1.Human umbilical cord mesenchymal stem cell-derived exosomes attenuate renal ischemia-reperfusion injury by up-regulating ATF3 to inhibit the TLR4/NF-κB pathway
Xingyu* WAN ; Yujia LIU ; Ruiyan WANG ; Hao WANG ; Yi ZHAO ; Lu GUO ; Zhihua YANG ; Xinghua LÜ
Organ Transplantation 2026;17(2):275-286
Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.
2.Research progress on the microbiota-gut-brain axis regulatory mechanisms and targeted dietary interventions in autism spectrum disorder
Mingyue HAO ; Jiajun CHANG ; Zhihua ZHANG ; Lan GAO
Acta Universitatis Medicinalis Anhui 2026;61(2):376-386
Autism spectrum disorder (ASD), also known as autism, is a series of neurodevelopmental disorders characterized by social disorders and repetitive stereotyped behaviors/narrow interests. Its pathogenesis is complex, and there is a lack of effective treatment drugs, with some cases having adverse outcomes. Recent studies have consistently revealed that individuals with autism spectrum disorder (ASD) commonly exhibit characteristics such as gut microbiota dysbiosis (abnormal Bacteroidetes/Firmicutes ratio), impaired intestinal barrier function (elevated serum levels of zonulin and LPS), and intestinal immune dysregulation (increased pro-inflammatory cytokines including IL-6 and TNF-α), suggesting that gastrointestinal abnormalities may influence central nervous system development through neuroendocrine, immunoregulatory, and metabolic pathways. Consequently, growing scholarly attention has focused on dietary interventions as potential approaches to alleviate clinical symptoms in children with ASD. This review systematically summarizes the role of gut microbiota and their metabolite alterations in ASD pathogenesis, along with recent advancements in understanding the microbiota-gut-brain axis mechanisms. Additionally, it elaborates on the therapeutic effects and underlying biological basis of restrictive diet therapy, modified diet therapy, and nutritional supplementation therapy in promoting the health of children with ASD. This systematic review reveals that children with ASD exhibit significant gut microbiota dysbiosis (e.g., increased Clostridium, decreased Faecalibacterium) and abnormal metabolite profiles (e.g., altered short-chain fatty acid spectra, elevated 4EPS levels). These alterations exacerbate neuroinflammation and immune dysregulation through the microbiota-gut-brain axis, thereby impacting nervous system development and function. Furthermore, interventions such as ketogenic diets, camel milk, and specific nutritional supplements can alleviate certain ASD symptoms by modulating gut microbiota, restoring intestinal barrier function, and improving metabolic pathways. Future investigations should aim to create multi-omics evaluation systems for pinpointing potential beneficiaries, devise individualized intervention strategies rooted in microbiome characteristics, and verify their therapeutic value and safety in large-scale randomized controlled trials. These efforts are crucial to transitioning ASD treatment from symptomatic control to address disease etiology, thereby paving the way for improving prognoses.
3.Consensus on informed consent for orthodontic treatment
Yang CAO ; Bing FANG ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Lin WANG ; Haiping LU ; Zhihe ZHAO ; Tianmin XU ; Weiran LI ; Min HU ; Jinlin SONG ; Jun WANG ; Fang JIN ; Ding BAI ; Xianglong HAN ; Yuehua LIU ; Bin YAN ; Jie GUO ; Jiejun SHI ; Yongming LI ; Zhihua LI ; Xiuping WU ; Jiangtian HU ; Linyu XU ; Lin LIU ; Yi LIU ; Yanqin LU ; Wensheng MA ; Shuixue MO ; Liling REN ; Shuxia CUI ; Yongjie FAN ; Jianguang XU ; Lulu XU ; Zhijun ZHENG ; Peijun WANG ; Rui ZOU ; Chufeng LIU ; Lunguo XIA ; Li HU ; Weicai WANG ; Liping WU ; Xiaoxing KOU ; Jiali TAN ; Yuanbo LIU ; Bowen MENG ; Yuantao HAO ; Lili CHEN
Chinese Journal of Stomatology 2025;60(12):1327-1336
This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.
4.The dominant deafness point mutation GJB2 p.D179N affects the oligomeric equilibrium of connexin 26
Huahong LUO ; Guohui HUANG ; Yunge GAO ; Tao YANG ; Hao WU ; Zhihua ZHANG
Journal of Audiology and Speech Pathology 2025;33(3):259-264
Objective To investigate the impact of the dominant deafness point mutation p.D179N on the oli-gomeric equilibrium state of Connexin 26(Cx26).Methods The wild-type Cx26 fusion protein(Cx26-WT-GFP)and mutant fusion proteins(Cx26-D179N-GFP,Cx26-D179C-GFP)were expressed in HEK293F cells.By using Fluorescence-detection size-exclusion chromatography(FSEC)and size-exclusion chromatography(SEC)to analysis the oligomeric state of the target protein based on malecular weight under the condition of solubilization and purifica-tion respectively.Cryo-electron microscopy(Cryo-EM)single particle analysis(SPA)was conducted to analysis the target protein's oligomeric states based on the 2D classification morphology of the protein particles.Results In vitro,the wild-type Cx26 protein(Cx26-WT)is almost exclusively dodecameric.The deafness mutation p.D179N protein(Cx26-D179N)exists as both dodecamers and hexamers,whereas the artificial mutation p.D179C protein(Cx26-D179C)does not form dodecamers.Conclusion The dominant deafness mutation GJB2 p.D179N could weaken the ability of docking between hexameric proteins,which could affect the balance between hexamers and do-decamers.
