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Osteosarcoma is a cancerous bone tumor that develops from mesenchymal cells and is characterized by early metastasis, easy drug resistance, high disability, and mortality. Immunological characteristics of the tumor microenvironment (TME) have attracted attention for the prognosis and treatment of osteosarcoma, and there is a need to explore a signature with high sensitivity for prognosis. In the present study, a total of 84 samples of osteosarcoma were acquired from the UCSC Xena database, analyzed for immune infiltration and classified into two categories depending on their immune properties, and then screened for DEGs between the two groups and analyzed for enrichment, with the majority of DEGs enriched in the immune domain. To further analyze their immune characteristics, the immune-related genes were obtained from the TIMER database. We performed an intersection analysis to identify immune-related differentially expressed genes (IR-DEGs), which were analyzed using a univariate COX regression, and LASSO analysis was used to obtain the ideal genes to construct the risk model, and to uncover the prognostic distinctions between high-risk scoring group and low-risk scoring group, a survival analysis was conducted. The risk assessment model developed in this study revealed a notable variation in survival analysis outcomes between the high-risk and low-risk scoring groups, and the conclusions reached by the model are consistent with the findings of previous scholars. They also yield meaningful results when analyzing immune checkpoints. The risk assessment model developed in this study is precise and dependable for forecasting outcomes and analyzing characteristics of osteosarcoma.

Muscle-specific kinase (MuSK) myasthenia gravis (MG) is relatively rare and has a higher incidence of myasthenic crisis compared with other subtypes. However, there is still a lack of effective treatment for refractory MuSK MG. We report the case of a 70-year-old female MuSK MG patient with recurrent fluctuations who stabilized on telitacicept in combination with anti-CD20 B-cell depletion therapy. This combination regimen deserves further investigation. Furthermore, we summarized the treatment protocols of 14 previously reported cases of MuSK MG.

BackgroundThe relationship between serial changes in physical activity and the risk of developing atrial fibrillation (AF) has been rarely studied.ObjectivesTo evaluate the association between changes in physical activity over time and the incidence of AF.MethodsA total of 11,828 participants without AF at baseline (visit 1: 1987–1989) from the ARIC Study were included. Physical activity was measured using the modified Baecke Physical Activity Questionnaire at three different visits between 1987 and 2013. Physical activity trajectories over 25 years were identified using latent class trajectory modeling. The primary outcome was the incidence of AF. Multivariable Cox hazard regression models were used to evaluate the relationship between physical activity trajectories and the incidence of AF.ResultsOver a median follow-up of 24 years, 2,108 AF cases (17.8%) occurred. Four distinct physical activity trajectories were identified: light [n = 5,266 (43.3%)]; reduced moderate [n = 3,583 (29.0%)]; moderate [n = 2,691 (25.0%)]; and vigorous intensity [n = 288 (2.8%)]. Compared to the light group, the hazard ratio (HR) and 95% confidence interval (CI) for AF were 1.18 (1.07–1.30) (p

Diabetic peripheral neuropathic pain (DPNP) is a major complication of diabetes that markedly affects the quality of life and health status of patients. Recent studies have investigated the potential regulatory influence of gut flora and bile acids on DPNP via the TGR5/TRPV1 signaling pathway. Dysbiosis of the gut flora not only directly affects bile acid metabolism but also significantly correlates with diabetes-associated neuropathy through interactions with the bile acid receptor TGR5 and the ion channel TRPV1. This review describes how alterations in the gut flora and bile acid metabolism contribute to the pathogenesis of DPNP through the TGR5/TRPV1 signaling pathway, revealing potential applications for this pathway in DPNP management. Furthermore, experimental and clinical studies have demonstrated the modulation of gut flora and bile acid metabolism as well as targeting the TGR5/TRPV1 signaling pathway as an innovative therapeutic approach. Further studies are warranted to elucidate the underlying mechanism and develop treatment modalities based on gut flora regulation and signaling pathway interventions, thus providing novel insights and approaches for DPNP therapy.

PurposeThis retrospective study aimed to explore the efficiency and untoward reaction of liposomal paclitaxel versus docetaxel for locally advanced nasopharyngeal carcinoma (NPC).MethodsThis retrospective study included 115 patients diagnosed with NPC at our hospital between January 2018 and December 2021. Patients were stratified into two groups based on their treatment with either liposomal paclitaxel (n = 71) or docetaxel (n = 44) as part of the neoadjuvant chemotherapy regimen. Objective response rate (ORR), progression-free survival (PFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were compared between the two groups.ResultsORR was significantly improved in the liposomal paclitaxel group than in the docetaxel group (62.0% versus 40.9%, p = 0.028). The 3-year PFS (PFS: 84.4% versus 77.5%, p = 0.303), LRFS (95.8% versus 94.4%, p = 0.810), DMFS (87.2% versus 83.0%, p = 0.443), and OS (90.7% versus 88.8%, p = 0.306) revealed no significance. The neutrophil-to-lymphocyte ratio [hazard ratio (HR): 3.510; p = 0.039] and distant metastasis (HR: 4.384; p = 0.035) were regarded as the risk factors using multivariate regression analysis. Moreover, the incidence of leukopenia at grades 1–2 in the liposomal paclitaxel group was significantly lower than that in the docetaxel group (28.1% versus 79.5%, p < 0.05).ConclusionsLiposomal paclitaxel had better efficacy in terms of short-term effects and lower incidence of leukopenia at grades 1–2 compared with the docetaxel group.

BackgroundNumerous experimental studies have shown that exercise can serve as an intervention with beneficial effects on children and adolescents with autism. However, a systematic review on the specific areas affected has not been conducted.MethodsPreliminary research sources were obtained by searching four databases, and two researchers independently screened the literature that met the study criteria. The study was conducted under the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.Results37 studies were included in the final analysis, of which 9 studies were quantitatively synthesized and 28 studies were qualitatively analyzed. Exercise interventions have positive effects on motor performance, cognitive function, individual and social relationships, behavioral problems, physical health, and brain function in children and adolescents with autism. The results of the meta-analysis indicate that exercise can effectively improve social skills [SMD=-0.53, 95%CI (-0.76, -0.3), P=0.000].ConclusionsLong-term, regular, chronic exercise is beneficial for children and adolescents with autism, particularly in the area of social skills.Systematic review registrationhttps://www.crd.york.ac.uk/prospero PROSPERO, identifier CRD42024554530.

Many systemic diseases, including Alzheimer disease (AD), diabetes mellitus (DM) and cardiovascular disease, are associated with microbiota dysbiosis. The oral and intestinal microbiota are directly connected anatomically, and communicate with each other through the oral-gut microbiome axis to establish and maintain host microbial homeostasis. In addition to directly, periodontal bacteria may also be indirectly involved in the regulation of systemic health and disease through the disturbed gut. This paper provides evidence for the role of periodontal bacteria in systemic diseases via the oral-gut axis and the far-reaching implications of maintaining periodontal health in reducing the risk of many intestinal and parenteral diseases. This may provide insight into the underlying pathogenesis of many systemic diseases and the search for new preventive and therapeutic strategies.

Colorectal cancer (CRC) ranks third in global incidence and second in mortality. However, a comprehensive predictive model for CRC prognosis, immunotherapy response, and drug sensitivity is still lacking. Various types of programmed cell death (PCD) are crucial for cancer occurrence, progression, and treatment, indicating their potential as valuable predictors. Fourteen PCD genes were collected and subjected to dimensionality reduction using regression methods to identify key hub genes. Predictive models were constructed and validated based on bulk transcriptomes and single-cell transcriptomes. Furthermore, the tumor microenvironment, immunotherapy response, and drug sensitivity profiles among patients with CRC were explored and stratified by risk. A risk score incorporating the PCD genes FABP4, AQP8, and NAT1 was developed and validated across four independent datasets. Patients with CRC who had a high-risk score exhibited a poorer prognosis. Unsupervised clustering algorithms were used to identify two molecular subtypes of CRC with distinct features. The risk score was combined with the clinical features to create a nomogram model with superior predictive performance. Additionally, patients with high-risk scores exhibited decreased immune cell infiltration, higher stromal scores, and reduced responsiveness to immunotherapy and first-line clinical drugs compared with low-risk patients. Furthermore, the top ten non-clinical first-line drugs for treating CRC were selected based on their predicted IC50 values. Our results indicate the efficacy of the model and its potential value in predicting prognosis, response to immunotherapy, and sensitivity to different drugs in patients with CRC.

