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Objective The aim of this study was to identify the expression of miRNA and lymphocyte subsets in the blood of gastric cancer (GC) patients, elucidate their clinical significance in GC, and establish novel biomarkers for the early diagnosis and prognosis of GC. Methods The expression of miRNAs in the serum of GC patients was screened using second-generation sequencing and detected using qRT-PCR. The correlation between miRNA expression and clinicopathological characteristics of GC patients was analyzed, and molecular markers for predicting cancer were identified. Additionally, flow cytometry was used to detect the proportion of lymphocyte subsets in GC patients compared to healthy individuals. The correlations between differential lymphocyte subsets, clinicopathological features of GC patients, and their prognosis were analyzed statistically. Results The study revealed that hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were expressed at lower levels in the blood of GC patients, which is consistent with miRNA-seq findings. The AUC values of hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were found to be effective predictors of GC occurrence. Additionally, hsa-miR-296-5p was found to be negatively correlated with CA724. Furthermore, hsa-miR-1306-5p, hsa-miR-3173-5p, and hsa-miR-296-5p were found to be associated with the stage of the disease and were closely linked to the clinical pathology of GC. The lower the levels of these miRNAs, the greater the clinical stage of the tumor and the worse the prognosis of gastric cancer patients. Finally, the study found that patients with GC had lower absolute numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and lymphocytes compared to healthy individuals. The quantity of CD4+ T lymphocytes and the level of the tumor marker CEA were shown to be negatively correlated. The ROC curve and multivariate logistic regression analysis demonstrated that lymphocyte subsets can effectively predict gastric carcinogenesis and prognosis. Conclusion These miRNAs such as hsa-miR-1306-5p, hsa-miR-3173-5p, hsa-miR-296-5p and lymphocyte subsets such as the absolute numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, lymphocytes are down-regulated in GC and are closely related to the clinicopathological characteristics and prognosis of GC patients. They may serve as new molecular markers for predicting the early diagnosis and prognosis of GC patients.

Abstract Sarcopenia is the age‐related loss of skeletal muscle mass and muscle strength or physical function. It is most common in elderly individuals. Due to its high incidence, insidious onset, and extensive impact on the body, it has a huge impact on the family medical burden and the social public health expenditure in China. The understanding of sarcopenia in China is still lacking, and the recommendations for prevention, control, and intervention are not clear and unified. The purpose of this consensus report is to standardize the prevention, control, and intervention methods for sarcopenia in elderly patients in China; improve the efficacy of intervention; reduce complications during the intervention process; and reduce the risk of falls, fractures, disability, hospitalization, and even death in elderly individuals.

AIM: To investigate the clinical efficacy of femtosecond laser-assisted phacoemulsification combined with goniosynechialysis in the treatment of acute angle-closure glaucoma complicated with cataract.METHODS: A total of 53 patients(60 eyes)with primary acute angle closure glaucoma complicated with cataract admitted to our hospital from April 2020 to February 2021 were selected. They were divided into two groups according to the surgical method, with 28 cases(30 eyes)who were treated with femtosecond laser-assisted phacoemulsification combined with goniosynechialysis in group A, and 25 cases(30 eyes)who were treated with traditional cataract phacoemulsification combined with goniosynechialysis in group B. The effective phacoemulsification time(EPT)and cumulative dissipated energy(CDE)during surgery in two groups were recorded. Patients were followed up to 3mo after surgery, and the intraocular pressure, anterior chamber depth(ACD), best corrected visual acuity, corneal endothelial cell loss rate(ECL)and surgical complications were observed in both groups.RESULTS: The postoperative intraocular pressure was significantly decreased and ACD was significantly increased(all P0.05). The postoperative best corrected visual acuity of the two groups was significantly better than that before surgery(P

