1.Mechanism of MEK/Ras/Raf/ERK Signaling Pathway Modulated by Mimenghua Prescription on Inflammatory Response in Dry Eye Animal Model
Shi TAN ; Pei LIU ; Yuan ZHONG ; Sainan TIAN ; Pengfei JIANG ; Genyan QIN ; Qinghua PENG ; Jun PENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):211-221
ObjectiveThis paper aims to investigate the effects and mechanism of Mimenghua prescription in modulating the mitogen-activated protein kinase kinase (MEK)/rat sarcoma viral oncogene homolog (Ras)/rapidly accelerated fibrosarcoma kinase (Raf)/extracellular signal-regulated kinase (ERK) signaling pathway to inhibit inflammatory responses in a dry eye animal model. MethodsA total of 60 C57BL/6J mice (eight weeks old, half male and half female) were used in the experiment. Ten mice were randomly selected as the blank control group, while the remaining 50 were exposed to a controlled dry system and received instillation of 0.2% benzalkonium chloride (BAC) into the eyes for four weeks to establish a dry eye mouse model. After successful modeling, the mice were randomly divided into five groups: Model group, sodium hyaluronate group, and Mimenghua prescription groups with low dose (4.83 g·kg-1), medium dose (9.67 g·kg-1), and high dose (19.34 g·kg-1). The mice in the model group received an equal volume of normal saline via gavage for four weeks. The mice in the sodium hyaluronate group received instillation of sodium hyaluronate eye drops twice daily for 14 consecutive days. The tear secretion volume, tear film break-up time (TBUT), and corneal fluorescein staining were evaluated once every two weeks. After four weeks of administration, mice were euthanized, and their lacrimal gland tissues and corneas were harvested. Hematoxylin-eosin (HE) staining was used to assess histopathological morphology. Western blot was performed to detect the protein expression levels of MEK, Ras, Raf, and ERK. Enzyme-linked immunosorbent assay (ELISA) was used to measure the contents and expressions of MEK, Ras, Raf, ERK, and interleukin (IL)-1β in lacrimal gland and corneal tissues of the mice in each group. Quantitative real-time polymerase chain reaction (Real-time PCR) was employed to determine mRNA expression levels of MEK, Ras, Raf, and ERK. ResultsThe Mimenghua prescription groups and the sodium hyaluronate group exhibited significantly increased tear secretion volume (P<0.05) and prolonged TBUT (P<0.05) after treatment. Ocular surface damage of mice was visibly recovered. Western blot results indicated that protein expression levels of MEK, Ras, Raf, and ERK in the lacrimal gland and corneal tissues were significantly downregulated in the sodium hyaluronate group and Mimenghua prescription group with high dose (P<0.05). ELISA results showed that IL-1β levels were highest in the model group but significantly reduced in the sodium hyaluronate group and Mimenghua prescription groups (P<0.05). Both ELISA and Real-time PCR results demonstrated that the expression levels of MEK, Ras, Raf, and ERK in the lacrimal glands and corneal tissues were significantly elevated in the model group (P<0.05), but markedly downregulated in the sodium hyaluronate group and Mimenghua prescription groups (P<0.05), suggesting that Mimenghua prescription can decrease the expressions of MEK, Ras, Raf, and ERK in the lacrimal glands and corneal tissues. ConclusionMimenghua prescription can reduce inflammatory responses, increase tear secretion, prolong TBUT, and promote corneal recovery by inhibiting the MEK, Ras, Raf, and ERK signaling pathways in lacrimal gland and corneal tissues.
2.Expert consensus on clinical application of parenteral direct thrombin inhibitors in perioperative period
Mingyu JIANG ; Yuan BIAN ; Lizhu HAN ; Qinan YIN ; Fengjiao KANG ; Anhua WEI ; Danjie ZHAO ; Lin WANG ; Ying SHAO ; Li TANG ; Yi WANG ; Shuhong LIANG ; Huijuan LIU ; Guirong XIAO ; Yue LI
China Pharmacy 2026;37(6):689-699
OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors (DTIs) in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (the Affiliated Hospital of UESTC), a multidisciplinary working group was established. Through literature review and the Delphi method, clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework; systematic searches were conducted in CNKI, Medline, Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment,Development and Evaluation (GRADE) approach, and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations (each with an expert consensus rate exceeding 90%) on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection, dosing ranges, key monitoring points, and safety management strategies for parenteral DTIs in various scenarios, including the perioperative period of ventricular assist device implantation, the perioperative period of cardiac surgery, perioperative patients with lower-extremity atherosclerotic disease, the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome, the perioperative period of carotid artery stenting in patients with carotid stenosis, the perioperative period of patients with right heart thrombosis, and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition, warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus, which is formulated based on the best available evidence, provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.
