Progress on the Effects of Permissive Hypercapnia on the CNS During the Intraoperative Period: A Narrative Review.

Previous experimental findings and clinical evidence have shown the important role of carbon dioxide (CO2) in regulating cerebral vascular tension. CO2 can affect the CNS through various mechanisms. With factors such as patient physiology or surgical interventions potentially causing increased arterial partial pressure of carbon dioxide (PaCO2) levels during mechanical ventilation in general anesthesia, it is important to explore the potential risks or benefits of intraoperative permissive hypercapnia on brain function. In November 2023, we conducted a thorough review of PubMed to establish the article outline. Articles that were non-English or repetitive were eliminated. We collected information on the year, topic, key findings, and opinions of each article. This review not only comprehensively summarizes the factors that contribute to the elevation of intraoperative PaCO2, but also explores the impact of fluctuations in PaCO2 levels on the CNS and the underlying mechanisms involved. At the same time, this article provides our understanding of the potential clinical significance of actively regulating PaCO2 levels. In addition, we propose that the aspects of permissive hypercapnia can be further studied to provide a reliable basis for clinical decision-making. The effects of permissive hypercapnia on the CNS remain a topic of debate. Further prospective randomized controlled studies are needed to determine if permissive hypercapnia can be safely promoted during mechanical ventilation in general anesthesia.

Body Mass Index and Risk of Female Reproductive System Tumors Subtypes: A Meta-Analysis Using Mendelian Randomization.

Introduction: A strong association was previously established between body mass index (BMI) and female reproductive system tumors; however, the causal relationship is unclear. We conducted a Mendelian randomization (MR) study to further explore this association. Methods: Genetic information for BMI was retrieved from a published genome-wide association study involving 339,224 participants. Genetic associations with five common female reproductive system tumors were obtained from the FinnGen, UK Biobank studies, and other large consortia. Results: Genetic predisposition towards BMI exhibits a significant association with multiple tumors of the female reproductive system. Specifically, for every 1-unit increase in BMI log-transformed odds ratio (OR). The OR fluctuations overall for patients with breast cancer ranged from 0.661 to 0.996 (95% confidence interval [CI],0.544-1.000, P < 0.05). When stratified by estrogen receptor (ER) status, the OR for patients with ER (+) breast cancer ranged from 0.782 to 0.844 (95% CI, 0.616-0.994, P < 0.05) and that for those with ER (-) breast cancer ranged from 0.663 to 0.789 (95% CI, 0.498-0.991, P < 0.05). Additionally, ORs were as follows for cancer types: 1.577-1.908 (95% CI, 1.049-2.371, P < 0.05) for endometrial carcinoma; 1.216-1.303 (95% CI, 1.021-1.591, P < 0.05) for high-grade serous ovarian cancer; 1.217 (95% CI, 1.034-1.432, P < 0.05) for low-grade malignant serous ovarian cancer; and 1.502 (95% CI, 1.112-2.029, P < 0.05) for endometrioid ovarian carcinoma. Furthermore, our findings indicated that genetic predisposition towards BMI did not exhibit a causal association with uterine fibroids, cervical precancerous lesions, or cervical cancer itself. Conclusion: A genetic association was established between a high BMI and high risk of developing multiple tumors of the female reproductive system and their associated subtypes. This underscores the significance of taking measures to prevent reproductive system tumors in women who have a high BMI.

Lightweight, Elastic, and Superhydrophobic Multifunctional Organic-Inorganic Fibrous Aerogels for Efficient Oily Wastewater Purification and Electromagnetic Microwave Absorption.

