Under the background of the Healthy China strategy， the integration of traditional Chinese medicine （TCM） into the public health emergency response system has become an important measure to enhance the capacity for coping with public health emergencies. In recent years， the role of TCM in responding to such emergencies has become increasingly prominent. Taking major emerging epidemics as an example， TCM has developed a rich theoretical system and practical experience in epidemic prevention and treatment over thousands of years， and has played a significant role in successive outbreaks with its unique advantages. Based on the concept of ''preventing disease before its onset'' and the theoretical framework of treatment based on syndrome differentiation， TCM has achieved remarkable results through early intervention and full participation in the integrated model of TCM and Western medicine， from severe acute respiratory syndrome （SARS） to corona virus disease-2019 （COVID-19）， in improving clinical symptoms and outcomes， reducing adverse reactions， and promoting recovery. From the perspective of the Healthy China strategy， this paper systematically reviews the historical development of TCM in epidemic prevention and treatment， with particular attention to recent epidemics such as SARS， influenza A （H1N1）， and COVID-19. It further examines the similarities and differences between TCM and Western medicine in responding to major emerging epidemics， as well as relevant policies related to TCM in epidemic prevention and control. In addition， it summarizes the existing problems in TCM's role in the prevention and treatment of major emerging epidemics， and explores measures to improve its rapid response capacity under the Healthy China strategy. This study not only provides a ''Chinese solution'' for the prevention and control of newly emerging infectious diseases worldwide， but also offers theoretical and practical references for strengthening the public health emergency response system， carrying strategic significance for promoting the modernization and internationalization of TCM.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

OBJECTIVES: To investigate the regulatory role of astrocytes in the dorsomedial hypothalamus (DMH) during sevoflurane anesthesia emergence. METHODS: Forty-two male C57BL/6 mice were randomized into 6 groups (n=7) for assessing astrocyte activation in the dorsomedial hypothalamus (DMH) under sevoflurane anesthesia. Two groups of mice received microinjection of agfaABC1D promoter-driven AAV2 vector into the DMH for GCaMP6 overexpression, and the changes in astrocyte activity during sevoflurane or air inhalation were recorded using calcium imaging. For assessing optogenetic activation of astrocytes, another two groups of mice received microinjection of an optogenetic virus or a control vector into the DMH with optic fiber implantation, and sevoflurane anesthesia emergence was compared using behavioral experiments. In the remaining two groups, electroencephalogram (EEG) recording during sevoflurane anesthesia emergence was conducted after injection of the hChR2-expressing and control vectors. Anesthesia induction and recovery were assessed by observing the righting reflex. EEG data were recorded under 2.0% sevoflurane to calculate the burst suppression ratio (BSR) and under 1.5% sevoflurane for power spectrum analysis. Immunofluorescence staining was performed to visualize the colocalization of GFAP-positive astrocytes with viral protein signals. RESULTS: Astrocyte activity in the DMH decreased progressively as sevoflurane concentration increased. During 2.0% sevoflurane anesthesia, the mice injected with the ChR2-expressing virus exhibited a significantly shortened wake-up time (P<0.05), and optogenetic activation of the DMH astrocytes led to a marked reduction in BSR (P<0.001). Under 1.5% sevoflurane anesthesia, optogenetic activation resulted in a significant increase in EEG gamma power and a significant decrease in delta power in ChR2 group (P<0.01). CONCLUSIONS Optogenetic activation of DMH astrocytes facilitates sevoflurane anesthesia emergence but does not significantly influence anesthesia induction. These findings offer new insights into the mechanisms underlying anesthesia emergence and may provide a potential target for accelerating postoperative recovery and managing anesthesia-related complications.
Animals ; Astrocytes/physiology* ; Sevoflurane ; Mice, Inbred C57BL ; Mice ; Male ; Electroencephalography ; Anesthetics, Inhalation/pharmacology* ; Hypothalamus/cytology* ; Anesthesia Recovery Period ; Methyl Ethers/pharmacology*

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

OBJECTIVE: To identify the protective effect of empagliflozin on ischemic brain injury and neurological dysfunction in mice, and further explore its potential mechanism. METHODS: Acute cerebral ischemia model was induced by the permanent middle cerebral artery occlusion surgery in C57BL/6J mice. Empagliflozin(10 and 30 mg·kg−1) was administered to mice one hour after the onset of occlusion. Brain infarct volume and neurological defect score were assayed 24 h after surgery. Mice were subjected to photo-thrombosis and further administered with empagliflozin 3, 10, 30 mg·kg−1 intragastricly for either 7 or 14 consecutive days. The grid-walking task and the cylinder task were performed daily to determine the sensory-motor function of the mice. Alternatively, the mice were treated with 10 mg·kg−1 empagliflozin simultaneously with 10% glucose(i.p.) for 7 consecutive days after the photo-thrombosis model to evaluate their motor sensory function. Immunofluorescence staining was used to detect the activation of microglia within the infarct area 7 d after the photo-thrombosis. RESULTS: One hour after permanent middle cerebral artery occlusion surgery, gavage of empagliflozin significantly increased the brain infarct volume and neurological dysfunction. While in photo-thrombosis surgery, treatment of empagliflozin(10 mg·kg−1) for consecutive 7 or 14 days significantly decreased the rate of false foot in grid-walking task and the assymetric index in cylinder task. At the dose of 30 mg·kg−1, however, empagliflozin even aggravated photo-thrombosis-induced neurological dysfunction, while the dose of 3 mg·kg−1 showed no effect. Unexpectedly, the protective effect of empagliflozin(10 mg·kg−1) could not be reversed by glucose treatment. The results of immunofluorescence showed that empagliflozin(10 mg·kg−1) significantly alleviated the microglia activation in the ischemic area after the photo-thrombosis operation. CONCLUSION Empagliflozin cannot protect against acute ischemia-induced brain injury in mice. Empagliflozin alleviated ischemia-induced neurological dysfunction with consecutive administration in a dose-related manner. Empagliflozin-conferred neuroprotection may not be attributable to its effects on lowing blood glucose. Alternatively, empagliflozin may play a neuroprotective effect by inhibiting the excessive activation of microglia in ischemic brains.

Objective To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey(dmPAG)in regulating excessive defensive behaviors in mice with post-traumatic stress disorder(PTSD).Methods Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno-associated viral vectors(rAAV2/9-CaMKⅡ-mCherry,rAAV2/9-CaMKⅡ-hM3Dq-mCherry and rAAV2/9-CaMKⅡ-hM4Di-mCherry)into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons,followed 2 weeks later by PTSD modeling by single prolonged stress.The looming test,response to whisker stimulation test and contextual fear conditioning(CFC)test were used to observe changes in defensive behaviors of the PTSD mice.The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining.Results Compared with the control mice,the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest,response scores of defensive behaviors and freezing time(all P<0.01).Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors.Activation of the glutamatergic neurons in the dmPAG(in PTSD hM3Dq group)did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice,whereas inhibiting the glutamatergic neurons in the dmPAG(in PTSD hM4Di group)caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice(P<0.05 or 0.01).Conclusion Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.

Objective To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey(dmPAG)in regulating excessive defensive behaviors in mice with post-traumatic stress disorder(PTSD).Methods Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno-associated viral vectors(rAAV2/9-CaMKⅡ-mCherry,rAAV2/9-CaMKⅡ-hM3Dq-mCherry and rAAV2/9-CaMKⅡ-hM4Di-mCherry)into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons,followed 2 weeks later by PTSD modeling by single prolonged stress.The looming test,response to whisker stimulation test and contextual fear conditioning(CFC)test were used to observe changes in defensive behaviors of the PTSD mice.The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining.Results Compared with the control mice,the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest,response scores of defensive behaviors and freezing time(all P<0.01).Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors.Activation of the glutamatergic neurons in the dmPAG(in PTSD hM3Dq group)did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice,whereas inhibiting the glutamatergic neurons in the dmPAG(in PTSD hM4Di group)caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice(P<0.05 or 0.01).Conclusion Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.