3.Analysis of Clinical Prognostic Characteristics in Patients with Primary Sjögren's Syndrome-Related Renal Fanconi Syndrome
Xiaoxiao SHI ; Yuan DONG ; Jiahe JIANG ; Peng XIA ; Shuo ZHANG ; Yubing WEN ; Dong XU ; Fengchun ZHANG ; Limeng CHEN
Medical Journal of Peking Union Medical College Hospital 2026;17(2):358-369
Renal Fanconi syndrome (FS) is a rare renal manifestation of primary Sjögren's syndrome (pSS). This study aims to analyze the clinical and prognostic characteristics of patients with pSS-associated renal FS (pSS-FS) and provide insights for clinical management. Patients diagnosed with pSS-FS via renal biopsy at Peking Union Medical College Hospital from 1993 to 2024 were enrolled. Data collected included age, sex, clinical symptoms (xerostomia, xerophthalmia, skin purpura, arthralgia, polyuria, and systemic symptoms), laboratory findings [serum immunoglobulin G (IgG) and IgM, complement (C3, C4), antinuclear antibody, anti-Sjögren's syndrome-associated antigen A antibody (SSA), anti-SSB antibody, 24-hour urinary protein quantification, tubular proteinuria, serum creatinine, serum electrolytes], treatment, and follow-up information. Systematic assessments included the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score, pulmonary involvement (including non-infectious interstitial pneumonia, pulmonary fibrosis, pulmonary hypertension, etc.), hematological involvement (anemia, leukopenia, thrombocytopenia), etc. Efficacy evaluations encompassed improvements in immunological parameters, renal function, and tubular function. Group comparisons were performed using chi-square/Fisher's exact tests, A total of 38 patients with pSS-FS were included, with 37(97.4%) being female. The median age at pSS diagnosis was 43(37, 57) years. Xerostomia (76.3%) and xerophthalmia (71.1%) were the predominant clinical symptoms. The most common renal tubular dysfunctions were generalized aminoaciduria (96.9%), tubular proteinuria (96.0%), and hypokalemia (94.7%). The median eGFR was 52.57(32.04, 76.10)mL/(min·1.73 m2), with 60.5% (23/38) of patients having an eGFR below 60 mL/(min·1.73 m2).After six months of immunosuppressive therapy, including moderate-to-high-dose glucocorticoids, significant improvements were observed in immunological parameters (improvement rate: 69.2%), renal tubular function (89.5%), and renal function (44.4%). Following immunosuppressive treatment, the median eGFR increased from 54.95(33.06, 76.10)mL/(min·1.73 m2) to 65.56(56.24, 83.58)mL/(min·1.73 m2).Compared to patients with normal or mildly impaired baseline eGFR [≥ 60 mL/(min·1.73 m2)], those with significantly decreased baseline eGFR [< 60 mL/(min·1.73 m2)] were older (46 years This study reports the clinical characteristics of the largest single-center cohort of pSS-FS patients internationally, characterized by varying degrees of proximal renal tubular dysfunction and renal impairment. Timely initiation of immunosuppressive therapy, including glucocorticoids, is crucial, particularly for patients with significantly reduced eGFR, who may experience more substantial renal function improvement.