Lightweight and robust aerogels with multifunctionality are highly desirable to meet the technological demands of current society. Herein, we designed lightweight, elastic, and superhydrophobic multifunctional organic-inorganic fibrous hybrid aerogels which were assembled with organic aramid nanofibers and inorganic hierarchical porous carbon fibers. Thanks to the organic-inorganic fiber hybridization strategy, the optimal aerogels possessed remarkable compressibility and elasticity. Benefiting from the microscopic hierarchical porous structure of carbon fibers and the macroscopic macroporous lamellar structure of aerogels, the optimal aerogels exhibited superb lightweight property, conspicuous electromagnetic microwave absorption ability, and outstanding oily wastewater purification capacity. As for electromagnetic microwave absorption, it achieved a strong reflection loss of -41.8 dB, and the effective absorption bandwidth reached 6.86 GHz. Besides, the oil adsorption capacity for trichloromethane reached as high as 93.167 g g-1 with a capacity retention of 95.6% after 5 cycles. Meanwhile, it could act as a gravity-driven separation membrane to continuously separate trichloromethane from a trichloromethane-water mixture with a high flux of 7867.37 L·m-2·h-1, even for surfactant-stabilized water-in-n-heptane emulsions of 3794.94 L·m-2·h-1. Such a strategy might shed some light on the construction of multifunctional aerogels toward broader applications.

Comprehensive Analysis of Immune Cell Infiltration and M2-Like Macrophage Biomarker Expression Patterns in Atrial Fibrillation.

Background: Macrophages play a crucial role in the progression of AF, closely linked to atrial inflammation and myocardial fibrosis. However, the functions and molecular mechanisms of different phenotypic macrophages in AF are not well understood. This study aims to analyze the infiltration characteristics of atrial immune cells in AF patients and further explore the role and molecular expression patterns of M2 macrophage-related genes in AF. Methods: This study integrates single-cell and large-scale sequencing data to analyze immune cell infiltration and molecular characterization of the LAA in patients with AF, using SR as a control group. CIBERSORT assesses immune cell types in LAA tissues; WGCNA identifies signature genes; cell clustering analyzes cell types and subpopulations; cell communication explores macrophage interactions; hdWGCNA identifies M2 macrophage gene modules in AF. AF biomarkers are identified using LASSO and Random Forest, validated with ROC curves and RT-qPCR. Potential molecular mechanisms are inferred through TF-miRNA-mRNA networks and single-gene enrichment analyses. Results: Myeloid cell subsets varied considerably between the AF and SR groups, with a significant increase in M2 macrophages in the AF group. Signals of inflammation and matrix remodeling were observed in AF. M2 macrophage-related genes IGF1, PDK4, RAB13, and TMEM176B were identified as AF biomarkers, with RAB13 and TMEM176B being novel markers. A TF-miRNA-mRNA network was constructed using target genes, which are enriched in the PPAR signaling pathway and fatty acid metabolism. Conclusion: Over infiltration of M2 macrophages may be an important factor in the progression of AF. The M2 macrophage-related genes IGF1, RAB13, TMEM176B and PDK4 may regulate the progression of AF through the PPAR signaling pathway and fatty acid metabolism.

[Analysis of Risk Factors for Pulmonary Infection in Patients with Acute Leukemia after Chemotherapy].

OBJECTIVE: To investigate the risk factors of pulmonary infection in patients with acute leukemia (AL) after chemotherapy. METHODS: A total of 294 patients with AL were collected and divided into infection group (n=93) and control group (n=201) according to whether the pulmonary infection occurred after chemotherapy. Analyze the correlation between sociodemographic data (sex, age, BMI), clinical data (disease type, ECOG score, invasive procedure, underlying disease, hormone therapy, empirical use of antibiotics, prognosis stratification, chemotherapy intensity, primitive cell count, white blood cell count, neutrophil count, duration of granulocyte deficiency, platelet count, hemoglobin, and albumin and pulmonary infection after chemotherapy. COX regression method was used to analyze the risk factors of pulmonary infection in AL patients after chemotherapy. RESULTS: Among 294 patients with AL, 11 died within 30 days after pulmonary infection. There were statistically significant differences in age, smoking history, ECOG score, invasive procedure, hormone therapy, empirical use of antibiotics, prognosis stratification, chemotherapy intensity, primitive cell count, neutrophil count, duration of granulocyte deficiency, platelet count, hemoglobin, albumin and fasting blood glucose between the 2 groups (P <0.05). COX regression analysis showed that smoking history, invasive procedure, unexperienced use of antibiotics, poor prognosis, long duration of granulocytopenia, low platelet level and low albumin were high risk factors for pulmonary infection in AL patients after chemotherapy (P <0.05). CONCLUSION: Smoking, invasive procedures, unexperienced use of antibiotics, poor prognosis, long duration of granulodeficiency, low platelet levels and low albumin are risk factors for pulmonary infection in AL patients after chemotherapy.

