Effect of Preoperative Nursing Visit on Anxiety and Postoperative Complications in Patients Undergoing Radical Prostatectomy: A Retrospective Study.

OBJECTIVE: This study aimed to explore the effect of preoperative nursing visit on anxiety and postoperative complications in patients undergoing radical prostatectomy and to provide a better perioperative management plan for patients with prostate cancer (PCa) undergoing surgical treatment. METHODS: The medical records of 199 patients who underwent PCa treatment in our hospital from June 2021 to June 2023 were retrospectively analysed. The reference group received preoperative routine nursing, whereas the observation group implemented preoperative nursing visit. The stress indexes, quality of life, negative emotion level and incidence of complications were compared between the two groups. RESULTS: Before management, no significant difference in the levels of epinephrine, norepinephrine and cortisol was found between the two groups (p > 0.05). After management, the levels of the abovementioned stress indicators in the observation group were lower than those in the reference group (p < 0.001). Before management, no significant difference in Short-Form-36 Health Survey (SF-36) scores was observed between the two groups (p > 0.05). After management, the observation group had higher SF-36 score than the reference group (p < 0.001). Before management, no significant difference in Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores was found between the two groups (p > 0.05). After management, the observation group had lower HAMA and HAMD scores than the reference group (p < 0.001). Furthermore, no significant difference in the incidence of complications was found between the two groups (p > 0.05). CONCLUSIONS: Preoperative nursing visit can reduce the anxiety of patients with PCa to a certain extent. This scheme can promote the postoperative recovery of patients, and it has certain clinical application and promoting values.

Efficacy of PD-1 or PD-L1 inhibitors for the therapy of cervical cancer with varying PD-L1 expression levels: a single-arm meta-analysis.

Objective: To assess the effectiveness and tolerability of both PD-1 and PD-L1 inhibitors in advanced cervical cancer (CC), focusing on varying PD-L1 levels. Methods: A comprehensive exploration was carried out on EMBASE, PubMed, Cochrane Library databases as well as Web of Science up to May 25, 2024, for studies involving advanced CC patients receiving PD-1/PD-L1 inhibitors. Inclusion criteria were studies reporting objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), as well as median overall survival (OS). Data extraction and quality assessment were performed by two reviewers using the JBI Case Series Critical Appraisal Checklist, followed by a meta-analysis via STATA/MP 16.0. Results: Five eligible studies comprising 223 patients were chosen. ORR and DCR were 42% (95% CI: 17%-66%, P = 0.00) and 70% (95% CI: 22%-117%, P = 0.00), respectively, in the PD-L1 positive patients and were 36% (95% CI: 17%-54%, P = 0.00) and 47% (95% CI: 30%-63%, P = 0.00), respectively, in patients with PD-L1 negativity. For patients exhibiting PD-L1 positivity, median PFS and median OS were 3.98 months (95% CI: 0.80-7.16, P = 0.01) and 11.26 months (95% CI: 3.01-12.58, P = 0.00), respectively. Conclusion: With PD-1/PD-L1 inhibitors, PD-L1 positive CC patients demonstrate superior ORR, DCR, median PFS, and median OS, underscoring PD-L1 as one biomarker for immunotherapy response.

Unveiling the therapeutic potential of epigallocatechin gallate in liver cancer: insights from network pharmacology and in vitro assays.