4.Mechanisms of Salvianolic Acid B in Inhibiting Epithelial-mesenchymal Transition in Non-small Cell Lung Cancer by Downregulating PAICS Expression
Bo XU ; Jixian ZHANG ; Linling HU ; Bo JIANG ; Shasha YUAN ; Yiling FAN ; Zhishen RUAN ; Yihan YU ; Qing MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):23-33
ObjectiveTo investigate the molecular mechanisms by which salvianolic acid B (SalB) inhibits epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) by downregulating phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) expression. MethodsNSCLC A549 cells and normal bronchial epithelial cells (bronchial epithelium transformed with Ad12-SV40 2B, BEAS-2B) were used as models. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay after treatment with SalB (0, 50, 100, 200, 300, 400, 500 μmol·L-1 for 24 or 48 h to determine effective and safe intervention concentrations. Cell proliferation, cell cycle distribution, and apoptosis were evaluated by 5-ethynyl-2′-deoxyuridine (EdU) staining and flow cytometry, respectively. Wound healing and Transwell invasion assays were performed to assess cell migration and invasion. RNA sequencing combined with bioinformatic analysis was conducted to identify differentially expressed genes and functional enrichment. Molecular docking was used to predict the binding ability between SalB and PAICS, and the cellular thermal shift assay (CETSA) was performed to evaluate the effect of SalB on the thermal stability of the PAICS protein. Western blot (WB) was used to detect the effects of SalB on PAICS and EMT-related proteins (E-cadherin, N-cadherin, Vimentin, Snail, and Slug). A functional rescue assay was conducted by PAICS overexpression via plasmid transfection. ResultsCompared with the control group, SalB inhibited A549 cell viability in a dose-dependent manner (P<0.05), and the effective concentrations (≤300 μmol·L-1) showed no significant cytotoxicity in BEAS-2B cells. Within this concentration range, SalB significantly inhibited A549 cell proliferation, migration, and invasion, and induced G0/G1 phase arrest and apoptosis (P<0.05). Transcriptomic analysis showed that SalB significantly downregulated PAICS expression, and its functions were enriched in cell proliferation and EMT. Bioinformatic analysis indicated that PAICS is highly expressed in lung adenocarcinoma and is associated with poor prognosis (P<0.01). Molecular docking showed that SalB has strong binding ability to PAICS (binding energy -9.1 kcal·mol-1. CETSA results showed that SalB significantly increased the thermal stability of the PAICS protein (P<0.05). WB results showed that, compared with the control group, SalB dose-dependently downregulated PAICS expression, upregulated E-cadherin, and downregulated N-cadherin, Vimentin, Snail, and Slug (P<0.05). Functional rescue experiments showed that, compared with the empty vector group, PAICS overexpression significantly enhanced A549 cell proliferation, migration, and invasion, promoted cell cycle progression, and inhibited apoptosis (P<0.05). Meanwhile, compared with the empty vector + SalB-H group, PAICS overexpression partially reversed the inhibitory effects of SalB on malignant phenotypes and EMT-related proteins (N-cadherin, Vimentin, Snail, and Slug), and downregulated E-cadherin expression (P<0.05,P<0.01), indicating that PAICS is a key functional target mediating the antitumor effects of SalB. ConclusionSalB effectively inhibits EMT progression and cell cycle progression in A549 cells by downregulating PAICS expression, thereby exerting anti-NSCLC effects. This study not only reveals that PAICS is a key functional target through which SalB regulates EMT, but also provides experimental evidence supporting SalB as a potential candidate drug for inhibiting NSCLC metastasis.
5.Eupatilin Inhibits Proliferation, Invasion, and Metastasis of Non-small Cell Lung Cancer via EZH2/H3K27me3 Signaling Pathway
Bo XU ; Yihan YU ; Linling HU ; Bo JIANG ; Yu QI ; Shasha YUAN ; Yiling FAN ; Jixian ZHANG ; Qing MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):58-69
ObjectiveTo investigate the mechanisms by which eupatilin (Eup) inhibits proliferation, invasion, and metastasis of non-small cell lung cancer (NSCLC) through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation (EZH2/H3K27me3) signaling pathway. MethodsIn vivo, a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry (IHC-P) was used to detect the expression of proliferation- and invasion/metastasis-related proteins, including proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGFA). In vitro, cell counting kit-8 (CCK-8) assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup (0-200 μmol·L-1) and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell (HUVEC) angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. ResultsIn the subcutaneous xenograft model, compared with the model group, Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors, and the tumor inhibition rate was significantly increased (P<0.05). IHC-P results showed that, compared with the model group, high-dose Eup significantly reduced the expression levels of PCNA, MMP-2, MMP-9, and VEGFA in vivo (P<0.05). In vitro, compared with the control group, Eup inhibited the proliferation, invasion, and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that, compared with the control group, Eup significantly downregulated EZH2 expression, and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that, compared with the model group, Eup significantly inhibited, in a dose-dependent manner, the expression levels of EZH2, H3K27me3, and proliferation- and invasion/metastasis-related proteins (PCNA, MMP-2, MMP-9, and VEGFA) in both in vivo and in vitro experiments (P<0.05). In vitro, compared with the control group, overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation, migration, and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.
6.Mechanisms of Salvianolic Acid B in Inhibiting Epithelial-mesenchymal Transition in Non-small Cell Lung Cancer by Downregulating PAICS Expression
Bo XU ; Jixian ZHANG ; Linling HU ; Bo JIANG ; Shasha YUAN ; Yiling FAN ; Zhishen RUAN ; Yihan YU ; Qing MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):23-33
ObjectiveTo investigate the molecular mechanisms by which salvianolic acid B (SalB) inhibits epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) by downregulating phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) expression. MethodsNSCLC A549 cells and normal bronchial epithelial cells (bronchial epithelium transformed with Ad12-SV40 2B, BEAS-2B) were used as models. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay after treatment with SalB (0, 50, 100, 200, 300, 400, 500 μmol·L-1 for 24 or 48 h to determine effective and safe intervention concentrations. Cell proliferation, cell cycle distribution, and apoptosis were evaluated by 5-ethynyl-2′-deoxyuridine (EdU) staining and flow cytometry, respectively. Wound healing and Transwell invasion assays were performed to assess cell migration and invasion. RNA sequencing combined with bioinformatic analysis was conducted to identify differentially expressed genes and functional enrichment. Molecular docking was used to predict the binding ability between SalB and PAICS, and the cellular thermal shift assay (CETSA) was performed to evaluate the effect of SalB on the thermal stability of the PAICS protein. Western blot (WB) was used to detect the effects of SalB on PAICS and EMT-related proteins (E-cadherin, N-cadherin, Vimentin, Snail, and Slug). A functional rescue assay was conducted by PAICS overexpression via plasmid transfection. ResultsCompared with the control group, SalB inhibited A549 cell viability in a dose-dependent manner (P<0.05), and the effective concentrations (≤300 μmol·L-1) showed no significant cytotoxicity in BEAS-2B cells. Within this concentration range, SalB significantly inhibited A549 cell proliferation, migration, and invasion, and induced G0/G1 phase arrest and apoptosis (P<0.05). Transcriptomic analysis showed that SalB significantly downregulated PAICS expression, and its functions were enriched in cell proliferation and EMT. Bioinformatic analysis indicated that PAICS is highly expressed in lung adenocarcinoma and is associated with poor prognosis (P<0.01). Molecular docking showed that SalB has strong binding ability to PAICS (binding energy -9.1 kcal·mol-1. CETSA results showed that SalB significantly increased the thermal stability of the PAICS protein (P<0.05). WB results showed that, compared with the control group, SalB dose-dependently downregulated PAICS expression, upregulated E-cadherin, and downregulated N-cadherin, Vimentin, Snail, and Slug (P<0.05). Functional rescue experiments showed that, compared with the empty vector group, PAICS overexpression significantly enhanced A549 cell proliferation, migration, and invasion, promoted cell cycle progression, and inhibited apoptosis (P<0.05). Meanwhile, compared with the empty vector + SalB-H group, PAICS overexpression partially reversed the inhibitory effects of SalB on malignant phenotypes and EMT-related proteins (N-cadherin, Vimentin, Snail, and Slug), and downregulated E-cadherin expression (P<0.05,P<0.01), indicating that PAICS is a key functional target mediating the antitumor effects of SalB. ConclusionSalB effectively inhibits EMT progression and cell cycle progression in A549 cells by downregulating PAICS expression, thereby exerting anti-NSCLC effects. This study not only reveals that PAICS is a key functional target through which SalB regulates EMT, but also provides experimental evidence supporting SalB as a potential candidate drug for inhibiting NSCLC metastasis.
