A Rapid Self-Assembling Peptide Hydrogel for Delivery of TFF3 to Promote Gastric Mucosal Injury Repair.

Self-assembled peptide-based nanobiomaterials exhibit promising prospects for drug delivery applications owing to their commendable biocompatibility and biodegradability, facile tissue uptake and utilization, and minimal or negligible unexpected toxicity. TFF3 is an active peptide autonomously secreted by gastric mucosal cells, possessing multiple biological functions. It acts on the surface of the gastric mucosa, facilitating the repair process of gastric mucosal damage. However, when used as a drug, TFF3 faces significant challenges, including short retention time in the gastric mucosal cavity and deactivation due to degradation by stomach acid. In response to this challenge, we developed a self-assembled short peptide hydrogel, Rqdl10, designed as a delivery vehicle for TFF3. Our investigation encompasses an assessment of its properties, biocompatibility, controlled release of TFF3, and the mechanism underlying the promotion of gastric mucosal injury repair. Congo red/aniline blue staining revealed that Rqdl10 promptly self-assembled in PBS, forming hydrogels. Circular dichroism spectra indicated the presence of a stable ß-sheet secondary structure in the Rqdl10 hydrogel. Cryo-scanning electron microscopy and atomic force microscopy observations demonstrated that the Rqdl10 formed vesicle-like structures in the PBS, which were interconnected to construct a three-dimensional nanostructure. Moreover, the Rqdl10 hydrogel exhibited outstanding biocompatibility and could sustainably and slowly release TFF3. The utilization of the Rqdl10 hydrogel as a carrier for TFF3 substantially augmented its proliferative and migratory capabilities, while concurrently bolstering its anti-inflammatory and anti-apoptotic attributes following gastric mucosal injury. Our findings underscore the immense potential of the self-assembled peptide hydrogel Rqdl10 for biomedical applications, promising significant contributions to healthcare science.

Knockdown of LncRNA Lcn2-204 alleviates sepsis-induced myocardial injury by regulation of iron overload and ferroptosis.

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2-204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2-204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2-204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2-204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.

Mangiferin attenuates lipopolysaccharide-induced neuronal injuries in primary cultured hippocampal neurons.

Mangiferin, a naturally occurring potent glucosylxanthone, is mainly isolated from the Mangifera indica plant and shows potential pharmacological properties, including anti-bacterial, anti-inflammation, and antioxidant in sepsis-induced lung and kidney injury. However, there was a puzzle as to whether mangiferin had a protective effect on sepsis-associated encephalopathy. To answer this question, we established an in vitro cell model of sepsis-associated encephalopathy and investigated the neuroprotective effects of mangiferin in primary cultured hippocampal neurons challenged with lipopolysaccharide (LPS). Neurons treated with 20 µmol/L or 40 µmol/L mangiferin for 48 h can significantly reverse cell injuries induced by LPS treatment, including improved cell viability, decreased inflammatory cytokines secretion, relief of microtubule-associated light chain 3 expression levels and several autophagosomes, as well as attenuated cell apoptosis. Furthermore, mangiferin eliminated pathogenic proteins and elevated neuroprotective factors at both the mRNA and protein levels, showing strong neuroprotective effects of mangiferin, including anti-inflammatory, anti-autophagy, and anti-apoptotic effects on neurons in vitro.

Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier.

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment, significantly curtailing the efficacy of these treatments and, in some cases, resulting in fatal consequences. Despite identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis, the paucity of effective treatments for such damage is evident. In our study, we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells, thereby fortifying the integrity of the intestinal mucus barrier. This enhanced barrier function serves to resist microbial invasion and subsequently reduces the inflammatory response. Importantly, this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy drugs. Mechanistically, E. copr up-regulates the expression of AUF1, leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet cells. An especially significant finding is that E. copr activates the AhR pathway, thereby promoting the expression of AUF1. In summary, our results strongly indicate that E. copr enhances the intestinal mucus barrier, effectively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUF1 pathway, consequently enhancing Muc2 mRNA stability.

Model and Data Dual-Driven Double-Point Observation Network for Ultra-Short MI EEG Classification.

