1.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
To explore the advantages of traditional Chinese medicine (TCM) and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications (DMC), refine key pathophysiological insights and treatment principles, and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine, hosted by the China Association of Chinese Medicine, was held in Beijing, 2024. Experts in TCM, Western medicine, and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis, diagnostic and treatment challenges, and mechanism research related to DMC, ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development, research prioritization, and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM, strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.
2.Glucocorticoids Combined with Cyclophosphamide and Rituximab in the Treatment of Elderly Patients with ANCA-associated Vasculitis and Renal Involvement: A Single Center Retrospective Study
Jiahui WANG ; Xin LEI ; Xiaohan HUANG ; Liangliang CHEN ; Yaomin WANG ; Pingping REN ; Lan LAN ; Jianghua CHEN ; Fei HAN
Medical Journal of Peking Union Medical College Hospital 2026;17(2):346-357
To investigate the efficacy and safety of glucocorticoids combined with cyclophosphamide (CTX) and rituximab (RTX) in elderly patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with renal involvement. Elderly patients (age ≥60 years) with ANCA-associated vasculitis and renal involvement admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from December 2019 to November 2022 were retrospectively enrolled. Based on different induction treatment regimens, patients were divided into a control group (glucocorticoids + CTX) and a combination therapy group (glucocorticoids + CTX + RTX). Differences in disease remission, end stage renal disease (ESRD), mortality, relapse, and incidence of adverse events were compared between the two groups. A total of 60 elderly patients with ANCA-associated vasculitis and renal involvement were ultimately included, with a median follow-up of 29.7(17.2, 38.7) months. The control group comprised 26 patients, with a median follow-up of 35.0(28.1, 40.3) months; the combination therapy group comprised 34 patients, with a median follow-up of 26.2(16.1, 35.1) months. The remission rate at 3 months (64.7% For elderly patients with ANCA-associated vasculitis and renal involvement, the regimen of glucocorticoids combined with CTX and individualized RTX demonstrates potential advantages in early remission rate, glucocorticoid tapering, and control of cumulative CTX dose, without increasing the risk of serious adverse events. This regimen may represent an alternative treatment option for this patient population; however, its long-term efficacy and safety require further validation through prospective randomized controlled trials.
3.Clinical Efficacy of Gandou Fumu Decoction in Treating Hepatolenticular Degeneration with Liver Fibrosis of Liver-kidney Deficiency and Phlegm-blood Stasis Syndrome
Pingping YANG ; Meixia WANG ; Changchang CAO ; Zhuang TAO ; Jiang DU ; Yun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):182-191
ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction (GDFMD) in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome, thereby providing evidence-based medical evidence for the treatment of Wilson's disease (WD)-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1, 2023, to October 1, 2024. Participants were divided into a control group and an observation group, with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate (DMPS). On this basis, the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days, for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses, respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement (LSM), liver serological markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅳ collagen (C-Ⅳ), laminin (LN), N-terminal propeptide of type Ⅲ procollagen (PⅢNP), and hyaluronic acid (HA)], fibrosis index based on 4 factors (FIB-4), AST to platelet ratio index (APRI), unified Wilson's disease rating scale part Ⅱ (UWDRS-Ⅱ), traditional Chinese medicine (TCM) syndrome score, 24-hour urinary copper, and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment, LSM levels decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses, and the improvement of LSM levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the levels of HA, LN, PⅢNP, and C-Ⅳ decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses, and the levels of HA, LN, and PⅢNP were more obvious (P<0.05). After four treatment courses in the observation group, the levels of HA, LN, PⅢNP, and C-Ⅳ were improved more significantly (P<0.05). Compared with those before treatment, ALT and AST levels decreased in both groups after two and four treatment courses (P<0.05). Compared with the control group after treatment, there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses, and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, APRI score and FIB-4 index level decreased in both groups after two and four treatment courses (P<0.05). Compared with those in control group after treatment, there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses, and the APRI score in the observation group was more obvious after four treatment courses (P<0.05), with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment, the levels of TCM syndrome scores decreased in both groups after two and four treatment courses (P<0.05). Compared with that of the control group after treatment, there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses, and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously, and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses (P<0.05). Compared with those of the control group after treatment, there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses, and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious (P<0.05). Compared with those before treatment, the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses (P<0.05). Compared with those in the control group after treatment, the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses (P<0.01). After two treatment courses, the 24-h urine copper level in the observation group showed a gradual decreasing trend, although it was higher than that before treatment. After four treatment courses, the control group had an improvement rate of 91.43%, an effective rate of 34.29%, and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%, an effective rate of 71.43%, and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group (P<0.05). Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy, and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety, which is worthy of clinical popularization and application.
4.Clinical Efficacy of Gandou Fumu Decoction in Treating Hepatolenticular Degeneration with Liver Fibrosis of Liver-kidney Deficiency and Phlegm-blood Stasis Syndrome
Pingping YANG ; Meixia WANG ; Changchang CAO ; Zhuang TAO ; Jiang DU ; Yun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):182-191
ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction (GDFMD) in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome, thereby providing evidence-based medical evidence for the treatment of Wilson's disease (WD)-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1, 2023, to October 1, 2024. Participants were divided into a control group and an observation group, with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate (DMPS). On this basis, the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days, for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses, respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement (LSM), liver serological markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅳ collagen (C-Ⅳ), laminin (LN), N-terminal propeptide of type Ⅲ procollagen (PⅢNP), and hyaluronic acid (HA)], fibrosis index based on 4 factors (FIB-4), AST to platelet ratio index (APRI), unified Wilson's disease rating scale part Ⅱ (UWDRS-Ⅱ), traditional Chinese medicine (TCM) syndrome score, 24-hour urinary copper, and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment, LSM levels decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses, and the improvement of LSM levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the levels of HA, LN, PⅢNP, and C-Ⅳ decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses, and the levels of HA, LN, and PⅢNP were more obvious (P<0.05). After four treatment courses in the observation group, the levels of HA, LN, PⅢNP, and C-Ⅳ were improved more significantly (P<0.05). Compared with those before treatment, ALT and AST levels decreased in both groups after two and four treatment courses (P<0.05). Compared with the control group after treatment, there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses, and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, APRI score and FIB-4 index level decreased in both groups after two and four treatment courses (P<0.05). Compared with those in control group after treatment, there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses, and the APRI score in the observation group was more obvious after four treatment courses (P<0.05), with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment, the levels of TCM syndrome scores decreased in both groups after two and four treatment courses (P<0.05). Compared with that of the control group after treatment, there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses, and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously, and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses (P<0.05). Compared with those of the control group after treatment, there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses, and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious (P<0.05). Compared with those before treatment, the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses (P<0.05). Compared with those in the control group after treatment, the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses (P<0.01). After two treatment courses, the 24-h urine copper level in the observation group showed a gradual decreasing trend, although it was higher than that before treatment. After four treatment courses, the control group had an improvement rate of 91.43%, an effective rate of 34.29%, and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%, an effective rate of 71.43%, and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group (P<0.05). Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy, and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety, which is worthy of clinical popularization and application.
5.Association between the perinatal adverse outcomes in acute fatty liver of pregnancy and intraoperative blood transfusion and its prediction model
Guihua DENG ; Huang HUANG ; Pingping WANG ; Xingyan LONG ; Huixing ZHOU ; Yachun SUN ; Yunping XU
Chinese Journal of Blood Transfusion 2026;39(6):734-742
Objective: To analyze the association between intraoperative blood transfusion and adverse perinatal outcomes(a composite of maternal death, hepatic encephalopathy, etc) in patients with acute fatty liver of pregnancy (AFLP), identify independent risk factors for these outcomes, and develop and validate a risk prediction model for early identification of high-risk patients. Methods: Clinical data of 56 AFLP patients admitted to our hospital from January 2008 to January 2025 were retrospectively analyzed. The chi-square test was used to compare the incidence of adverse perinatal outcomes between the transfusion group and the non-transfusion group. Univariate and multivariate Firth-penalized logistic regression analyses were performed to identify independent predictors of adverse outcomes. Based on the identified independent risk factors, a combined prediction model was developed. Internal validation was performed using the Bootstrap method (1 000 resamplings) to assess the model′s generalizability. Model performance was evaluated using receiver operating characteristic(ROC) curves and calibration curves. Finally, a nomogram for predicting adverse perinatal outcomes in AFLP was constructed. Results: Overall, 57.1%(32/56) of the patients received blood product transfusion during the termination of pregnancy. Multivariate Firth-penalized logistic regression analysis showed that, given the limited sample size, intraoperative blood transfusion had no independent statistical effect on adverse outcomes (OR=0.812, 95%CI:0.133-3.698, P=0.797). Mediation analysis also revealed no significant indirect effect. The independent risk factors were decreased preoperative fibrinogen (OR=14.062, 95%CI:2.389-126.656, P=0.003), pregnancy with infection (OR= 4.536, 95%CI:1.143-22.107, P=0.031), and cesarean section (OR=8.691, 95%CI:1.321-90.081, P=0.023). The combined prediction model achieved an AUC of 0.881 (95% CI:0.793-0.969, P<0.001), indicating good discrimination. At the optimal cut-off value, the sensitivity was 65.6%, specificity 95.8%, positive predictive value 95.5%, and negative predictive value 67.6%. Internal validation by the Bootstrap method showed that the predictive model had good discrimination and no obvious overfitting. The calibration curve demonstrated that the model′s predicted risk was consistent with the actual observed risk. Based on this, an AFLP perinatal adverse outcome nomogram model was constructed. Conclusion: Under the limited sample size of this study, no independent statistical effect of intraoperative blood product infusion on adverse perinatal outcomes in AFLP patients was detected. A multivariate Firth-penalized logistic regression model incorporating decreased preoperative fibrinogen, pregnancy with infection, and cesarean delivery demonstrated good discrimination and calibration. The derived nomogram may serve as an exploratory tool for early risk stratification and proactive intervention.
6.Study on preparation of universal platelet-rich plasma
Lu WANG ; Qiong WU ; Xinyue YAO ; Pingping MAO ; Yi YANG ; Kaiyun LUO ; Na LI ; Shujun WANG
Chinese Journal of Blood Transfusion 2026;39(7):840-845
Objective: To improve the efficiency of patient treatment in routine, emergency, and mass casualty scenarios (both peacetime and wartime), eliminate reliance on blood type compatibility, and promote the productization of platelet-rich plasma (PRP), this study investigated the optimal mixing ratio for developing a universal PRP formulation. Methods: PRP was prepared from donors with blood types O, A, B, and AB. Samples were mixed in varying proportions, and the optimal ratio was determined based on the trend of anti-A and anti-B antibody titers in the mixed PRP. Concentrations of the growth factors PDGF-AA, PDGF-BB, EGF, TGF-β1, and VEGF were measured by enzyme-linked immunosorbent assay (ELISA) before and after mixing. Results: A mixing ratio of A∶B∶AB=6∶2.5∶24 resulted in no detectable agglutination with either A or B cells in the microcolumn gel system, indicating the absence of immunological reactivity and confirming universal compatibility. Importantly, the levels of all measured growth factors remained unchanged following mixing, suggesting preservation of biological activity. Conclusion: These findings suggest that universal PRP can be prepared by neutralizing blood type antibodies through antigen-antibody reactions.
7.Risk of dietary cadmium exposure from commercially available foods among residents of Jinhua City, Zhejiang Province
Zhuxin WANG ; Jiahui ZHU ; Gongjin LYU ; Pingping SHENTU
Shanghai Journal of Preventive Medicine 2026;38(8):591-597
ObjectiveTo investigate the cadmium contamination levels in commercially available foods in Jinhua City, to assess the dietary cadmium exposure risk among Jinhua residents, and to provide a scientific basis for optimizing dietary recommendations and managing cadmium exposure risks. MethodsFrom 2013 to 2024, a total of 4 434 samples of 15 categories of commercially available foods from the Jinhua Food Safety Risk Monitoring System, including rice, milled and processed grains, fresh vegetables 1 (leafy vegetables, celery, and daylily flowers), fresh vegetables 2 (legume vegetables, root and tuber vegetables, and stem vegetables other than celery) , fresh vegetables 3 (all vegetables other than fresh vegetables 1 and fresh vegetables 2), fresh fruits, legumes and legume products, nuts and seeds, meat and meat products (excluding livestock and poultry offal and products made from them), eggs and egg products, milk and dairy products, fish, crustaceans (excluding sea crabs and mantis shrimp), sea crabs and mantis shrimp, and other aquatic products (bivalves, gastropods, cephalopods, and echinoderms), were collected from 9 counties (cities and districts) in Jinhua City to assess their cadmium contamination levels. Combining these results with data from the 2023 Jinhua City Resident Nutrition Surveillance Survey, the health risks associated with dietary cadmium exposure among residents of different ages and genders in Jinhua City were assessed according to the provisional tolerable monthly intake (PTMI, 25 μg·kg-1) and margins of safety (MOS) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). A MOS > 1 indicated that the risk of dietary cadmium exposure for residents was at an acceptable level,whereas a MOS ≤ 1 indicated that the risk of dietary cadmium exposure for residents was relatively high. ResultsThe cadmium detection rate in food was 73.55% (3 261/4 434), with 4.06% (180/4 434) of samples exceeding the limit. Foods with higher cadmium detection rates were in sea crabs and mantis shrimp (98.59%), fresh vegetables 1 (94.92%), and rice (87.93%). The median cadmium concentration was 0.010 mg·kg-1. Food categories with higher cadmium concentrations included sea crabs and mantis shrimp (0.644 mg·kg-1), rice (0.032 mg·kg-1), and fresh vegetables 1 (0.020 mg·kg-1). A total of 2 092 individuals were included in the population nutrition surveillance survey, and the average daily per capita food consumption was 887.97 g·d-1, consisting of fresh vegetables (342.17 g·d-1), meat and meat products (141.29 g·d-1), and rice (110.70 g·d-1). The 50th and 95th percentiles of cadmium mass fractions were used to define general and high exposure levels for assessing resident exposure risk. When assigning a value of 0 and the limit of detection (LOD) value to the contamination levels of undetected samples, at the general exposure level, the monthly average cadmium exposure for the residents was 5.08 and 5.15 μg·kg-1 (based on body weight; same below), with MOS values of 4.92 and 4.85; the range of average cadmium exposure across different age and gender groups was 3.91‒6.70 and 3.97‒6.80 μg·kg-1, with all MOS values >1, indicating that the dietary cadmium exposure risk for the residents was at an acceptable level. At the high exposure level, the average cadmium exposure for the residents was 36.02 μg·kg⁻¹, with an MOS value of 0.69; the average cadmium exposure levels for different age and gender groups ranged from 27.68 to 48.37 μg·kg⁻¹, with MOS values ranging from 0.52 to 0.90, all of which were <1; indicating that the dietary cadmium exposure risk for residents was relatively high. Dietary cadmium exposure among minors aged 6‒17 years in Jinhua City was higher than that among adults, and dietary cadmium exposure among females was higher than that among males. Rice and fresh vegetables were the major foods contributing to dietary cadmium exposure among residents in Jinhua City, each accounting for more than 30% of the total exposure contribution. ConclusionCommercially available foods in Jinhua City exhibit varying degrees of cadmium contamination, with higher levels primarily found in aquatic products such as sea crabs and mantis shrimp, fresh vegetables such as leafy greens, celery, and daylily flowers, as well as rice. The dietary cadmium exposure risk for residents of Jinhua City is at an acceptable level under general exposure conditions but poses a health risk under high exposure conditions. Monitoring of cadmium in relevant foods should be strengthened, and dietary guidance should be provided to high-risk groups including minors aged 6‒17 years and women.
8.Effect of Dictamni Cortex on Intestinal Barrier Damage by Untargeted Metabolomics and Targeted Metabolomics for Short-chain Fatty Acids
Xiaomin XU ; Donghua YU ; Yu WANG ; Pingping CHEN ; Jiameixue WO ; Suxia JIA ; Wenkai HU ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):40-47
ObjectiveThis study aims to investigate the effect of Dictamni Cortex on intestinal barrier damage in rats and its mechanism by untargeted metabolomics and targeted metabolomics for short-chain fatty acids (SCFAs). MethodsRats were randomly divided into a control group, a high-dose group of Dictamni Cortex (8.1 g·kg-1), a medium-dose group (2.7 g·kg-1), and a low-dose group (0.9 g·kg-1). Except for the control group, the other groups were administered different doses of Dictamni Cortex by gavage for eight consecutive weeks. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the ileal tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect the level of cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), in the ileal tissue of rats. Quantitative real-time fluorescence polymerase chain reaction (Real-time PCR) technology was used to detect the expression level of tight junction proteins, including zonula occludens-1 (ZO-1), Occludin, and Claudin-1 mRNAs, in the ileal tissue of rats to preliminarily explore the effects of Dictamni Cortex on intestinal damage. The dose with the most significant toxic phenotype was selected to further reveal the effects of Dictamni Cortex on the metabolic profile of ileal tissue in rats by non-targeted metabolomics combined with targeted metabolomics for SCFAs. ResultsCompared with the control group, all doses of Dictamni Cortex induced varying degrees of pathological damage in the ileum, increased TNF-α (P<0.01), IL-6 (P<0.01), and IL-1β (P<0.01) levels in the ileal tissue, and decreased the expression level of ZO-1 (P<0.05, P<0.01), Occludin (P<0.01), and Claudin-1 (P<0.05) in the ileal tissue, with the high-dose group showing the most significant toxic phenotypes. The damage mechanisms of the high-dose group of Dictamni Cortex on the ileal tissue were further explored by integrating non-targeted metabolomics and targeted metabolomics for SCFAs. The non-targeted metabolomics results showed that 21 differential metabolites were identified in the control group and the high-dose group. Compared with that in the control group, after Dictamni Cortex intervention, the level of 14 metabolites was significantly increased (P<0.05, P<0.01), and the level of seven metabolites was significantly decreased (P<0.05, P<0.01) in the ileal contents. These metabolites collectively acted on 10 related metabolic pathways, including glycerophospholipids and primary bile acid biosynthesis. The quantitative data of targeted metabolomics for SCFAs showed that Dictamni Cortex intervention disrupted the level of propionic acid, butyric acid, acetic acid, caproic acid, isobutyric acid, isovaleric acid, valeric acid, and isocaproic acid in the ileal contents of rats. Compared with those in the control group, the level of isobutyric acid, isovaleric acid, and valeric acid were significantly increased, while the level of propionic acid, butyric acid, and acetic acid were significantly decreased in the ileal contents of rats after Dictamni Cortex intervention (P<0.05, P<0.01). ConclusionDictamni Cortex can induce intestinal damage by regulating glycerophospholipid metabolism, primary bile acid biosynthesis, and metabolic pathways for SCFAs.
9.Underlying Mechanism of Wuwei Shenqintang in Amelioration of Pulmonary Fibrosis by Regulating "Lung-intestine Axis" Based on UPLC-Q-TOF-MS Metabolomics Technology
Mengdi SUN ; Fang LU ; Donghua YU ; Yu WANG ; Pingping CHEN ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):11-20
ObjectiveTo explore the mechanism of action of Wuwei Shenqintang in improving pulmonary fibrosis by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) for metabolomic analysis of lung tissue and feces. MethodsA rat model with pulmonary fibrosis was established by intratracheal injection of 5 mg·kg-1 bleomycin. The successfully modeled rats were randomly divided into a blank group, a model group, a prednisone (3.15 mg·kg-1) group, and low-dose, medium-dose, and high-dose groups of Wuwei Shenqintang (4.586, 9.172, 18.344 g·kg-1). The rats were given intragastric administration once a day for 28 consecutive days. Hematoxylin-eosin (HE) staining was used to measure the pathological changes in lung and colon tissue, and Masson staining was used to detect the degree of pulmonary fibrosis. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), and secretory immunoglobulin A (SIgA) in bronchoalveolar lavage fluid and intestinal mucus. Immunohistochemistry and reverse transcription quantitative polymerase chain reaction (Real-time PCR) were used to detect the expression of type Ⅰ collagen (Col-Ⅰ), fibronectin (FN), and alpha smooth muscle actin (α-SMA) in lung tissue. UPLC-Q-TOF-MS was used to study the changes in the metabolic network of lung tissue and feces in rats with pulmonary fibrosis treated with Wuwei Shenqintang, screen potential biomarkers for the treatment of pulmonary fibrosis by Wuwei Shenqintang, and perform pathway enrichment analysis. ResultsCompared with the blank group, the model group showed extensive inflammatory cell infiltration and continuous fibrotic lesions in lung tissue, colonic mucosal damage, and connective tissue hyperplasia. The expression of IL-6, IL-8, IL-1β, TNF-α, and SIgA in bronchoalveolar lavage fluid and intestinal mucus was significantly increased (P<0.01). The expression of Col-Ⅰ, FN, and α-SMA proteins and mRNAs in lung tissue was significantly upregulated (P<0.01). Compared with the model group, the groups of Wuwei Shenqintang exhibited significantly reduced inflammatory infiltration and blue collagen deposition in lung tissue, alleviated colonic damage, decreased expression of IL-6, IL-8, IL-1β, TNF-α, and SIgA in bronchoalveolar lavage fluid and intestinal mucus (P<0.01), and reduced average absorbance values and mRNA expression of Col-Ⅰ, FN, and α-SMA in lung tissue (P<0.05, P<0.01), with the prednisone group and the medium-dose and high-dose groups of Wuwei Shenqintang showing the most significant effects. The metabolomics results for lung tissue showed that compared with the blank group, the model group had 19 significantly different compounds (P<0.05, P<0.01). Wuwei Shenqintang could normalize 17 of these compounds compared with the model group (P<0.05, P<0.01). Fecal metabolomics results showed that compared with those in the blank group, there were 42 compounds with significant differences in the model group (P<0.05, P<0.01). Compared with the model control group, Wuwei Shenqintang could normalize 41 of these compounds (P<0.05, P<0.01). The combined analysis results indicated that Wuwei Shenqintang might inhibit pulmonary fibrosis by regulating the biosynthesis of phenylalanine, tyrosine, and tryptophan as well as the retinol metabolism pathway. ConclusionWuwei Shenqintang can ameliorate pulmonary fibrosis, which may be related to the regulation of the "lung-intestine axis".
10.Underlying Mechanism of Wuwei Shenqintang in Amelioration of Pulmonary Fibrosis by Regulating "Lung-intestine Axis" Based on UPLC-Q-TOF-MS Metabolomics Technology
Mengdi SUN ; Fang LU ; Donghua YU ; Yu WANG ; Pingping CHEN ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):11-20
ObjectiveTo explore the mechanism of action of Wuwei Shenqintang in improving pulmonary fibrosis by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) for metabolomic analysis of lung tissue and feces. MethodsA rat model with pulmonary fibrosis was established by intratracheal injection of 5 mg·kg-1 bleomycin. The successfully modeled rats were randomly divided into a blank group, a model group, a prednisone (3.15 mg·kg-1) group, and low-dose, medium-dose, and high-dose groups of Wuwei Shenqintang (4.586, 9.172, 18.344 g·kg-1). The rats were given intragastric administration once a day for 28 consecutive days. Hematoxylin-eosin (HE) staining was used to measure the pathological changes in lung and colon tissue, and Masson staining was used to detect the degree of pulmonary fibrosis. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), and secretory immunoglobulin A (SIgA) in bronchoalveolar lavage fluid and intestinal mucus. Immunohistochemistry and reverse transcription quantitative polymerase chain reaction (Real-time PCR) were used to detect the expression of type Ⅰ collagen (Col-Ⅰ), fibronectin (FN), and alpha smooth muscle actin (α-SMA) in lung tissue. UPLC-Q-TOF-MS was used to study the changes in the metabolic network of lung tissue and feces in rats with pulmonary fibrosis treated with Wuwei Shenqintang, screen potential biomarkers for the treatment of pulmonary fibrosis by Wuwei Shenqintang, and perform pathway enrichment analysis. ResultsCompared with the blank group, the model group showed extensive inflammatory cell infiltration and continuous fibrotic lesions in lung tissue, colonic mucosal damage, and connective tissue hyperplasia. The expression of IL-6, IL-8, IL-1β, TNF-α, and SIgA in bronchoalveolar lavage fluid and intestinal mucus was significantly increased (P<0.01). The expression of Col-Ⅰ, FN, and α-SMA proteins and mRNAs in lung tissue was significantly upregulated (P<0.01). Compared with the model group, the groups of Wuwei Shenqintang exhibited significantly reduced inflammatory infiltration and blue collagen deposition in lung tissue, alleviated colonic damage, decreased expression of IL-6, IL-8, IL-1β, TNF-α, and SIgA in bronchoalveolar lavage fluid and intestinal mucus (P<0.01), and reduced average absorbance values and mRNA expression of Col-Ⅰ, FN, and α-SMA in lung tissue (P<0.05, P<0.01), with the prednisone group and the medium-dose and high-dose groups of Wuwei Shenqintang showing the most significant effects. The metabolomics results for lung tissue showed that compared with the blank group, the model group had 19 significantly different compounds (P<0.05, P<0.01). Wuwei Shenqintang could normalize 17 of these compounds compared with the model group (P<0.05, P<0.01). Fecal metabolomics results showed that compared with those in the blank group, there were 42 compounds with significant differences in the model group (P<0.05, P<0.01). Compared with the model control group, Wuwei Shenqintang could normalize 41 of these compounds (P<0.05, P<0.01). The combined analysis results indicated that Wuwei Shenqintang might inhibit pulmonary fibrosis by regulating the biosynthesis of phenylalanine, tyrosine, and tryptophan as well as the retinol metabolism pathway. ConclusionWuwei Shenqintang can ameliorate pulmonary fibrosis, which may be related to the regulation of the "lung-intestine axis".

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