Background: The purpose of our study was to analyze the effects of hospital volume and region on in-hospital and long-term mortality, direct medical costs (DMCs), and length of hospital stay (LOS) in elderly patients following hip fracture, utilizing nationwide claims data. Methods: This retrospective nationwide study sourced its subjects from the Korean National Health Insurance Review and Assessment Service database spanning from January 2011 to December 2018. A generalized estimating equation model with a Poisson distribution and logarithmic link function was used to estimate adjusted odds ratios (aORs) and 95% CIs to assess the association of hospital volume with in-hospital and 1-year mortality, DMCs, and LOS . Results: A total of 172,144 patients were included. Comparing the risk of in-hospital death between high-volume and low-volume hospitals, the risk of in-hospital death was 1.2 times higher at low-volume hospitals (aOR, 1.20; 95% CI, 1.07–1.33; p = 0.002).Additionally, the risk of death at 1 year was 1.05 times higher at low-volume hospitals (aOR, 1.05; 95% CI, 1.01–1.09; p = 0.008) compared to high-volume hospitals. DMCs were 0.84 times lower at low-volume hospitals for in-hospital period (aOR, 0.84; 95% CI, 0.84–0.85; p < 0.001) and 0.87 times lower for 1 year (aOR, 0.87; 95% CI, 0.86–0.88; p < 0.001) compared to high-volume hospitals. In-hospital LOS was 1.21 times longer at low-volume hospitals (aOR, 1.21; 95% CI, 1.20–1.22; p < 0.001) than at high-volume hospitals. In addition, the risk of in-hospital death was 1.22 times higher (aOR, 1.22; 95% CI, 1.12–1.33; p < 0.001) and the risk of 1-year death was 1.07 times higher (aOR, 1.07; 95% CI, 1.04–1.10; p < 0.001) at rural hospitals compared to urban hospitals. Conclusions Clinicians should focus on improving clinical outcomes for hip fracture patients in low-volume and rural hospital settings, with a specific emphasis on reducing mortality rates.

Background: The purpose of our study was to analyze the effects of hospital volume and region on in-hospital and long-term mortality, direct medical costs (DMCs), and length of hospital stay (LOS) in elderly patients following hip fracture, utilizing nationwide claims data. Methods: This retrospective nationwide study sourced its subjects from the Korean National Health Insurance Review and Assessment Service database spanning from January 2011 to December 2018. A generalized estimating equation model with a Poisson distribution and logarithmic link function was used to estimate adjusted odds ratios (aORs) and 95% CIs to assess the association of hospital volume with in-hospital and 1-year mortality, DMCs, and LOS . Results: A total of 172,144 patients were included. Comparing the risk of in-hospital death between high-volume and low-volume hospitals, the risk of in-hospital death was 1.2 times higher at low-volume hospitals (aOR, 1.20; 95% CI, 1.07–1.33; p = 0.002).Additionally, the risk of death at 1 year was 1.05 times higher at low-volume hospitals (aOR, 1.05; 95% CI, 1.01–1.09; p = 0.008) compared to high-volume hospitals. DMCs were 0.84 times lower at low-volume hospitals for in-hospital period (aOR, 0.84; 95% CI, 0.84–0.85; p < 0.001) and 0.87 times lower for 1 year (aOR, 0.87; 95% CI, 0.86–0.88; p < 0.001) compared to high-volume hospitals. In-hospital LOS was 1.21 times longer at low-volume hospitals (aOR, 1.21; 95% CI, 1.20–1.22; p < 0.001) than at high-volume hospitals. In addition, the risk of in-hospital death was 1.22 times higher (aOR, 1.22; 95% CI, 1.12–1.33; p < 0.001) and the risk of 1-year death was 1.07 times higher (aOR, 1.07; 95% CI, 1.04–1.10; p < 0.001) at rural hospitals compared to urban hospitals. Conclusions Clinicians should focus on improving clinical outcomes for hip fracture patients in low-volume and rural hospital settings, with a specific emphasis on reducing mortality rates.

