1.Molecular Mechanisms Underlying Sleep Deprivation-induced Acceleration of Alzheimer’s Disease Pathology
Si-Ru YAN ; Ming-Yang CAI ; Ya-Xuan SUN ; Qing HUO ; Xue-Ling DAI
Progress in Biochemistry and Biophysics 2025;52(10):2474-2485
Sleep deprivation (SD) has emerged as a significant modifiable risk factor for Alzheimer’s disease (AD), with mounting evidence demonstrating its multifaceted role in accelerating AD pathogenesis through diverse molecular, cellular, and systemic mechanisms. SD is refined within the broader spectrum of sleep-wake and circadian disruption, emphasizing that both acute total sleep loss and chronic sleep restriction destabilize the homeostatic and circadian processes governing glymphatic clearance of neurotoxic proteins. During normal sleep, concentrations of interstitial Aβ and tau fall as cerebrospinal fluid oscillations flush extracellular waste; SD abolishes this rhythm, causing overnight rises in soluble Aβ and tau species in rodent hippocampus and human CSF. Orexinergic neurons sustain arousal, and become hyperactive under SD, further delaying sleep onset and amplifying Aβ production. At the molecular level, SD disrupts Aβ homeostasis through multiple converging pathways, including enhanced production via beta-site APP cleaving enzyme 1 (BACE1) upregulation, coupled with impaired clearance mechanisms involving the glymphatic system dysfunction and reduced Aβ-degrading enzymes (neprilysin and insulin-degrading enzyme). Cellular and histological analyses revealed that these proteinopathies are significantly exacerbated by SD-induced neuroinflammatory cascades characterized by microglial overactivation, astrocyte reactivity, and sustained elevation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) through NF‑κB signaling and NLRP3 inflammasome activation, creating a self-perpetuating cycle of neurotoxicity. The synaptic and neuronal consequences of chronic SD are particularly profound and potentially irreversible, featuring reduced expression of critical synaptic markers (PSD95, synaptophysin), impaired long-term potentiation (LTP), dendritic spine loss, and diminished neurotrophic support, especially brain-derived neurotrophic factor (BDNF) depletion, which collectively contribute to progressive cognitive decline and memory deficits. Mechanistic investigations identify three core pathways through which SD exerts its neurodegenerative effects: circadian rhythm disruption via BMAL1 suppression, orexin system hyperactivity leading to sustained wakefulness and metabolic stress, and oxidative stress accumulation through mitochondrial dysfunction and reactive oxygen species overproduction. The review critically evaluates promising therapeutic interventions including pharmacological approaches (melatonin, dual orexin receptor antagonists), metabolic strategies (ketogenic diets, and Mediterranean diets rich in omega-3 fatty acids), lifestyle modifications (targeted exercise regimens, cognitive behavioral therapy for insomnia), and emerging technologies (non-invasive photobiomodulation, transcranial magnetic stimulation). Current research limitations include insufficient understanding of dose-response relationships between SD duration/intensity and AD pathology progression, lack of long-term longitudinal clinical data in genetically vulnerable populations (particularly APOE ε4 carriers and those with familial AD mutations), the absence of standardized SD protocols across experimental models that accurately mimic human chronic sleep restriction patterns, and limited investigation of sex differences in SD-induced AD risk. The accumulated evidence underscores the importance of addressing sleep disturbances as part of multimodal AD prevention strategies and highlights the urgent need for clinical trials evaluating sleep-focused interventions in at-risk populations. The review proposes future directions focused on translating mechanistic insights into precision medicine approaches, emphasizing the need for biomarkers to identify SD-vulnerable individuals, chronotherapeutic strategies aligned with circadian biology, and multi-omics integration across sleep, proteostasis and immune profiles may delineate precision-medicine strategies for at-risk populations. By systematically examining these critical connections, this analysis positions sleep quality optimization as a viable strategy for AD prevention and early intervention while providing a comprehensive roadmap for future mechanistic and interventional research in this rapidly evolving field.
2.Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.
