHODS: A total of 172 patients were enrolled in the study who were aged 18 to 65 years, had a body mass index ≥30 kg/m², were classified as having American Society of Anaesthesiologists physical status Ⅱ to Ⅲ, and had undergone laparoscopic sleeve gastrectomy. The patients were randomly divided into an ESPB group and a sham group (treated with normal saline). The primary outcome was the QoR-15 score, measured using the questionnaire 24 and 48 hours after surgery. The secondary outcomes were postoperative pain score, postoperative cumulative analgesic drug consumption, number of patient-controlled analgesia (PCA) requests, rate of rescue analgesia required at 48 hours, incidence of respiratory complications, and nerve block-related complications. The time of discharge from the postanesthesia care unit, postoperative activity, and length of stay at the hospital were also recorded. FINDINGS: There was no significant difference in the global QoR-15 scores 24 and 48 hours after the operation. However, the groups' subdimension scores for the emotional state in QoR-15 at 24 and 48 hours after surgery were statistically different (P < 0.05). Meanwhile, patients in the ESPB group who indicated they were "feeling rested" at 24 and 48 hours after surgery and "having a feeling of general well-being" at 24 hours after surgery were significantly better than those in the sham group (P < 0.05). Compared with the sham group, participants in the ESPB group had lower resting pain scores at 6 and 12 hours after surgery and lower movement pain scores at 6, 12, 24, and 36 hours after surgery (P < 0.05). There was no statistical difference between the groups in postoperative cumulative analgesic drug consumption, number of PCA requests, incidence of respiratory complications, time of discharge from the postanesthesia care unit, or postoperative activity. IMPLICATIONS: Our results indicate that a single ESPB does not improve the global QoR-15 scores after laparoscopic sleeve gastrectomy. However, the visual analog scale score for postoperative pain is reduced.

Efficacy of hyperthermic intrathoracic chemotherapy for initially diagnosed lung cancer with symptomatic malignant pleural effusion.

Initially diagnosed malignant pleural effusion (MPE) has different systematic treatments, and defining the best drainage regimen according to the responsiveness of MPE to different systematic treatments is important. This study compared the efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) and pleural catheter drainage (IPCD) for initially diagnosed lung cancer with symptomatic MPE. We retrospectively reviewed the medical records of initially diagnosed lung cancer patients with symptomatic MPE between January 2018 and May 2022. The patients were treated with IPCD or HITHOC for local control of MPE after diagnosis. Systematic regimens were conducted during 1 month according to guidelines after local treatment. Intrathoracic MPE progression-free survival (iPFS) and overall survival (OS) were calculated, Univariate and multivariable Cox-regression were used to identify factors associated with iPFS and OS. A total of 33 patients were evaluated; 10 (30.3%) patients received IPCD, and 23 (69.7%) patients received HITHOC. No difference in the MPE control rate at 1 month was found between the IPCD group (90%) and HITHOC group (95.7%). However, this control rate was significantly higher in the HITHOC group (69.6%) than in the IPCD group (30%) at 3 months (P = 0.035). Multivariate analysis showed that receiving tyrosine kinase inhibitors (TKIs) or chemotherapy was a significant protective factor for iPFS (HR = 0.376, 95% CI 0.214-0.659, P = 0.007) and OS (HR = 0.321, 95% CI 0.174-0.594, P < 0.001). According to subgroup analysis, among patients treated with TKIs, those who received HITHOC had longer iPFS and OS than those who received IPCD (P = 0.011 and P = 0.002, respectively), but this difference was not found in the palliative care subgroup. Moreover, no patients treated with chemotherapy showed reaccumulation of MPE. Systematic TKIs or chemotherapy prolonged iPFS and OS for those initially diagnosed with lung cancer with symptomatic MPE. HITHOC prolonged iPFS and OS for those treated with systematic TKIs.

Virtual Pain Unit Is Associated with Improvement of Postoperative Analgesia Quality: A Retrospective Single-Center Clinical Study.

INTRODUCTION: Acute postoperative pain is a major concern among surgical patients. Thus, this study established a new acute pain management model and compared the effects of the acute pain service (APS) model in 2020 and the virtual pain unit (VPU) model in 2021 on postoperative analgesia quality. METHODS: This retrospective, single-center clinical study involved 21,281 patients from 2020 to 2021. First, the patients were grouped on the basis of their pain management model (APS and VPU). The incidence of moderate to severe postoperative pain (MSPP) [numeric rating scale (NRS) score ≥ 5], postoperative nausea and vomiting (PONV), and postoperative dizziness were recorded. RESULTS: The VPU group recorded significantly lower MSPP incidence (1-12 months), PONV, and postoperative dizziness (1-10 months and 12 months) compared with the APS group. In addition, the annual average incidence of MSPP, PONV, and postoperative dizziness in the VPU group was significantly lower than in the APS group. CONCLUSIONS: The VPU model reduces the incidence of moderate to severe postoperative pain, nausea, vomiting, and dizziness; hence, it is a promising acute pain management model.

Application of molecular dynamics simulation in self-assembled cancer nanomedicine.

Self-assembled nanomedicine holds great potential in cancer theragnostic. The structures and dynamics of nanomedicine can be affected by a variety of non-covalent interactions, so it is essential to ensure the self-assembly process at atomic level. Molecular dynamics (MD) simulation is a key technology to link microcosm and macroscale. Along with the rapid development of computational power and simulation methods, scientists could simulate the specific process of intermolecular interactions. Thus, some experimental observations could be explained at microscopic level and the nanomedicine synthesis process would have traces to follow. This review not only outlines the concept, basic principle, and the parameter setting of MD simulation, but also highlights the recent progress in MD simulation for self-assembled cancer nanomedicine. In addition, the physicochemical parameters of self-assembly structure and interaction between various assembled molecules under MD simulation are also discussed. Therefore, this review will help advanced and novice researchers to quickly zoom in on fundamental information and gather some thought-provoking ideas to advance this subfield of self-assembled cancer nanomedicine.