Postoperative fever and clinical outcomes after endoscopic surgery for spontaneous intracerebral hemorrhage: a retrospective database study.

BACKGROUND: Spontaneous intracerebral hemorrhage (SICH) is a severe stroke with high mortality and disability rates. Endoscopic surgery is an increasingly widely used minimally invasive method for the treatment of SICH. However, the impact of fever on patient outcomes remains unclear. METHODS: We retrospectively included patients aged 18 years or older with supratentorial SICH confirmed by CT, who underwent endoscopic hematoma evacuation within 48 h of symptom onset. The primary outcome was the modified Rankin Scale (mRS) score at 3 months. Secondary outcomes included hospital and neurosurgical intensive care unit (NSICU) stays, and perioperative complications. We analyzed the association between postoperative fever (highest temperature within 24 h after surgery) and these outcomes using multivariate analysis, generalized additive models, and segmented regression analysis. RESULTS: Of the 56 patients, 38 had favorable outcomes (mRS ≤ 3) and 18 had unfavorable outcomes (mRS > 3) at 3 months. A threshold effect at 38.2 °C was observed between postoperative body temperature and clinical outcomes. The mean age was 56 years (SD = 9) for the > 38.2 °C group and 58 years (SD = 8) for the ≤ 38.2 °C group, with a similar proportion of male patients (63% vs. 69%, P = 0.635). Patients with postoperative fever had larger hematoma volumes (65 vs. 56 mL; P = 0.008). Other characteristics were similar between the groups. Postoperative fever (> 38.2 °C) was independently associated with a 4.99-fold increased risk of unfavorable outcomes (95% CI = [1.13 to 25.90]; P = 0.040), which remained significant after excluding patients with postoperative complications (adjusted RR = 16.03, 95% CI = [1.69 to 417.24]; P = 0.033). The association was consistent across subgroups with different Glasgow Coma Scale scores, hematoma volumes, and intraventricular extension. Postoperative fever was also associated with longer NSICU stays (3.1 vs. 2.3 days; P = 0.023), longer hospital stays (17.2 vs. 13.6 days; P = 0.010), more residual hematoma, and greater edema volume. Different antipyretic therapies did not affect outcomes. CONCLUSIONS: This study identifies a temperature threshold (38.2 °C) associated with poor outcomes in SICH patients undergoing endoscopic surgery. Further research is needed to mitigate postoperative fever and improve patient outcomes.

Achieving a balance of rapid Zn2+ desolvation and hydrogen evolution reaction inertia at the interface of the Zn anode.

It is difficult to achieve fast kinetics of Zn2+(H2O)6 desolvation as well as HER inertia at the same electrolyte/Zn interface during long-term cycling of Zn plating/stripping in aqueous Zn-ion batteries. Herein, an effective interface construction strategy with hydrophilic transition metal oxides was proposed to achieve that balance using a CeO2 layer coating. The hydrophilic CeO2 layer can bring a balance between improving the access to the anode surface for Zn2+(H2O)6 electrolyte ions, providing uniform Zn2+ nucleation sites and HER inertia. What's more, Zn corrosion can be significantly inhibited benefiting from this coating layer. The efficiency of aqueous Zn-ion batteries showed a great enhancement. Ultra-long plating/stripping stability up to 1600 h and excellent recovery (returning to 0.5 from 20 mA cm-2) for the symmetric CeO2@Zn system were observed. A full cell with the MnO2 cathode (CeO2@Zn//MnO2) with good reversibility and stability (∼600 cycles) was fabricated for practical application. Our work provides a fundamental understanding and an essential solution to deal with the balance between rapid desolvation and inhibition of the hydrogen evolution reaction, which is important for promoting the practical application of rechargeable Zn batteries.

Scan-Rate-Dependent Ion Current Rectification in Bipolar Interfacial Nanopores.

