1.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.
2.Effects of PD-1 blockade on macrophage phagocytosis after Echinococcus multilocularis protoscoleces infection
Tao ZHANG ; Yao-Gang ZHANG ; Zi-Han YANG ; Yin-Hong SHEN ; Yan-Yan MA
Chinese Journal of Zoonoses 2023;39(11):1095-1099
This study analyzed the changes in macrophage phagocytosis after Echinococcus multilocularis protoscoleces(PSC)infection.The distribution of macrophages in hepatic alveolar echinococcosis patients was analyzed by immunohisto-chemistry.PD-1 blockade,PSCs and macrophages were co-cultured to analyze macrophage phagocytosis and the expression lev-els of CD47 and PD-1.Macrophages labeled by CD68 aggregated in close live tissue from the lession of alveolar echinococcosis patients.PSC infection resulted in lower intensity of Escherichia coli and higher expression of CD47 and PD-1 than observed in the control group(P<0.001).The intensity of Escherichia coli increasedin the PD-1 blockade group after PSC infection(q=40.63,P<0.05).PD-1 blockade restored macrophage phagocytosis after PSC infection.
3.Progress on clinical features, pathological mechanisms, assessment and prognosis of hearing loss in systemic lupus erythematosus.
Zi He ZHAO ; Ao LI ; Shao Qin CEN ; Guang Jie ZHU ; Han ZHOU ; Si Yu LI ; Yin CHEN ; Xiao Yun QIAN ; Xia GAO
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(2):165-170
4.Efficacy and safety of acupuncture for polycystic ovary syndrome: An overview of systematic reviews.
Han YANG ; Zhi-Yong XIAO ; Zi-Han YIN ; Zheng YU ; Jia-Jia LIU ; Yan-Qun XIAO ; Yao ZHOU ; Juan LI ; Jie YANG ; Fan-Rong LIANG
Journal of Integrative Medicine 2023;21(2):136-148
BACKGROUND:
Polycystic ovary syndrome (PCOS) is the primary cause of anovulatory infertility, bringing serious harm to women's physical and mental health. Acupuncture may be an effective treatment for PCOS. However, systematic reviews (SRs) on the efficacy and safety of acupuncture for PCOS have reported inconsistent results, and the quality of these studies has not been adequately assessed.
OBJECTIVE:
To summarize and evaluate the current evidence on the efficacy and safety of acupuncture for PCOS, as well as to assess the quality and risks of bias of the available SRs.
SEARCH STRATEGY:
Nine electronic databases (Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, Chinese National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Chinese Science and Technology Periodical Database, and China Biology Medicine disc) were searched from their establishment to July 27, 2022. Based on the principle of combining subject words with text words, the search strategy was constructed around search terms for "acupuncture," "polycystic ovary syndrome," and "systematic review."
INCLUSION CRITERIA:
SRs of randomized controlled trials that explored the efficacy and (or) safety of acupuncture for treating patients with PCOS were included.
DATA EXTRACTION AND ANALYSIS:
Two authors independently extracted study data according to a predesigned form. Tools for evaluating the methodological quality, risk of bias, reporting quality, and confidence in study outcomes, including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), were used to score the included SRs.
RESULTS:
A total of 885 studies were retrieved, and 11 eligible SRs were finally included in this review. The methodological quality of 2 SRs (18.18%) was low, while the other 9 SRs (81.82%) were scored as extremely low. Four SRs (36.36%) were considered to be of low risk of bias. As for reporting quality, the reporting completeness of 9 SRs (81.82%) was more than 70%. Concerning the confidence in study results, 2 study results were considered to have a high quality of evidence (3.13%), 14 (21.88%) a "moderate" quality, 28 (43.75%) a "low" quality, and 20 (31.24%) considered a "very low" quality. Descriptive analyses suggested that combining acupuncture with other medicines can effectively improve the clinical pregnancy rate (CPR) and ovulation rate, and reduce luteinizing hormone/follicle-stimulating hormone ratio, homeostasis model assessment of insulin resistance, and body mass index (BMI). When compared with medicine alone, acupuncture alone also can improve CPR. Further, when compared with no intervention, acupuncture had a better effect in promoting the recovery of menstrual cycle and reducing BMI. Acupuncture was reported to cause no adverse events or some adverse events without serious harm.
CONCLUSION
The efficacy and safety of acupuncture for PCOS remains uncertain due to the limitations and inconsistencies of current evidence. More high-quality studies are needed to support the use of acupuncture in PCOS.
Pregnancy
;
Humans
;
Female
;
Polycystic Ovary Syndrome/etiology*
;
Acupuncture Therapy/adverse effects*
;
Infertility, Female/etiology*
;
China
5.Molecular mechanism of ligustilide attenuating OGD/R injury in PC12 cells by inhibiting ferroptosis.
Lei SHI ; Chen-Chen JIANG ; Jia-Jun LU ; Zi-Xu LI ; Wang-Jie LI ; Xiu-Yun YIN ; Zhuo CHEN ; Xin-Ya ZHAO ; Hui ZHANG ; Hao-Ran HU ; Lu-Tan ZHOU ; Jun HAN
China Journal of Chinese Materia Medica 2023;48(11):3046-3054
The aim of this study is to explore the mechanism of ligustilide, the main active constituent of essential oils of traditional Chinese medicine Angelicae Sinensis Radix, on alleviating oxygen-glucose deprivation/reperfusion(OGD/R) injury in PC12 cells from the perspective of ferroptosis. OGD/R was induced in vitro, and 12 h after ligustilide addition during reperfusion, cell viability was detected by cell counting kit-8(CCK-8) assay. DCFH-DA staining was used to detect the level of intracellular reactive oxygen species(ROS). Western blot was employed to detect the expression of ferroptosis-related proteins, glutathione peroxidase 4(GPX4), transferrin receptor 1(TFR1), and solute carrier family 7 member 11(SLC7A11), and ferritinophagy-related proteins, nuclear receptor coactivator 4(NCOA4), ferritin heavy chain 1(FTH1), and microtubule-associated protein 1 light chain 3(LC3). The fluorescence intensity of LC3 protein was analyzed by immunofluorescence staining. The content of glutathione(GSH), malondialdehyde(MDA), and Fe was detected by chemiluminescent immunoassay. The effect of ligustilide on ferroptosis was observed by overexpression of NCOA4 gene. The results showed that ligustilide increased the viability of PC12 cells damaged by OGD/R, inhibited the release of ROS, reduced the content of Fe and MDA and the expression of TFR1, NCOA4, and LC3, and improved the content of GSH and the expression of GPX4, SLC7A11, and FTH1 compared with OGD/R group. After overexpression of the key protein NCOA4 in ferritinophagy, the inhibitory effect of ligustilide on ferroptosis was partially reversed, indicating that ligustilide may alleviate OGD/R injury of PC12 cells by blocking ferritinophagy and then inhibiting ferroptosis. The mechanism by which ligustilide reduced OGD/R injury in PC12 cells is that it suppressed the ferroptosis involved in ferritinophagy.
Animals
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Rats
;
PC12 Cells
;
Ferroptosis/genetics*
;
Reactive Oxygen Species
;
Transcription Factors
;
Glutathione
6. Paeonol regulates phenotypic conversion of macrophages via estrogen receptor-a
An Na-Qi LI ; Zi-Han ZHU ; Fan-Zhang YIN ; Wen-Wen LI ; Zhe-Yu ZHOU ; Zhong-Yang WANG ; Yu LI ; Xiang WU ; Hui-Min BIAN
Chinese Pharmacological Bulletin 2022;38(1):32-37
Aim To study the effect of paeonol on macrophage phenotvpe conversion based on estrogen receptora (ERa).Methods The macrophage Ml polarization model was established by 100 jjig • L"' LPS and 20 pug • L_1 I FN-7.ELISA was used to examine the effects of paeonol on tumor necrosis factor-a ( TNF-cx ) , interleukin-1 £ ( 1L-1 £ ) , interleukin-10 (IL-10), superoxide dismutase (SOD) , and malondi- aldehyde ( MDA).Western blot was used to detect the expression of M1 phenotvpe markers iNOS, CD86 and M2 phenotvpe markers Arg-1 and CD 163 in macrophages.Further, the methods of blockers and shRNA interference were used to verify whether the effect of paeonol was mediated by ERa.Results ELISA results shower] that paeonol reduced the content of TNF-a, IL- lp and MDA, and increased the content of IL-10 and SOD.Western blot results showed that paeonol reduced the expression of iNOS and CD86 proteins in model group, and increased the expression of Arg-1 and CD163 proteins.Both ERa selective blocker MPP and ERa shRNA reduced the efficacy of paeonol, while ERp selective blocker PHTPP had no significant effect on paeonol.Conclusion Paeonol can induce the transformation of macrophages into M2 type by ERa and alleviate the progression of atherosclerosis.
7.Skin diseases in the Da Qing Diabetes Study: a cross-sectional study.
Chang-Bing SHEN ; Xin QIAN ; Rui-Xing YU ; Xue-Lei JI ; Yin-Juan SHI ; Jing GAO ; Cheng-Xu LI ; Ke-Ke LI ; Wen-Min FEI ; Xue SHEN ; Zi-Yi WANG ; Yang HAN ; Xiao-Li NING ; Randy KO ; Yi-Hsiang HSU ; Xian-Yong YIN ; Guang-Wei LI ; Yong CUI
Chinese Medical Journal 2021;134(10):1191-1198
BACKGROUND:
The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM.
