ARHGAP17 Inhibits Hepatocellular Carcinoma Progression by Inactivation of Wnt/ß-Catenin Signaling Pathway.

As a member of Rho GAPs family, Rho GTPase-Activating Protein 17 (ARHGAP17) regulates cytoskeletal recombination, cell polarity, cell proliferation and cell migration. ARHGAP17 is identified as a tumor suppressor in numerous cancer types. Current study intends to examine ARHGAP17 expression and its possible influence on the progression of hepatocellular carcinoma (HCC). ARHGAP17 expression in HCC cells was verified by RT-PCR and western blot. The proliferation and invasion of HCC cells were evaluated by CCK8 assay and transwell assay, respectively. The mRNA expression of ARHGAP17, PCNA, E-cadherin, N-cadherin, ß-catenin, GSK-3ß, Axin1, and APC were detected by RT-PCR. The protein expression of ARHGAP17, PCNA, E-cadherin, N-cadherin, ß-catenin, p-ß-catenin, GSK-3ß, p-GSK-3ß, Axin1, and APC were detected by western blot. ARHGAP17 staining was evaluated by immunohistochemistry and immunofluorescence. ARHGAP17 expression decreased significantly in HCC tumors and HCC cells after EMT. In response to overexpression of ARHGAP17, the capacities of HCC cell proliferation and invasion were reduced significantly, which were also confirmed by tumorigenesis experiments in vivo. With overexpression of ARHGAP17 in HCC cells, the p-GSK3ß/GSK3ß decreased, while the p-ß-catenin/ß-catenin, Axin1 and APC increased. In conclusion, ARHGAP17 inhibits HCC progression by inactivating the Wnt/ß-catenin signaling pathway.

Correlation between serum leptin level and sleep monitoring indexes in patients with obstructive sleep apnea hypopnea syndrome and its predictive value: a cross-sectional analysis.

Objective: To investigate the association between serum leptin (LP) level and polysomnography (PSG) parameters in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: A cross-sectional study was conducted. The data of subjects who underwent PSG at hospital between January 2021 and December 2022 were collected retrospectively, 220 participants were included. The subjects were categorized into simple snoring group (n = 45), mild OSAHS group (n = 63), moderate OSAHS group (n = 52), and severe OSAHS group (n = 60). The general characteristics, PSG indices, and serological indices were collected retrospectively. Pearson correlation analysis was used to observe the correlation between serum LP level and PSG parameters. The value of serum LP level in predicting OSAHS was analyzed by receiver operating characteristic curve. Results: The serum LP level was positively correlated with micro-arousal count, micro-arousal index (MAI), high apnea hypopnea index, times of blood oxygen decreased by≥3% and time in saturation lower 90%, and negatively correlated with lowest nocturnal oxygen saturation and mean oxygen saturation (p < 0.05). The area under the curve (AUC) of serum LP level in predicting the occurrence of OSAHS was 0.8276 (95% CI: 0.7713-0.8839), and when the Youden index was 0.587, the sensitivity was 72.00%, and the specificity was 86.67% (p < 0.0001). In the population with high MAI, the AUC of serum LP level in predicting the occurrence of OSAHS was 0.8825 (95% CI: 0.7833-0.9817), and when the Youden index was 0.690, the sensitivity was 79.00% and the specificity was 90.00% (p < 0.0001). Conclusion: Serum LP level is associated with the severity of OSAHS. Serum LP level demonstrates a strong predictive value for the occurrence of OSAHS, particularly in population with high MAI.

Shear-wave elastography predicts T-restaging and pathologic complete response of rectal cancer post neoadjuvant chemoradiotherapy.

