Single-atom alloys (SAAs) have gained increasing prominence in the field of selective hydrogenation reactions due to their uniform distribution of active sites and the unique host-guest metal interactions. Herein, 15 SAAs are constructed to comprehensively elucidate the relationship between host-guest metal interaction and catalytic performance in the selective hydrogenation of 4-nitrostyrene (4-NS) by density functional theory (DFT) calculations. The results demonstrate that the SAAs with strong host-guest metal interactions exhibit a preference for NâO bond cleavage, and the reaction energy barrier of the hydrogenation process is primarily influenced by the host metal. Among them, Ir1Ni SAA stands out as the prime catalyst candidate, showcasing exceptional activity and selectivity. Furthermore, the Ir1Ni SAA is subsequently prepared through precise synthesis techniques and evaluated in the selective hydrogenation of 4-NS to 4-aminostyrene (4-AS). As anticipated, the Ir1Ni SAA demonstrates extraordinary catalytic performance (yield > 96%). In situ FT-IR experiments and DFT calculations further confirmed that the unique host-guest metal interaction at the Ir-Ni interface site of Ir1Ni SAA endows it with excellent 4-NS selective hydrogenation ability. This work provides valuable insights into enhancing the performance of SAAs catalysts in selective hydrogenation reactions by modulating the host-guest metal interactions.
Chemoselective hydrogenation of carbonyl in unsaturated aldehydes is a significant process in the chemical industry, in which the development of aqueous-phase reaction systems as a substitution to organic ones is challenging. Herein, we report Ir atomic cluster catalysts anchored onto WO3-x nanorods via a reduction treatment at various temperatures (denoted as Ir/WOx-T, T = 200, 300, 400, and 500 °C), which accelerates the chemoselective hydrogenation of carbonyl groups in aqueous solutions. The optimal catalyst Ir/WOx-300 exhibits exceptional activity (TOF value: 1313.7 min-1) and chemoselectivity toward cinnamaldehyde (CAL) hydrogenation to cinnamyl alcohol (COL) (yield: â¼98.0%) in water medium, which is, to the best of our knowledge, the highest level compared with previously reported heterogeneous catalysts in liquid-phase reaction. Ac-HAADF-STEM, XAFS, and XPS verify the formation of interface structure (Irδ+-Ov-W5+ (0 ≤ δ ≤ 4); Ov denotes oxygen vacancy) induced by metal-support interaction and the largest concentration of interfacial Ir (Irδ+) in Ir/WOx-300. In situ studies (Raman, FT-IR), isotopic labeling measurements combined with DFT calculations substantiate that the hydrogenation of the C=O group consists of two pathways: water-mediated hydrogenation (predominant) and direct hydrogenation via H2 dissociation (secondary). In the former case, W5+-Ov site accelerates the activation adsorption of H2O, while Ir0 site facilitates the H-H bond cleavage of H2 and Irδ+ promotes the CAL adsorption. H2O molecule, as the source of hydrogen species, participates directly in the hydrogenation of the carbonyl group through a hydrogen-bonded network, with a largely reduced energy barrier relative to the H2 dissociation path. This work demonstrates a green catalytic route that breaks the activity-selectivity trade-off toward the selective hydrogenation of unsaturated aldehydes, which shows great potential in heterogeneous catalysis.
The sintering of hydrate aggregates on the pipe wall is a major form of hydrate deposition. Understanding the sintering behavior of hydrates on the wall is crucial for promoting hydrate safety management and preventing pipeline blockage. However, limited research currently exists on this topic. In this study, the cohesive force strength of hydrate particles on the wall surface under different conditions was directly measured using a high-pressure micromechanical force device (HP-MMF). Subsequently, the effects of subcooling and glycine on the cohesive force were investigated. The results indicate that the cohesive force is influenced by different growth states during the process of free water on the wall surface gradually growing into hydrate. Three states with larger measured values during the growth process were selected for research. Observation showed that increased subcooling strengthened sintering by accelerating the growth rate of the hydrate film, resulting in a significant increase in cohesive force. The role of glycine in the methane hydrate system was then evaluated. Glycine was found to reduce the degree of sintering by reducing the growth rate of the hydrate film, thereby decreasing the cohesive force. The optimal concentration in the system was determined to be 0.25 wt %. Moreover, compared with low subcooling (1 °C), glycine had a better effect at high subcooling (5 °C). At 5 °C subcooling and the optimal concentration, the cohesive force in the wall droplet state decreases from 677.38 to 489.02 mN/m, the cohesive force at the low-saturation state decreases from 951.79 to 543.32 mN/m, and the cohesive force at the high-saturation state decreases from 1194.95 to 641.76 mN/m. These findings contribute to a better understanding of the cohesive force behavior of gas hydrate on the inner wall of the pipeline and provide basic data for reducing the risk of hydrate blockage.
