Objective To quantitatively assess the exposure-response association between exposure to heatwave and sudden death, estimate the attributable excess deaths, and identify potential vulnerable subgroups. Methods A time-stratified case-crossover study was conducted among residents who died from sudden death in Jiangsu Province, China between 2015 and 2021. Heatwave events in Jiangsu Province, defined using varying relative temperature thresholds and durations, were identified using temperature data from the China Meteorological Administration Land Data Assimilation System (CLDAS V2.0). Individual heatwave exposure was assessed based on each subject's residential address. The exposure-response association between heatwave and sudden death was evaluated using conditional logistic regression model combined with a Distributed Lag Nonlinear Model(DLNM). Heatwave-attributable excess deaths were estimated. Stratified analyses by sex and age were performed to assess potential effect modifications. Results Under all definitions, exposure to heatwave was significantly associated with an increased risk of sudden death, and the risk increased with the intensity of heatwave. Using the P95_3d definition (temperature exceeding the 95th percentile for ≥3 consecutive days), heatwave was significantlyassociated with a 56% increased risk of sudden death (95% CI: 31%, 86%). The population-attributable fraction of sudden death due to heatwave exposure was 1.45% (95% CI: 0.97%, 1.90%). Stratified analyses indicated no statistically significant differences in the association between heatwave exposure and sudden death across age or sex subgroups. Conclusion Heatwave exposure was associated with an increased risk of sudden death. Reducing heatwave exposure during summer may help lower the occurrence of sudden death.

OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

OBJECTIVES: This study aimed to compare the osteogenic performance differences of titanium surface coatings modified by dopamine or silanized graphene oxide, and to provide a more suitable modification scheme for titanium surface graphene oxide coatings. METHODS: Titanium was subjected to alkali-heat treatment and then modified with dopamine and silanization, respectively, followed by coating with graphene oxide. Control and experimental groups were designed as follows: pure titanium (Ti) group; titanium after alkali-heat treatment (Ti-NaOH) group; titanium after alkali-heat treatment and silanization modification (Ti-APTES) group; titanium after alkali-heat treatment and dopamine modification (Ti-DOPA) group; titanium with silanization-modified surface decorated with graphene oxide (Ti-APTES/GO) group; titanium with dopamine-modified surface decorated with graphene oxide (Ti-DOPA/GO) group. The physical and chemical properties of the material surfaces were analyzed using scanning electron microscopy (SEM), contact angle goniometer, X-ray photoelectron spectroscopy (XPS), and Raman spectrometer. The proliferation and adhesion morphology of mouse embryonic osteoblast precursor cells MC3T3-E1 on the material surfaces were observed by cell viability detection and immunofluorescence staining followed by laser confocal microscopy. The effects on the osteogenic differentiation of MC3T3-E1 cells were studied by alkaline phosphatase (ALP) staining, alizarin red staining and quantification, and real-time quantitative polymerase chain reaction. RESULTS: After modification with graphene oxide coating, a thin-film-like structure was observed on the surface under SEM. The hydrophilicity of all experimental groups was improved, among which the Ti-DOPA/GO group had the best hydrophilicity. XPS and Raman spectroscopy analysis showed that the modified materials exhibited typical D and G peaks, and XPS revealed the presence of a large number of oxygen-containing functional groups on the surface. CCK8 assay showed that all groups of materials had no cytotoxicity, and the proliferation level of the Ti-APTES/GO group was higher than that of the Ti-DOPA/GO group. Under the laser confocal microscope, the cells in the Ti-DOPA/GO and Ti-APTES/GO groups spread more fully. The Ti-DOPA/GO and Ti-APTES/GO groups had the deepest ALP staining, and the Ti-APTES/GO group had the most alizarin red-stained mineralized nodules and the highest quantitative result of alizarin red staining. In the Ti-DOPA/GO and Ti-APTES/GO groups, the expression of the early osteogenic-related gene RUNX2 reached a relatively high level, while in the expression of the late osteogenic-related genes OPN and OCN, the Ti-APTES/GO group performed better than the Ti-DOPA/GO group. CONCLUSIONS Ti-APTES/GO significantly outperformed Ti-DOPA/GO in promoting the adhesion, proliferation, and in vitro osteogenic differentiation of MC3T3-E1 cells.
Titanium/chemistry* ; Graphite/chemistry* ; Dopamine/chemistry* ; Animals ; Mice ; Osteogenesis ; Osteoblasts/cytology* ; Surface Properties ; Cell Proliferation ; Silanes/chemistry* ; Cell Adhesion ; Coated Materials, Biocompatible/chemistry* ; Cell Differentiation ; Alkaline Phosphatase/metabolism* ; Microscopy, Electron, Scanning