7.Eupatilin Inhibits Proliferation, Invasion, and Metastasis of Non-small Cell Lung Cancer via EZH2/H3K27me3 Signaling Pathway
Bo XU ; Yihan YU ; Linling HU ; Bo JIANG ; Yu QI ; Shasha YUAN ; Yiling FAN ; Jixian ZHANG ; Qing MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):58-69
ObjectiveTo investigate the mechanisms by which eupatilin (Eup) inhibits proliferation, invasion, and metastasis of non-small cell lung cancer (NSCLC) through the enhancer of zeste homolog 2/histone H3 lysine 27 trimethylation (EZH2/H3K27me3) signaling pathway. MethodsIn vivo, a subcutaneous xenograft tumor model was established in nude mice using H1299 cells to evaluate the anti-NSCLC effects of Eup. Immunohistochemistry (IHC-P) was used to detect the expression of proliferation- and invasion/metastasis-related proteins, including proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGFA). In vitro, cell counting kit-8 (CCK-8) assays were performed to determine the viability of H1299 cells treated with different concentrations of Eup (0-200 μmol·L-1) and to select appropriate concentrations. Colony formation and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to evaluate cell proliferation. Wound healing and invasion assays were conducted to assess cell migration and invasion. Human umbilical vein endothelial cell (HUVEC) angiogenesis assays were used to evaluate the effects of Eup on angiogenesis. Transcriptomic analysis was performed to identify the targets of Eup in H1299 cells and to explore its major functions. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and interaction stability between Eup and its target proteins. Western blot was used to detect the effects of Eup on the expression levels of EZH2/H3K27me3 pathway-related proteins and proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. ResultsIn the subcutaneous xenograft model, compared with the model group, Eup treatment dose-dependently inhibited the growth of H1299 xenograft tumors, and the tumor inhibition rate was significantly increased (P<0.05). IHC-P results showed that, compared with the model group, high-dose Eup significantly reduced the expression levels of PCNA, MMP-2, MMP-9, and VEGFA in vivo (P<0.05). In vitro, compared with the control group, Eup inhibited the proliferation, invasion, and metastasis of NSCLC cells in a concentration-dependent manner. Transcriptomic analysis further showed that, compared with the control group, Eup significantly downregulated EZH2 expression, and its functional effects were associated with inhibition of tumor metastasis. Molecular docking and molecular dynamics simulations indicated that Eup exhibited strong binding affinity with EZH2 and stable interactions. Western blot results demonstrated that, compared with the model group, Eup significantly inhibited, in a dose-dependent manner, the expression levels of EZH2, H3K27me3, and proliferation- and invasion/metastasis-related proteins (PCNA, MMP-2, MMP-9, and VEGFA) in both in vivo and in vitro experiments (P<0.05). In vitro, compared with the control group, overexpression of EZH2 via plasmid transfection partially reversed the inhibitory effects of Eup on the expression of key proteins involved in proliferation and invasion/metastasis in H1299 cells. ConclusionEup effectively inhibits the proliferation, migration, and invasion of H1299 cells both in vivo and in vitro. The underlying mechanism may be related to inhibition of the EZH2/H3K27me3 signaling pathway and downregulation of proliferation- and invasion/metastasis-related proteins, including PCNA, MMP-2, MMP-9, and VEGFA. Eup may serve as a potential therapeutic agent for suppressing proliferation and invasion/metastasis in NSCLC.
8.Association of microRNA gene polymorphisms with risk, clinicopathological characteristics and therapeutical efficacy among Chinese patients with Crohn's disease.
Yanlun ZHANG ; Xiaoxiao SHAO ; Daopo LIN ; Yuan XU ; Guolong MA ; Yi JIANG
Chinese Journal of Medical Genetics 2026;43(2):111-122
OBJECTIVE:
To assess the association of microribonucleic acid (miRNA) gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease (CD) and the influence of miRNA gene variants on the response to ustekinumab (UST) treatment among CD patients.
METHODS:
From January 2018 to February 2025, 312 patients diagnosed with CD and 527 gender- and age-matched normal controls were selected as the study subjects at the Department of Gastroenterology of the Second Affiliated Hospital of Wenzhou Medical University. Genotypes of miR-155 (rs767649), miR-21 (rs13137), miR-124 (rs531564) and miR-146a (rs57095329, rs2431697) were determined with multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. The patients were divided into different subgroups according to the Montreal Classification Criteria for CD. Harvey-Bradshaw index (HBI) and simplified endoscopic score for CD were respectively applied to assess the clinical and endoscopic disease activity of CD. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between the two groups, as well as their influence on the clinicopathological characteristics of CD patients. Among them, 185 CD patients received first-line UST treatment, with the first sufficient dose of UST (6 mg/kg) administered intravenously. Based on the changes in HBI at week 8, the response of patients to UST treatment was evaluated. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between clinically responsive group (the decline of HBI ≥ 3 scores compared to week 0) and non-responsive group. All of the P values were adjusted by Bonferroni correction. This study has been approved by the Medical Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (Ethics No.: 2025-K-12-01).