Although deep networks have succeeded in various signal classification tasks, the time sequence samples used to train the deep models are usually required to reach a certain length. Especially, in brain computer interface (BCI) research, around 3.5s-long motor imagery (MI) Electroencephalography (EEG) samples are needed to obtain satisfactory classification performance. This time-span requirement of the training samples makes real-time MI BCI systems impossible to implement based on deep networks, which restricts the related researches within laboratory and makes practical application hard to accomplish. To address this issue, a double-point observation deep network (DoNet) is developed to classify ultra-short samples buried in noise. First, an analytical solution is developed theoretically to perform ultra-short signal classification based on double-point couples. Then, a signal-noise model is constructed to study the interference of noise on classification based on double-point couples. Based on which, an independent identical distribution condition is utilized to improve the classification accuracy in a data-driven manner. Combining the theoretical model and data-driven mechanism, DoNet can construct a steady data-distribution for the double-point couples of the samples with the same label. Therefore, the conditional probability of each double-point couple of a test sample can be obtained. With a voting strategy, the samples can be accurately classified by fusing these conditional probabilities. Meanwhile, the noise interference can be suppressed. DoNet has been evaluated on two public EEG datasets. Compared to most state-of-the-art methods, the 1s-long EEG signal classification accuracy has been improved by more than 3%.

Network pharmacology and experimental evidence: ERK/CREB/BDNF signaling pathway is involved in the antidepressive roles of Kaiyu Zhishen decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Major Depressive Disorder (MDD) emerges as a complex psychosomatic condition, notable for its considerable suicidality and mortality rates. Increasing evidence suggests the efficacy of Chinese herbal medicine in mitigating depression symptoms and offsetting the adverse effects associated with conventional Western therapeutics. Notably, clinical trials have revealed the adjunctive antidepressant potential of Kaiyu Zhishen Decoction (KZD) alongside Western medication. However, the standalone antidepressant efficacy of KZD and its underlying mechanisms merit in-depth investigation. AIM OF THE STUDY: This research aims to elucidate the impact of KZD on MDD and delineate its mechanistic pathways through integrated network pharmacological assessments and empirical in vitro and in vivo analyses. MATERIALS AND METHODS: To ascertain the optimal antidepressant dosage and mechanism of KZD, a Chronic Unpredictable Mild Stress (CUMS)-induced depression model in mice was established to evaluate depressive behaviors. High-Performance Liquid Chromatography (HPLC) and network pharmacological approaches were employed to predict KZD's antidepressant mechanisms. Subsequently, hippocampal samples were subjected to 4D-DIA proteomic sequencing and validated through Western blot, immunofluorescence, Nissl staining, and pathway antagonist applications. Additionally, cortisol-stimulated PC12 cells were utilized to simulate neuronal damage, analyzing protein and mRNA levels of MAPK-related signals and cell proliferation markers. RESULTS: The integration of network pharmacology and HPLC identified kaempferol and quercetin as KZD's principal active compounds for MDD treatment. Proteomic and network pharmacological KEGG pathway analyses indicated the MAPK signaling pathway as a critical regulatory mechanism for KZD's therapeutic effect on MDD. KZD was observed to mitigate CUMS-induced upregulation of p-ERK/ERK, CREB, and BDNF protein expressions in hippocampal cells by attenuating oxidative stress, thereby ameliorating neuronal damage and exerting antidepressant effects. The administration of PD98059 counteracted KZD's improvements in depression-like behaviors and downregulated p-ERK/ERK and BDNF protein expressions in the hippocampus. CONCLUSIONS: This investigation corroborates KZD's pivotal, dose-dependent role in antidepressant activity. Both in vivo and in vitro experiments demonstrate KZD's capacity to modulate the ERK-CREB-BDNF signaling pathway by diminishing ROS expression induced by oxidative stress, enhancing neuronal repair, and thus, manifesting antidepressant properties. Accordingly, KZD represents a promising herbal candidate for further antidepressant research.

Sodium-Glucose Cotransporter-2 Inhibitors vs Sulfonylureas for Gout Prevention Among Patients With Type 2 Diabetes Receiving Metformin.

