Ovalbumin promotes innate immune response of Caenorhabditis elegans through DAF-16 and SKN-1 pathways in insulin/IGF-1 signaling.

Ovalbumin (OVA) is a major allergen in eggs and could induce severe allergic reactions in sensitive individuals, where the innate immune system works as a regulator. The mechanism of how innate immunity adjusts to food allergy is relatively well-studied, however, the effects of allergen uptake on the innate immune system remain unclear. Therefore, the Caenorhabditis elegans (C. elegans) model was utilized to assess the effects of OVA on its innate immune system. OVA enhanced the immune response of C. elegans with higher survival rates under Pseudomonas aeruginosa infection. Moreover, sustaining OVA treatment improved the health states that were reflected in the prolonged lifespan, alleviated oxidative stress, accelerated growth, and promoted motility. RNA-sequencing analysis and the slow-killing assays in the mutants of insulin/IGF-1 signaling (IIS)-related genes confirmed that IIS was necessary for OVA to regulate innate immunity. Besides, OVA activated SKN-1 temporarily and facilitated the nuclear localization of DAF-16 for improving immunity and health status in C. elegans. Together, OVA could enhance the innate immune responses via DAF-16 and SKN-1 pathways in the IIS of C. elegans, and this work will provide novel insights into the regulation of innate immunity by OVA in higher organisms.

Mechanistic Insights into the Effects of Ureas and Monomers on the Ring-Opening Alternating Copolymerization of Epoxides and Anhydrides Catalyzed by Organic Base/Urea.

Aliphatic polyester is an important polyester material with good biocompatibility and degradability, which can be synthesized through ring-opening alternating copolymerization (ROAC) of epoxides and anhydrides. Herein, density functional theory (DFT) is used to explore the mechanism of ROAC of epoxides (propylene oxide (PO), styrene oxide (SO), epichlorohydrin (ECH), and cyclohexane oxide (CHO)) and phthalic anhydride (PA) catalyzed by bis(triphenylphosphine) ammonium chloride (PPNCl) and ureas. It was found that the ring-opening polymerization (ROP) of epoxides is the rate-controlling step, and the benzyl alcohol (BnOH) as the initiator has little effect on the polymerization activity, which was consistent with previous experimental results. Calculated comparisons of the ROAC activity of CHO/PA catalyzed by four different ureas indicate that as the Lewis acidity of the urea increased, the energy barriers of the copolymerization increased and the activity decreased. The main reason was that the strong hydrogen-bonding interactions stabilized the key intermediate of the rate-controlling step and inhibited subsequent monomer insertion. Based on this, a series of new ureas with higher catalytic activity were designed by introducing electron-donating substituents. In SO polymerization, increasing the Lewis acidity of urea can improve the SO regioselectivity. In addition, the monomer ECH with CH2Cl shows higher activity of ROAC than PO and SO, which could be ascribed to the fact that the strong electron-withdrawing Cl atom stabilizes the transition state in the rate-controlling step and reduces the reaction energy barrier.

Proteome-wide association study and functional validation identify novel protein markers for pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy, largely due to the paucity of reliable biomarkers for early detection and therapeutic targeting. Existing blood protein biomarkers for PDAC often suffer from replicability issues, arising from inherent limitations such as unmeasured confounding factors in conventional epidemiologic study designs. To circumvent these limitations, we use genetic instruments to identify proteins with genetically predicted levels to be associated with PDAC risk. Leveraging genome and plasma proteome data from the INTERVAL study, we established and validated models to predict protein levels using genetic variants. By examining 8,275 PDAC cases and 6,723 controls, we identified 40 associated proteins, of which 16 are novel. Functionally validating these candidates by focusing on 2 selected novel protein-encoding genes, GOLM1 and B4GALT1, we demonstrated their pivotal roles in driving PDAC cell proliferation, migration, and invasion. Furthermore, we also identified potential drug repurposing opportunities for treating PDAC. SIGNIFICANCE: PDAC is a notoriously difficult-to-treat malignancy, and our limited understanding of causal protein markers hampers progress in developing effective early detection strategies and treatments. Our study identifies novel causal proteins using genetic instruments and subsequently functionally validates selected novel proteins. This dual approach enhances our understanding of PDAC etiology and potentially opens new avenues for therapeutic interventions.