PURPOSE: To investigate the value of shear-wave elastography (SWE) in assessing the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer. METHODS: In this study, 455 participants with locally advanced rectal cancer who underwent nCRT at our hospital between September 2021 and December 2022 were prospectively enrolled. The participants were randomly divided into training and test cohorts in a 3:2 ratio. Clinical baseline data, endorectal ultrasound examination data, and SWE measurements were collected for all participants. Logistic regression models were used to predict whether rectal cancer after nCRT had a low T staging (ypT 0-2 stage, Model A) and pathological complete response (pCR) (Model B). Paired Chi-square tests were used to compare the diagnostic performances of the radiologists to those of Models A and B. RESULTS: In total, 256 participants were included. The area under the receiver operating characteristic curve of Models A and B in the test cohort were 0.94 (0.87, 1.00) and 0.88 (0.80, 0.97), respectively. The optimal diagnostic thresholds for Models A and B were 14.9 kPa for peritumoral mesangial Emean and 15.2 kPa for tumor Emean, respectively. The diagnostic performance of the radiologists was significantly lower than that of Models A and B, respectively (p < 0.05). CONCLUSION: SWE can be used as a feasible method to evaluate the treatment response of nCRT for locally advanced rectal cancer.

Development and validation of a prediction model for frailty in breast cancer patients with extended survival.

BACKGROUND: Breast cancer (BC) patients with extended survival show a higher incidence of frailty. This study aimed to develop and validate a novel model combining sociodemographic factors (SF) and disease-related factors (DRF) to identify frailty in BC patients with extended survival. METHODS: This cross-sectional study examined data from 1167 patients admitted to a large urban academic medical centre. Three types of predictive models were constructed in the training set (817 patients): the SF model, the DRF model, and the SF + DRF model (combined model). The model performance and effectiveness were assessed using receiver operating characteristic (ROC) curves, calibration plots and decision curves analysis (DCA). Then the model was subsequently validated on the validation set. RESULTS: The incidence of frailty in BC patients with extended survival was 35.8%. We identified six independent risk factors including age, health status, chemotherapy, endocrine therapy, number of comorbidities and oral medications. Ultimately, we constructed an optimal model (combined model C) for frailty. The predictive model showed significantly high discriminative accuracy in the training set AUC: 0.754, (95% CI, 0.719-0.789; sensitivity: 76.8%, specificity: 62.2%) and validation set AUC: 0.805, (95% CI, 0.76-0.85), sensitivity: 60.8%, specificity: 87.1%) respectively. A prediction nomogram was constructed for the training and validation sets. Calibration and DCA were performed, which indicated that the clinical model presented satisfactory calibration and clinical utility. Ultimately, we implemented the prediction model into a mobile-friendly web application that provides an accurate and individualized prediction for BC. CONCLUSIONS: The present study demonstrated that the prevalence of frailty in BC patients with extended survival was 35.8%. We developed a novel model for screening frailty, which may provide evidence for frailty screening and prevention.

Label-Free Identification of AML1-ETO Positive Acute Myeloid Leukemia Using Single-Cell Raman Spectroscopy.

Acute myeloid leukemia (AML) is a malignant hematological tumor disease. Chromosomal abnormality is an independent prognostic factor in AML. AML with t(8:21) (q22; q22)/AML1-ETO (AE) is an independent disease group. In this research, a new method based on Raman spectroscopy is reported for label-free single-cell identification and analysis of AE fusion genes in clinical AML patients. Raman spectroscopy reflects the intrinsic vibration information of molecules in a label-free and non-destructive manner, and the fingerprint Raman spectrum of cells characterizes intracellular molecular types and relative concentration information, so as to realize the identification and molecular metabolism analysis of different kinds of cells. We collected the Raman spectra of bone marrow cells from clinically diagnosed AML M2 patients with and without the AE fusion gene. Through comparison of the average spectra and identification analysis based on multivariate statistical methods such as principal component analysis and linear discriminant analysis, the distinction between AE positive and negative sample cells in M2 AML patients was successfully achieved, and the single-cell identification accuracy was more than 90%. At the same time, the Raman spectra of the two types of cells were analyzed by the multivariate curve resolution alternating least squares decomposition method. It was found that the presence of the AE fusion gene may lead to the metabolic changes of lipid and nucleic acid in AML cells, which was consistent with the results of genomic and metabolomic multi-omics studies. The above results indicate that single-cell Raman spectroscopy has the potential for early identification of AE-positive AML.

Establishment and validation of a predictive model for tracheotomy in critically ill patients and analysis of the impact of different tracheotomy timing on patient prognosis.

