ObjectiveTo explore the mechanism of Sangpi Zhike prescription in treating cough after respiratory syncytial virus （RSV） infection through the "lung-intestine co-treatment" approach using network pharmacology and animal experimental validation. MethodsActive ingredients and targets of Sangpi Zhike prescription were retrieved from the Traditional Chinese Medicine Systems Pharmacology （TCMSP） database. Disease targets were obtained from GeneCards and Online Mendelian Inheritance in Man（OMIM） databases. Protein-protein interaction （PPI） networks and drug-component-target networks were constructed using overlapping targets between drugs and diseases to identify core targets. Gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analyses were performed on the overlapping targets. Sixty mouse models were established： 10 as the normal group， and the remaining mice were infected with RSV via slow nasal drip of RSV suspension， with cough induced using capsaicin solution. After modeling， mice were divided into a model group， a Montelukast Sodium group （1 mg·kg^-1·d^-1）， and low， medium， and high dose groups of Sangpi Zhike prescription （4.875，9.75，and 19.5 g·kg^-1·d^-1）， with 10 mice per group. From day 14 after RSV infection， the normal and model groups received saline via gavage， while other groups received corresponding drug treatments once daily for 5 d. Hematoxylin-eosin（HE） staining was used to observe pathological changes in lung and intestinal tissue. The protein content of extracellular signal-regulated kinase 1/2 （ERK1/2） and phosphorylated （p）-ERK1/2 in the lung and colon tissue of mice was detected by Western blot. Real-time polymerase chain reaction（Real-time PCR） detected ERK1/2 mRNA expression in lung and intestinal tissue. Immunohistochemistry assessed p-MEK1/2， p-ERK1/2， p-c-Fos protein levels， and inflammatory cytokines interleukin（IL）-4 and （TNF）-α in lung and colon tissue. ResultsNetwork pharmacology identified 184 active ingredients and 684 targets in Sangpi Zhike prescription， with 1 344 RSV-related disease targets and 209 overlapping targets. Core targets included TNF， Fos， and Jun. KEGG enrichment revealed 179 pathways， primarily mitogen-activated protein kinase（MAPK）， cancer， TNF， and IL-17 signaling pathways. Animal experiments showed that， compared to those of the normal group， the lung tissue sections of the model group showed typical inflammatory damage， infiltration of inflammatory cells， rupture of alveolar septa， extensive alveolar fusion， and disruption of tight junctions between single-layer columnar epithelial cells in the intestinal tissue. The values of p-ERK1/2 and ERK1/2 in lung and intestinal tissue were significantly increased （P<0.01）， and the expression level of ERK1/2 mRNA was significantly elevated （P<0.01）. The levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α along the ERK pathway were significantly increased （P<0.05， P<0.01）. Compared to the model group， Sangpi Zhike prescription groups showed reduced lung and intestinal inflammation， decreased p-ERK1/2/ERK1/2 ratios （P<0.05，P<0.01）， lower ERK1/2 mRNA levels， and downregulated ERK pathway proteins （P<0.05，P<0.01）. ConclusionSangpi Zhike prescription alleviates cough and intestinal symptoms after RSV infection via the "lung-intestine co-treatment" mechanism by suppressing expression levels of ERK1/2， p-MEK1/2， p-ERK1/2， p-c-Fos， IL-4， and TNF-α on ERK pathway components， thereby mitigating lung and intestinal pathological damage.

ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg^-1， respectively. The metformin hydrochloride group received 0.135 g·kg^-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

Cough variant asthma is a distinct subtype of asthma characterized by chronic irritant dry cough as the sole or predominant clinical manifestation. It is one of the primary causes of chronic cough in children. In traditional Chinese medicine, it belongs to the category of " spasmodic cough", " wind-induced cough", " chronic cough", and " asthmatic cough". At present, Western medicine treatment approaches mainly focus on symptomatic treatment, but fail to fully deal with its complex systemic mechanisms, and have limitations such as poor control of clinical symptoms and rebound exacerbation upon treatment cessation. Based on the theory of " systemic qi stagnation", this paper proposes that the core pathogenesis of cough variant asthma in children is qi stagnation, intermingling of phlegm and blood stasis, and obstruction of collaterals. Disease progression is fundamentally driven by exogenous pathogen activation of endogenous predispositions, particularly dysregulation of sanjiao qi movement, which serves as the primary disease-inducing factor. During the acute phase, the treatment principle focuses on dispelling wind and ventilating lung to restore physiological qi. As the disease progresses to the progressive phase, the focus shifts toward smoothing liver and purging lung to resolve qi counterflow. In the chronic phase, therapeutic strategy prioritizes dissipating phlegm and eliminating blood stasis to smooth collaterals. Finally, during the remission phase, treatment emphasizes strengthening spleen and kidney to consolidate the foundation and cultivate the vitality. This integrative approach synergizes the external elimination of latent pathogens, internal harmonization of qi movement, and dredging collaterals by dispelling blood stasis. It also incorporates the theory of " gentle dispersion to expel pathogens and moistening dryness to harmonize collaterals", aiming to provide a theoretical basis and effective prescriptions for the integrated traditional Chinese and Western medicine treatment of cough variant asthma in children.

Objective: To investigate the value of the Chinese visceral adiposity index (CVAI) in predicting hypertension risk, so as to provide a tool for the early assessment of hypertension risk. Methods: Health examination individuals aged ≥18 years were selected from four medical institutes in Jinhua City, Zhejiang Province in 2022. Data on basic information, lifestyle, disease history, body mass index, waist circumference, blood pressure, and blood biochemical indicators were collected through questionnaire surveys and physical examinations. CVAI was calculated to assess levels of visceral fat accumulation, divided by quartiles into Q1, Q2, Q3, and Q4 groups. The relationship between CVAI and hypertension was analyzed using a multivariable logistic regression model, and their dose-response relationship was examined using a restricted cubic spline model. The value of CVAI in predicting hypertension risk was evaluated using receiver operating characteristic (ROC) curve. Results: A total of 23 791 individuals were enrolled, with a median age of 68.00 (interquartile range, 14.00) years. Among them, 10 178 (42.78%) were males and 13 613 (57.22%) were females. The median CVAI was 111.40 (interquartile range, 48.23). Hypertension was identified in 15 563 cases, with a prevalence of 65.42%. After adjusting for lifestyle, disease history, and blood biochemical indicators, the multivariable logistic regression analysis revealed that hypertension risk in the CVAI Q2, Q3, and Q4 groups were 2.012 (95%CI: 1.865-2.170), 3.059 (95%CI: 2.826-3.311), and 5.099 (95%CI: 4.672-5.565) times that of the Q1 group, respectively. The restricted cubic spline model revealed a non-linear relationship between CVAI and hypertension risk (Pnon linearity<0.05). Hypertension risk increased more rapidly when the CVAI was ≥81.03. The area under the ROC curve for CVAI in predicting hypertension risk was 0.691, with an optimal cutoff value of 106.01, which falls within the Q2 group. Conclusions There was a nonlinear dose-response relationship between CVAI and hypertension. CVAI can predict the risk of hypertension, and 106.01 can serve as an early warning threshold for risk screening.

OBJECTIVE: To observe the clinical efficacy of Qihuang needle therapy for autism spectrum disorder (ASD) children with sleep disorder. METHODS: A total of 60 ASD children with sleep disorder were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with structured education intervention, 60 min each time, once a day, 6 times a week. Qihuang needle therapy was applied at Yintang (GV24⁺), Baihui (GV20) and bilateral Jueyinshu (BL14), Xinshu (BL15) in the observation group, multi-direction needling was delivered and without needle retaining. The treatment was given 2 times a week, each treatment was delivered at interval of 2 days at least. Behavioral intervention was adopted in the control group. Treatment for consecutive 12 weeks was required in both groups. Before and after treatment, the scores of children's sleep habits questionnaire (CSHQ), the autism behavior checklist (ABC), the childhood autism rating scale (CARS), and the childhood autism behavior scale (CABS) were observed in the two groups. RESULTS: After treatment, the scores of CSHQ, ABC, CARS and CABS were decreased compared with those before treatment (P<0.01), and the above scores in the observation group were lower than those in the control group (P<0.05). CONCLUSION Qihuang needle therapy can effectively treat ASD with sleep disorder, improve the core symptoms of ASD and the sleep quality.
Humans ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child ; Sleep Wake Disorders/physiopathology* ; Child, Preschool ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Sleep ; Needles

The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans ; Drug Resistance, Neoplasm/drug effects* ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Mutation/genetics* ; Neoplasms/genetics* ; Antineoplastic Agents/therapeutic use*

Objective:To investigate the protective effects and underlying mechanisms of carbon monoxide-releasing molecule-3 (CORM-3) against hypoxia-reoxygenation-induced injury in Caco-2 cells.Methods:A hypoxia-reoxygenation injury model was established in Caco-2 cell monolayers by culturing cells under glucose-free, serum-free hypoxic conditions (1% O 2) for 8 hours, followed by reoxygenation with glucose and serum restoration for 4 hours. Experimental groups included: blank control (Control), hypoxia-reoxygenation model (HR), and HR with 300 μmol/L (HR_C1), 400 μmol/L (HR_C2), or 500 μmol/L CORM-3 (HR_C3), plus HR with 500 μmol/L inactive iCORM-3 (HR_iC). CORM-3/iCORM-3 was administered during the hypoxic phase. Assessments included: cell viability (CCK-8 assay), apoptosis/necrosis rates (flow cytometry), monolayer permeability (sodium fluorescein), tight junction protein distribution (ZO-1, Occludin, Claudin2 immunofluorescence), protein expression (Western blot), and transcriptomic analysis of differentially expressed genes. Results:Compared to controls, HR group showed significantly reduced cell viability ( P<0.05), increased apoptosis/necrosis rates, elevated sodium fluorescein permeability (both P<0.05), disrupted tight junction structure, decreased Occludin and increased Claudin2 expression (both P<0.05). CORM-3 treatment significantly improved viability ( P<0.05), reduced apoptosis/necrosis rates and permeability (both P<0.05, concentration-dependent), mitigated tight junction damage, showed a non-significant trend toward increased Occludin, and significantly decreased Claudin2 expression ( P<0.05). Transcriptomics identified 25 differentially expressed genes, with KEGG analysis revealing 14 significant pathways (including MAPK signaling, inflammatory bowel disease, and cellular senescence). GO analysis highlighted immune-inflammatory responses and cell membrane barrier components, with TGFB3 as the primary immune-related gene. Conclusions:CORM-3 effectively reduces apoptosis/necrosis, preserves tight junctions, and mitigates hypoxia-reoxygenation injury in Caco-2 cells, potentially through MAPK signaling regulation and immune-inflammatory response modulation.

Cough variant asthma is a distinct subtype of asthma characterized by chronic irritant dry cough as the sole or predominant clinical manifestation.It is one of the primary causes of chronic cough in children.In traditional Chinese medicine,it belongs to the category of"spasmodic cough","wind-induced cough","chronic cough",and"asthmatic cough".At present,Western medicine treatment approaches mainly focus on symptomatic treatment,but fail to fully deal with its complex systemic mechanisms,and have limitations such as poor control of clinical symptoms and rebound exacerbation upon treatment cessation.Based on the theory of"systemic qi stagnation",this paper proposes that the core pathogenesis of cough variant asthma in children is qi stagnation,intermingling of phlegm and blood stasis,and obstruction of collaterals.Disease progression is fundamentally driven by exogenous pathogen activation of endogenous predispositions,particularly dysregulation of sanjiao qi movement,which serves as the primary disease-inducing factor.During the acute phase,the treatment principle focuses on dispelling wind and ventilating lung to restore physiological qi.As the disease progresses to the progressive phase,the focus shifts toward smoothing liver and purging lung to resolve qi counterflow.In the chronic phase,therapeutic strategy prioritizes dissipating phlegm and eliminating blood stasis to smooth collaterals.Finally,during the remission phase,treatment emphasizes strengthening spleen and kidney to consolidate the foundation and cultivate the vitality.This integrative approach synergizes the external elimination of latent pathogens,internal harmonization of qi movement,and dredging collaterals by dispelling blood stasis.It also incorporates the theory of"gentle dispersion to expel pathogens and moistening dryness to harmonize collaterals",aiming to provide a theoretical basis and effective prescriptions for the integrated traditional Chinese and Western medicine treatment of cough variant asthma in children.