Cortex Moutan is the root bark of the buttercup plant Paeonia suffruticosa Andr, of Ranunculaceae family. It has been utilized in Chinese medicine for thousands of years to treat a multitude of diseases, and traditional Chinese documents allege that it has heat-clearing, antipyretic, anti-inflammatory and detoxicating properties. Paeonol is a bioactive substance extracted from Cortex Moutan, which is considered to be one of its most effective metabolites. Recent studies have illustrated that paeonol treatment can alleviate skin damage, relieve the inflammatory response in patients with numerous dermatological conditions, and inhibit anomalous proliferation of skin tissue. Accordingly, paeonol may serve as a potential therapeutic agent for a variety of skin conditions. This review summarizes the physicochemical properties and pharmacokinetics (PK) characteristics of paeonol, and mechanisms of operation in diverse skin diseases, including dermatitis, psoriasis, pruritus, photoaging, hyperpigmentation, and hyperplasticscar. Additionally, much of the evidence is based on animal experiments. Furthermore, it explores the prospects of enhancing paeonol’s efficacy through extraction, synthesis, and formulation innovations, as well as strategies to overcome its limitations in dermatological therapy. This review aims to provide a more reliable theoretical basis for the clinical application of paeonol.

AimsTo describe weight management and perceptions in China.Materials and methodsData were from the Adelphi Real World Obesity Disease Specific Programme™, a cross-sectional survey between April and July 2022 of physicians managing people with obesity or overweight (PwO) and PwO in real-world clinical practice in China. At data collection, eligible PwO were aged ≥18 years, under weight management and/or had a body mass index (BMI) ≥28 kg/m2.ResultsIn total, 100 physicians and 801 PwO were enrolled. More than two thirds of PwO (70.7%; 531/751) were not diagnosed with obesity until a BMI ≥30 kg/m2. Most PwO (78%; 625/801) were on treatment for at least one obesity-related complication (ORC). Physicians commonly initiated weight loss discussions with PwO who already had an ORC (48.0%; 48/100). According to physicians and PwO, the mean target BMI was set at 25.8 kg/m2 and 24.3 kg/m2, and the mean target percentage weight loss was 19.6% and 23.7%, respectively. Over a median 6.4 months of weight management, the mean percentage weight loss was 4.1%. Few PwO achieved the weight loss target set by their physician (9.9%; 69/695) or themselves (2.0%; 14/696). Most physicians and PwO were unsatisfied with the current weight loss (92.3% [739/801] and 82.0% [650/793], respectively).ConclusionsThese findings suggest that earlier intervention may be needed to address obesity as a disease. Most physicians and PwO recognized the importance of normal weight, but few PwO achieved weight loss targets, which may suggest an unmet need for improved weight management.

Insomnia is the most common sleep disorder in which an individual has trouble falling or staying asleep. Chronic sleep loss interferes with daily functioning and adversely affects health. The main clinical drugs for insomnia are the positive allosteric modulator of the GABA (gamma-aminobutyric acid) A receptors (GABAARs) at the benzodiazepine site with selectivity of the GABA-α1 receptor. They are divided into benzodiazepine drugs and non-benzodiazepine drugs. Most recently, the first partial positive allosteric modulator of GABAAR Dimdazenil was approved by National Medical Products Administration (NMPA) and launched in China. This review summarized the mechanism of actions of current clinical drugs for insomnia, and the clinical applications of these drugs, which may help to understand their involvement in insomnia, and to search for more selective and potent ligands to be used in the treatment of insomnia.

Major depressive disorder (MDD) and bipolar disorder (BD) are two of the most prevalent mood disorders that seriously jeopardize both physical and mental health. The current diagnosis of MDD and BD relies primarily on clinical symptoms. However, correctly differentiating between MDD and BD during depressive episode states remains a substantial clinical challenge. The human gut hosts a large and diverse microbiota, which plays a pivotal role in various physiological processes. Emerging evidence suggests that the gut microbiota (GM) exerts beneficial effects on mental health disorders, including MDD, BD, and schizophrenia, through the microbe-gut-brain axis (MGBA). In recent years, the relationship between GM and mood disorders has garnered considerable attention, leading to intensive research in this area. The MGBA is a bidirectional communication system between the gut and the brain. Growing evidence indicates that the brain can influence the GM, which in turn may modulate the brain through this axis. This review aims to explore the changes in the GM of patients with MDD and BD and evaluate the effects of different treatments on their GM, including medication, probiotic, prebiotic and synbiotic interventions, and fecal microbiota transplantation (FMT). By doing so, we seek to identify potential disease-specific biomarkers, improve differential diagnosis, and offer novel therapeutic avenues for these disorders.

IntroductionRetinal diseases significantly impact patients’ quality of life and increase social medical costs. Optical coherence tomography (OCT) offers high-resolution imaging for precise detection and monitoring of these conditions. While deep learning techniques have been employed to extract features from OCT images for classification, convolutional neural networks (CNNs) often fail to capture global context due to their focus on local receptive fields. Transformer-based methods, on the other hand, suffer from quadratic complexity when handling long-range dependencies.MethodsTo overcome these limitations, we introduce the Multi-Resolution Visual Mamba (MRVM) model, which addresses long-range dependencies with linear computational complexity for OCT image classification. The MRVM model initially employs convolution to extract local features and subsequently utilizes the retinal Mamba to capture global dependencies. By integrating multi-scale global features, the MRVM enhances classification accuracy and overall performance. Additionally, the multi-directional selection mechanism (MSM) within the retinal Mamba improves feature extraction by concentrating on various directions, thereby better capturing complex, orientation-specific retinal patterns.ResultsExperimental results demonstrate that the MRVM model excels in differentiating retinal images with various lesions, achieving superior detection accuracy compared to traditional methods, with overall accuracies of 98.98\% and 96.21\% on two public datasets, respectively.DiscussionThis approach offers a novel perspective for accurately identifying retinal diseases and could contribute to the development of more robust artificial intelligence algorithms and recognition systems for medical image-assisted diagnosis.

BackgroundEncephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) results in a distinctive neuro-psychiatric syndrome. It has been reported that the serum phenylalanine-tyrosine (Phe/Tyr) ratio increases during infection. However, the connection between phenylalanine-tyrosine metabolism and psychiatric symptoms remains unclear.MethodsWe enrolled 24 individuals with anti-NMDAR encephalitis and 18 individuals with non-inflammatory neurological diseases (OND). Chromatography was used to measure serum levels of phenylalanine and tyrosine. Serum and cerebrospinal fluid (CSF) TNF-α levels were obtained from the clinical database. The modified Rankin Scale (mRS) score and Glasgow Coma Scale (GCS) score were recorded during the acute phase. The area under the curve (AUC) of the receiver operating characteristic curve was used to assess prediction efficacy.ResultsIn NMDAR patients, levels of serum Phe and the ratio of serum Phe/Tyr were higher compared to OND patients. The serum Phe/Tyr ratio was also elevated in NMDAR patients with psychiatric syndrome. Furthermore, serum Phe and Tyr levels were correlated with inflammatory indexes.ConclusionThe serum Phe/Tyr ratio is elevated in NMDAR patients with psychiatric syndrome and is associated with severity. Therefore, the serum Phe/Tyr ratio may serve as a potential prognostic biomarker.

Nonalcoholic fatty liver disease (NAFLD) is characterized by over 5% hepatic fat accumulation without secondary causes. The prevalence of NAFLD has escalated in recent years due to shifts in dietary patterns and socioeconomic status, making it the most prevalent chronic liver disease and a significant public health concern globally. Serum uric acid (SUA) serves as the end product of purine metabolism in the body and is intricately linked to metabolic syndrome. Elevated SUA levels have been identified as an independent risk factor for the incidence and progression of NAFLD. This paper reviews the relationship between SUA and NAFLD, the underlying mechanisms of SUA involved in NAFLD, and the potential benefits of SUA-lowering therapy in treating NAFLD. The aim is to raise awareness of SUA management in patients with NAFLD, and to encourage further investigation into pharmacological interventions in this area.

Solitary fibrous tumors (SFTs) are classified as fibroblastic/myofibroblastic tumors that originate from CD34-positive dendritic cells and usually occur in the pleura. In this paper, we describe a case of SFT within the joint cavity of the left knee. A 60-year-old man was admitted to hospital due to swelling in the left knee for the past 8 months without relevant trauma history. X-ray, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography–computed tomography (PET-CT) presented a large, ill-circumscribed, hypervascular, and highly enhanced mass with eccentric calcification and peripheral, intra-lesional vessels. Subsequently, the patient underwent surgical resection. Postoperative pathology confirmed the neoplastic cells to be positive for CD34, Bcl-2, and SATA6, therefore was finally diagnosed as malignant SFT. The patient developed bone metastases within 1 year after surgery. SFT in the joint cavity is rare, and it is difficult to make a preoperative diagnosis.

Pathogenesis of endometriosis (EN) is still unknown, but growing evidence suggests that immune regulation may be important, and the pattern of peripheral immune changes in reproductive women with EN has yet to be fully explored. In this study, we conducted a comprehensive and systematic analysis of immune cell subsets within T cells, B cells, NK cells, and γδ T cells in peripheral blood (PB) samples from women with EN, women with uterine fibroids (UF) but without EN (UF-alone), and healthy controls using multi-parameter flow cytometry. Our findings revealed that UF, a common comorbidity of EN, exhibited similar peripheral immune features to EN, particularly in T cell and B cell immunity. Compared to healthy controls, we constructed the peripheral immune profile of EN. This profile highlighted that the immunopathogenic factors in EN predominantly relate to the immune disorder of B cells and their subsets, as well as the functional abnormalities within immune cell subsets of CD4+ T cells, CD8+ T cells, and γδ T cells. Moreover, using the random forest (RF) machine-learning method, we developed a diagnostic model that can effectively identify the patients with EN from healthy controls. The immune factors identified within this model could be pivotal for unraveling the immune pathogenic mechanisms of EN. Our study is the first to present a comprehensive depiction of the circulating immune features in EN, although the detailed roles and underlying mechanisms of these immune factors in the context of EN require further investigation.

IntroductionChronic viral infection may lead to an immunosuppressive microenvironment, whereas the association between virus-related indicators and treatment response in hepatocellular carcinoma(HCC) patients undergoing immune checkpoint inhibitors(ICIs) therapy remains a topic of debate. We aim to investigate the influence of hepatitis virus on the ICI efficiency in HCC patients through a meta-analysis.MethodsWe searched PubMed, Cochrane Library, Embase, and Web of Science until 14 July 2024 to identify cohort studies involving ICIs treatments in HCC patients. We extracted data from the literature related to hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, baseline HBV load, and antiviral therapy. Overall survival (OS) and progression-free survival (PFS) were considered as the primary endpoints, while objective response rate (ORR) was regarded as a secondary endpoint.ResultsWe included 55 cohort studies published between 2019 and 2024, involving a patient population of 7180 individuals. Summarized hazard ratio (HR) comparing HBV infection with non-HBV infection in the context of ICIs therapy revealed no significant association between HBV infection and either mortality risk or progression risk with the pooled HR for OS of 1.04(95%CI: 0.93-1.16, P=0.483) and the pooled HR for PFS of 1.07(95%CI:0.96-1.20, P=0.342). HBV infected patients with HCC may have better tumor response than non-HBV infected patients receiving ICIs with the combined relative risk(RR) for ORR was 1.94 (95%CI: 1.12-3.38, P=0.002). High baseline HBV load is associated with poor survival outcomes in patients with HCC who receive ICIs with the pooled HR for OS was 1.74 (95%CI: 1.27-2.37, P=0.001), thereby antiviral therapy has the potential to significantly enhance prognostic outcomes with the pooled HR for OS was 0.24 (95% CI: 0.14-0.42 P

BackgroundGoutengsan (GTS) is a traditional Chinese medicine formula that can improve multiple nervous system diseases, such as methamphetamine (MA) dependence. However, the mechanism how GTS treats MA dependence remains unclear. This study was aimed to investigate the action mechanism of GTS on MA dependence using network pharmacology, in vivo/in vitro experimental validation, pharmacokinetics, and tissue distribution in the brain.Materials and MethodsThe bioactive ingredients from GTS and possible targeted genes for treating MA dependence were predicted using network pharmacology. The binding of key components of GTS to the predicted proteins was studied using molecular docking, and the key components were verified by HPLC. The effects of GTS on an MA-induced model in rats and SH-SY5Y cells were studied. The regulatory effects of GTS on the expressions of predicted MAPK pathway-related proteins in rat brain tissues and SH-SY5Y cells were validated. Furthermore, the plasma exposure and brain tissue distribution of GTS ingredients for MA dependence treatment and MAPK pathway regulation were studied in mice.ResultsNetwork pharmacology screened 53 active ingredients, and 287 potential targets of GTS, and showed the MAPK pathway was among the most relevant pathways. Molecular docking showed that key active ingredients (e.g., 6-gingerol, liquiritin and rhynchophylline) bound strongly with MAPK core targets, such as MAPK3, and MAPK8. Five compounds of GTS were detected by HPLC, including 6-gingerol, chlorogenic acid, liquiritin, 5-o-methylviscumaboloside and hesperidin. GTS had a therapeutic effect on MA-dependent rats, and reduced hippocampal CA1 damage and relative expressions of p-MAPK3/MAPK3, p-MAPK8/MAPK8 in brain tissues induced by MA. GTS counteracted aberrant alterations in cAMP, 5-TH and cellular morphology induced by MA induction and exerts therapeutic effects on MA-induced SH-SY5Y cell models. GTS also can antagonize the high expressions of MAPK-related proteins in MA-induced SH-SY5Y cells. Pharmacokinetic experiment revealed the four ingredients of GTS (e.g., chlorogenic acid, 5-o-methylviscumaboloside, hesperidin and rhynchophylline) were exposed in the plasma and brain, which demonstrates its pharmacological effect on MA dependence.ConclusionGTS treats MA dependence by regulating the MAPK pathway via multiple bioactive ingredients. The network pharmacology, experimental validation and pharmacokinetics integrated strategy is efficient in discovering the key pharmacological mechanism of herbal formulae.

Exosomes, which are small extracellular vesicles, are of particular interest in studies on SARS-CoV-2 infection because of their crucial role in intercellular communication. These vesicles are released by several cell types and are rich in “cargo” such as proteins, lipids, and nucleic acids, which are vital for regulating immune response and viral pathogenesis. Exosomes have been reported to be involved in viral transmission, immune escape mechanisms, and illness development in SARS-CoV-2 infection. This review examines the current research on the contribution of exosomes to the interplay between the virus and host cells, highlighting their potential as diagnostic biomarkers and therapeutic targets in combating COVID-19.

IntroductionPeyer's patches (PPs) are crucial antigen-inductive sites of intestinal mucosal immunity. Prior research indicated that, in contrast to other ruminants, PPs in the small intestine of Bactrian camels are found in the duodenum, jejunum, and ileum and display polymorphism. Using this information, we analyzed the microbial and metabolic characteristics in various segments of the Bactrian camel's small intestine to further elucidate how the immune system varies across different regions. MethodsIn this study, the microbiota and metabolite of 36 intestinal mucosal samples, including duodenal (D-PPs), jejunal (J-PPs), and ileal PPs (I-PPs), were profiled for six Bactrian camels using 16S rRNA gene sequencing and liquid chromatography with tandem mass spectrometry (LC-MS/MS). To confirm meaningful associations, we conducted connection analyses on the significantly different objects identified in each group's results. ELISA was used to analyze the levels of IgA, IgG, and IgM in the same tissues. ResultsThe microbiota and metabolite profiles of J-PPs and I-PPs were found to be similar, whereas those of D-PPs were more distinct. In J-PPs and I-PPs, the dominant bacterial genera included Clostridium, Turicibacter, and Shigella. In contrast, D-PPs had a significant increase in the abundance of Prevotella, Fibrobacter, and Succinobacter. Regarding the metabolomics, D-PPs exhibited high levels of polypeptides, acetylcholine, and histamine. On the other hand, J-PPs and I-PPs were characterized by an enrichment of free amino acids, such as L-arginine, L-glutamic acid, and L-serine. These metabolic differences mainly involve amino acid production and metabolic processes. Furthermore, the distribution of intestinal immunoglobulins highlighted the specificity of D-PPs. Our results indicated that proinflammatory microbes and metabolites were significantly enriched in D-PPs. In contrast, J-PPs and I-PPs contained substances that more effectively enhance immune responses, as evidenced by the differential distribution of IgA, IgG, and IgM.DiscussionThe intestinal microenvironment of Bactrian camels displays distinct regional disparities, which we propose are associated with variations in immunological function throughout different segments of the small intestine. This study highlights the specific traits of the intestinal microbiota and metabolites in Bactrian camels, offering a valuable reference for understanding the relationship between regional intestinal immunity and the general health and disease of the host.

IntroductionNon-invasive brain stimulation has been combined with mirror visual feedback (MVF) as a priming strategy to enhance therapeutic efficacy. However, a superior combined effect is hindered by the lack of emphasis on MVF-relevant embodiment perception.ObjectiveThis study assessed the priming effect of repeated transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) and dorsolateral prefrontal cortex (dlPFC) on embodiment perception during MVF.MethodsIn the experiment, 15 healthy participants were required to complete tasks using their left hand while keeping their right hand static behind a mirror. They first received excitatory TMS over the left M1 or dlPFC, or sham-TMS in random order during three trial rounds and then performed three subsequent motor tasks and two task-oriented evaluations during MVF in each trial. Latency time (LT), number of embodiment occurrences, embodiment questionnaire (EQ) score, and time required to complete the task-oriented activities were recorded.ResultsThe results showed that the LT of forearm rotation in the dlPFC-TMS round was shorter than that in the sham-TMS round, although a greater number of occurrences were obtained in both the M1-TMS and dlPFC-TMS rounds compared to the sham-TMS round within the three motor tasks, which suggested that TMS priming facilitated the elicitation of embodiment perception. The EQ results indicated strengthened embodiment perception after TMS priming, especially in the dlPFC-TMS round.ConclusionThis study provides evidence that TMS priming over motor process-related regions, specifically the dlPFC, contributes to eliciting and intensifying embodiment perception during MVF, which benefited from a superior MVF paradigm for improving rehabilitation outcomes.Clinical Trial RegistrationIdentifier ChiCTR2400089499 https://www.chictr.org.cn/showproj.html?proj=240385.

IntroductionCannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects.MethodsHerein, an investigation into the antiproliferative effects of natural cannabinoids on human ovarian cancer Caov-3 cells identified cannabidiol (CBD) as the most promising cannabinoid. Furthermore, chemical modifications of CBD yielded a group of derivatives with enhanced cytotoxicity in Caov-3 cells.ResultsTwo CBD piperazinyl derivatives (19 and 21) showed augmented antiproliferative effects with an IC50 of 5.5 and 4.1 µM, respectively, compared to CBD’s IC50 of 22.9 µM. Further studies suggest that modulation of apoptosis and ferroptosis may contribute to the cytotoxic effects of CBD and its derivatives. In addition, CBD and its derivatives (19 and 21) were explored for their potential synergistic antiproliferative effects in combination with chemotherapeutic agent cisplatin. Compounds 19 or 21 (5 µM) combined with cisplatin (1 µM) showed a synergistic effect with a combination index of 0.23 and 0.72, respectively. This effect was supported by elevated levels of reactive oxygen species in Caov-3 cells treated with cisplatin combined with 19 or 21.DiscussionFindings from this study suggest that CBD derivatives with enhanced antiproliferative effects may exert synergistic effects with chemotherapeutic drugs, providing insight into the development of cannabinoid-based adjuvant agents for the management of ovarian cancer.

Within the research field of bilingual lexical representation and organization, much attention has been given to whether two languages share a conceptual system and what factors modulate the connection between this conceptual system and the lexical systems of a bilingual’s L1 and L2. One of the most valid ways in the psycholinguistics domain to explore these doubts is to examine the masked translation priming effect and the priming asymmetry through cross-language priming experiments. In this study, a masked priming lexical decision task was conducted with unbalanced English-Chinese bilinguals to investigate whether the masked translation priming effect exists in both translation directions, and to further reveal how the number of translations, which can be categorized into one-translation pair and more-than-one-translation pair conditions, affects the priming effects and modulates translation priming asymmetry. It was demonstrated that both translation direction and the number of translations influence the priming effect. Specifically, the priming effect was observable from L1 to L2 but not from L2 to L1, and the priming for one-translation pairs was significantly greater when compared to that for more-than-one-translation pairs. Moreover, the impacts of translation direction on the priming effect differed between the one-translation pair and more-than-one-translation pair conditions: under the former condition, substantial priming occurred in both directions, whereas for the latter condition, it was observed only in the L1–L2 direction. Several models of the bilingual mental lexicon, mainly the Revised Hierarchical Model and the Distributed Conceptual Feature Model, were used to elucidate the above results.

IntroductionBlack-bone chicken meat is rich in nutritional substances and bioactive compounds. Stewing is a traditional and healthy cooking style for black-bone chicken meat. However, the alteration of metabolites in chicken meat during stewing is still unknown.MethodsA comprehensive analysis of Lueyang black-bone chicken meat metabolites was performed in fresh chicken meat (FM), short-term heat-pretreated meat (PM), fully cooked meat (CM) and chicken soup (CS) via untargeted metabolomics.ResultsBy comparison, 200, 992 and 891 significantly differentially metabolites (DMs) were identified in the PM vs. FM, CM vs. FM and CS vs. FM comparisons, respectively. These DMs mainly included amino acids, peptides, carbohydrates and lipids. During the heating process, the abundances of Ser, Ala, Tyr, niacinamide, galactose, guanosine 3′-monophosphate and inosine 5′-monophosphate in chicken meat significantly decreased and were partially dissolved in the soup. Due to the hydrolysis of phospholipids, the relative contents of unsaturated lipids, especially a range of lysophosphatidylcholines, lysophosphatidylethanolamines, arachidonic acid and derivatives, increased in fully cooked meat.DiscussionPretreatment had little impact on the changes in metabolites in chicken meat. During stewing, the dissolved amino acids, carbohydrates and nucleic acids could enhance the taste quality of chicken soup, and the high abundance of unsaturated lipids could promote the nutritional quality of black-bone chicken meat. In summary, these data provide helpful information for nutritional quality studies on the metabolite profiles of black-bone chicken meat.

ObjectiveTo investigate the associations between comorbidities and multimorbidity patterns with motor and neuropsychiatric symptoms in patients with Parkinson’s disease (PD) in prodromal PD.MethodsMultimorbidity is defined as the coexistence of two or more long-term conditions (LTCs) (also known as multiple comorbidities). A total of 921 participants without PD were included in the Parkinson’s Progression Markers Initiative (PPMI) database and were categorized according to the LTC count. Participants were evaluated on motor and psychiatric symptoms. Pearson correlation to examine relationship of comorbidities and target symptoms. The baseline population was analyzed using Multiple linear regression model, while mixed effects model was utilized for longitudinal analysis. Fuzzy C-means clustering analysis was conducted to identify comorbidity patterns, followed by multiple linear regression for further analysis.ResultsAt baseline, a higher LTC count was significantly correlated with more severe motor (MDS-UPDRS I, II, ADL, all P < 0.05) and neuropsychiatric symptoms (QUIP, P < 0.001). Three multimorbidity patterns were identified. Among them, the cardiometabolic multimorbidity pattern (CAR) had the most significant correlation with the aforementioned symptoms. Our longitudinal analysis indicated that an increase in the LTC count was associated with the exacerbation of motor and neuropsychiatric symptoms.ConclusionComorbidities were cross-sectionally and longitudinally associated with the motor and neuropsychiatric symptoms of patients with prodromal PD. Among the three multimorbidity patterns, CAR posed the highest threat to the risk of more severe motor and neuropsychiatric symptoms.

Depression is a serious cognitive disorder that results in significant and pervasive deficits in social behavior. These deficits can be traced back to the intricate interplay between social, psychological, and biological factors. Inflammatory depression, a treatment-resistant or non-responsive subtype of depression, may be related to the interaction between the gut microbiota and interleukin-17-producing CD4+ T cells (Th17 cells). The heterogeneity, plasticity, and effector role of Th17 cells in depression may be influenced by microbiota factors. Commensals-elicited homeostatic Th17 cells preserve the morphological and functional integrity of the intestinal barrier. In addition to pathogen-elicited inflammatory Th17 cells, commensal-elicited homeostatic Th17 cells can become conditionally pathogenic and contribute to the development of inflammatory depression. This review delves into the possible involvement of Th17 cells in inflammatory depression and examines the interplay between gut microbiota and either homeostatic or inflammatory Th17 cells.

BackgroundSuicidal behavior including suicidal ideation (SI) and suicide attempts (SA) is a common clinical feature of adolescent patients with major depressive disorders (MDD). We hypothesized that differences in functional connectivity density (FCD) exist between adolescent patients with SA and SI, and aimed to investigate the different suicidal behaviors in adolescents patients with MDD17.Methods37 MDD adolescents with SA, 34 MDD adolescents with SI, 20 MDD adolescents without SA and SI (non-suicidal group), and 20 adolescents healthy controls (HC) were enrolled in this study. All participants were scanned using functional magnetic resonance imaging (fMRI) to evaluated the FCD. Between-group differences of all variables were analyzed. The relationships between FCD values and clinical scale scores were also analyzed.ResultsThe FCD of the left inferior occipital gyrus in the SI group was higher than those in the other groups. The FCD in the SA group was higher than that in the control group. The FCD of the right dorsolateral superior frontal gyrus in the SI group was lower than that in the other three groups. The FCD values of the left precentral gyrus in the SI group were higher than those in the other three groups. The left inferior occipital gyrus FCD positively correlated with the suicide factor score of Hamilton Depression Scale (HAMD), and the right dorsolateral superior frontal gyrus negatively correlated with the HAMD suicide factor score but not with the HAMD total score.ConclusionChanges in FCD in adolescent patients with depression and SI can reflect changes in functional connections in the brain.

BackgroundOver the past decade, the proportion of hepatitis C virus (HCV) genotypes (GT) 1 and 2 has decreased in almost all regions of China, while GT 3 and 6 have emerged as new challenges. GT 6 is unique in many respects, like high genetic variability and emerging resistant variants. This study aims to assess the efficacy of sofosbuvir (SOF)-based treatments in patients with GT 6 chronic hepatitis C (CHC).MethodsA retrospective analysis was conducted on patients with GT 6 HCV infection, who were diagnosed between July 2018 and May 2023. All patients received a 12-week course of SOF-based treatments. The primary efficacy endpoint was sustained virologic response (SVR), which is defined as having undetectable HCV RNA at 12 weeks after treatment completion (SVR12). The efficacy data for SVR12 were analyzed using both the evaluated population (EP) and per-protocol population (PP). For the PP populations, efficacy data were stratified using Forrester plots.ResultsA total of 201 patients were included in the study. In PP population, the end of treatment virological response rate was 99.48% (190/191), the SVR12 rate was 99.31% (143/144), and the SVR24 rate was 100.00% (75/75). Only one patient with genotype 6a experienced a relapse 12 weeks after the completion of treatment, but her HCV RNA was undetectable both at the end of treatment and 24 weeks after the end of treatment. Additionally, the normalization rates of alanine transaminase (ALT) and aspartate aminotransferase (AST) were significantly higher at the end of treatment (EOT) compared to baseline (27.36% vs. 93.03%, 36.32% vs. 95.02%, p

BackgroundAlthough the association between HHEX, IGF2BP2, and FTO polymorphisms and the risk of GDM has been investigated in several studies, the findings have been inconsistent across different populations. The study aimed to investigate the association between genetic polymorphisms and GDM risk in a Chinese population.Methods502 control volunteers and 500 GDM patients were enrolled. IGF2BP2 rs11705701 and rs4402960, FTO rs9939609, and HHEX rs1111875 and rs5015480 were all genotyped using the SNPscan™ genotyping assay. The independent sample t-test, logistic regression, and chi-square test were used to assess the variations in genotype and allele and their relationships with the risk of GDM. The blood glucose level, gestational week of delivery, and newborn weight were compared using a one-way ANOVA.ResultsAfter adjusting for confounding factors, the results show that the rs1111875 heterozygous (OR=1.370; 95% CI: 1.040-1.805; P = 0.025) and overdominant (OR=1.373; 95% CI: 1.049-1.796; P = 0. 021) models are significantly associated with an increased risk of GDM, especially for the age ≥ 30 years group: heterozygote (OR=1.646; 95% CI: 1.118-2.423; P=0.012) and overdominant (OR=1.553; 95% CI: 1.064-2.266; P = 0.022) models. In the age ≥ 30 years, the rs5015480 overdominant model (OR=1.595; 95% CI: 1.034-2.459; P = 0.035) and the rs9939609 heterozygote model (OR=1.609; 95% CI: 1.016-2.550; P=0.043), allele (OR=1. 504; 95% CI: 1.006-2.248; P = 0.047), dominant model (OR=1.604; 95% CI: 1.026-2.505; P = 0.038), and overdominant model (OR=1.593; 95% CI: 1.007-2.520; P = 0.047) were associated with a significantly increased risk of GDM; Additionally, people with the TC genotype of rs1111875 had a substantially higher 1-hour blood glucose level than TT genotype (P < 0.05). The results of the meta-analysis showed that the A allele of rs11705701 was associated with an increased risk of diabetes mellitus (P < 0.05).ConclusionThe study indicates that the TC genotype of rs1111875 is linked to a higher risk of GDM, particularly in women aged 30 years or older. Additionally, rs5015480 and rs9939609 were significantly associated with GDM in the same age group. These SNPs may therefore be more closely linked to GDM in older mothers.

ObjectiveThe objective of the study was to investigate the application effect of scenario simulation teaching based on the Mini-Clinical Evaluation Exercise (Mini-CEX) and direct observation of procedural skills (DOPS) rating scales in urology clinical apprenticeship training.Materials and methodsA total of 32 students from the class of 2015–2017 who completed their traineeship in the Department of Urology of our hospital were selected and divided into a research group and a routine group. Routine teaching was implemented for the trainees in the control group, while situational simulation teaching based on the Mini-CEX and DOPS scoring scales was implemented for the trainees in the research group. The Mini-CEX and DOPS scores and student satisfaction were compared at the time of admission and discharge between the two groups.ResultsAt the time of admission, there was no statistically significant difference between the Mini-CEX and DOPS scores of the two groups of trainees (p > 0.05). However, at the time of discharge, the Mini-CEX and DOPS scores of the trainees in the study group were 53.21 ± 4.52 and 81.23 ± 3.57, respectively, which were significantly higher than those in the conventional group (p

ObjectiveThis study aims to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of specific corticosteroids, including but not limited to hydrocortisone, methylprednisolone, prednisolone, and dexamethasone, in the treatment of severe community-acquired pneumonia (SCAP). Efficacy will be assessed using specific outcomes, such as 30-day mortality and the requirement for mechanical ventilation. Safety evaluations will include adverse events like gastrointestinal bleeding and healthcare-associated infections. The study seeks to address the gaps identified in the latest guidelines regarding the optimal use of different corticosteroid types and to provide recommendations for clinical practice.Data SourcesThis study conducted a comprehensive search of Medline, Embase, and the Cochrane Central Register of Controlled Trials, covering the period from inception until 22 June 2023. Randomized clinical trials for corticosteroid use among adults with SCAP were collected.Study SelectionTwo researchers independently assessed study eligibility based on titles and abstracts, with any disagreements resolved through discussion or consultation with a third researcher.Data ExtractionTwo researchers independently collected and clarified study details, with a third researcher adjudicating in case of disputes.Data SynthesisThe data from 13 randomized clinical trials involving 2,495 patients, were analyzed using a random-effects model. Eleven trials were assessed as low risk, while two were assessed as high risk. Trials were rated as having low bias risk. Results, presented as risk ratios (RR) with a 95% confidence interval (CI), indicated that hydrocortisone outperformed prednisolone (RR 0.35; 95% CI 0.10–0.94), methylprednisolone (RR 0.41; 95% CI 0.15–0.89), and placebo (RR 0.35; 95% CI 0.16–0.59) in reducing 30-day mortality. A rankogram plot suggested that hydrocortisone had the highest probability of being the most effective treatment for this outcome within the analyzed group.ConclusionIn this network meta-analysis, while hydrocortisone showed greater efficacy than prednisolone, methylprednisolone, and placebo in reducing 30-day mortality in patients with SCAP, further Randomized Controlled Trials (RCTs) are required to confirm these findings before drawing definitive conclusions.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=438389, identifier CRD42023438389.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment modality, offering promising outcomes for various malignancies. However, the efficacy of ICIs varies among patients, highlighting the essential need of accurate predictive biomarkers. This review synthesizes the current understanding of biomarkers for ICI therapy, and discusses the clinical utility and limitations of these biomarkers in predicting treatment outcomes. It discusses three US Food and Drug Administration (FDA)-approved biomarkers, programmed cell death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and microsatellite instability (MSI), and explores other potential biomarkers, including tumor immune microenvironment (TIME)-related signatures, human leukocyte antigen (HLA) diversity, non-invasive biomarkers such as circulating tumor DNA (ctDNA), and combination biomarker strategies. The review also addresses multivariable predictive models integrating multiple features of patients, tumors, and TIME, which could be a promising approach to enhance predictive accuracy. The existing challenges are also pointed out, such as the tumor heterogeneity, the inconstant nature of TIME, nonuniformed thresholds and standardization approaches. The review concludes by emphasizing the importance of biomarker research in realizing the potential of personalized immunotherapy, with the goal of improving patient selection, treatment strategies, and overall outcomes in cancer treatment.

Achieving the dual goals of improving water quality and reducing carbon emissions requires a systematic study of the combined effects of economic and environmental policies on industrial systems. A CGE-IWCR model is developed to examine the long-term evolution of industrial economic and environmental responses in the Yangtze River Economic Belt (YREB) under varying levels of carbon and water pollution taxes. The CGE-IWCE model offers several advantages: i) under the dual tax (carbon and water pollution tax) interventions, it can effectively forecast industrial CO2 and water pollution emissions driven by both macro and local factors from 2025 to 2060; ii) it quantitatively captures the interactions between various policy interventions, thereby providing guidance for comprehensive regional policy formulation. It is discovered that in the double-tax scenario, various combinations of carbon and water pollution taxes significantly impact direct carbon emissions and direct water pollution emissions, and from local consumption, imports, and exports in industrial sectors. Among them, the dual pressure of high carbon and water pollution taxes, which significantly raise production costs. In addition, increasing the carbon tax from 10 ¥/tonne to 50 ¥/tonne, the water pollution equivalent (WPE) reduction rate rises from 20.79% to 52.67% with the increase in the carbon tax from 2050 to 2060, when the water pollution tax is low. Between 2025 and 2060, the carbon tax plays a significant role in influencing the total industrial output change rate in YREB. from 2025 to 2060, the water pollution tax will play a more significant role in CO2 reduction in YREB’s industrial sector. The results will offer decision-making support for water pollution reduction and carbon mitigation in the YREB’s industrial sector, quantitatively identify the interactions between the dual taxes, and provide new insights for analyzing the impacts of pollution reduction and carbon mitigation policies.

BackgroundMetabolic reprogramming is a hallmark of cancer, including alterations in the hexosamine biosynthesis pathway (HBP). Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the key regulatory enzyme in the HBP; however, its role in invasive breast carcinoma remains underexplored.MethodsThis study utilized integrated data from The Cancer Genome Atlas (TCGA) to assess GFPT1 expression in breast cancer (BRCA) patients. Functional enrichment and mutational landscape analyses were performed, along with chemosensitivity predictions. In vitro experiments were conducted by silencing GFPT1 in malignant breast epithelial cells to evaluate changes in proliferation, migration, and apoptosis.ResultsElevated GFPT1 expression was linked to advanced-stage breast cancer and identified as an independent prognostic marker for overall survival (OS). High GFPT1 levels were associated with increased cytoplasmic translation, activation of oncogenic pathways, and infiltration of M2 macrophages. The GFPT1-High group also showed a higher mutational burden, with frequent TP53 mutations. Chemosensitivity analysis revealed increased IC50 values for chemotherapy drugs in this group. GFPT1 silencing led to reduced cell proliferation and migration, along with enhanced apoptosis.ConclusionThese findings indicate that GFPT1 is a novel prognostic biomarker and a predictive indicator of chemotherapy response in invasive breast carcinoma. GFPT1 influences mRNA translation, cell cycle regulation, and M2 macrophage infiltration, thereby promoting cancer cell proliferation and metastasis.

A low-cost rolling base isolation system (RBIS) for rubble stone masonry buildings in the Himalayan mountain range was presented and the feasibility of RBIS in the initial conditions installed in the buildings were evaluated in experiments and simple numerical simulations. The base isolation layer is composed of styrofoam, concrete slab and cast-iron balls. The styrofoam and concrete slab are the upper and lower elements of the isolation layer. The styrofoam boards are used for the embedment of the cast-iron balls and form panels for the casting concrete of the tie beams above the isolation layer. In the case of large earthquakes, these balls roll and horizontally squeeze into the styrofoam boards. The proposed RBIS satisfies two issues for the base isolation system in rubble stone masonry buildings in the Himalayan Mountain range; i.e. (i) use of locally available materials in the isolation layer and (ii) simple construction procedure of the isolation layer by local workers. The quasi-static cyclic loading experiments were conducted. The rolling coefficients of the RBIS were 0.06–0.14. Shaking table experiments were also conducted. It was found that the recorded maximum accelerations are approximately 0.2g. The restoring force characteristics of RBIS in the shaking table experiment were created and the behavior of the experiment was simulated by the response history analyses (RHAs). The behavior of the rubble stone masonry building associated with RBIS under large earthquakes was also evaluated in RHAs. Assuming that the traditional masonry buildings can resist the earthquake ground motions with a PGA under 0.15g, the buildings installed with RBIS can resist the ground motions with a PGA under 0.5g.

Cognitive ability plays a crucial role in adolescents’ academic performance and subsequent career development. Although previous studies have demonstrated that physical activity, self-education expectations, and learning behaviors positively affect the cognitive development of adolescents, the extent of their influence and their mediating roles require further elucidation. This study is based on tracking survey data from 2,688 adolescents in Chinese households collected in 2018. Multiple linear regression, Propensity Score Matching, and Quantile regression were employed to analyze the impact and heterogeneity of physical activity on adolescents’ cognitive ability. Furthermore, the Bootstrap mediation test was used to explore the mediating roles of self-education expectations and learning behaviors in this process. The results indicate the following: Physical activity significantly promotes adolescents’ cognitive ability; for those with poorer cognitive ability, it exerts a greater impact. Moreover, in addition to its direct effects, physical activity indirectly enhances adolescents’ cognitive ability through the mediation of three factors (self-education expectations, learning behaviors, self-education expectations and learning behaviors). These discoveries offer significant insights into diverse strategies for developing cognitive ability in adolescents, contributing to both theoretical research and practical interventions.

BackgroundAcute Respiratory Distress Syndrome (ARDS) is a severe lung condition posing significant health risks. Observational studies have indicated a potential linkage between ARDS and various interleukins, such as Interleukin-8, −2, −6, and −1β. However, the causal relationships between specific interleukins, their receptors, and ARDS remain unclear.MethodsThis study employed bidirectional Mendelian Randomization (MR) to investigate the causal associations between 197 different interleukins, interleukin receptors, and ARDS. GWAS summary data for interleukins and their receptors were sourced from publicly available studies, while ARDS data were derived from the FinnGen database. Wald Ratio and Inverse Variance Weighted (IVW) methods were primarily utilized in the MR analyses. Reverse MR was also conducted to explore reverse causations.ResultsThe study identified significant causal relationships between several interleukins, their receptors and ARDS. Specifically, Interleukin-17 receptor D (IL-17RD) (OR = 0.67, 95%CI = 0.51–0.89, p = 0.006), Interleukin-22 receptor subunit alpha-1 (IL22RA-1) (OR = 1.45, 95%CI = 1.08–1.96, p = 0.014), Interleukin-20 receptor subunit alpha (IL20RA) (OR = 0.53, 95%CI = 0.32–0.89, p = 0.016), Interleukin-22 (IL-22) (OR = 3.60, 95%CI = 1.20–10.83, p = 0.022), Interleukin-23 receptor (IL-23R) (OR = 2.14, 95%CI = 1.10–4.17, p = 0.025), Single Ig IL-1-related receptor (SIGIRR) (OR = 1.22, 95%CI = 1.00–1.48, p = 0.047) showed notable associations with ARDS. No reverse causal relationships were found on results above, and neither heterogeneity nor pleiotropy was detected in the analysis.ConclusionThis study elucidates the causal connections between specific interleukins, their receptors and ARDS, contributing significantly to the understanding of ARDS pathogenesis. These findings offer a foundation for further research and potential therapeutic interventions targeting these interleukins and receptors in ARDS management. The absence of reverse causation and pleiotropy, heterogeneity reinforces the robustness of these associations.