[Research Progress of Bispecific Antibodies in Treatment of Multiple Myeloma--Review].

Multiple myeloma (MM) is an incurable malignant plasma cell diseases, the incidence of which is increasing year by year. The application of immunomodulators drugs, proteasome inhibitors, anti-CD38 antibodies, CAR-T, and HSCT have significantly improved the prognosis of patients with MM, however new therapeutic tools need to be developed to improve the prognosis of patients with relapsed/refractory after conventional regimens treatment. Bispecific antibodies are a novel immunotherapeutic approach that generates immune synapses by binding to targets on malignant plasma cells and cytotoxic immune effector cells (T cells/natural killer cells), leading to T/NK cells activation and malignant plasma cell lysis. Several preclinical and phase I clinical studies have shown good efficacy, bringing new possibilities for patients with relapsed/refractory MM to improve their prognosis in the future in combination with the rest of the treatment options. This article summarizes the classification of bispecific antibodies developed in recent years, and the results of preclinical and clinical trials, which will provide some reference for treating MM.

Anchoring Single-Atomic Metal Sites in Metalloporphyrin-Based Covalent Organic Frameworks for Enhanced Photocatalytic Hydrogen Evolution.

A photoactive covalent organic framework (COF) was built from metalloporphyrin and bipyridine monomers and single-atomic Pt sites were subsequently installed. Integrating photosensitizing metalloporphyrin and substrate-activating Pt(bpy) moieties in a single solid facilitates multielectron transfer and accelerates photocatalytic hydrogen evolution with a maximum production rate of 80.4 mmol h-1 gPt -1 and turnover frequency (TOF) of 15.7 h-1 observed. This work demonstrates that incorporation of single-atomic metal sites with photoactive COFs greatly enhances photocatalytic activity and provides an effective strategy for the design and construction of novel photocatalysts.

BmNPV p35 regulates apoptosis in Bombyx mori via a novel target of interaction with the BmVDAC2-BmRACK1 complex.

Voltage-dependent anion channel 2 (VDAC2) is an important channel protein that plays a crucial role in the host response to viral infection. The receptor for activated C kinase 1 (RACK1) is also a key host factor involved in viral replication. Our previous research revealed that Bombyx mori VDAC2 (BmVDAC2) and B. mori RACK1 (BmRACK1) may interact with Bombyx mori nucleopolyhedrovirus (BmNPV), though the specific molecular mechanism remains unclear. In this study, the interaction between BmVDAC2 and BmRACK1 in the mitochondria was determined by various methods. We found that BmNPV p35 interacts directly with BmVDAC2 rather than BmRACK1. BmNPV infection significantly reduced the expression of BmVDAC2, and activated the mitochondrial apoptosis pathway. Overexpression of BmVDAC2 in BmN cells inhibited BmNPV-induced cytochrome c (cyto c) release, decrease in mitochondrial membrane potential as well as apoptosis. Additionally, the inhibition of cyto c release by BmVDAC2 requires the involvement of BmRACK1 and protein kinase C. Interestingly, overexpression of p35 inhibited cyto c release during mitochondrial apoptosis in a RACK1 and VDAC2-dependent manner. Even the mutant p35, which loses Caspase inhibitory activity, could still bind to VDAC2 and inhibit cyto c release. In summary, our results indicated that BmNPV p35 interacts with the VDAC2-RACK1 complex to regulate apoptosis by inhibiting cyto c release. These findings confirm the interaction between BmVDAC2 and BmRACK1, the interaction between p35 and the VDAC2-RACK1 complex, and a novel target that BmNPV p35 regulates apoptosis in Bombyx mori via interaction with the BmVDAC2-BmRACK1 complex. The result provide an initial exploration of the function of this interaction in the BmNPV-induced mitochondrial apoptosis pathway.