Shuo ZHANG ; Hong-Jin LI ; Chun-Mei YANG ; Liu LIU ; Xiao-Ying SUN ; Jiao WANG ; Si-Ting CHEN ; Yi LU ; Man-Qi HU ; Ge YAN ; Ya-Qiong ZHOU ; Xiao MIAO ; Xin LI ; Bin LI
Chinese journal of integrative medicine 2024;30(3):222-229
OBJECTIVE:
To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.
METHODS:
Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.
RESULTS:
TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).
CONCLUSIONS
TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male
;
Animals
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Mice
;
Tripterygium
;
Psoriasis/drug therapy*
;
Keratinocytes
;
Skin Diseases/metabolism*
;
Cytokines/metabolism*
;
Imiquimod/metabolism*
;
Dermatitis/pathology*
;
Disease Models, Animal
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Mice, Inbred BALB C
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Skin/metabolism*
3.Simulated Microgravity can Promote the Apoptosis and Change Inflammatory State of Kupffer Cells
Ge JUN ; Liu FEI ; Nie HONGYUN ; Yue YUAN ; Liu KAIGE ; Lin HAIGUAN ; Li HAO ; Zhang TAO ; Yan HONGFENG ; Xu BINGXIN ; Sun HONGWEI ; Yang JIANWU ; Si SHAOYAN ; Zhou JINLIAN ; Cui YAN
Biomedical and Environmental Sciences 2024;37(10):1117-1127
Objective In this study,we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Methods Rotary cell culture system was used to construct a simulated microgravity model.GO and KEGG analyses were conducted using the DAVID database.GSEA was performed using the R language.The STRING database was used to conduct PPI analysis.qPCR was used to measure the IL1B,TNFA,CASP3,CASP9,and BCL2L11 mRNA expressions.Western Blotting was performed to detect the level of proteins CASP3 and CASP 9.Flow cytometry was used to detect apoptosis and mitochondrial membrane cells.Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Results Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells.Simulated microgravity improved the CASP3,CASP9,and BCL2L11 expressions in Kupffer cells.Annexin-V/PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells.Simulated microgravity causes M1 polarization in Kupffer cells. Conclusion Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization,which can secrete TNFA to promote apoptosis.
4.Research on species identification of commercial medicinal and food homology scented herbal tea
Jing SUN ; Zi-yi HUANG ; Si-qi LI ; Yu-fang LI ; Yan HU ; Shi-wen GUO ; Ge HU ; Chuan-pu SHEN ; Fu-rong YANG ; Yu-lin LIN ; Tian-yi XIN ; Xiang-dong PU
Acta Pharmaceutica Sinica 2024;59(9):2612-2624
The adulteration and counterfeiting of herbal ingredients in medicinal and food homology (MFH) have a serious impact on the quality of herbal materials, thereby endangering human health. Compared to pharmaceutical drugs, health products derived from traditional Chinese medicine (TCM) are more easily accessible and closely integrated into consumers' daily life. However, the authentication of the authenticity of TCM ingredients in MFH has not received sufficient attention. The lack of clear standards emphasizes the necessity of conducting systematic research in this area. This study utilized DNA barcoding technology, combining ITS2,
5.Background, design, and preliminary implementation of China prospective multicenter birth cohort
Si ZHOU ; Liping GUAN ; Hanbo ZHANG ; Wenzhi YANG ; Qiaoling GENG ; Niya ZHOU ; Wenrui ZHAO ; Jia LI ; Zhiguang ZHAO ; Xi PU ; Dan ZHENG ; Hua JIN ; Fei HOU ; Jie GAO ; Wendi WANG ; Xiaohua WANG ; Aiju LIU ; Luming SUN ; Jing YI ; Zhang MAO ; Zhixu QIU ; Shuzhen WU ; Dongqun HUANG ; Xiaohang CHEN ; Fengxiang WEI ; Lianshuai ZHENG ; Xiao YANG ; Jianguo ZHANG ; Zhongjun LI ; Qingsong LIU ; Leilei WANG ; Lijian ZHAO ; Hongbo QI
Chinese Journal of Perinatal Medicine 2024;27(9):750-755
China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.