5.The comparative study of TyG and TyG-BMI index with occurrence of hyperuricemia in physical examina-tion population
Qian NIE ; Xuemei ZHANG ; Zhihua HAO ; Ruolin XIE ; Huanxin LIU ; Xiaoqian WU ; Luping REN
The Journal of Practical Medicine 2025;41(8):1192-1198
Objective To investigate the predictive capacity of the Triglyceride-Glucose(TyG)index and the Triglyceride-Glucose-Body Mass Index(TyG-BMI)for the development of hyperuricemia(HUA)in a health examination population,and to identify suitable indicators as risk assessment tools for HUA.Methods This study ultimately included 12 004 participants from a health examination cohort.According to SUA levels,the partici-pants were categorized into a normal group(n=9 952)and a hyperuricemia(HUA)group(n=2 052).The TyG index and TyG-BMI index were calculated,and participants were further stratified into four groups(Q1—Q4)based on the quartiles of these indices.Binary logistic regression analysis was performed to assess the association between TyG,TyG-BMI,and HUA.The predictive value of TyG,TyG-BMI,and their combination for HUA was evaluated using Receiver Operating Characteristic(ROC)curves and the Area Under the Curve(AUC).Subgroup analyses were carried out by gender and age.Results The TyG and TyG-BMI indices were significantly elevated in the HUA group compared to the normal group.The prevalence of HUA was markedly higher in the TyG-Q4 and TyG-BMI-Q4 groups than in the other three corresponding quartile groups.Binary logistic regression analysis revealed a positive association between TyG,TyG-BMI levels,and the risk of HUA.The AUC values for predicting HUA using TyG,TyG-BMI,and their combination were 0.700,0.747,and 0.822,respectively.Specifically,for males,the AUC values were 0.641,0.674,and 0.709,respectively,whereas for females,they were 0.742,0.776,and 0.829,respectively.Among individuals younger than 60 years old,the AUC values were 0.716,0.759,and 0.835,respectively,while for those aged 60 years or older,the values were 0.614,0.645,and 0.731,respectively.Conclusions TyG and TyG-BMI are significantly associated with the risk of HUA.Specifically,TyG-BMI demon-strates superior predictive performance compared to TyG alone.Moreover,the combination of TyG and TyG-BMI further improves predictive accuracy,particularly among female and middle-aged or younger populations.
6.Consensus on informed consent for orthodontic treatment
Yang CAO ; Bing FANG ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Lin WANG ; Haiping LU ; Zhihe ZHAO ; Tianmin XU ; Weiran LI ; Min HU ; Jinlin SONG ; Jun WANG ; Fang JIN ; Ding BAI ; Xianglong HAN ; Yuehua LIU ; Bin YAN ; Jie GUO ; Jiejun SHI ; Yongming LI ; Zhihua LI ; Xiuping WU ; Jiangtian HU ; Linyu XU ; Lin LIU ; Yi LIU ; Yanqin LU ; Wensheng MA ; Shuixue MO ; Liling REN ; Shuxia CUI ; Yongjie FAN ; Jianguang XU ; Lulu XU ; Zhijun ZHENG ; Peijun WANG ; Rui ZOU ; Chufeng LIU ; Lunguo XIA ; Li HU ; Weicai WANG ; Liping WU ; Xiaoxing KOU ; Jiali TAN ; Yuanbo LIU ; Bowen MENG ; Yuantao HAO ; Lili CHEN
Chinese Journal of Stomatology 2025;60(12):1327-1336
This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.
7.The dominant deafness point mutation GJB2 p.D179N affects the oligomeric equilibrium of connexin 26
Huahong LUO ; Guohui HUANG ; Yunge GAO ; Tao YANG ; Hao WU ; Zhihua ZHANG
Journal of Audiology and Speech Pathology 2025;33(3):259-264
Objective To investigate the impact of the dominant deafness point mutation p.D179N on the oli-gomeric equilibrium state of Connexin 26(Cx26).Methods The wild-type Cx26 fusion protein(Cx26-WT-GFP)and mutant fusion proteins(Cx26-D179N-GFP,Cx26-D179C-GFP)were expressed in HEK293F cells.By using Fluorescence-detection size-exclusion chromatography(FSEC)and size-exclusion chromatography(SEC)to analysis the oligomeric state of the target protein based on malecular weight under the condition of solubilization and purifica-tion respectively.Cryo-electron microscopy(Cryo-EM)single particle analysis(SPA)was conducted to analysis the target protein's oligomeric states based on the 2D classification morphology of the protein particles.Results In vitro,the wild-type Cx26 protein(Cx26-WT)is almost exclusively dodecameric.The deafness mutation p.D179N protein(Cx26-D179N)exists as both dodecamers and hexamers,whereas the artificial mutation p.D179C protein(Cx26-D179C)does not form dodecamers.Conclusion The dominant deafness mutation GJB2 p.D179N could weaken the ability of docking between hexameric proteins,which could affect the balance between hexamers and do-decamers.