Epigallocatechin gallate (EGCG) is a prominent catechin found in green tea polyphenols and has shown promising anti-tumor properties. However, the exact regulatory mechanism of EGCG on liver cancer is not fully revealed. In this study, we conducted integrative analyses using the SwissTargetPrediction and GeneCards repositories, which identified 98 targets. These targets were used to construct a protein-protein interaction network using STRING and visualised with Cytoscape. Central to this network are hub proteins, notably TNF and PIK3CA, suggesting pivotal roles in the therapeutic landscape. Gene Ontology (GO) enrichment analysis unveiled 1,570 biological terms with a notable preponderance within oxidative stress response processes. Complementary pathway enrichment via the Kyoto Encyclopaedia of Genes and Genomes (KEGG) highlighted 134 pathways, with the PI3K-Akt pathway emerging as prominent. In silico molecular docking supported these findings, revealing binding energies of EGCG-target complexes below -7.0 kcal/mol, indicative of robust interactions. Moreover, cellular assays including CCK-8, wound-healing, and Transwell modalities, established EGCG's inhibitory concentration-dependent effects on HepG2 cell proliferation, migration, and invasion. Apoptotic assays affirmed by FACS, evidenced enhanced apoptosis with escalating EGCG concentrations, underpinned by modulations in caspase activity and apoptotic protein levels. Notably, Western blot analysis demonstrated the attenuation of the PI3K/AKT signalling cascade by EGCG, paralleling the inhibitory profile of LY294002. These multifaceted inhibitory effects underscore EGCG's potential as an anti-tumor agent, deploying a strategic blockade of oncogenic pathways and augmenting apoptotic mechanisms, which provide a strong rationale for its application in liver cancer therapeutics.

Efficacy and safety of PD-1 monoclonal antibody combined with interferon-alpha 1b and anlotinib hydrochloride as the second-line therapy in patients with unresectable advanced melanoma: A retrospective study.

BACKGROUND: Immune-checkpoint inhibitors are now used more commonly in combination than monotherapy as the first-line choice in patients with unresectable advanced melanoma. Nevertheless, for cases that progressed after the initial combination therapy, the subsequent regimen option can be very difficult. Herein, we reported the efficacy and safety of a triple combination regimen in Chinese unresectable advanced melanoma patients who had poor responses to the first-line immune therapy. METHODS: We reviewed the clinical profiles of patients diagnosed with stage IIIC-IV melanoma between June 1, 2020, and September 30, 2023. The patients who failed the prior immune therapies and received anti-PD-1 mono antibody plus interferon(IFN)-alpha 1b and anlotinib hydrochloride as the second-line therapy were enrolled in the retrospective analysis. Additionally, we examined the exhaustion of T-cells using mIHC staining in available tumor samples. RESULTS: Fifty-five patients were included in this study. The median follow-up period was 13.6 months. The objective response rate evaluated by the investigators was 9.1%(1CR, 4PR). The disease control rate was 47.3%. The median overall survival was 17.6 months, and the median progression-free survival was 2.8 months. The adverse events rate of any grade was 100%. Grade 3 or 4 irAEs were observed in 29.1% of cases. Multiplex immunohistochemical staining revealed an increased trend of TIM3 expression on tumor-infiltrating T cells in patients without objective response. CONCLUSION: PD-1 monoclonal antibody plus interferon-alpha 1b plus anlotinib showed acceptable tolerability and anticancer benefits in Chinese metastatic melanoma patients as a second-line therapy.

[Diagnostic Value of Interleukin 6, Interleukin 12P70, Serum Amyloid A, and Procalcitonin for Rheumatoid Arthritis and Their Relationship With the Disease Activity]. / ç™½ä»‹ç´ 6ã€ç™½ä»‹ç´ 12P70ã€è¡€æ¸ æ·€ç²‰æ ·è›‹ç™½é ¶Aå’Œé™é’™ç´ åŽŸå¯¹ç±»é£Žæ¹¿å ³èŠ‚ç‚Žçš„è¯Šæ–­ä»·å€¼åŠä¸Žç–¾ç— æ´»åŠ¨åº¦çš„å ³ç³».

