ObjectiveTo investigate the mechanism by which Wumeiwan suppresses the development and progression of colorectal cancer（CRC） through the regulation of fatty acid metabolic reprogramming， thereby providing new experimental evidence for the prevention and treatment of CRC. MethodsA total of 120 C57BL/6 mice were randomly divided into the blank group， model group， Wumeiwan high-， medium-， and low-dose groups（54， 27， 13.5 g·kg^-1）， and the mesalazine group（0.01 g·kg^-1）， with 20 mice in each group. Except for the blank group， all mice were subjected to azoxymethane（AOM）/dextran sulfate sodium（DSS） treatment to establish an inflammation-associated CRC model. One week after AOM injection， mice in the treatment groups received intragastric administration of the designated drugs， while the blank and model groups received an equal volume of purified water， continuing until 20 d after the intervention endpoint. Hematoxylin-eosin（HE） staining was used to observe colonic histopathological alterations， and immunohistochemistry for vascular endothelial growth factor（VEGF） was performed to evaluate neovascularization and tumor invasion. Metabolomics combined with Kyoto Encyclopedia of Genes and Genomes（KEGG） and metabolite set enrichment analysis（MSEA） was applied to identify key CRC-related metabolic pathways， which were further validated by transcriptomic Gene Ontology（GO） enrichment and gene heatmap analysis. Subsequently， Western blot was performed to determine the expression levels of core proteins in these pathways， and immunofluorescence was used to analyze their localization and co-expression patterns in tissues， thereby elucidating the mechanism of Wumeiwan from multiple biological dimensions. ResultsCompared with the blank group， mice in the model group exhibited a significant decrease in body weight and a significant increase in the disease activity index（DAI） score（P<0.05）， with pronounced colonic mucosal damage accompanied by aggravated tumor invasion. Compared with the model group， Wumeiwan intervention markedly improved body weight loss and reduced DAI score， attenuated mucosal injury， and significantly decreased VEGF expression level（P<0.05）. Multi-omics analysis revealed that differential metabolites and genes across groups were commonly enriched in fatty acid metabolism， fatty acid biosynthesis， and other lipid-related pathways. Relative to the blank group， the model group showed significant upregulation levels of fatty acid synthesis-related genes， including sterol regulatory element-binding protein 1（SREBP1）， fatty acid synthase（FASN）， stearoyl-CoA desaturase 1（SCD1）， as well as saturated fatty acids（P<0.05）. Compared with the model group， treatment with Wumeiwan significantly reduced the expression of key genes involved in fatty acid metabolic pathways， including SREBP1， FASN， and SCD1（P<0.05）. Western blot results further confirmed that proteins in this pathway were significantly elevated in the model group， whereas they were markedly downregulated following Wumeiwan treatment（P<0.05）. Immunofluorescence analysis demonstrated enhanced co-localization of SREBP1 with the cancer-associated fibroblast（CAF） marker α-smooth muscle actin（SMA） in the model group， whereas this co-localization signal was attenuated after Wumeiwan intervention（P<0.05）. ConclusionWumeiwan can improve survival outcomes and alleviate colonic pathological damage in CRC mice， its therapeutic mechanism may be closely associated with the regulation of fatty acid metabolic reprogramming mediated by the SREBP1/FASN/SCD1 signaling pathway.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective: To quantitatively assess the health risk of preservatives from beverages around primary schools in Anshun City, and to provide scientific basis for precise food safety supervision. Methods: From December 2023 to July 2024, 602 beverage samples were randomly collected from within 100 meters of 19 primary schools in Anshun City. The content of benzoic acid, sorbic acid, and dehydroacetic acid was detected according to GB 5009 series standards. Combined with children s physiological parameters (body weight 30 kg, daily intake 0.15 L), the Hazard Quotient (HQ) and Hazard Index (HI) models were used to evaluate health risks. Results: The total detection rate of preservatives from beverages around primary schools was 63.0%, and the total over limit rate was 9.0%. The detection rate of preservatives in flavored beverages was the highest (72.6%), and the highest over limit rate of preservatives in special purpose beverages was the highest (17.2%). The single preservative HQ (benzoic acid up to 0.47 ) and mixed HI (up to 0.55) of all samples were below 1(safety threshold). However, the HQ value of benzoic acid in flavored beverages (0.47) was 2.9 times that of sorbic acid (0.16), contributing significantly to health risk. Sensitivity analysis showed that if the daily consumption increased to 0.3 L, the HI value of flavored beverages would rise to 1.11, exceeding the safety threshold. Enterprise scale analysis showed that the exceedance rate of special purpose beverages in large enterprises reached 30.0%, while micro enterprises, accounting for a dominant market share (52.2%), constituted the main source of children s daily exposure to their products. Conclusions The overall health risk of perservatives in beverages sold near primary schools in Anshun City is controllable, but there is a noticeable risk of gradient. The risk of children’s exposure to preservatives through beverage consumption should not be ignored.

