Microglial functions are linked to Ca²⁺ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca²⁺ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca²⁺ transients in controls and normalized Ca²⁺ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca²⁺ receptors in both homeostatic and AD microglia, providing insights into microglial Ca²⁺ malfunctions in AD.
Animals ; Microglia/pathology* ; Alzheimer Disease/pathology* ; Phagocytosis/drug effects* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Disease Models, Animal ; Mice ; Cell Movement/drug effects* ; Mice, Transgenic ; Calcium Signaling/physiology* ; Calcium/metabolism* ; Mice, Inbred C57BL ; Male ; Endoplasmic Reticulum/metabolism*

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

ObjectiveTo investigate the supply satisfaction with community-embedded elderly care services in Nanchang city， which can assist in optimizing its supply system of elderly care services and build a policy system for high-quality development of community-embedded elderly care services for reference. MethodsA total of 15 indicators from three dimensions： resource embeddedness， functional embeddedness， and operational-mode embeddedness， were selected to design the Elderly Care Service Supply Satisfaction Scale. A simple random sampling method was used to survey elderly residents in 25 community-embedded elderly care institutions in Nanchang city， and the binary logistic regression model and structural equation model were used for analysis. ResultsFirst， resource embeddedness and operational-mode embeddedness had a significantly positive impact on supply satisfaction. Second， the weight of resource embeddedness， functional embeddedness， and operational-mode embeddedness on supply satisfaction decreased gradually. Third， the “number of service personnel” and “adequacy of service types” in the resource embeddedness dimension， the “entertainment services” and “medical services” in the functional embeddedness dimension， and the “charging standard” and “service response degree” in the operational-mode embeddedness dimension had a greater impact on supply satisfaction in their corresponding dimensions. ConclusionTo develop community-embedded elderly care， it is essential to strengthen the construction of the team of elderly care professionals， enrich the supply content of elderly care services， and increase the development support with the help of resource embeddedness； establish a unified charging system for elderly care， improve the responsiveness of elderly care services， and enhance the development internal driving force based on operational-mode embeddedness； improve the level of integrated medical and elderly care， emphasize the return of the family as the main body， and perfect the development system by using functional embeddedness as a link.

Objective To establish primary breast cancer cell lines from patient tissues and offer a new cancer cell model for basic research.Methods Breast cancer biopsy tissues were digested with typeⅡcollagenase and cultured in BCMI medium.When the cells proliferated rapidly,the medium was switched to DMEM.STR genotyping was per-formed to identify specific genetic markers of the four primary breast cancer cell lines.Colony expansion assays and sphere formation assays were conducted to analyze its tumorigenicity.Real-time PCR and Western blot experiments were used to analyze the expression of the epithelial-mesenchymal transition(EMT)molecule markers.Migration and invasion assays were performed to assess the metastatic potential of the primary breast cancer cells.Results We es?tablished four primary breast cancer cell lines:BC25#,BC51#,BC56#,and BC57#.These cell lines were cultured in DMEM medium,passaged multiple times and tagged with details about their clinical past.STR genotyping identified specific genetic markers for each of the four primary breast cancer cell lines.Clonogenic and sphere formation assays revealed that the four lines have a stronger tumor?forming capability compared to the classic breast cancer cell line T?47D.Real?time PCR and Western blot experiments showed that,compared to T?47D,the four primary breast cancer cell lines have decreased E?cadherin expression and increased vimentin expression.Migration and invasion assays indicated that BC25#had a higher metastatic potential than the traditional breast cancer cell line T?47D.Conclusions Four primary breast cancer cell lines,BC25#,BC51#,BC56#and BC57#are successfully estab?lished,which may act as new cancer cell model for laboratory research of breast cancer.

[Objective]To explore new pathways for cultural education in Chinese medicine institutions,delve deeply into the educational elements embedded in traditional Chinese medicine(TCM)culture,and establish a new educational system that gives full play to the advantages and characteristics of TCM culture.[Methods]Through the status analysis on TCM culture-based education in Chinese medicine institutions,based on the exploration of the main bodies,content,forms and effectiveness of education,concrete ideas and practical pathways for reforming the curriculum system and the practice system were advanced,and the achievements of student cultivation were listed as evidence.[Results]The practice of cultivating students through TCM culture in Chinese medicine institutions was confronted with multiple issues,including the need to strengthen collaborative education,the need to integrate education and teaching content,and the necessity to enhance the talent-nurturing mechanism through campus culture.Zhejiang Chinese Medical University has fostered a campus culture rich in TCM characteristics by establishing a curriculum and practical system that merges TCM culture into the five dimensions of education and constructs a comprehensive and interconnected support system.The social recognition won by the students at this university has fully proved the effectiveness in enhancing students'comprehensive qualities and fostering cultural confidence.[Conclusion]To fulfill the missions of moral and cultural education,Chinese medical universities must establish a new TCM culture-based educational system,with seamless cooperation of all departments throughout the entire educational process and the integration of the five dimensions of education.Through the aforementioned practice,Zhejiang Chinese Medical University has effectively addressed issues such as the lack of a collaborative education among all departments and how TCM culture can promote the"integration of the five dimensions of education",providing a paradigm for Chinese medicine institutions to carry out TCM culture-based education.