Importance: Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are a revolutionary treatment for type 2 diabetes (T2D) with cardiovascular, kidney, and serum urate-lowering benefits. Objective: To compare risk of incident gout and rate of recurrent flares between patients with T2D initiating SGLT2i vs sulfonylurea, most common second-line glucose-lowering therapy, when added to metformin monotherapy. Design, Setting, and Participants: This sequential, propensity score-matched, new-user comparative effectiveness study using target trial emulation framework included adults with T2D receiving metformin monotherapy in a Canadian general population database from January 1, 2014, to June 30, 2022. Exposures: Initiation of SGLT2i vs sulfonylurea. Main Outcomes and Measures: The primary outcome was incident gout diagnosis, ascertained by emergency department (ED), hospital, outpatient, and medication dispensing records. Secondary outcomes were gout-primary hospitalizations and ED visits and major adverse cardiovascular events (MACE), as well as recurrent flare rates among prevalent gout patients. Heart failure (HF) hospitalization was assessed as positive control outcome and osteoarthritis encounters as negative control. For target trial emulations, we used Cox proportional hazards and Poisson regressions with 1:1 propensity score matching (primary analysis) and overlap weighting (sensitivity analysis). The analysis was conducted from September to December, 2023. Results: Among 34 604 propensity score matched adults with T2D initiating SGLT2i or sulfonylurea (20 816 [60%] male, mean [SD] age, 60 [12.4] years), incidence of gout was lower among SGLT2i initiators (4.27 events per 1000 person-years) than sulfonylurea initiators (6.91 events per 1000 person-years), with a hazard ratio (HR) of 0.62 (95% CI, 0.48-0.80) and a rate difference (RD) of -2.64 (95% CI, -3.99 to -1.29) per 1000 person-years. Associations persisted regardless of sex, age, or baseline diuretic use. SGLT2i use was also associated with fewer recurrent flares among gout patients (rate ratio, 0.67; 95% CI, 0.55-0.82; and RD, -20.9; 95% CI, -31.9 to -10.0 per 1000 person-years). HR and RD for MACE associated with SGLT2i use were 0.87 (95% CI, 0.77-0.98) and -3.58 (95% CI, -6.19 to -0.96) per 1000 person-years. For control outcomes, SGLT2i users had lower risk of HF (HR, 0.53; 95% CI, 0.38-0.76), as expected, with no difference in osteoarthritis (HR, 1.11; 95% CI, 0.94-1.34). Results were similar when applying propensity score overlap weighting. Conclusions: In this population-based cohort study, the gout and cardiovascular benefits associated with SGLT2i in these target trial emulations may guide selection of glucose-lowering therapy in patients with T2D, at risk for or already with gout.

Fe3O4 nanoparticles entrapped in the inner surfaces of N-doped carbon microtubes with enhanced biomimetic activity.

Tubular structured composites have attracted great interest in catalysis research owing to their void-confinement effects. In this work, we synthesized a pair of hollow N-doped carbon microtubes (NCMTs) with Fe3O4 nanoparticles (NPs) encapsulated inside NCMTs (Fe3O4@NCMTs) and supported outside NCMTs (NCMTs@Fe3O4) while keeping other structural features the same. The impact of structural effects on the catalytic activities was investigated by comparing a pair of hollow-structured nanocomposites. It was found that the Fe3O4@NCMTs possessed a higher peroxidase-like activity when compared with NCMTs@Fe3O4, demonstrating structural superiority of Fe3O4@NCMTs. Based on the excellent peroxidase-like catalytic activity and stability of Fe3O4@NCMTs, an ultra-sensitive colorimetric method was developed for the detection of H2O2 and GSH with detection limits of 0.15 µM and 0.49 µM, respectively, which has potential application value in biological sciences and biotechnology.

Platelet-to-lymphocyte ratio predicts tumor response and survival of patients with hepatocellular carcinoma undergoing immunotherapies.

BACKGROUND: Lymphocyte-related factors were associated with survival outcome of different types of cancers. Nevertheless, the association between lymphocytes-related factors and tumor response of immunotherapy remains unclear. METHODS: This is a retrospective study. Eligible participants included patients with unresectable or advanced hepatocellular carcinoma (HCC) who underwent immunotherapy as their first-line treatment. Radiological assessment of tumor response adhered to RECIST 1.1 and HCC-specific modified RECIST (mRECIST) criteria. Univariate and multivariate logistic analyses were employed to analyze clinical factors associated with tumor response. Kaplan-Meier survivial analysis were employed to compare progression-free survival (PFS) and overall survival (OS) across different clinical factors. Furthermore, patients who received treatment with either a combination of bevacizumab and anti-PD-1(L1) antibody (Beva group) or tyrosine-kinase inhibitor (TKI) and anti-PD-1 antibody (TKI group) were examined to explore the relation between clinical factors and tumor response. RESULTS: A total of 208 patients were enrolled in this study. The median PFS and OS were 9.84 months and 24.44 months,respectively. An independent factor associated with a more favorable tumor response to immunotherapy was identified when PLR<100. Patients with PLR<100 had longer PFS than other patients, while OS showed no significant difference. Further analysis revealed that PLR exhibited superior prognostic value in patients of the Beva group as compared to those in the TKI group. CONCLUSIONS: There exisits an association between PLR and tumor response as well as survival outcomes in patients receiving immunotherapy, particularly those treated with the combination of bevacizumab and anti-PD-1.

Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients.

BACKGROUND: Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) plays a crucial role in regulating insulin signaling and glucose metabolism. Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14 (MODY14). Currently, only two mutations [c.1655T>A (p.Leu552*) and c.281G>A p.(Asp94Asn)] have been identified in association with this disease. Given the limited understanding of MODY14, it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations. AIM: To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain. METHODS: Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study. Whole exome sequencing was performed on the patients as well as their family members. The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis. In addition, the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments. Finally, the impact of these variants on APPL1 protein expression and the insulin pathway were assessed, and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored. RESULTS: A total of five novel mutations were identified, including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions. The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster. In addition, multiple alignment of amino acid sequences showed that the Arg532Gln, Asp632Tyr, and Arg633His variants were conserved across different species. Moreover, in in vitro functional experiments, both the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels, indicating their pathogenic nature. Therefore, based on the patient's clinical and family history, combined with the results from bioinformatics analysis and functional experiment, the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were classified as pathogenic mutations. Importantly, all these mutations were located within the phosphotyrosine-binding domain of APPL1, which plays a critical role in the insulin sensitization effect. CONCLUSION: This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.

Contact neuro-endoscopy-assisted cerebral hematoma evacuation under direct vision.

Neuro-endoscopic hematoma evacuation is a crucial therapeutic approach for intracerebral hemorrhage. Our research team has developed a portable and contact neuro-endoscopy technique to enhance the conventional endoscopy procedure. compared to traditional endoscopy, this innovative approach involves miniaturizing the lens, light source, and camera system. These components are integrated into a stainless steel tube with a diameter of 4 mm, referred to as the portable endoscopy in this study. The portable endoscopy is powered by a USB cable and the video is displayed on a tablet computer. This portable endoscope facilitates easier operation with both hands by a single surgeon.

L-shaped association of triglyceride glucose index and sensorineural hearing loss: results from a cross-sectional study and Mendelian randomization analysis.

Background: The association between the sensorineural hearing loss (SNHL) and triglyceride-glucose (TyG) index remains inadequately understood. This investigation seeks to elucidate the connection between the TyG index and SNHL. Methods: In this cross-sectional study, we utilized datasets sourced from the National Health and Nutrition Examination Survey (NHANES). A comprehensive analysis was conducted on 1,851 participants aged 20 to 69, utilizing complete audiometry data from the NHANES database spanning from 2007 to 2018. All enrolled participants had accessible hearing data, and the average thresholds were measured and calculated as both low-frequency pure-tone average and high-frequency pure-tone average. Sensorineural hearing loss (SNHL) was defined as an average pure tone of 20 dB or higher in at least one better ear. Our analysis involved the application of multivariate linear regression models to examine the linear relationship between the TyG index and SNHL. To delineate any non-linear associations, we utilized fitted smoothing curves and conducted threshold effect analysis. Furthermore, we conducted a two-sample Mendelian randomization (MR) study, leveraging genetic data from genome-wide association studies (GWAS) on circulating lipids, blood glucose, and SNHL. The primary analytical method for the MR study was the application of the inverse-variance-weighted (IVW) approach. Results: In our multivariate linear regression analysis, a substantial positive correlation emerged between the TyG index and SNHL [2.10 (1.80-2.44), p < 0.0001]. Furthermore, using a two-segment linear regression model, we found an L-shaped relationship between TyG index, fasting blood glucose and SNHL with an inflection point of 9.07 and 94 mg/dL, respectively. Specifically, TyG index [3.60, (1.42-9.14)] and blood glucose [1.01, (1.00-1.01)] concentration higher than the threshold values was positively associated with SNHL risk. Genetically determined triglyceride levels demonstrated a causal impact on SNHL (OR = 1.092, p = 8.006 × 10-4). In addition, blood glucose was found to have a protective effect on SNHL (OR = 0.886, p = 1.012 × 10-2). Conclusions: An L-shaped association was identified among the TyG index, fasting blood glucose, and SNHL in the American population. TyG index of more than 9.07 and blood glucose of more than 94 mg/dL were significantly and positively associated with SNHL risk, respectively.