In this paper, we investigate the spin squeezing in a hybrid quantum system consisting of a Silicon-Vacancy (SiV) center ensemble coupled to a diamond acoustic waveguide via the strain interaction. Two sets of non-overlapping driving fields, each contains two time-dependent microwave fields, are applied to this hybrid system. By modulating these fields, the one-axis twist (OAT) interaction and two-axis two-spin (TATS) interaction can be independently realized. In the latter case the squeezing parameter scales to spin number as ξ R2â¼1.61N -0.64 with the consideration of dissipation, which is very close to the Heisenberg limit. Furthermore, this hybrid system allows for the study of spin squeezing generated by the simultaneous presence of OAT and TATS interactions, which reveals sensitivity to the parity of the number of spins Ntot, whether it is even or odd. Our scheme enriches the approach for generating Heisenberg-limited spin squeezing in spin-phonon hybrid systems and offers the possibility for future applications in quantum information processing.
Non-small cell lung cancer (NSCLC) is the most common type of lung tumor; however, we lack effective early detection indicators and therapeutic targets. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is vital to initiate protein synthesis, acting as a scaffolding protein for the eukaryotic protein translation initiation factor complex, EIF4F, which regulates protein synthesis together with EIF4A, EIF4E, and other translation initiation factors. However, EIF4G1's function in NSCLC cancer is unclear. Herein, transcriptome sequencing showed that knockdown of EIF4G1 in H1299 NSCLC cells upregulated the expression of various inflammation-related factors. Inflammatory cytokines were also significantly overexpressed in NSCLC tumor tissues, among which CXCL8 (encoding C-X-C motif chemokine ligand 8) showed the most significant changes in both in the transcriptome sequencing data and tumor tissues. We revealed that EIF4G1 regulates the protein level of TNF receptor superfamily member 10a (TNFRSF10A) resulting in activation of the mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NFκB) pathways, which induces CXCL8 secretion, leading to targeted chemotaxis of immune cells. We verified that H1299 cells with EIF4G1 knockdown showed increased chemotaxis compared with the control group and promoted increased chemotaxis of macrophages. These data suggested that EIF4G1 is an important molecule in the inflammatory response of cancer tissues in NSCLC.
OBJECTIVE: The aim of the study is to investigate the use of incidences and characteristics of Prevocalic Electroglottographic Signal (PVES) derived from electroglottography (EGG) in characterizing glottal stops (GS) in cleft palate speech. METHODS: Mandarin nonaspirated monosyllabic first-tone words were used for the speech sampling procedure. A total of 1680 utterances (from 83 patients with repaired cleft palates) were divided into three categories based on the results of auditory-perceptual evaluation of recorded speech sounds by three independent reviewers: [Category A (absence of GS agreed by all three reviewers) (n = 1192 tokens), Category B (two out of three reviewers agreed on the presence of a GS) (n = 181 tokens) and Category C (all three reviewers agreed on the presence of a GS) (n = 307 tokens)]. The EGG signals of the 1680 utterances were analyzed using a MATLAB program to automatically mark the instances of PVES (amplitude and time-interval) in the GS utterances. RESULTS: The result showed that the incidence of EGG PVES presented good positive correlation with auditory-perceptual evaluation (r = 0.703, Pï¼0.000). Statistical analysis revealed a significant difference in mean PVES amplitude among different groups (Pï¼0.05). There was a significant distinction in the time interval between groups A and B, as well as in groups A and C (Pï¼0.05). CONCLUSIONS: The study suggests PVES can be an objective means of identifying GS in cleft palate speech. It also indicates that proportion of amplitude and time interval of PVES tend to be positively correlate with subjective assessment.
Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022. We show that prepandemic IG had no appreciable cross-reactivity or neutralizing activity against SARS-CoV-2. Anti-spike antibody titers and neutralizing activity against SARS-CoV-2 WA1/2020 D614G increased gradually after the pandemic started and reached levels comparable to vaccinated healthy donors 18 months after the diagnosis of the first COVID-19 case in the United States in January 2020. The average time between production to infusion of IG products was 8 months, which resulted in poor neutralization of the variant strain circulating at the time of infusion. Despite limited neutralizing activity, IG prophylaxis with clinically relevant dosing protected susceptible K18-hACE2-transgenic mice against clinical disease, lung infection, and lung inflammation caused by the XBB.1.5 Omicron variant. Moreover, following IG prophylaxis, levels of XBB.1.5 infection in the lung were higher in FcγR-KO mice than in WT mice. Thus, IG replacement products with poor neutralizing activity against evolving SARS-CoV-2 variants likely confer protection to patients with immune deficiency disorders through Fc effector function mechanisms.
COVID-19 , Humans , Animals , Mice , COVID-19/prevention & control , SARS-CoV-2 , Antibodies , Cross Reactions , Mice, Transgenic
When the workpiece surface exhibits strong reflectivity, it becomes challenging to obtain accurate key measurements using non-contact, visual measurement techniques due to poor image quality. In this paper, we propose a high-precision measurement method shaft diameter based on an enhanced quality stripe image. By capturing two stripe images with different exposure times, we leverage their different characteristics. The results extracted from the low-exposure image are used to perform grayscale correction on the high-exposure image, improving the distribution of stripe grayscale and resulting in more accurate extraction results for the center points. The incorporation of different measurement positions and angles further enhanced measurement precision and robustness. Additionally, ellipse fitting is employed to derive shaft diameter. This method was applied to the profiles of different cross-sections and angles within the same shaft segment. To reduce the shape error of the shaft measurement, the average of these measurements was taken as the estimate of the average diameter for the shaft segment. In the experiments, the average shaft diameters determined by averaging elliptical estimations were compared with shaft diameters obtained using a coordinate measuring machine (CMM) the maximum error and the minimum error were respectively 18 µm and 7 µm; the average error was 11 µm; and the root mean squared error of the multiple measurement results was 10.98 µm. The measurement accuracy achieved is six times higher than that obtained from the unprocessed stripe images.
INTRODUCTION: A prospective observational study was modified to assess the efficacy of surgery alone for the treatment of locally advanced oral squamous cell carcinoma. (LA-OSCC) MATERIALS AND METHODS: This prospective, single-institution, single-arm study involved 174 patients who underwent major surgery for LA-OSCC. Participating patients did not receive postoperative radiation. After initial curative treatment, patients were routinely monitored via clinical examination and imaging. The follow-up period was 3-70 months. Tumour recurrence and death were considered as the Clinical End Point in Research. RESULTS: The 5-year overall survival (OS), disease-free survival (DFS), and locoregional control rates for 174 patients were 66.7% (95% confidence interval [CI], 59.8 to 73.6), 66.1% (95% CI, 59.2 to 73.0), and 82.4% (95% CI, 76.5 to 88.3), respectively. CONCLUSION: A study of patients with LA-OSCC treated with surgery alone may have the optimal therapeutic impact for LA-OSCC, as evidenced by solid data for our next RCT trial. This conclusion still needs to be validated in higher-level RCTs.
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/surgery , Squamous Cell Carcinoma of Head and Neck , Prospective Studies , Neoplasm Recurrence, Local/pathology
Materials exhibiting X-ray-induced photochromism have consistently piqued the interest of researchers. Exploring the photochromic properties of such materials is valuable for understanding the structural changes and electron transfer processes that occur under high energy radiation, such as X-ray irradiation. Here, a crystalline silver(I) nanocluster synthesized from tert-butylacetylene silver was found to have the ability to exhibit color and photoluminescence changes upon exposure to X-ray radiation. The responsive behavior was observed across a wide temperature range of 100-300 K, with the ability to respond particularly well to soft X-rays (λ > 1 Å) and exhibit light responsiveness to hard X-rays (λ < 1 Å). By combining experimental findings including X-ray diffraction, X-ray photoelectron spectroscopy, electron spin resonance, etc. with theoretical calculations, we have proposed that X-ray irradiation induces electron transfer from chloride (Cl-) located in the center of the silver(I) nanocluster to the surrounding Ag14 in the skeleton. This represents the first documented example in which electron transfer induced by X-ray excitation has been observed, accompanied by a photochromism process, in silver nanoclusters. This study contributes to our understanding of X-ray-induced photochromism and the electron transfer process in silver cluster compounds. It also provides valuable insights and potential design strategies for applications such as photochromism, photoluminescence color change, and photoenergy conversion.