In this research, V-type porous starch (VPS) with high oil absorption capacity was obtained by enzymatic hydrolysis of V-type granular starch (VGS) in ethanol aqueous solution. Firstly, the reaction condition of V-type granular starch (VGS) was optimized with oil absorption capacity and V-type crystal crystallinity as indexes. In 50% ethanol, aqueous solution the oil absorption capacity of VGS obtained by reaction 100 ℃ was the highest (176.23%). Then, the influence of enzymatic hydrolysis time, temperature and speed on the degree of hydrolysis, yield and oil absorption capacity of VPS were investigated. The optimal preparation conditions of VPS were obtained through single factor and orthogonal experiments: enzymatic hydrolysis time 4 h, temperature 25 ℃, and enzymatic hydrolysis speed 300 r/min. The oil absorption capacity of the optimal VPS was the highest (550.28%). Finally, the difference in the crystalline structure, granular morphology, specific surface area and bulk density were compared among normal maize starch (NMS), traditional A-type porous starch, VGS and VPS. VPS exhibited a unique sponge shaped irregular dense honeycomb structure, the highest specific surface area (39.94 m2/g) and the lowest bulk density (0.19 g/cm3), which were the reasons for its higher oil absorption capacity.

Abstract Antioxidation is in demand in living systems, as the excessive reactive oxygen species (ROS) in organisms lead to a variety of diseases. The conventional antioxidation strategies are mostly based on the introduction of exogenous antioxidants. However, antioxidants usually have shortcomings of poor stability, non-sustainability, and potential toxicity. Here, we proposed a novel antioxidation strategy based on ultra-small nanobubbles (NBs), in which the gas–liquid interface was employed to enrich and scavenge ROS. It was found that the ultra-small NBs (~ 10 nm) exhibited a strong inhibition on oxidization of extensive substrates by hydroxyl radicals, while the normal NBs (~ 100 nm) worked only for some substrates. Since the gas–water interface of the ultra-small NBs is non-expendable, its antioxidation would be sustainable and its effect be cumulative, which is different to that using reactive nanobubbles to eliminate free radicals as the gases are consumptive and the reaction is unsustainable. Therefore, our antioxidation strategy based on ultra-small NB would provide a new solution for antioxidation in bioscience as well as other fields such as materials, chemical industry, food industry, etc.

Abstract Petroleum hydrocarbon contamination is of environmental and public health concerns due to its toxic components. Bioremediation utilizes microbial organisms to metabolism and remove these contaminants. The aim of this study was to enrich a microbial community and examine its potential to degrade petroleum hydrocarbon. Through successive enrichment, we obtained a bacterial consortium using crude oil as sole carbon source. The 16 S rRNA gene analysis illustrated the structural characteristics of this community. Metagenomic analysis revealed the specific microbial organisms involved in the degradation of cyclohexane and all the six BTEX components, with a demonstration of the versatile metabolic pathways involved in these reactions. Results showed that our consortium contained the full range of CDSs that could potentially degrade cyclohexane, benzene, toluene, and (o-, m-, p-) xylene completely. Interestingly, a single taxon that possessed all the genes involved in either the activation or the central intermediates degrading pathway was not detected, except for the Novosphingobium which contained all the genes involved in the upper degradation pathway of benzene, indicating the synergistic interactions between different bacterial genera during the hydrocarbon degradation.

Abstract Background Intraoperative goal-directed fluid therapy (GDFT) has been reported to reduce postoperative complications of patients undergoing major abdominal surgery. The clinical benefits of pleth variability index (PVI)-directed fluid management for gastrointestinal (GI) surgical patients remain unclear. Therefore, this study aimed to evaluate the impact of PVI-directed GDFT on GI surgical outcomes in elderly patients. Methods This randomised controlled trial was conducted in two university teaching hospitals from November 2017 to December 2020. In total, 220 older adults undergoing GI surgery were randomised to the GDFT or conventional fluid therapy (CFT) group (n = 110 each). The primary outcome was a composite of complications within 30 postoperative days. The secondary outcomes were cardiopulmonary complications, time to first flatus, postoperative nausea and vomiting, and postoperative length of stay. Results The total volumes of fluid administered were less in the GDFT group than in the CFT group (2.075 L versus [vs.] 2.5 L, P = 0.008). In intention-to-treat analysis, there was no difference in overall complications between the CFT group (41.3%) and GDFT group (43.0%) (odds ratio [OR] = 0.935; 95% confidence interval [CI], 0.541–1.615; P = 0.809). The proportion of cardiopulmonary complications was higher in the CFT group than in the GDFT group (19.2% vs. 8.4%; OR = 2.593, 95% CI, 1.120–5.999; P = 0.022). No other differences were identified between the two groups. Conclusions Among elderly patients undergoing GI surgery, intraoperative GDFT based on the simple and non-invasive PVI did not reduce the occurrence of composite postoperative complications but was associated with a lower cardiopulmonary complication rate than usual fluid management. Trial registration This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-17012220) on 1 August 2017.