Highly sensitive dual-function sensor for refractive index and temperature using D-shaped microchannel photonic crystal fiber.

An innovative ultra-sensitive, dual-functional sensor employing a D-shaped microchannel photonic crystal fiber (PCF) for refractive index (RI) and temperature measurements is proposed and comprehensively investigated. Its high-sensitivity is achieved through the incorporation of gold (Au) and magnesium fluoride (MgF2) as plasmonic materials in the micro-rectangular channel. This configuration significantly enhances the interaction between the surface plasmon polaritons (SPPs) field and y-polarized evanescent field on external surfaces. Additionally, the integration of a temperature-sensitive fluid within the sensor allows for precise detection of temperature changes. Our simulations demonstrate a broad detection spectrum, covering RI values from 1.27 to 1.43 and temperatures ranging from 45°C to 100°C. The sensor achieves peak sensitivities of 31800nm/RIU for RI and 49 nm/°C for temperature. Besides, the sensor only has a cladding consisting of three air holes to enhance coupling and reduce the difficulty of preparation. Importantly, the sensor's performance remains robust against minor structural alterations in the PCF, indicating high fault tolerance. Given its high sensitivity, extensive detection range, and strong fabrication stability, this PCF-SPR sensor offers significant potential for applications in biochemical sensing and environmental monitoring.

Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

The prognostic model and immune landscape based on cancer-associated fibroblast features for patients with locally advanced rectal cancer.

Background: This study aimed to construct a nomogram based on CAF features to predict the cancer-specific survival (CSS) rates of locally advanced rectal cancer (LARC) patients. Methods: The EPIC algorithm was employed to calculate the proportion of CAFs. based on the differentially expressed genes between the high and low CAF proportion subgroups, prognostic genes were identified via LASSO and Cox regression analyses. They were then used to construct a prognostic risk signature. Moreover, the GSE39582 and GGSE38832 datasets were used for external validation. Lastly, the level of immune infiltration was evaluated using ssGSEA, ESTIMATE, CIBERSORTx, and TIMER. Results: A higher level of CAF infiltration was associated with a worse prognosis. Additionally, the number of metastasized lymph nodes and distant metastases, as well as the level of immune infiltration were higher in the high CAF proportion subgroup. Five prognostic genes (SMOC2, TUBAL3, C2CD4A, MAP1B, BMP8A) were identified and subsequently incorporated into the prognostic risk signature to predict the 1-, 3-, and 5-year CSS rates in the training and validation sets. Differences in survival rates were also determined in the external validation cohort. Furthermore, independent prognostic factors, including TNM stage and risk score, were combined to established a nomogram. Notably, our results revealed that the proportions of macrophages and neutrophils and the levels of cytokines secreted by M2 macrophages were higher in the high-risk subgroup. Finally, the prognostic genes were significantly associated with the level of immune cell infiltration. Conclusion: Herein, a nomogram based on CAF features was developed to predict the CSS rate of LARC patients. The risk model was capable of reflecting differences in the level of immune cell infiltration.

Protective effect of resveratrol on nickel-refining fumes-induced inflammatory damage.

Nickel (Ni), a ductile and hard silver-white transition metal, is commonly found in occupational environments and can harm the human body. Since it is a toxic compound, long-term Ni exposure can cause pneumonia, rhinitis, and other types of respiratory inflammatory diseases. Resveratrol (Res) is a plant antitoxin polyphenol, which also has anti-cancer and anti-inflammatory properties. In this report, the toxicity of Ni-refining fumes on the human lung bronchial epithelial (BEAS-2B) cells, as well as the protective effects of Res were investigated in vitro, and the specific mechanism of its anti-inflammatory effect was explained. The experimental observations of this study revealed that Ni-refining fumes induce BEAS-2B cell damage, increase reactive oxygen species (ROS) content, activate NLRP3 (LRR-, NOD-, and pyrin domain-containing 3) inflammasome, and promote the secretion of the cytokine Interleukin (IL)-1ß, leading to cellular inflammation and reducing cell activity. Resveratrol (20 µmol/L) activated sirtuin 1 (SIRT1) in BEAS-2B cells to increase protein and mRNA expression. SIRT1 was observed to inhibit the transcriptional activity of nuclear factor-kappaB (NF-κB), reduced the expression of NLRP3 protein and mRNA, and inhibited NLRP3 inflammation. The level of inflammasome activation and IL-1ß overexpression could reduce the inflammatory damage caused by the Ni-refining fume particles on the BEAS-2B cells and exert anti-inflammatory protective effects. In vivo experiments further confirmed that resveratrol could effectively alleviate the acute inflammatory injuries caused due to exposure to the Ni-refining fume particles in the lung tissues of the Wistar rats, and verified that resveratrol could exert its anti-inflammatory impact through the SIRT1-NF-κB-NLRP3 pathway. These results provide an important theoretical basis for developing novel protective drugs and investigating the mechanism of action for inflammatory injury in occupational populations caused by exposure to nickel and other heavy metals.