Inhibiting apoptosis and GSDME-mediated pyroptosis attenuates hepatic injury in septic mice.

BACKGROUND: Sepsis is characterized by severe inflammation and organ dysfunction resulting from a dysregulated organismal response to infection. Although pyroptosis has been presumably shown to be a major cause of multiple organ failure and septic death, whether gasdermin E (GSDME)-mediated pyroptosis occurs in septic liver injury and whether inhibiting apoptosis and GSDME-mediated pyroptosis can attenuate septic liver injury remain unclear. This study investigated the role of apoptosis and GSDME-mediated pyroptosis in septic liver injury. METHODS: Adult male C57BL/6 mice were randomly divided into four groups: sham, cecal ligation puncture (CLP), CLP + Z-DEVD-FMK (a caspase-3 inhibitor, 5 mg/kg), and CLP + Ac-DMLD-CMK (a GSDME inhibitor, 5 mg/kg). Sepsis severity was assessed using the murine sepsis score (MSS). Hepatic tissue damage was observed by the hematoxylin-eosin staining method, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the levels of malondialdehyde (MDA), the concentrations of interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) were measured according to the related kits, and the changes in the hepatic tissue reactive oxygen species (ROS) levels were detected by immunofluorescence (IF). The protein expression levels of cleaved caspase-3, GSDME-N, IL-1ß, B-cell lymphoma-2 (Bcl-2), cytochrome C (Cyt-c), and acetaldehyde dehydrogenase 2 (ALDH2) were detected using western blotting. GSDME expression was detected by immunohistochemistry. RESULTS: Compared with the Sham group, CLP mice showed high sepsis scores and obvious liver damage. However, in the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups, the sepsis scores were reduced and liver injury was alleviated. Compared with the Sham group, the serum ALT and AST activities, MDA and ROS levels, and IL-1ß and TNF-α concentrations were increased in the CLP group, as well as the protein expression of cleaved caspase-3, GSDME-N, IL-1ß, Cyt-c, and GSDME positive cells (P < 0.05). However, the expression levels of Bcl-2 and ALDH2 protein were decreased (P < 0.05). Compared with the CLP group, the CLP + Z-DEVD-FMK and CLP + Ac-DMLD-CMK groups showed low sepsis scores, ALT and AST activities, MDA and ROS levels, decreased IL-1ß and TNF-α concentrations, and decreased expression of cleaved caspase-3, GSDME-N, IL-1ß protein expression, and GSDME positive cells (P < 0.05). The expression levels of Bcl-2 and ALDH2 protein were increased (P < 0.05). CONCLUSION: Apoptosis and GSDME-mediated pyroptosis are involved in the development of sepsis-induced hepatic injury. Inhibition of apoptosis and GSDME-mediated pyroptosis attenuates injury. ALDH2 plays a protective role by inhibiting apoptosis and pyroptosis.

Effect of comprehensive nursing intervention on quality of life and treatment outcomes in elderly patients with Gout and Hyperuricemia complicated with hypertension.

Objective: To evaluate the effect of comprehensive nursing intervention on the quality of life and treatment outcomes of elderly patients with gout and hyperuricemia complicated with hypertension. Methods: This is a clinical comparative study. One hundred and twenty elderly patients with gout and hyperuricemia complicated with hypertension who were hospitalized at Baoding No.1 Central Hospital were included from March 20, 2021 to March 20, 2022, and randomly divided into two groups. Patients in the control group were given conventional nursing care in the perioperative period, while those in the experimental group were given comprehensive nursing intervention on the basis of the control group. The differences between the two groups in terms of clinical effects, quality of life were compared and analyzed. Results: The response rate of the experimental group was higher than control group,with a statistically significant difference. After the intervention, the above indicators improved significantly in the experimental group compared to the control group, with statistically significant differences. There was no significant difference in Self-Rating Anxiety Scale(SAS) and Self-rating depression scale(SDS) levels between the two groups before the intervention. After the intervention, SAS and SDS decreased significantly in the experimental group compared to the control group, with statistically significant differences . The patient satisfaction rate of the experimental group was also higher than control group, with a statistically significant difference. Conclusion: Comprehensive nursing intervention is an effective treatment option for elderly patients with gout and hyperuricemia complicated with hypertension, resulting in obvious improvements in patient quality of life, improved mood, patient satisfaction and treatment outcomes.