Abstract Background Experimental studies suggested that intercellular adhesion molecule 4 (ICAM-4) might be implicated in ischemic stroke, but the population-based evidence on the relationship between ICAM-4 and ischemic stroke were limited. Herein, we performed a two-sample Mendelian randomization (MR) analysis to investigate the associations of genetically determined plasma ICAM-4 with the risks of ischemic stroke and its subtypes. Methods A total of 11 single-nucleotide polymorphisms associated with ICAM-4 were selected as instrumental variables based on the genome-wide association studies (GWAS) with 3,301 European individuals. Summary-level data about ischemic stroke and its subtypes were obtained from the Multi-ancestry GWAS launched by the International Stroke Genetics Consortium. We used the inverse-variance weighted method followed by a series of sensitivity analyses to evaluate the associations of genetically determined ICAM-4 with the risks of ischemic stroke and its subtypes. Results Genetically determined higher ICAM-4 levels were significantly associated with increased risks of ischemic stroke (in the IVW method fitted to multiplicative random effects model: odds ratio [OR] per standard deviation [SD] increase, 1.04; 95% confidence interval [CI], 1.01–1.07; P = 0.006; in the IVW analysis with fixed effects model: OR per SD increase, 1.04; 95% CI, 1.01–1.07; P = 0.003) and cardioembolic stroke (in multiplicative random effects model: OR per SD increase, 1.08; 95% CI, 1.02–1.14; P = 0.004; in fixed effects model: OR per SD increase, 1.08; 95% CI, 1.03–1.13; P = 0.003). There was no association of ICAM-4 with the risks of large artery stroke and small vessel stroke. MR-Egger regression showed no directional pleiotropy for all associations, and the sensitivity analyses with different MR methods further confirmed these findings. Conclusions We found positive associations of genetically determined plasma ICAM-4 with the risks of ischemic stroke and cardioembolic stroke. Future studies are needed to explore the detailed mechanism and investigate the targeting effect of ICAM-4 on ischemic stroke.

In the design of shield tunnels, it is expected that a design can be more economical as more site investigation data are available. Nevertheless, the cost of site investigation will also increase as more site investigation data are required. It is thus important to assess the potential benefit of a site investigation program before it is conducted considering the uncertainty in the soil properties and the site investigation outcomes. In this paper, a probabilistic framework is suggested to assess the effectiveness of a site investigation program for the design of shield tunnels through the random field theory. An efficient method based on the generalized extreme value distribution is used to calculate the failure probability of the tunnel, through which the expected benefit from a site investigation program can be estimated conveniently. The result shows that a site investigation program is more valuable when a greater target design reliability index is needed. The expected benefit from a site investigation program increases as the borehole intensity increases, and it also increases as the scale of fluctuation of the soil properties increases. The method suggested in this paper provides a useful tool for planning borehole layout for the design of shield tunnels, which is promising for the optimization of site investigation.

