1.Hypoglycemic Effect and Mechanism of ICK Pattern Peptides
Lin-Fang CHEN ; Jia-Fan ZHANG ; Ye-Ning GUO ; Hui-Zhong HUANG ; Kang-Hong HU ; Chen-Guang YAO
Progress in Biochemistry and Biophysics 2025;52(1):50-60
Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM1, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.
2.Association Between the Coexistence of Chronic Non-communicable Diseases and Quality of Life in Middle-aged and Elderly People Living with HIV/AIDS
Yao ZHANG ; Chi ZHANG ; Cong LIU ; Haidan ZHONG ; Peishan DU ; Quanmin LI ; Linghua LI ; Jing GU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(1):161-171
ObjectiveTo investigate the prevalence rate of chronic non-communicable diseases (NCDs) and the association with quality of life in middle-aged and elderly patients with HIV/AIDS. MethodsThis cross-sectional study surveyed 432 patients with HIV/AIDS (aged≥45 years) in the Infectious Disease Center in Guangzhou Eighth People’s Hospital of Guangzhou Medical University, and 366 participants were included in the analysis after quality control. A questionnaire and the EuroQol 5-Dimensional 3-level version (EQ-5D-3L) were used to investigate NCDs and quality of life and Tobit regression model was used to estimate the association between chronic diseases and quality of life. ResultsAmong the 366 participants, 29(7.9%) had cardiovascular disease, 45(12.3%) had hypertension, 122(33.3%) had hyperglycemia, 151(41.3%)had hyperlipidemia,7(1.9%) had cancer, 17 (4.6%) had chronic kidney disease, 38 (10.4%) had chronic liver disease, 21(5.7%) had musculoskeletal disorders, and 253(69.1%) suffered from at least one type of chronic diseases. The median (lower and upper quartiles) of EQ-5D utility index was 1.000(0.964~1.000). Multivariate Tobit regression results of the total population showed that cancer [ba=-0.08,95%CI (-0.15,-0.01),P=0.036], chronic kidney disease [ba=-0.07, 95%CI (-0.12,-0.02),P=0.006], musculoskeletal disease [ba=-0.09, 95%CI (-0.13, -0.05),P<0.001], and ≥3 types of chronic diseases[ba=-0.05, 95%CI(-0.08,-0.01),P=0.013] were negatively correlated with EQ-5D utility index. The stratified analysis results of different CD4+T cell levels showed that hypertension [ba=-0.07, 95%CI (-0.12, -0.02), P=0.007], chronic kidney disease [ba=-0.10,95%CI (-0.18,-0.03), P=0.006], musculoskeletal disease [ba=-0.15, 95%CI (-0.22,-0.07), P<0.001] and ≥3 types of chronic diseases [ba=-0.09, 95%CI (-0.09, -0.01), P<0.001] were negatively correlated with EQ-5D utility index in the group with CD4≤500 (cells/μL), whereas cancer[ba=-0.11, 95%CI (-0.20,-0.01), P=0.031] was negatively correlated with EQ-5D utility index in the group with CD4>500(cells/μL). ConclusionsThe prevalence rate of chronic non-communicable diseases in middle-aged and elderly patients with HIV/AIDS is relatively high. The classification of NCDs such as cancer or chronic kidney disease or other chronic diseases and the numbers of NCDs categories are negatively correlated with quality of life. However,this association varies among patients with HIV/AIDS of different CD4+T cell levels. It is suggested that we should try to prevent and identify NCDs at an early stage, strengthen linkages and integration of health services for AIDS and chronic NCDs, and jointly manage and control AIDS with chronic diseases to improve the quality of life among people living with HIV/AIDS.
