1.Fabrication and in vitro biocompatibility of porous Ti/chitason/hydroxyapatite composite scaffold
Xiang LI ; Chendong FENG ; Lin WANG ; Chengtao WANG
Chinese Journal of Orthopaedic Trauma 2016;18(1):6-10
Objective To evaluate the feasibility of the porous titanium/chitosan/hydroxyapatite (Ti/Ch/HA) composite scaffold as a bone repair substitute.Methods Additive manufacturing (3D printing) technology was used to fabricate porous Ti scaffolds as supporting structures.Chitosan/hydroxyapatite (Ch/HA) sponge was prepared within the macro-pores of Ti scaffolds using freeze drying technology.Thus,a kind of composite porous Ti/Ch/HA scaffold with good cell affinity was obtained.Osteoblastic cells were seeded and cultured in pure porous Ti scaffolds and composite Ti/Ch/HA scaffolds for 7 days.The cellular morphology,seeding efficiency and proliferation were examined and compared between the 2 kinds of scaffolds using scanning electron microscopy (SEM) and MTT assay.Results The SEM examination showed that the macro-pores of Ti/Ch/HA scaffolds were full of the composite sponge structure of Ch/HA,with a micropore size of 50 to 200 μm.Like the pure porous Ti scaffolds,composite Ti/Ch/HA ones have a compressive strength of 168.2 to 192.6 MPa,a yielding strength of 137.1 to 154.1 MPa,and a Young's modulus of 3.21 to 4.51 GPa.After culture for 7 days,a large number of flat cells adhered onto the surface of Ti scaffolds while the cells adhering onto the Ti/Ch/HA composite scaffolds were fusiform.The seeding efficiency of osteoblastic cells in the composite Ti/Ch/HA scaffolds (73.218% ± 3.748%) was significantly higher than that in the pure porous Ti scaffolds (21.352% ±4.365%) (P <0.05);the OD value of the composite Ti/Ch/HA scaffolds (0.783 ±0.043) was significantly higher than that of the pure porous Ti scaffolds (0.382 ± 0.036) (P < 0.05).Conclusions Ti/Ch/HA composite scaffolds can match human bone in mechanical properties.Compared with pure porous Ti scaffolds,the Ti/Ch/HA composite ones are more suitable for adhesion and proliferation of osteoblasts,making them an ideal kind of bone repair substitute.
3.Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer
Chenyang LI ; Chujun CAI ; Chendong WANG ; Xiaoping CHEN ; Bixiang ZHANG ; Zhao HUANG
Clinical and Molecular Hepatology 2025;31(2):350-381
The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.
4.Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer
Chenyang LI ; Chujun CAI ; Chendong WANG ; Xiaoping CHEN ; Bixiang ZHANG ; Zhao HUANG
Clinical and Molecular Hepatology 2025;31(2):350-381
The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.
5.Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer
Chenyang LI ; Chujun CAI ; Chendong WANG ; Xiaoping CHEN ; Bixiang ZHANG ; Zhao HUANG
Clinical and Molecular Hepatology 2025;31(2):350-381
The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.
6.Relationship between serum CC?16,MCP?1 level and disease severity and prognosis in patients with acute respiratory distress syndrome
Yadong CHENG ; Hui LIU ; Chen CUI ; Aiwen WANG ; Yangzhou WANG ; Fang WANG ; Xiaohui LI ; Yanfang GAO ; Chendong WU
Clinical Medicine of China 2019;35(4):290-295
Objective To observe the changes of serum clara cell protein?16 ( CC?16 ) and monocyte chemotaxis protein?1 (MCP?1) level in patients with acute respiratory distress syndrome (ARDS) and to explore their relationship with the disease severity and prognosis of ARDS??Methods One hundred and fourteen patients with ARDS who were admitted to Changzhi People′s hospital from January 2017 to March 2018 were selected as the subjects??They were divided into mild group ( n=37),moderate group (n=41) and severe group ( n=36) according to the severity of ARDS??Sixty healthy persons in out?patient examination were selected as control group??The survival situation of patients in 4 weeks were recorded,the patients were divided into survival group ( n=65) and death group ( n=49) according to their survival situation??The age,gender,body mass index (BMI),smoking history,acute physiology and acute physiology and chronic health evaluation II ( APACHE II) score,sequential organ failure assessment ( SOFA) score, serum CC?16 and MCP?1 level were analyzed in each group??The relationship between serum CC?16,MCP?1 level and disease and prognosis of patients with ARDS were analyzed??Results With the increase of disease severity,APACHE II score, SOFA score and serum CC?16, MCP?1 level in patients with ARDS were significantly increased??The differences were statistically significant ( F=1 216??886,1 339??247,290??879, 417??262; all P=0??000)??The APACHE II score,SOFA score and serum CC?16,MCP?1 levels in the death group were (22??13± 2??47) scores,( 15??09 ± 1??97) scores,( 23??85 ± 4??27) μg/L, ( 36??64 ± 5??21) ng/L respectively,which were significantly higher than those in the survival group (18??25±2??35) scores,(13??23 ±2??03) scores,(17??34±4??13) μg/L,(27??93±4??88) ng/L,the differences were statistically significant (t=8??538,4??905,8??211,9??146;all P=0??000)??Pearson correlation analysis showed that there was a positive correlation between serum CC?16 level and MCP?1 level in patients with ARDS ( r=0??589, P =0??000)??Meanwhile,the CC?16,MCP?1 were positive correlation with APACHE II score,SOFA score and mortality (CC?16:r=0??504,0??549,0??472;P=0??000,0??000,0??012;MCP?1:r=0??493,0??528,0??435;P=0??006, 0??000,0??025)??APACHE II score ( OR=3??083,95%CI:0??025-1??364,P<0??05),CC?16 ( OR=5??403, 95%CI:0??011-6??561, P<0??05) and MCP?1 ( OR=2??892, 95%CI: 0??034-1??619, P<0??05) were all closely related to ARDS death??CC?16 independent detection, MCP?1 independent detection and the two combined detection predicted the under?curve area, sensitivity and specificity of ARDS patients with in 4 weeks were 0??830, 82??35% and 72??16%; 0??719, 79??25% and 72??19%; 0??866, 85??06% and 80??72%respectively??Conclusion CC?16,MCP?1 are abnormally high expression in serum of patients with ARDS, and its levels are closely related to the severity and prognosis of patients with ARDS??CC?16 combined with MCP?1 detection has high diagnostic value for patients with ARDS,which can be used as an effective index to judge the disease and prognosis of patients with ARDS??
7.Glabridine regulates NETs to inhibit pyrodeath and alleviate lung injury in sepsis
Lingqing YANG ; Chendong MA ; Lei WANG ; Min WANG ; Zengliang LI ; Lipeng ZHANG
Chinese Journal of Emergency Medicine 2024;33(2):179-185
Objective:To investigate the effect of glabridin on neutrophil extracellular traps (NETs) formation and pyroptosis in rats with sepsis-induced lung injury.Methods:Twenty-four male Wistar rats were divided into three groups according to the random number table method. The sepsis group was established by cecal ligation and puncture (CLP). The Glabridin group underwent CLP and glabridin gavage (30 mg/kg)(CLP+GLA). The sham operation group underwent cecal exploration, and only the abdomen was closed after cecal turning(Sham). After 12 hours, plasma、alveolar lavage fluid and lung tissue samples were taken for detection . Then, protein content of the alveolar lavage fluid was determined; The wet/dry weight(W/D) ratio of the lung tissue was determined; The pathological changes in lung tissue were observed after hematoxylin-eosin (HE) staining. The levels of NETs marker MPO-DNA complex and related inflammatory factors IL-18 and IL-1β in plasma were detected by enzyme-linked immunosorbent assay. The changes of Caspase-1and Cleaved-caspase-1 protein in lung tissue were detected by Western blot.Results:The total protein concentration of alveolar lavage fluid was significantly higher in the sepsis group compared with the Sham group ( P<0.01), and it decreased in the glabridin group compared with the sepsis group ( P<0. 05). Significant aggravation of pulmonary edema in the sepsis group, and the glabridin group reduced pulmonary edema compared with the sepsis group.The pathological results of lung tissue under the light microscope showed: The structure of lung tissue in the Sham group was normal, and the alveoli were clear; In the sepsis group, the alveolar wall was thickened widely and inflammatory cells infiltrated obviously; Compared with the sepsis group, the lung tissue injury was significantly reduced in the light licorice group. The enzyme-linked immunosorbent assay results showed that the levels of NETs marker MPO-DNA complex and inflammatory factors IL-18 and IL-1β in the plasma of the sepsis group were significantly higher than those in the Sham group ( P<0.001). The levels of NETs marker MPO-DNA complex and inflammatory factors IL-18 and IL-1β in the glabridin group were significantly lower than those in the sepsis group (MPO-DNA: P<0. 01; IL-18、IL-1β: P<0.05) . Western blot Technical results showed that the expression of Caspase-1 and Cleaved-caspase-1 protein positive signal was significantly enhanced in the lung tissue of the rats in the sepsis group compared with the Sham group; the distribution of Caspase-1 positive cells in the lung tissue of the sepsis + glabridin group was similar to that of the Sham group, and the expression of Cleaved-caspase-1 positive signal was higher than that of the Sham group. Conclusions:Glabridin can effectively reduce lung inflammation and play a protective role in lung injury in septic rats by inhibiting NETs production and pyroptosis.
8.Effects of Fe₃O₄ on the denitrification performance of Pseudomonas stutzeri.
Shanshan XU ; Jindeng ZHOU ; Chendong SHUANG ; Qing ZHOU ; Aimin LI
Chinese Journal of Biotechnology 2021;37(10):3685-3695
Biological denitrification is the most widely used technology for nitrate removal in wastewater treatment. Conventional denitrification requires long hydraulic retention time, and the nitrate removal efficiency in winter is low due to the low temperature. Therefore, it is expected to develop new approaches to enhance the denitrification process. In this paper, the effect of adding different concentrations of Fe₃O₄ nanoparticles on the denitrification catalyzed by Pseudomonas stutzeri was investigated. The maximum specific degradation rate of nitrate nitrogen improved from 18.0 h⁻¹ to 23.7 h⁻¹ when the concentration of Fe₃O₄ increased from 0 mg/L to 4 000 mg/L. Total proteins and intracellular iron content also increased along with increasing the concentration of Fe₃O₄. RT-qPCR and label-free proteomics analyses showed that the relative expression level of denitrifying genes napA, narJ, nirB, norR, nosZ of P. stutzeri increased by 55.7%, 24.9%, 24.5%, 36.5%, 120% upon addition of Fe₃O₄, and that of denitrifying reductase Nap, Nar, Nir, Nor, Nos increased by 85.0%, 147%, 16.5%, 47.1%, 95.9%, respectively. No significant difference was observed on the relative expression level of denitrifying genes and denitrifying reductases between the bacteria suspended and the bacteria adhered to Fe₃O₄. Interestingly, the relative expression level of electron transfer proteins of bacteria adhered to Fe₃O₄ was higher than that of the bacteria suspended. The results indicated that Fe₃O₄ promoted cell growth and metabolism through direct contact with bacteria, thereby improving the denitrification. These findings may provide theoretical support for the development of enhanced denitrification.
Aerobiosis
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Denitrification
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Nitrates
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Nitrogen
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Pseudomonas stutzeri/genetics*
9.Development of the novel ACLY inhibitor 326E as a promising treatment for hypercholesterolemia.
Zhifu XIE ; Mei ZHANG ; Qian SONG ; Long CHENG ; Xinwen ZHANG ; Gaolei SONG ; Xinyu SUN ; Min GU ; Chendong ZHOU ; Yangming ZHANG ; Kexin ZHU ; Jianpeng YIN ; Xiaoyan CHEN ; Jingya LI ; Fajun NAN
Acta Pharmaceutica Sinica B 2023;13(2):739-753
Hepatic cholesterol accumulation is an important contributor to hypercholesterolemia, which results in atherosclerosis and cardiovascular disease (CVD). ATP-citrate lyase (ACLY) is a key lipogenic enzyme that converts cytosolic citrate derived from tricarboxylic acid cycle (TCA cycle) to acetyl-CoA in the cytoplasm. Therefore, ACLY represents a link between mitochondria oxidative phosphorylation and cytosolic de novo lipogenesis. In this study, we developed the small molecule 326E with an enedioic acid structural moiety as a novel ACLY inhibitor, and its CoA-conjugated form 326E-CoA inhibited ACLY activity with an IC50 = 5.31 ± 1.2 μmol/L in vitro. 326E treatment reduced de novo lipogenesis, and increased cholesterol efflux in vitro and in vivo. 326E was rapidly absorbed after oral administration, exhibited a higher blood exposure than that of the approved ACLY inhibitor bempedoic acid (BA) used for hypercholesterolemia. Chronic 326E treatment in hamsters and rhesus monkeys resulted in remarkable improvement of hyperlipidemia. Once daily oral administration of 326E for 24 weeks prevented the occurrence of atherosclerosis in ApoE-/- mice to a greater extent than that of BA treatment. Taken together, our data suggest that inhibition of ACLY by 326E represents a promising strategy for the treatment of hypercholesterolemia.
10.Short-term efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy for the treatment of non-small cell lung cancer
Yixing LI ; Heng ZHAO ; Bohao LIU ; Jizhao WANG ; Yanpeng ZHANG ; Chendong GUO ; Chuchen ZHAO ; Kun FAN ; Hongyi WANG ; Runyi TAO ; Zhiyu WANG ; Jia ZHANG ; Junke FU ; Guangjian ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(03):369-374
Objective To explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. Methods The clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. Results After preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. Conclusion Pembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.