Objective: To observe the diagnostic value of four serum inflammatory biomarkers, including interleukin 6 (IL-6), interleukin 12P70 (IL-12P70), serum amyloid A (SAA), and procalcitonin (PCT), in rheumatoid arthritis (RA) and to analyze their relationship with the disease activity. Methods: The study included 60 RA patients admitted to the Department of Rheumatology at Anhui Provincial Hospital of Traditional Chinese Medicine between December 2022 and December 2023. Thirty healthy individuals from the hospital's physical examination center served as the control group. Serum levels of IL-6 and IL-12P70 were detected using flow cytometry. SAA levels were determined by immunoturbidimetry, and PCT levels were assessed by chemiluminescence. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and anticyclic citrullinated peptide (ACCP) were detected using an automated biochemical analyzer. The 28-joint disease activity scores (DAS28-ESR) based on ESR were observed. Statistical analysis included t-tests, rank-sum tests, and Kruskal-Wallis H tests to compare the expression differences of the biomarkers among different groups. The diagnostic value of these biomarkers for RA was analyzed by ROC curve analysis. Spearman correlation analysis was performed to assess the relationships between the four inflammatory biomarkers and CRP, ESR, RF, ACCP, and DAS28-ESR. Results: 1) The expression levels of SAA, IL-6, and IL-12P70 in the RA group were significantly higher than those in the control group (P<0.01). 2) ROC curve analysis showed that the area under the curve (AUC) for PCT was 0.611 (95% confidence interval [CI]: 0.488-0.735, P>0.05), for SAA, it was 0.819 (95% CI: 0.733-0.906, P<0.01), for IL-6, it was 0.875 (95% CI: 0.803-0.946, P<0.01), and for IL-12P70, it was 0.832 (95% CI: 0.746-0.917, P<0.01). The combined index of IL-6, IL-12P70, SAA, and PCT had an AUC of 0.973 (95% CI: 0.942-1.000, P<0.01). This indicates that the four inflammatory biomarkers can assist in the diagnosis of rheumatoid arthritis. 3) The expression levels of PCT and SAA varied significantly among the high, moderate, and low activity RA groups (P<0.01). 4) In RA patients, CRP was positively correlated with SAA (rs =0.75, P<0.01), and IL-6 (rs =0.52, P<0.01). ESR was positively correlated with SAA (rs =0.36, P<0.01). DAS28-ESR was positively correlated with PCT (rs =0.34, P=0.01), SAA (rs =0.51, P<0.01) and IL-6 (rs =0.33, P=0.01). Conclusion: The four inflammatory biomarkers (PCT, SAA, IL-6, and IL-12P70) are closely related to rheumatoid arthritis disease activity and can serve as serum indicators to assist in the diagnosis and assessment of RA.

Plant-derived exosome-like nanoparticles - from Laboratory to factory, a landscape of application, challenges and prospects.

Recent decades have witnessed substantial interest in extracellular vesicles (EVs) due to their crucial role in intercellular communication across various biological processes. Among these, plant-derived exosome-like Nanoparticles (ELNs) have rapidly gained recognition as highly promising candidates. ELNs, characterized by diverse sources, cost-effective production, and straightforward isolation, present a viable option for preventing and treating numerous diseases. Furthermore, ELNs hold significant potential as carriers for natural or engineered drugs, enhancing their attractiveness and drawing considerable attention in science and medicine. However, translating ELNs into clinical applications poses several challenges. This study explores these challenges and offers critical insights into potential research directions. Additionally, it provides a forward-looking analysis of the industrial prospects for ELNs. With their broad applications and remarkable potential, ELNs stand at the forefront of biomedical innovation, poised to revolutionize disease management and drug delivery paradigms in the coming years.

Coptis Chinensis Franch: Substance Basis, Mechanism of Action and Quality Control Standard Revealed Based on the Q-marker Concept and New Strategy of Systemic Pharmacology and Biosynthesis Research.

Coptis chinensis Franch. (Ranunculaceae, Coptis), a traditional Chinese medicine (TCM) with thousands of years of clinical use history, also a natural medicine available in many countries, has wide pharmacological mechanisms and significant bioactivity according to its traditional efficacy combined with modern scientific research. The quality marker (Q-marker) of C. chinensis Franch. is predicted in this paper based on the chemical composition and pharmacological effects of the plant, as well as the current system pharmacology, plant relatedness, biosynthetic pathways and quantitative analysis of multi-components (QAMS). Natural medicine has the advantage of being multi-component, multi-pathway and multi-target. However, there are few reports on safety evaluation. This review predicts the Q-marker of C. chinensis, and the safety and efficacy of C. chinensis is provided. Studies from 1975 to 2023 were reviewed from PubMed, Elsevier, ScienceDirect, Web of Science, SpringerLink, and Google Scholar. Alkaloids and organic acids are the two main component categories of Q-Markers. The specific alkaloids identified through predictive results include berberine, coptisine, palmatine, epiberberine, jatrorrhizine, columbamine, and berberrubine. Quinic acid and malic acid, due to their influence on the content of alkaloids and their ability to aid in identifying the active components of C. chinensis, are also considered Q-markers. The research strategy of "exploring chemical components, exploring pharmacological activities, constructing pharmacological mechanism network and locating biosynthetic pathways" was used to accurately screen the quality markers of C. chinensis in this review and summarise the quality evaluation methods and criteria. In addition, we updated the biosynthetic pathway of C. chinensis and refined the specific synthetic pathways of jatrorrhizine (quality markers) and epiberberine (quality markers). Finally, we summarised the quality evaluation methods of C. chinensis, which provide an important reference for resource evaluation and provide a key reference for the discovery of new functional chemical entities for natural medicines.

