1.Research progress on calcium activities in astrocyte microdomains.
Fu-Sheng DING ; Si-Si YANG ; Liang ZHENG ; Dan MU ; Zhu HUANG ; Jian-Xiong ZHANG
Acta Physiologica Sinica 2025;77(3):534-544
Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology*
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Humans
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Animals
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Calcium/metabolism*
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Calcium Signaling/physiology*
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Brain/physiology*
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Aging/physiology*
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Membrane Microdomains/physiology*
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Neurodegenerative Diseases/physiopathology*
2.Effect of the sequence of intermediate instrumentation and distraction-reduction of the injured vertebra on the treatment of thoracolumbar burst fractures with high rate of spinal canal encroachment.
Yue WANG ; Liang-Sheng LI ; Heng-Mei CHEN ; Hai-Lun ZHENG ; Shi-Jie CHEN ; Jian-Quan CHEN ; Chun WANG
China Journal of Orthopaedics and Traumatology 2025;38(5):508-516
OBJECTIVE:
To investigate the effect of the sequence of intermediate instrumentation and distraction-reduction of the injured vertebra on the surgical efficacy of short-segment percutaneous pedicle screw fixation for thoracolumbar burst fractures with high rate of spinal canal encroachment.
METHODS:
From January 2016 to January 2022, 38 patients with thoracolumbar burst fractures with high rate of spinal canal encroachment (spinal canal encroachment rate >40%, complete posterior longitudinal ligament, no flipping bone block in the posterior marginal of the vertebra) without spinal cord injury who were were treated with short-segment percutaneous pedicle screw fixation were retrospectively analyzed. During the operation, 18 cases were used distraction-reduction first and then intermediate instrumentation on injured vertebral and sequential distraction-reduction again(the distraction-reduction first group) including 8 females and 10 males with a mean age of 46.5 (38.5, 50.0) years old, and the other 20 cases were used intermediate instrumentation on injured vertebral first and then direct distraction-reduction(the intermediate instrumentation first group) including 10 males and 10 females with a mean age of 46.0 (35.8, 50.8) years. The anterior height ratio of the injured vertebra, local Cobb's angle of the injured vertebrae, the spinal canal encroachment rate, and the improvement rate of spinal canal encroachment were compared and evaluated.
RESULTS:
All patients were followed up for more than 1 year, and no complications such as spinal cord and root injury, screw loosening and screw rod fracture were found. The anterior height ratio of the injured vertebra, local Cobb' angle of the injured vertebra in the two groups were significantly improved compared with preoperative data(P<0.05), and those at 3 months and 1 year after operation was lost compared with that at the previous time point(P<0.05). Although the spinal canal encroachment rate of the two groups 1 day and 1 year after operation was improved compared with that before operation(P<0.05), the improvement of spinal canal volume in the distraction-reduction first group was significantly better than that in the intermediate instrumentation first group (P<0.01).
CONCLUSION
In the treatment of patients with thoracolumbar fractures with high rate of spinal canal encroachment, short-segment percutaneous pedicle screw internal fixation with distraction-reduction first and then intermediate instrumentation and sequential distraction-reduction again can more effectively reduce the bony encroachment in the spinal canal and achieve indirect decompression effect better.
Humans
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Female
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Male
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Adult
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Middle Aged
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Spinal Fractures/surgery*
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Thoracic Vertebrae/surgery*
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Lumbar Vertebrae/surgery*
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Fracture Fixation, Internal/instrumentation*
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Pedicle Screws
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Retrospective Studies
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Spinal Canal/surgery*
3.Cytoplasmic and nuclear NFATc3 cooperatively contributes to vascular smooth muscle cell dysfunction and drives aortic aneurysm and dissection.
Xiu LIU ; Li ZHAO ; Deshen LIU ; Lingna ZHAO ; Yonghua TUO ; Qinbao PENG ; Fangze HUANG ; Zhengkun SONG ; Chuanjie NIU ; Xiaoxia HE ; Yu XU ; Jun WAN ; Peng ZHU ; Zhengyang JIAN ; Jiawei GUO ; Yingying LIU ; Jun LU ; Sijia LIANG ; Shaoyi ZHENG
Acta Pharmaceutica Sinica B 2025;15(7):3663-3684
This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.
