1.Impact of Maxing Kugan Decoction on Inflammatory Response and Apoptosis in Oleic Acid-induced Acute Lung Injury in Rats via p38 MAPK/NF-κB Signaling Pathway
Taiqiang JIAO ; Yi NAN ; Ling YUAN ; Jiaqing LI ; Yang NIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):108-116
ObjectiveTo investigate the effects of Maxing Kugan decoction (MKD) on inflammatory response and apoptosis in rats with oleic acid (OA)-induced acute lung injury (ALI) and explore its mechanism of action. MethodsSixty Sprague-Dawley (SD) rats were randomly assigned into six groups: a control group, a model group, a dexamethasone-treated group (2 mg·kg-1), and three MKD-treated groups at low, medium, and high doses (3.1, 6.2,12.4 g·kg-1). Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA (0.2 mL·kg-1). Twelve hours after modeling, blood gas analyses were conducted, and the wet-to-dry (W/D) weight ratio of lung tissue was measured for each group. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin (HE) staining and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assays, and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the control group, the model group exhibited a significant decrease in partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), and oxygenation index (PaO2/FiO2), along with a marked increase in partial pressure of carbon dioxide (PaCO2) and lung W/D ratio (P<0.01). Additionally, levels of TNF-α, IL-6, and IL-1β in BALF were significantly elevated (P<0.01). Histopathological analysis of lung tissue showed significant inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK, NF-κB p65, inhibitor of NF-κB (IκBα), B-cell lymphoma-2 associated x protein (Bax), and Caspases-3, as well as the protein expression levels of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3, while the mRNA and protein expression of Bcl-2 was downregulated (P<0.01). Compared with the model group, MKD significantly elevated PaO2, SaO2, and PaO2/FiO2 while reducing PaCO2 and W/D ratio in rats (P<0.01). It also greatly reduced TNF-α, IL-6, and IL-1β levels in BALF (P<0.01) and alleviated inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Additionally, it downregulated the mRNA expression of p38 MAPK, NF-κB p65, IκBα, Bax, Caspases-3, as well as protein expression of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3 in lung tissue (P<0.05, P<0.01), while significantly upregulating mRNA and protein expression of Bcl-2 (P<0.01). ConclusionMKD exerts a protective effect on OA-induced ALI rats, potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.
2.Impact of Maxing Kugan Decoction on Inflammatory Response and Apoptosis in Oleic Acid-induced Acute Lung Injury in Rats via p38 MAPK/NF-κB Signaling Pathway
Taiqiang JIAO ; Yi NAN ; Ling YUAN ; Jiaqing LI ; Yang NIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):108-116
ObjectiveTo investigate the effects of Maxing Kugan decoction (MKD) on inflammatory response and apoptosis in rats with oleic acid (OA)-induced acute lung injury (ALI) and explore its mechanism of action. MethodsSixty Sprague-Dawley (SD) rats were randomly assigned into six groups: a control group, a model group, a dexamethasone-treated group (2 mg·kg-1), and three MKD-treated groups at low, medium, and high doses (3.1, 6.2,12.4 g·kg-1). Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA (0.2 mL·kg-1). Twelve hours after modeling, blood gas analyses were conducted, and the wet-to-dry (W/D) weight ratio of lung tissue was measured for each group. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin (HE) staining and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assays, and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the control group, the model group exhibited a significant decrease in partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), and oxygenation index (PaO2/FiO2), along with a marked increase in partial pressure of carbon dioxide (PaCO2) and lung W/D ratio (P<0.01). Additionally, levels of TNF-α, IL-6, and IL-1β in BALF were significantly elevated (P<0.01). Histopathological analysis of lung tissue showed significant inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK, NF-κB p65, inhibitor of NF-κB (IκBα), B-cell lymphoma-2 associated x protein (Bax), and Caspases-3, as well as the protein expression levels of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3, while the mRNA and protein expression of Bcl-2 was downregulated (P<0.01). Compared with the model group, MKD significantly elevated PaO2, SaO2, and PaO2/FiO2 while reducing PaCO2 and W/D ratio in rats (P<0.01). It also greatly reduced TNF-α, IL-6, and IL-1β levels in BALF (P<0.01) and alleviated inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Additionally, it downregulated the mRNA expression of p38 MAPK, NF-κB p65, IκBα, Bax, Caspases-3, as well as protein expression of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3 in lung tissue (P<0.05, P<0.01), while significantly upregulating mRNA and protein expression of Bcl-2 (P<0.01). ConclusionMKD exerts a protective effect on OA-induced ALI rats, potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.
3.Resveratrol activates extracellular-regulated protein kinase 5 signaling protein to promote proliferation of mouse MC3T3-E1 cells
Yongkang NIU ; Zhiwei FENG ; Yaobin WANG ; Zhongcheng LIU ; Dejian XIANG ; Xiaoyuan LIANG ; Zhi YI ; Hongwei ZHAN ; Bin GENG ; Yayi XIA
Chinese Journal of Tissue Engineering Research 2025;29(5):908-916
BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.
4.Application of shockwave balloon in the treatment of TASCⅡ C/D femoropopliteal atherosclerosis obliterans
Yi HE ; Hongyu WU ; Shanshan DING ; Yanqing QI ; Fei WU ; Xiaoyang NIU ; Yanling WANG ; Weilong LU ; Bing WANG
Chinese Journal of Radiology 2025;59(5):572-576
Objective:To evaluate the short-and medium-term therapeutic efficacy of shockwave balloon therapy for TASCⅡ C/D femoropopliteal artery atherosclerosis obliteration.Methods:This retrospective cohort study included 25 patients who received shockwave balloon therapy in five vascular centers from August 2022 to June 2023. All patients were diagnosed with TASC Ⅱ C/D femoropopliteal arteriosclerosis obliterans (13 cases of type C and 12 cases of type D), and underwent intravascular shock wave lithotripsy (IVL) to treat calcified lesions. The immediate effectiveness (residual stenosis<30% and no flow-limiting dissection), safety (whether there were adverse vascular events during the operation) and the rate of salvage stent implantation were recorded. The observation indexes of patients before operation, early postoperative period (immediately after operation or before discharge) and postoperative follow-up period (3, 6, 12 months after operation) were collected. The observation indexes included ankle-brachial index (ABI), Rutherford classification, and minimum lumen diameter (MLD). Repeated measures ANOVA was used to evaluate the changes of observation indexes in the early postoperative and follow-up stages compared with those before operation; Kaplan-Meier survival analysis was used to evaluate the one-stage patency rate at follow-up and the target lesion revascularization rate free from clinical drive.Results:The immediate effectiveness of surgery was 100% in all patients, with no vascular related adverse events occurred, and no remedial stent implantation was performed. The ABI, Rutherford grade and MLD of the patients in the early postoperative period and each follow-up stage were improved compared with those before operation, with statistically significant differences ( P<0.05). Kaplan-Meier survival analysis showed that the primary patency rate at 12 months after surgery was 0.78 (95% CI 0.64-0.84), and the revascularization rate of target lesions free from clinical drive was 0.87 (95% CI 0.85-0.95). Conclusion:Shockwave balloon therapy for complex calcified femoropopliteal artery lesions is safe and reliable, with satisfactory short-and medium-term efficacy.
5.Association of tumor circumferential involvement range with neoadjuvant therapy efficacy and long-term outcomes in locally advanced rectal cancer
Ganbin LI ; Xiaoyuan QIU ; Xiao ZHANG ; Lai XU ; Beizhan NIU ; Guannan ZHANG ; Junyang LU ; Bin WU ; Yi XIAO ; Guole LIN
Chinese Journal of Oncology 2025;47(8):750-755
Objective:To detect the association of tumor circumferential involvement range (CIR) with neoadjuvant chemoradiotherapy (NCRT) efficacy and long-term survival outcomes in locally advanced rectal cancer (LARC) patients.Methods:Clinical data of 451 patients admitted to our hospital from January, 2018 to January, 2022 were retrospectively collected. According to the CIRs as determined by rectal magnetic resonance imaging, patients were divided into the High group (≥2/3 cycle, 270 patients) and the Low group (<2/3 cycle, 181 patients). The primary outcome was three-year disease-free survival. The baseline characteristics, pathological features, and survival outcomes were compared.Results:Compared to patients in the Low group, patients in the High group exhibited significantly larger tumor vertical diameters [(4.7±1.7) vs. (3.6±1.4)cm, P<0.001], higher rates of mrT4 stage (37.8% vs. 13.2%, P<0.001), and higher rates of positive mesorectal fascia (54.1% vs. 29.8%, P<0.001) and extramural vascular invasion (55.6% vs. 38.1%, P<0.001). Patients in the High group were mainly pT3-4 stages (46.7% vs. 30.9%, P=0.002), with significantly lower rates of pathological complete response (22.2% vs. 33.1%, P=0.010) , poorer tumor regression grades (48.9% vs. 60.8%, P=0.013), and higher rates of positive peripheral nerve invasion (11.5% vs. 5.5%, P=0.031), as compared to patients in the Low group. The median follow-up time was 40 months. About 11 (2.4%) and 48 patients (10.6%) experienced tumor local recurrence and distant metastasis, respectively. The recurrence rates were 2.2% and 2.6%, and the distant metastasis rates were 7.7% and 12.6%, respectively, in the Low group and the High group, with no statistical significance ( P=0.957, P=0.096). The three-year disease-free survival in the High group was significantly lower than that in the Low group (84.4% vs. 92.4%, P=0.014). Conclusions:The CIR is closely related to tumor burden, which can judge tumor response to NCRT, and is negatively related to survival prognosis. For patients who have more than a 2/3 cycle of CIR, intensified or consolidated treatments may be required to improve survival outcomes.
6.Nano-ITO induce pulmonary alveolar proteinosis through oxidative stress and activation of NF-κB/Nrf2 signaling pathway
Yinqiao LIN ; Yi ZHANG ; Xiaoyang CHEN ; Weikang LI ; Yujing NIU ; Xuefei WANG ; Nan LIU ; Gai LI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(2):81-90
Objective:To investigate the role of the nuclear factor-kappa B (NF-κB) /nuclear factor E2 related factor 2 (Nrf2) pathway in the occurrence of lung tissue in the pulmonary alveolar proteinosis (PAP) model of rats induced by indium tin oxide nanoprticles (Nano-ITO) .Methods:In October 2019, 120 SD rats were divided into 3, 7, 14, 28, 56, and 84 day Nano ITO exposure groups and corresponding time point control groups, with 10 rats in each group; the exposure group was treated with 6 mg/kg·bw Nano-ITO via non exposed tracheal injection, twice a week. Time-course studies were performed to examine the pulmonary toxicity induced by Nano-ITO. At the end of the experiment, cytokines levels and oxidative stress were analyzed in the bronchoalveolar lavaged fluid (BALF). Rat lung tissues were also harvested for staining with HE, PAS, Masson, and Oil Red O. Ultrastructure of lung tissue cells was observed by transmission electron microscope. The localization and expression of NF-κB p65, IκB-α, IKK-β, Nrf2, NQO1, HO-1 were observed by immunohistochemistry, Western blot and real-time fluorescent quantitative PCR. The comparison between the two groups was analyzed by independent sample T test, and the comparison between the multiple groups was analyzed by one-way ANOVA.Results:Nano-ITO intratracheal instillation caused pulmonary toxicity by inducing acute inflammation, granuloma (nodule) formation, and alveolar proteinosis. ELISA analysis showed that, compared with the corresponding time points control groups, the levels of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), malondialdehyde (MDA), interleukin (IL) -1β, IL-6, tumor necrosis factor alpha (TNF-α), IL-10, total protein (TP), and lactate dehydrogenase (LDH) in BALF of rats exposed to Nano ITO were all increased ( P<0.05) ; The protein expression of Nrf2 and NF-κB p65 was upregulated in rat lung tissue, while the protein expression of KK-β was increased ( P<0.01). Nrf2 and its downstream proteins NQO1 and HO-1 were highly expressed in Nano-ITO-induced PAP rat. Conclusion:NF-κB/Nrf2 signal pathway is involved in the process of Nano-ITO induced pulmonary alveolar proteinosis in rats.
7.Risk analysis for coil adverse events based on FDA MAUDE database
Jian-wei YANG ; Lin HUANG ; Yu-juan ZHAO ; Yi XUAN ; Jian-jun CAO ; Chang-qing LIU ; Hui-fang NIU ; Xia LI
Chinese Medical Equipment Journal 2025;46(6):83-87
The coil adverse events in the U.S.Food and Drug Administration Manufacturer and User Facility Device Experience(MAUDE)database from January 2021 to June 2024 were analyzed retrospectively.The risks of coils during the clinical application and their causes were explored with hospital survey and expert demonstration in Shandong Province.Some improving measures were put forward for the safe use of coils,including implementing the main responsibility of the registrant,enhancing the professional skills of the using institutions and strengthening the supervision of the supervisory authorities.[Chinese Medical Equipment Journal,2025,46(6):83-87]
8.Evaluating the factors influencing hospitalization costs of malnourished patients based on variations in DRG cost coefficients
Jian-Mei NIU ; Qian ZHAO ; Qian MO ; Hai-Yan WANG ; LI-Qi ; Jing-Yi LIANG ; Qian-Wen YANG ; Ji-Chuan ZHAO ; Rong-Liang SUN
Parenteral & Enteral Nutrition 2025;32(5):273-277
Objectives:The aim is to analyze the cost structure and coefficient of variation for hospitalized patients with malnutrition based on Diagnosis-Related Groups(DRG),providing a reference for the further application and promotion of DRG.Method:Data were collected from patients admitted to Ningxia Hui Autonomous Region People's Hospital between March 2023 and August 2023.A diagnostic system based on artificial intelligence was used to identify malnourished patients.The composition of hospitalization costs for these individuals was described and analyzed,as was the coefficient of variation for various costs within DRG groupings.A multivariate regression analysis was conducted to identify the factors that influence patient hospitalization costs.Results:The average age of hospitalized patients with malnutrition was(68.12±16.43)years,with an average length of stay of(14.55±8.47)days,with an average hospitalization cost of(32 128.89±35 345.61)yuan.Among patients within the same DRG group,the coefficient of variation for various costs was found to be lower in the malnutrition group than in the normal group.This suggests that when assessed individually,the malnutrition group exhibited a higher degree of homogeneity in their cost structures.The factors influencing total hospitalization costs were found to be:length of hospital stay(P=0.001),nutritional monitoring fees(P=0.020),number of chronic diseases(P=0.003),and Karnofsky Performance Status(KPS)score(P=0.038).Hospitalization costs were positively correlated with both length of stay and nutritional assessment fees,but negatively correlated with the number of chronic diseases and KPS scores.Conclusions:Malnutrition has a profound impact on health outcomes,medical expenses,length of hospital stay,and disease severity.The implementation of the DRG system aims to standardize and improve the nutritional diagnosis and treatment process by categorizing different stages of malnutrition.This approach can minimize variations within DRG groups,making it easier to allocate medical resources more precisely and efficiently.Furthermore,it is a valuable reference tool for promoting DRG payment reform in different regions.
9.Simultaneous Determination of 50 Kinds of Steroid Hormones in Surface Water by Online Solid Phase Extraction Coupled with Ultra Performance Liquid Chromatography-Triple Quadrupole Mass Spectrometry
Fang-Xi XU ; He NIU ; Yu-Tao GE ; Guo-Hua ZHU ; Hang-Bin LYU ; Jin-Song LI ; Lang-Sha YI ; Jian-Jie FU ; Gui-Bin JIANG
Chinese Journal of Analytical Chemistry 2025;53(6):998-1009,中插22-中插41
A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1%and 119%,with relative standard deviations(RSDs)of 0.2%to 9.9%.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.
10.Progress in Methods for Electrochemical Detection of Thrombin
Di WU ; Xi-Yao ZHANG ; Jing-Jing XU ; Yi-Ting CHEN ; Wen-Qi TANG ; Wen-Hui XU ; Song-Min CHEN ; Qiong HU ; Li NIU
Chinese Journal of Analytical Chemistry 2025;53(9):1403-1410
As a serine protease,thrombin can convert soluble fibrinogen into insoluble fibrin and plays a pivotal role in the coagulation cascade.Therefore,the accurate quantitative assay of thrombin levels is of great value in the evaluation of coagulation function,clinical screening and prognostic monitoring of coagulation-related diseases,and screening of drugs for targeted therapy.Existing methods for thrombin detection can be divided into two categories,e.g.,the assay of concentration levels using nucleic acid aptamers as the affinity elements and the assay of activity levels based on the hydrolytic cleavage of substrate peptides.In recent years,electrochemical biosensors have attracted much attention in thrombin detection due to high sensitivity,high selectivity,simple instrument,fast response,and good portability.In this review,the latest research progress in methods for electrochemical detection of thrombin was summarized,focusing on the detection principles and the applied signal amplification strategies of related electrochemical biosensors.In addition,the challenges with respect to the practical use of electrochemical thrombin biosensors and the prospects were discussed.

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