ObjectiveINF2 is a member of the formins family. Abnormal expression and regulation of INF2 have been associated with the progression of various tumors, but the expression and role of INF2 in hepatocellular carcinoma (HCC) remain unclear. HCC is a highly lethal malignant tumor. Given the limitations of traditional treatments, this study explored the expression level, clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets. MethodsIn this study, we used public databases to analyze the expression of INF2 in pan-cancer and HCC, as well as the impact of INF2 expression levels on HCC prognosis. Quantitative real time polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues. The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples. Subsequently, the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments. Finally, the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments. ResultsINF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival, liver cirrhosis and pathological differentiation of HCC patients. The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC. In vivo and in vitro HCC models, upregulated expression of INF2 triggers the proliferation and migration of the HCC cell, while knockdown of INF2 could counteract this effect. INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression, thus promoting tumor progression. ConclusionINF2 is highly expressed in HCC and is associated with poor prognosis. High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression, and targeting INF2 may be beneficial for HCC patients with high expression of INF2.

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

As a novel iron-dependent form of cell death, ferroptosis is characterized by the excessive accumulation of phospholipids containing polyunsaturated fatty acids (PUFA) on the cell membrane and peroxidation. Lipid droplets are always in the dynamic transition of generation and decomposition, play a central role in regulating lipid metabolism, and are always in the dynamic transition of generation and decomposition. Lipid droplet metabolism is closely related to the occurrence of ferroptosis and plays an important role in the disease caused by ferroptosis. This review firstly focuses on the lipid droplet metabolism process and its effects on the storage and release of PUFA, and further elucidates the regulatory mechanism and key regulatory proteins of lipid drop metabolism on ferroptosis, in order to reveal the intrinsic relationship between lipid droplets and ferroptosis, and provide a new strategy for disease prevention and treatment.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective:To understand the current and integrated disease burden and economic burden caused by breast cancer in females in China.Methods:Based on six updated data sources, including the series of Chinese Cancer Registry Annual Report, China Death Cause Surveillance Datasets, China Health Statistical Yearbook, GLOBOCAN, Cancer Incidence in Five Continents, Global Burden of Disease Study (GBD), the information about incidence, mortality and disability adjusted life years (DALY) of breast cancer were extracted for the analysis on the current incidence and time trend of breast cancer and predicted disease burden of breast cancer in females in China. Software Joinpoint was used for time trend analysis. The data of economic burden were systematically updated and analyzed by literature review.Results:1) GLOBOCAN 2022 estimated that the age-standardized incidence rate (ASIR) age-standardized mortality rate (ASMR) and one- year prevalence rate of breast cancer in females were 33.0/100 000, 6.1/100 000 and 40.1/100 000, respectively, in China in 2022. According to Chinese Cancer Registry Annual Report, the ASIR and ASMR were 28.4/100 000 and 5.8/100 000, respectively, in 2018. The China Death Cause Surveillance Datasets showed that the ASMR was 4.5/100 000 in 2021, and the urban to rural area mortality ratio was 1.2∶1. GBD reported that the DALYs of breast cancer were 2.921 million in China in 2021, accounting for 14.4% of the global total. 2) Chinese Cancer Registry Annual Report data showed that the ASIR and ASMR of breast cancer decreased by 2.1% and 11.4%, respectively, in China from 2009 to 2018, while increased by 43.9% and 8.2% in rural area, respectively. The Joinpoint analysis showed that the average annual percentage change (AAPC) of ASIR and ASMR in China were -0.2% ( P>0.05) and -1.6% ( P<0.05). The AAPC of ASIR and ASMR in rural area were 3.9% ( P<0.05) and 0.6% ( P>0.05), and -0.3% ( P>0.05) and -1.2% ( P<0.05) in urban area, respectively. China Health Statistical Yearbook data showed that the urban ASMR decreased by 12.3% from 2014 to 2021 with AAPC of -2.6% ( P<0.05). 3) The GLOBOCAN 2022 predicted that, the breast cancer case count and death count in China would be 387 776 and 111 133 by 2050, an increase of 8.6% and 48.2%, respectively, compared with 2022, the increases would be more obvious in people over 65 years old, an increase of 80.8% and 124.9%, respectively. 4) Thirteen individual- based studies reported that the median medical expenditure per patient ( M=21 000 to 39 000 Yuan) and length of hospital stay ( M=11.0 to 30.5 days) for breast cancer treatment decreased from 2010 to 2019, while the average medical expenditure per visit ( M=9 000 to 23 000 Yuan) showed an upward trend. There was only one national-level analysis, which showed that the treatment cost of breast cancer was 25.24 billion Yuan in China in 2018, accounting for 6.4% of the total cancer treatment cost. Conclusions:According to the above updated multi-source data, the incidence and mortality of female breast cancer in China were stable in the past ten years, but the increasing trend in rural area should be noted. The direct medical expenditure of breast cancer treatment per case might decrease, but the population-level economic burden would remain heavy due to population aging.