Full-length transcriptome reveals the pivotal role of ABA and ethylene in the cold stress response of Tetrastigma hemsleyanum.

Tetrastigma hemsleyanum is a valuable herb widely used in Chinese traditional and modern medicine. Winter cold severely limits the artificial cultivation of this plant, but the physiological and molecular mechanisms upon exposure to cold stress in T. hemsleyanum are unclear. T. hemsleyanum plants with different geographical origins exhibit large differences in response to cold stress. In this research study, using T. hemsleyanum ecotypes that exhibit frost tolerance (FR) and frost sensitivity (FS), we analyzed the response of cottage seedlings to a simulated frost treatment; plant hormones were induced with both short (2 h) and long (9 h) frost treatments, which were used to construct the full-length transcriptome and obtained 76,750 transcripts with all transcripts mapped to 28,805 genes, and 27,215 genes, respectively, annotated to databases. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed enrichment in plant hormone signaling pathways. Further analysis shows that differently expressed genes (DEGs) concentrated on calcium signaling, ABA biosynthesis and signal transduction, and ethylene in response to cold stress. We also found that endogenous ABA and ethylene content were increased after cold treatment, and exogenous ABA and ethylene significantly improved cold tolerance in both ecotypes. Our results elucidated the pivotal role of ABA and ethylene in response to cold stress in T. hemsleyanum and identified key genes.

CPXM1 correlates to poor prognosis and immune cell infiltration in gastric cancer.

Background: Gastric cancer (GC) is the fourth most common cause of cancer-related death and the fifth most frequent malignant cancer, especially advanced GC. Carboxypeptidase X member 1 (CPXM1) is an epigenetic factor involved in many physiological processes, including osteoclast differentiation and adipogenesis. Several studies have shown the association of CPXM1 with multiple tumors; however, the mechanism of CPXM1 involvement in the progression of GC is yet to be characterized. Method: CPXM1 expression data were obtained from the Tumor Immune Estimation Resource. The Cancer Genome Atlas and the Gene Expression Omnibus databases were used to obtain patient-matched clinicopathological information, and the Kaplan-Meier plot database was utilized for the prognosis analysis of GC patients. The Catalog of Somatic Mutations in Cancer and cBioportal databases were adopted to study CPXM1 mutations in tumors. Next, we utilized the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis for mechanism research. Furthermore, we performed tumor microenvironment and immune infiltration analysis based on CPXM1. Finally, we predicted sensitivity to several targeted drugs in GC patients based on CPXM1.CPXM1 is upregulated in GC and is correlated with poor prognosis, gender, and tumor stage in GC patients. Gene enrichment analysis suggested that CPXM1 may regulate the occurrence and progression of GC via the PI3K-AKT and TGF-ß pathway. Moreover, CPXM1 expression results in an increase in the proportion of immune and stromal cells. Additionally, the proportion of plasma cells was inversely related to the expression of CPXM1, whereas macrophage M2 expression was proportionate to CPXM1 expression. Finally, six small-molecule drugs that showed notable variations in IC50 between two groups were screened. Conclusion: These results suggested that CPXM1 regulates the progression of GC and may represent a novel target for the detection and treatment of GC.

Phenotypes of osteoarthritis-related knee pain and their transition over time: data from the osteoarthritis initiative.