RESULTS:
No significant difference was found in the distribution of miRNA gene polymorphisms between the two groups (all P > 0.05). The variant genotype (TC+CC) of rs2431697 was more common among patients with terminal ileal-type and ileocolic-type CD than those with the colonic-type CD (OR = 4.98, 95%CI: 1.49~16.68, P = 0.009, adjusted P = 0.045). However, the opposite conclusion was drawn for the homozygous variant genotype (TT) of rs13137 and variant genotype (GC+CC) of rs531564 (OR = 0.37, 95%CI: 0.18~0.76, P = 0.007, adjusted P = 0.035; OR = 0.36, 95%CI: 0.18~0.73, P = 0.004, adjusted P = 0.020). Compared to patients with non-stricturing and penetrating CD, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common in those with stricturing and penetrating CD (OR = 4.06, 95%CI: 2.46~6.71, P < 0.001, adjusted P < 0.005; OR = 3.12, 95%CI: 2.06~4.73, P < 0.001, adjusted P < 0.005). However, the frequencies of variant genotype (AT+TT) and variant allele (T) of rs13137 were lower among patients with stricturing and penetrating CD than in those without (OR = 0.25, 95%CI: 0.15~0.41, P < 0.001, adjusted P < 0.005; OR = 0.45, 95%CI: 0.33~0.63, P < 0.001, adjusted P < 0.005). Additionally, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common among those with moderately to severely endoscopic activity than those with mildly endoscopic activity (OR = 2.01, 95%CI: 1.19~3.42, P = 0.009, adjusted P = 0.045; OR = 2.04, 95%CI: 1.28~3.25, P = 0.003, adjusted P = 0.015). In total 117 cases had shown clinical response by week 8, while 68 cases showed no response. Compared with t he clinically non-responsive group, the variant genotype (TC+CC) and variant allele (C) of rs2431697 were more common in the clinically responsive group (OR = 3.86, 95%CI: 1.80~8.32, P = 0.001, adjusted P = 0.005; OR = 2.60, 95%CI: 1.34~5.06, P = 0.005, adjusted P = 0.025). However, the variant genotype (TA+AA) of rs767649 was less frequent in the clinically responsive group than the non-responsive group (OR = 0.40, 95%CI: 0.21~0.74, P = 0.004, adjusted P = 0.020). The same conclusion was drawn for the variant genotype (AT+TT) and variant allele (T) of rs13137 when the clinically responsive group was compared with the non-responsive group (OR = 0.30, 95%CI: 0.14~0.63, P = 0.002, adjusted P = 0.010; OR = 0.54, 95%CI: 0.35~0.82, P = 0.005, adjusted P = 0.025).
CONCLUSION
Genetic polymorphisms of miRNAs are not associated with the risk of developing CD. The miR-146a (rs57095329) variant may increase the endoscopic activity of CD and the risk for stenosis or penetration. However, the miR-146a (rs2431697) variant may increase the risk of ileal involvement. The miR-21 (rs13137) variant may reduce the risk of ileal involvement and the risk of stenosis or penetration. The miR-124 (rs531564) variant may reduce the risk of ileal involvement. Among patients receiving UST treatment, the miR-146a (rs2431697) variant may increase the clinical response by week 8. However, both the miR-155 (rs767649) and miR-21 (rs13137) variants may decrease the clinical response by week 8.
