Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

OBJECTIVE: To analyze the distribution characteristics of glucose-6-phosphate-dehydrogenase (G6PD) mutations and their enzyme activity in newborns patients with G6PD deficiency in Guilin region. METHODS: From July 2022 to July 2024, umbilical cord blood samples from 4 554 newborns in Guilin were analyzed for G6PD mutations using fluorescence PCR melting curve analysis. Enzyme activity was detected in 4 467 cases using the rate assay. RESULTS: Among 4 467 newborns who underwent G6PD activity testing, 162 newborns (3.63%) were identified as G6PD-deficient, including 142 males (6.04%) and 20 females (0.94%), the prevalence of G6PD deficiency was significantly higher in males than in females (P < 0.001). Genetic analysis of 4 554 newborns detected G6PD mutations in 410 cases (9%), including 171 males (7.13%) and 239 females (11.09%), with a significantly higher mutation detection rate in females than in males (P < 0.001). A total of nine single mutations and four compound heterozygous mutations were identified. The most common mutations were c.1388G>A (33.66%), c.1376G>T (23.66%) and c.95A>G (16.34%). Among newborns who underwent both enzyme activity and genetic mutation testing, males with G6PD mutations had significantly lower enzyme activity than that of females with G6PD mutations(P < 0.001). Specifically, among newborns carrying the mutations c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T or c.871G>A, males consistently exhibited lower enzymatic activity than females with the same mutations (P < 0.001). Furthermore, in male G6PD-deficient newborns, the enzyme activity levels in those carrying c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T, or c.871G>A were lower than those in both the control group and the c.519C>T group (P < 0.05). CONCLUSION This study provides a comprehensive profile of G6PD deficiency incidence and mutation spectrum in the Guilin region. By analyzing enzyme activity and genetic mutation results, this study provides insights into potential intervention strategies and personalized management approaches for the prevention and treatment of neonatal G6PD deficiency in the region.
Humans ; Infant, Newborn ; Glucosephosphate Dehydrogenase Deficiency/epidemiology* ; Glucosephosphate Dehydrogenase/genetics* ; Female ; Male ; Mutation ; China/epidemiology*

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Aim To investigate the effect of colchicine on lipopolysaccharide (LPS) induced endothelial to mesenchymal transition (EndMT) in human umbilical vein vascular endothelial cells (HUVECs) and its related mechanisms. Methods The EndMT model was established by treating HUVECs with LPS. Cell proliferation rate was detected by CCK-8 assay, cytotoxicity was detected by LDH assay, and the optimal drug concentration was screened. The cells were divided into the normal control group, the normal control + colchicine (10 nmol • L) group, the LPS (10 mg • L) model group, and the LPS + colchicine (10 nmol • L) group. The morphologic changes of the cells were observed under an inverted microscope, the cell migration ability was detected by Transwell assay, and the ability of tube formation was analyzed by tube formation assay. The expression of endothelial markers (CD31/ VE-cadherin) and mesenchymal cell markers (a-SMA/FSP-1) were detected by Western blot. NF-KB inhibitor was used to detect the changes in related signaling pathways. Results CCK-8 and LDH experiments showed that 10 nmol • L colchicine was the optimal concentration. LPS could induce morphological changes in HUVECs, and colchicine could reverse morphological changes in HUVECs to a certain extent. Transwell experiment showed that the migration ability of HUVECs in the LPS treatment group was significantly enhanced (P < 0. 05), and colchicine could significantly reverse this phenomenon (P < 0. 05) . Tube formation experiment showed that LPS decreased the endothelial tube formation ability of HUVECs (P < 0. 05), while colchicine treatment markedly improved LPS-induced tube formation defects (P < 0. 05) . Western blot assay showed that after colchicine co-cultured with LPS, the expression levels of CD31 and VE-cadherin significantly increased compared with the model group (P < 0. 05), while the expression levels of a-SMA and FSP-1 significantly decreased compared with the model group (P < 0. 05) . During the induction of EndMT by LPS, colchicine could inhibit the activation of the NF-KB/Snail signaling pathway. Conclusions Colchicine can effectively inhibit EndMT induced by LPS, and the mechanism may be related to the regulation of the NF-KB/Snail signaling pathway.

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.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