Leaky gut, circulating immune complexes, arthralgia, and arthritis in IBD: coincidence or inevitability?

Most host-microbiota interactions occur within the intestinal barrier, which is essential for separating the intestinal epithelium from toxins, microorganisms, and antigens in the gut lumen. Gut inflammation allows pathogenic bacteria to enter the blood stream, forming immune complexes which may deposit on organs. Despite increased circulating immune complexes (CICs) in patients with inflammatory bowel disease (IBD) and discussions among IBD experts regarding their potential pathogenic role in extra-intestinal manifestations, this phenomenon is overlooked because definitive evidence demonstrating CIC-induced extra-intestinal manifestations in IBD animal models is lacking. However, clinical observations of elevated CICs in newly diagnosed, untreated patients with IBD have reignited research into their potential pathogenic implications. Musculoskeletal symptoms are the most prevalent extra-intestinal IBD manifestations. CICs are pivotal in various arthritis forms, including reactive, rheumatoid, and Lyme arthritis and systemic lupus erythematosus. Research indicates that intestinal barrier restoration during the pre-phase of arthritis could inhibit arthritis development. In the absence of animal models supporting extra-intestinal IBD manifestations, this paper aims to comprehensively explore the relationship between CICs and arthritis onset via a multifaceted analysis to offer a fresh perspective for further investigation and provide novel insights into the interplay between CICs and arthritis development in IBD.

Triglyceride-glucose index: A promising biomarker for predicting risks of adverse pregnancy outcomes in Hangzhou, China.

Introduction: The triglyceride-glucose (TyG) index has been recommended as an alternative indicator of insulin resistance (IR). However, the association between the TyG index and adverse pregnancy outcomes remains to be elucidated. Methods: The present retrospective study was conducted at Women's Hospital, Zhejiang University School of Medicine and involved a total of 8,514 participants. Maternal fasting lipid profiles and glucose concentrations were measured. Based on the TyG index, the participants were categorized into quartiles. Logistic regression analysis was used to calculate odds ratios (ORs) for each quartile with reference to the first quartile, while receiver operating characteristic (ROC) curve analysis, Hosmer-Lemeshow test, and calibration curve analysis were employed to evaluate the predictive ability of the TyG index for adverse pregnancy outcomes. Results: The TyG index was higher in patients with preeclampsia, preterm birth, and macrosomia. On univariate analysis, there was an increased risk of developing adverse pregnancy outcomes with increasing quartiles of the TyG. After adjusting for potential confounders in multivariable logistic regression analysis, a positive independent correlation was found between the TyG index and preeclampsia, preterm birth, and macrosomia. In ROC curve analysis for predicting the risks of preeclampsia, preterm birth, and macrosomia, the area under the curve (AUC) could reach 0.665, 0.588, and 0.606, respectively. These predictive models demonstrated good calibration (all P > 0.05). Conclusions: The TyG index showed a good predictive capacity for assessing the risk of adverse pregnancy outcomes, and it should receive sufficient clinical attention.

Bmo-miR-6498-5p suppresses Bombyx mori nucleopolyhedrovirus infection by down-regulating BmPLPP2 to modulate pyridoxal phosphate content in B. mori.