6.Relationship between sugar metabolism and acid production and cariogenicity of Prevotella denticola
Yuan SI ; Yanfei SUN ; Xuejiao SONG ; Junli WAN ; Min LI ; Fang YANG
Journal of Practical Stomatology 2024;40(6):753-758
Objective:To explore the potential relationship between sugar metabolism,acid production and cariogenicity of Prevotella denticola.Methods:Morphological features of Prevotella denticola were observed and respectively cultured under incubation conditions with and without sugar and at different pH values.The growth characteristics of Prevotella denticola were detected by UV-Vis spectro-photometer and pH meter,the organic acid content in the culture supernatants of the cultures was detected by HPLC.Dentin slices were divided into control group,phosphoric acid group and the Prevotella denticola group and cultured in the corresponding mediu for 1 and 2 weeks respectively,the degree of demineralization of the samples was examined SEM and VHM.Results:Prevotella denticola fermen-ted sucrose and glucose,produced acids with its final pH values as low as 4.7,Succinic acid and acetic acid were its main metabolites.Prevotella denticola was moderately acid-tolerant.Furthermore,Prevotella denticola was able to cause dentin demineralization,and the Vickers hardness value of dentin samples in the Prevotella denticola group was significantly decreased compared with the control group(P<0.05).Conclusion:The cariogenic capacity of Prevotella denticola may be related to its sugar metabolism and acid production.
7.Analysis of Employment Status of Undergraduate Graduates in Health Services and Management in China
Hongkun CHEN ; Yuchen ZHOU ; Yuhuan SUN ; Yang YI ; Jianping SI ; Shucong LIU ; Jianping REN ; Dahui WANG
Chinese Journal of Health Management 2024;18(10):777-782
Objective:To investigate and analyze the employment status of college graduates majoring in health service and management in China.Methods:From April 2023 to June 2024, a cross-sectional survey was conducted on undergraduate graduates majoring in health service and management from 34 universities in China using convenient sampling method. General information was collected (such as gender, household registration at graduation, only child status, average monthly family income, previous experience as a student cadre, average grade point, part-time job experience, entrepreneurial experience, whether a first batch graduate of the university and the major, self-assessment of professional competence level) alongside employment status. Statistical descriptive analysis was employed to analyze the graduates′ basic employment situation, job competence and professional skill demand, types of certificates valued by employers, factors influencing job selection, evaluation of work and profession, and perceptions of professional employment prospects. A total of 1 417 questionnaires were collected in this study, with 1 315 valid responses (92.8%). Chi-square tests were used to compare employment differences among various factors, and binary logistic regression was used to analyze factors influencing employment outcomes.Results:Among 564 employed graduates in the Health Services and Management field, 98 (17.4%) work in health management companies and 97 (17.2%) in hospitals. Regarding important job competencies, 413 (73.2%), 409 (72.5%), and 364 (64.5%) respectively emphasized the importance of information collection and statistical analysis, organizational coordination, and communication skills. Key professional skills highly valued by employers included health risk assessment 175 (66.3%), health measurement 160 (60.6%), and health education and promotion 152 (57.6%). Additionally, 281 (49.8%) highlighted the importance of Health Management Professional Qualification Certificates. Factors influencing job choices included salary and benefits 454 (80.5%) and personal interests and hobbies 279 (49.5%). While 397 (70.4%) of the graduates provided positive feedback on their profession, only 274 (48.6%) were optimistic about their future job prospects. Binary logistic regression analysis indicated significant correlations (all P<0.05) between employment outcomes and factors such as part-time work experience ( OR=1.31) and average grade point ( OR=0.61, 0.68). Conclusions:The employment rate of undergraduate graduates majoring in health service and management in China is low in the health service market, with a low degree of job specialization matching. Graduates are not optimistic about the future employment prospects in their field, possibly due to unclear positioning in talent cultivation in universities and an imperfect job market.