Humans
;
MicroRNAs/genetics*
;
Crohn Disease/pathology*
;
Male
;
Female
;
Adult
;
Polymorphism, Single Nucleotide
;
Middle Aged
;
Asian People/genetics*
;
Genetic Predisposition to Disease
;
Genotype
;
Young Adult
;
Case-Control Studies
;
Adolescent
;
East Asian People
9.From Cathartic Colon to Cathartic-dependent Constipation: Diagnostic-therapeutic Strategies from Integrative Medicine Perspective
Youcheng HE ; Fengru JIANG ; Yanru WANG ; Minghan HUANG ; Yue WU ; Chunyu ZHOU ; Lian MO ; Lifeng WEI ; Keyi PAN ; Shuyu CAI ; Jianye YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):162-172
Both cathartic colon (CC) and cathartic-dependent constipation (CDC) are caused by the abuse of stimulant laxatives, while their concepts are not completely the same.Starting from the disease name of CC, this article traced the origin and evolution of the concept of CC, summarizes and compared the similarities and differences between CC, CDC, and slow transit constipation (STC), and called for strict differentiation among the three.Furthermore, this article explored the specific contents of Western medicine clinical subtypes and traditional Chinese medicine (TCM) syndrome differentiation of CDC and delved into the TCM pathogenesis of CDC according to both literature and clinical practice.The relationship between clinical subtypes and TCM syndromes was established, and the syndrome characteristics of CDC of different clinical subtypes and TCM syndromes were summarized.The recommended prescriptions for corresponding syndromes were listed.A systematic CDC diagnosis and treatment approach of "clinical subtypes-syndrome differentiation-syndrome characteristics-recommended prescriptions" was thus formed.Additionally, the paper provides an overview of current research on CDC in both Western medicine and TCM contexts, identifies future research directions, and suggests research pathways for refining and advancing CDC studies.
10.Clinical Efficacy of Yiqi Yangyin Huoxue Prescription in Treatment of Cathartic Colon and Analysis of Influencing Factors of Disease Severity
Youcheng HE ; Jingyi SHAN ; Fengru JIANG ; Yue WU ; Chunyu ZHOU ; Lu HANG ; Yan ZHOU ; Lian MO ; Shuyu CAI ; Keyi PAN ; Lifeng WEI ; Jianye YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):173-184
ObjectiveTo observe the clinical efficacy of the Yiqi Yangyin Huoxue prescription (YYHP) in the treatment of cathartic colon (CC) and its effects on fecal short-chain fatty acids (SCFAs), and to explore the correlations among CC severity indicators and between these indicators and patient history. MethodsAccording to the inclusion and exclusion criteria, 98 patients meeting the diagnostic criteria of both traditional Chinese and Western medicine for CC with the syndrome of Qi-Yin deficiency complicated by blood stasis were randomly assigned to an observation group and a control group. The observation group received YYHP granules, while the control group received lactulose. Both medications were administered twice daily, one sachet each time, half an hour after breakfast and dinner, with a treatment course of 8 weeks. The primary constipation symptom score, Patient Assessment of Constipation Quality of Life (PAC-QOL) score, and TCM syndrome score were assessed before and after treatment and at the 8th week after the end of treatment. The overall clinical effective rate, as well as the efficacy attenuation index and degree, were evaluated. Fecal SCFA levels were measured using gas chromatography-mass spectrometry (GC-MS). Spearman correlation analysis was performed to explore the correlations among CC severity indicators and between these indicators and patient history. ResultsThe overall clinical effective rate in the observation group (95.83%) was higher than that in the control group (78.72%) (P<0.05). After treatment, the total scores for primary constipation symptoms, PAC-QOL, and TCM syndromes decreased in both groups (P<0.05), with more significant reductions in the observation group (P<0.05). The severity of all primary constipation symptoms was alleviated in both groups (P<0.05). In terms of "excessive straining and difficult defecation", "anal heaviness, incomplete evacuation, and bloating sensation", "abdominal distension", and "defecation frequency", the observation group showed better efficacy than the control group (P<0.05). Scores of the four PAC-QOL dimensions and the scores and severity of primary and secondary TCM symptoms were reduced in both groups (P<0.05), with more significant reductions in the observation group (P<0.05). After treatment, acetic acid, propionic acid, butyric acid, and total SCFAs in the observation group increased significantly (P<0.05). The efficacy attenuation index and degree in the observation group were lower than those in the control group (P<0.05). No severe adverse reactions occurred in either group, and there was no statistically significant difference in the incidence of adverse reactions between the two groups. Positive correlations of varying degrees were observed among the total scores of primary constipation symptoms, PAC-QOL, and TCM syndromes, as well as between these scores and the history of stimulant laxative use, disease duration, and age. ConclusionYYHP can effectively alleviate the primary constipation symptoms in CC patients, improve quality of life, and ameliorate TCM syndromes, with good safety. It also has the advantage of a lower rebound degree after drug withdrawal, and its mechanism may be related to increasing fecal SCFA levels. Long-term abuse of stimulant laxatives may aggravate the severity of CC and prolong the disease course.

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