Strong metal-support interaction (SMSI) has been extensively studied in heterogeneous catalysis because of its significance in stabilizing active metals and tuning catalytic performance, but the origin of SMSI is not fully revealed. Herein, by using Pt/CeO2 as a model catalyst, we report an embedding structure at the interface between Pt and (110) plane of CeO2, where Pt clusters (â¼1.6 nm) are embedded into the lattice of ceria within 3-4 atomic layers. In contrast, this phenomenon is absent in the CeO2(100) support. This unique geometric structure, as an effective motivator, triggers more significant electron transfer from Pt clusters to CeO2(110) support accompanied by the formation of interfacial structure (Ptδ+-Ov-Ce3+), which plays a crucial role in stabilizing Pt nanoclusters. A comprehensive investigation based on experimental studies and theoretical calculations substantiates that the interfacial sites serve as the intrinsic active center toward water-gas shift reaction (WGSR), featuring a moderate strength CO activation adsorption and largely decreased energy barrier of H2O dissociation, accounting for the prominent catalytic activity of Pt/CeO2(110) (a reaction rate of 15.76 molCO gPt-1 h-1 and a turnover frequency value of 2.19 s-1 at 250 °C). In addition, the Pt/CeO2(110) catalyst shows a prominent durability within a 120 h time-on-stream test, far outperforming the Pt/CeO2(100) one, which demonstrates the advantages of this embedding structure for improving catalyst stability.
Copper-based catalysts serve as the predominant methanol steam reforming material although several fundamental issues remain ambiguous such as the identity of active center and the aspects of reaction mechanism. Herein, we prepare Cu/Cu(Al)Ox catalysts with amorphous alumina-stabilized Cu2O adjoining Cu nanoparticle to provide Cu0-Cu+ sites. The optimized catalyst exhibits 99.5% CH3OH conversion with a corresponding H2 production rate of 110.8 µmol s-1 gcat-1 with stability over 300 h at 240 °C. A binary function correlation between the CH3OH reaction rate and surface concentrations of Cu0 and Cu+ is established based on kinetic studies. Intrinsic active sites in the catalyst are investigated with in situ spectroscopy characterization and theoretical calculations. Namely, we find that important oxygen-containing intermediates (CH3O* and HCOO*) adsorb at Cu0-Cu+ sites with a moderate adsorption strength, which promotes electron transfer from the catalyst to surface species and significantly reduces the reaction barrier of the C-H bond cleavage in CH3O* and HCOO* intermediates.
Actinomycins are known for their anti-tumor, antibacterial and antiviral activities, and in particular for the ability of actinomycin D as a clinical drug to treat a variety of cancers. In our ongoing work to obtain novel natural products from endophytic actinomycetes derived from traditional Chinese herbs, we identified the potential to produce actinomycins in YINM00002, a Kitasatospora strain derived from Polygonatum kingianum. According to genome mining, we isolated actinomycins D and V (1 and 2) and small amounts of 4-methyl-3-hydroxyanthranilic acid (4-MHA) derivates (3 and 4) from strain fermentation broth. The presence of actinrhater A (3) and actinrhater B (4) reveals a mysterious shunt pathway in the early stages of actinomycin D biosynthesis. Our study provides a fresh perspective for further discovery and modification of novel actinomycins.