The RNA interference pathway mediated by microRNAs (miRNAs) is one of the methods to defend against viruses in insects. Recent studies showed that miRNAs participate in viral infection by binding to target genes to regulate their expression. Here, we found that the Bombyx mori miRNA, miR-6498-5p was down-regulated, whereas its predicted target gene pyridoxal phosphate phosphatase PHOSPHO2 (BmPLPP2) was up-regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Both in vivo and in vitro experiments showed that miR-6498-5p targets BmPLPP2 and suppresses its expression. Furthermore, we found miR-6498-5p inhibits BmNPV genomic DNA (gDNA) replication, whereas BmPLPP2 promotes BmNPV gDNA replication. As a pyridoxal phosphate (PLP) phosphatase (PLPP), the overexpression of BmPLPP2 results in a reduction of PLP content, whereas the knockdown of BmPLPP2 leads to an increase in PLP content. In addition, exogenous PLP suppresses the replication of BmNPV gDNA; in contrast, the PLP inhibitor 4-deoxypyridoxine facilitates BmNPV gDNA replication. Taken together, we concluded that miR-6498-5p has a potential anti-BmNPV role by down-regulating BmPLPP2 to modulate PLP content, but BmNPV induces miR-6498-5p down-regulation to promote its proliferation. Our findings provide valuable insights into the role of host miRNA in B. mori-BmNPV interaction. Furthermore, the identification of the antiviral molecule PLP offers a novel perspective on strategies for preventing and managing viral infection in sericulture.

USP7 as an emerging therapeutic target: A key regulator of protein homeostasis.

Maintaining protein balance within a cell is essential for proper cellular function, and disruptions in the ubiquitin-proteasome pathway, which is responsible for degrading and recycling unnecessary or damaged proteins, can lead to various diseases. Deubiquitinating enzymes play a vital role in regulating protein homeostasis by removing ubiquitin chains from substrate proteins, thereby controlling important cellular processes, such as apoptosis and DNA repair. Among these enzymes, ubiquitin-specific protease 7 (USP7) is of particular interest. USP7 is a cysteine protease consisting of a TRAF region, catalytic region, and C-terminal ubiquitin-like (UBL) region, and it interacts with tumor suppressors, transcription factors, and other key proteins involved in cell cycle regulation and epigenetic control. Moreover, USP7 has been implicated in the pathogenesis and progression of various diseases, including cancer, inflammation, neurodegenerative conditions, and viral infections. Overall, characterizing the functions of USP7 is crucial for understanding the pathophysiology of diverse diseases and devising innovative therapeutic strategies. This article reviews the structure and function of USP7 and its complexes, its association with diseases, and its known inhibitors and thus represents a valuable resource for advancing USP7 inhibitor development and promoting potential future treatment options for a wide range of diseases.

[Research Progress of NK Cell Therapy in Multiple Myeloma Treatment --Review].

Multiple myeloma (MM) is a hematologic neoplasm characterized by malignant proliferation of monoclonal plasma cells in the bone marrow. NK cells, a class of innate lymphocytes with potent natural killer activity, are capable of recognizing and destroying tumor cells and virally infected cells, and have attracted attention as a potential anticancer therapy. In patients with MM, NK cells are suppressed in number and function, resulting in reduced immune surveillance and clearance of myeloma cells. Restoring or enhancing the killing effect of NK cells on myeloma cells is an important strategy for MM immunotherapy, and some progress has been made in clinical trials targeting NK cellrelated therapies. This article reviews the research progress on the applications prospects of NK cell in MM immunotherapy.

Triglyceride-glucose index is a risk factor for breast cancer in China: a cross-sectional study.

BACKGROUND: This research delved into the association between the risk of the Chinese population suffering from breast cancer (BC) and the triglyceride-glucose (TyG) index. METHODS: A total of 2,111 sufferers with benign breast disease (BBD) and 477 sufferers with BC were enrolled, and their TyG index was measured. Participants with varying TyG index values were categorized into quartiles. Logistic regression analysis was employed to assess the relationship between the TyG index and BC risk. The diagnostic performance of the TyG index for different stages of BC was measured using the receiver operating characteristic (ROC) curve. RESULTS: The TyG index of BC sufferers exceeded that of BBD (P < 0.001). A continuous increase in the risk of BC was found to be positively correlated with an ever-increasing TyG index. In the unadjusted model, the risk of getting BC mounted with quartiles of the TyG index growing (P < 0.001). In a logistic regression analysis that included all confounders, the highest quartile of the TyG index was strongly linked to BC risk [1.43 (1.01, 2.02), P < 0.05]. Moreover, with the adjustment of potential confounders, a high TyG index was found to result in a 2.53-fold higher risk of being diagnosed with advanced BC. CONCLUSIONS: The risen TyG index was positively correlated to the heightening risk of BC and had the potential to serve as a promising biomarker for BC. Individuals with a high TyG index ought to be mindful of the heightened risk of BC onset and progression.