ObjectiveTo utilize bibliometric analysis to examine the literature about immunotherapy for castration-resistant prostate cancer published within the past two decades. Through this method, we aim to visualize and analyze the research progress in this field and identify the most recent trends and developments.MethodsThis research conducted a comprehensive literature review on immunotherapy for castration-resistant prostate cancer. The time frame spanned from January 2003 to December 2022, and the data were extracted from the Web of Science Core Collection database. The application of various software tools, such as CiteSpace, Bibliometrix, and VOSviewer, facilitated the visualization and analysis of the gathered data. These technological utilities illustrated the progression of prominent focus areas within the field.ResultsAfter excluding irrelevant studies, 373 papers were selected for this study. The findings suggested that the field of immunotherapy for castration-resistant prostate cancer was rapidly developing. The USA was considered to have a significant early entrant advantage in this area and profoundly influenced the field. Similarly, China’s National Cancer center demonstrated notable advantages as a recent participant in this research domain. Major research institutions contributing to the field include the University of California, San Francisco; the University of Washington; and the Memorial Sloan Kettering Cancer Research Center. Notably, US authors James L. Gulley, Charles G. Drake, and Lawrence Fong had the largest number of publications in this area. The main research trends for immunotherapy of castration-resistant prostate cancer are membrane antigen expression, checkpoints T-lymphocyte-associated protein 4 (CTLA4) blockade, radium-223, and vaccines, and the refinement of establishing organoid models might fuel castration-resistant prostate cancer immunotherapy research in the ongoing development.ConclusionThe key trends in immunotherapy research for castration-resistant prostate cancer are membrane antigen expression, CTLA4 blockade, radium-223, and vaccines. Exploring new immune pathways and combining different therapeutic approaches to enhance immune response will be a major trend in the field in the future.

BackgroundsThe impact of immediate implant-based breast reconstruction (IBBR) on the delivery of radiotherapy plans remains controversial. This study aimed to compare the differences in radiotherapy dosimetry, complications of radiotherapy, and quality of life in patients who underwent modified radical mastectomy combined with or without IBBR.MethodsWe retrospectively collected 104 patients with breast cancer who underwent intensity-modulated radiation therapy after modified radical mastectomy with IBBR (n =46) or not (n =58) from January 2017 to December 2021. The dosimetric differences in radiotherapy of planning target volume (PTV) and organs at risk and the differences in complications of radiotherapy between the two groups were compared. We also applied the functional assessment of cancer therapy-breast cancer (FACT-B) score to compare the difference in quality of life. The chi-square test and independent samples t-test were used to analyze the above data.ResultsIBBR group was associated with higher PTV volumes, PTV D98, V95, and lower PTV Dmean, D2 compared with the non-reconstruction group (P 0.05). Moreover, FACT-B scores at 6 months after radiotherapy in patients with IBBR were higher than those without reconstruction (P < 0.05).ConclusionPatients with IBBR achieved better radiation dosimetry distribution and higher quality of life without more complications of radiotherapy.

ObjectiveIncreased inflammation and cytokine levels are considered risk factors and promoters of preterm birth (PTB). However, the regulatory mechanism of pregnancy-related inflammation remains unclear. Toll-like receptor 4 (TLR4) plays a critical role in inflammatory responses in various diseases. Therefore, our study aimed to investigate whether TLR4 is involved in the inflammatory responses during uterine activation for labor, with the goal of identifying potential biomarkers for uterine activation at term.Materials and methodsWe used flow cytometry to detect TLR4 expression on CD14+ maternal blood monocytes in the first, second, and third trimesters. ELISA was employed to measure TLR4 and cytokines levels in the maternal serum of term non-labor (TNL), term labor (TL) women and LPS induced preterm labor and PBS injected controls. TLR4siRNA was transfected into the human myometrial smooth muscle cells (HMSMCs), which were subsequently treated with IL-1β. The mRNA and protein levels of TLR4, uterine contraction-related protein connexin 43 (CX43), oxytocin receptor (OTR), MAPK/NF-κB signaling pathway, and cytokines were analyzed using qRT-PCR, western blotting, and immunohistochemistry.ResultsThe study revealed TLR4 expression on CD14+ maternal blood monocytes was higher in the third trimester group compared to the first and second trimester groups (p