8.Neuromuscular electrical stimulation promoting the recovery of motor function in mice after spinal cord injury by regulating interleukin-6/signal transducer and activator of transcription-3 signaling pathway
Jian-Feng QIN ; Hai-Wang SONG ; Bao-Fei SUN ; Yang-Dan JI ; Si-Fang LONG ; Dan YANG
Acta Anatomica Sinica 2024;55(3):260-267
Objective To observe the effect of neuromuscular electrical stimulation(NMES)on interleukin-6(IL-6)/STAT3 signaling pathway in mice after spinal cord injury,and to explore the mechanism of its effect on motor function recovery.Methods Seventy-two SPF grade mice were randomly divided into sham operation group,spinal cord injury(SCI)group and NMES group.BMS score,inclined plane test and neuromuscular electrophysiology(EMG)were used to evaluate the recovery of spinal cord injury in mice.Western blotting and Real-time PCR were used to detect the expression of inflammatory factors,IL-6/STAT3,glial fibrillary acidic protein(GFAP)and brain-derived neurotrophic factor(BDNF)in spinal cord tissues of three groups of mice.HE staining was used to observe the pathological changes of spinal cord injury.Results BMS scores and the inclined plane test of mice in the NMES group were higher than those in SCI group(P<0.05).The maximum amplitude of motor evoked potential in NMES group was higher than that in SCI group(P<0.05).The expressions of TNF-α,IL-12A and GFAP in the spinal cord of NMES group were lower than that of SCI group(P<0.05),while the expressions of TGF-β,IL-10 and BDNF were higher than that of SCI group(P<0.05).The protein expressions of IL-6/STAT3 signaling pathway of NMES group were lower than that of SCI group(P<0.05).Conclusion Neuromuscular electrical stimulation plays an anti-inflammatory role by inhibiting the IL-6/STAT3 signaling pathway,thereby promoting the recovery of hind limb motor function in mice after spinal cord injury.
9.Surgical decision-making types and its influencing factors for obesity patients participating in bariatric metabolic surgery
Aoli SUN ; Ningli YANG ; Yiming SI ; Kang ZHAO ; Hui LIANG
Chinese Journal of Digestive Surgery 2024;23(8):1049-1056
Objective:To investigate the surgical decision-making types and its influencing factors for obesity patients participating in bariatric metabolic surgery.Methods:The survey targets were patients who were scheduled to bariatric metabolic surgery in The First Affiliated Hospital of Nanjing Medical University, and the survey period was from January 1 to May 30, 2024. The survey was conducted using the general demographic questionnaire, control preference scale, and shared-decision requirements questionnaire for bariatric metabolic surgery. Count data were expressed as absolute numbers and percentages, and comparison between groups was performed using the chi-square test. Comparison of ordinal data was performed using the non parametric test. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was conducted using the willingness of patients to participate in bariatric metabolic surgery decision-making (passive decision-making=1, shared decision-making=2, active decision-making=3) as the dependent variable, and the statistically significant variables in univariate analysis were included as independent variables for disordered multi-class Logistic regression analysis.Results:(1) Results of survey. A total of 568 questionnaires were distributed and collected. After removing 48 unqualified questionnaires, 520 valid questionnaires were collected. Of the 520 patients who completed the questionnaire survey, there were 231 cases participating as the passive decision-making type, 140 cases as shared decision-making type, and 149 as active decision-making type in bariatric metabolic surgery decision-making. (2) Influencing factors for decision-making type of obesity patients participating in bariatric metabolic surgery. Results of multivariate analysis showed that taking the shared decision-making type as a reference, the number of complication (0 compared to ≥4, 1?3 compared to ≥4), medical payment method (medical insurance compared to self-payment), degree of disease understanding (not very understanding compared to general understanding, not understanding compared to general understanding), and the interval between knowing and accep-ting surgery (1-3 months compared to >6 months) were independent factors influencing the willingness of passive decision-making patients to participate in bariatric metabolic surgery deci-sions ( odds ratios=3.520, 2.457, 2.255, 3.147, 1.920, 1.854, 