Objective: To evaluate the effectiveness of TruScreen (TS) for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with abnormal ThinPrep cytologic test (TCT) results. Methods: 466 women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) were enrolled and underwent TS, colposcopy and biopsy examination. Results: Compared with the high-risk human papillomavirus (hrHPV) test for CIN2+, significantly higher specificity of TS, combined TS and hrHPV (69.6 and 75.0 vs 36.8% in ASCUS; 59.0 and 69.9 vs 30.1% in LSIL), significantly higher positive predictive value of combined TS and hrHPV were observed (32.7 vs 24.6% in ASCUS; 47.9 vs 35.6% in LSIL). Conclusion: TS combined with hrHPV showed better performance in diagnosing CIN2+ in ASCUS/LSIL.
Atypical Squamous Cells of the Cervix , Papillomavirus Infections , Squamous Intraepithelial Lesions , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/pathology , Vaginal Smears , Sensitivity and Specificity , Uterine Cervical Dysplasia/diagnosis , Squamous Intraepithelial Lesions/diagnosis , Papillomavirus Infections/diagnosis , Papillomaviridae/genetics
Introduction: Fanconi anemia complementation group E (FANCE) is a subunit of fanconi anemia (FA) pathway and plays a key role in repairing DNA interstrand cross-links (ICLs) damage. We investigate detailed functions and mechanisms of FANCE in endometrial cancer (EC). Methods: FANCE protein and RNA expression in EC and non-cancerous tissues were detected by Western blotting (WB), immunohistochemistry (IHC), and real-time polymerase chain reaction (RT-PCR) assays. Using lentiviral transfection and siRNA interference techniques, we constructed overexpressing FANCE (OE-FANCE) and FANCE-knockdown (FANCE-KD) EC cells. We then investigated DNA damage repair capacity of FANCE in EC cells including comet assay and γH2AX immunofluorescence assay. In vitro assays including CCK8, EDU and colony formation for chemoresistance and proliferation, transwell assay for metastasis were performed. Flow cytometer assay, cell cycle synchronization for cell cycle progression and EC cells RNA sequencing were determined. Finally, in vivo mouse models were used to detect tumor growth. Results: We found FANCE RNA and protein expression was significantly decreased in endometrioid adenocarcinoma (EAC) compared with normal and atypical hyperplasia endometrium. FANCE promoted the repair of ICL damage and double-strand break (DSB) in OE-FANCE EC cells. Furthermore, FANCE increased drug resistance in OE-FANCE EC cells by upregulating FA pathway and homologous recombination (HR) associated proteins. FANCE inhibited cell proliferation and metastasis through G2/M cell cycle arrest in vitro and vivo. FANCE participated in regulating several pathways. Conclusion: The study demonstrates the reduction of FANCE expression leads to genomic instability, thereby promoting the development of EC by regulating cell cycle.
Plant growth is directly influenced by biotic and abiotic stress factors resulting from environmental changes. Plant growth-promoting rhizobacteria (PGPR) have become a crucial area of research aimed at addressing these challenges. However, a knowledge gap exists regarding how PGPR impacts the microenvironments surrounding plant roots. The purpose of this study is to elucidate the effects of two distinct PGPR strains, Streptomyces griseorubiginosus BTU6 (known for its resistance to smut disease) and S. chartreusis WZS021, on sugarcane roots. Additionally, we compare the resultant modifications in the physicochemical characteristics of the rhizospheric soil and root architecture. The results reveal that following the inoculation of S. chartreusis WZS021, there was a significant increase in the active chemicals associated with nitrogen metabolism in sugarcane roots. This enhancement led to a substantial enrichment of nitrogen-cycling microbes like Pseudomonas and Gemmatimona. This finding supports earlier research indicating that S. chartreusis WZS021 enhances sugarcane's capacity to utilize nitrogen effectively. Furthermore, after treatment with S. chartreusis, Aspergillus became the predominant strain among endophytic fungi, resulting in alterations to their community structure that conferred drought resistance. In contrast, the relative abundance of Xanthomonas in the root environment decreased following inoculation with S. griseorubiginosus. Instead, Gemmatimona became more prevalent, creating a favorable environment for plants to bolster their resistance against disease. Notably, inoculations with S. chartreusis WZS021 and S. griseorubiginosus BTU6 led to substantial changes in the chemical composition, enzymatic activity, and microbial community composition in the soil surrounding sugarcane roots. However, there were distinct differences in the specific alterations induced by each strain. These findings enhance plant resilience to stress by shedding light on PGPR-mediated modifications in root microenvironments.
