1.Hippocampal Extracellular Matrix Protein Laminin β1 Regulates Neuropathic Pain and Pain-Related Cognitive Impairment.
Ying-Chun LI ; Pei-Yang LIU ; Hai-Tao LI ; Shuai WANG ; Yun-Xin SHI ; Zhen-Zhen LI ; Wen-Guang CHU ; Xia LI ; Wan-Neng LIU ; Xing-Xing ZHENG ; Fei WANG ; Wen-Juan HAN ; Jie ZHANG ; Sheng-Xi WU ; Rou-Gang XIE ; Ceng LUO
Neuroscience Bulletin 2025;41(12):2127-2147
Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca2+ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals
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Laminin/genetics*
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Hippocampus/metabolism*
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Neuralgia/metabolism*
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Cognitive Dysfunction/etiology*
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Male
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Peripheral Nerve Injuries/metabolism*
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Extracellular Matrix/metabolism*
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Integrin beta1/metabolism*
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Pyramidal Cells/metabolism*
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Signal Transduction
2.Key technology and equipment development status of first-aid robotics
Zhen-bao WANG ; Zi-jian WANG ; Xin-xi XU ; Xin LIU ; Tao CHENG ; Pei-peng LIU ; Xiu-guo ZHAO ; Chen SU
Chinese Medical Equipment Journal 2025;46(3):96-114
The development status of the key technologies of first-aid robotics was introduced in autonomous system,embo-died intelligence,digital twins,large artificial intelligence model and autonomous unmanned medical treatment.The present situation in first-aid robotics equipment was reviewed for first-aid diagnosis,treatment,assistance and transportation.The development trends of the key technology and equipment of first-aid robotics were analyzed.It was pointed out the involve-ment of big model-based embodied intelligence technology and digital twins technology in first aid might provide new pers-pectives for the application and advancement of specialized first-aid robotics.[Chinese Medical Equipment Journal,2025,46(3):96-114]
3.Antagonistic effect of Lactobacillus reuteri on testicular reproductive toxicity of neonicotinoid insecticides in mice
Zhen-han XU ; Pei-gen CHEN ; Jin-tao GUO ; Lin-yan LÜ ; Hai-cheng CHEN ; Gui-hua LIU
National Journal of Andrology 2025;31(2):131-137
Objective:To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insec-ticides(NNI).Methods:Fifteen C57BL/6 male mice were randomly divided into control group(CTRI.group),exposure group(NNI group)and Lactobacillus intervention group(NNI-L group).The mice in CTRL group were given 0.02ml/g of 0.5%carboxym-ethyl cellulose sodium solution by gavage for 14 days.The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days.The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5 × 108cfu/ml of Lactobacillus reuteri powder so-lution for 14 days.Then,the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining,immunofluores-cence staining and RNA sequencing.Results:Compared with CTRL group,the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner.And the decline in the number of spermatogenic cells and sperm was observed.And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group.The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequen-cing,with significant down-regulation being found in NPFF and IGF2.While the expression of HSD3B8 was significantly up-regulated.The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri.Conclusion:Testicular spermatogenesis and endocrine function can be damaged by NNI exposure.And oral administration of Lactoba-cillus reuteri protects testis from the adverse effects of NNI toxicity.
4.Exploring mechanism of action of hypericin in antidepressant effects based on single-cell sequencing
Hui-xin NI ; Hai-xin LIU ; Bing-can ZHOU ; Ming-heng CHEN ; Ping-yan LIN ; Zheng-tao GAO ; Xin-pei LIN ; Yao LIN ; Fang-zhen WU ; Qian XU
Chinese Pharmacological Bulletin 2025;41(5):837-843
Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.
5.Key technology and equipment development status of first-aid robotics
Zhen-bao WANG ; Zi-jian WANG ; Xin-xi XU ; Xin LIU ; Tao CHENG ; Pei-peng LIU ; Xiu-guo ZHAO ; Chen SU
Chinese Medical Equipment Journal 2025;46(3):96-114
The development status of the key technologies of first-aid robotics was introduced in autonomous system,embo-died intelligence,digital twins,large artificial intelligence model and autonomous unmanned medical treatment.The present situation in first-aid robotics equipment was reviewed for first-aid diagnosis,treatment,assistance and transportation.The development trends of the key technology and equipment of first-aid robotics were analyzed.It was pointed out the involve-ment of big model-based embodied intelligence technology and digital twins technology in first aid might provide new pers-pectives for the application and advancement of specialized first-aid robotics.[Chinese Medical Equipment Journal,2025,46(3):96-114]
6.Exploring mechanism of action of hypericin in antidepressant effects based on single-cell sequencing
Hui-xin NI ; Hai-xin LIU ; Bing-can ZHOU ; Ming-heng CHEN ; Ping-yan LIN ; Zheng-tao GAO ; Xin-pei LIN ; Yao LIN ; Fang-zhen WU ; Qian XU
Chinese Pharmacological Bulletin 2025;41(5):837-843
Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.
7.Treatment of Chronic Bronchitis Based on Theory of "Warming Lung Yang and Protecting Yin Skin"
Zhen LU ; Qingyin LIU ; Weiwei YAO ; Weiwei TAO ; Lina LIU ; Ke PEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(15):215-223
Chronic bronchitis (CB) is a common respiratory system disease that is classified as a lung disease in traditional Chinese medicine (TCM) and is closely related to lung dysfunction. Lung Yang is the Yang Qi of the lungs,which drives the physiological activities within the lungs. It has physiological functions such as warming the lung system,regulating lung fluid,and dispersing the protective Yang. It can be distributed on the surface of the airway's Yin skin through sweat pores in the form of airflow and fluid,playing a protective and nourishing role. If the protective Yang fails to guard the Yin skin or if the lung fluid cannot nourish the Yin skin,the structural integrity of the airway's Yin skin may be compromised. This may weaken lung Yang's functions, such as clearing phlegm turbidity,dispersing lung fluid,and resisting external pathogens. Consequently, the retention of phlegm turbidity,insufficient nourishment of the Yin skin,and invasion by external pathogens all damage the lung Yang,burn the lung fluid,and exacerbate the pathological state of Yin skin unprotected,forming a vicious cycle that ultimately results in lung Yang asthenia and then the onset of CB. Based on the intrinsic connection between "Yin skin unprotected" and "lung Yang asthenia",this paper interprets the etiology and pathogenesis of CB. It proposes that "Yin skin unprotected" in the airway is the basic cause of CB and "lung Yang asthenia" caused by "Yin skin unprotected" is the core pathogenesis of CB. By integrating micro differentiation indicators with macro differentiation syndromes, the study explores its modern biological basis. Guided by the theory of "warming the lung Yang and protecting the Yin skin" and based on modern pharmacology research,this study further explores the scientific connotation of single TCM and compound formulations for treating TCM by warming the lung Yang and protecting the Yin skin. Furthermore, it proposes methods for dispelling pathogenic factors and protecting the Yin skin during the acute exacerbation phase,as well as nourishing and warming lung Yang during the remission phase,in order to provide new ideas for the early prevention and treatment of TCM.
8.Spatial epidemiological analysis of severe hand, foot and mouth disease in Guangxi, 2014-2018
PENG Yuan-jun ; HE Wei-tao ; ZHENG Zhi-gang ; PAN Pei-jiang ; JU Yu ; LU Zhen-wei ; LIAO Yan-yan
China Tropical Medicine 2023;23(5):473-
Abstract: Objective To explore the spatial epidemiological characteristics of severe cases hand, foot and mouth disease (HFMD) in Guangxi, China, from 2014 to 2018, and to provide a basis for identifying the high-risk regions as well as the prevention and control of severe cases of HFMD in Guangxi. Methods Spatial-temporal scanning analysis, global and local spatial autocorrelation analysis were used to analyze the spatial clustering of HFMD. The trend surface analysis was used to evaluate the spatial distribution trend of HFMD. Results From 2014 to 2018, the incidence and severe case fatality rates of HFMD were 3.89/100 000 and 4.23%, respectively. Monte Carlo scanning analysis showed that the first cluster region was Cenxi City, the second cluster was mainly concentrated in northwest of Guangxi, and the aggregation time was mainly concentrated in April to May and August to October. The global spatial autocorrelation analysis showed that the severe HFMD was significant clustering distribution, and the Moran's I coefficients of the sever cases, severe morbidity and severe case fatality rate were 0.088, 0.118, 0.197, respectively (P<0.05). Local spatial autocorrelation analysis showed that hotspots of severe HFMD cases were concentrated in the southern Guangxi, mainly in Lingshan County. Anselin local Moran's I clustering and outlier analysis indicated that 5 high-high (H-H) clustering regions for fatality were Lingshan, Pubei, Zhongshan, Zhaoping and Pinggui County. There were 6 high-high (H-H) clustering regions for severe incidence rate, namely Lingshan, Qinnan, Lingyun, Youjiang, Bama Yao Autonomous and Pinggui County, and 1 high-low (H-L) clustering region, Cenxi County. The trend surface analysis showed that the overall number of severe cases of death decreased from east or west to the middle, and increased from north to middle, and then decreased to south. Conclusions Severe HFMD cases in Guangxi have obvious spatial-temporal clustering, and the hop spots are mainly concentrated in southern Guangxi. The prevention and control of HFMD in areas with high incidence of severe cases should be strengthened to reduce the burden of HFMD cases.
9.Wnt/b-Catenin Promotes the Osteoblastic Potential of BMP9 Through Down-Regulating Cyp26b1 in Mesenchymal Stem Cells
Xin-Tong YAO ; Pei-pei LI ; Jiang LIU ; Yuan-Yuan YANG ; Zhen-Ling LUO ; Hai-Tao JIANG ; Wen-Ge HE ; Hong-Hong LUO ; Yi-Xuan DENG ; Bai-Cheng HE
Tissue Engineering and Regenerative Medicine 2023;20(5):705-723
BACKGROUND:
All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1.
METHODS:
ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism.
RESULTS:
We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1.
CONCLUSIONS
Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.
10.Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture (version 2023)
Zhonghua XU ; Lun TAO ; Zaiyang LIU ; Yang LI ; Jie LI ; Jun ZHANG ; Xia ZHANG ; Min WANG ; Changqing LI ; Guangxing CHEN ; Liu YANG ; Dawei ZHANG ; Xiaorui CAO ; Guoqiang ZHANG ; Pingyue LI ; Nirong BAO ; Chuan LI ; Shenghu ZHOU ; Zhengqi CHANG ; Bo WU ; Wenwei QIAN ; Weiguo WANG ; Ming LYU ; Hao TANG ; Hu LI ; Chuan HE ; Yunsu CHEN ; Huiwu LI ; Ning HU ; Mao NIE ; Feng XIE ; Zhidong CAO ; Pengde KANG ; Yan SI ; Chen ZHU ; Weihua XU ; Xianzhe LIU ; Xinzhan MAO ; Jie XIE ; Xiaogang ZHANG ; Boyong XU ; Pei YANG ; Wei WANG ; Xiaofeng LI ; Eryou FENG ; Zhen ZHANG ; Baoyi LIU ; Jianbing MA ; Hui LI ; Yuanchen MA ; Li SUN ; Zhifeng ZHANG ; Shuo GENG ; Guanbao LI ; Yuji WANG ; Erhu LI ; Zongke ZHOU ; Wei HUANG ; Yixin ZHOU ; Li CAO ; Wei CHAI ; Yan XIONG ; Yuan ZHANG
Chinese Journal of Trauma 2023;39(11):961-973
Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

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