8.The comparative study of TyG and TyG-BMI index with occurrence of hyperuricemia in physical examina-tion population
Qian NIE ; Xuemei ZHANG ; Zhihua HAO ; Ruolin XIE ; Huanxin LIU ; Xiaoqian WU ; Luping REN
The Journal of Practical Medicine 2025;41(8):1192-1198
Objective To investigate the predictive capacity of the Triglyceride-Glucose(TyG)index and the Triglyceride-Glucose-Body Mass Index(TyG-BMI)for the development of hyperuricemia(HUA)in a health examination population,and to identify suitable indicators as risk assessment tools for HUA.Methods This study ultimately included 12 004 participants from a health examination cohort.According to SUA levels,the partici-pants were categorized into a normal group(n=9 952)and a hyperuricemia(HUA)group(n=2 052).The TyG index and TyG-BMI index were calculated,and participants were further stratified into four groups(Q1—Q4)based on the quartiles of these indices.Binary logistic regression analysis was performed to assess the association between TyG,TyG-BMI,and HUA.The predictive value of TyG,TyG-BMI,and their combination for HUA was evaluated using Receiver Operating Characteristic(ROC)curves and the Area Under the Curve(AUC).Subgroup analyses were carried out by gender and age.Results The TyG and TyG-BMI indices were significantly elevated in the HUA group compared to the normal group.The prevalence of HUA was markedly higher in the TyG-Q4 and TyG-BMI-Q4 groups than in the other three corresponding quartile groups.Binary logistic regression analysis revealed a positive association between TyG,TyG-BMI levels,and the risk of HUA.The AUC values for predicting HUA using TyG,TyG-BMI,and their combination were 0.700,0.747,and 0.822,respectively.Specifically,for males,the AUC values were 0.641,0.674,and 0.709,respectively,whereas for females,they were 0.742,0.776,and 0.829,respectively.Among individuals younger than 60 years old,the AUC values were 0.716,0.759,and 0.835,respectively,while for those aged 60 years or older,the values were 0.614,0.645,and 0.731,respectively.Conclusions TyG and TyG-BMI are significantly associated with the risk of HUA.Specifically,TyG-BMI demon-strates superior predictive performance compared to TyG alone.Moreover,the combination of TyG and TyG-BMI further improves predictive accuracy,particularly among female and middle-aged or younger populations.
9.Not Available.
Weile YE ; Jiaojiao WANG ; Peter J LITTLE ; Jiami ZOU ; Zhihua ZHENG ; Jing LU ; Yanjun YIN ; Hao LIU ; Dongmei ZHANG ; Peiqing LIU ; Suowen XU ; Wencai YE ; Zhiping LIU
Acta Pharmaceutica Sinica B 2024;14(1):1-19
Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.
10.Near-infrared fluorescence imaging for intraoperative neuroimaging:current applications and future development
Wenping GAO ; Zhihua ZHANG ; Fei HAN ; Weiguo HAO
Chinese Journal of Tissue Engineering Research 2024;28(32):5225-5230
BACKGROUND:Existing neuroimaging techniques,including magnetic resonance imaging,computed tomography,and high-resolution ultrasound,lack the capability to provide real-time intraoperative positioning images to surgeons.However,the clinical implementation of near-infrared fluorescence imaging technology has made it possible to directly visualize surgical target areas,offering a novel solution for real-time nerve identification during surgery. OBJECTIVE:To provide a summary and overview of the research progress in near-infrared fluorescence imaging technology for intraoperative neuroimaging. METHODS:The first author used the computer to search for the documents published from January 2010 to July 2023 in WanFang,CNKI,and PubMed with the key words of"near-infrared fluorescence imaging,optical imaging,nerve imaging"in Chinese and English.A few classic old documents were also included.Initial screening was performed by reading the titles and abstracts;duplicate,low-quality,and irrelevant content documents were excluded.A total of 69 articles were finally included for review. RESULTS AND CONCLUSION:Near-infrared fluorescence imaging guided by indocyanine green has been clinically used to identify and locate tubular organs such as blood vessels,ureters,and bile ducts,as well as various tumors during surgery.This technique is currently considered a well-established imaging method in precision surgery.In the field of intraoperative neurofluorescence imaging,indocyanine green is currently the only near-infrared fluorescent dye used in clinical research.The ideal neuroimaging agent should possess certain characteristics,including easy administration in the perioperative period,logD between 0.5 and 3 at pH=7.4,molecular mass below 500 Da,excitation and emission wavelengths within the near-infrared window,long-term retention in nerve tissue,high signal-to-background ratio,and high safety.In the future,the development of near-infrared neurofluorescence imaging agents should focus on synthesizing complexes of indocyanine green and neural-specific targets.This technology not only enables intraoperative neurofluorescence imaging,but also holds promising prospects for in-situ monitoring of nerve regeneration and diagnosis of neurological diseases.

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