3.Research progress on female reproductive toxicity of bisphenols
Jia PENG ; Xiangzhu YAN ; Jiasi LIU ; Xiaopeng ZHONG ; Simin YAO ; Yiyan MA ; Shuhua TAN
Journal of Environmental and Occupational Medicine 2025;42(7):862-869
Bisphenols (BPs) are extensively used in food packaging, personal care products, and plastics, making them prevalent in both living and working environments, which has raised significant concern. As endocrine-disrupting chemicals, BPs exert toxic effects on the female reproductive system by binding to estrogen receptors, thereby activating or inhibiting the expression of genes related to reproductive functions, which disrupts the normal function of the endocrine system. This paper reviewed the effects of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) on female reproductive function, focusing on three key aspects: the effects on the female reproductive organs, the occurrence of associated reproductive disorders, and the mechanisms of toxicity. Specifically, this review highlighted the effects on ovarian function, uterine morphology and function, and fallopian tube function, as well as their correlation with polycystic ovary syndrome, endometriosis, miscarriage, and eclampsia. Additionally, the toxic mechanisms of BPs exposure were summarized, providing a scientific basis for future research on the impact of BPs on the female reproductive system, as well as for the assessment of potential health risks and the development of preventive measures.
4.The Critical Roles of GABAergic Interneurons in The Pathological Progression of Alzheimer’s Disease
Ke-Han CHEN ; Zheng-Jiang YANG ; Zi-Xin GAO ; Yuan YAO ; De-Zhong YAO ; Yin YANG ; Ke CHEN
Progress in Biochemistry and Biophysics 2025;52(9):2233-2240
Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the leading cause of dementia in the elderly, is characterized by severe cognitive decline, loss of daily living abilities, and neuropsychiatric symptoms. This condition imposes a substantial burden on patients, families, and society. Despite extensive research efforts, the complex pathogenesis of AD, particularly the early mechanisms underlying cognitive dysfunction, remains incompletely understood, posing significant challenges for timely diagnosis and effective therapeutic intervention. Among the various cellular components implicated in AD, GABAergic interneurons have emerged as critical players in the pathological cascade, playing a pivotal role in maintaining neural network integrity and function in key brain regions affected by the disease. GABAergic interneurons represent a heterogeneous population of inhibitory neurons essential for sustaining neural network homeostasis. They achieve this by precisely modulating rhythmic oscillatory activity (e.g., theta and gamma oscillations), which are crucial for cognitive processes such as learning and memory. These interneurons synthesize and release the inhibitory neurotransmitter GABA, exerting potent control over excitatory pyramidal neurons through intricate local circuits. Their primary mechanism involves synaptic inhibition, thereby modulating the excitability and synchrony of neural populations. Emerging evidence highlights the significant involvement of GABAergic interneuron dysfunction in AD pathogenesis. Contrary to earlier assumptions of their resistance to the disease, specific subtypes exhibit vulnerability or altered function early in the disease process. Critically, this impairment is not merely a consequence but appears to be a key driver of network hyperexcitability, a hallmark feature of AD models and potentially a core mechanism underlying cognitive deficits. For instance, parvalbumin-positive (PV+) interneurons display biphasic alterations in activity. Both suppressing early hyperactivity or enhancing late activity can rescue cognitive deficits, underscoring their causal role. Somatostatin-positive (SST+) neurons are highly sensitive to amyloid β-protein (Aβ) dysfunction. Their functional impairment drives AD progression via a dual pathway: compensatory hyperexcitability promotes Aβ generation, while released SST-14 forms toxic oligomers with Aβ, collectively accelerating neuronal loss and amyloid deposition, forming a vicious cycle. Vasoactive intestinal peptide-positive (VIP+) neurons, although potentially spared in number early in the disease, exhibit altered firing