Objective: To explore the action mechanism of hsa_circ_0000231 in the occurrence and development of tongue squamous cell carcinoma (TSCC). Methods: Tissue samples of 60 TSCC patients were examined. The patients, including 32 males and 28 females, aged from 36 to 84 years old, underwent surgery in the Affiliated Hospital of Nantong University and Affiliated Tumor Hospital of Nantong University from December 2014 to December 2017. Saliva samples were obtained from healthy volunteers (5 males and 5 females, aged from 40 to 75 years old) and 10 TSCC patients. The TSCC cell lines (CAL-27, Tca-8113 and HN-4) were used. The expression levels of hsa_circ_0000231 in 60 pairs of freshly matched TSCC and para-carcinoma tissue samples, 10 pairs of saliva samples and 3 TSCC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). hsa_circ_0000231 gene interference and lentiviral transfection were constructed, hsa_circ_0000231 in TSCC cell lines CAL-27 and Tca-8113 was knocked down, and the expressions of hsa_circ_0000231 in hsa_circ_0000231 interference group (sh-circ) and no-load lentivirus group (negative control) were tested with qRT-PCR. Cells with the highest knock-down efficiency were selected for CCK-8 test, colony formation assay, transwell invasion assay and scratch assay. The expressions of EMT-related proteins including E-cadherin, snail protein, N-cadherin and vimentin and proteins related to Wnt/β-catenin signaling pathway including β-catenin, C-myc, Bcl-2, MMP-9 and Cyclin D1 were measured by western blot. After TSCC cells in the interference group were co-cultured with Wnt/β-catenin pathway activator LiCl, the expressions of above proteins were re-measured by western blot. TSCC cells in interference group and control group were subcutaneously injected into nude mice to compare the effect of hsa_circ_0000231 knockdown on the growths of the tumors grafted subcutaneously in the nude mice. Statistical analysis software 25.0 was used for data analysis, and t-test or chi-square test was used for comparison between groups. Results: hsa_circ_0000231 was highly expressed in the tissue and saliva samples of TSCC patients and cell lines CAL-27, Tca-8113 and HN-4, but lowly expressed in paired para-carcinoma tissues, saliva samples of healthy people and normal human oral keratinocytes (all P<0.05). Log-rank univariate analysis showed that hsa_circ_0000231 expression level, tumor differentiation degree and T stage were related to the survival of TSCC patients (all P<0.05). Multivariate Cox risk regression model analysis suggested that hsa_circ_0000231 expression level (χ²=5.77,P=0.016) and T stage (χ²=5.27,P=0.029) were independent factors for the poor prognosis of TSCC patients. Western blot showed the expressions of snail protein, N-cadherin and vimentin were down-regulated, but E-cadherin was up-regulated in interference group compared with control group. In interference group, the expressions of β-catenin, C-myc, Bcl-2, MMP-9 and CyclinD1 were down-regulated, which were reversed after TSCC cells were co-cultured with LiCl. The knockdown of hsa_circ_0000231 reduced the proliferation, invasion and metastasis abilities of CAL-27 and Tca-8113 cells, which were reversed after TSCC cells were co-cultured with LiCl. The growth rate and volume of the tumors grafted subcutaneously in interference group using LiCl were greater than those in negative control group. Conclusion: hsa_circ_0000231 is an independent prognostic factor of TSCC. Highly expressed hsa_circ_0000231 can promote the proliferation, invasion and metastasis of TSCC cells.
Male ; Animals ; Mice ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Tongue Neoplasms ; Wnt Signaling Pathway/genetics* ; Carcinoma, Squamous Cell/genetics* ; beta Catenin/metabolism* ; Mice, Nude ; Vimentin ; Matrix Metalloproteinase 9/metabolism* ; RNA, Circular ; Gene Expression Regulation, Neoplastic ; Cell Proliferation/genetics* ; Cadherins/genetics* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Tongue

The quality of Paeoniae Radix Alba and Paeoniae Radix Rubra is evaluated by root thickness, and paeoniflorin serves as a common quality indicator of them. However, the correlation between the content of bioactive compounds and the root size is still unclear. Therefore, this study characterized the distribution patterns and content of seven bioactive compounds including paeoniflorin in different tissues of Paeonia lactiflora roots, analyzed the correlation between the root size and the content of bioactive compounds based on the xylem-to-bark ratio, and further determined the index components for quality assessment. Nine samples of fresh P. lactiflora roots were collected from the genuine cultivation area. The distribution of bioactive compounds in different tissues on the cross-section of the root was firstly analyzed by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI). Subsequently, the content of bioactive compounds was determined in the xylems and barks of the roots by UPLC. The compounds with the largest difference between the xylem and the bark were selected by orthogonal partial least squares discriminant analysis(OPLS-DA). The results indicated that paeoniflorin, benzoylpaeoniflorin, oxypaeoniflorin, gallic acid, and 1,2,3,4,6-pentagalloylglucose were significantly accumulated in the xylems, while albiflorin and catechin were mainly distributed in the barks. Paeoniflorin and albiflorin, with the largest differences in the xylem and the bark, had the highest content in the two tissues. The root diameter was positively correlated with paeoniflorin content and negatively correlated with albiflorin content. As isomers with different efficacies, paeoniflorin or albiflorin can be chosen as the quality marker corresponding to specific clinical application to launch quality classification evaluation of multi-functional Chinese medicines.
Bridged-Ring Compounds ; Catechin/analysis* ; Chromatography, High Pressure Liquid/methods* ; Gallic Acid/analysis* ; Monoterpenes/analysis* ; Paeonia/chemistry* ; Plant Roots/chemistry* ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVE: To evaluate the clinical characteristics, treatment and prognosis of systemic anaplastic large cell lymphoma(sALCL). METHODS: The clinical data of 90 cases with sALCL treated in the Department of Hematology of the Affiliated Xijing Hospital of Air Force Medical University from November 2018 to October 2021 were retrospectively analyzed. The clinical features, treatment and prognosis were summarized and the prognostic factors were investigated. RESULTS: There were 58 males and 32 females, with a median age of 32 (12-73) years old. 69 (76.7%) patients had Ann Arbor stage Ⅲ-Ⅳ disease and half of the patients had extranodal infiltration. The median age was 27(12-72) years of the 60 ALK⁺ patients while 53(15-73) years of the 30 ALK^- patients, and it was significantly different in the age of onset between the two group(P<0.01). 88 patients received first line chemotherapy, and 50(568%) cases achieved complete remission(CR). IPI score≥3 was an independent risk factor for CR. The median progressive free survival(PFS) and overall survival(OS) of the patients were not reached. Multivariate analysis showed that no achievement of CR after first-line therapy was a significant prognostic factor influencing PFS and OS. CONCLUSION sALCL mainly occurs in males and most patients were in advanced stage. Half of the patients had extranodal involvement. The CR rate after first-line chemotherapy was 568%, and IPI score≥3 was a significant prognostic factor for CR. No achievement of CR after first-line therapy is poorly prognostic for PFS and OS.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Disease-Free Survival ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/diagnosis* ; Male ; Middle Aged ; Prognosis ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Young Adult