BACKGROUND:Sarcopenia is an age-related systemic skeletal muscle disease,which is associated with a variety of adverse outcomes such as falls,functional decline,frailty,and death.Postmenopausal women are one of the high-risk groups for sarcopenia.OBJECTIVE:To develop a predictive model for assessing the risk of sarcopenia in Chinese postmenopausal women based on high-quality database.METHODS:Data for this study were derived from 2 370 postmenopausal women from the China Health and Retirement Longitudinal Study(CHARLS),and sarcopenia was assessed using the Asian Working Group on Sarcopenia 2019(AWGS2019)recommended metrics.The study cohort was randomized into a training set(70％)and a validation set(30％).Risk factors for sarcopenia in postmenopausal women were screened using the least absolute shrinkage and selection operator,ten-fold cross-validation,and logistic regression.Nomogram predicting the risk of sarcopenia in postmenopausal women was constructed based on the risk factors,and the model efficacy was evaluated by the receiver operating characteristic curve and area under the curve(AUC),calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:The prevalence of sarcopenia in this study was 23.50％and age,place of residence,sleep quality,cognitive function,depression,and the number of chronic diseases were selected as predictors of sarcopenia in postmenopausal women.The nomogram model showed good discrimination between the training and validation sets,with an AUC value of 0.751(95％confidence interval=0.724-0.778,P＜0.001),a specificity of 72.2％,and a sensitivity of 63.2％in the training set,and an AUC value of 0.763(95％confidence interval=0.721-0.805,P＜0.001),with a specificity of 69.6％and a sensitivity of 70.8％.The calibration curve showed a relatively significant agreement between the nomogram model and the actual observations,and the decision curve analysis demonstrated broad and good clinical utility.To conclude,the nomogram to assess the risk of sarcopenia constructed based on age,place of residence,sleep quality,cognitive function,depression,and number of chronic diseases,provides an effective tool for identifying and eliminating risk factors for sarcopenia in Chinese postmenopausal women,and helps to reduce the incidence of sarcopenia.

BACKGROUND:Sarcopenia is an age-related systemic skeletal muscle disease,which is associated with a variety of adverse outcomes such as falls,functional decline,frailty,and death.Postmenopausal women are one of the high-risk groups for sarcopenia.OBJECTIVE:To develop a predictive model for assessing the risk of sarcopenia in Chinese postmenopausal women based on high-quality database.METHODS:Data for this study were derived from 2 370 postmenopausal women from the China Health and Retirement Longitudinal Study(CHARLS),and sarcopenia was assessed using the Asian Working Group on Sarcopenia 2019(AWGS2019)recommended metrics.The study cohort was randomized into a training set(70％)and a validation set(30％).Risk factors for sarcopenia in postmenopausal women were screened using the least absolute shrinkage and selection operator,ten-fold cross-validation,and logistic regression.Nomogram predicting the risk of sarcopenia in postmenopausal women was constructed based on the risk factors,and the model efficacy was evaluated by the receiver operating characteristic curve and area under the curve(AUC),calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:The prevalence of sarcopenia in this study was 23.50％and age,place of residence,sleep quality,cognitive function,depression,and the number of chronic diseases were selected as predictors of sarcopenia in postmenopausal women.The nomogram model showed good discrimination between the training and validation sets,with an AUC value of 0.751(95％confidence interval=0.724-0.778,P＜0.001),a specificity of 72.2％,and a sensitivity of 63.2％in the training set,and an AUC value of 0.763(95％confidence interval=0.721-0.805,P＜0.001),with a specificity of 69.6％and a sensitivity of 70.8％.The calibration curve showed a relatively significant agreement between the nomogram model and the actual observations,and the decision curve analysis demonstrated broad and good clinical utility.To conclude,the nomogram to assess the risk of sarcopenia constructed based on age,place of residence,sleep quality,cognitive function,depression,and number of chronic diseases,provides an effective tool for identifying and eliminating risk factors for sarcopenia in Chinese postmenopausal women,and helps to reduce the incidence of sarcopenia.

Obesity represents a critical global health challenge characterized by a complex pathogenesis involving dysregulated adipogenesis and lipid metabolism. In recent years, long non-coding RNAs (lncRNAs) have been established as crucial regulators in the initiation and progression of obesity. These RNA molecules, typically exceeding 200 nucleotides in length, have emerged as key modulators of various biological processes through multiple molecular mechanisms. This review innovatively defines lncRNAs as “molecular switches” in energy metabolism—they regulate adipogenesis and lipid metabolism through key signaling pathways, and exert bidirectional control over obesity via ceRNA mechanisms or recruitment of chromatin-modifying complexes in tissues such as adipose and liver. Additionally, circulating lncRNAs, owing to their tissue specificity and stability, hold promise as non-invasive liquid biopsy biomarkers for obesity and related metabolic disorders. Furthermore, we systematically summarize lncRNA-based intervention strategies, including targeting pathogenic lncRNAs using antisense oligonucleotides (ASOs) or CRISPR/Cas gene editing systems, utilizing viral vectors (such as adeno-associated virus, AAV) to deliver or mimic beneficial lncRNAs in target tissues, and employing exercise as a non-pharmacological intervention that ameliorates obesity and its related complications at multiple levels, offering novel insights for personalized therapeutic approaches. We also critically assess the current challenges in clinical translation, particularly addressing issues related to delivery efficiency, target specificity, and long-term safety concerns. Future research should focus on the following directions: integrating multi-omics with functional screening to elucidate the regulatory networks of lncRNAs in obesity and its complications; leveraging artificial intelligence to construct predictive models of lncRNA-target gene interactions; developing efficient and safein vivo delivery systems, and optimizing drug design to enhance specificity and safety; establishing highly sensitive detection methods and stable circulating lncRNA biomarkers to enable precise patient stratification and real-time monitoring of therapeutic responses; investigating the synergistic effects of lncRNAs with existing treatments (e.g., GLP-1 receptor agonists, lifestyle interventions) to develop combination therapies and establish a multidimensional, personalized precision medicine framework for obesity. This review aims to provide novel perspectives for understanding the molecular mechanisms underlying obesity and to establish a solid theoretical foundation for developing lncRNA-targeted precision medicine strategies against obesity and its associated metabolic complications.

Obesity represents a critical global health challenge characterized by a complex pathogenesis involving dysregulated adipogenesis and lipid metabolism. In recent years, long non-coding RNAs (lncRNAs) have been established as crucial regulators in the initiation and progression of obesity. These RNA molecules, typically exceeding 200 nucleotides in length, have emerged as key modulators of various biological processes through multiple molecular mechanisms. This review innovatively defines lncRNAs as “molecular switches” in energy metabolism—they regulate adipogenesis and lipid metabolism through key signaling pathways, and exert bidirectional control over obesity via ceRNA mechanisms or recruitment of chromatin-modifying complexes in tissues such as adipose and liver. Additionally, circulating lncRNAs, owing to their tissue specificity and stability, hold promise as non-invasive liquid biopsy biomarkers for obesity and related metabolic disorders. Furthermore, we systematically summarize lncRNA-based intervention strategies, including targeting pathogenic lncRNAs using antisense oligonucleotides (ASOs) or CRISPR/Cas gene editing systems, utilizing viral vectors (such as adeno-associated virus, AAV) to deliver or mimic beneficial lncRNAs in target tissues, and employing exercise as a non-pharmacological intervention that ameliorates obesity and its related complications at multiple levels, offering novel insights for personalized therapeutic approaches. We also critically assess the current challenges in clinical translation, particularly addressing issues related to delivery efficiency, target specificity, and long-term safety concerns. Future research should focus on the following directions: integrating multi-omics with functional screening to elucidate the regulatory networks of lncRNAs in obesity and its complications; leveraging artificial intelligence to construct predictive models of lncRNA-target gene interactions; developing efficient and safein vivo delivery systems, and optimizing drug design to enhance specificity and safety; establishing highly sensitive detection methods and stable circulating lncRNA biomarkers to enable precise patient stratification and real-time monitoring of therapeutic responses; investigating the synergistic effects of lncRNAs with existing treatments (e.g., GLP-1 receptor agonists, lifestyle interventions) to develop combination therapies and establish a multidimensional, personalized precision medicine framework for obesity. This review aims to provide novel perspectives for understanding the molecular mechanisms underlying obesity and to establish a solid theoretical foundation for developing lncRNA-targeted precision medicine strategies against obesity and its associated metabolic complications.