BACKGROUND: In critically ill patients receiving invasive mechanical ventilation (IMV), it is unable to determine early which patients require tracheotomy and whether early tracheotomy is beneficial. METHODS: Clinical data of patients who were first admitted to the ICU and underwent invasive ventilation for more than 24 h in the Medical Information Marketplace in Intensive Care (MIMIC)-IV database were retrospectively collected. Patients were categorized into successful extubation and tracheotomy groups according to whether they were subsequently successfully extubated or underwent tracheotomy. The patients were randomly divided into model training set and validation set in a ratio of 7:3. Constructing predictive models and evaluating and validating the models. The tracheotomized patients were divided into the early tracheotomy group (< = 7 days) and the late tracheotomy group (> 7 days), and the prognosis of the two groups was analyzed. RESULTS: A total of 7 key variables were screened: Glasgow coma scale (GCS) score, pneumonia, traumatic intracerebral hemorrhage, hemorrhagic stroke, left and right pupil responses to light, and parenteral nutrition. The area under the receiver operator characteristic (ROC) curve of the prediction model constructed through these seven variables was 0.897 (95% CI: 0.876-0.919), and 0.896 (95% CI: 0.866-0.926) for the training and validation sets, respectively. Patients in the early tracheotomy group had a shorter length of hospital stay, IMV duration, and sedation duration compared to the late tracheotomy group (p < 0.05), but there was no statistically significant difference in survival outcomes between the two groups. CONCLUSION: The prediction model constructed and validated based on the MIMIC-IV database can accurately predict the outcome of tracheotomy in critically ill patients. Meanwhile, early tracheotomy in critically ill patients does not improve survival outcomes but has potential advantages in shortening the duration of hospitalization, IMV, and sedation.

Polyene phosphatidylcholine promotes tibial fracture healing in rats by stimulating angiogenesis dominated by the VEGFA/VEGFR2 signaling pathway.

One of the factors that predispose to fractures is liver damage. Interestingly, fractures are sometimes accompanied by abnormal liver function. Polyene phosphatidylcholine (PPC) is an important liver repair drug. We wondered if PPC had a role in promoting fracture healing. A rat model of tibial fracture was developed using the modified Einhorn model method. X-rays were used to detect the progression of fracture healing. Progress of ossification and angiogenesis at the fracture site were analyzed by Safranin O/fast green staining and CD31 immunohistochemistry. To investigate whether PPC has a direct angiogenesis effect, HUVECs were used. We performed MTT, wound healing, Transwell migration, and tube formation assays. Finally, RT-qPCR and Western blot analysis were used to study the underlying mechanism. The results showed that PPC significantly shortened the apparent recovery time of mobility in rats. PPC treatment significantly promoted the formation of cartilage callus, endochondral ossification, and angiogenesis at the fracture site. In vitro, PPC promoted the proliferative viability of HUVECs, their ability to heal wounds, and their ability to penetrate membranes in the Transwell apparatus and increased the tube formation of cells. The transcription of VEGFA, VEGFR2, PLCγ, RAS, ERK1/2 and MEK1/2 was significantly up regulated by PPC. Further, the protein level results demonstrated a significant increase in the expression of VEGFA, VEGFR2, MEK1/2, and ERK1/2 proteins. In conclusion, our findings suggest that PPC promotes angiogenesis by activating the VEGFA/VEGFR2 and downstream signaling pathway, thereby accelerating fracture healing.

Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2-Amino-bicyclo[2.1.1]hexenes.

Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf)3-catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2-amino-bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB-based cycloaddition chemistry.

Extraction, characterization and intestinal anti-inflammatory and anti-oxidative activities of polysaccharide from stems and leaves of Chuanminshen violaceum M. L. Sheh & R. H. Shan.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.

Stretchable and Breathable Electroluminescent Displays Based on Ultrathin Nanocomposite Designs.

Stretchable electroluminescent devices represent an emerging optoelectronic technology for future wearables. However, their typical construction on sub-millimeter-thick elastomers has limited moisture permeability, leading to discomfort during long-term skin attachment. Although breathable textile displays may partially address this issue, they often have distinct visual appearances with discrete emissions from fibers or fiber junctions. This study introduces a convenient procedure to create stretchable, permeable displays with continuous luminous patterns. The design utilizes ultrathin nanocomposite devices embedded in a porous elastomeric microfoam to achieve high moisture permeability. These displays also exhibit excellent deformability, low-voltage operation, and excellent durability. Additionally, the device is decorated with fluorinated silica nanoparticles to achieve self-cleaning and washable capabilities. The practical implementation of these nanocomposite devices is demonstrated by creating an epidermal counter display that allows intimate integration with the human body. These developments provide an effective design of stretchable and breathable displays for comfortable wearing.

LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.

Pancreatic cancer is a malignancy with high mortality. In addition to the few symptoms until the disease reaches an advanced stage, the high fatality rate is attributed to its rapid development, drug resistance and lack of appropriate treatment. In the selection and research of therapeutic drugs, gemcitabine is the first-line drug for pancreatic cancer. Solving the problem of gemcitabine resistance in pancreatic cancer will contribute to the progress of pancreatic cancer treatment. Long non coding RNAs (lncRNAs), which are RNA transcripts longer than 200 nucleotides, play vital roles in cellular physiological metabolic activities. Currently, our group and others have found that some lncRNAs are aberrantly expressed in pancreatic cancer cells, which can regulate the process of cancer through autophagy and Wnt/ß-catenin pathways simultaneously and affect the sensitivity of cancer cells to therapeutic drugs. This review presents an overview of the recent evidence concerning the node of lncRNA for the cross-talk between autophagy and Wnt/ß-catenin signaling in pancreatic cancer, together with the practicability of lncRNAs and the core regulatory factors as targets in therapeutic resistance.

Injectable Photothermal PDA/Chitosan/ß-Glycerophosphate Thermosensitive Hydrogels for Antibacterial and Wound Healing Promotion.

Controlling infections while reducing the use of antibiotics is what doctors as well as researchers are looking for. As innovative smart materials, photothermal materials can achieve localized heating under light excitation for broad-spectrum bacterial inhibition. A polydopamine/chitosan/ß-glycerophosphate temperature-sensitive hydrogel with excellent antibacterial ability is synthesized here. Initially, the hydrogel has good biocompatibility. In vitro experiments reveal its noncytotoxic property when cocultured with gingival fibroblasts and nonhemolytic capability. Concurrently, the in vivo biocompatibility is confirmed through liver and kidney blood markers and staining of key organs. Crucially, the hydrogel has excellent photothermal conversion performance, which can realize the photothermal conversion of hydrogel up to 3 mm thickness. When excited by near-infrared light, localized heating is attainable, resulting in clear inhibition impacts on both Staphylococcus aureus and Escherichia coli, with the inhibition rates of 91.22% and 96.69%, respectively. During studies on mice's infected wounds, it is observed that the hydrogel can decrease S. aureus' presence in the affected area when exposed to near-infrared light, and also lessen initial inflammation and apoptosis, hastening tissue healing. These findings provide valuable insights into the design of antibiotic-free novel biomaterials with good potential for clinical applications.

Delaying age at first sexual intercourse provides protection against oral cavity cancer: a mendelian randomization study.

Aim: To investigate whether age at first sexual intercourse could lead to any changes in the risk of oral cavity cancer. Methods: A two-sample mendelian randomization was conducted using genetic variants associated with age at first sexual intercourse in UK biobank as instrumental variables. Summary data of Northern American from a previous genome-wide association study aimed at oral cavity cancer was served as outcome. Three analytical methods: inverse variance-weighted, mendelian randomization Egger, and weighted median were used to perform the analysis, among which inverse variance-weighted was set as the primary method. Robustness of the results was assessed through Cochran Q test, mendelian randomization Egger intercept tests, MR PRESSO, leave one out analysis and funnel plot. Results: The primary analysis provided substantial evidence of a positive causal relationship age at first sexual intercourse and the risk of oral cavity cancer (p = 0.0002), while a delayed age at first sexual intercourse would lead to a decreased risk of suffering oral cavity cancer (ß = -1.013). The secondary outcomes confirmed the results (all ß < 0) and all assessments supported the robustness, too (all p > 0.05). Conclusion: The study demonstrates that a delayed sexual debut would provide protection against OCC, thus education on delaying sexual intercourse should be recommended.

Subjective benefits from wearing self-fitting over-the-counter hearing aids in the real world.

Introduction: In 2022, the US Food and Drug Administration enacted final regulations to establish the category of over-the-counter (OTC) hearing aids aimed at reducing barriers to access hearing health care for individuals with self-perceived mild to moderate hearing loss. However, given the infancy of this device category, the effectiveness of OTC hearing aids in real-world environments is not yet well understood. Methods and results: To gain insights into the perceived benefit of self-fitting OTC hearing aids, a two-pronged investigation was conducted. In the primary investigation, 255 active users of a self-fitting OTC hearing aid were surveyed on their perceived benefit using an abridged form of the Satisfaction with Amplification in Daily Living (SADL) scale. The mean global (4.9) and subscale scores (Positive Effect (PE): 4.3; Negative Features (NF): 4.3; Personal Image (PI): 6.1) were within the range of those previously reported for users of prescription hearing aids. In the secondary investigation, 29 individuals with self-reported hearing impairment but no prior experience with the investigational self-fitting OTC hearing aids used the devices and reported their perceived benefit and satisfaction following short-term usage. For this prospective group, the global SADL (5.4) and subscale scores (PE: 4.8; NF: 4.9; PI: 6.5) following a minimum of 10 weeks of real-world use were also within the range of those previously reported for traditional hearing aid users. In addition, this prospective group was also asked quality of life questions which assessed psychological benefits of hearing aid use. Responses to these items suggest hearing aid related improvements in several areas spanning emotional health, relationships at home and at work, social life, participation in group activities, confidence and feelings about one's self, ability to communicate effectively, and romance. Discussion: Converging data from these investigations suggest that self-fitting OTC hearing aids can potentially provide their intended users with a level of subjective benefit comparable to what prescription hearing aid users might experience.

Dietary Replacement of Soybean Meal with Zanthoxylum bungeanum Seed Meal on Growth Performance, Blood Parameters, and Nutrient Utilization in Broiler Chickens.

Zanthoxylum bungeanum seed meal (ZBM), a novel plant protein raw material, has shown promising potential in enhancing the growth of broiler chickens as a substitute for soybean meal (SBM) in feed. In the artificial digestive experiment of vitro experiments, the digestibility of ZBM and SBM were assessed using the SDS-III Single Stomach Animal Biometric Digestion System. Subsequently, 180 1-day old AA chicks were divided into three groups for in vivo experiments: corn-soybean-meal-based diet (CON group); ZBM replacing 5% soybean meal in the basal diet (ZBM-1 group); ZBM replacing 10% soybean meal in the basal diet (ZBM-2 group). The experiment period lasted for 42 days. Compared to SBM, ZBM demonstrated higher crude protein content, dry matter digestibility, and extracorporeal digestible protein. Compared with the CON group, the broilers in the ZBM-2 group showed improved ADG and ADFI during the 1-21 d, 22-42 d, and 1-42 d periods (p < 0.05). Furthermore, the ZBM groups exhibited significant increases in slaughter performance compared with the CON group (p < 0.05). The substitution of ZBM for SBM also leads to a significant reduction in serum enzyme indicators (p < 0.05). Additionally, the lipoprotein and total cholesterol of the ZBM groups were significantly lower than those of the CON group (p < 0.05). Substituting SBM with ZBM significantly enhances the activity of superoxide dismutase and the content of immunoglobulin G in broiler serum, while reducing the content of malondildehyde (p < 0.05). The ZBM groups showed significantly higher utilization of dry matter, crude protein, and energy compared with the CON group (p < 0.05). In conclusion, the study confirmed that the substitution of SBM with 5-10% ZBM in broiler diets has a significant positive effect on growth, development, antioxidant capacity, immune function, and nutrient utilization. This study not only provides a theoretical foundation for the utilization of ZBM in broiler diets but also offers an effective approach for reducing reliance on soybean meal.

A Novel Dual-Band Circularly Polarized Wearable Antenna.