[The application of inflammation-related cytokines in early diagnosis and disease assessment of rheumatoid arthritis].

Objective To measure the serum contents of cytokines in patients with rheumatoid arthritis (RA) and explore the clinical application value of combined detection of inflammatory cytokines in evaluating the severity of RA. Methods This study recruited 28 RA patients and 15 healthy individuals who received health checkups during the same period. The expression of inflammatory cytokines including interleukin 1ß (IL-1ß), IL-2, IL-5, IL-6, IL-8, IL-12P70, IL-17, tumor necrosis factor-α (TNF-α), interferon α (IFN-α), IFN-γ, IL-4 and IL-10 were detected with the multiplexed microsphere-based flow cytometric immunoassay. C-reactive protein (CRP) was detected with an automatic biochemical instrument, and erythrocyte sedimentation rate (ESR) was measured by the Westergren method. The disease activity score in 28 joints (DAS28) in the RA group was calculated, and the area under the curve (AUC) of each cytokine and RA disease activity was compared. The correlation of serum levels of inflammatory cytokines with CRP and ESR was analyzed in RA patients. Results In RA patients, the serum levels of IL-2, IL-6, IL-12P70, IL-4 and IL-10 were significantly correlated with the indicator of RA disease activity DAS28-CRP, and the serum levels of IL-12P70, TNF-α and IL-4 were markedly correlated with the indicator of RA disease activity DAS28-ESR. CRP was positively correlated with IL-6 (r=0.515), IL-12P70 (r=0.530), IL-4 (r=0.539), and IL-10(r=0.434). ESR was positively correlated with IL-6 (r=0.403), IL-12P70 (r=0.475), TNF-α (r=0.497), and IL-4 (r=0.450). Compared with the normal CRP and ESR group, the abnormal CRP group showed an increase in the levels of IL-6, IL-12P70, IL-2, IL-4 and IL-10, and the abnormal ESR group exhibited an elevation in the levels of IL-12P70, IL-4 and TNF-α. The expression of IL-8, IFN-α and IFN-γ was higher in the experimental group than in the control group. Conclusion Serum inflammatory cytokines detection has shed light on the early diagnosis and severity evaluation of RA and can be used as a pivotal indcator for the diagnosis of RA.

FXR, MRP-1 and SLC7A5: New Targets for the Treatment of Hepatocellular Carcinoma.

Detect the expression of Farnesoid X Receptor(FXR), Multiple Drug Resistance Associated Protein-1(MRP-1) and Solute Carrier Family 7, Member 5 (SLC7A5) in hepatocellular carcinoma(HCC) of rat model, so as to provide new therapeutic targets for gene therapy of HCC. Sixty male Wistar rats were randomly divided into three groups. The rats in experimental group were given 0.2% diethylnitrosamine (DEN) by gavage with a dose of 10 mg/kg, 3 times a week, and it stopped at 12 weeks. The control group rats were given physiological saline by gavage, while the sham operation group did not receive anything by gavage. At 10 weeks, one rat in the experimental group was euthanized, and the changes of livers were recorded. The procedure was repeated at 12 weeks. After 12 weeks, HCC only occurred in the experimental group. After confirming the formation of the tumor through pathological examination, liver tissues and tumor tissues were taken from the three groups. FXR, MRP-1 and SLC7A5 expression in liver tissues and tumor tissues was detected. After 7 weeks the rats in experimental group ate less, and their weight was significantly reduced. Three months later, HCC was detected in 15 rats in the experimental group. The ratio of FXR/GAPDH mRNA, MRP-1/GAPDH mRNA, SLC7A5/GAPDH mRNA were significantly different among the three groups. Under the light microscope the FXR protein, MRP-1 protein, and SLC7A5 protein react with their respective antibodies, and they showed granular expression. Every pathological section included different numbers of positive cells in each group. FXR expression in HCC of rats was significantly lower than that in normal liver tissues, but MRP-1 and SLC7A5 expression in HCC were significantly higher than that in normal liver tissues, suggesting that drugs targeting FXR, MRP-1 and SLC7A5 may be new strategies for the treatment of HCC.

