ObjectiveTo observe the effects of Jiangtang No. 3 prescription on inflammatory pathways and insulin resistance-related indicators in rats with type 2 diabetes mellitus （T2DM）， and to elucidate its molecular mechanism in combating diabetes. MethodsA T2DM rat model was established using a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. Successfully modeled rats were randomly assigned to the model group， metformin group， and low-， medium-， and high-dose Jiangtang No. 3 prescription groups， and a normal group was also set. Daily gavage was administered for 8 weeks as follows： metformin at 0.1 g·kg^-1·d^-1， Jiangtang No. 3 prescription granules at 1.62， 3.24， 6.48 g·kg^-1·d^-1 for the respective dose groups， and sterile water for the normal and model groups. Rat body weight， fasting blood glucose （FBG）， oral glucose tolerance test （OGTT）， and insulin tolerance test （ITT） were measured. After drug intervention， enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL）， high-density lipoprotein cholesterol （HDL）， non-esterified fatty acids （NEFA）， interleukin （IL）-1β， IL-18， and insulin （INS）. Hematoxylin-eosin （HE） staining was used to observe morphological changes in adipose tissue. Real-time quantitative PCR was used to detect the mRNA expression of Toll-like receptor 4 （TLR4）， nuclear factor-κB （NF-κB）， NOD-like receptor protein 3 （NLRP3）， Caspase-1， IL-1β， IL-18， and gasdermin D （GSDMD） in adipose tissue. Western blot was used to measure the corresponding protein expression levels. ResultsCompared with the model group， Jiangtang No. 3 prescription groups exhibited significantly increased body weight （P<0.05， P<0.01）， significantly reduced FBG （P<0.05， P<0.01）， significant reductions in TC， TG， NEFA， and LDL （P<0.05， P<0.01）， and a significant increase in HDL （P<0.01）. Serum levels of inflammatory mediators IL-1β and IL-18 were significantly decreased （P<0.01）， the homeostatic model assessment of insulin resistance （HOMA-IR） index was significantly reduced （P<0.05， P<0.01）， and adipose tissue pathology was improved. The protein expression levels of TLR4， NF-κB， NLRP3， Caspase-1， IL-1β， IL-18， and GSDMD were markedly decreased （P<0.05， P<0.01）， and the mRNA expression levels of these indicators were also significantly downregulated （P<0.05， P<0.01）. Some effects were superior to those of the positive control drug metformin， and certain indicators exhibited dose-dependent improvements. ConclusionT2DM rats display significant inflammatory responses， disordered glucose and lipid metabolism， and insulin resistance. Jiangtang No. 3 prescription effectively suppresses inflammatory mediators， improves glucose and lipid metabolism and insulin resistance， and ameliorates pathological changes in adipose tissue. Its mechanism may be related to the regulation of the TLR4/NF-κB/NLRP3 signaling pathway in visceral adipose tissue， thereby influencing downstream inflammatory mediators.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

p21 (encoded by the CDKN1A gene) is a critical cell cycle regulatory protein endowed with versatile biological functions. In various sex hormone-related cancers, p21 exhibits a paradoxical dual role, capable of both inhibiting tumorigenesis and promoting cancer progression, exerting dual, often opposing, effects on cellular fate that are dictated by the specific context. The clinical targeting of p21 remains elusive, largely due to its functionally pleiotropic and context-dependent nature within intricate regulatory networks. During the initial, hormone-dependent phase of cancers like breast and prostate cancer, p21 expression and activity are largely governed by the transcriptional programs of estrogen or androgen receptor signaling. This hormonal regulation contributes to the control of tumor cell proliferation and underpins the initial efficacy of endocrine therapies. In contrast, as these diseases advance to late stages or evolve into non-hormone-dependent subtypes—exemplified by castration-resistant prostate cancer (CRPC) and specific forms of triple-negative breast cancer (TNBC)—these conventional hormonal control mechanisms often become dysfunctional or are entirely bypassed. This fundamental transition creates a critical therapeutic void, highlighting the urgent need to identify and exploit alternative molecular pathways to effectively target p21’s function. Promising strategies may include the precise modulation of its upstream transcriptional regulators, downstream effector proteins, or the intersecting parallel signaling networks that critically influence its activity. This review provides a systematic synthesis of the intricate and interconnected mechanisms that underpin the dual effects of p21 in sex hormone-related tumors. These mechanisms are categorized into three core, interrelated functional domains. (1) cell cycle regulation: p21 executes its canonical tumor-suppressive role by binding to and inhibiting cyclin-dependent kinases (CDKs) and by directly interacting with proliferating cell nuclear antigen (PCNA), thereby inducing cell cycle arrest, predominantly at the G1/S checkpoint; (2) apoptosis modulation: p21 exerts a highly context-dependent influence on programmed cell death, functioning either as a pro-apoptotic agent under severe genotoxic stress or as a pro-survival factor by inhibiting apoptosis through interactions with proteins like Bcl-2; (3) hormonal and signaling crosstalk: p21 is an integral node within broader cellular networks, engaging in direct physical interactions with hormone receptors(e.g., AR, ER) and participating in complex feedback loops with key oncogenic pathways, including PI3K/AKT, MAPK/ERK, and p53. Critically, the role of p21 is not static but highly dynamic. It can undergo a functional switch from tumor-suppressive to tumor-promoting in response to therapeutic pressures, metabolic alterations, or evolving tumor microenvironment cues. These adaptive shifts are frequently implicated in the development of therapy resistance and disease recurrence, particularly in advanced, hormone-resistant cancers. By synthesizing these insights, this review aims to establish a coherent theoretical framework to guide the future development of novel therapeutic strategies that target the p21 pathway. It underscores the necessity of moving beyond a simplistic, binary view of p21 and emphasizes the forthcoming challenges, such as the discovery of reliable biomarkers to predict its functional state and the rational design of context-specific pharmacological modulators to selectively harness its therapeutic potential.