Alphaproteobacteria , Streptomyces , Plant Roots/microbiology , Plant Development , Nitrogen , Soil/chemistry , Streptomyces/genetics , Soil Microbiology
Endometrial cancer (EC) is one of the most common cancers of the female reproductive system. Multi-epitope vaccine may be a promising and effective strategy against EC. In this study, we designed a novel multi-epitope vaccine based on the antigenic proteins PRAME and TMPRSS4 using immunoinformatics and bioinformatics approaches. After a rigorous selection process, 14 cytotoxic T lymphocyte (CTL) epitopes, 6 helper T lymphocyte (HTL) epitopes, and 8 B cell epitopes (BCEs) were finally selected for vaccine construction. To enhance the immunogenicity of the vaccine candidate, the pan HLA DR-binding epitope was included in the vaccine design as an adjuvant. The final vaccine construct had 455 amino acids and a molecular weight of 49.8 kDa, and was predicted to cover 95.03% of the total world population. Docking analysis showed that there were 10 hydrogen bonds and 19 hydrogen bonds in the vaccine-HLA-A*02:01 and vaccine-HLA-DRB1*01:01 complexes, respectively, indicating that the vaccine has a good affinity to MHC molecules. This was further supported by molecular dynamics (MD) simulation. Immune simulation showed that the designed vaccine was able to induce higher levels of immune cell activity, with the secretion of numerous cytokines. The codon adaptation index (CAI) value and GC content of the optimised codon sequences of the vaccine were 0.986 and 54.43%, respectively, indicating that the vaccine has the potential to be highly expressed. The in silico analysis suggested that the designed vaccine may provide a novel therapeutic option for the individualised treatment of EC patients in the future.Communicated by Ramaswamy H. Sarma.
BACKGROUND: Few relevant literature reports on applying acupoint press-needle embedding combined with emotional nursing in patients with a gynecological malignant tumor. AIM: To explore the effect of traditional Chinese medicine acupoint needle embedding combined with emotional nursing on chemotherapy-related nausea and vomiting (CINV), cancer-related fatigue (CRF) and psychological state in patients with gynecological malignant tumors. METHODS: Retrospective analysis of the clinical information of 84 patients with gynecological malignant tumors treated in our hospital from August 2020 to December 2022 Led to the development of an observation group (n = 42) and a control group (n = 42) based on various nursing approaches. Ondansetron hydrochloride injection was administered to the individuals in the control group. However, the observation group received emotional nursing based on the control group and acupoint press-needle embedding of traditional Chinese medicine. Patients in both groups received the chemotherapy regimen of paclitaxel liposome + carbo-platin/ cisplatin. For four weeks, both groups intervened. The CINV grade, quality of life, CRF, psychological status and sleep quality scores of the two groups before and after intervention were compared. RESULTS: After intervention, the degree of CINV in the observation group was significantly better than that in the control group. After intervention, the scores of each dimension and total score of FLIE scale were significantly higher than those in the control group. After intervention, the scores of each dimension and total score of Piper Fatigue Scale were significantly lower than those in the control group (P < 0.05). After intervention, the scores of avoidance and yield dimensions in the observation group were significantly lower than those in the control group, and the scores of confrontation dimension were significantly higher than those in the control group (P < 0.05). After intervention, the sleep quality score of the observation group was significantly lower than that of the control group, and the Karnofsky Performance Status scale score was significantly higher than that of the control group (P < 0.05). CONCLUSION: The acupuncture point needle embedding of traditional Chinese medicine combined with emotional nursing can further reduce the incidence of chemotherapy-related nausea and vomiting in patients with gynecological malignant tumors, improve the quality of life and the degree of CRF, alleviate the bad psychological state, adopt a positive way to face the disease and treatment, and improve the quality of sleep and quality of life.
