1.Quercetin Ameliorates Gouty Arthritis in Rats via ROS/NLRP3/IL-1β Signaling Pathway
Baowei FENG ; Yan WANG ; Chang LI ; Yujing ZHANG ; Dingxing FAN ; Xin LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):145-153
ObjectiveTo investigate the effect of quercetin on acute gouty arthritis (GA) in rats by inhibiting the reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) signaling pathway. MethodsSixty SPF-grade male SD rats were randomized into normal, model, colchicine (0.3 mg·kg-1), and low-, medium-, and high-dose (25, 50, 100 mg·kg-1, respectively) quercetin groups (n=10). The rats in the dosing groups were administrated with the corresponding drugs (10 mL·kg-1) by gavage once a day for one week. An equal volume of normal saline was given by gavage to rats in normal and model groups. One hour after drug administration on day 5, an acute GA model was established in other groups except the control group via intra-articular injection of monosodium urate (MSU) suspension into the right posterior ankle joint cavity. The joint swelling and gait were scored at the time points of 6, 12, 24, 48 h after modeling. Histopathological alterations in the ankle joint tissue from each group were assessed by hematoxylin-eosin (HE) staining. Malondialdehyde (MDA), xanthine oxidase (XOD), and total superoxide dismutase (T-SOD) assay kits were used to assess the levels of MDA, XOD, and T-SOD in the serum. The levels of tumor interleukin-6 (IL-6), necrosis factor-α (TNF-α), and IL-1β in the rat serum, as well as ROS in the ankle joint tissue, were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to determine the protein levels of NLRP3, thioredoxin-interacting protein (TXNIP), apoptosis-associated speck-like protein containing a CARD domain (ASC), precursor cysteinyl aspartate-specific proteinase-1 (pro-Caspase-1), cleaved Caspase-1 (Caspase-1 p20), and IL-1β in the ankle joint tissue. Real-time PCR was employed to assess the mRNA levels of TXNIP, NLRP3, ASC, IL-1β, and TNF-α in the ankle joint tissue. ResultsCompared with the normal group, the model group exhibited decreased spontaneous activity, mental fatigue, increased ankle joint swelling and gait scores (P<0.01), aggravated synovial tissue edema and inflammatory cell infiltration (P<0.01), elevated levels of XOD, MDA, TNF-α, IL-1β, and IL-6 in the serum and ROS in the joint tissue (P<0.01), a declined level of T-SOD (P<0.01), up-regulated protein levels of NLRP3, TXNIP, ASC, pro-Caspase-1, Caspase-1 p20, and IL-1β in the ankle joint tissue (P<0.01), and up-regulated mRNA levels of NLRP3, TXNIP, ASC, IL-1β, and TNF-α in the ankle joint tissue (P<0.01). Compared with the model group, the medium- and high-dose quercetin groups showed improved general conditions, decreased gait scores (P<0.05, P<0.01), reduced joint swelling (P<0.01), alleviated synovial tissue edema and inflammatory cell infiltration (P<0.05, P<0.01), lowered levels of XOD, MDA, TNF-α, IL-1β, and IL-6 in the serum and ROS in the joint tissue (P<0.01), increased levels of T-SOD (P<0.01), down-regulated protein levels of TXNIP, NLRP3, ASC, pro-Caspase-1, Caspase-1 p20, and IL-1β in the ankle joint tissue (P<0.05, P<0.01), and down-regulated mRNA levels of TXNIP, NLRP3, ASC, IL-1β, and TNF-α in the ankle joint tissue (P<0.01). Low-dose quercetin also ameliorated some of the above parameters (P<0.05, P<0.01). ConclusionQuercetin exerts anti-GA effects by blocking the ROS/NLRP3/IL-1β signaling pathway, downregulating NLRP3 inflammasome activation, and inhibiting the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6.
2.Sanren Runchang Formula Regulates Brain-gut Axis to Treat IBS-C: A Randomized Controlled Trial
Teng LI ; Xinrong FAN ; He YAN ; Zhuozhi GONG ; Mengxi YAO ; Na YANG ; Yuhan WANG ; Huikai HU ; Wei WEI ; Tao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):154-161
ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome (IBS-C) by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), and substance P (SP). MethodsA randomized controlled design was adopted, and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups (36 cases).The observation group received Sanren Runchang formula granules twice daily, and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale (IBS-SSS), IBS Quality of Life Scale (IBS-QOL), and Bristol Stool Form Scale (BSFS) were used to assess clinical symptoms, and bowel movement frequency was recorded. The Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT, VIP, and SP. ResultsThe total response rate in the observation group was 91.67% (33/36), which was higher than that (77.78%, 28/36) in the control group (χ2=4.50, P<0.05). After treatment, both groups showed increased defecation frequency and BSFS scores, decreased IBS-SSS total score, abdominal pain and bloating scores, IBS-QOL health anxiety, anxiety, food avoidance, and behavioral disorders scores, SAS and SDS scores, serum 5-HT and VIP levels, and increased SP levels (P<0.05, P<0.01). Moreover, the observation group showed more significant changes in the indicators above than the control group (P<0.05, P<0.01). The SP level showed no significant difference between the two groups. During the 4-week follow-up, the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group, and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients, with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP, suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However, its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.
3.Mechanisms of Sini San in Regulation of Gut Microbiota Against Depression and Liver Injury in CUMS Rats
Junling LI ; Yan ZHANG ; Lei WANG ; Fang QI ; Zhenzhen CHEN ; Tianxing CHEN ; Yuhang LIU ; Xueying WANG ; Xianwen TANG ; Yubo LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):33-40
ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley (SD) rats were randomly divided into a normal group, model group (M), Sini San group (MS, 2.5 g·kg-1), and fluoxetine group (MF, 2 mg·kg-1). Except for the normal group, rats in the other three groups were subjected to chronic unpredictable mild stress (CUMS). After 8 weeks, the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing factor (CRF), lipopolysaccharide (LPS), Zonulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex, and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy, and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group, the sucrose preference of rats in the model group was significantly reduced (P0.01), whereas it was significantly increased in the Sini San group compared with the model group (P0.05). Compared with the normal group, hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased (P0.05), and compared with the model group, both were significantly increased in the Sini San group (P0.05, P0.01). Compared with the normal group, serum LPS and Zonulin levels in the model group were significantly increased (P0.05, P0.01), and compared with the model group, Zonulin levels in the Sini San group were significantly decreased (P0.05). No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group, widened and blurred tight junctions, sparse and shortened microvilli, and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group, which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators, liver function, and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.
4.Mechanisms of Sini San in Regulation of Gut Microbiota Against Depression and Liver Injury in CUMS Rats
Junling LI ; Yan ZHANG ; Lei WANG ; Fang QI ; Zhenzhen CHEN ; Tianxing CHEN ; Yuhang LIU ; Xueying WANG ; Xianwen TANG ; Yubo LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):33-40
ObjectiveTo explore the efficacy and mechanisms of Sini San in the treatment of depression and liver injury based on gut microbiota. MethodsThirty-two male Sprague-Dawley (SD) rats were randomly divided into a normal group, model group (M), Sini San group (MS, 2.5 g·kg-1), and fluoxetine group (MF, 2 mg·kg-1). Except for the normal group, rats in the other three groups were subjected to chronic unpredictable mild stress (CUMS). After 8 weeks, the open-field test and sucrose preference test were conducted. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing factor (CRF), lipopolysaccharide (LPS), Zonulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex, and brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect hippocampal BDNF mRNA expression. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using the ultraviolet lactate dehydrogenase method. The ultrastructure of the intestinal epithelium was observed by electron microscopy, and gut microbiota in rat feces were analyzed using 16S rDNA high-throughput sequencing. ResultsCompared with the normal group, the sucrose preference of rats in the model group was significantly reduced (P<0.01), whereas it was significantly increased in the Sini San group compared with the model group (P<0.05). Compared with the normal group, hippocampal GABA protein levels and BDNF mRNA expression in the model group were significantly decreased (P<0.05), and compared with the model group, both were significantly increased in the Sini San group (P<0.05, P<0.01). Compared with the normal group, serum LPS and Zonulin levels in the model group were significantly increased (P<0.05, P<0.01), and compared with the model group, Zonulin levels in the Sini San group were significantly decreased (P<0.05). No obvious changes were observed in the ultrastructure of the jejunal mucosa among groups. Compared with the normal group, widened and blurred tight junctions, sparse and shortened microvilli, and mitochondrial swelling with cristae disruption in epithelial cells were observed in the ileal and colonic mucosa of the model group, which were markedly improved in the Sini San and fluoxetine groups. The results of 16S rDNA high-throughput sequencing showed that Sini San improved CUMS-induced dysbiosis of Bacteroidetes and Proteobacteria. Correlation analysis indicated that Bacteroidetes and Proteobacteria were significantly correlated with depression-related indicators, liver function, and intestinal mucosal permeability. ConclusionSini San exerts antidepressant and hepatoprotective effects by improving Bacteroidetes and Proteobacteria and inhibiting the increase in intestinal mucosal permeability in CUMS rats.
5.Effects and mechanism of curcumin on neurological injury in neonatal rats with bacterial meningitis
Yueyun LI ; Yanrui WANG ; Yan FU
China Pharmacy 2026;37(1):17-23
OBJECTIVE To investigate the effects and potential mechanism of curcumin on neurological injury in neonatal rats with bacterial meningitis based on the signal transducer and activator of transcription 1( STAT1)/ nucleotide-binding domain leucine- rich repeat and pyrin domain-containing receptor 3 (NLRP3) signaling pathway. METHODS Neonatal rats, with an equal number of males and females, were randomly divided into control group, model group, curcumin low-dose (Cur-L), medium-dose (Cur- M) and high-dose (Cur-H) groups, and Cur-H+STAT1 transcription enhancer [2-(1,8-naphthyridin-2-yl)phenol] group (Cur-H+2- NP group), with 15 rats in each group. Except for the control group, rats in other groups were injected with a suspension of group B Streptococcus (1×104 cfu/mL, 10 μL) into the cerebellomedullary cistern to establish a bacterial meningitis model. After successful model establishment, rats in Cur-L, Cur-M and Cur-H groups were intraperitoneally injected with 1.25, 2.5 and 5 mg/kg curcumin, respectively, and those in the Cur-H+2-NP group were intraperitoneally injected with 5 mg/kg curcumin and 0.5 mg/kg 2- NP, once a day, for 3 consecutive weeks. After the last administration, modified Loeffler score was conducted, white blood cells (WBC) count in cerebrospinal fluid as well as the contents of inflammatory factors [tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β and IL-18], brain water content and blood-brain barrier permeability were detected; the histopathological changes of hippocampus and cortex tissues were observed. The percentage of apoptosis in hippocampal/cortical tissue cells, the positive expression of ionized calcium-binding adapter molecule-1 (Iba-1), the co-localization of Iba-1 and NLRP3, as well as the expressions of proteins related to the STAT1/NLRP3 signaling pathway (phosphorylated STAT1, NLRP3, apoptosis-associated speck-like protein containing a CARD, gasdermin D, caspase-1, IL-1β and IL-18) were examined. RESULTS Compared with the control group, the neurons in the hippocampal/cortical tissues of rats in the model group exhibited significant morphological abnormalities, accompanied by neuronal edema and necrosis, as well as infiltration of inflammatory cells. The modified Loeffler score and the number of Nissl bodies were significantly decreased/reduced in the model group, while the WBC count, levels of inflammatory factors, brain water content, blood-brain barrier permeability, HE staining score, number of degenerated neurons, percentage of apoptotic cells, positive expression of Iba-1, percentage of Iba-1 and NLRP3 co-localization- positive cells, and expressions of pathway-related proteins were all significantly rose/increased/upregulated (P<0.05). Compared with the model group, the histopathological changes in the hippocampal/cortical tissues of rats in all curcumin dosage groups were alleviated to varying degrees, with significant improvements in all quantitative indicators (P<0.05); conversely, 2-NP significantly reversed the ameliorative effects of curcumin on these quantitative indicators (P<0.05). CONCLUSIONS Curcumin can alleviate cerebral edema and blood-brain barrier damage, reduce neuroinflammation, inhibit cell apoptosis and pyroptosis, and thereby alleviate neuronal injury in neonatal rats with bacterial meningitis. The underlying mechanism may be related to the inhibition of the STAT1/NLRP3 signaling pathway.
6.Active Ingredients of Traditional Chinese Medicine Regulate Ferroptosis to Inhibit Breast Cancer: A Review
Yan LIU ; Zhenyao YANG ; Chengzhi WANG ; Jiuxian LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):299-306
Breast cancer (BC), a common malignant tumor in women, is characterized by high incidence and mortality rates, posing a serious threat to women's life and health. Currently, the commonly used treatments for BC include surgery, radiotherapy, chemotherapy, molecular targeted therapy, and endocrine therapy. Although radiotherapy and chemotherapy can effectively kill tumor cells and inhibit the proliferation and differentiation of tumor cells, they can induce adverse reactions such as hematopoietic dysfunction and impaired immune function. The other treatment methods also have problems such as drug resistance, high recurrence rates, reduced quality of life, and poor clinical efficacy. Therefore, it is urgent to explore new drugs with better efficacy and lower toxicity. Ferroptosis is a form of iron-dependent, non-apoptotic programmed cell death triggered by lipid peroxidation. In recent years, ferroptosis has become a hot topic in the field of cancer treatment and has been gradually proven to effectively inhibit the proliferation and metastasis of BC cells, reduce the drug resistance of BC to chemotherapy drugs, and enhance the sensitivity of BC to radiotherapy. Traditional Chinese medicine (TCM), with multiple components, multiple targets, and mild side effects, is widely used in the treatment of BC. A large number of studies have shown that active ingredients of TCM, such as saponins, flavonoids, terpenoids, phenols, and polysaccharides, can inhibit the proliferation and metastasis of BC cells by modulating ferroptosis-related pathways. These include iron metabolism, lipid metabolism, cystine/glutamate antiporter system Xc-/glutathione/glutathione peroxidase 4, Specifically, these ingredients elevate the levels of lipid peroxidation, reactive oxygen species, malondialdehyde, and Fe2+ in BC cells, thereby inducing ferroptosis-mediated suppression of tumor progression. This article reviews the relevant literature at home and abroad in recent years, summarizes the mechanisms of ferroptosis in regulating BC and the research progress in the active components of TCM targeting ferroptosis in the intervention of BC, aiming to provide ideas for the development of new drugs for the treatment of BC.
7.Explainable Machine Learning Model for Predicting Prognosis in Patients with Malignant Tumors Complicated by Acute Respiratory Failure: Based on the eICU Collaborative Research Database in the United States
Zihan NAN ; Linan HAN ; Suwei LI ; Ziyi ZHU ; Qinqin ZHU ; Yan DUAN ; Xiaoting WANG ; Lixia LIU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):98-108
To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework. Clinical data of patients with malignant tumors and ARF were extracted from the eICU Collaborative Research Database in the United States, including demographic characteristics, comorbidities, vital signs, laboratory test indicators, and major interventions within the first 24 hours after ICU admission.The study outcome was ICU death.Enrolled patients were randomly divided into a training set and a validation set at a ratio of 7:3.Predictor variables were selected using least absolute shrinkage and selection operator (LASSO) regression.Five machine learning algorithms-extreme gradient boosting (XGBoost), support vector machine (SVM), Logistic regression, multilayer perceptron (MLP), and C5.0 Decision Tree-were employed to construct predictive models.Model performance was evaluated based on the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and other metrics.The optimal model was further interpreted using the Shapley additive explanations (SHAP) algorithm. A total of 3196 patients with malignant tumors complicated by ARF were included.The training set comprised 2, 261 patients and the validation set 935 patients; 683 patients died during ICU stay, while 2513 survived.LASSO regression ultimately selected 12 variables closely associated with patient ICU outcomes, including sepsis comorbidity, use of vasoactive drugs, and within the first 24 hours after ICU admission: minimum mean arterial pressure, maximum heart rate, maximum respiratory rate, minimum oxygen saturation, minimum serum bicarbonate, minimum blood urea nitrogen, maximum white blood cell count, maximum mean corpuscular volume, maximum serum potassium, and maximum blood glucose.After model evaluation, the XGBoost model demonstrated the best performance.The AUCs for predicting ICU mortality risk in the training and validation sets were 0.940 and 0.763, respectively; accuracy was 88.3% and 81.2%;sensitivity was 98.5% and 95.9%.Its predictive performance also remained optimal in sensitivity analyses.SHAP analysis indicated that the top five variables contributing to the model's predictions were minimum oxygen saturation, minimum serum bicarbonate, minimum mean arterial pressure, use of vasoactive drugs, and maximum white blood cell count. This study successfully developed a mortality risk prediction model for ICU patients with malignant tumors complicated by ARF based on a large-scale dataset and performed explainability analysis.The model aids clinicians in early identification of high-risk patients and implementing individualized interventions.