A high-precision jujube disease spot detection based on SSD during the sorting process.

The development of automated grading equipment requires achieving high throughput and precise detection of disease spots on jujubes. However, the current algorithms are inadequate in accomplishing these objectives due to their high density, varying sizes and shapes, and limited location information regarding disease spots on jujubes. This paper proposes a method called JujubeSSD, to boost the precision of identifying disease spots in jujubes based on a single shot multi-box detector (SSD) network. In this study, a diverse dataset comprising disease spots of varied sizes and shapes, varying densities, and multiple location details on jujubes was created through artificial collection and data augmentation. The parameter information obtained from transfer learning into the backbone feature extraction network of the SSD model, which reduced the time of spot detection to 0.14 s. To enhance the learning of target detail features and improve the recognition of weak information, the traditional convolution layer was replaced with deformable convolutional networks (DCNs). Furthermore, to address the challenge of varying sizes and shapes of disease spot regions on jujubes, the path aggregation feature pyramid network (PAFPN) and balanced feature pyramid (BFP) were integrated into the SSD network. Experimental results demonstrate that the mean average precision at the IoU (intersection over union) threshold of 0.5 (mAP@0.5) of JujubeSSD reached 97.1%, representing an improvement of approximately 6.35% compared to the original algorithm. When compared to existing algorithms, such as YOLOv5 and Faster R-CNN, the improvements in mAP@0.5 were 16.84% and 8.61%, respectively. Therefore, the proposed method for detecting jujube disease spot achieves superior performance in jujube surface disease detection and meets the requirements for practical application in agricultural production.

The interaction of Synapsin 2a and Synaptogyrin-3 regulates fear extinction in mice.

The mechanisms behind a lack of efficient fear extinction in some individuals are unclear. Here, by employing a principal components analysis-based approach, we differentiated the mice into extinction-resistant and susceptible groups. We determined that elevated synapsin 2a (Syn2a) in the infralimbic cortex (IL) to basolateral amygdala (BLA) circuit disrupted presynaptic orchestration, leading to an excitatory/inhibitory imbalance in the BLA region and causing extinction resistance. Overexpression or silencing of Syn2a levels in IL neurons replicated or alleviated behavioral, electrophysiological, and biochemical phenotypes in resistant mice. We further identified that the proline-rich domain H in the C-terminus of Syn2a was indispensable for the interaction with synaptogyrin-3 (Syngr3) and demonstrated that disrupting this interaction restored extinction impairments. Molecular docking revealed that ritonavir, an FDA-approved HIV drug, could disrupt Syn2a-Syngr3 binding and rescue fear extinction behavior in Syn2a-elevated mice. In summary, the aberrant elevation of Syn2a expression and its interaction with Syngr3 at the presynaptic site were crucial in fear extinction resistance, suggesting a potential therapeutic avenue for related disorders.

Hydrogen-bonded organic frameworks in solution enables continuous and high-crystalline membranes.

Hydrogen-Bonded organic frameworks (HOFs) are a type of emerging porous materials. At present, little research has been conducted on their solution state. This work demonstrates that HOFs fragment into small particles while maintaining their original assemblies upon dispersing in solvents, as confirmed by Cryo-electron microscopy coupled with 3D electron diffraction technology. 1D and 2D-Nuclear Magnetic Resonance (NMR) and zeta potential analyses indicate the HOF-based colloid solution and the isolated molecular solution have significant differences in intermolecular interactions and aggregation behavior. Such unique solution processibility allows for fabricating diverse continuous HOF membranes with high crystallinity and porosity through solution-casting approach on various substrates. Among them, HOF-BTB@AAO membranes show high C3H6 permeance (1.979 × 10-7 mol·s-1·m-2·Pa-1) and excellent separation performance toward C3H6 and C3H8 (SF = 14). This continuous membrane presents a green, low-cost, and efficient separation technology with potential applications in petroleum cracking and purification.