OBJECTIVE: To compare the effectiveness and advantages of the double reverse traction reduction versus open reduction internal fixation for treating complex tibial plateau fractures. METHODS: A clinical data of 25 patients with Schatzker type Ⅴ or Ⅵ tibial plateau fractures, who met the selection criteria and were admitted between January 2019 and January 2023, was retrospectively analyzed. Thirteen patients underwent double reverse traction reduction and internal fixation (double reverse traction group), while 12 patients underwent open reduction and internal fixation (traditional open group). There was no significant difference in the baseline data (age, gender, injury mechanism, Schatzker classification, interval between injury and operation) between the two groups ( P>0.05). The effectiveness were evaluated and compared between the two groups, included operation time, intraoperative blood loss, incision length, hospital stay, full weight-bearing time, complications, fracture healing, Rasmussen radiological score (reduction quality), knee Hospital for Special Surgery (HSS) score, and knee flexion/extension range of motion. RESULTS: The double reverse traction group demonstrated significantly superior outcomes in operation time, intraoperative blood loss, hospital stay, incision length, and time to full weight-bearing ( P<0.05). Two patients in traditional open group developed incisional complications, while the double reverse traction group had no complication. There was no significant difference in the incidence of complication between the two groups ( P>0.05). All patients were followed up 24-36 months (mean, 30 months), with no significant difference in follow-up duration between groups ( P>0.05). Fractures healed in both groups with no significant difference in healing time ( P>0.05). At 6 months after operation, Rasmussen radiological scores and grading showed no significant difference between the two groups ( P>0.05); the double reverse traction group had significantly higher HSS scores compared to the traditional open group ( P<0.05). At 12 months after operation, knee flexion/extension range of motion were significantly greater in the double reverse traction group than in the traditional open group ( P<0.05). CONCLUSION Double reverse traction reduction offers advantages over traditional open reduction, including shorter operation time, reduced blood loss, minimized soft tissue trauma, and improved joint functional recovery. It is a safe and reliable method for complex tibial plateau fractures.
Humans ; Tibial Fractures/surgery* ; Fracture Fixation, Internal/methods* ; Male ; Female ; Traction/methods* ; Retrospective Studies ; Middle Aged ; Adult ; Open Fracture Reduction/methods* ; Treatment Outcome ; Range of Motion, Articular ; Fracture Healing ; Operative Time ; Length of Stay ; Blood Loss, Surgical ; Aged ; Tibial Plateau Fractures

Objective To verify the mechanism of bromodomain PHD finger transcription factor(BPTF)affecting develop-ment of glioma and ferroptosis by regulating the expression of solute carrier family 40 member 1(SLC40A1)in glioma cells by in v itro and invivo experiments.Methods U87MG cells were divided into sh-NC group,sh-BPTF group,sh-BPTF+ov-NC group and sh-BPTF+ov-SLC40A1 group.Cell lines were stably transfected by lentivirus,and the transfection efficiency was verified by qRT-PCR and Western blotting.Cell proliferation ability was detected by CCK-8 and plate clone formation test.Cell migra-tion and invasion ability were detected by Transwell.Cells were injected subcutaneously into nude mice to detect the tumor growth.To evaluate theferroptosis of cells,the reactive oxygen species(ROS)level,iron content,malondialdehyde(MDA)con-tent and reduced glutathione/oxidized glutathione(GSH/GSSG)ratio in cells were detected by corresponding kits.Co-immuno-precipitation(Co-IP)experiment was used to verify the interaction between BPTF and c-Myc protein.Chromatin immunoprecipi-tation(ChIP)experiment was used to verify that BPTF and c-Myc combined with SLC40A1 promoter.Double luciferase reporter gene experiment was used to verify theeffect of BPTF on SLC40A1 transcription.Results After BPTF knockdown,theexpres-sion of SLC40A1 in glioma cell was decreased,cell proliferation,migration,invasion in vitro,and tumor growth in vivo were in-hibited,iron content,ROS level and MDA content in cells were increased,and GSH/GSSG ratio in cell was de-creased.Overexpression of SLC40A1 reversed the inhibitory effect of BPTF on the proliferation,migration,invasion and tumor grow th in vivo,decreased the iron content,ROS level and MDA content in cells,and increased the GSH/GSSG ratio in cells.There was an interaction between BPTF and c-Myc proteins in gliomacells.A potential binding site of c-Mycin SLC40A1 promoter was verified,BPTF and c-Myc protein bound to SLC40A1 promoter.BPTF knockdown reduced the transcriptional ac-tivity of SLC40A1 promoter,and BPTF knockdown after binding site mutation did not affect the transcriptional activity of SLC40A1 promoter.Conclusion BPTF may upregulate the expression of its downstream target gene SLC40A1 by interacting with c-Myc,thereby inhibiting ferroptosis in glioma cells and promoting glioma progression.

