A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias.

De-biased Disentanglement Learning for Pulmonary Embolism Survival Prediction on Multimodal Data.

Health disparities among marginalized populations with lower socioeconomic status significantly impact the fairness and effectiveness of healthcare delivery. The increasing integration of artificial intelligence (AI) into healthcare presents an opportunity to address these inequalities, provided that AI models are free from bias. This paper aims to address the bias challenges by population disparities within healthcare systems, existing in the presentation of and development of algorithms, leading to inequitable medical implementation for conditions such as pulmonary embolism (PE) prognosis. In this study, we explore the diversity of biases in healthcare systems, which highlights the need for a holistic framework to reduce bias by complementary aggregation. By leveraging de-biasing deep survival prediction models, we propose a framework that disentangles identifiable information from images, text reports, and clinical variables to mitigate potential biases within multimodal datasets. Our study offers several advantages over traditional clinical-based survival prediction methods, including richer survival-related characteristics and bias-complementary predicted results. By improving the robustness of survival analysis through this framework, we aim to benefit patients, clinicians, and researchers by improving fairness and accuracy in healthcare AI systems. The code is available at https://github.com/zzs95/fairPE-SA.

[Optimization of prediction model for personalized water pills based on semantic analysis of traditional Chinese medicine materials].

This study aims to optimize the prediction model of personalized water pills that has been established by our research group. Dioscoreae Rhizoma, Leonuri Herba, Codonopsis Radix, Armeniacae Semen Amarum, and calcined Oyster were selected as model medicines of powdery, fibrous, sugary, oily, and brittle materials, respectively. The model prescriptions were obtained by uniform mixing design. With hydroxypropyl methylcellulose E5(HPMC-E5) aqueous solution as the adhesive, personalized water pills were prepared by extrusion and spheronizaition. The evaluation indexes in the pill preparation process and the multi-model statistical analysis were employed to optimize and evaluate the prediction model of personalized water pills. The prediction equation of the adhesive concentration was obtained as follows: Y_1=-4.172+3.63X_A+15.057X_B+1.838X_C-0.997X_D(adhesive concentration of 10% when Y_1<0, and 20% when Y_1>0). The overall accuracy of the prediction model for adhesive concentration was 96.0%. The prediction equation of adhesive dosage was Y_2=6.051+94.944X_A~(1.5)+161.977X_B+70.078X_C~2+12.016X_D~(0.3)+27.493X_E~(0.3)-2.168X_F~(-1)(R~2=0.954, P<0.001). Furthermore, the semantic prediction model for material classification of traditional Chinese medicines was used to classify the materials contained in the prescription, and thus the prediction model of personalized water pills was evaluated. The results showed that the prescriptions for model evaluation can be prepared with one-time molding, and the forming quality was better than that established by the research group earlier. This study has achieved the optimization of the prediction model of personalized water pills.

[Essential oil of Cinnamomum camphora mitigates depression-like behavior in mice by regulating Nrf2/HO-1 pathway and inhibiting inflammatory cytokines].

This study aims to investigate the essential oil(EOL) of Cinnamomum camphora regarding its anti-depression effect and mechanism in regulating inflammatory cytokines and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. A mouse model of depression was established by intraperitoneal injection of lipopolysaccharide(LPS). Open field, elevated plus maze, and forced swimming tests were carried out to examine mouse behaviors. Western blot and qRT-PCR were employed to determine the expression of proteins and genes in the Nrf2/HO-1 pathway in the hippocampus. The levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1ß in the serum were measured by enzyme-linked immunosorbent assay(ELISA). The changes of apoptosis in mouse brain were detected by Tunel staining. Compared with the blank control group, the model group showed shortened distance travelled and time spent in the central zone and reduced number of entries in the central zone in the open field test. In the elevated plus maze test, the model group showed reduced open arm time(OT%) and open arm entries(OE%). In the force swimming test, the model group showed extended duration of immobility compared with the blank control group. Compared with the model group, the treatment with EOL significantly increased the distance travelled and time spent in the central zone and increased the number of entries in the central zone in the open field test. In addition, EOL significantly increased the OT% and OE% in the elevated plus maze and shor-tened the immobility duration in the forced swimming test. The model group showed lower expression levels of Nrf2 and HO-1 and hig-her levels of TNF-α, IL-6, and IL-1ß than the blank control group. Compared with the model group, the treatment with EOL up-regulated the expression levels of Nrf2 and HO-1 and lowered the levels of TNF-α, IL-6, and IL-1ß. The Tunel staining results showed that the apoptosis rate in the brain tissue of mice decreased significantly after the treatment with EOL. To sum up, EOL can mitigate the depression-like behaviors of mice by up-regulating the expression of Nrf2 and HO-1 and preventing hippocampal inflammatory damage. The findings provide empirical support for the application of EOL and aromatherapy in the treatment of depression.

Clinical study on simultaneous resection of liver metastases combined with hyperthermic intraperitoneal chemotherapy for synchronous colorectal cancer liver metastasis.

PURPOSE: This study aimed to analyze the clinical effect of simultaneous resection of liver metastases combined with hyperthermic intraperitoneal chemotherapy (HIPEC) on synchronous colorectal cancer liver metastasis. METHODS: A total of 144 patients with synchronous colorectal cancer liver metastasis who were admitted to our hospital between January 2018 and January 2019 were randomly assigned into a control group and an intervention group. The patients in the control group received simultaneous resection of liver metastases. The patients in the intervention group obtained simultaneous resection of liver metastases combined with HIPEC. The recent total effective rate of the 2 groups was compared, and the disease control rate of the 2 groups was calculated at 3 months after treatment. The patients were followed up for 3 years. The survival time of the 2 groups was observed and compared. Fasting venous blood was collected from patients in the 2 groups, and the carcinoembryonic antigen (CEA) level was compared. The level of quality of life scale (Short Form 36-item Health Survey) and the occurrence of adverse reactions were compared between the 2 groups. RESULTS: The R0 complete resection rate in the intervention group was significantly higher than that in the control group (P < .05). The recent total effective rate in the intervention group (87.50%) was significantly higher than that in the control group (59.72%) (P < .05). The negative change of CEA in the intervention group was 72.22%, which was prominently higher than that in the control group of 43.06% (χ2 = 12.542, P < .001). After a 36-month follow-up, the overall survival rate of the observation group was significantly higher than that of the control group (hazard ratio, 2.54; 95% CI, 1.05-5.48; P < .001). The patients in the intervention group had significantly higher life quality scores of health status, social function, emotional function, physical function, and mental health than in the control group (P < .05). There was no significant difference in the incidence of complications between the 2 groups (P > .05). Age > 60 years, preoperative comorbidities, moderate and high differentiation of tumors, intraoperative blood loss > 150 mL, and less experienced surgeons were risk factors affecting the occurrence of complications after treatment and were closely correlated with the prognosis and survival of patients (P < .05). Patients with age ≤ 60 years, no preoperative comorbidities, low tumor differentiation, intraoperative blood loss ≤ 150 mL, more experienced surgeons, and complete R0 resection had a longer survival time. Age > 60 years, preoperative comorbidities, moderate and high differentiation of tumors, intraoperative blood loss > 150 mL, and less experienced surgeons were independent risk factors affecting the prognosis of patients with colorectal cancer liver metastases (P < .05), whereas R0 surgery was an independent protective factor for the prognosis (P < .05). CONCLUSION: In the treatment of synchronous colorectal cancer liver metastases, simultaneous resection of liver metastases in conjunction with HIPEC demonstrated superior efficacy. This approach may potentially extend patient survival and enhance quality of life and deserve to be extensively used in clinical practice.

Morus alba L. (Sangzhi) alkaloids mitigate atherosclerosis by regulating M1/M2 macrophage polarization.

BACKGROUND: Atherosclerosis (AS) is an important cause of cardiovascular disease, posing a substantial health risk. Recognized as a chronic inflammatory disorder, AS hinges on the pivotal involvement of macrophages in arterial inflammation, participating in its formation and progression. Sangzhi alkaloid (SZ-A) is a novel natural alkaloid extracted from the mulberry branches, has extensive pharmacological effects and stable pharmacokinetic characteristics. However, the effects and mechanisms of SZ-A on AS remain unclear. PURPOSE: To explore the effect and underlying mechanisms of SZ-A on inflammation mediated by macrophages and its role in AS development. METHODS: Atherosclerosis was induced in vivo in apolipoprotein E-deficient mice through a high-fat and high-choline diet. We utilized macrophages and vascular endothelial cells to investigate the effects of SZ-A on macrophage polarization and its anti-inflammatory properties on endothelial cells in vitro. The transcriptomic analyses were used to investigate the major molecule that mediates cell-cell interactions and the antiatherogenic mechanisms of SZ-A based on AS, subsequently validated in vivo and in vitro. RESULTS: SZ-A demonstrated a significant inhibition in vascular inflammation and alleviation of AS severity by mitigating macrophage infiltration and modulating M1/M2 macrophage polarization in vitro and in vivo. Moreover, SZ-A effectively reduced the release of the proinflammatory mediator C-X-C motif chemokine ligand (CXCL)-10, predominantly secreted by M1 macrophages. This reduction in CXCL-10 contributed to improved endothelial cell function, reduced recruitment of additional macrophages, and inhibited the inflammatory amplification effect. This ultimately led to the suppression of atherogenesis. CONCLUSION: SZ-A exhibited potent anti-inflammatory effects by inhibiting macrophage-mediated inflammation, providing a new therapeutic avenue against AS. This is the first study demonstrating the efficacy of SZ-A in alleviating AS severity and offers novel insights into its anti-inflammatory mechanism.

Job boredom as an antecedent of four states of mental health: life satisfaction, positive functioning, anxiety, and depression symptoms among young employees - a latent change score approach.

BACKGROUND: Job boredom has been generally associated with poorer self-rated health but the evidence is mainly cross-sectional and there is a lack of a holistic mental health approach. We examined the temporal relationships between job boredom and mental health indicators of life satisfaction, positive functioning, anxiety, and depression symptoms. METHODS: We analyzed a two-wave postal survey data of adults aged 23 to 34 that was collected from the Finnish working population between 2021 and 2022 (n = 513). Latent change score modelling was used to estimate the effects of prior levels of job boredom on subsequent changes in mental health indicators, and of prior levels of mental health indicators on subsequent changes in job boredom. RESULTS: Job boredom was associated with subsequent decreases in life satisfaction and positive functioning and increases in anxiety and depression symptoms. Of these associations, job boredom was more strongly associated with changes in positive functioning and anxiety symptoms than with changes in life satisfaction. CONCLUSIONS: Our two-wave study suggests that job boredom, a motivational state of ill-being in the work domain, spills over into general mental health by decreasing life satisfaction and positive functioning and increasing anxiety and depression symptoms. Our findings contribute to the understanding of the potential detrimental effects of job boredom and its nomological network. From a practical perspective, workplaces are adviced to improve working conditions that mitigate job boredom and thus promote employees' mental health.

Effects of folic acid supplementation on cognitive impairment: A meta-analysis of randomized controlled trials.

OBJECTIVE: With the increasing number of patients with cognitive impairment, nonpharmacological ways to delay cognitive impairment have attracted people's attention, such as lifestyle changes and nutritional supplementation. Folic acid supplementation appears to be a promising treatment option. However, it remains controversial whether folic acid supplementation is effective in delaying adult's cognitive impairment. Therefore, we conducted a meta-analysis to analyze the effects of folic acid supplementation on different cognitive impairments. METHODS: We systematically searched PubMed, Web of Science, EMbase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), WanFang and VIP databases for randomized controlled trials on January 22, 2024. The included population comprised those diagnosed with cognitive impairment. We included trials that compared folic acid treatment with placebo, other dosing regimens, or other intervention controls. Conducting quality evaluation of included studies according to the Cochrane Risk of Bias tool. Statistical analyses were performed using Review Manager software. RESULTS: Twenty-two trials, including 3604 participants, met inclusion criteria. Compared with controls, the cognitive function of Alzheimer's disease (AD) patients showed improvement with folic acid supplementation: supplementation with < 3 mg (standardized mean differences (SMD) = 0.15, 95% confidence interval (CI) -0.10 to 0.41), and supplementing with ≥ 3 mg folic acid could improve cognitive function in AD patients (SMD = 1.03, 95% CI 0.18 to 1.88). Additionally, it reduced homocysteine (HCY) levels (mean differences (MD) = -4.74, 95% CI -8.08 to -1.39). In mild cognitive impairment (MCI) patients, cognitive function improved with folic acid supplementation: supplementation with > 400 µg (SMD = 0.38, 95% CI 0.13 to 0.63), and supplementation with ≤ 400 µg (SMD = 1.10, 95% CI 0.88 to 1.31). It also reduced HCY levels at intervention ≤ 6 months (MD = -3.93, 95% CI -5.05 to -2.82) and intervention > 6 months (MD = -4.38, 95% CI -5.15 to -3.61). However, supplementing with folic acid did not improve cognitive function in vascular cognitive impairment (VCI) patients, with folic acid supplements < 3 mg (SMD = -0.07, 95% CI -0.23 to -0.08), folic acid supplements ≥ 3 mg (SMD = 0.46, 95% CI -0.57 to 1.49), however, it reduced HCY levels at intervention > 6 months (MD = -5.91, 95% CI -7.13 to -4.69) and intervention ≤ 6 months (MD = -11.15, 95% CI -12.35 to -9.95). CONCLUSIONS: Supplement folic acid is beneficial to the cognitive profile of patients with MCI, supplementation with ≥ 3 mg folic acid can improve cognitive function in AD patients.

Untargeted urine metabolomics and machine learning provide potential metabolic signatures in children with autism spectrum disorder.

Background: Complementary to traditional biostatistics, the integration of untargeted urine metabolomic profiling with Machine Learning (ML) has the potential to unveil metabolic profiles crucial for understanding diseases. However, the application of this approach in autism remains underexplored. Our objective was to delve into the metabolic profiles of autism utilizing a comprehensive untargeted metabolomics platform coupled with ML. Methods: Untargeted metabolomics quantification (UHPLC/Q-TOF-MS) was performed for urine analysis. Feature selection was conducted using Lasso regression, and logistic regression, support vector machine, random forest, and extreme gradient boosting were utilized for significance stratification. Pathway enrichment analysis was performed to identify metabolic pathways associated with autism. Results: A total of 52 autistic children and 40 typically developing children were enrolled. Lasso regression identified ninety-two urinary metabolites that significantly differed between the two groups. Distinct metabolites, such as prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, were revealed to be associated with autism through the application of four different ML methods (p<0.05). The alterations observed in the phosphatidylinositol and inositol phosphate metabolism pathways were linked to the pathophysiology of autism (p<0.05). Conclusion: Significant urinary metabolites, including prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, exhibit associations with autism. Additionally, the involvement of the phosphatidylinositol and inositol phosphate pathways suggests their potential role in the pathophysiology of autism.

Efficacy and safety of compound kushen injection for treating advanced colorectal cancer: A protocol for a systematic review and meta-analysis.

Introduction: Compound Kushen Injection (CKI) is a traditional Chinese medicine extracted from Sophora flavescens Aiton and Heterosmilax japonica Kunth. Widely utilized in China for the comprehensive treatment of colorectal cancer (CRC), this study aims to systematically assess the efficacy and safety of CKI when combined with chemotherapy for the treatment of advanced CRC, based on available data. Methods: Randomized controlled trials investigating the efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC will be comprehensively searched from databases, including PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang, Chinese Biomedicine Database Searches, Chinese Clinical Trial Registry, and ClinicalTrials.gov until November 2022. Two independent reviewers will screen the studies, assess the risk of bias, and extract data in duplicate. The ROB2 tool will be employed to assess the quality of included studies. Stata 16 will be used for data analysis, and publication bias will be assessed using funnel plots and Egger's test. The quality of evidence will be evaluated according to GRADE, and trial sequence analysis (TSA) will be utilized to calculate the final total sample size required for the meta-analysis. The results of this systematic review will be published in a peer-reviewed journal. The proposed review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022380106). Discussion: This systematic review will integrate current evidence on CKI in advanced CRC and analyze the clinical efficacy and safety of CKI combined with different chemotherapy regimens, providing valuable guidance on the use of CKI in CRC patients.