Bioinformatics and Network Pharmacology Explore the Role of Immune Cells in the Occurrence of Anti-Vascular Endothelial Growth Factor (VEGF) Resistance in Patients with Neovascular Age-Related Macular Degeneration(nAMD) and the Application of Complementary Medicine Treatment.

PURPOSE: This study explores the immune cells' role in anti-VEGF resistance in nAMD patients, and the potential of Zi-Yin-Jiang-Huo-Tang (ZYJHT), a Traditional Chinese Medicine formula, as complementary therapy. METHODS: Aqueous humor proteomics data from 10 nAMD patients with anti-VEGF resistance and 10 nAMD patients without anti-VEGF resistance were analyzed, investigating immune cells's role in anti-VEGF resistance and its underlying mechanism. Network pharmacology methods are employed to analyze the active ingredients in ZYJHT that contribute to therapeutic effects and their mechanisms. Real-time PCR (polymerase chain reaction) was used to detect changes in the expression of SOD1 (superoxide dismutase 1) after treatment with compounds targeting SOD1 in ARPE-19 cells. RESULTS: nAMD patients with anti-VEGF resistance showed enhancement of biological processes linked to the positive regulation of immune function, along with decreased cellular resistance to oxidative stress. Infiltration of B cells memory, plasma cells, CD8+and γδ-T cells were higher in nAMD patients with anti-VEGF resistance. SOD1 was identified as a hub gene in the occurrence of anti-VEGF resistance and a core therapeutic target of ZYJHT, negatively correlated with B and T cell infiltration. Compounds diosgenin, naringenin, and liquiritin in ZYJHT can bind to SOD1 and upregulating SOD1 expression in ARPE-19 cells.

Effect of 4 weeks vs 8 weeks of acupuncture for knee osteoarthritis in China: protocol for a randomised controlled trial.

INTRODUCTION: Knee osteoarthritis represents the prevalent and incapacitating disease. Acupuncture, a widely used clinical treatment for knee osteoarthritis, has been shown to ameliorate pain and enhance joint function in affected individuals. However, there is a lack of evidence comparing different courses of acupuncture for knee osteoarthritis. In this trial, we will assess the effect of 4 weeks vs 8 weeks of acupuncture in patients with knee osteoarthritis. METHODS AND ANALYSIS: The protocol is a pragmatic, parallel, two-arm randomised controlled trial, with the data analyst and assessor being blinded. 148 eligible patients with knee osteoarthritis will be randomly allocated in a 1:1 ratio to receive 4-week or 8-week acupuncture. Electroacupuncture will be administered three times per week for 4 or 8 weeks, respectively. Patients with knee osteoarthritis in both groups will be followed up to 26 weeks. The primary outcome is the response rate at week 26, and secondary outcomes include knee joint pain, knee joint function, knee joint stiffness, quality of life, patient global assessment, the Osteoarthritis Research Society International response rate and rescue medicine. A cost-effectiveness analysis will be carried out over 26 weeks. ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethical Committee of Beijing University of Chinese Medicine (2023BZYL0506). The study findings will be disseminated through presentation in a medical journal. Additionally, we plan to present them at selected conferences and scientific meetings. TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry (ChiCTR2300073383; https://www.chictr.org.cn/showproj.html?proj=199310).

Cuproptosis-Associated lncRNA Gene Signature Establishes New Prognostic Profile and Predicts Immunotherapy Response in Endometrial Carcinoma.

Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment. METHODS: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed. RESULTS: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated. CONCLUSIONS: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic.