OBJECTIVE To predict and validate the mechanisms of Chaiqi yigan granules （CQYG） improving hepatocellular carcinoma （HCC）. METHODS The signaling pathways of CQYG intervention in HCC were predicted using network pharmacology. A mice model of transplanted hepatocellular carcinoma was established by injecting H22 hepatoma cells into the axilla. Successfully modeled mice were randomly divided into model group （normal saline）， sorafenib group （positive control， 50 mg/kg）， and CQYG low-， medium- and high-dose groups （24.83， 49.66， 99.32 g/kg）， with 10 mice in each group. Mice in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， for 14 consecutive days. After last administration， pathological morphological changes in the tumor tissues of mice were observed in each group. Immunohistochemical staining was performed to detect the expression of the nuclear proliferation antigen Ki-67 in tumor tissues of mice. Western blot assay was used to measure the expression of proteins related to epithelial-mesenchymal transition （EMT） [N-cadherin， E-cadherin， Vimentin， matrix metalloproteinase 7 （MMP7）] and the mitogen-activated protein kinase （MAPK） signaling pathway [p38 MAPK， phosphorylated p38 MAPK， c-Jun N-terminal kinase （JNK）， phosphorylated JNK， extracellular regulated protein kinase 1/2 （ERK1/2）， phosphorylated ERK1/2] in tumor tissue of mice. RESULTS Network pharmacology analysis revealed that metabolic pathways， pathways in cancer， and the MAPK signaling pathway were key signaling pathways through which CQYG exert their anti-hepatocellular carcinoma effects. In animal experiments， the tumor tissues of mice in the model group exhibited dense tumor cells and vigorous growth. Compared with model group， CQYG high-dose group showed a decreased density of tumor cells in the tumor tissues of mice. Moreover， the expression levels of Ki-67， N-cadherin， MMP7 and Vimentin proteins， along with the phosphorylation levels of ERK1/2 and JNK proteins， were all significantly reduced （ P ＜0.05）. The expression level of E-cadherin protein was significantly increased （ P ＜0.05）， the phosphorylation level of p38 MAPK protein was increased， the difference was not statistically significant （ P ＞0.05）. CONCLUSIONS CQYG can inhibit EMT by regulating the MAPK signaling pathway， thereby suppressing tumor cell invasion and metastasis and ultimately exerting a therapeutic effect in improving HCC.

ObjectiveTo investigate the effect and mechanism of Shuangshen Ningxin capsules （SSNX） in regulating the nuclear factor-κB （NF-κB） and mitogen-activated protein kinase （MAPK） pathways to inhibit inflammation and alleviate myocardial ischemia-reperfusion injury （MIRI） in rats. MethodsThe 45 healthy male Sprague-Dawley （SD） rats were divided into sham operation group， model group， and SSNX capsules group （90 mg·kg^-1）. The left anterior descending coronary artery was ligated to establish the MIRI model. Cardiac function was evaluated by echocardiography， and microvascular reperfusion was analyzed using contrast echocardiography. Myocardial inflammation and injury were assessed by hematoxylin and eosin （HE） staining， immunohistochemistry， and TdT-mediated dUTP nick end labeling （TUNEL）. The expression levels of cardiac inflammatory cytokines， including interleukin-1α （IL-1α）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Core differentially expressed genes （DEGs） and enriched pathways were screened by transcriptome sequencing. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to verify the mRNA expression of Toll-like receptor 2 （TLR2）， chemokine （C-X-C motif） ligand 1 （CXCL1） and prostaglandin-endoperoxide synthase 2 （PTGS2）， as well as the protein expression of Caspase-3， cleaved Caspase-3， p-NF-κB/NF-κB， phosphorylated extracellular signal-regulated kinase 1/2 （p-ERK1/2/ERK1/2） and p-p38 MAPK/p38 MAPK. ResultsCompared with the sham operation group， the ejection fraction （EF）， fractional shortening （FS）， stroke volume （SV） and cardiac output （CO） of the model group were significantly decreased （P<0.01）， the peak time of myocardial perfusion was prolonged （P<0.01）， hypoxia-inducible factor （HIF）-1α and α-smooth muscle actin （SMA） expression increased （P<0.01）， the concentrations of inflammatory factors IL-1α， IL-6， TNF-α， TLR2， CXCL1 and PTGS2 increased （P<0.01）， and the expression of cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins was significantly increased （P<0.01）. SSNX could improve cardiac function （P<0.05， P<0.01）， and significantly shorten the peak time of myocardial perfusion （P<0.01）. Moreover， it could also down-regulate HIF-1α and a-SMA expression （P<0.05， P<0.01）， and reduce the concentrations of IL-1α， IL-6， TNF-α （P<0.01）， and the mRNA expression of TLR2， CXCL1 and PTGS2 （P<0.01）. Additionally， SSNX inhibited the apoptosis rate （P<0.01） and significantly reduced the expression of Cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins （P<0.01）. ConclusionSSNX can alleviate cardiac inflammation by regulating the NF-κB and MAPK signaling pathways， thereby effectively preventing and alleviating myocardial reperfusion injury.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic

OBJECTIVE: The results of limited studies on the relationship between environmental pollution and dementia have been contradictory. We analyzed the combined effects of PM _2.5 and smoking on the prevalence of dementia and cognitive impairment in an elderly community-dwelling Chinese population. METHODS: We assessed 24,117 individuals along with the annual average PM _2.5 concentrations from 2012 to 2016. Dementia was confirmed in the baseline survey at a qualified clinical facility, and newly suspected dementia was assessed in 2017, after excluding cases of suspected dementia in 2015. National census data were used to weight the sample data to reflect the entire population in China, with multiple logistic regression performed to analyze the combined effects of PM _2.5 and smoking frequency on dementia and cognitive impairment. RESULTS: Individuals exposed to the highest PM _2.5 concentration and smoked daily were at higher risk of dementia than those in the lowest PM _2.5 concentration group ( OR, 1.603; 95% CI [1.626-1.635], P < 0.0001) and in the nonsmoking group ( OR, 1.248; 95% CI [1.244-1.252]; P < 0.0001). Moderate PM _2.5 exposure and occasional smoking together increased the short-term risk of cognitive impairment. High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia, so more efforts are needed to reduce this risk through environmental protection and antismoking campaigns. CONCLUSION High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia. Lowering the ambient PM _2.5, and smoking cessation are recommended to promote health.
Humans ; Dementia/etiology* ; Male ; Aged ; Female ; Cognitive Dysfunction/etiology* ; China/epidemiology* ; Particulate Matter/analysis* ; Smoking/epidemiology* ; Air Pollutants/analysis* ; Aged, 80 and over ; Environmental Exposure/adverse effects* ; Prevalence ; Middle Aged

OBJECTIVES: This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival. METHODS: An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival. RESULTS: Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival. CONCLUSIONS FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology* ; Transcriptome ; Metabolomics ; Foam Cells/microbiology* ; Humans ; Metabolome ; Tuberculosis/microbiology* ; Gene Expression Profiling

Objective:To investigate the impact of ginseng alcohol extract(GEE)on improving sleep quality in the aged Drosophila model by regulating the redox balance,and to elucidate its associated mechanism.Methods:Thirty-two male drosophila melanogaster(7-days-old)were randomly selected as young group,while 64 male Drosophila melanogaster flies(35-days-old)were randomly assigned to aged model group(n=32)and GEE group(n=32).The sleep parameters,including total sleep duration,daytime sleep duration,night sleep duration,0-4 h of sleep duration after lights off(ZT0-4 sleep duration),deep sleep duration,sleep episodetimes,sleep fragmentation,and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after administration.The grouping of the drosophila was as above,and there were 100 drosophila ineach group.The differentially expressed proteins in drosophila brain tissue were screened,identified,and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF/TOF-MS)proteomic methods.The grouping of the drosophila was as above,and there were 100 drosophila in each group.The activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the levels of lipid peroxidation product(MDA)in brain tissue of the drosophila were determined using assay kits.Results:Compared with young group,the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased(P<0.05 or P<0.01);and the sleep rhythm amplitude was shortened.Compared with aged group,the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened(P<0.01).Compared with young group,the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the sleep rhythm amplitude was shortened.Compared with young group,the ZT0-4 sleep duration,deep sleep duration,and single sleep fragment of the drosphila in GEE group were significantly prolonged(P<0.01),and the sleep amplitude was increased.Compared with young group,there was no significant difference in diurnal spontaneous activity or total spontaneous activity of the drosophila in aged group(P>0.05),while the nocturnal spontaneous activity was significantly increased(P<0.05).Compared with aged group,the diurnal spontaneous activity,nocturnal spontaneous activity,and total spontaneous activity of the drosophila in GEE group were significantly decreased(P<0.05 or P<0.01).A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping.Compared with young group,the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase,peroxiredoxin 1 and dihydrolipoic dehydrogenase,which were related to redox balance.Compared with young group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the level of MDA was increased(P<0.01);compared with aged group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased(P<0.05 or P<0.01),and the MDA level was decreased(P<0.05).Conclusion:GEE has improvement effect on the sleep quality of aged drosophila,and its possible mechanism may be related to upregulating the activities of antioxidant enzymes,inhibiting the accumulation of lipid peroxidation products,and maintaining redox balance.

Radiation prevention and treatment drugs are a rapidly developing field.Radiation prevention and treatment drugs can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds,which are widely used in medical,scientific research and other fields.This paper reviews the classification of radiation prevention and treatment drugs,which can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds.At the same time,its mechanism of action and clinical application are elaborated in detail,and the risk assessment is carried out from the aspects of effectiveness,safety and drug interaction.Finally,the risk reduction strategies are summarized from the aspects of clinical medication specification and monitoring,continuous drug safety research,improvement of emergency reserve and support capacity and construction of full-cycle regulatory system,so as to provide reference for the rational application and further research of radiation prevention and treatment drugs.

Objective:To evaluate the clinical outcomes of patients with paroxysmal sympathetic hyperactivity (PSH) after moderate to severe brain injury.Methods:Clinical data describing 580 patients of the Rehabilitation Center of Fuxing Hospital with moderate to severe brain injury were analyzed retrospectively. They were divided into a PSH group and a non-PSH group depending on whether PSH attacks occurred. Propensity score matching was performed to create a 1∶1 ratio between the two groups. The patients′ baseline characteristics were analyzed before the matching and with the matched cohorts, and the clinical outcomes of the patients in the matched cohorts were compared.Results:Seventy-five of the patients experienced PSH attacks and were included in the PSH group, while the others formed the non-PSH group. Before matching, the two groups had significant differences in age, atrial fibrillation, hypertension, chest trauma, Glasgow Coma Scale (GCS) score, tracheotomy, hydrocephalus, heart rate at admission, respiration rate, muscle tone, and limited joint activity. After the propensity score matching, 67 patients were included in the PSH and non-PSH groups. The differences in heart rate, respiration rate, muscle tone, and limited joint activity between the two groups at admission were then statistically significant. However, unlike the non-PSH group, the PSH group showed a significant decrease in its average GCS score and Glasgow Outcome Scale (GOS) score at discharge, as well as a significant increase in its average Disability Rating Scale score. Compared with the non-PSH group at the same time point, the GOS score of the PSH group had decreased by 0.47 at discharge ( CI: 0.41-0.56). Then, three months after discharge the average GOS score of the PSH group had decreased by 0.55 ( CI: 0.48-0.61. By six months that was 0.75 ( CI: 0.66-0.82) and by twelve months 0.87 ( CI: 0.77-0.97). Conclusions:PSH can affect the consciousness of patients with moderate to severe brain injury and their ability in the activities of daily life. The prognosis of PSH patients is relatively poor.

Objective:To explore the advantages of internet-based smart healthcare for full-cycle transcatheter edge-to-edge repair (TEER) management in reducing postoperative adverse events rate, improving cardiac function, and enhancing quality of life.Methods:This retrospective study enrolled patients with mitral regurgitation who underwent transcatheter TEER at Beijing Anzhen Hospital Valve Intervention Center between June 2021 and September 2023. Patients were classified into degeneration mitral regurgitation (DMR) and functional mitral regurgitation (FMR) according to etiology, with further stratification by enrollment period into usual care group (June 2021 to October 2022) and full-cycle management group (November 2022 to September 2023). The 1-year postoperative follow-up data were collected and compared between subgroups with the same etiology. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the differences in major endpoint event-free survival rates between the two groups. Univariate and multivariate Cox regression and logistic regression analyses were performed to evaluate the impact of the full-cycle management system on patients′ outcomes.Results:A total of 130 patients were included, aged (72.0±8.6) years, including 82 (63%) males. DMR was identified in 84 cases (40 in the usual care group and 44 in the full-cycle management group), while FMR was observed in 46 cases (27 in the usual care group and 19 in the full-cycle management group). Kaplan-Meier analysis demonstrated higher 1-year major endpoint event-free survival rates in the full-cycle management group compared to the usual care group, though the difference was not statistically significant (log-rank P>0.05). Compared to the usual care group, the full-cycle management group showed significantly higher proportions of New York Heart Association classification Ⅰ-Ⅱ patients (DMR: 67% vs. 52%, P=0.031; FMR: 68% vs. 52%, P=0.021), greater 6-minute walking distances (DMR: (346.39±70.41) m vs. (294.11±60.47) m, P=0.012; FMR: (356.60±54.68) m vs. (318.55±39.02) m, P=0.004), and superior Kansas City Cardiomyopathy Questionnaire scores (DMR: 81.50 (74.50, 85.00) points vs. 71.00 (66.00, 82.25) points, P=0.014; FMR: 83.00 (76.00, 85.00) points vs. 74.00 (70.75, 80.00) points, P=0.030). Multivariate logistic regression confirmed the full-cycle management system as an independent predictor for the above improved outcomes (all P<0.05). Conclusion:Smart healthcare-based full-cycle management improves cardiac function and quality of life in mitral regurgitation patients after TEER, demonstrating lower rates of major endpoint events compared to usual care.