Alzheimer’s disease （AD） is an age-related neurodegenerative disorder. Marrow-sea insufficiency serves as the fundamental basis for the onset of AD. Early syndrome differentiation-based intervention helps to delay disease progression， and improve patients’ cognitive function. Qifu yin is a representative specialized prescription for AD with marrow-sea insufficiency syndrome. Studies demonstrate that Qifu yin exerts neuroprotective effects through multiple pathways， including inhibiting the abnormal deposition of amyloid β -protein and hyperphosphorylation of tau protein， alleviating neuroinflammation， regulating oxidative stress and mitochondrial dysfunction， modulating the cholinergic system， and improving synaptic plasticity. Qifu yin combined with Western medicine such as donepezil， memantine， and butylphthalide， or combined with external therapies such as acupuncture， can effectively improve cognitive function and activities of daily living in AD patients with favorable safety. Future research should focus on the core pathogenesis and key targets of AD with marrow-sea insufficiency syndrome， provide in-depth elucidation of the scientific connotation of Qifu yin’s “tonifying the kidney to produce marrow”， and further conduct high-quality clinical studies to provide scientific evidence for the prevention and treatment of AD with marrow-sea insufficiency syndrome.

Purpose: The optimal sequencing of targeted therapies and the role of primary tumor resection (PTR) in KRAS wild-type metastatic colorectal cancer (mCRC) remain unclear. This study compared survival outcomes in patients treated with first-line cetuximab plus FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) versus bevacizumab plus FOLFIRI, followed by second-line oxaliplatin-based chemotherapy and later-line trifluridine/tipiracil or regorafenib. Methods: This retrospective cohort study used Taiwan’s National Health Insurance Research Database and the Taiwan Cancer Registry. Patients diagnosed with mCRC between 2013 and 2019 were included if they received first-line cetuximab or bevacizumab plus FOLFIRI, followed by later-line trifluridine/tipiracil or regorafenib. Patients were stratified by PTR status. Primary endpoints were overall survival and survival during trifluridine/tipiracil or regorafenib treatment. Secondary endpoints included time to treatment discontinuation (TTD) and TTD during trifluridine/tipiracil or regorafenib therapy. Stabilized inverse probability of treatment weighting was used for adjustment. Results: Among 559 patients, 278 were assigned to the non-PTR group and 281 to the PTR group. In the non-PTR group, the cetuximab cohort demonstrated significantly longer survival during trifluridine/tipiracil or regorafenib therapy (6.2 months vs. 4.9 months; hazard ratio [HR], 0.72) and longer TTD1 (the interval between initiation of first-line therapy and the start of second-line chemotherapy; 11.8 months vs. 9.5 months; HR, 0.67) than the bevacizumab cohort. Survival differences between regimens were less pronounced among patients who underwent PTR. Conclusion First-line cetuximab plus FOLFIRI may confer a survival advantage over bevacizumab in patients with KRAS wild-type mCRC without PTR, including during later-line therapy with trifluridine/tipiracil or regorafenib, whereas bevacizumab appears to provide more consistent benefits in those with PTR.

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.

The c-Jun N-terminal kinase （JNK） signaling pathway， a key member of the mitogen-activated protein kinase （MAPK） family， plays a central role in the pathogenesis and progression of central nervous system （CNS） diseases by regulating core biological processes such as apoptosis， inflammatory responses， synaptic plasticity， and autophagy. This article sorts out and analyzes relevant literature published domestically and internationally in recent years， summarizing the mechanisms of action of the JNK signaling pathway in common CNS diseases and the research progress in traditional Chinese medicine （TCM） interventions in CNS diseases through the regulation of the JNK signaling pathway. Studies have shown that active components of TCM， such as berberine， paeoniflorin， and astragaloside Ⅳ， as well as compound formulations like Heixiaoyao san， Ditan tang， and Buyang huanwu tang， can exert neuroprotective effects in various CNS disorders， including Alzheimer’s disease， Parkinson’s disease， cerebral ischemia-reperfusion injury， and epilepsy， by inhibiting the aberrant activation of the JNK signaling pathway， thereby alleviating neuroinflammation， oxidative stress， and neuronal apoptosis， while improving synaptic function and cognitive behavioral deficits， regulating autophagy， and maintaining blood-brain barrier integrity.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

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

AIM To study the chemical constituents from Tetrastigma hemsleyanum Diels et Gilg and their antitumor activity in vitro.METHODS Silica gel,ODS,Sephadex LH-20 and semi-preparative HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activity in vitro was determined by MTT mothod.RESULTS Twenty-eight compounds were isolated and identified as triphyllin A(1),eruberin B(2),(2S,4R)-5,7-dihydroxy-4,4'-dimethyl-6,8-dimethyl-flavan-5-O-β-D-6-acetylglucopyranoside-7-O-β-D-glucopyranoside(3),eruberin A(4),abacopterin Ⅰ(5),matteucinol(6),homoerodictyol(7),(2S)-5,3',4'-trihydroxy-7-methoxy-flavanone(8),(2S)-5,2',5'-trihydroxy-7-methoxyflavanone(9),galinsonside B(10),quercetin-3-O-β-D-glucopyranoside(11),kaempferol 3-O-robinobioside(12),rutin(13),geniposide(14),jasminoside A(15),β-sitostenone(16),sitosterol palmitate(17),β-sitosterol(18),ursolic acid(19),hyptadienic acid(20),3,4-dihydroxybenzoic acid(21),3,4-dimethoxybenzoic acid(22),gallic acid(23),dibutylphthalate(24),bis-(2-ethylhexyl)phthalate(25),9-nonadecenoic acid(26),triacylglycerol(27),crocin Ⅰ(28).The IC50 values of compound 1 for human gastric adenocarcinoma cells BGC-823 and human colon cancer cells HCT-116 were(22.07±0.38),(20.67±0.11)μmol/L,respectively.The IC50 value of compound 9 for BGC-823 cells was(21.58±0.05)μmol/L,and the IC50 value of compound 4 for HCT-116 cells was(16.67±0.36)μmol/L.CONCLUSION Compounds 1-10,14-15 and 28 are first isolated from Tetrastigma genus.Compounds 1,4,9 have weak antitumor activity in vitro.

