Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

Obesity is a multi-factorial disease involving genetics, individual behavior, socio-economic status, and environmental factors, and has become a global public health issue. The food environment, as an external factor amenable to direct intervention, affects the development of obesity by shaping individual food acquisition and consumption behaviors. The food environment refers to the physical and social environment where food is accessible, and can be assessed from dimensions such as availability, accessibility, and affordability through geographic information system spatial analysis, field surveys, commercial databases, and questionnaires. Studies indicate that the food environment can influence obesity through the spatial shaping effects of dietary structure and sociobehavioral pathways. A healthy food environment is negatively correlated with the risk of obesity, whereas an unhealthy food environment is positively correlated with the risk of obesity. This paper reviews studies related to the correlation between the food environment and obesity, covering the prevalence of obesity, the definition and assessment methods of the food environment, and the mechanisms by which the food environment affects obesity. It summarizes food environment intervention strategies centered on urban planning, policies and regulations, and community education to provide a reference for obesity prevention and control.

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.

Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

ObjectiveTo explore the risk factors and alterations in functional connectivity of brain networks in end-stage renal disease （ESRD） patients complicated by frailty. MethodsA total of 84 patients with ESRD were enrolled and divided into the frailty group （31 cases） and non-frailty group （53 cases） according to the Chinese version of the Tilburg Frailty Indicator （TFI）. Cranial magnetic resonance imaging （MRI） data， neuropsychological test results and clinical data were collected for all subjects. Logistic regression analysis was used to explore risk factors for frailty in ESRD patients， and image preprocessing and independent component analysis were performed to compare differences in brain network functional connectivity between the two groups. ResultsLogistic regression analysis showed that high blood urea nitrogen level， depression， malnutrition， and sleep disturbance were risk factors for frailty in patients with ESRD （P<0.05）， while a higher level of education served as a protective factor （P<0.05）. Compared with the non-frailty group， the frailty group exhibited significantly weakened functional connectivity between the sensorimotor network and the visual network （P<0.05）. ConclusionHigh levels of blood urea nitrogen， depression， malnutrition， and sleep disorders can increase the risk of frailty in patients with end-stage renal disease （ESRD）， while a higher educational level may reduce this risk. Patients with ESRD complicated by frailty exhibit a significant decrease in functional connectivity between the sensorimotor network （SMN） and visual network （VN）， which provides novel imaging evidence for exploring the central neural mechanisms underlying the development of frailty in ESRD patients.

Introduction: The 2021 IDF-DAR risk calculator had been previously evaluated in multiple studies and subsequently widely accepted and applied in clinical practice as a practical standardized tool for patient risk stratification. Recently updated, the 2026 IDF-DAR Risk calculator enables a more individualized, evidence-related evaluation of patientrelated and disease-related risk factors, incorporating modern diabetes technologies, including continuous glucose monitoring (CGM), automated insulin delivery (AID) systems, and advanced insulin formulations to enhance risk stratification. This tool allows medical professionals to tailor Ramadan practices based on overall factors toward promoting safe fasting. Methodology: This prospective multicentre observational study recruited adults with Type 1 and Type 2 diabetes attending public hospitals nationwide. People with diabetes (PwD) intending to perform Ramadan fasting were invited to participate and assessed using the 2026 IDF-DAR Risk Calculator in the 6-week pre-Ramadan period between 30th January and 19th March 2026. Results: A total of 458 PwD were evaluated and stratified into low (15.7%), moderate (41%), and high risk (43.3%) categories. Most participants had Type 2 diabetes (83.6%), with 60.3% having a disease duration exceeding 10 years and 43% exhibiting poor glycemic control (hemoglobin A1c >9%). Insulin therapy was used by 76.4% of participants, including two individuals with Type 1 diabetes using AID systems. Most participants reported no recent hypoglycemia (76.4%), 81.0% performed glucose monitoring, and 3.3% used CGM. Severe comorbidities were uncommon, with 1.1% having unstable macrovascular disease and 4.4% advanced chronic kidney disease (estimated glomerular filtration rate <30). Notably, 72.2% received structured Ramadan education. Conclusion Majority of PwD attending tertiary diabetes clinics were in the moderate- to high-risk category and intended to fast despite medical advice against fasting in some cases. Although most participants were on insulin therapy, hypoglycemia was low in the pre-Ramadan period. Integration of modern technologies, advanced insulin therapies, and structured education may support safer fasting practices.
Risk Assessment ; Diabetes Mellitus ; Hospitals ; Fasting