Nodal staging score for adequacy of nodal staging in cervical cancer.

Background: Cervical cancer remains the fourth most common female malignancy with increasing newly cases around the world. It is of clinical value to precisely evaluate whether false negative nodal existed and develop a nodal staging model in cervical cancer. Materials and methods: Clinical data of cervical cancer patients was retrieved from the Surveillance, Epidemiology, and End Results database. Probability of missing nodal disease and nodal staging score (NSS) was computed to assess the nodal status of each individual.Prognostic value of NSS was assessed. Results: A total of 9056 individuals were in this study, with 5115 squamous cell carcinoma, 2791 adenocarcinoma, 512 adenosquamous carcinoma, and 638 other type individuals. A beta-binomial model was used to compute the probability of nodal disease in four histological types, respectively. False negative probability drastically decreased as more nodes examined. To reach 0.05 of false negative probability, it required at least 17 lymph nodes in squamous cell carcinoma patients,18 in adenocarcinoma, 12 in adenosquamous carcinoma patients and 14 in other types. To reach 0.95 of NSS, it took 10 lymph nodes in squamous cell carcinoma, 6 in adenocarcinoma, 10 in adenosquamous carcinoma and 7 in other types. Significant prognostic values of NSS quartiles subsets were found in all four histological sets. Conclusion: NSS tool enables adequate nodal staging of cervical cancer with significant prognostic value. Exact number of lymph nodes required for surgery in cervical cancer is specified based on histologic type.

Metastatic clear cell sarcoma of the pancreas: A rare case report.

BACKGROUND: Clear cell sarcoma (CCS) is a rare soft-tissue sarcoma. The most common metastatic sites for CCS are the lungs, bones and brain. CCS is highly invasive and mainly metastasizes to the lung, followed by the bone and brain; however, pancreatic metastasis is relatively rare. CASE SUMMARY: We report on a rare case of CCS with pancreatic metastasis in a 47-year-old man. The patient had a relevant medical history 3 years ago, with abdominal pain as the main clinical manifestation. No abnormalities were observed on physical examination and the tumor was found on abdominal computed tomography. Based on the medical history and postoperative pathology, the patient was diagnosed with CCS with pancreatic metastasis. The patient was successfully treated with surgical interventions, including distal pancreatectomy and splenectomy. CONCLUSION: This report summarizes the available treatment modalities for CCS and the importance of regular postoperative follow-up for patients with CCS.

Diagnosis of poorly differentiated adenocarcinoma of the stomach by confocal laser endomicroscopy: A case report.

BACKGROUND: In recent years, confocal laser endomicroscopy (CLE) has become a new endoscopic imaging technology at the microscopic level, which is extensively performed for real-time in vivo histological examination. CLE can be performed to distinguish benign from malignant lesions. In this study, we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma. CASE SUMMARY: A 63-year-old woman was diagnosed with gastric mucosal lesions, which may be gastric cancer, in the small curvature of the stomach by gastroscopy. She consented to undergo CLE for morphological observation of the gastric mucosa. Through the combination of CLE diagnosis and postoperative pathology, the intraoperative CLE diagnosis was considered to be reliable. According to our experience, CLE can be performed as the first choice for the diagnosis of gastric cancer. CONCLUSION: CLE has several advantages over pathological diagnosis. We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.

Pylorus-preserving gastrectomy for early gastric cancer.