Combined aqupla, paclitaxel liposome, and docetaxel treatment: survival and biomarker outcomes in recurrent ovarian cancer patients.

As one lethal malignancy in women's reproductive systems, ovarian cancer (OC) is frequently detected at an advanced phase during diagnosis. when the disease has spread widely. The absence of obvious symptoms and powerful screening tools in the early stages makes treatment difficult and the prognosis poor. Despite the clinical remission that can be achieved in some patients after initial treatment, the recurrence rate is conspicuous, posing a considerable challenge in treating recurrent OC (ROC). In the retrospective analysis, we compared the effects of two treatment regimens, aqupla combined with paclitaxel liposome (NP group) versus aqupla combined with docetaxel (ND group), on survival and biomarkers in patients with ROC. The study included 121 OC patients, and clinical data were collected through an electronic medical record system, outpatient review records, and a follow-up record system. The results revealed a notably higher overall remission rate in the ND group than the NP group, but revealed no notable inter-group discrepancy in toxicities, implying that the aqupla combined with docetaxel regimen may be more effective in platinum-sensitive ROC patients. Additionally, post-treatment CA125 levels were lower in patients in the ND group, suggesting that the regimen may be more effective in reducing tumour load. Survival analysis further revealed that treatment regimen, FIGO stage, number of recurrent lesions, and pretreatment CA125 level were independent prognostic factors affecting patients' 5-year OS and PFS. Overall for ROC patients, especially platinum-sensitive patients, the aqupla in combination with docetaxel regimen provided an improved survival benefit with a comparable safety profile, highlighting the importance of individualised treatment strategies.

Application of artificial intelligence combined with near infrared spectroscopy in the continuous counter-current extraction process of Angelica dahurica formula granules.

The establishment of near infrared (NIR) spectroscopy model mostly relies on chemometrics, and spectral analysis combined with artificial intelligence (AI) provides a new way of thinking for pharmaceutical quality inspection, new algorithms such as back propagation artificial neural networks (BP-ANN) and swarm intelligence optimization algorithms such as sparrow search algorithm (SSA) provide core technical support. In order to explore the application of AI in the pharmaceutical field, in this study, Angelica dahurica formula granules with a relatively complex system were selected as the research object. Quantitative analysis models were established by using partial least squares regression (PLSR) with a micro-NIR spectrometer, and BP-ANN modeling results were compared. For the best PLSR models of six characteristic components in the continuous counter-current extract of Angelica dahurica, R2v of imperatorin was lower than 0.90, and the RPD values of imperatorin, phellopterin, and isoimperatorin were even lower than 1. When the prediction model established by SSA-BP-ANN was used for quantitative analysis, R2v of six components were all higher than 0.92, and the RPD values all higher than 1.5, which proved that the BP-ANN method was better than PLSR. This study confirmed that in the continuous counter-current extraction progress of Angelica dahurica formula granules, the use of micro-NIR spectrometer combined with AI could realize the rapid prediction of the contents of six characteristic components. The comparison results provided a scientific reference for the process analysis and on-line monitoring in the production process of traditional Chinese medicine by micro-NIR spectrometer combined with AI.

Preparation empty peptide-receptive MHC class I complex for large-scale detection through photolabile peptide ligands.