This study presents a theoretical investigation into the voltammetric behavior of bipolar interfacial nanopores due to the effect of potential scan rate (1-1000 V/s). Finite element method (FEM) is utilized to explore the current-voltage (I-V) properties of bipolar interfacial nanopores at different bulk salt concentrations. The results demonstrate a strong impact of the scan rate on the I-V response of bipolar interfacial nanopores, particularly at relatively low concentrations. Hysteresis loops are observed in bipolar interfacial nanopores under specific scan rates and potential ranges and divided by a cross-point potential that remains unaffected by the scan rate employed. This indicates that the current in bipolar interfacial nanopores is not just reliant on the bias potential that is imposed but also on the previous conditions within the nanopore, exhibiting history-dependent or memory effects. This scan-rate-dependent current-voltage response is found to be significantly influenced by the length of the nanopore (membrane thickness). Thicker membranes exhibit a more pronounced scan-rate-dependent phenomenon, as the mass transfer of ionic species is slower relative to the potential scan rate. Additionally, unlike conventional bipolar nanopores, the ion current passing through bipolar interfacial nanopores is minimally affected by the membrane thickness, making it easier to detect.

Coating Fe3O4 quantum dots with glutamic acid to achieve enhanced catalysis for facile and sensitive detection of chromium(VI) in water.

A universal green synthesis approach for Glu-Fe3O4 quantum dots (QDs) with ultrasmall size (∼3.3 nm) and enhanced catalysis was demonstrated using glutamic acid (Glu) as a dopant. Abundant carboxylic groups and amino groups on the surfaces with a zeta potential of -6.28 mV resulted in greatly improved environmental stability. The Glu-Fe3O4 QDs exhibited oxidoreductase-like catalytic activity. The steady-state kinetic assays indicated that the QDs had a high binding affinity for the substrate TMB. A facile and sensitive colorimetric platform was developed using the Glu-Fe3O4 QDs for the detection of Cr(VI) in naturally sourced water and waste water, which showed a detection limit of 31.02 nM, much lower than the maximum Cr(VI) level permitted in drinking water by the World Health Organization (WHO) and the industrial water threshold. This universal green synthesis approach and the unique catalytic activity of Fe3O4 QDs open a new horizon in materials chemistry and the development of colorimetric biosensors for environmental protection and public health.

Mesenchymal stem cells alleviate inflammatory responses through regulation of T-cell subsets.

Immune-mediated inflammatory disease (IMID) is a complex disorder characterized by excessive immune responses involving T cells and their subsets, leading to direct tissue damage. T cells can be broadly categorized into CD4+ T cells and CD8+ T cells. CD4+ T cells are composed of several subsets, including T helper (Th)1, Th2, Th9, Th17, Th22, follicular helper T cells (Tfhs), and regulatory T cells (Tregs), while effector CD8+ T cells consist mainly of cytotoxic T cells (CTLs). Current therapies for IMID are ineffective, prompting exploration into mesenchymal stem cells (MSCs) as a promising clinical treatment due to their immunomodulatory effects and self-renewal potential. Recent studies have shown that MSCs can suppress T cells through direct cell-to-cell contact or secretion of soluble cytokines. Nevertheless, the precise effects of MSCs on T cell subsets remain inadequately defined. In this review, we summarize the most recent studies that have examined how MSCs modulate one or more effector T-cell subsets and the mechanisms behind these modifications in vitro and several mouse models of clinical inflammation. This also provides theoretical support and novel insights into the efficacy of clinical treatments involving MSCs. However, the efficacy of MSC therapies in clinical models of inflammation varies, showing effective remission in most cases, but also with exacerbation of T-cell-mediated inflammatory damage in some instances.

Directly Characterizing the Capture Radius of Tethered Double-Stranded DNA by Single-Molecule Nanopipette Manipulation.

The tethered molecule exhibits characteristics of both free and fixed states, with the electrodynamics involved in its diffusion, electrophoresis, and stretching processes still not fully understood. We developed a Single-Molecule Manipulation, Identification, and Length Examination (SMILE) system by integrating piezoelectric devices with nanopipettes. This system enabled successful capture and stretching of tethered double-stranded DNA within the nanopore. Our research unveiled distinct capture (rcapture) and stretch radii (rstretch) surrounding the DNA's anchor point. Notably, consistent ratios of capture radius for DNA of varying lengths (2k, 4k, and 6k base pairs) were observed across different capturing voltages, approximately 1:1.4:1.83, showing a resemblance to their gyration radius ratios. However, the ratios of stretch radius are consistent to their contour length (L0), with the stretching ratio (rstretch/L0) increasing from 70 to 90% as the voltage rose from 100 to 1000 mV. Additionally, through numerical simulations, we identified the origin of capture and stretch radii, determined by the entropic elasticity-induced capture barrier and the electric field-dominant escape barrier. This research introduces an innovative methodology and outlines research perspectives for a comprehensive exploration of the conformational, electrical, and diffusion characteristics of tethered molecules.