Expression of Caudal-Type Homologous Transcription Factor-2 (CDX2) in Duodenal Carcinoma and its Relationship with Prognosis.

Objective: Caudal-type homologous transcription factor 2 (CDX2) has been shown to be associated with prognosis in colorectal cancer, with those with high expression having a good prognosis and those with low expression having a poor prognosis. As duodenal and colorectal cancers are similar in histological origin, we suspect that CDX2 expression in duodenal cancer may also be related to prognosis. Therefore, the aim of this study was to investigate the expression of CDX2 in duodenal cancer and its relationship with prognosis. Methods: We collected the clinical data and pathological sections of 61 patients diagnosed with duodenal cancer by histopathology or cytology at Shanghai Changhai Hospital, Naval Medical University, from November 2011 to December 2022. CDX2 expressionin in duodenal cancer was detected by immunohistochemical analysis (streptavidin-peroxidasemethod, SP). Survival analysis was conducted using the Kaplan-Meier method and the Log-rank test. Multivariate analysis was performed using the Cox regression analysis. Results: The positive rate of CDX2 in duodenal carcinoma was 78.7% (48/61). The positive rate of CDX2 expression in patients with stage I/II was higher than that in patients with stage III/IV (P < .05), and there was no correlation between CDX2 expression and gender, age, degree of differentiation, CEA and anemia (P > .05). Univariate analysis by Kaplan-Meier and Log-rank test showed that the expression of CDX2, degree of differentiation, TNM staging and CEA were associated with the prognosis of CDX2 in the negative and positive for the OS 21.6 months and 49.8 months, respectively (P = .015). The median OS of poorly differentiated patients and moderately/well-differentiated patients were 13 months and 82.5 months, respectively (P < .001). The median OS for Stage I/II and Stage III/IV patients was 72.3 and 13 months, respectively (P < .001). The median OS of CEA < 5 ug/L and ≥5 ug/L were 49.8 months and 9.4 months, respectively (P = .002). Age, gender and whether anemia were not associated with prognosis (P > .05). Multivariate analysis by Cox regression analysis showed that the expression of CDX2 (RR=2.697, 95%CI: 1.191-6.106, P = .017) was an independent prognostic factor of duodenal carcinoma. The results suggest that the expression of CDX2 in duodenal cancer is closely related to the prognosis. Those with positive expression have a better prognosis and those with negative expression have a worse prognosis. Conclusion: CDX2 serves as an autonomous prognostic determinant in individuals diagnosed with duodenal cancer. Notably, patients exhibiting positive CDX2 expression demonstrate a considerably improved prognosis compared to those with negative CDX2 expression. CDX2 may play an important role as an tumor suppressor gene in the development of duodenal cancer. CDX2 can be used as an important factor for evaluating the prognosis of patients with duodenal cancer, and it has the potential to be a target for duodenal cancer therapy.

Programming Intracellular Clustering of Spiky Nanoparticles via Liposome Encapsulation.

The intracellular clustering of anisotropic nanoparticles is crucial to the improvement of the localized surface plasmon resonance (LSPR) for phototherapy applications. Herein, we programmed the intracellular clustering process of spiky nanoparticles (SNPs) by encapsulating them into an anionic liposome via a frame-guided self-assembly approach. The liposome-encapsulated SNPs (lipo-SNPs) exhibited distinct and enhanced lysosome-triggered aggregation behavior while maintaining excellent monodispersity, even in acidic or protein-rich environments. We explored the enhancement of the photothermal therapy performance for SNPs as a proof of concept. The photothermal conversion efficiency of lipo-SNPs clusters significantly increased 15 times compared to that of single lipo-SNPs. Upon accumulation in lysosomes with a 2.4-fold increase in clustering, lipo-SNPs resulted in an increase in cell-killing efficiency to 45% from 12% at 24 µg/mL. These findings indicated that liposome encapsulation provides a promising approach to programing nanoparticle clustering at the target site, which facilitates advances in the development of smart nanomedicine with programmable enhancement in LSPR.

Drought Stress Induced Different Response Mechanisms in Three Dendrobium Species under Different Photosynthetic Pathways.

Many Dendrobium species, which hold a high status and value in traditional Chinese medicine, grow on barks and rocks in the wild, often encountering harsh environments and facing droughts. However, the molecular mechanisms underlying the shift in the photosynthetic pathway induced by drought remain unclear. To address this issue, three Dendrobium species with different photosynthetic pathways were selected for sequencing and transcriptome data analysis after drought treatment. The findings included 134.43 GB of sequencing data, with numerous Differentially Expressed Genes (DEGs) exhibiting different response mechanisms under drought stress. Gene Ontology (GO)-KEGG-based enrichment analysis of DEGs revealed that metabolic pathways contributed to drought tolerance and alterations in photosynthetic pathways. Phosphoenolpyruvate Carboxylase (PEPC) was subjected to phylogenetic tree construction, sequence alignment, and domain analysis. Under drought stress, variations were observed in the PEPC gene structure and expression among different Dendrobium species; the upregulation of Dc_gene2609 expression may be caused by dof-miR-384, which resulted in the shift from C3 photosynthesis to CAM, thereby improving drought tolerance in Dendrobium. This study revealed the expression patterns and roles of PEPC genes in enhancing plant drought tolerance and will provide an important basis for in-depth research on Dendrobium's adaptation mechanisms in arid environments.

Telocinobufagin, a PLK1 suppressor that inhibits tumor growth and metastasis by modulating CDC25c and CTCF in HNSCC cells.

BACKGROUND: The high metastasis and mortality rates of head and neck squamous cell carcinoma (HNSCC) urgently require new treatment targets and drugs. A steroidal component of ChanSu, telocinobufagin (TBG), was verified to have anti-cancer effects in various tumors, but its activity and mechanism in anti-HNSCC were still unknown. PURPOSE: This study tried to demonstrate the anti-tumor effect of TBG on HNSCC and verify its potential mechanism. METHODS: The effect of TBG on cell proliferation and metastasis were performed and the TBG changed genes were detected by RNA-seq analysis in HNSCC cells. The GSEA and PPI analysis were used to identify the pathways targeted for TBG-regulated genes. Meanwhile, the mechanism of TBG on anti-proliferative and anti-metastasis were investigated in vitro and in vivo. RESULTS: The in vitro and in vivo experiments confirmed that TBG has favorable anti-tumor effects by induced G2/M phase arrest and suppressed metastasis in HNSCC cells. Further RNA-seq analysis demonstrated the genes regulated by TBG were enriched at the G2/M checkpoint and PLK1 signaling pathway. Then, the bioinformatic analysis of clinical data found that high expressed PLK1 were closely associated with poor overall survival in HNSCC patients. Furthermore, PLK1 directly and indirectly modulated G2/M phase and metastasis (by regulated CTCF) in HNSCC cells, simultaneously. TBG significantly inhibited the protein levels of PLK1 in both phosphorylated and non-phosphorylated forms and then, in one way, inactivated PLK1 failed to activate G2/M phase-related proteins (including CDK1, CDC25c, and cyclin B1). In another way, be inhibited PLK1 unable promote the nuclear translocation of CTCF and thus suppressed HNSC cell metastasis. In contrast, the anti-proliferative and anti-metastasis effects of TBG on HNSCC cell were vanished when cells high-expressed PLK1. CONCLUSION: The present study verified that PLK1 mediated TBG induced anti-tumor effect by modulated G2/M phase and metastasis in HNSCC cells.

The functional and anatomical characterization of three spinal output pathways of the anterolateral tract.

The nature of spinal output pathways that convey nociceptive information to the brain has been the subject of controversy. Here, we provide anatomical, molecular, and functional characterizations of two distinct anterolateral pathways: one, ascending in the lateral spinal cord, triggers nociceptive behaviors, and the other one, ascending in the ventral spinal cord, when inhibited, leads to sensorimotor deficits. Moreover, the lateral pathway consists of at least two subtypes. The first is a contralateral pathway that extends to the periaqueductal gray (PAG) and thalamus; the second is a bilateral pathway that projects to the bilateral parabrachial nucleus (PBN). Finally, we present evidence showing that activation of the contralateral pathway is sufficient for defensive behaviors such as running and freezing, whereas the bilateral pathway is sufficient for attending behaviors such as licking and guarding. This work offers insight into the complex organizational logic of the anterolateral system in the mouse.

Bibliometric Analysis of Research on Traditional Chinese Exercise and Osteoarthritis.

Background: Osteoarthritis (OA) is a common disease in geriatric rehabilitation medicine caused by the progressive destruction of articular cartilage. Traditional Chinese exercise (TCE) is an important component of traditional sports in China and aims to stretch the musculoskeletal tract and relieve joint pain. Bibliometrics can help researchers find suitable partners and understand the research hotspots and trends in a certain field. However, there is still a lack of bibliometric analysis in the field of TCE and OA. Methods: All the literature was obtained from the Web of Science Core Collection database. The last search was performed on July 28, 2023. The bibliometric indicators, such as publications, citations, and H-index, were recorded. Bibliometrix and CiteSpace were used for visualization analysis. In addition, randomized controlled trials were included to summarize the exercise prescription of TCE for OA. Results: A total of 170 articles were included. The field of OA with TCE had great development potential and was in the rising period. The countries, institutions, and authors with the most publications were the United States, Tufts Medical Center, and Harvey WF, respectively. The most popular journal was Osteoarthritis and Cartilage. The recent burst keywords in this field were mainly "hip", "pilot", and "risk". Tai Chi was the most studied TCE with the most detailed content of exercise prescription, followed by Baduanjin and Wuqinxi. Conclusion: Our study provides a basis for researchers in this field to choose appropriate partner and academic journals. Moreover, pain, muscle strength, and quality of life management of elderly OA patients are research hotspots in this field. The intervention of hip OA risk through TCE is expected to become a research direction for emerging teams. The TCE prescription we summarized can better provide researchers with more treatment details.

The Extraction, Determination, and Bioactivity of Curcumenol: A Comprehensive Review.

Curcuma wenyujin is a member of the Curcuma zedoaria (zedoary, Zingiberaceae) family, which has a long history in traditional Chinese medicine (TCM) due to its abundant biologically active constituents. Curcumenol, a component of Curcuma wenyujin, has several biological activities. At present, despite different pharmacological activities being reported, the clinical usage of curcumenol remains under investigation. To further determine the characteristics of curcumenol, the extraction, determination, and bioactivity of the compound are summarized in this review. Existing research has reported that curcumenol exerts different pharmacological effects in regard to a variety of diseases, including anti-inflammatory, anti-oxidant, anti-bactericidal, anti-diabetic, and anti-cancer activity, and also ameliorates osteoporosis. This review of curcumenol provides a theoretical basis for further research and clinical applications.

[Analysis of metabolites in simulated gastric fluid of Saposhnikoviae Radix polysaccharides].

To fully understand whether Saposhnikoviae Radix polysaccharides(SP) can be metabolized in gastric fluid and the meta-bolic behavior, this study systematically analyzed the metabolites in simulated gastric fluid of SP by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry(HPLC-IT-TOF-MS) technology in combination with zebrafish immune activity evaluation. Based on the obtained accurate relative molecular mass, chromatographic retention behavior, MS fragmentation patterns, refe-rence standards, and relevant literature reports, 19 metabolites were analyzed and identified. Among them, five monosaccharides and 14 oligosaccharides were generated as metabolites. Several reducing sugars, including mannose, glucose, rhamnose, and xylose, were accurately identified in the gastric fluid metabolites. Zebrafish pharmacological evaluation results indicated that SP maintained good immune activity after gastric fluid metabolism, with the most significant increase in immune cell density observed at W3(simulated gastric fluid metabolism for 2 hours). Among the gastric fluid metabolites, M1 and M3(Hex-Hex-Man) may be most closely related to pharmacological activity and could be further studied as potential active fragments.

Withanolides from the active extract of Physalis angulate and their anti-hepatic fibrosis effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L., a traditional Chinese medicine called "Kuzhi" in China, was used traditionally to treat liver diseases (eg. icterus, hepatitis) as well as malaria, asthma, and rheumatism. AIM OF THE STUDY: Our study aimed to investigate the withanolides with anti-hepatic fibrosis effect from P. angulate. MATERIALS AND METHODS: Withanolides were obtained from the EtOH extract of P. angulate by bioassay-molecular networking analysis-guided isolation using column chromatography and normal/reversed-phase semipreparative HPLC. The structures of new withanolides were elucidated by combinations of spectroscopic techniques with NMR and ECD calculations. MTT cell viability assay, AO/EB staining method, cell wound healing assay, ELISA and Western blot experiments were employed to evaluate the anti-hepatic fibrosis activity and to uncover related mechanism. Molecular docking analysis and cellular thermal shift assay were used to evaluate and verify the interaction between the active withanolides and their potential targets. RESULTS: Eight unreported withanolides, withagulides A-H (1-8), along with twenty-eight known ones were obtained from P. angulate. Withanolides 6, 9, 10, 24, 27, and 29-32 showed marked anti-hepatic fibrosis effect with COL1A1 expression inhibition above 50 %. Physalin F (9), the main component in the active fraction, significantly decreased the TGF ß1-stimulated expressions of collagen I and α-SMA in LX-2 cells. Mechanism study revealed that physalin F exerted its anti-hepatic fibrosis effect via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: This study suggested that withanolides were an important class of natural products with marked anti-hepatic fibrosis effect. The main withanolide physalin F might be a promising candidate for hepatic fibrosis treatment. The work provided experimental foundation for the use of P. angulate to treat hepatic fibrosis.

Triacanthine enhances the sensitivity of colorectal cancer cells to 5-fluorouracil by regulating RRM2.

BACKGROUND: According to the literatures, triacanthine is isolated from the leaves of Gleditsia triacanthos L. and acts as an anti-hypertensive agent, also cardiotonic, antispasmodic and a respiratory analeptic. The 5-fluorouracil (5-FU) is widely used to treat the patients of colorectal cancer (CRC), but the resistance to 5-FU treatment restricts the therapeutic efficacy of CRC patients. PURPOSE: This study aims to explore a novel therapeutics regimen overcoming CRC resistance to 5-FU. METHODS: The cell proliferation of CRC cells was determined by SRB and colony formation assay. Transwell and wound-healing assay were applied to explore the potential metastatic abilities of CRC cells. qRT-PCR and Western blot were performed to evaluate the level of indicated mRNAs and proteins respectively. Xenograft assay was used to explore the anti-CRC effect of triacanthine. RESULTS: Triacanthine statistically restrained CRC proliferation both in vitro and in vivo. Triacanthine induced cell cycle G1/G0 phase arrest in CRC cells. Meanwhile, triacanthine also inhibited the migrative and invasive abilities of CRC cells. A Venn diagram was generated showing that O-6-Methylguanine-DNA Methyltransferase (MGMT) might be a molecular target of triacanthine in treating CRC. Furthermore, triacanthine plus 5-FU significantly suppressed the cell proliferation of CRC cells compared with single agent treatment alone, and highly synergistic anti-cancer effects were scored when 5-FU was combined with triacanthine in CRC cells. In addition, triacanthine sensitized the anti-cancer activity of 5-FU via regulating Ribonucleotide Reductase Regulatory Subunit M2 (RRM2). MGMT or RRM2 might be novel biomarkers for evaluating the therapeutical efficiency of 5-FU in CRC patients. CONCLUSION: We firstly demonstrated triacanthine suppressed cell proliferation and metastasis abilities and found the novel molecular targets of triacanthine in CRC cells. This is the first study to evaluate the anti-cancer efficiency of triacanthine plus 5-FU. Our study has revealed triacanthine as a pertinent sensitizer to 5-FU, and provided novel strategies for predicting outcomes and reversing resistance of 5-FU therapy.