Peptide-major histocompatibility complex (pMHC) multimers are wide recognized as the premier technique for detecting, characterizing, and isolating antigen-specific CD8+ T-cell subsets. These multimers are specifically useful in studying infections, autoimmune conditions, and cancer through single-cell analysis techniques such as flow cytometry and fluorescence microscopy. However, the development of high-throughput assays with commercially available pMHC tetramers can be expensive, while in-house production may pose challenges for most biology research laboratories. In this context, we introduce a cost-friendly and uncomplicated protocol to prepare empty MHC class I tetramers using disulfide-stabilized molecules and photolabile peptide ligands. Our method relies on disulfide bond-stabilized MHC-I molecules, which demonstrated stability when folded into stable monomers in the presence of a photolabile epitope. These monomers, upon ultraviolet irradiation and streptavidin binding, efficiently assemble into tetramers devoid of any peptide. Following a short incubation with the peptide of interest under gentle conditions, the resulting pMHC tetramer effectively detects patient-sourced, neoantigen-specific T cells. Our unique approach streamlines large-scale pMHC generation, thus paving the way for advancements in T cell-based diagnostics and personalized therapies.

Increased ecological land and atmospheric CO2 dominate the growth of ecosystem carbon sinks under the regulation of environmental conditions in national key ecological function zones in China.

Increased ecological land (IEL) such as forests and grasslands can greatly enhance ecosystem carbon sinks. Understanding the mechanisms for the magnitude of IEL-induced ecosystem carbon sinks is crucial for achieving carbon neutrality. We estimated the impact of IEL, specifically the increase in forests and grasslands, as well as global changes including atmospheric CO2 concentration, nitrogen deposition, and climate change on net ecosystem productivity (NEP) in National Key Ecological Function Zones (NKEFZs) in China using a calibrated ecological process model. The NEP in NKEFZs in China was calculated to be 119.4 Tg C yr-1, showing an increase of 42.6 Tg C yr-1 from 2001 to 2021. Compared to the slight contributions of climate change (-8.0%), nitrogen deposition (11.5%), and reduction in ecological land (-3.5%), the increase in NEP was primarily attributed to CO2 (66.5%) and IEL (33.5%). Moreover, the effect of IEL (14.8 Tg C yr-1) surpassed that of global change (13.1 Tg C yr-1) in the land use change zone. The IEL-induced NEP is significantly associated with CO2 fertilization, regulated by precipitation and nitrogen deposition. The high values of IEL-induced NEP occurred in areas with precipitation exceeding 800 mm and nitrogen deposition exceeding 25 kg N ha-1 yr-1. We recommend prioritizing the expansion of ecological land in areas with sufficient water and nutrients to enhance CO2 fertilization, while avoiding increasing ecological land in regions facing unfavorable climate change conditions. This study serves as a foundation for comprehending the NEP response to ecological restoration and global change.

Progress based on a multi-omics research strategy in the biosynthesis and modernization of active ingredients of Herpetospermum pedunculosum seeds.

Herpetospermum pedunculosum seeds also known as Herpetospermum caudigerum Wall. is the mature seed of the Herpetospermum pedunculosum(Ser.) C. B. Clarke,Cucurbitaceae. Modern pharmacological studies have shown that H. pedunculosum has hepatoprotective, anti-inflammatory, anti-gout and antibacterial pharmacological activities. The biologically active chemical components include lignin compounds such as Herpetin, Herpetetrone, Herpetoriol and so on. The natural product displays considerable skeletal diversity and structural complexity, offering significant opportunities for novel drug discovery. Based on the multi-omics research strategy and the 'gene-protein-metabolite' research framework, the biosynthetic pathway of terpenoids and lignans in H. pedunculosum has has been elucidated at multiple levels. These approaches provide comprehensive genetic information for cloning and identification of pertinent enzyme genes. Furthermore, the application of multi-omics integrative approaches provides a scientific means to elucidate entire secondary metabolic pathways. We investigated the biosynthetic pathways of lignin and terpene components in H. pedunculosum and conducted bioinformatics analysis of the crucial enzyme genes involved in the biosynthetic process using genomic and transcriptomic data. We identified candidate genes for six key enzymes in the biosynthetic pathway. This review reports on the current literature on pharmacological investigations of H. pedunculosum, proposing its potential as an antidiabetic agent. Moreover, we conclude, for the first time, the identification of key enzyme genes potentially involved in the biosynthesis of active compounds in H. pedunculosum. This review provides a scientific foundation for the discovery of novel therapeutic agents from natural sources.