Effectiveness of DL-3-n-butylphthalide in the treatment of poststroke cognitive impairment and its associated predictive cytokines: a systematic review and meta-analysis.

BACKGROUND: The efficacy of DL-3-n-butylphthalide (NBP) in the treatment of post-stroke cognitive impairment (PSCI) has been reported previously. However, the course of treatment that shows curative effect and cytokines predictive of the efficacy of NBP in the treatment of PSCI have not been systematically evaluated. This study aimed to assess the efficacy, course of treatment, and cytokines that can predict the effectiveness of NBP in treating poststroke cognitive impairment PSCI. METHODS: This study has been registered with PROSPERO (registration number CRD42024518768). Randomized controlled trial (RCT) data dated by November 12, 2023 were retrieved from the PubMed, Embase, Cochrane Library, Web of Science, Wanfang, CNKI, CSTJ, and SinoMed databases using medical subject terms combined with free words. The updated Cochrane RoB-I Risk of Bias tool was utilized for literature quality evaluation. Statistical analysis were carried out using Review Manager 5.4.1 software. RESULTS: Thirty-eight original studies involving 5417 PSCI patients were analyzed. The results showed that NBP had a beneficial impact on cognitive function in PSCI patients when used alone or in combination therapy, as assessed by the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scale. The effect sizes were significant for both monotherapy and combination therapy. Subgroup analyses based on treatment cycle indicated that NBP enhanced cognitive function in PSCI patients from 1 week after intervention: MMSE (SMD = 0.43, 95% CI [0.28, 0.58], P < 0.001), MoCA (SMD = 0.44, 95% CI [0.27, 0.61], P < 0.001). There was a cumulative enhancement in cognitive function within 6 months after NBP treatment based on the MoCA scores (SMD = 0.61, 95% CI [0.30, 0.91], P < 0.001). Furthermore, decreased levels of the cytokines Hs-CRP, TNF-α, IL-6, IL-8, Hcy, NSE, MDA, MMP-9, and Cys-C (SMD = -2.28, 95% CI [-2.97, 1.58], P < 0.001) and increased levels of BDNF, VEGF, and TIMP-1 (SMD = 2.80, 95% CI [1.66, 3.94], P < 0.001) were also predictive of treatment efficacy. CONCLUSION: NBP plays a beneficial role in improving cognitive function in PSCI patients, and their prognoses could be predicted by serum cytokine levels. However, high-quality, multicenter, multisample, and RCTs are still needed to confirm the clinical validity of NBP due to its low methodological quality.

Glycolysis-related genes predict prognosis and indicate immune microenvironment features in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a major contributor to cancer-related mortality. Glycolysis plays a pivotal role in tumor microenvironment (TME) reprogramming. In this research, the functions of glycolysis-associated genes (GRGs) were evaluated to predict the outcome and reveal the characteristics of the immune microenvironment in individuals with stomach cancer. METHODS: The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) cohort provided gene expression and clinical data for gastric cancer (GC) patients, which were further authenticated using datasets sourced from the Gene Expression Omnibus (GEO). By referencing the Molecular Signatures Database (MSigDB), a total of 326 GRGs were pinpointed. The various subtypes of GC were outlined through consensus clustering, derived from the expression patterns of these GRGs. Utilizing multivariate Cox regression analysis, a multigene risk score model was formulated. Both the CIBERSORT and ESTIMATE algorithms played a pivotal role in assessing the immune microenvironment. To delve into the biological functions of the key genes, wound healing, transwell invasion, and MTT assays were conducted. RESULTS: Based on the expression patterns of GRGs, patients were categorized into two distinct groups: the metabolic subtype, designated as cluster A, and the immune subtype, labeled as cluster B. Patients belonging to cluster B exhibited a poorer prognosis. A prognostic risk score model, formulated upon the expression levels of six key GRGs - ME1, PLOD2, NUP50, CXCR4, SLC35A3, and SRD35A3 - emerged as a viable tool for predicting patient outcomes. The downregulation of CXCR4 notably diminished the glycolytic capacity of gastric cancer (GC) cells, alongside their migratory, invasive, and proliferative capabilities. Intriguingly, despite the adverse prognostic implications associated with both the immune subtype (cluster B) and the high-risk cohort, these groups exhibited a favorable immune microenvironment coupled with elevated expression of immune checkpoint genes. Our investigations revealed a positive correlation between high CXCR4 expression and low ME1 expression with the infiltration of CD8+ T cells, as well as an enhanced responsiveness to treatment with an anti-PD-1 immune checkpoint inhibitor. CONCLUSIONS: In this study, we discovered that the expression profiles of GRGs hold the potential to forecast the prognosis of gastric cancer (GC) patients, thereby possibly aiding in clinical treatment decision-making.