BACKGROUND: Responsiveness to opioid analgesics differs among patients with acute postoperative pain. OBJECTIVE: Our study presents the most recent evidence on the effect of genetic variations on postoperative pain, opioid consumption, nausea, and vomiting in patients treated with opioids. STUDY DESIGN: An updated systematic review and meta-analysis on the association between single-nucleotide polymorphisms and opioids administered to patients with acute postoperative pain. METHODS: PubMed, Embase, ISI Web of Science, and the Cochrane Library databases were searched for articles published from February 1, 2014, through December 31, 2021. RESULTS: Added to the previous meta-analysis, 39 studies (a total of 7,455 patients) were included in the final meta-analysis. Highlights of the findings include: 1) human µ-opioid receptor gene 118G allele carriers required more opioids during the first postoperative 24 hours (standard mean difference [SMD] = -0.27; 95% CI,-0.40 to -0.14; P < 0.0001) and 48 hours (SMD = -0.52; 95% CI, -0.83 to -0.20; P = 0.001), and reported higher pain scores during the first 24 hours but not at the 48-hour postoperative period (SMD = -0.09, 95% CI, -0.15 to -0.03; P = 0.002) compared to homozygous 118AA patients. 2) patients with the CYP3A4 *1G allele required fewer opioids during the first 24-hour postoperative period (SMD = 0.59; 95% CI, 0.05 to 1.14; P = 0.03) compared to patients with the homozygous CYP3A4*1/*1 allele. 3) Adenosine triphosphate-binding cassette subfamily B member-1 (ABCB1) 3435T allele carriers required more opioids during the 48-hour postoperative period (SMD = -0.21; 95% CI, -0.38 to -0.04; P = 0.02) compared to homozygous CC carriers. 4) Catechol-O-methyl transferase 158A allele carriers required fewer opioids during the first 24-hour postoperative period (SMD = 0.33; 95% CI, 0.15 to 0.51; P = 0.0004) compared to homozygous GG carriers. No significant differences were observed in patients with CYP2D6*10 and ABCB1 G2677A/T genetic polymorphisms. LIMITATIONS: Several loci were not analyzed in detail due to insufficient clinical data. Furthermore, nongenetic factors that affected analgesic efficacy and the clinical outcome of postoperative pain were not discussed and were not the aim of this meta-analysis. CONCLUSIONS: In combination with previous systematic reviews and meta-analyses, our results indicate that the A118G allele variant of OPRM1 and the *1*1G allele variant of CYP3A4 have a profound influence on individual differences in opioid reactivity in patients with postoperative pain. Our results, together with the identification of additional single nucleotide polymorphisms in future studies, may provide a theoretical basis for precise clinical analgesia. KEY WORDS: Single nucleotide polymorphism, postoperative pain, opioid, meta-analysis.
Analgesics, Opioid , Catechol O-Methyltransferase , Humans , Analgesics, Opioid/therapeutic use , Catechol O-Methyltransferase/genetics , Catechol O-Methyltransferase/therapeutic use , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 CYP3A/therapeutic use , Pain, Postoperative/drug therapy , Pain, Postoperative/genetics , Polymorphism, Single Nucleotide/genetics
Introduction: Immunogenic cell death (ICD) is a form of regulated cell death that activates an adaptive immune response in an immunocompetent host and is particularly sensitive to antigens from tumor cells. Kidney clear cell carcinoma (KIRC) is an immunogenic tumor with extensive tumor heterogeneity. However, no reliable predictive biomarkers have been identified to reflect the immune microenvironment and therapeutic response of KIRC. Methods: Therefore, we used the CIBERSORT and ESTIMATE algorithms to define three ICD clusters based on the expression of ICD-related genes in 661 KIRC patients. Subsequently, we identified three different ICD gene clusters based on the overlap of differentially expressed genes (DEGs) within the ICD clusters. In addition, principal component analysis (PCA) was performed to calculate the ICD scores. Results: The results showed that patients with reduced ICD scores had a poorer prognosis and reduced transcript levels of immune checkpoint genes regulated with T cell differentiation. Furthermore, the ICD score was negatively correlated with the tumor mutation burden (TMB) value of KICD. patients with higher ICD scores showed clinical benefits and advantages of immunotherapy, indicating that the ICD score is an accurate and valid predictor to assess the effect of immunotherapy. Discussion: Overall, our study presents a comprehensive KICD immune-related ICD landscape that can provide guidance for current immunotherapy and predict patient prognosis to help physicians make judgments about the patient's disease and treatment modalities, and can guide current research on immunotherapy strategies for KICD.