Pylorus-preserving gastrectomy (PPG) has been widely accepted as a function-preserving gastrectomy for middle-third early gastric cancer (EGC) with a distal tumor border at least 4 cm proximal to the pylorus. The procedure essentially preserves the function of the pyloric sphincter, which requires to preserve the upper third of the stomach and a pyloric cuff at least 2.5 cm. The suprapyloric and infrapyloric vessels are usually preserved, as are the hepatic and pyloric branches of the vagus nerve. Compared with distal gastrectomy, PPG has significant advantages in preventing dumping syndrome, body weight loss and bile reflux gastritis. The postoperative complications after PPG have reached an acceptable level. PPG can be considered a safe, effective, and superior choice in EGC, and is expected to be extensively performed in the future.

Lusutrombopag as a Repurposing Drug in Combination with Aminoglycosides against Vancomycin-Resistant Enterococcus.

Due to the widespread abuse of antibiotics, drug resistance in Enterococcus has been increasing. However, the speed of antibiotic discovery cannot keep pace with the acquisition of bacterial resistance. Thus, drug repurposing is a proposed strategy to solve the crises. Lusutrombopag (LP) has been approved as a thrombopoietin receptor agonist by the Food and Drug Administration. This study demonstrated that LP exhibited significant antimicrobial activities against vancomycin-resistant Enterococcus in vitro with rare resistance occurrence. Further, LP combined with tobramycin exhibited synergistic antimicrobial effects in vitro and in vivo against Enterococcus. No in vitro or in vivo detectable toxicity was observed when using LP. Mechanism studies indicated that the disrupted proton motive force may account for LP's antimicrobial activity. In summary, these results demonstrate that LP has the previously undocumented potential to serve as an antibacterial agent against refractory infections caused by Enterococcus.

[Tibiotalocalcaneal arthrodesis for end-stage ankle and hindfoot arthropathy: Short- and mid-term clinical outcomes].

OBJECTIVE: To analyze the clinical data of patients with end-stage ankle and hindfoot arthropathy who underwent tibiotalocalcaneal (TTC) arthrodesis by the same surgeon, explore the short- and mid-term clinical results, complications and functional improvement, and discuss the clinical prognosis and precautions of TTC arthrodesis. METHODS: Retrospective analysis was made on the clinical data of 40 patients who underwent TTC arthrodesis by the same surgeon from March 2011 to December 2020. In this study, 23 males and 17 females were included, with an average age of (49.1±16.0) years. All the patients underwent unilateral surgery. The clinical characteristics, imaging manifestations, main diagnosis and specific surgical techniques of the patients were recorded. The clinical outcomes were evaluated by comparison of the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) between pre-operation and at the last follow-up. The fusion healing time, symptom improvement (significant improvement, certain improvement, no improvement or deterioration) and postoperative complications were also recorded. RESULTS: The median follow-up time was 38.0 (26.3, 58.8) months. The preoperative VAS score was 6.0 (4.0, 7.0), and the AOFAS score was 33.0 (25.3, 47.3). At the last follow-up, the median VAS score was 0 (0, 3.0), and the AOFAS score was 80.0 (59.0, 84.0). All the significantly improved compared with their preoperative corresponding values (P < 0.05). There was no wound necrosis or infection in the patients. One patient suffered from subtalar joint nonunion, which was syphilitic Charcot arthropathy. The median bony healing time of other patients was 15.0 (12.0, 20.0) weeks. Among the included patients, there were 25 cases with significant improvement in symptom compared with that preoperative, 8 cases with certain improvement, 4 cases with no improvement, and 3 cases with worse symptoms than that before operation. CONCLUSION: TTC arthrodesis is a reliable method for the treatment of the end-stage ankle and hindfoot arthropathy. The function of most patients was improved postoperatively, with little impact on daily life. The causes of poor prognosis included toe stiffness, stress concentration in adjacent knee joints, nonunion and pain of unknown causes.

Intelligent Biogenic Missile for Two-Photon Fluorescence Imaging-Guided Combined Photodynamic Therapy and Chemotherapy in Tumors.