EGFR-TKIs Combined with Allogeneic CD8+ NKT Cell Immunotherapy to Treat Patients with Advanced EGFR-Mutated Lung Cancer.

Background: To evaluate the efficacy and safety of allogenic CD8 + natural killer T (CD8+ NKT) immunotherapy combined with gefitinib in the treatment of advanced or metastatic EGFR mutant non-small cell lung cancer (NSCLC). Methods: This study is prospective. The NSCLC patients with exon 19 (Ex19del) or exon 21 L858R point mutations, and response to gefitinib treatment were enrolled into the trial to be randomly assigned into the gefitinib arm and the gefitinib/NKT arm. Allogenic CD8+ NKT cells were cultured in vitro and adaptive transferred into the patients via vein in the gefitinib/NKT arm. The primary endpoint was progression-free survival (PFS). Secondary endpoint analysis included time to disease progression (TTP), overall survival (OS), levels of serum tumour markers for carcinoembryonic antigen (CEA) and alanine aminotransferase (ALT) in the blood, the response rate and safety. From July 2017 to June 2021, 19 patients were randomly assigned to the gefitinib arm (n = 8) and the gefitinib/NKT arm (n = 11). Results: The estimated median survival PFS in the gefitinib/NKT arm was significantly longer than that of the gefitinib arm (12 months vs 7 months). Similar results were also observed for the median TTP. Moreover, the gefitinib/NKT arm had better CEA control than the gefitinib arm. Clinical grade 3 adverse reactions occurred in 64% and 39% of patients in the gefitinib/NKT arm and the gefitinib arm, respectively. The most common grade 3 adverse events in the gefitinib/NKT arm included abnormal liver function in 8 cases (73%) and diarrhoea in 1 case (9%), both of which resolved after drug intervention. Conclusion: The PFS of EGFR-mutated advanced NSCLC treated with allogenic CD8+ NKT cells combined with gefitinib was longer than that of gefitinib alone. No obvious serious adverse reactions occurred, and the patients compliance and survival status were good.

Research Progress on Saccharide Molecule Detection Based on Nanopores.

Saccharides, being one of the fundamental molecules of life, play essential roles in the physiological and pathological functions of cells. However, their intricate structures pose challenges for detection. Nanopore technology, with its high sensitivity and capability for single-molecule-level analysis, has revolutionized the identification and structural analysis of saccharide molecules. This review focuses on recent advancements in nanopore technology for carbohydrate detection, presenting an array of methods that leverage the molecular complexity of saccharides. Biological nanopore techniques utilize specific protein binding or pore modifications to trigger typical resistive pulses, enabling the high-sensitivity detection of monosaccharides and oligosaccharides. In solid-state nanopore sensing, boronic acid modification and pH gating mechanisms are employed for the specific recognition and quantitative analysis of polysaccharides. The integration of artificial intelligence algorithms can further enhance the accuracy and reliability of analyses. Serving as a crucial tool in carbohydrate detection, we foresee significant potential in the application of nanopore technology for the detection of carbohydrate molecules in disease diagnosis, drug screening, and biosensing, fostering innovative progress in related research domains.