Background: The purpose of our study was to analyze the effects of hospital volume and region on in-hospital and long-term mortality, direct medical costs (DMCs), and length of hospital stay (LOS) in elderly patients following hip fracture, utilizing nationwide claims data. Methods: This retrospective nationwide study sourced its subjects from the Korean National Health Insurance Review and Assessment Service database spanning from January 2011 to December 2018. A generalized estimating equation model with a Poisson distribution and logarithmic link function was used to estimate adjusted odds ratios (aORs) and 95% CIs to assess the association of hospital volume with in-hospital and 1-year mortality, DMCs, and LOS . Results: A total of 172,144 patients were included. Comparing the risk of in-hospital death between high-volume and low-volume hospitals, the risk of in-hospital death was 1.2 times higher at low-volume hospitals (aOR, 1.20; 95% CI, 1.07–1.33; p = 0.002).Additionally, the risk of death at 1 year was 1.05 times higher at low-volume hospitals (aOR, 1.05; 95% CI, 1.01–1.09; p = 0.008) compared to high-volume hospitals. DMCs were 0.84 times lower at low-volume hospitals for in-hospital period (aOR, 0.84; 95% CI, 0.84–0.85; p < 0.001) and 0.87 times lower for 1 year (aOR, 0.87; 95% CI, 0.86–0.88; p < 0.001) compared to high-volume hospitals. In-hospital LOS was 1.21 times longer at low-volume hospitals (aOR, 1.21; 95% CI, 1.20–1.22; p < 0.001) than at high-volume hospitals. In addition, the risk of in-hospital death was 1.22 times higher (aOR, 1.22; 95% CI, 1.12–1.33; p < 0.001) and the risk of 1-year death was 1.07 times higher (aOR, 1.07; 95% CI, 1.04–1.10; p < 0.001) at rural hospitals compared to urban hospitals. Conclusions Clinicians should focus on improving clinical outcomes for hip fracture patients in low-volume and rural hospital settings, with a specific emphasis on reducing mortality rates.

Background: The purpose of our study was to analyze the effects of hospital volume and region on in-hospital and long-term mortality, direct medical costs (DMCs), and length of hospital stay (LOS) in elderly patients following hip fracture, utilizing nationwide claims data. Methods: This retrospective nationwide study sourced its subjects from the Korean National Health Insurance Review and Assessment Service database spanning from January 2011 to December 2018. A generalized estimating equation model with a Poisson distribution and logarithmic link function was used to estimate adjusted odds ratios (aORs) and 95% CIs to assess the association of hospital volume with in-hospital and 1-year mortality, DMCs, and LOS . Results: A total of 172,144 patients were included. Comparing the risk of in-hospital death between high-volume and low-volume hospitals, the risk of in-hospital death was 1.2 times higher at low-volume hospitals (aOR, 1.20; 95% CI, 1.07–1.33; p = 0.002).Additionally, the risk of death at 1 year was 1.05 times higher at low-volume hospitals (aOR, 1.05; 95% CI, 1.01–1.09; p = 0.008) compared to high-volume hospitals. DMCs were 0.84 times lower at low-volume hospitals for in-hospital period (aOR, 0.84; 95% CI, 0.84–0.85; p < 0.001) and 0.87 times lower for 1 year (aOR, 0.87; 95% CI, 0.86–0.88; p < 0.001) compared to high-volume hospitals. In-hospital LOS was 1.21 times longer at low-volume hospitals (aOR, 1.21; 95% CI, 1.20–1.22; p < 0.001) than at high-volume hospitals. In addition, the risk of in-hospital death was 1.22 times higher (aOR, 1.22; 95% CI, 1.12–1.33; p < 0.001) and the risk of 1-year death was 1.07 times higher (aOR, 1.07; 95% CI, 1.04–1.10; p < 0.001) at rural hospitals compared to urban hospitals. Conclusions Clinicians should focus on improving clinical outcomes for hip fracture patients in low-volume and rural hospital settings, with a specific emphasis on reducing mortality rates.

Interferon stimulating factor STING, a transmembrane protein residing in the endoplasmic reticulum, is extensively involved in the sensing and transduction of intracellular signals and serves as a crucial component of the innate immune system. STING is capable of directly or indirectly responding to abnormal DNA originating from diverse sources within the cytoplasm, thereby fulfilling its classical antiviral and antitumor functions. Structurally, STING is composed of 4 transmembrane helices, a cytoplasmic ligand binding domain (LBD), and a C terminal tail structure (CTT). The transmembrane domain (TM), which is formed by the transmembrane helical structures, anchors STING to the endoplasmic reticulum, while the LBD is in charge of binding to cyclic dinucleotides (CDNs). The classical second messenger, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), represents a key upstream molecule for STING activation. Once cGAMP binds to LBD, STING experiences conformational alterations, which subsequently lead to the recruitment of Tank-binding kinase 1 (TBK1) via the CTT domain. This, in turn, mediates interferon secretion and promotes the activation and migration of dendritic cells, T cells, and natural killer cells. Additionally, STING is able to activate nuclear factor-κB (NF-κB), thereby initiating the synthesis and release of inflammatory factors and augmenting the body’s immune response. In recent years, an increasing number of studies have disclosed the non-classical functions of STING. It has been found that STING plays a significant role in organelle regulation. STING is not only implicated in the quality control systems of organelles such as mitochondria and endoplasmic reticulum but also modulates the functions of these organelles. For instance, STING can influence key aspects of organelle quality control, including mitochondrial fission and fusion, mitophagy, and endoplasmic reticulum stress. This regulatory effect is not unidirectional; rather, it is subject to organelle feedback regulation, thereby forming a complex interaction network. STING also exerts a monitoring function on the nucleus and ribosomes, which further enhances the role of the cGAS-STING pathway in infection-related immunity. The interaction mechanism between STING and organelles is highly intricate, which, within a certain range, enhances the cells’ capacity to respond to external stimuli and survival pressure. However, once the balance of this interaction is disrupted, it may result in the occurrence and development of inflammatory diseases, such as aseptic inflammation and autoimmune diseases. Excessive activation or malfunction of STING may trigger an over-exuberant inflammatory response, which subsequently leads to tissue damage and pathological states. This review recapitulates the recent interactions between STING and diverse organelles, encompassing its multifarious functions in antiviral, antitumor, organelle regulation, and immune regulation. These investigations not only deepen the comprehension of molecular mechanisms underlying STING but also offer novel concepts for the exploration of human disease pathogenesis and the development of potential treatment strategies. In the future, with further probing into STING function and its regulatory mechanisms, it is anticipated to pioneer new approaches for the treatment of complex diseases such as inflammatory diseases and tumors.

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.

Aim To investigate the synergistic sensiti-zation effect of saikosaponin D(SSD)combined with temozolomide(TMZ)on glioblastoma cells(GBM)and its molecular mechanism.Methods The sensitiv-ity of RG-2,U251 and LN-428 GBM cell lines to SSD and TMZ was analyzed by CCK-8 method combined with HE staining,and the optimal compatible concen-tration was screened.The effect of HE staining com-bined with Hoechst fluorescence staining on the prolif-eration of GBM cell line was detected by clonal forma-tion experiment.The autophagosome formation of GBM cells was observed by monodansylcadaverine(MDC)staining.The expression and distribution of endoplas-mic reticulum stress-related factors and apoptosis and autophagy proteins were detected by Western blot and ICC.Results The sensitivity order of GBM cells to TMZ was RG-2＞U251＞LN-428.The results of com-bined administration showed the synergistic inhibitory effect of SSD combined with TMZ on proliferation of GBM cell lines,which was confirmed by cell cloning formation experiment.Compared with the TMZ group,Hoechst fluorescence staining showed a significant in-crease in the number of nuclear bright staining in the combined administration group.MDC fluorescence staining showed that there were more dense green parti-cles in the cytoplasm of SSD/TMZ plus group than that of TMZ group.Western blot results showed that com-pared with TMZ group,the expression of ER stress markers GRP78,CHOP,p-PERK and ATF6 signifi-cantly increased in SSD/TMZ group(P＜0.05).The expressions of apoptosis proteins caspase-12,caspase-9,caspase-3,cleaved caspase-3,Bax and autophagy proteins LC3 and Beclin-1 significantly increased(P＜0.05),which were verified by ICC test.Conclusions SSD can cooperate with TMZ to inhibit the prolifera-tion of GBM cells and induce apoptosis and autophagy,and enhance the sensitivity of GBM cells to TMZ by ac-tivating endoplasmic reticulum stress pathway.

Chinese Expert Consensus on Clinical Application of Tongxinluo in Prevention and Treatment of Coronary Heart Disease strictly follows the consensus formulation specifications,with evidence-based medicine as the main,consensus as the supplement,and experience as the reference,aiming to standardize the reasonable application of Tongxinluo in the treatment of coronary heart disease.In combination with conventional treatment,Tongxinluo can increase clinical benefits for common types of coronary heart disease.

The establishment and maintenance of latent cellular reservoirs of human immunodeficiency virus(HIV)within days after infection remains a major obstacle to achieving functional HIV cure.Epigenetics pertains to the regulation of gene ex-pression through means beyond mutations in DNA sequences.Research on epigenetic modifications in recent decades has facili-tated in-depth understanding of HIV pathogenesis and ongoing AIDS therapy strategies.This review briefly introduces princi-ples of epigenetics,and summarizes current epigenetic findings observed during HIV infection,particularly regarding the roles of epigenetic mechanisms including DNA methylation,histone modification,RNA modification,and non-coding RNAs in the processes of viral latency and formation of reservoirs.In addition,the implications and challenges of these epigenetic regulatory mechanisms in functional AIDS cure strategies are discussed.This review is aimed at encouraging more research groups to focus on epigenetic studies in HIV-infected populations,to develop more therapeutic drugs based on epigenetics,and to propose more rational and feasible functional AIDS cure strategies.

Objective:To explore the optimal storage condition and time of umbilical cord blood from collection to preparation.Methods:Collect cord blood samples from 30 healthy newborns,with each new born's umbilical cord blood was divided into two parts on average.One part was stored in cold storage(4 ℃)and the other was stored at room temperature(20-24 ℃).Samples were taken at 24,36,48,60 and 72 h,respectively,total nucleated cells(TNC)count and TNC viability was analyzed.Flow cytometry was used to detect the ratio of viable CD34+cells to viable CD45+cells and viability of CD34+cells,and colony-forming unit-granulocyte-macrophage(CFU-GM)count was performed by hematopoietic progenitor cell colony culture.The change trend of each index over time was observed,and the differences in each index was compared between cold storage and room temperature storage under the same storage time.Results:The TNC count(r4℃=-0.9588,r20-24℃=-0.9790),TNC viability(r4℃=-0.9941,r20 24 ℃=-0.9970),CD34+cells viability(r4℃=-0.9932,r20-24℃=-0.9828)of cord blood stored in cold storage(4 ℃)and room temperature storage(20-24 ℃)showed a consistent downward trend with the prolongation of storage time.The percentage of viable CD34+cells(r4℃=0.9169,r20-24 ℃=0.7470)and CFU-GM count(r4℃=-0.2537,r20-24℃=-0.8098)did not show consistent trends.When the storage time was the same,the TNC count,TNC viability,CD34+cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature.Under the same storage time(24,36,48,60 or 72 h),TNC viability in room temperature storage was significantly lower than that in cold storage(P＜0.001),but TNC count,percentage of viable CD34+cells and CFU-GM count were not significantly different between room temperature storage and cold storage.When stored at room temperature for 24 h and 36 h,the viability of CD34+cells was significantly lower than that in cold storage(P＜0.001,P＜0.01),when the storage time for 48,60 and 72 h,there was no significant difference in the CD34+cells viability between room temperature storage and cold storage.Conclusion:It is recommended that cord blood be stored in cold storage(4 ℃)from collection to preparation,and processed as soon as possible.