Photodynamic therapy (PDT) is a significant noninvasive therapeutic modality, but it is often limited in its application due to the restricted tissue penetration depth caused by the wavelength limitations of the light source. Two-photon (TP) fluorescence techniques are capable of having an excitation wavelength in the NIR region by absorbing two NIR photons simultaneously, which offers the potential to achieve higher spatial resolution for deep tissue imaging. Thus, the adoption of TP fluorescence techniques affords several discernible benefits for photodynamic therapy. Organic TP dyes possess a high fluorescence quantum yield. However, the biocompatibility of organic TP dyes is poor, and the method of coating organic TP dyes with silica can effectively overcome the limitations. Herein, based on the TP silica nanoparticles, a functionalized intelligent biogenic missile TP-SiNPs-G4(TMPyP4)-dsDNA(DOX)-Aptamer (TGTDDA) was developed for effective TP bioimaging and synergistic targeted photodynamic therapy and chemotherapy in tumors. First, the Sgc8 aptamer was used to target the PTK7 receptor on the surface of tumor cells. Under two-photon light irradiation, the intelligent biogenic missile can be activated for TP fluorescence imaging to identify tumor cells and the photosensitizer assembled on the nanoparticle surface can be activated for photodynamic therapy. Additionally, this intelligent biogenic missile enables the controlled release of doxorubicin (DOX). The innovative strategy substantially enhances the targeted therapeutic effectiveness of cancer cells. The intelligent biogenic missile provides an effective method for the early detection and treatment of tumors, which has a good application prospect in the real-time high-sensitivity diagnosis and treatment of tumors.

Magnetic ionic crystals with light controllable mobility and CO2 physisorption/desorption.

Magnetic responsive ionic liquid (MIL) demonstrated an advanced photomobility in confined narrow spaces through the doping of photoresponsive azobenzene by the interplay of supramolecular π-cations. Moreover, reversible physisorption/desorption of CO2 was achieved based on the photocontrolled solid-liquid transitions of the mixtures. Our approach opens opportunities to obtain multi-stimuli response through the coordinated supramolecular interplay of each responsive component.

Tau Aggregation-Dependent Lipid Peroxide Accumulation Driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau Complex Inhibits Epithelial Ovarian Cancer Peritoneal Metastasis.

Intraperitoneal dissemination is the main method of epithelial ovarian cancer (EOC) metastasis, which is related to poor prognosis and a high recurrence rate. Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures that are implicated in the regulation of tumor development. In this study, hsa_circ_0001546 is downregulated in EOC primary and metastatic tissues vs. control tissues and this phenotype has a favorable effect on EOC OS and DFS. hsa_circ_0001546 can directly bind with 14-3-3 proteins to act as a chaperone molecule and has a limited positive effect on 14-3-3 protein stability. This complex recruits CAMK2D to induce the Ser324 phosphorylation of Tau proteins, changing the phosphorylation status of Tau bound to 14-3-3 and ultimately forming the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex. The existence of this complex stimulates the production of Tau aggregation, which then induces the accumulation of lipid peroxides (LPOs) and causes LPO-dependent ferroptosis. In vivo, treatment with ferrostatin-1 and TRx0237 rescued the inhibitory effect of hsa_circ_0001546 on EOC cell spreading. Therefore, based on this results, ferroptosis caused by Tau aggregation occurs in EOC cells, which is not only in Alzheimer's disease- or Parkinson's disease-related cells and this kind of ferroptosis driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau complex is LPO-dependent rather than GPX4-dependent is hypothesized.

[Effect of Zuogui Jiangtang Qinggan Formula on lipid metabolism in db/db mouse model of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease].

This study aims to explore the effect of Zuogui Jiangtang Qinggan Formula(ZGJTQGF) on the lipid metabolism in the db/db mouse model of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD) via the insulin receptor(INSR)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/sterol-regulatory element-binding protein 2(SREBP-2) signaling pathway. Twenty-four db/db mice were randomized into positive drug(metformin, 0.067 g·kg~(-1)) and low-(7.5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) ZGJTQGF groups. Six C57 mice were used as the blank group and administrated with an equal volume of distilled water. The mice in other groups except the blank group were administrated with corresponding drugs by gavage for 6 consecutive weeks. At the end of drug administration, fasting blood glucose(FBG) and blood lipid levels were measured, and oral glucose tolerance test was performed. Compared with the blank group, the mice treated with ZGJTQGF showed decreased body mass and liver weight coefficient, lowered levels of FBG, total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL), and weakened liver function. The pathological changes and lipid accumulation in the liver tissue were examined. Western blot was employed to measure the protein levels of INSR, AMPK, p-AMPK, and SREBP-2. Compared with the blank group, the model group showed down-regulated protein levels of INSR and p-AMPK/AMPK and up-regulated protein level of SREBP-2. Compared with the model group, high-dose ZGJTQGF up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2. Low-dose ZGJTQGF slightly up-regulated the protein levels of INSR and p-AMPK/AMPK and down-regulated the protein level of SREBP-2, without significant differences. The results suggested that ZGJTQGF may alleviate insulin resistance and improve lipid metabolism in db/db mice by activating the INSR/AMPK/SREBP-2 signaling pathway.