The methylerythritol phosphate (MEP) pathway is responsible for producing isoprenoids, metabolites with essential functions in the bacterial kingdom and plastid-bearing organisms including plants and Apicomplexa. Additionally, the MEP-pathway intermediate methylerythritol cyclodiphosphate (MEcPP) serves as a plastid-to-nucleus retrograde signal. A suppressor screen of the high MEcPP accumulating mutant plant (ceh1) led to the isolation of 3 revertants (designated Rceh1-3) resulting from independent intragenic substitutions of conserved amino acids in the penultimate MEP-pathway enzyme, hydroxymethylbutenyl diphosphate synthase (HDS). The revertants accumulate varying MEcPP levels, lower than that of ceh1, and exhibit partial or full recovery of MEcPP-mediated phenotypes, including stunted growth and induced expression of stress response genes and the corresponding metabolites. Structural modeling of HDS and ligand docking spatially position the substituted residues at the MEcPP binding pocket and cofactor binding domain of the enzyme. Complementation assays confirm the role of these residues in suppressing the ceh1 mutant phenotypes, albeit to different degrees. In vitro enzyme assays of wild type and HDS variants exhibit differential activities and reveal an unanticipated mismatch between enzyme kinetics and the in vivo MEcPP levels in the corresponding Rceh lines. Additional analyses attribute the mismatch, in part, to the abundance of the first and rate-limiting MEP-pathway enzyme, DXS, and further suggest MEcPP as a rheostat for abundance of the upstream enzyme instrumental in fine-tuning of the pathway flux. Collectively, this study identifies critical residues of a key MEP-pathway enzyme, HDS, valuable for synthetic engineering of isoprenoids, and as potential targets for rational design of antiinfective drugs.

In this study, coix seed starch nanoparticles were prepared by nano-precipitation method using three different systems (alkali solution, water-ethanol system and dimethyl sulfoxide (DMSO)-ethanol system). The structures and physicochemical properties of the three nanoparticles were investigated by analysis of their particle characteristics, molecular characteristics, crystallization characteristics and thermal characteristics. The results showed that the nanoparticles prepared using alkaline solution had the highest proportion of nanoparticles (85.65%). Both the nanoparticles prepared using alkaline solution and water-ethanol system had an A-type crystalline structure, while the crystalline structure of the nanoparticles prepared using DMSO-ethanol system changed from A-type to amorphous. The nanoparticles prepared using alkali solution at 45 ℃ had the smallest particle size (348 nm), the highest polydispersity, higher degree of order, relative crystallinity and thermal stability, indicating that alkali solution was the most suitable to prepare coix seed starch nanoparticles. This study may provide a theoretical basis for the preparation of starch nanoparticles and the study of their structural properties as well as the expansion of the application of coix seed starch.

Abstract Background Epigenetic variants carried by circulating tumor DNA can be used as biomarkers for early detection of hepatocellular carcinoma (HCC) by noninvasive liquid biopsy. However, traditional methylation analysis method, bisulfite sequencing, with disadvantages of severe DNA damage, is limited in application of low-amount cfDNA analysis. Results Through mild enzyme-mediated conversion, enzymatic methyl sequencing (EM-seq) is ideal for precise determination of cell-free DNA methylation and provides an opportunity for HCC early detection. EM-seq of methylation control DNA showed that enzymatic conversion of unmethylated C to U was more efficient than bisulfite conversion. Moreover, a relatively large proportion of incomplete converted EM-seq reads contains more than 3 unconverted CH site (CH = CC, CT or CA), which can be removed by filtering to improve accuracy of methylation detection by EM-seq. A cohort of 241 HCC, 76 liver disease, and 279 normal plasma samples were analyzed for methylation value on 1595 CpGs using EM-seq and targeted capture. Model training identified 283 CpGs with significant differences in methylation levels between HCC and non-HCC samples. A HCC screening model based on these markers can efficiently distinguish HCC sample from non-HCC samples, with area under the curve of 0.957 (sensitivity = 90%, specificity = 97%) in the test set, performing well in different stages as well as in serum α-fetoprotein/protein induced by vitamin K absence-II negative samples. Conclusion Filtering of reads with ≥ 3 CHs derived from incomplete conversion can significantly reduce the noise of EM-seq detection. Based on targeted EM-seq analysis of plasma cell-free DNA, our HCC screening model can efficiently distinguish HCC patients from non-HCC individuals with high sensitivity and specificity.