BackgroundThe prevalence， disability rate and mortality rate of cerebral small vessel disease （CSVD） are relatively high among the elderly population， imposing a heavy burden on families and society. Among the various clinical manifestations of CSVD， cognitive impairment is the most common， and it is also the most closely related neuro-psychiatric syndrome to clinical practice in psychiatry. Previous studies on CSVD-related cognitive impairment （CSVD-CI） have mostly focused on the field of imaging， while studies on non-invasive electrophysiological and cerebral hemodynamic assessments are relatively scarce. ObjectiveTo analyze the characteristics of event-related potential （ERP） and functional near-infrared spectroscopy （fNIRS） in patients with CSVD-CI， and to explore their correlations with the severity of white matter lesions， in order to provide references for the objective assessment and early identification of CSVD-CI. MethodsA total of 40 patients with CSVD who met the diagnostic criteria of the Chinese Guideline for Diagnosis and Treatment of Cerebral Small Vessel Disease （2020） and had cognitive impairment， as well as were admitted to the Affiliated Hospital of North Sichuan Medical College from December 2024 to December 2025， were enrolled as the case group. Meanwhile， 40 healthy volunteers matched for gender， age and education level were recruited as the control group. Both groups underwent assessment using the Mini-Mental State Examination （MMSE）， ERP-P300 detection， and fNIRS examination. The ERP-P300 indicators， functional connectivity strength of the whole brain and cognitive-related regions of interest （ROI） in fNIRS of the two groups were compared. The severity of the patients' white matter lesions was classified as follows： the Fazekas grade I group （mild white matter lesions） and the Fazekas grades II to III group （moderate to severe white matter lesions）. Spearman correlation analysis was employed to investigate the correlation between the Fazekas grading of brain white matter lesions and the latency of ERP-P300， as well as the strength of functional connectivity measured by fNIRS. ResultsThe MMSE score of the CSVD-CI group was lower than that of the control group （Z=-6.250， P<0.01）， and ERP-P300 lantency was significantly longer than that of the control group （t=12.291， P<0.01）. The MMSE score of the sub-group with Fazekas grade I was higher than that of the sub-groups with grades II to III （Z=-2.420， P<0.05）， and showed a shorter P300 latency than that of the sub-groups with grades II to III （Z=-4.210， P<0.01）. All the differences were statistically significant. The resting-state whole-brain functional connectivity strength in the CSVD-CI group was lower than that in the control group， and the difference was statistically significant （t=10.243， P<0.05）. Compared with the control group， the differences in the functional connectivity strength within the left premotor cortex （PMC）， right PMC， left frontopolar cortex （FPC）， right FPC， left dorsolateral prefrontal cortex （DLPFC）， right DLPFC， left orbitofrontal cortex （OFC）， and right OFC regions in the CSVD-CI group were all statistically significant （P_{FDR correction}<0.01）. The differences in the functional connectivity strength between multiple prefrontal-related brain regions between the CSVD-CI group and the control group were all statistically significant （P_{FDR correction}<0.01）. The severity of white matter lesions in CSVD-CI patients was positively correlated with the P300 latency （r_s=0.891， P<0.05）， and negatively correlated with the fNIRS functional connectivity strength （r_s=-0.359， P<0.05）. ConclusionPatients with CSVD-CI exhibit prolonged P300 latency， as well as decreased functional connectivity strength in multiple brain regions including the whole brain and the prefrontal lobe during the resting state. Moreover， these indicators are correlated with the severity of white matter lesions.