properties (e.g., broader spikes, lower frequency), contributing to network dysfunction (e.g., in CA1). Furthermore, VIP release induced by 40 Hz sensory stimulation (GENUS) enhances glymphatic clearance of Aβ, demonstrating a direct link between VIP neuron function and modulation of amyloid pathology. Given their central role in network stability and their demonstrable dysfunction in AD, GABAergic interneurons represent promising therapeutic targets. Current research primarily explores three approaches: increasing interneuron numbers (e.g., improving cortical PV+ interneuron counts and behavior in APP/PS1 mice with the antidepressant citalopram; transplanting stem cells differentiated into functional GABAergic neurons to enhance cognition), enhancing neuronal activity (e.g., using low-dose levetiracetam or targeted activation of specific molecules to boost PV+ interneuron excitability, restoring neural network γ‑oscillations and memory; non-invasive neuromodulation techniques like 40 Hz repetitive transcranial magnetic stimulation (rTMS), GENUS, and minimally invasive electroacupuncture to improve inhibitory regulation, promote memory, and reduce Aβ), and direct GABA system intervention (clinical and animal studies reveal reduced GABA levels in AD-affected brain regions; early GABA supplementation improves cognition in APP/PS1 mice, suggesting a therapeutic time window). Collectively, these findings establish GABAergic interneuron intervention as a foundational rationale and distinct pathway for AD therapy. In conclusion, GABAergic interneurons, particularly the PV+, SST+, and VIP+ subtypes, play critical and subtype-specific roles in the initiation and progression of AD pathology. Their dysfunction significantly contributes to network hyperexcitability, oscillatory deficits, and cognitive decline. Understanding the heterogeneity in their vulnerability and response mechanisms provides crucial insights into AD pathogenesis. Targeting these interneurons through pharmacological, neuromodulatory, or cellular approaches offers promising avenues for developing novel, potentially disease-modifying therapies.
5.Status risk factors and prevention and control strategies of familial aggregation of Helicobacter pylori infection
Lihua SONG ; Sijing HAN ; Shuqin REN ; Wen YANG ; Sihong DING ; Yixin ZHONG ; Yao QIN ; Huiyue ZHANG ; Yang ZHANG
Journal of Public Health and Preventive Medicine 2024;35(2):148-151
Objective To investigate the status of familial aggregation of Helicobacter pylori (Hp) infection in Jinniu District, Chengdu, and analyze its risk factors so as to provide a basis for developing prevention and control strategies of family aggregation of Hp infection. Methods A total of 172 subjects in the Second Affiliated Hospital of Chengdu Medical College · 416 Hospital of Nuclear Industry from January 2022 to January 2023 were selected as the research subjects. All subjects underwent 13C-urea breath test (13C-UBT) to diagnose whether there was Hp infection. Analyze the current situation of family aggregation of Hp infection in the region, collect general data of survey subjects, analyze the relevant factors affecting Hp family aggregation infection, and develop prevention and control strategies based on this. Results A total of 242 people from 97 households were surveyed, and the Hp family aggregation rate was 29.33%. Univariate analysis showed that there were statistically significant differences in family aggregation of Hp infection in terms of different age groups (χ2=9.719, P=0.008), marital status (χ2=8.496, P=0.014), occupations (χ2=19.462, P<0.001), frequencies of dining out (χ2=5.457, P=0.019), previous Hp test results (χ2 =4.131, P=0.042) and test results after treatment (χ2=12.000, P=0.001), with statistical significance (P<0.05). Multivariate logistic regression analysis showed that the frequency of dining out 2 days or more per week and a positive Hp test results in the past were risk factors for family aggregation of Hp infection, while the occupation of teachers/medical staff/management/technology personnel and a negative Hp results after treatment were protective factors (P<0.05). Conclusion Family aggregation of Hp infection is related to family members' occupation, frequency of dining out, previous Hp test results and Hp test results after eradication, which deserves attention in clinical practice.