Rumen-protected glucose (RPG) and taurine (TAU) are crucial for the nutrition and physiology of ruminants, enhancing production performance and mitigating negative energy balance. This study aimed to assess the impact of RPG levels and TAU supplementation on the body weight, antioxidant capacity, immune function and stress responses in yaks before and after transport. Thirty-two healthy male yaks, aged 3 years and weighing 172.5 ± 10.2 kg, were randomly assigned to one of four dietary treatments: (1) low RPG and low TAU (LRLT), with 1% RPG and 5 g/d TAU; (2) low RPG and high TAU (LRHT), with 1% RPG and 15 g/d TAU; (3) high RPG and low TAU (HRLT), with 3% RPG and 5 g/d TAU; and (4) high RPG and high TAU (HRHT), with 3% RPG and 15 g/d TAU. The yaks were treated with the corresponding diet for 7 days, then received 9 h of transportation, and finally fed the same diet at their destination for 30 days. The weight was measured before and on days 0 and 30 after transport, and the plasma was collected before and on day 0, 10, and 30 after transport for analysis of biochemical, antioxidant, immune, and stress response indicators. We observed that transport increased plasma concentrations of total cholesterol, total protein, lactate dehydrogenase, creatine kinase, malondialdehyde, cortisol and lipopolysaccharides of yaks among treatments, while decreased their BW and plasma IL-10 concentration. Increasing TAU supplementation reduced weight loss (8.42 vs. 11.9 kg) and weight loss percent (4.83% vs. 6.87%) in yaks after transport. The concentration of MDA in plasma was lower in HRHT than in LRLT at day 0 after transport (p = 0.03). The activity of GSH-PX was higher in HRHT than in LRLT at day 10 after transport (p = 0.04). Concentrations of IL-10 at day 0 and 10 after transport was higher in HRHT than in LRLT and HRLT (p = 0.02, p = 0.01, respectively). With the increase of TAU supplementation, concentrations of IL-1β at day 30 after transport (p = 0.02), TNF-α at day 0 after transport (p = 0.02), COR at day 10 (p = 0.03) and 30 (p = 0.05) after transport as well as LPS at day 0 after transport (p = 0.04) decreased. In addition, concentrations of COR at day 0 after transport was lower in LRHT and HRHT than in LRLT (p = 0.03). Based on all the results, we demonstrated that increasing TAU supplementation levels reduced post-transport weight loss in yaks, improved their antioxidant capacity and immune function, and alleviated stress responses. Considering the effect of resistance to transport stress and costs, the optimal treatment identified in this study involved a diet containing 1% RPG and supplemented with 15 g/d TAU.

ObjectiveTo determine the diagnostic and prognostic value of soluble suppression of tumorigenicity 2 (sST2) in patients with sepsis.MethodsA total of 113 critically ill patients were enrolled at the emergency department of Beijing Chaoyang Hospital Jing Xi Branch. Venous blood levels of sST2 were measured using the AFIAS-6 dry fluorescence immunoassay analyzer. Based on Sepsis 3.0 criteria, patients were categorized into a sepsis group (76 cases) and a non-sepsis group (37 cases). The sepsis group was further divided into non-survivors (38 cases) and survivors (38 cases) based on 28-day survival outcomes. The vital signs, blood gas analysis, routine blood tests, liver and kidney function tests, procalcitonin (PCT), C-reactive protein (CRP), sST2, left ventricular ejection fraction (LVEF), and other basic characteristics of the patients were recorded. Further, the SOFA, qSOFA and APACHE II scores of each patient were calculated. Statistical analysis was performed using SPSS 25.0, including logistic regression and ROC curve analysis to assess prognostic factors.ResultsThe serum sST2 levels in the sepsis group (125.00 ± 60.32 ng/mL) were significantly higher than in the non-sepsis group (58.55 ± 39.03 ng/mL) (p

Castleman disease (CD) is a rare lymphoproliferative disease known as angiofollicular lymph node hyperplasia, firstly reported in 1954. It mainly occurs in adults, presenting with a wide range of clinical manifestations, including paraneoplastic pemphigus (PNP). PNP is a rare and often life-threatening autoimmune disorder characterized by painful blisters and erosions on the skin and mucous membranes. In children, PNP is often linked to Castleman disease, as evidenced in case reports. So far, less than 30 pediatric cases have been reported, with the pathogenesis remaining unclear and treatment approaches varied. Here, we present a pediatric case initially suspected as Behçet's disease due to persistent oral ulcers and conjunctivitis, and undergone a sudden aggravation of clinical features following an allergic reaction. New involvement of skin rashes and imaging findings prompted the final diagnosis as PNP linked to Unicentral Castleman disease (UCD).Through detailing the progression of clinical features and diagnostic work, we aim to arise the awareness of physicians and put emphasize on early recognition and multidisciplinary management, which can improve patient outcomes.

IntroductionAmdizalisib (HMPL-689) is an ATP-competitive PI3Kδ inhibitor currently under investigation for treating Hodgkin’s lymphoma. This study aimed to evaluate the metabolism, excretion, pharmacokinetics, and safety profile of amdizalisib in healthy human subjects to support its clinical application.MethodsThis Phase I clinical trial included six healthy Chinese male volunteers who received a single oral dose of 30 mg/100 µCi [14C]amdizalisib suspension. Blood, urine, and fecal samples were collected to analyze pharmacokinetics, metabolic pathways, and excretion patterns.ResultsAmdizalisib was rapidly absorbed, with a median Tmax of 2.5 h. The Cmax of 244 ± 48.9 ng/mL, and AUC0-t was 1870 ± 474 h ng/mL after a single oral dose. The blood-to-plasma total radioactivity ratio ranged from 0.561 to 0.645, indicating no significant affinity of [14C]amdizalisib and its metabolites to blood cells and the radioactive material is mainly distributed in plasma. Excretion was primarily via feces and urine, with 62.08% ± 3.00% and 37.15% ± 2.84% of the dose recovered, respectively, and over 94% of the drug excreted within 96 h. The parent drug was the main radioactive component in plasma (51.45% of total radioactivity). Additionally, 11 metabolites were identified, and the metabolic pathways include oxidation on the benzene or pyrimidine rings and conjugation with cysteine or glucuronic acid. The major metabolites in plasma were the di-oxidized and hydrogenated product (M424) and the mono-oxidized product (M406-2), accounting for 16.67% and 20.91%, respectively. Both of them are also the major radioactive components in urine and feces, among of which M424 accounted for 21.01% and 14.26%, M406-2 accounted for 8.08% and 11.30%, of the administered dose in urine and feces, respectively. In addition, the di-oxidized and methylated product (M436) was one of the major metabolites in feces accounting for 17.7% of the administered dose. Few of the parent drug was found in urine and feces, suggesting primary metabolized in the liver. No serious adverse events or drug-related deaths occured, with diarrhea as the most common adverse event.DiscussionThese findings demonstrate that amdizalisib is rapidly absorbed, extensively metabolized, and primarily excreted via feces and urine, supporting its continued development as a potential therapeutic for Hodgkin's lymphoma.Systematic Review Registration:https://www.chinadrugtrials.org.cn/, identifier CTR20212448.

IntroductionThe COVID-19 pandemic has greatly impacted the way that the world views vaccines. While safe and effective, COVID-19 vaccines were, and continue to be met with hesitancy and misinformation. We aimed to understand public perceptions and trust in COVID-19 vaccinations and how the pandemic has impacted perceptions of non-COVID-19 vaccines.MethodsSurvey data were collected between August 7, 2023–August 16, 2023, from 7,000 respondents aged 18 years and older from the United States (n = 1,000); Nigeria (n = 1,000); United Kingdom (n = 1,000); France (n = 1,000); Canada (n = 1,000); Brazil (n = 1,000); and India (n = 1,000).ResultsTrust in COVID-19 vaccines was highest in Brazil (84.6%) and India (80.4%) and lowest in the United States (63.5%) and France (55.0%). 47.5% of respondents agreed that they trust traditional protein-based vaccines more than mRNA vaccines, 13.5% disagree and 39.0% are neutral about their trust in protein-based versus mRNA vaccines. Overall, 53.9% of respondents reported that the COVID-19 pandemic impacted their perceptions of vaccines with half of these respondents (51.7%) reporting that the pandemic made them think that other vaccines are more important as they understand how critical vaccines can be at preventing serious illnesses.DiscussionThese data can be used by health system decision makers, public health and researchers to understand how vaccine trust impacts perceptions of COVID-19 and influenza vaccines globally and develop tailored interventions that address local concerns.