4.Lumbar temperature change after acupuncture or moxibustion at Weizhong (BL40) or Chize (LU5) in healthy adults: A randomized controlled trial.
Si-Yi ZHENG ; Xiao-Ying WANG ; Li-Nan LIN ; Shan LIU ; Xiao-Xiao HUANG ; Yi-Yue LIU ; Xiao-Shuai YU ; Wei PAN ; Jian-Qiao FANG ; Yi LIANG
Journal of Integrative Medicine 2025;23(2):145-151
BACKGROUND:
There is a gap in understanding the effects of different acupoints and treatment methods (acupuncture and moxibustion) on microcirculatory changes in the lumbar region.
OBJECTIVE:
This study aimed to assess the thermal effects of acupuncture at Weizhong (BL40), with acupuncture at Chize (LU5) and moxibustion at both acupoints as control interventions.
DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:
In this randomized controlled trial, 140 healthy participants were equally divided into four groups: acupuncture at BL40 (Acu-BL40), acupuncture at LU5 (Acu-LU5), moxibustion at BL40 (Mox-BL40) and moxibustion at LU5 (Mox-LU5). Participants underwent a 30-minute session of their assigned treatment. Infrared thermal imaging was used to collect temperature data on the areas of interest for analysis.
MAIN OUTCOME MEASURES:
The primary measure was the change in average temperature of the observed area after the intervention. The secondary measures included periodic temperature changes every 5 min and the temperature changes of the Governor Vessel and Bladder Meridian in the observed area after the intervention.
RESULTS:
Significant interactions were observed between treatments and acupoints affecting temperature (P < 0.001). The Acu-BL40 group showed a notably higher increase in mean temperature after 30 min compared to the Acu-LU5 and Mox-BL40 groups, with increases of 0.29 (95% confidence interval [CI] = 0.17 to 0.41) and 0.24 (95% CI = 0.08 to 0.41) °C, respectively.
CONCLUSION:
Acupuncture at BL40 acupoint can significantly increase the mean temperature in the observed area, highlighting the specific thermal effect of acupuncture compared to moxibustion in the lumbar area. This suggests a potential therapeutic benefit of acupuncture at BL40 for managing lumbar conditions.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT05665426). Please cite this article as: Zheng SY, Wang XY, Lin LN, Liu S, Huang XX, Liu YY, Yu XS, Pan W, Fang JQ, Liang Y. Lumbar temperature change after acupuncture or moxibustion at Weizhong (BL40) or Chize (LU5) in healthy adults: A randomized controlled trial. J Integr Med. 2025; 23(2): 145-151.
Adult
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Female
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Humans
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Male
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Young Adult
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Acupuncture Points
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Acupuncture Therapy
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Body Temperature
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Healthy Volunteers
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Lumbosacral Region/physiology*
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Moxibustion
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Adolescent
5.International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025).
Sheng-Sheng ZHANG ; Lu-Qing ZHAO ; Xiao-Hua HOU ; Zhao-Xiang BIAN ; Jian-Hua ZHENG ; Hai-He TIAN ; Guan-Hu YANG ; Won-Sook HONG ; Yu-Ying HE ; Li LIU ; Hong SHEN ; Yan-Ping LI ; Sheng XIE ; Jin SHU ; Bin-Fang ZENG ; Jun-Xiang LI ; Zhen LIU ; Zheng-Hua XIAO ; Jing-Dong XIAO ; Pei-Yong ZHENG ; Shao-Gang HUANG ; Sheng-Liang CHEN ; Gui-Jun FEI
Journal of Integrative Medicine 2025;23(5):502-518
Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy*
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Humans
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Medicine, Chinese Traditional/methods*
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Practice Guidelines as Topic
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Drugs, Chinese Herbal/therapeutic use*
6.Expert consensus on clinical randomized controlled trial design and evaluation methods for bone grafting or substitute materials in alveolar bone defects.