ObjectiveTo investigate the contamination status of ochratoxin A (OTA) in commercially available food products in Shanghai, and to assess OTA exposure levels and the associated non-carcinogenic and carcinogenic risks among pregnant women by integrating dietary consumption data of this population. MethodsThe levels of OTA contamination in 1 520 food samples collected in Shanghai from 2022 to 2023 were determined using liquid chromatography-tandem mass spectrometry. An exposure assessment model was developed based on the dietary consumption levels of pregnant women from the 2016‒2017 Shanghai Pregnant Women Dietary Monitoring Survey to calculate the estimated daily intake (EDI) of OTA, the margin of exposure for non-carcinogenic toxicity (MOE₁), and the margin of exposure for carcinogenic toxicity (MOE₂). An MOE₁ greater than 200 and an MOE₂ greater than 10 000 indicate that the non-carcinogenic toxicity and carcinogenic toxicity resulting from exposure are negligible, respectively. For samples with OTA contamination levels below the limit of detection (LOD), which accounted for more than 80% of the samples, the OTA levels were assigned values of 0 and LOD, respectively, for subsequent calculations. ResultsThe detection rates of OTA in cereals, nuts, dried fruits, and alcohol samples collected in 2022 were 2.03%, 0, 0, and 0, respectively. The OTA detection rates in cereals, nuts, dried fruits, beans, and alcohol samples collected in 2023 were 2.50%, 0.39%, 2.47%, 1.67%, and 13.33%, respectively. For pregnant women in Shanghai in 2022, simulation results indicated that when assigning a value of 0 and the LOD, theP₅₀ values of EDI for dietary OTA exposure were 0.05 and 0.72 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.25 and 2.40 ng·(kg·d)^-1, respectively. For pregnant women in Shanghai in 2023, the P₅₀ values of EDI for dietary OTA exposure were 0.04 and 1.00 ng·(kg·d)^-1, respectively, and the P₉₅ values of EDI for dietary OTA exposure were 0.23 and 2.67 ng·(kg·d)^-1, respectively, both substantially below the tolerable daily intake (TDI) for OTA [17 ng·(kg·d)^-1]. The EDI for dietary OTA exposure in 100.0% of Shanghai pregnant women was lower than the TDI, indicating an overall low level of dietary OTA exposure among this population. For 100.0% of pregnant women, the MOE₁ for dietary OTA exposure exceeded 200. When assigned a value of 0, the MOE₂ for 100.0% of pregnant women in both 2022 and 2023 exceeded10 000. When assigned the LOD value, 72.3% and 81.8% of pregnant women in 2022 and 2023, respectively, had an MOE₂ exceeding 10 000. ConclusionFrom 2022 to 2023, samples of cereals, nuts, dried fruits, beans, and alcohol sold in Shanghai exhibited varying degrees of OTA contamination. The overall EDI of OTA exposure among pregnant women in Shanghai remained at a low level. The non-carcinogenic and carcinogenic risks associated with OTA exposure were generally low and at controllable levels.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