Is Dosage Adjustment Based on Age Necessary for Intravenous Lidocaine in Patients Undergoing General Anesthesia: A Prospective Multi-Arm Comparative Study.

It remains unclear whether dosage adjustment of intravenous lidocaine is necessary during general anesthesia for elderly patients over 75 years old. This study aimed to investigate the effects of age on the pharmacokinetics (PK) and safety of intravenous lidocaine in patients undergoing general anesthesia. A total of 599 plasma samples were collected from 76 general anesthesia patients across three age groups: 18-64, 65-74, and ≥ 75 years. Lidocaine was administered intravenously at a dose of 1.5 mg/kg for the 18-64 and 65-74 years groups, while the dose was adjusted to 1.0 mg/kg for the ≥ 75 years group. The plasma concentrations of lidocaine and its active metabolites were measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were analyzed using a noncompartmental analysis. The results revealed no significant age-related differences in the PK of lidocaine and its metabolites. Among the three age groups, over 90 % of patient achieved a lidocaine concentration within a safe and effective range when the dosage was normalized to 1.5 mg/kg. In conclusion, age-based dosage adjustment was unnecessary for intravenous lidocaine in patients below 86 years undergoing general anesthesia.

A novel nomogram model for lung adenocarcinoma subtypes based on RNA-modification regulatory genes.

Background: In non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) is the most common subtype. RNA modification has become the frontier and hotspot of current tumor research. Results: In this study, 109 genes that regulate RNA modifications were identified according to The Cancer Genome Atlas (TCGA). A differential gene expression analysis identified 46 differentially expressed RNA modification regulatory genes (DERRGs). LUAD samples were stratified into two distinct clusters based on the expression of these DERRGs. A significant correlation was observed between these clusters and patient survival rates, as well as clinical features. Furthermore, a four-DERRG signature (EIF3B, HNRNPC, IGF2BP1, and METTL3) developed using LASSO regression. According to the calculated risk scores from this signature, LUAD patients were categorized into high-risk and low-risk groups. Patients in the low-risk group exhibited a more favorable prognosis. A prognostic nomogram was crafted, integrating the four-DERRGs signature with clinical parameters. The nomogram was revealed that OS, age, clinical stage, immune cell infiltration, and immune checkpoint molecule expression were significantly linked to the OS of LUAD. GSEA analysis found that the DERRGs were primarily regulated immune pathways. Conclusions: This study developed four DERRGs signatures and formulated a nomogram model for precise prognosis estimation in LUAD patients. The study's insights are instrumental for advancing diagnosis, prognosis, and therapeutic strategies for LUAD.

CD69+ Vδ1γδ T cells are anti-tumor subpopulations in hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC), one of the malignancies with a wide expression of stress ligands recognized by Vδ1γδ T cells, has received much attention in adoptive immunotherapy of γδ T cells. In this study, we aimed to identify the potential anti-tumor Vδ1γδ T subpopulations in HCC. METHODS: Healthy donors (HDs) and HCC patients were recruited from the Affiliated Cancer Hospital of Zhengzhou University. Blood and tumor tissue samples were obtained respectively. Bioinformatics methods were used to analyze total γδ T cells and subsets infiltration, overall survival of HCC patients with high and low infiltration level of Vδ1γδ T cells, and IFNG, granzyme A, granzyme B and perforin expression in TRDV1high/lowCD69high/low groups. CD69 expression and Vδ1γδT cells infiltration in HCC were detected by immunofluorescence. Phenotypic analysis of Vδ1γδ T cells in blood and tumor tissue samples were performed by flow cytometry. RESULTS: Vδ1γδ T cells infiltrating in HCC were associated with better clinical outcome. Study in tumor micro-environment (TME) of HCC demonstrated that not total Vδ1γδ T but CD69+ Vδ1γδ subset infiltration was associated with smaller tumor volume. Moreover, HCC patients simultaneously with high TRDV1 and CD69 expression produced more effector molecules and had longer survival time. Since Vδ1γδ T cells in the tumor microenvironment were often difficult to access, we demonstrated that CD69+ Vδ1γδ T cells also existed in peripheral blood mononuclear cells (PBMC) of HCC and displayed enhanced cytotoxic potentials than HDs. Finally, we investigated the functions and found that CD69+ Vδ1γδ T cells exhibited stronger tumor reactivities when challenged by tumor cells. CONCLUSIONS: CD69+ Vδ1γδ T cells are functional Vδ1γδ T cell subsets in patients with HCC. Circulating CD69+ Vδ1γδ T cell is a promising candidate in immunotherapy of HCC.

