This study aims to delve into the influences and underlying mechanisms of Banxia Xiexin Decoction(BXD) on the proliferation, apoptosis, invasion, and migration of colon cancer cells. Firstly, the components of BXD in blood were identified by UPLC-MS/MS, and subsequently the content of these components were determined by HPLC. Then, different concentrations of BXD were used to treat both the normal intestinal epithelial cells(NCM460) and the colon cancer cells(HT29 and HCT116). The cell viability and apoptosis were examined by the cell counting kit-8(CCK-8) and flow cytometry, respectively. Western blot was employed to determine the expression of the apoptosis regulators B-cell lymphoma-2(Bcl-2) and Bcl-2-associated X(Bax). The cell wound healing assay and Transwell assay were employed to measure the cell migration and invasion, respectively. Additionally, Western blot was employed to determine the expression levels of epithelial-mesenchymal transition(EMT)-associated proteins, including epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), and vimentin. The protein and mRNA levels of the factors in the poly(ADP-ribose) glycohydrolase(PARG)/poly(ADP-ribose) polymerase 1(PARP1)/nuclear factor kappa-B p65(NF-κB p65) signaling pathway were determined by Western blot and RT-qPCR, respectively. The results demonstrated that following BXD intervention, the proliferation of HT29 and HCT116 cells was significantly reduced. Furthermore, BXD promoted the apoptosis, enhanced the expression of Bcl-2, and suppressed the expression of Bax in colon cancer cells. At the same time, BXD suppressed the cell migration and invasion and augmented the expression of E-cadherin while diminishing the expression of N-cadherin and vimentin. In addition, BXD down-regulated the protein and mRNA levels of PARG, PARP1, and NF-κB p65. In conclusion, BXD may inhibit the malignant phenotypes of colon cancer cells by mediating the PARG/PARP1/NF-κB signaling pathway.
Colonic Neoplasms/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Phenotype ; Signal Transduction/drug effects* ; Cell Proliferation/drug effects* ; Apoptosis ; Cell Movement/drug effects* ; Neoplasm Invasiveness ; HCT116 Cells ; Proto-Oncogene Proteins c-bcl-2/biosynthesis* ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Glycoside Hydrolases ; bcl-2-Associated X Protein ; NF-kappa B p50 Subunit

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

Construct Validity and Reliability of the Malay Version of Rosenberg Self Esteem Scale (RSES) among youth in Southern Malaysia: A Confirmatory Factor Analysis IntroductionThe Rosenberg Self-Esteem Scale (RSES) is widely used to measure self-esteem among adults and youth. This study aims to determine the construct validity and reliability of the Rosenberg Self-Esteem Scale Malay version (RSES-M) among Malaysian youth using Confirmatory Factor Analysis (CFA).MethodologyWe administered the Malay-language RSES to 378 Form Four students in the Kota Tinggi District, selected through multistage sampling. The construct validity of RSES-M was assessed using confirmatory factor analysis (CFA), while internal consistency was measured using Cronbach alpha. AMOS version 26 and SPSS version 20 were used for statistical analysis. We compared three measurement models of the RSES-M for the best relative fit: one uni-dimensional model and two different two-domain models (with different items assigned to each domain for each model).ResultsThe findings indicate that the best model for the RSES-M was a two-domain model, with domain one representing positive self-esteem and domain two representing negative self-esteem. The item “I wish I could respect myself more” demonstrated a strong fit within the CFA model when included under the positive domain of self-esteem (Model 3) compared to negative domain ((Model 2) (Chi-Square/degree of freedom (df) = 3.341, goodness of fit (GFI) = 0.967, Comparative Fit Index (CFI) = 0.905, Incremental Fit Index (IFI) = 0.906, and the Root Mean Squared Error of Approximation (RMSEA) = 0.079 and substantial reliability (Cronbach's alpha for domain one = 0.765, and domain two = 0.648). This finding diverges from the original RSES developed by Morris Rosenberg in 1965, which conceptualised the RSES as a unidimensional construct, and other studies that categorised the item "I wish I could respect myself more" under the negative self-esteem domain.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Objective: Limited evidence exists regarding real-world 3-monthly paliperidone palmitate (PP3M) treatment retention and associated factors. Methods: We conducted a retrospective, nationwide cohort study using the Taiwan National Health Insurance Research Database between October 2017 and December 2019. Adult patients with schizophrenia initiated on PP3M were enrolled. The primary outcomes were time to PP3M discontinuation, time to psychiatric hospitalization, and the proportions of patients receiving the next PP3M dose within 120 days among first-, second-, and third-dose completers. Key covariates included prior PP1M duration and adequate PP3M initiation. Results: The PP3M treatment retention rates were 79.7%, 66.3%, and 52.5% after 6, 12, and 24 months, respectively, with 86.4%, 90.6%, and 90.0% of respective first-, second-, and third-dose completers receiving the next PP3M dose. Adequate PP3M initiation and prior PP1M treatment duration ＞ 180 days were associated with favorable PP3M treatment retention. In multivariate analyses, PP1M durations of 180−360 days (adjusted relative risk [aRR], 1.76) or ＜ 180 days (aRR, 2.79) were associated with PP3M discontinuation at the second dose. Inadequate PP3M initiation was associated with discontinuation at the third dose (aRR, 2.18). Patients fully adherent to PP3M treatment in the first year had a higher probability of being free from psychiatric hospitalization (86.7% at 2 years), compared with those partially adherent or non-adherent to PP3M in the first year. Conclusion Prior PP1M duration and adequate PP3M initiation are major factors affecting PP3M treatment retention. Higher PP3M treatment retention is associated with a lower risk of psychiatric hospitalization.

Illness anxiety disorder (IAD) is a psychiatric disorder defined by excessive worry about having or developing a serious undiagnosed medical condition. IAD can affect the social functions of patients and increase burdens imposed on the family and society. The concept of IAD was first proposed in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013. However, the rates of screening and identification of IAD are at a relatively low level in clinical practice, and the effectiveness of pharmacological and psychological intervention on IAD are still in the process of exploration and validation. The recognition of IAD should be enhanced and the efficacy of intervention need to be further improved. This article reviews the progress of clinical studies on IAD to improve clinicians′ understanding of the disease, and help them adopt appropriate treatments as early as possible to alleviate patient suffering and improve disease prognosis.

Illness anxiety disorder (IAD) is a psychiatric disorder defined by excessive worry about having or developing a serious undiagnosed medical condition. IAD can affect the social functions of patients and increase burdens imposed on the family and society. The concept of IAD was first proposed in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013. However, the rates of screening and identification of IAD are at a relatively low level in clinical practice, and the effectiveness of pharmacological and psychological intervention on IAD are still in the process of exploration and validation. The recognition of IAD should be enhanced and the efficacy of intervention need to be further improved. This article reviews the progress of clinical studies on IAD to improve clinicians′ understanding of the disease, and help them adopt appropriate treatments as early as possible to alleviate patient suffering and improve disease prognosis.

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CL^pro) and papain-like protease (PL^pro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CL^pro and PL^pro with IC₅₀ values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC₅₀ of 11.83 ± 3.23 μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CL^pro, and K157, E167 and A246 of PL^pro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.