This paper reports the diagnosis and treatment process of a patient with severe anemia caused by hookworm and Ascaris lumbricoides co-infections, so as to provide insights into clinical diagnosis and treatment and avoid misdiagnosis and under-diagnosis of parasitic infections. Living parasites were found by endoscopy, which were morphologically identified as hookworm and A. lumbricoides, and routine stool examinations detected hookworm and A. lumbricoides eggs. The patient was diagnosed with severe anemia caused by hookworm and A. lumbricoides co-infections by means of clinical symptoms, epidemiological history, endoscopic findings, and laboratory tests. Following blood transfusion, hemostasis, oral administration with albendazole, and symptomatic treatments, the patient showed remarkable symptomatic improvement and had a good prognosis.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Aim To explore the effects of Kui Jie Kang(KJK)on modulating the farnesoid X receptor(FXR)pathway in the gut microbiota and bile acid metabolism in mice with ulcerative colitis(UC).Methods Mice were subjected to DSS-induced UC and randomly as-signed to the control(CON),model(MOD),and two KJK-dosed groups(KJK.H at 12.8 g·kg-1,KJK.L at 3.2 g·kg-1).Mouse body weight was recorded,and disease activity index(DAI)was scored.The his-topathological changes in colonic tissue were observed via HE staining,and the number of goblet cells and mucosal layer repair were assessed using PAS and Al-cian blue staining.Bile acid content in feces was measured using LC-MS/MS,gut microbiota composition was analyzed by 16S rRNA gene sequencing,and the expression of FXR target genes and related proteins was detected by RT-qPCR and Western blot.Results KJK significantly ameliorated colonic shortening,de-creased disease activity index in UC mice,reduced his-topathological scores,increased the number of goblet cells and mucus secretion,altered the levels of primary and secondary bile acids,and increased the relative a-bundance of beneficial bacteria such as Lactobacillus.Additionally,it significantly upregulated the expression of FXR and FGF15 mRNA and protein in colonic tissue and downregulated the expression of hepatic CYP7A1 mRNA,and the correlation analysis in this study clearly revealed a significant correlation between bile acid me-tabolism disorders and gut microbiota imbalance in UC.Conclusion KJK activates the intestinal FXR-FGF15-CYP7A1 pathway,thereby regulating bile acid metabolism and restoring gut microbiota balance,which may be key to its improvement of UC.

Objective:Bidirectional causal associations of 41 cytokines with atopic dermatitis(AD)were explored based on a Mendelian randomization(MR)approach.Methods:Pooled data from genome wide association study(GWAS)of 41 cytokines and AD were utilized for instrumental variable(IV)screening,and single nucleotide polymorphism(SNP)affecting the results of MR analyses was excluded by the MR-PRESSO outlier test as well as by the MR Steiger filtering method.Two-sample bidirectional MR analyses were performed using inverse variance weighting(IVW),MR-Egger regression,and weighted median methods(WM).MR-Egger intercept term test and Cochran's Q test were performed to test the pleiotropy and heterogeneity of IV,and MR results were visu-alized by scatterplots,funnel plots,and leave-one-out plots.Results:Forward MR analysis showed that MIG(IVW:OR=0.89;95%CI:0.81～0.97;P=0.006)reduced the risk of AD development.In contrast,IL-5(IVW:OR=1.17;95%CI:1.01～1.36;P=0.042)and IL-18(MR Egger:OR=1.17;95%CI:1.03～1.33;P=0.030)increased the risk of AD development.Inverse MR analysis showed a potential causal association between AD and increased MIG(IVW:Beta=0.10;95%CI:0.02～0.17;P=0.014).None of the sensitivity analyses indicated pleiotropy and heterogeneity of the included IV.Conclusion:MIG may be an important marker in the progression of AD with a potential bidirectional causal association with risk of morbidity.IL-5 and IL-18 have a potential positive causal association for AD.

Depression is a prevalent mental and emotional disor-der that often results in significant emotional disturbances,cog-nitive dysfunction,and memory impairments.It is characterized by a high incidence rate,a substantial disability burden,and limited therapeutic efficacy.Currently,the long-term use of medications for the treatment of depression can result in a range of adverse reactions,highlighting the urgent need to explore no-vel approaches that can effectively alleviate depressive symptoms while minimizing side effects.Curcumin,a natural polyphenolic compound derived from the rhizome of turmeric,demonstrates considerable potential in the prevention and treatment of depres-sion,owing to its diverse array of biological activities.In recent years,numerous studies have investigated the use of curcumin for the treatment of depression.This article aims to provide a comprehensive review of the mechanisms of action underlying curcumin's efficacy in treating depression.Specifically,it focu-ses on its ability to improve neurotransmitter imbalances,restore neural plasticity,alleviate neural damage,mitigate dysfunction of the hypothalamic-pituitary-adrenal(HPA)axis,regulate in-flammatory factors and neuroinflammatory signaling pathways,and inhibit oxidative stress.This review is intended to offer in-sights and methodological references for basic research on curcu-min,as well as for the development of novel therapeutic agents for the treatment of depression.