8.Five-year survival analysis and influencing factors of elderly lung cancer patients with chronic obstructive pulmonary disease in Mianyang City
Haishi XUE ; Ling HUANG ; Junjie XIA ; Yu QIU ; Ke GE ; Jincheng WANG ; Yuting CHEN ; Runjiao CHEN ; Lingna LI ; An LAN ; Yan HOU
Journal of Public Health and Preventive Medicine 2026;37(1):138-141
Objective To study the five-year survival status and influencing factors of elderly patients with lung cancer complicated with chronic obstructive pulmonary disease (COPD). Methods A cohort study was conducted to follow up 450 patients with lung cancer and chronic obstructive pulmonary disease who were hospitalized in our hospital from January 2018 to December 2023. The endpoint of the follow-up was the end of a five-year period or death. The Life Tables method was used to calculate survival rates and plot survival curves. The Cox proportional hazards model was used to analyze the influencing factors of five-year survival. Results The results indicated that the overall five-year survival rate of patients was 4.89%, and it decreased year by year. Cox regression analysis showed that age, gender, family functioning, and psychological status significantly influenced patient survival rate (all P<0.05). Stratified analysis found that the smoking status, family functioning, and psychological status of male patients all had an impact on survival rate (all P<0.05), while the psychological status of female patients had a more significant impact on survival (P=0.008). Conclusion This study provides a scientific basis for comprehensive intervention of elderly lung cancer patients with COPD. It is recommended that clinical attention should be paid to psychological and family factors to improve patient prognosis.
9.Research progress on the tumor microenvironment of liver cancer
Tianhao SONG ; Weiheng XU ; Yan WANG ; Li CHEN
Journal of Pharmaceutical Practice and Service 2026;44(2):65-70
Liver cancer, one of the most common primary malignancies in humans, is a malignant tumor characterized by multifactorial induction, polygenic involvement, and intricate molecular mechanisms. This disease is characterized by its treatment challenges and poor prognosis, which are closely related to its unique tumor microenvironment composition. The tumor microenvironment of liver cancer is a dynamic ecosystem composed of heterogeneous cellular populations, soluble cytokines, and remodeled extracellular matrix. In recent years, significant progress has been made in the study of the tumor microenvironment of liver cancer, revealed an important role in the occurrence, development, and treatment of liver cancer. The key regulatory elements of the tumor microenvironment in liver cancer were systematically summarized, such as activation of hepatic stellate cells, dysfunction of immune cells, abnormalities of platelet, and remodeling of the extracellular matrix, which provided theoretical foundations for prevention and treatment strategies against liver cancer.
10.Bibliometric visualization analysis of research literature of Angelica sinensis at home and abroad from 2012 to 2022 based on CiteSpace
Feifei LIU ; Liping CHEN ; Yan ZHONG ; Rong WANG ; Wenbin LI
Journal of Pharmaceutical Practice and Service 2026;44(2):88-95
Objective Based on the visualization graph analysis of the research hotspots of Angelica sinensis, predict the future research trends, and provide references for the next step of Angelica sinensis research. Methods Chinese and English literatures on Angelica sinensis collected from CNKI, WanFang, VIP and Web of Science from 2012 to 2022 were retrieved. CiteSpace 6.1.R6 software was used to perform visualization econometrics analysis on the number of publications, authors, institutions, journals, keywords and other topics. Results


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