Experimental Investigation on the Interfacial Characteristics of Tight Oil Rocks Induced by Tuning Brine Chemistry.

Currently, research on enhancing imbibition oil recovery in tight oil reservoirs through the ion-tuning technique remains limited. Two critical parameters for capillary imbibition are the wettability and interfacial tension between oil and water. In this investigation, we manipulate the properties of two types of formation water for both aged and unaged samples by diluting brine and altering ion composition. Subsequently, we employ captive and pendant-drop methods to assess rock wettability and interfacial tension under varied brine conditions. Additionally, we elucidate the primary mechanisms underlying changes in rock wettability and interfacial tension. Meanwhile, we analyze capillarity characteristics and assess the relative significance of wettability and interfacial tension. Results indicate that there is a critical interfacial tension with progressive dilution of two types of formation water. However, modifying ion composition leads to a complex trend in interfacial tension, which can be explained qualitatively through the Gibbs adsorption isotherm. For unaged samples, the contact angle demonstrates a pronounced water-wet characteristic, showing a nonmonotonic trend with respect to dilution times. Remarkably, the rock surface exhibits the strongest water-wet, particularly evident in the case of FW-10, largely influenced by variations in interfacial tension. Conversely, aged samples demonstrate strong oil-wet, with a critical salinity resulting in the lowest contact angle, while altering brine ion types can alter rock wettability from strongly oil-wet to intermediate-wet, which is not sufficient to result in the wettability alteration. The removal of multivalent cations is proposed as the most effective method for wettability modification. Furthermore, capillarity variations among different brine cases are primarily contingent upon contact angle changes, and interfacial tension does not have a significant change when regulating the brine properties. Consequently, we emphasize the significance of wettability in the adoption of ion-tuned brine techniques for tight oil reservoirs. Overall, our study underscores the potential of reasonably regulating brine properties to enhance capillarity and, thereby, improve imbibition oil recovery.

Phytic Acid-Gallium Network on a Polyimide Fiber Woven Fabric as an Artificial Ligament for Boosting Ligament-Bone Healing and Infection Treatment.

The development of an artificial ligament with a multifunction of promoting bone formation, inhibiting bone resorption, and preventing infection to obtain ligament-bone healing for anterior cruciate ligament (ACL) reconstruction still faces enormous challenges. Herein, a novel artificial ligament based on a PI fiber woven fabric (PIF) was fabricated, which was coated with a phytic acid-gallium (PA-Ga) network via a layer-by-layer assembly method (PFPG). Compared with PIF, PFPG with PA-Ga coating significantly suppressed osteoclastic differentiation, while it boosted osteoblastic differentiation in vitro. Moreover, PFPG obviously inhibited fibrous encapsulation and bone absorption while accelerating new bone regeneration for ligament-bone healing in vivo. PFPG remarkably killed bacteria and destroyed biofilm, exhibiting excellent antibacterial properties in vitro as well as anti-infection ability in vivo, which were ascribed to the release of Ga ions from the PA-Ga coating. The cooperative effect of the surface characteristics (e.g., hydrophilicity/surface energy and protein absorption) and sustained release of Ga ions for PFPG significantly enhanced osteogenesis while inhibiting osteoclastogenesis, thereby achieving ligament-bone integration as well as resistance to infection. In summary, PFPG remarkably facilitated osteoblastic differentiation, while it suppressed osteoclastic differentiation, thereby inhibiting osteoclastogenesis for bone absorption while accelerating osteogenesis for ligament-bone healing. As a novel artificial ligament, PFPG represented an appealing option for graft selection in ACL reconstruction and displayed considerable promise for application in clinics.

Effect of Membrane Thickness on Ion Transport in pH-Regulated Zero-Depth Interfacial Nanopores.