BACKGROUND: Identification of knee osteoarthritis (OA) pain phenotypes, their transition patterns, and risk factors for worse phenotypes, may guide prognosis and targeted treatment; however, few studies have described them. We aimed to investigate different pain phenotypes, their transition patterns, and potential risk factors for worse pain phenotypes. METHODS: Utilizing data from the Osteoarthritis Initiative (OAI), pain severity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. We identified the activity-related pain phenotypes and estimated the transition probabilities of pain phenotypes from baseline to the 24-month using latent transition analysis. We examined the risk factors at baseline with the 24-month pain phenotypes and the transition of pain phenotypes. RESULTS: In 4796 participants, we identified four distinct knee pain phenotypes at both baseline and 24-month follow-up: no pain, mild pain during activity (Mild P-A), mild pain during both rest and activity (Mild P-R-A), and moderate pain during both rest and activity (Mod P-R-A). 82.9% knees with no pain at baseline stayed the same at 24-month follow-up, 17.1% progressed to worse pain phenotypes. Among "Mild P-A" at baseline, 32.0% converted to no-pain, 12.8% progressed to "Mild P-R-A", and 53.2% remained. Approximately 46.1% of "Mild P-R-A" and 54.5% of "Mod P-R-A" at baseline experienced remission by 24-month. Female, non-whites, participants with higher depression score, higher body mass index (BMI), higher Kellgren and Lawrence (KL) grade, and knee injury history were more likely to be in the worse pain phenotypes, while participants aged 65 years or older and with higher education were less likely to be in worse pain phenotypes at 24-month follow-up visit. Risk factors for greater transition probability to worse pain phenotypes at 24-month included being female, non-whites, participants with higher depression score, higher BMI, and higher KL grade. CONCLUSIONS: We identified four distinct knee pain phenotypes. While the pain phenotypes remained stable in the majority of knees over 24 months period, substantial proportion of knees switched to different pain phenotypes. Several socio-demographics as well as radiographic lesions at baseline are associated with worse pain phenotypes at 24-month follow-up visit and transition of pain phenotypes.

Risk of venous thromboembolism in patients with rheumatoid arthritis: a meta-analysis of observational studies.

BACKGROUND: Thrombotic events, such as venous thromboembolism (VTE) are a major health complication linked to rheumatoid arthritis (RA). We performed a meta-analysis to evaluate the risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in adults with RA compared to the general population. METHODS: MEDLINE and EMBASE databases were searched from inception to April 2022 to identify publications meeting the following criteria: (1) prospective and retrospective original data from cohort or case-control studies; (2) pre-specified RA definition; (3) clearly defined VTE outcomes; (4) reported risk estimate and 95% confidence intervals (95% CIs); (5) at least sex- and age-matched to comparison group; and (6) English language. Of 372 studies screened, 14 were included (602,760 RA patients, 123,076 VTE events) and their quality was assessed by an adaptation of the STROBE quality scoring scale. RESULTS: The pooled risk ratios of VTE, DVT and PE in patients with RA were 1.57 (95% CI 1.41-1.76), 1.58 (95% CI 1.26-1.97) and 1.57 (95% CI 1.30-1.88), respectively. The I2 value of 92%, 94% and 92% for VTE, DVT and PE analyses, suggesting considerable heterogeneity. There were no significant differences in risk estimates among the five subgroup analyses: quality score (P = 0.35, I2 = 0%); sex (P = 0.31, I2 = 1.7%); study year (P = 0.81, I2 = 0%); population source (P = 0.35, I2 = 0%); study design (P = 0.62, I2 = 0%). CONCLUSIONS: Results show that patients with RA are at a higher risk of VTE, DVT and PE compared to the general population.

3D Visual Discomfort Assessment With a Weakly Supervised Graph Convolution Neural Network Based on Inaccurately Labeled EEG.

Visual discomfort significantly limits the broader application of stereoscopic display technology. Hence, the accurate assessment of stereoscopic visual discomfort is a crucial topic in this field. Electroencephalography (EEG) data, which can reflect changes in brain activity, have received increasing attention in objective assessment research. However, inaccurately labeled data, resulting from the presence of individual differences, restrict the effectiveness of the widely used supervised learning methods in visual discomfort assessment tasks. Simultaneously, visual discomfort assessment methods should pay greater attention to the information provided by the visual cortical areas of the brain. To tackle these challenges, we need to consider two key aspects: maximizing the utilization of inaccurately labeled data for enhanced learning and integrating information from the brain's visual cortex for feature representation purposes. Therefore, we propose the weakly supervised graph convolution neural network for visual discomfort (WSGCN-VD). In the classification part, a center correction loss serves as a weakly supervised loss, employing a progressive selection strategy to identify accurately labeled data while constraining the involvement of inaccurately labeled data that are influenced by individual differences during the model learning process. In the feature extraction part, a feature graph module pays particular attention to the construction of spatial connections among the channels in the visual regions of the brain and combines them with high-dimensional temporal features to obtain visually dependent spatio-temporal representations. Through extensive experiments conducted in various scenarios, we demonstrate the effectiveness of our proposed model. Further analysis reveals that the proposed model mitigates the impact of inaccurately labeled data on the accuracy of assessment.