[Objective]To explore new pathways for cultural education in Chinese medicine institutions,delve deeply into the educational elements embedded in traditional Chinese medicine(TCM)culture,and establish a new educational system that gives full play to the advantages and characteristics of TCM culture.[Methods]Through the status analysis on TCM culture-based education in Chinese medicine institutions,based on the exploration of the main bodies,content,forms and effectiveness of education,concrete ideas and practical pathways for reforming the curriculum system and the practice system were advanced,and the achievements of student cultivation were listed as evidence.[Results]The practice of cultivating students through TCM culture in Chinese medicine institutions was confronted with multiple issues,including the need to strengthen collaborative education,the need to integrate education and teaching content,and the necessity to enhance the talent-nurturing mechanism through campus culture.Zhejiang Chinese Medical University has fostered a campus culture rich in TCM characteristics by establishing a curriculum and practical system that merges TCM culture into the five dimensions of education and constructs a comprehensive and interconnected support system.The social recognition won by the students at this university has fully proved the effectiveness in enhancing students'comprehensive qualities and fostering cultural confidence.[Conclusion]To fulfill the missions of moral and cultural education,Chinese medical universities must establish a new TCM culture-based educational system,with seamless cooperation of all departments throughout the entire educational process and the integration of the five dimensions of education.Through the aforementioned practice,Zhejiang Chinese Medical University has effectively addressed issues such as the lack of a collaborative education among all departments and how TCM culture can promote the"integration of the five dimensions of education",providing a paradigm for Chinese medicine institutions to carry out TCM culture-based education.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Purpose This study uses the diffusion tensor imaging to explore diffusion metrics changes of corpus callosum subregion,and to further analyze the relationship among these changes and the cognitive and emotional in adults with primary hypothyroidism.Materials and Methods From October 2019 to September 2021,32 hypothyroidism patients were recruited from Gansu Provincial Hospital,whereas 33 healthy controls were recruited through advertisements.The comprehensive thyroid-related hormone levels tests,as well as neurocognitive/neuropsychiatric assessment and diffusion tensor imaging data of all participants were carried out.The differences in corpus callosum subgroups of diffusion metrics between the two groups were recorded and compared,the partial relationships between these diffusion metrics and thyroid-related hormone levels and neurocognitive/neuropsychiatric function were analyzed and measured.Receiver operating characteristic curves were constructed to evaluate the diagnostic performance.Results Lower fraction anisotropy,higher mean diffusivity and radial diffusivity in genu and body of the corpus callosum and higher axial diffusivity in genu of the corpus callosum were found in hypothyroidism compared with healthy controls(P<0.01).These diffusion metrics were negatively correlated with cognition and emotion(r=-0.448-0.440,P=0.010-0.043),and the fraction anisotropy value in genu of the corpus callosum had the largest area under the curve(0.777).Conclusion Hypothyroidism patients show widespread microstructural changes within the genu and body of the corpus callosum,which,respectively,associated with cognition and emotion.This study provides a new perspective to further understanding the pathophysiology of the cerebral impairment in hypothyroidism.

Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.

Objective: To study the effect of a space stabilizing device on the capacity for osteogenesis in the bone-grafted area. Methods: Patients with anterior teeth defects as well as labial alveolar ridge defects were randomly divided into two groups: the experimental group was treated using a space stabilization device after guided bone regeneration whereas the control group received regular guided bone regeneration. The CBCT data was analyzed prior to, immediately and 6 months after procedure to compare the osteogenesis with or without the device. Results: Seventeen bone-grafted sites were examined(7 in the experimental group and 10 in the control group). At 2 mm and 4 mm below the alveolar ridge, the horizontal bone resorption rate in the experimental group was significantly lower than the corresponding level in the control group(P=0.001). The horizontal bone resorption rate at 2 mm below the alveolar ridge of each group was significantly higher than that at 4 mm below the alveolar ridge in corresponding groups(P=0.003). Conclusion The space stabilizing device used in this study has a positive clinical impact on preserving space stability and minimizing bone resorption.