Zero-depth interfacial nanopores, which are formed by two crossed nanoscale channels at their intersection interface, have been proposed to increase the spatial resolution of solid-state nanopores. However, research on zero-depth interfacial nanopores is still in its early stages. Although it has been shown that the current passing through an interfacial nanopore is largely independent of the membrane thickness, existing studies have not fully considered the impact of membrane thickness on other ion transport characteristics within these nanopores. In this paper, we investigate the electrokinetic ion transport phenomenon in the zero-depth interfacial nanopores, especially focusing on the influence of membrane thickness on the ion transport phenomenon. Our model incorporates the Poisson-Nernst-Planck equations and the Navier-Stokes equations, featuring a pH-regulated surface charge density. We find that when the thickness of the nanochannels is close to the interface size of the formed interfacial nanopore, the phenomenon of ion transport in the interfacial nanopore is similar to that in a conventional cylindrical nanopore. However, when the thickness of the nanochannels is much greater than the interface size of the formed interfacial nanopore, several distinct phenomena occur. The surface charge density on the inner walls of the interfacial nanopores has a small peak at the interface of the two crossing nanochannels, and the anion concentration changes greatly between the two nanochannels; that is, a much greater anion concentration forms in the nanochannel near the anode side than in the nanochannel near the cathode side. When the surface charge is nonzero, the electric field within the interfacial nanopore creates three extreme points, and the directions of the local electric fields are opposite at the ends of the membrane.

Chemoradiotherapy-induced ACKR2+ tumor cells drive CD8+ T cell senescence and cervical cancer recurrence.

Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8+ T cell senescence, driven by atypical chemokine receptor 2 (ACKR2)+ CCRT-resistant tumor cells. Mechanistically, ACKR2 expression is increased in response to CCRT and is also upregulated through the ligation of CC chemokines that are produced by activated myeloid and T cells. Subsequently, ACKR2+ tumor cells are induced to produce transforming growth factor ß to drive CD8+ T cell senescence, thereby compromising antitumor immunity. Moreover, retrospective analysis reveals that ACKR2 expression and CD8+ T cell senescence are enhanced in patients with cervical cancer who experienced recurrence after CCRT, indicating poor prognosis. Overall, we identify a subpopulation of CCRT-resistant ACKR2+ tumor cells driving CD8+ T cell senescence and tumor recurrence and highlight the prognostic value of ACKR2 and CD8+ T cell senescence for chemoradiotherapy recurrence.

An On-Treatment Decreased Trend of Serum IL-6 and IL-8 as Predictive Markers Quickly Reflects Short-Term Efficacy of PD-1 Blockade Immunochemotherapy in Patients with Advanced Gastric Cancer.

Objective: Immunotherapy has proven effective in treating advanced gastric cancer (AGC), yet its benefits are limited to a subset of patients. Our aim is to swiftly identify prognostic biomarkers using cytokines to improve the precision of clinical guidance and decision-making for PD-1 inhibitor-based cancer immunotherapy in AGC. Materials and Methods: The retrospective study compared 36 patients with AGC who received combined anti-PD-1 immunotherapy and chemotherapy (immunochemotherapy) with a control group of 20 patients who received chemotherapy alone. The concentrations of TNF-α, IL-1ß, IL-2R, IL-6, IL-8, IL-10, and IL-17 in the serum were assessed using chemiluminescence immunoassay at three distinct time intervals following the commencement of immunochemotherapy. Results: When compared to controls, patients undergoing immunochemotherapy demonstrated a generalized rise in cytokine levels after the start of treatment. However, patients who benefited from immunochemotherapy showed a decrease in IL-6 or IL-8 concentrations throughout treatment (with varied trends observed for IL-1ß, IL-2R, IL-10, IL-17, and TNF-α) was evident in patients benefiting from immunochemotherapy but not in those who did not benefit. Among these markers, the combination of IL-6, IL-8, and CEA showed optimal predictive performance for short-term efficacy of immunochemotherapy in AGC patients. Conclusion: Reductions in IL-6/IL-8 levels observed during immunochemotherapy correlated with increased responsiveness to treatment effectiveness. These easily accessible blood-based biomarkers are predictive and rapid and may play a crucial role in identifying individuals likely to derive benefits from PD-1 blockade immunotherapy.

Gastric Cancer Mesenchymal Stem Cells Trigger Endothelial Cell Functional Changes to Promote Cancer Progression.