95% confidence interval as 1.552-7.984, 1.215-4.968, 1.335-3.809, 1.865-5.311, 1.025-3.596, 1.065-3.230, P<0.05). Body mass index (BMI) (28.0-31.9 kg/cm 2 compared to ≥37.0 kg/cm 2, 32.0-36.9 kg/cm 2 compared to ≥37.0 kg/cm 2), number of complication (0 compared to ≥4, 1?3 compared to ≥4), family and social support status (poor compared to good), and the interval between knowing and accepting surgery (1?3 months compared to >6 months) were independent factors influencing the willingness of passive decision-making patients to participate in bariatric metabolic surgery decisions ( odds ratios=2.391, 2.478, 6.918, 3.335, 2.974, 2.139, 95% confidence intervals as 1.207-4.735, 1.345-4.563, 2.498-19.159, 1.350-8.242, 1.755-5.039, 1.156-3.957, P<0.05). Taking the passive decision-making type as a reference, BMI (28.0-31.9 kg/cm 2 compared to ≥37.0 kg/cm 2, 32.0-36.9 kg/cm 2 compared to ≥37.0 kg/cm 2) and family social support status (poor compared to good) were independent factors influencing the willingness of passive decision-making patients to participate in bariatric metabolic surgery decisions ( odds ratios=0.404, 0.554, 0.336, 95% confidence interval as 0.221-0.740, 0.327-0.938, 0.212-0.534, P<0.05). (3) Analysis of decision support needs for bariatric metabolic surgery. Results of shared-decision requirements questionnaire showed that the information needs of obesity patients from high to low were surgical indications, postoperative physical changes and dietary habits adjust-ments, surgical costs, surgical complications and risks, and surgical outcomes. The demand for content preference from high to low were in the form of sharing patient experience after bariatric metabolic surgery, comparing before and after bariatric metabolic surgery, popularizing science after bariatric metabolic surgery, introducing surgical methods, live streaming of medical staff, and introducing the hospital environment. In terms of recognition of networked support pathways, 94.04%(489/520) of patients believed that implementing shared decision support based on networked pathways was reliable. Conclusions:Obesity patients are more willing to participate in bariatric metabolic surgery decision-making. But the proportion of patients selecting passive decision-making is relatively high. BMI, number of complication, medical payment method, degree of disease under-standing, family and social support status and the interval between knowing and accepting surgery are independent factors influencing the willingness of obesity patients to paticipate in bariatric metabolic surgery decisions.
10.Development of biological safety protection third-level laboratory based on folding-modular shelters
Si-Qing ZHAO ; Jian-Qiao XIA ; Zhong-Jie SUN ; Kang OUYANG ; Xiao-Jun JIN ; Kang-Li ZHOU ; Wei XIE ; Hai-Yang LI ; Da-Peng JIANG ; Yan-Yan GAO ; Bei SUN
Chinese Medical Equipment Journal 2024;45(3):41-46
Objective To develop a biological safety protection third-level(BSL-3)laboratory based on folding-modular shelters to solve the problems of the existing laboratories in space and function expansion,large-scale deployment and low-cost transportation.Methods The BSL-3 laboratory was composed of a folding combined shelter module,a ventilation and purification module,a power supply and distribution module,a monitoring and communication module,a control system module and an equipment module.The folding combined shelter module used a leveling base frame as the foundation and a lightweight panel as the enclosure mechanism,and was divided into an auxiliary area and a protection protected area;the ventilation and purification module was made up of an air supply unit and an air exhaust unit,the air supply unit was integrated with a fresh-air air conditioner and the exhaust unit was equipped with a main fan,a standby fan and a bag in/bag out filter;the control system module adopted a supervision mode of decentralized control and centralized management,which executed communication with the data server as the center and Profinet protocol and MODBUS-TCP.Results The BSL-3 laboratory proved to meet the requirements of relevant standards in internal microenvironment,airflow direction,airtightness,working condition and disinfection effect.Conclusion The BSL-3 laboratory is compatible with large-scale transport and deployment and facilitates reliable and safe experiments for epidemic prevention and control and cross-regional support.[Chinese Medical Equipment Journal,2024,45(3):41-46]

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