6.Mechanism of aggravated severity in hypertriglyceridemia-associated acute pancreatitis:insights from the pathogenesis of"fat-turbidity-toxic heat"
Yuying LI ; Xinmin YANG ; Shaoqi ZHONG ; Yulin LENG ; Linbo YAO ; Tingting LIU ; Tao JIN ; Qing XIA ; Wei HUANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):672-678
Hypertriglyceridemia-associated acute pancreatitis is an inflammatory disorder of exocrine pancreas caused by metabolism disturbances of triglyceride-rich lipoproteins.Currently,hypertriglyceridemia-associated acute pancreatitis is characterized by an escalating incidence rate,a tendency for more severe cases,and a lack of therapeutic drugs.Traditional Chinese medicine has distinct advantages in treating this disease,but its theoretical framework has not yet been established.Hypertriglyceridemia-associated acute pancreatitis manifests itself as a febrile disease,aberrant accumulation of fat and turbidity may stem from dietary imbalances and visceral dysfunction in ordinary individuals.The prolonged accumulation of fat and turbidity can transform into turbid pathogen,subsequently engendering heat,constituting a pivotal pathogenic factor.Throughout the progression of the disease,the fiery pathogen consumes the fat and turbidity,resulting in the generation of toxic heat,which is a crucial mechanism in the exacerbation of the disease severity.Thus,this article posits therapeutic principles aimed at averting the transformation of fat and turbidity into turbid pathogen and counteracting toxic heat in this disease.This article reviews two key theories from traditional Chinese medicine classics relevant to hypertriglyceridemia-associated acute pancreatitis:the theory of fat-turbidity associated with hypertriglyceridemia and the febrile disease related to acute pancreatitis.Combining these traditional theories with modern research on the mechanisms that intensify hypertriglyceridemia-associated acute pancreatitis and the corresponding targets of traditional Chinese medicine,it suggests that the pathogenesis of"fat-turbidity-toxic heat"serves as the theoretical basis of traditional Chinese medicine for the aggravated severity of hypertriglyceridemia-associated acute pancreatitis.The article aims to offer new insights for the treatment of hypertriglyceridemia-associated acute pancreatitis.
7.Progress in plasma exchange for severe immune-related dermatoses
Chinese Journal of Blood Transfusion 2024;37(2):244-248
Plasma exchange (PE) is effective in a part of autoimmune diseases, and its main action mechanisms include removing pathogenic factors from the patient's blood, regulating immune function, replenishing normal plasma components. The use of PE in the treatment of severe immune-related skin diseases, such as pemphigus vulgaris, toxic epidermal necrolysis and clinically amyopathic dermatomyositis, has become more widespread. This review provides an overview of the progress of PE application in severe immune-related skin diseases at home and abroad in recent years to provide new ideas for the treatment of clinical severe skin diseases.
8.Toxicity evaluation of alcohol extract of Polygonum multiflorum based on 3D hepatocyte ball model
Hua-Long SU ; Xiang-Cao YAO ; Jia-Min CHEN ; Bo-Hong CEN ; Ping WANG ; Zong-Zheng CHEN ; Zhong-Yuan XU
The Chinese Journal of Clinical Pharmacology 2024;40(9):1272-1276
Objective To explore the toxicity of Polygonum multiflorum alcohol extract on 3D hepatospheres.Methods Variations in culture conditions and cell ratios were implemented,followed by the assessment of cell sphere diameter,density,and roundness,aiming to explore the optimal culture conditions.The 3D hepatocyte spheres were divided into control group and experimental-L,-M,-H groups.The experimental-L,-M,-H groups were treated with 0.25,1.00 and 2.50 mg·mL-1 Polygounm multiforum alcohol extract,and the control group was given the same amount of culture medium.The cell viability of the cell spheroids was tested by CellTiter-Glo reagent,the expression level of liver function related genes was detected by fluorescent quantitative polymerase chain reaction(RT-qRCR).The toxicity of cell spheres was detected by double fluorescent staining of living and dead cells.Results The ideal culture condition of cell sphere was 500 cells per micropore,and the cell ratio was HepG2-Huvec-LX-2=8∶1∶1.It displayed the values of 0.91±0.07 for circularity,0.91±0.02 for firmness,1.12±0.14 for aspect ratio,and(170.97±14.79)μm for diameter.On the 3rd,7th,10th and 14th days,the expression levels of albumin(ALB)mRNA were 1.00±0.02,0.96±0.02,0.54±0.07,0.52±0.07,and the expression levels of cytochrome P450 1A2(CYP1A2)mRNA were 1.00±0.10,2.15±0.16,2.45±0.33,1.30±0.03,respectively.The expression levels of multidrug resistance protein 2(MPR2)in the control group and the experimental-L,-M,-H groups were 1.00±0.31,1.38±0.24,1.48±0.06 and 1.90±0.08,respectively;spheroid viability were(98.19±0.49)%,(88.53±0.90)%,(71.60±2.91)%and(56.65±5.41)%.There were statistically significant differences in the above indexes between the experimental-L,-M,-H groups and the control group(all P<0.05).Conclusion The established hepatocyte sphere co-culture model showed varying degrees of expression of phase Ⅰ/Ⅱ drug metabolism enzymes,transporters,and liver cell specific marker molecule albumin and can be used to evaluate the toxicity of multiflorum multiflorum,which provides further reference for the clinical application of multiflorum multiflorum.
9.Effects of compatibility ratio and processing method on contents of nine constituents in combination use of Toosendan Fructus and Foeniculi Fructus
Jian-Zhong HOU ; Shun-Juan ZHU ; Yao LI ; Xiao-Peng WANG ; Jian-Ming HAO ; Yun-Fei CAO
Chinese Traditional Patent Medicine 2024;46(1):156-161
AIM To investigate the effects of different compatibility ratios and processing method on the content of rutin,isoquercetin,ferulic acid,quercetin,isotoosendanin,kaempferol,toosendanin,α-pinene,trans-anethole in the combination use of Toosendan Fructus and Foeniculi Fructus,and to explore the optimal compatibility ratio for its use.METHODS The analysis of HPLC-DAD was performed on a 30℃thermostatic ZORBAX SB C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the use of DAD detector.SPSS 24.0 software was used to analyze the data differences.RESULTS Nine constituents showed good linear relationships within their own ranges(r≥0.999 1),whose average recoveries were 96.19%-103.13%with the RSDs of 1.86%-2.67%.Generally higher total content of nine constituents were detected in the combination use groups when Toosendan Fructus-Foeniculi Fructus were at ratios of 1 ∶ 1,1 ∶ 2,and 2 ∶ 1 than those single uses(P<0.05),and among which the 1 ∶ 1 ratio contributed the highest total content.After salt processing,decreased content of toosendanin and isotoosendanin,α-pinene and trans-anethole(P<0.05,P<0.01)),increased isoquercetin content(P<0.01),and no significant content changes of other ingredients were detected.CONCLUSION Through this method of high accuracy and good reproducibility,we learn that the combination use of Toosendan Fructus and Foeniculi Fructus promotes the dissolution of the nine constituents,and the maximum content is achieved at ratio of 1 ∶ 1.
10.Reflection on general and innovative education of palliative care in China
Xiaona QI ; Qiang YAO ; Qinming YU ; Miaomiao ZHAO ; Yan WANG ; Menglan ZHONG ; Lijuan YU
Chinese Medical Ethics 2024;37(3):332-338
With the process of China’s aging population intensifying, palliative care, as an important guarantee for improving the quality of life of terminally ill patients, is receiving more and more social attention, and the demand is constantly increasing. Palliative care needs versatile professionals, and general education can enhance people’s awareness and understanding of it, enabling more people to understand, accept, and participate in palliative care. With the advancement of knowledge and technology in palliative care, the traditional cramming education models are no longer able to meet the actual needs. Therefore, there is an urgent need to innovate palliative care education strategies. By analyzing the current problems in the general education of palliative care in China, this paper proposed thoughts and suggestions for general and innovative education of palliative care in several aspects, such as establishing general and innovative education systems and evaluation systems of palliative care, diversifying educational contents and methods, strengthening medical staffs training, promoting diversified student groups, and strengthening the popularization of palliative care knowledge among the public.


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