A circularly polarized wearable antenna operating in the 2.45/5.8 GHz ISM dual bands is proposed, which consists of a coplanar waveguide-fed rectangular monopole antenna and two parasitic branches. The monopole rectangular radiation patch can generate 2.45 and 7 GHz frequency bands and has linear polarization characteristics. By adding L-shaped parasitic branches and L-like grounded branches on both sides of the monopole, the 7 GHz operating frequency band can be moved to the 5.8 GHz frequency band, and circular polarization characteristics can be achieved in both the 2.45 and 5.8 GHz frequency bands. The size of the antenna is 48.7 mm × 42.1 mm × 1.016 mm. The simulated -10 dB impedance bandwidths of the antenna are 1.8-2.66 GHz and 5.48-6.98 GHz, respectively. The 3 dB axial ratio bandwidths are 2.34-2.67 GHz and 5.58-6.39 GHz, respectively, and it has dual-band circular polarization characteristics. In addition, the radiation characteristics of the antenna and its safety performance near the human body were analyzed. The antenna prototype has been constructed, and the measurement and simulation results have good consistency. The proposed antenna is suitable for application in wearable devices.

The efficacy and safety of apatinib combined with S-1 for advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Advanced gastric cancer (AGC) that does not respond to first-line therapy poses a challenge to clinical management. The objective of this study was to compare the efficacy and safety of apatinib combined with S-1 in second-line and above treatment of AGC. METHODS: Cochrane Library, Science Direct, EMBASE, PubMed, and CNKI were searched for randomized controlled trial until August 2023. Only patients who met "Standardized Diagnosis and Treatment Guide for Gastric Cancer" were included in the study. The accurate data and distinguishing between follow-up time and drug dose were extracted to reduce heterogeneity and the risk of bias of the included trials was evaluated according to the Cochrane Handbook. Finally, the survival benefit of the treatment was evaluated based on clinical response rate, survival period, biochemical index, and adverse event occurrence in the trial. RESULTS: The meta-analysis included 29 randomized controlled trials involving 2149 participants. Statistically significant increases in clinical effective rate (odds ratios = 2.61, 95% confidence interval [2.13-3.20], P < .00001) and disease control rate (odds ratios = 3.16, 95% confidence interval [2.54-3.94], P < .00001) were found when apatinib combined with S-1, and also had obvious advantages in reducing tumor markers and regulating immune factors. In addition, apatinib combined with S-1 significantly increased the risk of hypertension but reduced damage to liver function, while the improvement of other adverse events was not pronounced. DISCUSSION: Apatinib combined with S-1 is more effective and safe for second-line and above treatment of AGC. This study minimized the conclusion bias caused by the basic data sources, but more high-quality studies are still needed to validate these conclusions.

Comparison of electrical microstimulation artifact removal methods for high-channel-count prostheses.

BACKGROUND: Neuroprostheses are used to electrically stimulate the brain, modulate neural activity and restore sensory and motor function following injury or disease, such as blindness, paralysis, and other movement and psychiatric disorders. Recordings are often made simultaneously with stimulation, allowing the monitoring of neural signals and closed-loop control of devices. However, stimulation-evoked artifacts may obscure neural activity, particularly when stimulation and recording sites are nearby. Several methods have been developed to remove stimulation artifacts, but it remains challenging to validate and compare these methods because the 'ground-truth' of the neuronal signals may be contaminated by artifacts. NEW METHOD: Here, we delivered stimulation to the visual cortex via a high-channel-count prosthesis while recording neuronal activity and stimulation artifacts. We quantified the waveforms and temporal properties of stimulation artifacts from the cortical visual prosthesis (CVP) and used them to build a dataset, in which we simulated the neuronal activity and the stimulation artifacts. We illustrate how to use the simulated data to evaluate the performance of six software-based artifact removal methods (Template subtraction, Linear interpolation, Polynomial fitting, Exponential fitting, SALPA and ERAASR) in a CVP application scenario. RESULTS: We here focused on stimulation artifacts caused by electrical stimulation through a high-channel-count cortical prosthesis device. We find that the Polynomial fitting and Exponential fitting methods outperform the other methods in recovering spikes and multi-unit activity. Linear interpolation and Template subtraction recovered the local-field potentials. CONCLUSION: Polynomial fitting and Exponential fitting provided a good trade-off between the quality of the recovery of spikes and multi-unit activity (MUA) and the computational complexity for a cortical prosthesis.

Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.