The blood-brain barrier （BBB） is a physical and biochemical barrier that precisely regulates brain homeostasis and plays a central role in controlling the transport of endogenous and exogenous drugs and related metabolites across the blood-brain interface. These functions of the BBB are mediated by its major components， including brain microvascular endothelial cells （BMECs）， tight junction protein complexes， and influx and efflux transporter proteins. One of the pathological features of ischemic stroke （IS） is BBB disruption， which plays an important role in the development of post-stroke brain injury and subsequent neurological dysfunction. Therefore， given the increasing incidence of IS， there is an urgent need to develop new therapeutic strategies to prevent BBB dysfunction and thereby protect injured brain tissue after IS. This study describes the pathological mechanisms by which BMEC injury after IS leads to BBB dysfunction and elucidates the association between BMECs and IS， including the regulation of apoptosis， autophagy， inflammatory responses， oxidative stress， neurotoxic effects， and cerebral edema. In addition， this article summarizes Chinese herbal medicines that may prevent and treat IS by targeting BMECs. These include monomeric compounds and single herbs such as flavonoids， glycosides， phenols， phthalides， terpenoids， and Styrax. Traditional Chinese medicine （TCM） compound formulas and preparations include oral formulations such as Buyang Huanwu decoction， Sailuotong， Naoxintong capsules， Dandeng Tongnao capsules， and Shexiang Tongxin dropping pills， as well as injectable preparations such as Tongluo Jiunao injection， Xingnaojing injection， Danshen polyphenolic acid for injection， Yiqi Fumai injection， and Shuxuetong injection. This study aims to explore the protective effects of TCM against IS through targeted regulation of BMEC function， providing new insights into the mechanisms of IS and endovascular therapeutic strategies.

OBJECTIVE To explore the effects of Polygala tenuifolia compatibility on toxicity， anti-inflammatory and analgesic efficacy of sand-ironing Strychnos nux-vomica （SS）. METHODS The preparation of SS single decoction， SS-P. tenuifolia core-removed （PC） （1∶2.5） or （1∶5） combined decoction， and SS-PC （1∶5） mixture were carried out to investigate their median lethal dose （LD50）. Using aspirin as positive control， the number of writhing movements， analgesic rate， pain latency， ear swelling degree and inflammation inhibition rate induced by the above-mentioned medicinal liquids in mice were compared. The contents of the active and toxic components， strychnine and brucine， in the above-mentioned medicinal liquids were also determined. RESULTS The LD50 values of SS single decoction， SS-PC （1∶2.5） combined decoction， SS-PC （1∶5） combined decoction and SS- PC （1∶5） mixture were 302.00， 614.47， 1 445.44 and 1 778.28 mg/kg， respectively. Compared with control group， the number of writhing movements and ear swelling degree in the mice of the above-mentioned medicinal liquid groups were reduced or decreased significantly （P＜0.05 or P＜0.01）； pain latency [at 90 and 120 minutes in the SS single decoction group， at 60 and 90 minutes in the SS-PC （1∶2.5） combined decoction group， and at 60，90， 120 minutes in the SS-PC （1∶5） combined decoction group and SS-PC （1∶5） mixture group] was significantly prolonged （P＜0.05 or P＜0.01）； analgesic rates of the respective medicinal liquids were 39.30%， 70.87%， 80.00% and 82.46%， and inflammation inhibition rates were 38.08%，TD 57.89%， 76.47% and 50.46%； analgesic and anti-inflammatory effects of combined decoction and mixture were generally better than those of the single decoction （P＜0.05 or P＜0.01）. In the above-mentioned four medicinal liquids， the total contents of strychnine were 0.71%， 0.42%， 0.47% and 0.64%， and the total contents of brucine were 0.88%， 0.63%， 0.57% and 0.88%， respectively. CONCLUSIONS The combination of P. tenuifolia can reduce the toxicity of SS and enhance its anti-inflammatory and analgesic effects. Moreover， there is a tendency for the toxicity-reducing and efficacy-enhancing effects to increase with the increasing dosage of P. tenuifolia. Additionally， the combined decoction of SS and P. tenuifolia can reduce the contents of the active and toxic components， strychnine and brucine， in SS.