With the advancement of high-quality development in the healthcare system, the quality of the home page of medical records has become increasingly prominent, as an important data source for hospital management, performance evaluation, and medical insurance payment. In 2022, a grade-A tertiary hospital took improving the quality of the main diagnosis and surgical operations related data on the home page of medical records as the core goal, and constructed a quality control system for the home page of inpatient medical records based on the national medical security disease diagnosis-related groups (CHS-DRG). This system included two parts: the CHS-DRG grouper and early warning rules for high-risk medical records, which could issue warnings for abnormal data in the grouping results. Then, based on this system, a human-machine collaborative quality control mechanism for the home page of medical records, namely " system warning-coder review-communication between coders and clinical doctors", was established and applied since January 2022, realizing closed-loop management of quality control for the home page of medical records. Compared with 2020-2021, the accuracy rates of main diagnosis filling, main surgeries filling, and main diagnosis coding in 2022-2023 increased by 16.31, 12.45, and 1.70 percentage points respectively ( P<0.05); the number of diagnosis items increased by 0.91 ( P<0.05), and the coding time consumption decreased by 4.59 d ( P<0.05). Meanwhile, after the application, the quality improvement effect on the non-DRG payment group was higher than that on the DRG payment group ( P<0.05). The application of this system not only helps to improve the information-based means of medical record quality control and enrich the method system of medical record quality control, but also comprehensively improves the quality and work efficiency of the home page of medical records under different payment methods, which can provide reference for other hospitals to continuously improve the quality control work of the home page of medical records.

Objective:To explore the impact of DRG payment reform on high-ratio cases and their hospitalization expenses, so as to provide references for deepening the reform of the medical insurance payment system.Methods:Data were collected from inpatient medical record home pages within 2019 to 2023 in a reform pilot hospital in Wuhan. All cases were grouped by the CHS-DRG grouper. The high-ratio cases were identified as hospitalization expenses exceeding 2.5 times the standard expenses. Interrupted time series model was used to analyse the impact of DRG payment reform on the proportion of high-rate cases and their hospitalization expenses. The period from January 2019 to December 2020 was the stage before the reform, and the period from January 2021 to December 2023 was the stage after the reform.Results:This study included 1 364 711 grouped cases, among which there were 159 506 high-ratio cases(78 679 cases before the reform and 80 827 cases after the reform). After the implementation of DRG payment, the proportion of high-ratio cases was decreased from 17.29% to 8.89%. The average DRG weight increased from 0.94 before the reform to 1.12 after the reform, and the average total hospitalization cost increased from 45 677.18 yuan to 52 179.32 yuan. Results from interrupted time series model showed that the proportion of high-ratio cases appear a downward trend after the reform( P=0.008). The total hospitalization cost showed an upward trend both before and after the reform( P<0.05), but the growth trend slowed down after the reform. The diagnosis cost exhibited an upward trend both before and after the reform( P<0.05), but there was a significant immediate decrease immediately after the implementation of the reform( P=0.016); The treatment cost showed an upward trend after the reform( P<0.001); The consumable cost had an upward trend before the reform( P=0.007), but the change trend after the reform was not statistically significant( P=0.544). In addition, the treatment expenses of the surgical group and the internal medical group both showed a significant upward trend after the reform( P<0.001); The consumable cost of the procedural group and the diagnosis cost of the internal medicine group both decreased immediately after the reform( P<0.05). Conclusions:DRG payment helps reduce the high-ratio cases and has a certain optimizing effec on their structure of hospitalization cost.

AIM To investigate the effects of rice wine type and wine processing method on chemical constituents and anti-coagulation effect of Angelicae sinensis Radix.METHODS Wine-washed products and wine-stir-fried products were prepared by different types and ages of rice wine,respectively,after which HPLC was adopted in the content determination of tryptophan,chlorogenic acid,vanillic acid,phthalic acid,ferulic acid,senkyunolide I,senkyunolide H,coniferyl ferulate and ligustilide,and PT,APTT,TT were detected in rabbit plasma.RESULTS Phenolic acids and volatile constituents demonstrated lower contents in the wine-stir-fried products than those in the raw product(P＜0.05),while those in the wine-washed products displayed no obvious changes(except for senkyunolide I)(P＞0.05).The contents of volatile constituents in the wine-washed products were higher than those in the wine-stir-fried products(P＜0.05).After being processed with dry rice wine,various constituents exhibited increased contents as compared with those after being processed with sweet rice wine(P＜0.05).Compared with the raw product,prolonged PT,APTT and TT were observable in the processed products prepared by 3-year semi-dry rice wine(P＜0.05).CONCLUSION The optimal rice wine type is determined to be 3-year semi-dry.Wine-washed Angelicae sinensis Radix shows high contents of ferulic acid and volatile constituents,whose activating blood and resolving stasis effect may be stronger.