Xiaoyu LIAO ; Yang XUE ; Xueni ZHENG ; Enbo WANG ; Jian PAN ; Duohong ZOU ; Jihong ZHAO ; Bing HAN ; Changkui LIU ; Hong HUA ; Xinhua LIANG ; Shuhuan SHANG ; Wenmei WANG ; Shuibing LIU ; Hu WANG ; Pei WANG ; Bin FENG ; Jia JU ; Linlin ZHANG ; Kaijin HU
West China Journal of Stomatology 2025;43(5):613-619
Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans
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Bone Substitutes/therapeutic use*
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Randomized Controlled Trials as Topic/methods*
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Consensus
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Bone Transplantation
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Research Design
7.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
8.Relationship between serum levels of E-cadherin and p-catenin and calcium phosphorus metabolism and carotid artery calcification in patients with diabetic nephropathy
Jian GAO ; Zheng LIANG ; Fei ZHAO ; Xiaojing LIU ; Ning MA
International Journal of Laboratory Medicine 2024;45(12):1469-1473
Objective To investigate the relationship between serum levels of E-cadherin and β-catenin and calcium phosphorus metabolism and carotid artery calcification in patients with diabetic nephropathy.Methods A total of 112 patients with diabetic nephropathy admitted to the hospital from May 2019 to No-vember 2022 were selected as the study group,and were divided into a carotid artery calcification group(n=44)and a non-carotid artery calcification group(n=68)according to the results of bilateral carotid artery col-or Doppler ultrasound.In addition,90 healthy people who underwent physical examination in the hospital dur-ing the same period were selected as the control group.Serum E-cadherin,β-catenin,calcium phosphorus me-tabolism levels were detected and compared.Pearson correlation analysis was used to explore the relationship between serum E-cadherin,β-catenin and calcium phosphorus metabolism in patients with diabetic nephropa-thy.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum E-cad-herin and β-catenin for carotid artery calcification in patients with diabetic nephropathy.Multivariate Logistic regression analysis was used to explore the influencing factors of carotid artery calcification in patients with di-abetic nephropathy.Results The levels of glycosylated hemoglobin,serum phosphorus,calcium-phosphorus product,parathyroid hormone(iPTH),creatinine,alkaline phosphatase and β-catenin in the study group were higher than those in the control group,and the level of E-cadherin was lower than that in the control group(P<0.05).The levels of serum phosphorus,serum calcium,calcium phosphorus product,iPTH,creatinine,al-kaline phosphatase and β-catenin in the carotid artery calcification group were higher than those in the non-ca-rotid artery calcification group,and the level of E-cadherin was lower than that in the non-carotid artery calci-fication group(P<0.05).Pearson correlation analysis showed that serum E-cadherin level in patients with di-abetic nephropathy was negatively correlated with serum phosphorus,serum calcium,calcium phosphorus product,iPTH,creatinine and alkaline phosphatase(r=-0.453,-0.654,-0.365,-0.490,-0.411,-0.377,all P<0.001).The level of serum β-catenin was positively correlated with serum phosphorus,serum calcium,calcium phosphorus product,iPTH,creatinine,and alkaline phosphatase(r=0.444,0.345,0.421,0.398,0.651,0.622,all P<0.001).ROC curve analysis showed that the area under the curve of serum E-cad-herin,β-catenin and their combination for predicting carotid artery calcification in diabetic nephropathy were 0.844(95%CI 0.795-0.894),0.853(95%CI 0.801-0.901)and 0.901(95%CI 0.801-0.901),respec-tively.Multivariate Logistic regression analysis showed that serum E-cadherin(OR=3.789,95%CI 2.055-6.983),β-catenin(OR=4.104,95%CI 1.795-9.385),calcium phosphorus product(OR=2.998,95%CI 1.895-4.743)and iPTH(OR=2.713,95%CI 1.787-4.118)were the influencing factors of carotid artery calcification in patients with diabetic nephropathy(P<0.05).Conclusion The level of β-catenin is increased and the level of E-cadherin is decreased in patients with diabetic nephropathy.β-catenin and E-cadherin are closely related to calcium phosphorus metabolism and carotid artery calcification,which could be used as effec-tive indicators to evaluate carotid artery calcification in patients with diabetic nephropathy.The combination ofβ-catenin and E-cadherin has a higher predictive value for carotid artery calcification.