BackgroundAnemia is a common complication in patients with heart failure and is associated with left ventricular systolic dysfunction. However, its role in right ventricular (RV) function has not been evaluated.MethodsWe retrospectively analyzed the electronic medical data of 1,014 Heart Failure with Preserved Ejection Fraction (HFpEF) patients to evaluate the relationship between anemia and RV dysfunction in patients with HFpEF and whether this relationship is influenced by classical risk factors such as smoking and hypertension.ResultsThe study showed that anemic patients were older and had significantly higher New York Heart Association functional class and tricuspid regurgitation (TR) than non-anemic patients. The level of hemoglobin (Hb) had a weak negative linear correlation with NT-pro-BNP (log-transform, r = 0.30, P

Helicobacter pylori (H. pylori, HP), recognized globally as one of the most widespread bacteria, serves as primary etiological agent for numerous gastroduodenal diseases, highlighting the urgent need to develop rapid and sensitive diagnostic method for H. pylori infection. Here, we devised a new diagnostic test that merged multiple cross displacement amplification (MCDA) with nanoparticle‐based lateral flow biosensor (LFB), termed HP‐MCDA‐LFB, to facilitate the rapid and sensitive detection of H. pylori. The whole detection workflow, which includes stages such as DNA template extraction (~15 min), MCDA pre-amplification (~40 min), and result readout (~2 min), was efficiently completed within 1 h. After optimization, the HP-MCDA-LFB assay demonstrated remarkable sensitivity in detecting H. pylori, with a detection threshold as low as 60 fg of genomic DNA (~56 copies) per microliter. Furthermore, the HP-MCDA-LFB assay also achieved a perfect specificity rate of 100%, exhibiting no cross-reactivity with non-Helicobacter isolates. Particularly, the clinical feasibility of HP-MCDA-LFB assay was validated using 40 antral mucosa samples, among which 17 tested positive for H. pylori, which was in complete agreement with the results obtained from the rapid urease test. In conclusion, the HP‐MCDA‐LFB method developed in this study is a rapid, sensitive, and specific method for diagnosing H. pylori infection, indicating great potential for H. pylori eradication therapy.

IntroductionAvian pathogenic Escherichia coli (APEC) is a critical bacterial pathogen that causes severe infections in poultry. Diverse serotypes increase the complexity of treatment and controlling APEC infections. Recent epidemiological investigations indicate O145 is emerging as a predominant serogroup of APEC in China. However, limited information is known about this newly emerged serogroup.MethodsA virulent strain, NC22, was selected to elucidate the mechanisms underlying APEC O145-related pathogenicity and host adaptation. Whole-genome sequencing and pathogenicity assays was conducted on this strain. We further performed a transcriptional analysis of the bacteria during the early colonization stage in the duck liver and compared them with those in liquid cultures in vitro.ResultsSubcutaneous inoculation of NC22 induced typical symptoms in ducks. The bacterial loads in the blood and various tissues peaked at 2 and 3 days post infection, respectively. The affected tissues included the heart, liver, spleen, lung, kidney, bursa of Fabricius, duodenum, jejunum, and cecum. We then analyzed the transcriptome profiles of NC22 during growth in duck liver versus lysogeny broth and identified 87 genes with differential expression levels.These included key metabolic enzymes and recognized host adaptation factors. Analysis of the metabolic pathways revealed an inhibition of the metabolic shift from glycolysis towards pentose phosphate pathway and an interference of the citrate cycle. Moreover, significantly differentially expressed small regulatory RNAs were examined, such as SroC, CsrC, and GadY.DiscussionThese findings enhance our understanding of the pathogenicity of APEC O145 and the molecular mechanisms underlying APEC-related pathogen−host interactions.

BackgroundIt is common for older adults to move to urban communities after retirement, living with their adult children and caring for grandchildren in China. This impacts their social networks and, consequently, their psychological and physical health. However, research on proactive ways to mitigate the negative effects of social dislocation is lacking. This study examined how dancing with care (DWC), a new form of preventative care, promotes social integration among older adults in Chinese communities, focusing specifically on participants’ experiences related to community engagement, mutual support, volunteer activity, social connections, and advanced learning through their involvement with DWC.MethodsSemi-structured interviews were conducted with 60 older adults who regularly participated in DWC in communities in southern China.ResultsDWC’s dimensions play a vital role in addressing the social integration of older adults. Through DWC, older adults participate in community activities, engage in mutual support, volunteer in various activities, develop social connections, and learn different things, including the use of advanced technologies.ConclusionDWC addresses older people’s social integration by providing opportunities to be involved in the community. It provides a promising path for older adults to actively engage in the revival of social capital within their social networks in the community. This study offers valuable insights for enhancing social involvement for older adults.

BackgroundKalimeris indica (L.) Sch. Bip., (K. indica) is a plant classified under the genus Kalimeris within the Asteraceae family. The herb of K. indica has been historically utilized as a traditional medicine. The consumption of excessive amounts of alcohol represents a lifestyle choice that can induce tissue damage and contribute to the development of various health conditions.MethodThe HPLC-MS method was used to reveal the chemical composition of K. indica extract. HepG2 cells were used to test the in vitro oxidative stress. C57BL/6 mice were used to construct the in vivo alcohol-induced liver injury. H/E staining and serum ALT and AST levels were tested to assess the in vivo protective effect of ML (50 and 200 mg/kg). GSH, SOD, and CAT levels along with byproduct MDA levels were used to evaluate the in vivo oxidative stress. Immunohistochemical experiments were used to examine the in vivo Nrf2 and HO-1 levels. 16S rRNA gene-based profiling method was used to test the alteration in gut microbiota.Results16 compounds were identified from K. indica extract. K. indica treatment reduced oxidative stress in HepG2 cells treated with 5% alcohol. H/E staining results showed that K. indica (50 and 200 mg/kg) alleviated liver injury caused by alcohol administration, eliciting a similar protective effect to the positive drug silymarin. Serum ALT and AST examination gave a consistent result, showing that ML could restore serum ALT and AST levels in mice treated with alcohol. Furthermore, K. indica could also restore GSH, SOD, CAT, and MDA levels in alcohol-treated mice, showing a potent effect on oxidative stress alleviation. Immunohistochemical experiments indicated that K. indica showed the liver protective effect through Nrf2/HO-1 pathway. 16S rRNA gene-based profiling revealed that alcohol treatment caused the alteration in gut microbiota, while K. indica treatment could result in a significantly richer variety of microbial communities compared to the alcohol group.ConclusionK. indica (ML) has a protective effect on liver injury caused by alcohol administration. The Nrf2/HO-1 pathway and gut microbiota regulation were involved in the ML-induced liver protection. All the results indicate that K. indica has a potential in the treatment of alcohol-induced liver injury.

ObjectiveIschemic stroke-associated pneumonia (iSAP) affects about 10% of acute ischemic stroke patients during hospitalization. Current prediction scales for iSAP are insufficient. Identifying early biomarkers for stroke-associated pneumonia is crucial for improving patient outcomes. This study aimed to investigate the predictive value of euthyroid sick syndrome (ESS) for iSAP in acute-stage of ischemic stroke patients.MethodsWe studied 1767 acute ischemic stroke patients within one week of symptom onset, categorizing them into an infection group (iSAP, n=376) and control group (control, n=1391). COX regression analysis was used to identify the potential risk and protected factors. Kaplan-Meier time-event curves and Log-Rank tests were performed to differentiate infection time in patients with ESS or normal T3 group.ResultsThe iSAP group had higher rates of risk factors like older age, atrial fibrillation, COPD, and ESS, along with elevated levels of WBC, CRP,and FT4 levels (all P < 0.001). Conversely, iSAP patients had lower GCS scores, eGFR, TSH, T3, FT3 (all P < 0.001) and T4 levels (P = 0.005) upon admission. No significant differences were observed in sex, smoking history, hypertension, diabetes, or LDL-C levels (P > 0.05). COX regression analysis identified age, KWST scores, leukocyte count, CRP, and ESS (all P < 0.001) as significantly correlated with iSAP. ROC analysis revealed ESS as a predictor with sensitivity of 35.64% and specificity of 87.92% for SAP prediction, like atrial fibrillation and higher than COPD and eGFR.ConclusionESS at admission predicts a higher risk of stroke-associated pneumonia in acute-stage of ischemic stroke.