1.Mechanism of Yantiao Prescription in Treating Lipopolysaccharide-induced Acute Lung Injury Based on Arachidonic Acid Metabolic Pathways
Pengcheng LI ; Tianyang CHEN ; Rong FANG ; Anna ZHANG ; Sijia WU ; Wei LIU ; Qian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):101-110
ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide (LPS)-induced acute lung injury (ALI), and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid (AA) in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight: normal group, model group, dexamethasone group (2 mg·kg-1), low-dose Yantiao prescription group (18 g·kg-1), and high-dose Yantiao prescription group (36 g·kg-1), with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days, and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in serum was detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to assess lung tissue pathology. The wet/dry weight ratio (W/D) and myeloperoxidase (MPO) activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry (LC-MS/MS). ResultsCompared with the conditions in the normal group, the content of serum pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in the model group was significantly increased (P<0.01). The alveolar structure in mice was severely damaged, with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased (P<0.01). The content of AA metabolites, including prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), 11(S)-hydroxy-eicosatetraenoic acid [11(S)-HETE], and 5-hydroxy-eicosatetraenoic acid (5-HETE) in serum and lung tissue was significantly increased (P<0.05), while the content of 11,12-epoxyeicosatrienoic acid (11,12-EET) and 14,15-epoxyeicosatrienoic acid (14,15-EET) in serum was significantly decreased (P<0.01). Compared with the results in the model group, the content of serum pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in the dexamethasone group, low-dose Yantiao prescription group, and high-dose Yantiao prescription group was significantly reduced (P<0.05). Mild thickening of alveolar walls, scattered inflammatory cell infiltration, and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced (P<0.01). The content of AA metabolites PGD2, PGE2, 11(S)-HETE, and 5-HETE in serum from the dexamethasone group was significantly decreased (P<0.05), while the content of 14,15-EET in serum significantly increased (P<0.01), and the content of 5-HETE in lung tissue significantly decreased (P<0.01). In the low-dose and high-dose Yantiao prescription groups, the content of AA metabolites PGD2, PGE2, 11(S)-HETE, and 5-HETE in serum and lung tissue was significantly decreased (P<0.05), while the content of 11,12-EET in both serum and lung tissue was significantly increased (P<0.05). ConclusionYantiao prescription has significant protective effects against LPS-induced ALI, which are related to its regulation of AA metabolic pathways in vivo.
2.Material Basis and Its Distribution in vivo of Qili Qiangxin Capsules Analyzed by UPLC-Q-Orbitrap-MS
Jianwei ZHANG ; Jiekai HUA ; Rongsheng LI ; Qin WANG ; Xinnan CHANG ; Wei LIU ; Jie SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):185-193
ObjectiveBased on ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap-MS), the chemical constituents of Qili Qiangxin capsules was identified, and their distribution in vivo was analyzed. MethodsUPLC-Q-Orbitrap-MS was used to detect the sample solution of Qili Qiangxin capsules, as well as the serum, brain, heart, lung, spleen, liver and kidney tissues of mice after oral administration. Using the Thermo Xcalibur 2.2 software, the compound information database was constructed, and the molecular formulas of compounds corresponding to the quasi-molecular ions were fitted. Based on the information of retention time, accurate relative molecular mass and fragments, the compounds and their distribution in vivo were analyzed by comparing with the data of reference substances and literature. ResultsA total of 233 compounds, including 70 terpenoids, 60 flavonoids, 23 organic acids, 17 alkaloids, 20 steroids, 7 coumarins and 36 others, were identified or predicted from Qili Qiangxin capsules, 73 of which were identified matching with standard substances. Tissue distribution results showed that 71, 17, 38, 33, 32, 58 and 43 migrating components were detected in blood, brain, heart, lung, spleen, liver and kidney, respectively. Thirty-seven components were absorbed into the blood and heart, including quinic acid, benzoylaconitine benzoylmesaconine and so on. Fourteen components were absorbed into the blood and six tissues, including calycosin, methylnissolin, formononetin, alisol B, alisol A and so on. ConclusionThis study comprehensively analyzes the chemical components of Qili Qiangxin capsules and their distribution in vivo. Among them, astragaloside Ⅳ, salvianolic acid B, ginsenoside Rb1, ginsenoside Rb3, ginsenoside Rd, ginsenoside Rg3, calycosin-7-glucoside, and sinapine may be the important components for the treatment of heart failure, which can provide useful reference for its quality control and research on pharmacodynamic material basis.
3.Effect of Tuina at "Weizhong (BL 40)" on Spinal Microglial Activation-related Proteins and the IL-10/β-EP Pathway in a Rat Model of Chronic Sciatic Nerve Compression Injury
Tianwei ZHANG ; Xiangqian LYU ; Yani XING ; Liuchen ZHU ; Qingguang ZHU ; Lingjun KONG ; Yanbin CHENG ; Zhen YAN ; Wuquan SUN ; Min FANG ; Zhiwei WU
Journal of Traditional Chinese Medicine 2025;66(7):734-740
ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong (BL 40)" on neuropathic pain in a rat model of chronic constriction injury (CCI) of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups (8 rats in each group), sham-operated group, model group, Tuina group, and blockade group. The CCI model was established in the model group, Tuina group, and the blockade group by ligating the sciatic nerve with catgut, while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14, rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong (BL 40)" using a dynamic pressure distribution measurement system (5 N pressure, 2 Hz frequency, 10 min per session, once daily). The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline (10 mg/kg) once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold (MWT) and paw withdrawal latency (PWL) were measured before surgery and on day 3, 7, 10, and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair, measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 (Iba-1), CD206, CD68, interleukin-10 (IL-10), and β-endorphin (β-EP) precursor pro-opiomelanocortin (POMC) in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group, the model group showed significantly reduced MWT and PWL on day 3, 7, 10, and 14 (P<0.01). Compared with the model group, the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 (P<0.05). Compared with the Tuina group, the blockade group exhibited higher MWT on day 7, 10, and 14, and higher PWL on day 10 (P<0.05). Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group, while the model group exhibited myelin collapse, distortion, and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse, whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group, the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn (P<0.05 or P<0.01). Compared with the model group, the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally, the Tuina group showed elevated levels of CD206, IL-10, and POMC, whereas the blockade group had decreased CD206 levels (P<0.05). ConclusionTuina at "Weizhong (BL 40)" alleviates neuropathic pain in CCI rats, potentially by regulating microglial activation in the spinal cord, inhibiting M1 polarization while promoting M2 polarization, and activating the IL-10/β-EP pathway to exert analgesic effects.
4.Diagnosis and Treatment of Cough Associated with Interstitial Lung Disease from Collaterals Deficiency with Latent Wind
Fang SUN ; Shiqi SUN ; Yan XUE ; Wei ZHANG
Journal of Traditional Chinese Medicine 2025;66(10):1057-1059
It is believed that the basic mechanism of cough associated with interstitial lung disease is collaterals deficiency with latent wind: the deficiency of the lung organs and lung collaterals is the basis of its pathogenesis, and latent wind in lung collaterals is the key mechanism of the cough which is difficult to cure. Treatment is based on the principle of supplementing deficiency and treating wind, dispelling the pathogens and unblocking the collaterals. Supplementing deficiency should supplement lungs, boost kidneys, and strengthen spleens to consolidate the root and banking up the origin, and regulate and tonify the lung collaterals; dispelling the pathogens should treat the internal and external winds at the same time, and taking into account the combined pathogens of phlegm, stasis and dampness to clear the stagnation of the lung collaterals.
5.FANG Min's Experiences Using Tuina for Chronic Spinal Disease Based on the Principle of "Focusing on Sinews and Fine-Regulating Bones"
Journal of Traditional Chinese Medicine 2025;66(13):1322-1326
To summarise clinical experience of Professor FANG Min in treating chronic spinal disease with tuina therapy based on the principle of "focusing on sinews and fine-regulating bones". It is believed that the key mechanism of chronic spinal disease lies in the imbalance of sinews and bones, with sinews being the first, accordingly, the basic treatment principle of "focusing on sinews and fine-regulating bones" is put forward. Combining with the modern anatomical science and the theory of traditional Chinese medicine acupoints and meridians, the treatment of chronic spinal disease adopts the principles of "causing instability in the first, making adjustments in the reverse direction, then recovering and standing up" and "layering tuina, and combining points, lines and surfaces organically", which can often achieve a more satisfactory therapeutic effect.
6.The role of gut microbiota homeostasis in the occurrence and development of hepatocellular carcinoma and targeted intervention strategies
Yan CUI ; Junzhe JIAO ; Ruijuan YAN ; Shuguang YAN ; Hailiang WEI ; Zhanjie CHANG ; Haibo ZHANG ; Jingtao LI
Journal of Clinical Hepatology 2025;41(9):1913-1919
Hepatocellular carcinoma (HCC), as the sixth most common malignant tumor worldwide, poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota (GM) homeostasis in the development and progression of HCC, in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis, intestinal leakage, microbial-associated molecular pattern, bacterial translocation, and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape, thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC, deeply analyzes the mechanism of action of GM in the development and progression of HCC, investigates the role of bile acid-related metabolites, short-chain fatty acid-related metabolites, and other metabolites in HCC, and explores the strategies for targeting GM in the treatment of HCC, including probiotics, prebiotics, antibiotics, Toll-like receptor 4 antagonists, and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC, which provides a direction for developing new diagnosis and treatment strategies.
7.Application of magnetic resonance imaging-proton density fat fraction in liver fat quantification
Chen YANG ; Shanghai YU ; Feipeng XU ; Hua ZHANG
Journal of Clinical Hepatology 2024;40(3):600-605
Hepatic steatosis can be observed in chronic liver diseases of different etiologies. The main predisposing factors for hepatic steatosis include chronic viral hepatitis, cholestatic liver disease, alcoholic liver disease, and nonalcoholic fatty liver disease. Simple fatty liver disease is the initial manifestation of hepatic steatosis, followed by steatohepatitis, liver fibrosis, liver cirrhosis, and even hepatocellular carcinoma. With the development of medical imaging technology, magnetic resonance imaging-proton density fat fraction (MRI-PDFF) has been widely used in the diagnosis of fatty liver disease (FLD) in clinical practice. MRI-PDFF is gradually becoming the gold standard for the noninvasive diagnosis of FLD due to its high accuracy and good repeatability. This article reviews the clinical application of MRI-PDFF in liver fat quantification and related research advances.
8.Quantitative Analysis of Multi-components in Gnaphalium affine Based on UPLC-Q-Exactive Orbitrap MS
Chunyan CAO ; Jiaqi ZHANG ; Zhenduo ZHAO ; Qin SHEN ; Shenglan QI ; Wei LIU ; Lichao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):148-155
ObjectiveTo establish a rapid and stable liquid chromatography-mass spectrometry(LC-MS) for simultaneous analysis of 17 chemical components in Gnaphalium affine aboveground parts with flowers, so as to provide experimental basis for improving the quality standard of this herb. MethodUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was used for the quantitative analysis of 17 constituents in 15 batches of G. affine from different origins, the separation was performed on an ACQUITY UPLC® BEH C18 column(2.1 mm×100 mm, 1.7 μm) with the mobile phase of methanol(A)-0.1% formic acid aqueous solution(B) for gradient elution(0-1.0 min, 8%A; 1.0-4.0 min, 8%-26%A; 4.0-9.0 min, 26%A; 9.0-14.0 min, 26%-34%A; 14.0-14.5 min, 34%-45%A; 14.5-15.0 min, 45%-60%A; 15.0-18.0 min, 60%-90%A; 18.0-19.0 min, 90%A; 19.0-19.01 min, 90%-8%A; 19.01-20.0 min, 8%A), the flow rate was 0.3 mL·min-1, the column temperature was 40 ℃ and the injection volume was 2 μL. And the electrospray ionization was used with full scanning in both positive and negative ion modes, and the scanning range was m/z 100-1 000. ResultThe established method has been verified by the methodology and could be used for the simultaneous quantification of 17 components in G. affine. The content ranges of the 17 components(quinic acid, gallic acid, protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, 1,3-O-dicaffeoylquinic acid, isochlorogenic acid A, isoquercitrin, 1,5-O-dicaffeoylquinic acid, apigenin-7-O-glucoside, astragalin, isochlorogenic acid C, luteolin, apigenin and hispidulin) in 15 batches of G. affine samples was 39.60-179.12, 0.17-0.84, 2.41-8.38, 4.33-31.50, 13.63-180.38, 2.43-14.75, 1.16-19.68, 0.49-5.63, 55.77-445.16, 0.23-10.26, 62.04-530.10, 1.11-18.01, 11.36-90.61, 12.22-65.98, 7.22-69.84, 3.37-45.65, 0.30-2.59 μg·g-1, respectively. The content of organic acids was higher than that of flavonoids in G. affine, and the contents of 1,5-O-dicaffeoylquinic acid, isochlorogenic acid A, quinic acid and chlorogenic acid were higher. Meanwhile, the content of flavonoids in the samples from Guizhou was higher than that from Jiangsu, while the content of organic acids in the samples from Jiangsu was higher than that from Guizhou. ConclusionThe established method can be used for the rapid and accurate determination of 17 components in G. affine, which clarifies the content range of the main components in this herb, and can provide a reference for the selection of quality control markers of G. affine.
9.Evaluation of analgesic effect of nalbuphine in patients with non-mechanical ventilation in intensive care unit: a multi-center randomized controlled trail
Yi ZHOU ; Shaohua LIU ; Song QIN ; Guoxiu ZHANG ; Yibin LU ; Xiaoguang DUAN ; Haixu WANG ; Ruifang ZHANG ; Shuguang ZHANG ; Yonggang LUO ; Yu FANG ; Xiaoyun FU ; Tao CHEN ; Lening REN ; Tongwen SUN
Chinese Journal of Emergency Medicine 2024;33(1):59-64
Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.
10.Discussion on the Difference of Acupuncture Points Efficacy in Improving Ulcerative Colitis by"Zusanli"or"Neiguan"Based on Transcriptomics Data
Longcong DONG ; Ruibin ZHANG ; Yuan SHEN ; Hongying LI ; Qin HUANG ; Shuguang YU ; Qiaofeng WU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):119-128
Objective To observe the intervention effect of acupuncture at"Zusanli"(ST36)or"Neiguan"(PC6)on the ulcerative colitis(UC)model mice.And to analyze the similarities and differences of gene transcription expression between the diseased colon and the non-diseased heart after acupuncture intervention by using transcriptomics,to explore whether there are efficacy differences between the two acupoints.Methods The UC mouse model was established by inducing dextran sulfate sodium salt(DSS).After successful modeling,the mice were randomly divided into model group,Zusanli group,and Neiguan group,with 9 mice in each group.Zusanli group and Neiguan group intervened with acupuncture at"Zusanli"and"Neiguan",respectively,30 min each time,once a day,for 5 consecutive days.The control and model groups were only bound without acupuncture.Observe the general situation of mice in each group,calculate the disease activity index(DAI),observe the morphological changes of colon tissue by HE staining.Use transcriptome sequencing technology to sequence and biologically analyze the colon tissue of mice in each group,and compare and study whether the two acupoints have differences in acupoint efficacy from the perspective of diseased tissue.At the same time,take the heart tissues of each group for comparative analysis,and discuss whether the effects of the two acupoints are different from the perspective of non-diseased tissue.Results Compared with control group,the DAI score of the model group increased significantly(P<0.001),and HE staining results showed significant pathological damage;after acupuncture at Zusanli or Neiguan,the DAI scores of UC mice were reduced considerably(P<0.05),and the pathological damage was significantly improved.The results of transcriptome sequencing and bioinformatics analysis showed that the effects of acupuncture at Zusanli or Neiguan on the colon of diseased tissue involved multiple genes,and 825 differential genes with similar changes(co-DEGs)were mainly enriched in white blood cells and chemokine pathways;there were 168 differentially expressed genes(ST36 only-DEGs)affected only by Zusanli,which were enriched to gastric acid secretion and other pathways;there were 325 differentially expressed genes(PC6 only-DEGs)only affected by Neiguan,which were enriched in cytokine-cytokine receptor interaction and other pathways.There were 95 co-DEGs in the heart of non-diseased tissue,which were mainly enriched in positive regulation of defense response and response to interleukin-1;there were 28 ST36 only-DEGs;there were114 PC6 only-DEGs,which were enriched in cardiovascular diseases and other pathways.Conclusion Acupuncture of"Zusanli"and"Neiguan"could improve UC mice's symptoms and pathological colon changes.However,through transcriptomic analysis,it was found that the two acupoints had differences in gene transcription effects on the colon of diseased tissue and the heart of non-diseased tissue,suggesting that acupoints with different distribution positions had some similarities in macro efficacy.Still,there were some differences at a micro level.

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