Assessment of the efficacy of alkaline water in conjunction with conventional medication for the treatment of chronic gouty arthritis: A randomized controlled study.

BACKGROUND: Chronic gouty arthritis, a prevalent metabolic disorder, has prompted interest in the role of diet and lifestyle in its management. This study examines alkaline water as a non-pharmacological adjunct to traditional medicine, hypothesizing its positive effects on uric acid levels and gout symptoms. METHODS: In this research, 400 chronic arthritis patients from Guangdong Hydropower Hospital (September 2021-September 2023) were randomly assigned to groups receiving varying concentrations of alkaline water alongside conventional Western medicine, or Western medicine alone. A 1-year follow-up involved assessments using visual analogue scales, joint swelling scores, functional assessment scales, and biochemical markers (serum uric acid, creatinine, urea nitrogen) for comprehensive evaluation. RESULTS: Pain relief: High-concentration alkaline water significantly reduced VAS pain scores posttreatment (P < .05). Joint swelling: Greatest improvement observed in high-concentration group (P < .001). Daily activity capability: Notable enhancements in daily activity scores in experimental groups (P < .05). Range of joint motion: All groups showed significant improvement posttreatment (P < .05). Inflammatory markers: Experimental groups experienced a notable decrease in C-reactive protein, especially in the low concentration group (P < .001). Erythrocyte sedimentation rate decreases were marginal and not statistically significant (P > .05). Interleukin-1ß and tumor necrosis factor-α levels significantly decreased, particularly in the low concentration group. Serum uric acid levels: Significant reduction in serum uric acid observed in all alkaline water groups (P < .05), contrasting with the control group. CONCLUSION: Alkaline water, particularly at high concentrations, effectively alleviated pain, reduced joint swelling, enhanced daily activities, and improved joint motion in chronic gouty arthritis treatment. It significantly reduced key inflammatory markers (C-reactive protein, interleukin-1ß, tumor necrosis factor-α) and serum uric acid levels, suggesting its potential as a valuable adjunct in gout management. The limited impact on erythrocyte sedimentation rate warrants further investigation.

Nomogram predictive models for adult patients with acute lymphoblastic leukaemia based on real-world treatment outcomes.

This study aimed to analyse the characteristics and treatment outcomes of adult patients with acute lymphoblastic leukaemia (ALL) and construct nomogram predictive models for prognosis prediction. Between January 2017 and June 2022, 462 adult patients with ALL were included in this retrospective analysis. Patients' ages ranged from 14 to 84 years. B-cell origin was observed in 82.7% of these patients, while 17.3% of the cases were of T-cell origin. The BCR/ABL1 fusion gene was detected in 32.9% of those with B-ALL. Complete remission was achieved in 83.7% of the patients after induction chemotherapy. The median disease-free survival (DFS) and overall survival (OS) of patients were 19.0 and 39.1 months, respectively. The 5-year DFS and OS rates were 29.5% and 41.8%, respectively. The BCR/ABL1 fusion gene had a significant adverse impact on DFS and OS when patients were treated with tyrosine kinase inhibitors (TKIs) and chemotherapy; however, this effect was eliminated when patients underwent transplantation. Multivariate analysis identified that age ≥ 35 years, white blood cell count ≥ 30 × 109/L, platelet count < 100 × 109/L, failure to achieve complete remission after induction chemotherapy, positive measurable residual disease (MRD), and absence of transplantation were independent adverse prognostic factors for DFS and/or OS. Nomogram predictive models constructed by the rms package in R software based on these prognostic factors demonstrated precise predictive value. In conclusion, adult patients with ALL experience poor survival. TKIs in combination with transplantation can eliminate the adverse effects of BCR/ABL1 fusion genes on prognosis. Nomogram predictive models were accurate for prognostic prediction and will be useful in clinical practice.

Identification of Hedyotis diffusa Willd-specific mRNA-miRNA-lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification.

Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA-miRNA-lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW's regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA's progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA.