1.Properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle Chlorella and its effects on healing of infected full-thickness skin defect wounds in mice
Zhenzhen YAN ; Yuxiang WANG ; Tinglin ZHANG ; Jingnan XUN ; Yicheng MA ; Chao JI ; Jie GAO ; Shichu XIAO
Chinese Journal of Burns 2024;40(1):33-42
Objective:To explore the properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle (AgNP) Chlorella (hereinafter referred to as the composite hydrogel) and its effects on healing of infected full-thickness skin defect wounds in mice. Methods:The research was an experimental research. The simple gelatin-polyethylene glycol hydrogel (hereinafter referred to as the simple hydrogel) and the composite hydrogel were prepared, and the appearance and injectability of the two hydrogels were observed at 55 and 37 ℃, and under the irradiation of 808 nm near-infrared light, respectively. An electronic universal testing machine was employed to assess the tensile and compressive stress-strain properties of both types of hydrogels at room temperature. Additionally, the cyclic compressive stress-strain properties of the composite hydrogel were examined at 80% of the maximum compressive stress. Staphylococcus aureus or Escherichia coli solution was added to phosphate buffer solution (PBS), simple hydrogel, and composite hydrogel, respectively. The part of composite hydrogel containing Staphylococcus aureus or Escherichia coli solution was irradiated with near-infrared light for 5 minutes. After each sample was incubated for 6 h, the dilution plating method was used to detect and calculate the mortality rates of the two bacteria at 24 h of culture ( n=5). The discarded foreskin tissue was taken from a 6-year-old healthy boy admitted to the Department of Urology of the First Affiliated Hospital of Naval Medical University for circumcision. Primary human fibroblasts (HFbs) were isolated using the enzyme extraction method, routinely cultured to the 3 rd to 6 th passages for subsequent cellular experiments. Composite hydrogel extracts with final mass concentrations of 100.0, 50.0, 25.0, 12.5, and 0 mg/mL were respectively prepared and used to culture HFbs, and the cell proliferation after 24 h of culture was detected using a cell counting kit 8 ( n=3). A total of twenty 6-8 weeks old C57BL/6J female mice were utilized, and a full-thickness skin defect was surgically created on the back of each mouse. The wounds were infected with Staphylococcus aureus solution. The infected mice were divided into blank control group, simple hydrogel group, composite hydrogel group, and combined treatment group according to the random number table, and the wounds were treated with PBS, simple hydrogel, composite hydrogel, and composite hydrogel+light irradiation (under the irradiation of 808 nm near-infrared light for 5 min), respectively, with 5 mice in each group. On post injury day (PID) 0 (immediately after the first wound treatment), 3, 7, and 14, an overall assessment of wound exudation and healing were conducted, and the wound healing rates on PID 7 and 14 were calculated ( n=5). On PID 14, hematoxylin-eosin staining was performed to observe histopathological changes in the mouse wound. Results:Both simple hydrogel and composite hydrogel were in a solution state at 55 ℃ and transition to a gel state when cooling to 37 ℃. After the two hydrogels were irradiated by near-infrared light, only the composite hydrogel reheated up and returned to the solution state again with injectability. The maximum tensile stress of the composite hydrogel was up to 301.42 kPa, with a corresponding strain of 87.19%; the maximum compressive stress was up to 413.79 kPa, with a corresponding strain of 91.67%, which was similar to the tensile and compressive properties of the simple hydrogel. After 10 compression cycles, the maximum compressive stress of the composite hydrogel still reached 84.1% of the first compressive stress. After 24 h of culture, the mortality rate of Staphylococcus aureus treated with simple hydrogel was significantly higher than that treated with PBS ( P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel alone were significantly higher than those treated with simple hydrogel ( P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel+light irradiation were significantly higher than those treated with composite hydrogel alone ( P<0.05). After 24 h of culture, compared with that cultured in composite hydrogel immersion solution with final mass concentration of 0 mg/mL, the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentrations of 25.0 and 50.0 mg/mL was significantly enhanced ( P<0.05), while the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentration of 100 mg/mL was significantly decreased ( P<0.05). On PID 0 and 3, more purulent secretions were seen in the wounds of mice in blank control group and simple hydrogel group, while only a small amount of exudate was observed in the wounds of mice in composite hydrogel group, and no obvious infection was observed in the wounds of mice in combined treatment group. On PID 7 and 14, the wound healing rates of mice in simple hydrogel group were significantly higher than those in blank control group ( P<0.05); the wound healing rates of mice in composite hydrogel group were significantly higher than those in simple hydrogel group ( P<0.05); the wound healing rates in combined treatment group were significantly higher than those in composite hydrogel group ( P<0.05). On PID 14, the wounds of mice in blank control group exhibited a high infiltration of inflammatory cells with no new epithelial layer observed; the wounds of mice in simple hydrogel group displayed a short length of newly formed epithelium with a small amount of inflammatory cells; the wounds of mice in composite hydrogel group exhibited continuous formation of new epithelium and a large amount of immature granulation tissue; the wounds of mice in combined treatment group showed continuous epithelialization with less immature granulation tissue. Conclusions:The prepared composite hydrogel exhibits excellent thermosensitivity, photothermal properties, and injectability, as well as excellent mechanical properties, antibacterial properties, and biocompatibility, and can promote the healing of infected full-thickness skin defect wounds in mice.
2.Latest research and prospect of CD47 in kidney transplantation
Yuxiang CHEN ; Zhuocheng LI ; Liang GAO ; Xuyuan ZHU ; Yu ZHANG ; Tao LI ; Hongtao JIANG
Organ Transplantation 2024;15(2):282-288
CD47 is a transmembrane protein widely expressed on cell surface, which is considered as a key molecule for immune escape. With an increasing number of related studies, the role of CD47 and its ligands in immunomodulatory effects has been gradually understood. Recent studies have investigated the role of CD47 in ischemia-reperfusion injury of allogenetic kidney transplantation, rejection and xenotransplantation. Nevertheless, the specific role and the key mechanism remain elusive. In this article, the structure and function of CD47, common CD47 ligands, the relationship between CD47 and kidney transplantation, and the application of CD47 in kidney transplantation were reviewed, the latest research progress of CD47 in kidney transplantation was summarized, and the limitations of current research and subsequent research direction were analyzed, aiming to provide reference for subsequent application of CD47 in allogeneic and kidney xenotransplantation.
3.Research progress in roles of circular RNA in brain function regulation and drug addiction
Xixi YANG ; Feifei GAO ; Xiaoyu YANG ; Jingqi GAO ; Yuxiang ZHANG ; Chunxia YAN
Chinese Journal of Pharmacology and Toxicology 2024;38(1):46-55
Circular RNA(circRNA)is an emerging class of endogenous non-coding RNA,which is widely expressed in the brain and plays an important role in a variety of biological processes.Research has shown that circRNA plays a key role in physiological and pathological processes of the brain,such as neurodevelopment,synaptic plasticity and neurodegenerative diseases through a variety of mecha-nisms such as adsorption of microRNA,binding to proteins and translation of peptides.In the field of drug addiction,the expression of circRNA is significantly changed in animal models and brains of addicts,and the regulation involves neural adaptation in brain regions that form the reward circuit such as the nucleus accumbens and prefrontal cortex.Additionally,addiction-related circRNAs are closely associated with neurotransmitter systems,signaling pathways,and neuroinflammatory responses,and they influ-ence the formation and maintenance of drug addiction by modulating gene expression networks related to drug addiction.Here,the biogenesis and regulatory mechanism of circRNA as well as its important role in brain function and drug addiction are reviewed in order to provide a new perspective for explora-tions of the pathological mechanism of drug addiction.
4.Fluorescent probes and imaging techniques for deep-tissue optical imaging:a review
Yuxiang GAO ; Le GUO ; Hui LI ; Xueliang ZHANG ; Nuernisha ALIFU
Chinese Journal of Medical Physics 2024;41(2):169-174
The research advancements in probes for deep-tissue imaging and adaptive optical imaging technologies are summarized,aiming to offer a new perspective for life science and interdisciplinary research.The review firstly gives an introduction on the probes emitting in the near-infrared-Ⅱ region,including fluorescence,bioluminescence,chemiluminescence,and persistent luminescence,and then elaborates direct sensing methods for rapid measurement and correction of wavefront distortions,as well as indirect sensing methods for correcting complex optical aberrations.The continuous updating of the above techniques and methods has enabled optical imaging to successfully penetrate deeper tissues with a remarkable reduction of background noise for higher image quality.
5.Expression and significance of MMR protein,HER2 and Ki-67 in colorectal cancer
Fei YANG ; Yaming ZHANG ; Chaoping ZHOU ; Datian WANG ; Bin GAO ; Jun MA ; Daibin TANG ; Jianwei YUAN ; Yuxiang WANG
Chongqing Medicine 2024;53(9):1317-1322
Objective To investigate the expression and clinical significance of mismatch repair (MMR) protein,human epidermal growth factor receptor (HER)2 and Ki-67 in colorectal cancer.Methods The clini-cal data of 559 patients with colorectal cancer who underwent surgical treatment in the hospital from October 2017 to May 2022 were retrospectively analyzed.The expressions of MMR protein (MLH1,MSH2,PMS2, MSH6),HER2 and Ki-67 in colorectal cancer were detected by immunohistochemistry,and the relationship between them and the clinicopathological features of colorectal cancer was analyzed.Results Among the 559 patients with colorectal cancer,43 cases (7.7%) were deficient mismatch repair (dMMR),8 cases(1.4%) were HER2 +++,and 251 cases (44.9%) were Ki-67 +++.The expression rate of dMMR in the colorec-tal cancer patients with different age,tumor location,tumor maximum diameter,gross type,histological grade,lymph node metastasis and TNM stage was significantly different (P<0.05).The expression rate of HER2 ++/+++ in the patients with different gross types of colorectal cancer was statistically significant (P<0.05).The expression rate of Ki-67 +++ in the colorectal cancer patients with different histological types,histological grades,lymph node metastasis,distant metastasis and TNM staging was statistically signifi-cant (P<0.05).There was no correlation between MMR protein and the expression of HER2 and Ki-67 (P>0.05).Conclusion The expression of MMR proteins in colorectal cancer is closely related to its clinicopatho-logical features.
7.Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis
Shanghao LIU ; Hongmei ZU ; Yan HUANG ; Xiaoqing GUO ; Huiling XIANG ; Tong DANG ; Xiaoyan LI ; Zhaolan YAN ; Yajing LI ; Fei LIU ; Jia SUN ; Ruixin SONG ; Junqing YAN ; Qing YE ; Jing WANG ; Xianmei MENG ; Haiying WANG ; Zhenyu JIANG ; Lei HUANG ; Fanping MENG ; Guo ZHANG ; Wenjuan WANG ; Shaoqi YANG ; Shengjuan HU ; Jigang RUAN ; Chuang LEI ; Qinghai WANG ; Hongling TIAN ; Qi ZHENG ; Yiling LI ; Ningning WANG ; Huipeng CUI ; Yanmeng WANG ; Zhangshu QU ; Min YUAN ; Yijun LIU ; Ying CHEN ; Yuxiang XIA ; Yayuan LIU ; Ying LIU ; Suxuan QU ; Hong TAO ; Ruichun SHI ; Xiaoting YANG ; Dan JIN ; Dan SU ; Yongfeng YANG ; Wei YE ; Na LIU ; Rongyu TANG ; Quan ZHANG ; Qin LIU ; Gaoliang ZOU ; Ziyue LI ; Caiyan ZHAO ; Qian ZHAO ; Qingge ZHANG ; Huafang GAO ; Tao MENG ; Jie LI ; Weihua WU ; Jian WANG ; Chuanlong YANG ; Hui LYU ; Chuan LIU ; Fusheng WANG ; Junliang FU ; Xiaolong QI
Chinese Journal of Laboratory Medicine 2023;46(1):52-61
Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.
8.The E3 ubiquitin ligase NEDD4-1 protects against acetaminophen-induced liver injury by targeting VDAC1 for degradation.
Yiwei ZHU ; Lin LEI ; Xinghui WANG ; Linfang CHEN ; Wei LI ; Jinxia LI ; Chenchen ZHAO ; Xiliang DU ; Yuxiang SONG ; Wenwen GAO ; Guowen LIU ; Xinwei LI
Acta Pharmaceutica Sinica B 2023;13(4):1616-1630
Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.
9.Preoperative interventional embolization for intracranial hypervascular tumors
Chao GAO ; Wei NI ; Hanqiang JIANG ; Jiabin SU ; Heng YANG ; Yuxiang GU
Chinese Journal of Neuromedicine 2023;22(2):135-141
Objective:To investigate the therapeutic value of interventional embolization on feeding artery in intracranial hypervascular tumors.Methods:Forty-five patients with intracranial hypervascular tumors, admitted to and accepted interventional embolization of the feeding artery before craniotomy in Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from March 2019 to August 2022, were chosen; a retrospective analysis was performed on the clinical data of these patients. The imaging characteristics, pathological types, preoperative embolization indications, embolization effects and embolism-related complications were summarized to evaluate the safety and effecacy of preoperative interventional embolization.Results:Among the 45 patients, 21 patients had hemangioblastomas, 15 had meningiomas, 5 had hemangiopericytomas, and 4 had glomus jugular tumors. The technical success rate of interventional embolization was 97.8% (44/45); in this frustrated case, the middle meningeal artery was too circuitous for microcatheter to pass. Among the successful ones, 41 patients used liquid embolism agent onyx and 3 patients applied liquid embolism agent NBCA. Seven, 26 and the rest 11 patients achieved complete embolization, sub-total embolization and partial embolization, respectively. Four patients had embolism-related complications, including 2 with rupture of middle meningeal arteries, 1 with Marathon catheter failed to be pulled out, and 1 with functional glomus jugular tumor having pheochromocytoma crisis; these 4 patients were treated timely without serious complications.Conclusion:For intracranial hypervascular tumors, preoperative interventional embolization is safe and effective; it is necessary to master embolization indications and select appropriate embolization methods and materials.
10.The preference for Front-of-Pack Labeling and its association with the understanding of Nutrition Facts Panel among residents aged 18 to 70: results of a survey in 6 provinces of China
Yiluan HU ; Ruijie YAN ; Yan JIANG ; Jingwen ZHANG ; Lihong YE ; Lin XIANG ; Jia CUI ; Yuxiang TANG ; Chao GAO ; Li XIAO ; Yuexin YANG ; Juan ZHANG
Chinese Journal of Preventive Medicine 2022;56(7):952-959
Objective:To investigate the preference for Front-of-Pack Labeling (FOP) and its association with the understanding of the Nutrition Facts Panel among Chinese residents.Methods:A multi-stage sampling strategy was adopted to select 3 002 people aged between 18 and 70 years old from the eastern region of China (Beijing, Jiangsu Province, Guangdong Province), the northeast region (Heilongjiang Province), the central region (Henan Province) and the western region (Sichuan Province) from July 2020 to March 2021. Socio-demographic characteristics of participants and their understanding of the Nutrition Facts Panel and preference for FOP were collected. The χ2 test was conducted to compare the preference for FOP in different groups of population, and multivariate logistic regression was used to analyze the association between the preference for FOP and the understanding of the Nutrition Facts Panel. Results:The mean age of 3 002 participants was (42.3±13.4) years, of which 1 914 (63.8%) were females and 69.3% could not understand the Nutrition Facts Panel. About 2 458 respondents (81.9%) suggested that FOP could be promoted. The top three nutrients that should be labeled were sugar (68.4%), salt (68.2%) and total fat (62.4%). The number of participants who believed that the Multiple Traffic Lights (MTL) could be easier to help consumers to quickly choose healthy food, attract attention and provide the most needed information was 1 064 (35.4%), 1 026 (34.2%) and 1 140 (38.0%), respectively. The multivariate logistic regression analysis showed that, compared with the Guideline Daily Amount (GDA) system, participants who could not understand the Nutrition Facts Panel preferred (1) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could quickly help you choose food more easily?"[ OR (95% CI): 2.21 (1.62-3.02), 1.64 (1.22-2.22), 1.79 (1.31-2.45), respectively]; (2) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could attract your attention the most?"[ OR (95% CI): 2.62 (1.92-3.59), 1.96 (1.45-2.66), 2.25 (1.66-3.04), respectively]; and (3) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could provide you with the most needed information?"[ OR (95% CI): 2.33 (1.70-3.21), 2.21 (1.66-2.95), 2.01 (1.50-2.71), respectively]. Conclusion:The residents from six provinces in China have a supportive attitude towards FOP. The interpretive FOP with color information, specific nutrient information and summary indicator can be launched. The nutrition information of sugar, salt and total fat could be prioritized to be labeled on the FOP.

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