Safety, tolerability, and pharmacokinetic of HY0721 in Chinese healthy subjects: A first-in-human randomized, double-blind, placebo-controlled dose escalation phase I study.

BACKGROUND: HY0721 is a novel inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) for the treatment of acute ischemic stroke. This study aimed to evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of single and multiple intravenous administration of HY0721 in Chinese healthy subjects. METHODS: The study enrolled 48 and 30 healthy volunteers in the single-ascending dose (SAD) cohort (20, 60, 120, 240, and 320 mg) and multiple-ascending dose (MAD) cohort (60, 120, and 160 mg/bid), respectively, to receive the corresponding dosage of HY0721 or placebo. Safety monitoring included but was not limited to recording adverse events (AEs), vital signs, electrocardiograms, and laboratory tests. The blood samples were collected from subjects to determine the concentrations of HY0721 for PK evaluation. RESULTS: The administration of HY0721 showed good safety and tolerability up to 320 mg in the SAD study and up to 160 mg twice daily in the MAD study. The most common AE was injection site reaction, and no AE led to discontinuation of administration or subject dropout. The exposures of HY0721 increased greater than dose proportional manner at the dosages of 20 to 320 mg in the SAD study. A linear PK profile was observed following multiple doses ranging from 60 to 160 mg twice daily, with no evidence of accumulation. Additionally, the human effective dose of HY0721 was estimated to be 120 mg. CONCLUSION: This study demonstrated the intravenous administration of HY0721 is safe and well-tolerated in Chinese healthy subjects and provided 60 to 160 mg b.i.d. as the recommended dosing range for further clinical trials. TRIAL REGISTRATION: ChinaDrugTrials.Org.cn; No. CTR20202604, 18 December 2020.

Micro-Infusion of 5-HT1a Receptor Antagonists into the Ventral Subiculum Ameliorate MK-801 Induced Schizophrenia-Like Behavior in Rats.

Recent studies have shown that the 5-HT1a receptor (5-HT1aR) in the central 5-HT (Serotonergic) system is involved in the pathophysiology of schizophrenia through its various receptors, and the dysfunction of the ventral hippocampus may be a key causative factor in schizophrenia. To date, whether the 5-HT1a receptor is involved in ventral hippocampal dysfunction and its internal mechanism remain unclear. In this study, schizophrenia-like animal model was induced by intraperitoneal injection of aspartate receptor antagonist MK-801 in male Sprague Dawley rats, and the role of 5-HT1aR in this animal model was investigated by bilaterally micro-infusing the 5-HT1aR antagonist WAY100635 into the ventral subiculum (vSub) of the hippocampus of rats. Behavioral experiments such as open field test (OFT) and prepulse inhibition (PPI) were performed. The results showed that MK-801 induced hyperactivity and impaired prepulse inhibition in rats, whereas, micro-infusion of 5-HT1aR antagonist WAY100635 into the vSub ameliorated these phenomena. Immunofluorescence analysis revealed that WAY100635 significantly increased the c-Fos expression in vSub. Western blot and immunohistochemical analysis showed that MK-801 induced up-regulation of 5-HT1aR and phospho-extracellular regulated protein kinase (p-ERK) pathway, while micro-infusion of the WAY100635 down-regulated 5-HT1aR and p-ERK in the vSub. Therefore, the results of the present study suggested that in vSub, the 5-HT1aR antagonist WAY100635 may attenuate MK-801-induced schizophrenia-like activity by modulating excitatory neurons and downregulating p-ERK.