1.rTMS Improves Cognitive Function and Brain Network Connectivity in Patients With Alzheimer’s Disease
Gui-Zhi XU ; Lin LIU ; Miao-Miao GUO ; Tian WANG ; Jiao-Jiao GAO ; Yong JI ; Pan WANG
Progress in Biochemistry and Biophysics 2025;52(8):2131-2145
ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease (AD), but the neurobiological mechanisms linking synaptic pathology, neural oscillatory dynamics, and brain network reorganization remain unclear. This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments, molecular profiling, and neurophysiological monitoring. MethodsIn this prospective double-blind trial, 12 AD patients underwent a 14-day protocol of 20 Hz rTMS, with comprehensive multimodal assessments performed pre- and post-intervention. Cognitive functioning was quantified using the mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA), while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living (ADL) scale and combined neuropsychiatric inventory (NPI)-Hamilton depression rating scale (HAMD). Peripheral blood biomarkers, specifically Aβ1-40 and phosphorylated tau (p-tau181), were analyzed to investigate the effects of rTMS on molecular metabolism. Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients, while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization. Furthermore, systematic assessment of correlations between cognitive scale scores, blood biomarkers, and network characteristics was performed to elucidate cross-modal therapeutic associations. ResultsClinically, MMSE and MOCA scores improved significantly (P<0.05). Biomarker showed that Aβ1-40 level increased (P<0.05), contrasting with p-tau181 reduction. Moreover, the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores. Post-intervention analyses revealed significant modulations in oscillatory power, characterized by pronounced reductions in delta (P<0.05) and theta bands (P<0.05), while concurrent enhancements were observed in alpha, beta, and gamma band activities (all P<0.05). Network analysis revealed frequency-specific reorganization: clustering coefficients were significantly decreased in delta, theta, and alpha bands (P<0.05), while global efficiency improvement was exclusively detected in the delta band (P<0.05). The alpha band demonstrated concurrent increases in average nodal degree (P<0.05) and characteristic path length reduction (P<0.05). Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181. Additionally, the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band. However, the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands. Conclusion20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) significantly improves cognitive function and enhances the metabolic clearance of β-amyloid and tau proteins in AD patients. This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation, which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks. These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales, blood biomarkers, and EEG——in understanding and monitoring the progression of AD. This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.
2.Association between household solid fuel use for cooking and depressive symptoms among middle-aged and elderly adults in rural China: Evidence from the China Family Panel Studies Database
Ting YANG ; Yong LIU ; Xufeng LI ; Yun GAI ; Zhihao XIE ; Junkui WANG ; Yong YU ; Jingxuan WANG
Journal of Environmental and Occupational Medicine 2025;42(8):926-931
Background Although current evidence suggests a link between outdoor air pollution and depressive symptoms, the effect of solid fuel use (a significant indoor air pollutant) on depressive symptoms in China's rural middle-aged and elderly population remains poorly understood. Objective To explore the association between solid fuel use for cooking and depressive symptoms among middle-aged and elderly people in rural areas of China, and to provide a basis for the prevention and control of depressive symptoms among residents in rural areas. Methods Data were obtained from the 2020 China Family Panel Studies (CFPS), depressive symptoms were assessed using 8-item Center for Epidemiologic Studies Depression Scale (CES-D), and cooking fuel type was self-reported. Subsequently, two-level binary unconditional logistic regression models were fitted to assess the impact of solid fuel use for cooking on depressive symptoms. Results A total of
3.Network pharmacology, molecular docking, and animal experiments reveal mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children.
Yong-Kai YIN ; Chang-Miao NIU ; Li-Ting LIANG ; Mo DAN ; Tian-Qi GAO ; Yan-Hong QIN ; Xiao-Ning YAN
China Journal of Chinese Materia Medica 2025;50(1):228-238
Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals
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Drugs, Chinese Herbal/pharmacology*
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Molecular Docking Simulation
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Adipose Tissue/immunology*
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Mice
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Male
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Humans
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Network Pharmacology
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Macrophages/immunology*
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Mice, Inbred C57BL
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Child
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Protein Interaction Maps/drug effects*
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Obesity/genetics*
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Inflammation/drug therapy*
4.Prediction of quality markers for cough-relieving and phlegm-expelling effects of Kening Granules based on plasma pharmacology combined with network pharmacology and pharmacokinetics.
Qing-Qing CHEN ; Yuan-Xian ZHANG ; Qian WANG ; Jin-Ling ZHANG ; Lin ZHENG ; Yong HUANG ; Yang JIN ; Zi-Peng GONG ; Yue-Ting LI
China Journal of Chinese Materia Medica 2025;50(4):959-973
This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage*
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Network Pharmacology
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Cough/blood*
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Male
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Humans
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Animals
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Rats
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Rats, Sprague-Dawley
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Biomarkers/blood*
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Quality Control
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Chromatography, High Pressure Liquid
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Antitussive Agents/chemistry*
5.Mechanism and Application of Chinese Herb Medicine in Treatment of Peripheral Nerve Injury.
Yu-Qing CHEN ; Yan-Xian ZHANG ; Xu ZHANG ; Yong-Mei LYU ; Zeng-Li MIAO ; Xiao-Yu LIU ; Xu-Chu DUAN
Chinese journal of integrative medicine 2025;31(3):270-280
Peripheral nerve injury (PNI) encompasses damage to nerves located outside the central nervous system, adversely affecting both motor and sensory functions. Although peripheral nerves possess an intrinsic capacity for self-repair, severe injuries frequently result in significant tissue loss and erroneous axonal junctions, thereby impeding complete recovery and potentially causing neuropathic pain. Various therapeutic strategies, including surgical interventions, biomaterials, and pharmacological agents, have been developed to enhance nerve repair processes. While preclinical studies in animal models have demonstrated the efficacy of certain pharmacological agents in promoting nerve regeneration and mitigating inflammation, only a limited number of these agents have been translated into clinical practice to expedite nerve regeneration. Chinese herb medicine (CHM) possesses a longstanding history in the treatment of various ailments and demonstrates potential efficacy in addressing PNI through its distinctive, cost-effective, and multifaceted methodologies. This review critically examines the advancements in the application of CHM for PNI treatment and nerve regeneration. In particular, we have summarized the most commonly employed and rigorously investigated CHM prescriptions, individual herbs, and natural products, elucidating their respective functions and underlying mechanisms in the context of PNI treatment. Furthermore, we have deliberated on the prospective development of CHM in both clinical practice and fundamental research.
Drugs, Chinese Herbal/pharmacology*
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Humans
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Peripheral Nerve Injuries/drug therapy*
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Animals
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Nerve Regeneration/drug effects*
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Medicine, Chinese Traditional
6.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
7.Expert Consensus on Perioperative Nursing Care for Follicular Unit Extraction(2025)
Chunhua ZHANG ; Weiwei BIAN ; Congmin WANG ; Lin SHEN ; Yong MIAO ; Na LIU ; Shan JIA ; Junhong AN ; Hongxia WANG ; Dongmei ZHANG
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1606-1613
To promote the standardization and normalization of perioperative care for follicular unit extraction(FUE) hair transplantation, ensure treatment efficacy, and align with advancements in the specialty, the Nursing Branch of the Chinese Association of Plastic and Aesthetics organized a panel of domestic experts. By integrating evidence-based medicine with clinical practice experience, and following thorough discussions, these experts developed the Clinical Practice
8.Correlation analysis between systemic immune inflammation index and risk stratification of acute pulmonary embolism
Chang DU ; Yong MA ; Miao SHI ; Jihong ZHU
Chinese Journal of Emergency Medicine 2024;33(9):1286-1290
Objective:To analyze the relationship between the systemic immune inflammation index (SII) and risk stratification of acute pulmonary embolism.Methods:The clinical data of patients with moderate to critical pulmonary embolism admitted to the emergency department of Peking University People's Hospital from January 2018 to May 2022 were respectively collected. The patients divided into a medium to high-risk group and a medium to low-risk group according to risk stratification. The SII index, simplified pulmonary embolism severity index (sPESI), general information, disease history, laboratory test results, and other indicators between two groups of patients were compared. Logistic regression was used to analyze the relationship between SII and risk stratification in patients with acute pulmonary embolism.Results:A total of 97 patients with moderate to critical pulmonary embolism were included, including 43 were in the medium high risk group and 54 were in the medium low risk group. The data of SII index, white blood cell count, C-reactive protein, and sPESI of patients in the medium to high-risk group were significantly higher than those in the medium to low-risk group (all P<0.05), and lower lymphocyte count than those in the medium to low-risk group ( P<0.05). Logistic regression analysis showed that SII ( OR=1.001, 95% CI: 1.000-1.002, P=0.027) and sPESI ( OR=2.000, 95% CI: 1.155-3.464, P=0.013) were the main factors affecting risk stratification in patients with acute pulmonary embolism. The AUC of SII, sPESI score, and their combined evaluation of acute pulmonary embolism risk stratification were 0.710, 0.625, and 0.739, respectively. The combined evaluation value of the two indicators was higher than that of a single indicator ( P=0.007). Conclusion:SII has good application value in risk stratification of acute pulmonary embolism, and the combined sPESI score has higher value.
9.Improved YOLOv8-based measurement method of anterior segment parameters of ultrasonic biological microscopy images
Yong-Qiang HE ; Qing-Hao MIAO ; Cai-Lian XIONG ; Jun YANG
Chinese Medical Equipment Journal 2024;45(2):8-16
Objective To propose a measurement method based on improved YOLOv8 for the anterior segment parameters of ultrasonic biological microscopy(UBM)images to solve the problems of the ophthalmic ultrasound images in low quantity,high annotation cost and weak model generalization ability.Methods Firstly,data enhancement using StyleGAN3 was carried out to improve YOLOv8 model in decreased sensitivity to UBM images and increased generalization ability;secondly,the pseudo-labels of virtual UBM images were generated based on the YOLOv8 model with the original UBM images as the dataset and the method of pseudo-label self-training in semi-supervised learning;finally,the YOLOv8 model was trained with the expan-ded dataset and improved with the global context network(GCNet)module,and the prediction results of the YOLOv8 model were sorted using the key-point ranking algorithm,and the measurements of the anterior segment physiological parameters were computed after screening qualified images based on prior knowledge.Results Compared with the hand-labeled results by the ophthalmologists,the localization error of the StyleGAN3 data-enhanced and self-trained YOLOv8 model was(61.94±40.66)μm,and the mean relative errors for the measurements of anterior chamber angle distance,pupil diameter,ciliary sulcus distance,central corneal thickness,anterior chamber depth and lens thickness were 0.62%,1.35%,0.68%,4.87%,0.93%and 0.75%,respectively.Conclusion The method proposed enhances the accuracy of the measurement method for anterior segment parameters of UBM images,and can meet real-time requirements.[Chinese Medical Equipment Journal,2024,45(2):8-16]
10.Preliminary experiences of management on acute carotid artery occlusion during perioperative period of carotid endarterectomy
Hongwei ZHANG ; Dong ZHANG ; Xiao MIAO ; Shaomin WANG ; Xiguang LIU ; Yan GU ; Yong SUN ; Shiwei YAN ; Aimin LI
Chinese Journal of Postgraduates of Medicine 2024;47(11):994-1000
Objective:To investigate the treatment and prognosis of acute carotid artery occlusion during perioperative period of carotid endarterectomy (CEA).Methods:The clinical data of 112 carotid artery stenosis patients who underwent CEA from January 2017 to December 2021 in Lianyungang Hospital Affiliated to Xuzhou Medical University were retrospectively analyzed. The patients were followed up at 6 to 9 months after surgery, the clinical prognosis was evaluated by Glasgow outcome score (GOS), and the head and neck CT angiography (CTA) was performed.Results:Among the 112 patients, 5 patients underwent acute carotid artery occlusion during the perioperative period, including 1 case of intraoperative acute occlusion of internal carotid artery and 1 case of intraoperative internal carotid artery combined with external carotid artery cute occlusion, both of them were re-sutured, and multi-mode monitoring showed that each carotid artery was unobstructed; 2 cases of intraoperative external carotid artery occlusion, no re-suture was performed during the operation; 1 case of intraoperative monitoring showed no obvious abnormality, and the contralateral limb hemiplegia was observed after surgery, and the muscle strength was grade 1, the carotid color Doppler ultrasound showed the occlusion of the internal carotid artery on the operation side. The CT and CTA examination showed focal infarction and common carotid artery on the operation side, and drugs and conservative treatment were given. The follow-up result: GOS 5 scores was in 4 cases, and 4 scores in 1 case; the muscle strength of hemiplegia patient recovered to grade 4; head and neck CTA examination, except for 1 case of common arterial occlusion, the other 4 cases showed no special abnormality.Conclusions:Intraoperative acute carotid artery occlusion can be detected timely by intraoperative multi-mode hemodynamic monitoring during CEA. Vascular recanalization after acute occlusion is possible by adopting active and effective treatment methods, the occurrence of postoperative ischemic stroke can be effectively prevented and the prognosis of patients can be improved.

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