Objective To isolate E.scherichia coli-specific bacteriophages from hospital waste water,analyze their biological character-istics and detect their cleavage effects on bacterial biofilms.Methods The phages were isolated and purified by double-layer agar plate method and their morphology was observed by transmission electron microscopy.Their one-step growth curve,in vitro lysis curve,tem-perature and acid-base stability were determined.Whole genome sequencing was used to analyze the genome composition and character-istics of bacteriophages.The crystal violet staining was used to evaluate the scavenging effects of phage on host biofilms.Results A novel Escherichia coli-specific bacteriophage named vB_EcoP-R1 was isolated from hospital sewage.Transmission electron microscopy revealed that the morphology of vB_EcoP-R1 was similar to that of Podoviridae,a member of Caudovirales,and it could survive stably in the temperature range of-20 ℃ to 50 ℃ and pH 5.0 to 11.0.The total length of the vB_EcoP-R1 genome was 40 875 bp and the GC content was 49.94％.There were no virulence genes and drug resistance genes in the phage genome.vB_EcoP-R1 was capable of lysing clinically isolated Escherichia coli and showed high species and genus specificity.After the phage acted on the host bacteria preformed biofilm for 4 h,the clearance rate of the biofilm reached 80.16％.Conclusion vB_EcoP-R1 should be a novel Escherichia coli-specif-ic bacteriophage with strong lysis and high specificity for species and genus.The bacteriophage could lyse the biofilm formed by the host bacteria,and is expected to be used as an alternative treatment for Escherichia coli infection.

Chimeric antigen receptor(CAR)T cell therapy,one of the most promising tumor treatments,combines the targeted recognition of antigen and antibody with the killing effect of T cells.CAR-T has shown a strong therapeutic effect in lymphoid tumors and been applied in clinical practice.However,in the treatment of acute myeloid leukemia(AML),no effective and specific target like CD 19 in lymphoid tumors has been found.Therefore,the key research direction is to try multiple probabilities and use optimization strategies to enhance efficacy and reduce toxicity.This review introduces the latest research progress of AML targets in CAR-T therapy in recent years,analyzes the related problems that need to be solved at present,and summarizes the optimization construction strategies mentioned in the research.Hope it can provide reference for related research and clinical application of related product.

In recent years,the importance of long non-coding RNA(lncRNA)in acute myeloid leukemia(AML)has attracted wide attention.Among them,lncRNAs that play a role in promoting cancer mainly include HOTAIR,UCA1,H19,ITGB2-AS1 and some genes of SNHG family,while in tumor suppression mainly include H22954,NEAT1,SNHG4,LINC01128,etc.This article reviews the role of lncRNAs in the occurrence and development of AML,as well as those related to AML resistance and prognosis assessment,so as to provide a theoretical basis for the diagnosis and prognosis analysis of AML.