OBJECTIVE To systematically analyze the trends in the volume and value of out-licensing deals by Chinese biopharmaceutical companies over the past two decades， and to quantitatively identify factors associated with deal value， thereby providing an evidence base for policymakers and corporate managers. METHODS Based on the PharnexCloud database， information on out-licensing deals disclosed by Chinese biopharmaceutical companies between January 1， 2005 and December 31， 2025 was collected， and executed deals with disclosed specific financial terms were included for analysis. Descriptive statistical analyses of deal value， product characteristics and deal characteristics were performed using Stata SE 18.0； with the natural logarithm of deal value as the dependent variable， stepwise multiple regression models were constructed to examine the associations of product and deal characteristics with deal value. RESULTS A total of 210 out-licensing deals were included， with a cumulative deal value of approximately 214.151 billion dollars and a mean deal value of 1.020 billion dollars . The trading market expanded rapidly from 2020 onward， with the annual deal value reaching a record 95.687 billion dollars in 2025. Multiple regression analysis showed that the deal value of products at the drug discovery stage was significantly lower than that at the preclinical stage [regression coefficient （ β ） ＝－1.995， 95% confidence interval （CI）： －3.256 to －0.734， P ＜0.05 ] ； the deal value of oncology products was significantly higher than that of other therapeutic areas （ β ＝0.828， 95%CI： 0.224 to 1.431， P ＜0.05）； global licensing （ β ＝1.690， 95%CI： 1.107 to 2.273， P ＜0.05） and co-development arrangements （ β ＝0.849， 95%CI： 0.084 to 1.615， P ＜0.05） were significantly associated with higher deal value. CONCLUSIONS Out-licensing deals by Chinese biopharmaceutical companies have achieved significant growth in both volume and value over the past two decades. Oncology products， global licensing， and co-development arrangements are significantly and positively associated with higher deal value.

Introduction: Cushing’s disease in adolescents is rare and frequently difficult to diagnose due to overlapping features with common pubertal and metabolic conditions. We present an adolescent who underwent inferior petrosal sinus sampling (IPSS) with possible cyclical Cushing’s disease, highlighting the diagnostic challenges and the interpretive value of IPSS. Case: A 16-year-old female presented with progressive weight gain, acne, hirsutism, secondary amenorrhea, proximal myopathy, violaceous striae, and facial plethora over 1 year. Her 24-hour urinary cortisol was >3,310 nmol/L with failure of suppression following a 1-mg overnight dexamethasone suppression test (701 nmol/L). Her adrenocorticotropic hormone (ACTH) was raised (77.9 pg/mL), consistent with ACTH-dependent Cushing syndrome. Her hemoglobin A1c was 5.9%, and she has low bone mass for age with a Z score of -2.9 at the Lumbar spine. Pituitary magnetic resonance imaging identified a rightsided microadenoma measuring 0.6 × 0.5 cm, while computed tomography of the thorax, abdomen, and pelvis showed no ectopic source. IPSS with desmopressin stimulation was performed to confirm the ACTH source. No steroidogenesis inhibitors were administered prior to testing. Notably, cortisol levels during IPSS were relatively low, with midnight cortisol of 91 nmol/L and morning cortisol of 200 nmol/L, suggesting testing during a trough phase of possible cyclical hypercortisolism. Despite this, IPSS demonstrated a significant central-to-peripheral ACTH gradient supporting a pituitary source. Conclusion This case highlights the diagnostic dilemma of interpreting IPSS in suspected cyclical Cushing’s disease. Fluctuating cortisol secretion may result in discordant biochemical findings and complicate localization studies. IPSS findings should be interpreted cautiously and integrated with clinical features, imaging, and serial biochemical monitoring. Recognition of cyclical disease patterns is essential to ensure appropriate management in adolescent patients.
Adolescent ; Humans ; Petrosal Sinus Sampling