9.Correlation analysis between serum GDF-11 and S100A4 levels and disease severity and disease outcome in diabetic nephropathy patients
Jian GAO ; Zheng LIANG ; Fei ZHAO ; Xiaojing LIU ; Ning MA
International Journal of Laboratory Medicine 2024;45(19):2349-2353,2359
Objective To investigate the relationship between serum levels of growth differentiation factor-11(GDF-11)and S100 calcium binding protein A4(S100A4)and the severity and disease outcome in diabetic nephropathy(DN)patients.Methods A total of 95 DN patients admitted to the hospital from May 2021 to January 2023 were selected as the study group,and 110 healthy people were selected as the healthy group.The DN patients were divided into mild group(n=66)and severe group(n=29)according to the severity of the disease.The patients were followed up for half a year after discharge,and were divided into good prognosis group(n=64)and poor prognosis group(n=31)according to the prognosis.Serum GDF-11 and S100A4 lev-els were detected by enzyme-linked immunosorbent assay.Spearman rank correlation analysis was used to ex-plore the relationship between serum GDF-11,S100A4 levels and the severity of the disease.Receiver operat-ing characteristic(ROC)curve was used to evaluate the predictive value of serum GDF-11 and S100A4 for dis-ease outcome in DN patients,and multivariate Logistic regression was used to analyze the influencing factors of disease outcome in DN patients.Results The levels of serum GDF-11 and S100A4 in mild group and severe group were higher than those in healthy group,and those in severe group were higher than those in mild group(P<0.05).Serum GDF-11 and S100A4 levels were positively correlated with the severity of DN patients(P<0.05).The good prognosis group had significantly lower serum levels of GDF-11 and S100A4 than the poor prognosis group(P<0.05).The area under the curve(AUC)of serum GDF-11 and S100A4 in predicting the outcome of DN patients was 0.785 and 0.839,respectively,and the AUC of combined prediction was 0.902.The proportion of type 2 diabetes(T2DM)duration,glomerular grade Ⅲ-Ⅳ,interstitial inflammation score 2,interstitial fibrosis and tubular atrophy(IFTA)score 2-3 points,estimate glomerular filtration rate<60 mL/(min·1.73 m2)and the levels of total cholesterol,triglyceride,low-density lipoprotein choles-terol,24 h urinary protein,glycosylated hemoglobin,C-peptide,hematocrit,and erythrocyte sedimentation rate in the good prognosis group were higher than those in the good prognosis group(P<0.05).Multivariate Lo-gistic regression analysis showed that the duration of T2DM ≥12.0 years,IFTA score ≥2 points,GDF-11≥700.82 ng/mL,S100A4 ≥ 211.53 ng/L were risk factors for poor prognosis in DN patients(P<0.05).Conclusion The levels of serum S100A4 and GDF-11 are highly expressed in patients with diabetes mellitus,and are related to the severity and outcome of the disease,which are expected to be potential markers for eval-uating the condition and prognosis of diabetes mellitus.
10.Nanomaterial-based Therapeutics for Biofilm-generated Bacterial Infections
Zhuo-Jun HE ; Yu-Ying CHEN ; Yang ZHOU ; Gui-Qin DAI ; De-Liang LIU ; Meng-De LIU ; Jian-Hui GAO ; Ze CHEN ; Jia-Yu DENG ; Guang-Yan LIANG ; Li WEI ; Peng-Fei ZHAO ; Hong-Zhou LU ; Ming-Bin ZHENG
Progress in Biochemistry and Biophysics 2024;51(7):1604-1617
Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.

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