Our previous studies have highlighted the pivotal role of gastric cancer mesenchymal stem cells (GCMSCs) in tumor initiation, progression, and metastasis. In parallel, it is well-documented that endothelial cells (ECs) undergo functional alterations in response to challenging tumor microenvironment. This study aims to elucidate whether functional changes in ECs might be induced by GCMSCs and thus influence cancer progression. Cell proliferation was assessed through CCK-8 and colony formation assays, while cell migration and invasion capabilities were evaluated by wound-healing and Transwell assays. Immunohistochemistry was employed to examine protein distribution and expression levels. Additionally, quantitative analysis of protein and mRNA expression was carried out through Western blotting and qRT-PCR respectively, with gene knockdown achieved using siRNA. Our findings revealed that GCMSCs effectively stimulate cell proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs), both in vitro and in vivo. GCMSCs promote the migration and invasion of gastric cancer cells by inducing the expression of Slit2 in HUVECs. Notably, the inhibition of phosphorylated AKT partially mitigates the aforementioned effects. In conclusion, GCMSCs may exert regulatory control over Slit2 expression in ECs via the AKT signaling pathway, thereby inducing functional changes in ECs that promote tumor progression.

Fast Fabrication Nanopores on a PMMA Membrane by a Local High Electric Field Controlled Breakdown.

The sensitivity and accuracy of nanopore sensors are severely hindered by the high noise associated with solid-state nanopores. To mitigate this issue, the deposition of organic polymer materials onto silicon nitride (SiNx) membranes has been effective in obtaining low-noise measurements. Nonetheless, the fabrication of nanopores sub-10 nm on thin polymer membranes remains a significant challenge. This work proposes a method for fabricating nanopores on polymethyl methacrylate (PMMA) membrane by the local high electrical field controlled breakdown, exploring the impact of voltage and current on the breakdown of PMMA membranes and discussing the mechanism underlying the breakdown voltage and current during the formation of nanopores. By improving the electric field application method, transient high electric fields that are one-seven times higher than the breakdown electric field can be utilized to fabricate nanopores. A comparative analysis was performed on the current noise levels of nanopores in PMMA-SiNx composite membranes and SiNx nanopores with a 5 nm diameter. The results demonstrated that the fast fabrication of nanopores on PMMA-SiNx membranes exhibited reduced current noise compared to SiNx nanopores. This finding provides evidence supporting the feasibility of utilizing this technology for efficiently fabricating low-noise nanopores on polymer composite membranes.

Evaluating the learning curve of endoscopic surgery for spontaneous intracerebral hemorrhage: A single-center experience in a county hospital.

BACKGROUND: Endoscopic surgery has shown promise in treating Spontaneous Intracerebral Hemorrhage (sICH), but its adoption in county-level hospitals has been hindered by the high level of surgical expertise required. METHODS: In this retrospective study at a county hospital, we utilized a Cumulative Sum (CUSUM) control chart to visualize the learning curve for two neurosurgeons. We compared patient outcomes in the learning and proficient phases, and compared them with expected outcomes based on ICH score and ICH functional outcome score, respectively. RESULTS: The learning curve peaked at the 12th case for NS1 and the 8th case for NS2, signifying the transition to the proficient stage. This stage saw reductions in operation time, blood loss, rates of evacuation < 90 %, rebleeding rates, intensive care unit stay, hospital stay, and overall costs for both neurosurgeons. In the learning stage, 6 deaths occurred within 30 days, less than the 10.66 predicted by the ICH score. In the proficient stage, 3 deaths occurred, less than the 15.88 predicted. In intermediate and high-risk patients by the ICH functional outcome score, the proficient stage had fewer patients with an mRS ≥ 3 at three months than the learning stage (23.8 % vs. 69.2 %, P = 0.024; 40 % vs. 80 %, P = 0.360). Micromanipulating bipolar precision hemostasis and aspiration devices in the endoport's channels sped up the transition from learning to proficient. CONCLUSION: The data shows a learning curve, with better surgical outcomes as surgeons gain proficiency. This suggests cost benefits of surgical proficiency and the need for ongoing surgical education and training in county hospitals.

First-line camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and chemotherapy for advanced gastric cancer (SPACE): a phase 1 study.

Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).