METHODS:
We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated.
RESULTS:
In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses". The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses". Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01).
CONCLUSIONS
There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.
Aged
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Aged, 80 and over
;
Blood Glucose
;
Cross-Sectional Studies
;
Diabetes Mellitus, Type 2/epidemiology*
;
Female
;
Glucose Intolerance/epidemiology*
;
Glucose Tolerance Test
;
Humans
;
Male
;
Middle Aged
;
Skin Diseases/epidemiology*
8.Influencing factors for myopia among primary and secondary schoolstudents in Suzhou
HU Jia ; DING Zi Yao ; HAN Di ; HAI Bo ; YIN Jie Yun ; SHEN Hui
Journal of Preventive Medicine 2021;33(3):241-245
Objective:
To investigate the influencing factors for myopia among primary and secondary school students in Suzhou, so as to provide basis for myopia prevention and control.
Methods:
The students in Grade 4-12 were recruited by stratified cluster random sampling method. Gender, grade, parents' myopia history, outdoor activity time and video display terminal time were collected through the questionnaire of National Surveillance Program of Influencing Factors for Common Diseases and Health in Students. Uncorrected visual acuity and cycloplegic refraction were tested. Multivariate logistic regression analysis was performed to explore myopia-related factors.
Results:
A total of 990 questionnaires were distributed, and 882 valid questionnaires were recovered, with an effective rate of 89.09%. The prevalence rate of myopia was 78.23% ( 690 cases ). Multivariate logistic regression analysis showed that females ( OR=1.703, 95%CI: 1.173-2.474 ) , middle school students ( OR:5.597-11.949, 95%CI: 3.573-28.349 ) , both parents'myopia ( OR=2.445, 95%CI: 1.597-3.742 ) , video display terminal time over 3 hours per day ( OR=2.026, 95%CI: 1.235-3.325 ) were risk factors for myopia; outdoor activity time over 2 hours per day ( OR: 0.493-0.510, 95%CI: 0.273-0.943 ) was a protective factor for myopia.
Conclusion
The prevalence of myopia among primary and secondary school students in Suzhou is 78.23%. Gender, grade, parents' myopia history, outdoor activity time and video display terminal time are influencing factors for myopia.
9.Retrospect and prospect of researches on acupoint property: commemorating the 40th anniversary of
Chinese Acupuncture & Moxibustion 2021;41(9):957-960
The researches on acupoint property at modern times have been reviewed. Under the influence of TCM theory and modern technology, acupoint property is classified into generality, individuality and bidirectional regulation. It is affected mainly by acupoint compatibility, intervention measures, body state, etc. The research of acupoint property should be based on the connotation and clinical application of acupoint, adhere to the guidance of TCM theory, strengthen the exploration on the richness of acupoint property, implement the intersection of multi-disciplines to discover the specificity of acupoint, as well as investigate the relevant factors of acupoint property.
Acupuncture Points
;
Acupuncture Therapy
;
Anniversaries and Special Events
;
China
;
Moxibustion
10.Rule mining of acupoint and medication selection of acupoint application therapy for functional constipation.
Fu-Min WANG ; Si-Han SUN ; Zi-Han YIN ; Yu-Yi GUO ; Yun-Hong YANG ; Jing XIONG ; Zhao-Xuan HE ; Fang ZENG
Chinese Acupuncture & Moxibustion 2021;41(10):1166-1170
OBJECTIVE:
To analyze the rules of acupoint and medication selection of acupoint application therapy for functional constipation (FC) by data mining technology.
METHODS:
The clinical research literature regarding acupoint application therapy for FC from published to February 26, 2020 was searched in CNKI, VIP, Wanfang, SinoMed and PubMed. The prescriptions were extracted, and by using SPSS24.0 and SPSS Modeler14.0 software, the use of high-frequency acupoints and medication was summarized. The association rule analysis, cluster analysis and core prescription analysis of acupoints and medication were analyzed.
RESULTS:
A total of 122 prescriptions of acupoint application therapy were included, involving 32 acupoints. The core prescription of acupoints was Tianshu (ST 25), Dachangshu (BL 25), Shenque (CV 8) and Guanyuan (CV 4). The high-frequency meridians mainly included conception vessel,
CONCLUSION
The use of local acupoint and regulating-
Acupuncture Points
;
Acupuncture Therapy
;
Constipation/drug therapy*
;
Data Mining
;
Humans
;
Meridians


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