Objective To analyze the factors influencing iodine nutritional status in pregnant women dur-ing pregnancy,based on thyroid function and thyroid autoantibody levels,and to explore the association between iodine nutritional abnormalities and pregnancy outcomes.Methods A total of 838 pregnant women who underwent routine prenatal checkups at Qinghai Provincial People's Hospital between January 2021 and June 2023 were pro-spectively enrolled in this study.All participants were followed until delivery.Seven cases were lost to follow-up,resulting in a final sample size of 831 participants.Among them,276 were in the first trimester,384 in the second trimester,and 171 in the third trimester.Data on urinary iodine concentration(UIC),urinary creatinine(UCr),thyroid function indicators,and thyroid autoantibodies were collected.Based on their iodine nutritional status,the participants were categorized into either the iodine-sufficient group or the iodine-abnormal group(including iodine-deficient,iodine-hyper-sufficient,and iodine-excessive subgroups).This study analyzed the iodine nutritional sta-tus of pregnant women during different gestational periods,compared thyroid function indices,prevalence of thy-roid diseases,and the positivity rates of thyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb),and thyroid-stimulating hormone receptor antibody(TRAb)among different iodine status groups.Additionally,ad-verse pregnancy outcomes were compared across groups.Multivariate logistic regression analysis was conducted to identify risk factors associated with iodine abnormalities during pregnancy,and a predictive model was developed to assess its potential predictive value.Results Among the 831 pregnant women included in the study,373 cases(44.89％)exhibited iodine sufficiency,while 458 cases(55.11％)presented with iodine abnormalities,including 282 cases of iodine deficiency,144 cases of iodine hypersufficiency,and 32 cases of iodine excess.No statistically significant differences were observed in the iodine nutritional status across different trimesters(P>0.05).The se-rum level of thyroid-stimulating hormone(TSH)was significantly higher in the iodine abnormal group compared to the iodine sufficient group(P<0.05).Additionally,the iodine abnormal group demonstrated higher positivity rates of TPOAb alone,TGAb,and TRAb,as well as increased incidence of thyroid dysfunction and total adverse pregnancy outcomes compared to the iodine sufficient group(all P<0.05).These adverse indicators were also sig-nificantly elevated in the iodine-deficient,iodine super-sufficient,and iodine overdose subgroups compared to the iodine sufficient group(P<0.05).Elevated serum TSH levels and the presence of TPOAb,TGAb,and TRAb were identified as risk factors for iodine abnormalities during pregnancy(P<0.05).The predictive model con-structed for identifying iodine abnormalities in pregnant women demonstrated an area under the curve(AUC)of 0.876,with a sensitivity of 72.27％and a specificity of 89.01％.Conclusions The prevalence of iodine nutritional abnormalities among pregnant women during pregnancy was high,with most cases presenting iodine deficiency.These abnormalities were associated with thyroid function,thyroid autoimmunity,and pregnancy outcomes,but showed no significant correlation with gestational age.Furthermore,the prediction model developed based on iden-tified risk factors demonstrated effective performance in predicting iodine nutritional abnormalities during preg-nancy.

Objective To investigate the effect of the rs3765467 polymorphism of glucagon-like peptide-1 receptor(GLP-1R)gene on the efficacy of Liraglutide(Lir)in patients with type 2 diabetes mellitus(T2DM)and metabolic associated fatty liver disease(MAFLD).Methods A total of 281 patients with T2DM from May 2022 to May 2023 were selected,including 125 patients with simple T2DM(T2DM group)and 156 patients with T2DM combined with MAFLD(T2DM+MAFLD group).120 healthy individuals during the same period were selected as the control(NC)group.The related indexes of glucose and lipid metabolism were detected.The polymorphism of GLP-1R gene rs3765467 was detected.Results BMI,FPG,HbA1c,HOMA-IR and TG in each group increased in turn(P<0.05),while the distribution frequency of genotype GG and allele G decreased in turn(P<0.05).TC and LDL-C in T2DM and T2DM+MAFLD groups were higher than those in NC group(P<0.05).TC and TG levels in genotype GA/AA patients were significantly higher than those in genotype GG patients(P<0.05).Compared with before treatment,the levels of BMI,FPG,HbA1c,HOMA-IR,TC,TG and LDL-C in T2DM patients with MAFLD were significantly decreased after Lir treatment(P<0.05).There was no significant difference in BMI and related indexes of glucose and lipid metabolism in GG and GA/AA patients before and after Lir treatment(P>0.05).Conclusions The distribution frequency of GG and G allele at rs3765467 of GLP-1R gene is reduced in T2DM patients with MAFLD.The carrying of allele A was associated with increased TC and TG levels,but did not affect the efficacy of Lir in reducing weight and improving glycolipid metabolism.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.