BACKGROUND:Angiogenesis is the main treatment target of cardiovascular diseases.Bone morphogenetic protein 2 can modulate angiogenesis,but the regulatory effect of endothelial cell-specific bone morphogenetic protein 2 on angiogenesis is unclear. OBJECTIVE:To investigate the effect of endothelial-specific bone morphogenetic protein 2 on angiogenesis. METHODS:(1)Bioinformatics analysis:Cellular expression specificity and abundance of bone morphogenetic protein 2 were meta-analyzed by the PanglaoDB single-cell transcriptome database.The endothelial cell transcriptome sequencing dataset of the mouse hindlimb model and endocardial transcriptome dataset of mice overexpressing bone morphogenetic protein 2 were reanalyzed to evaluate the effect of endothelial cell bone morphogenetic protein 2 on the angiogenesis pathway.(2)Validation in vivo:After establishing the mouse hindlimb model,we compared the blood perfusion between the affected and sham limb at 7,14,and 21 days.The expression of the colocation of bone morphogenetic protein 2 and CD31 was explored by immunofluorescence and immunohistochemical staining.(3)Validation in vitro:The cultured human umbilical vein endothelial cells in vitro were divided into a control group,a hypoxia group,and a bone morphogenetic protein 2 inhibitor Noggin intervention group.After being cultured for 24 hours,the angiogenesis of endothelial cells in each group was observed. RESULTS AND CONCLUSION:(1)Endothelial cells are an important cell subgroup expressing bone morphogenetic protein 2.Both in the mouse hindlimb ischemia model and endocardial cells overexpressing bone morphogenetic protein 2,bone morphogenetic protein 2 was significantly up-regulated,and the angiogenesis pathway was significantly activated.(2)In the mouse hindlimb model,bone morphogenetic protein 2-positive blood vessels around neoangiogenesis increased significantly at 7 days of ischemia(P<0.05),and decreased significantly after 2 weeks of ischemia(P<0.001).(3)In umbilical vein endothelial cells cultured in vitro,after hypoxic intervention,the migration and sprouting of endothelial cells increased significantly,and the expression of angiogenesis factors vascular endothelial growth factor and platelet-derived growth factor was significantly increased.Noggin significantly reduced hypoxia-induced endothelial cell angiogenesis(P<0.001)and down-regulated the expression of vascular endothelial growth factor and platelet-derived growth factor(P<0.01).(4)These findings verify that endothelial cell-specific bone morphogenetic protein 2 can regulate angiogenesis,and targeting endothelial cell bone morphogenetic protein 2 is a promising way to improve angiogenesis.

Objective The purpose of this study was to investigate the differences in the anti cyclic fatigue perfor-mance of Woride KS(WKS),Proteper Gold(PTG),and Hyflex CM(HCM)nickel titanium instruments with different tip diameters in curved root canal models,and to provide reference for the targeted selection of suitable nickel titanium in-struments in clinical preparation of curved root canals.Methods Three kinds of new nickel titanium files with 20#and 25#(0.20 mm and 0.25 mm)tip diameters were selected,including WKS(20/0.06),WKS(25/0.06),PTG(20/0.07),PTG(25/0.08),HCM(20/0.06),and HCM(25/0.06),each with 20 files.According to the recommended speed and torque of the motor,the anti cycle fatigue performance of the nickel titanium file was tested in 30° and 60° stainless steel root canal models.The time from rotation to fatigue fracture(TTF)of the nickel titanium file was recorded with a camera and timer,and the fragment length(FL)was measured and recorded with a Vernier scale.Results Com-parison of TTF of the same type of file.① WKS:the TTF of files with the same tip diameter in a 30° curved root canal was longer than 60°(P＜0.05);The TTF of 25# nickel titanium files in the same angle curved root canal was longer than that of 20# nickel titanium files(P＜0.05).②PTG:the 20# nickel titanium files had a TTF longer than 60° in a 30° curved root canal(P＜0.05),while the 25# nickel titanium files had no statistically significant difference in TTF be-tween the 30° curved root canal and 60° curved root canal(P＞0.05);In a 30° curved root canal,the TTF of 20# nickel titanium files was longer than that of 25# nickel titanium files(P＜0.05).In a 60° curved root canal,there were no sta-tistically significant difference between the TTF of 20# nickel titanium files and 25# nickel titanium files(P＞0.05).③HCM:the TTF of files with the same tip diameter in a 30° curved root canal was longer than 60°(P＜0.05);The TTF of 20# nickel titanium files in the same angle curved root canal is longer than that of 25# nickel titanium filea.Compari-son of TTF of different files:in a 30° curved root canal,there was no statistically significant difference in TTF among the three types of 20# nickel titanium files(P＞0.05).The TTF of 25# WKS was longer than that of other files(P＜0.05);In a 60 ° curved root canal,the TTF of 20# HCM was longer than other files with the same tip diameter(P＜0.05),and the TTF of 25# WKS was longer than HCM with the same tip diameter(P＜0.05).The FL of 20# PTG,25#PTG,and 20# HCM in the 30° curved root canal model is significantly longer than that of 60°(P＜0.05),while there is no statistical difference in FL among 20# WKS,25# WKS,and 25# HCM in the 30° and 60° curved root canal models.Conclusion The anti cyclic fatigue performance of WKS is significantly superior to PTG and HCM in a 30° curved root canal.In a 60° curved root canal,20# HCM had a significant advantage in terms of anti cyclic fatigue performance compared to other files,while only 25# WKS had a significant advantage in anti cyclic fatigue performance compared to HCM.

Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasomes in curcumin-induced reduction of sevoflurane-induced postoperative cognitive dysfunction in rats.Methods:Forty SPF healthy male Sprague-Dawley rats, aged 17-18 months, with body mass index of 580-600 g, were divided into 4 groups ( n=10 each) by a random number table method: control group (C group), postoperative cognitive dysfunction group (P group), curcumin group (CU group), and curcumin+ NLRP3 inflammasome activator group (CN group). The rat model of postoperative cognitive dysfunction was prepared by inhaling 1.5% sevoflurane to explore the abdominal cavity. Curcumin suspension 300 mg/kg was given by intragastric administration in CU group and CN group, and the rats received intragastric administration of nidrisin sodium 5 mg/kg simultaneously in CN group, once a day for 6 consecutive days. Rats received the equal volume of normal saline instead in C group and P group. The frequency of crossing the original platform and time spent in the target quadrant were measured by the Morris water maze test. The histopathological changes of hippocampus were observed by HE staining, neuronal apoptosis was detected by TUNEL staining, and the expression of NLRP3, Bcl-2 and Bax was detected by Western blot. Results:Compared with C group, the frequency of crossing the original platform was significantly reduced, the time spent in the target quadrant was shortened, the apoptosis rate of neurons was increased, and the expression of NLRP3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in P group ( P<0.05). Compared with P group, the frequency of crossing the original platform was significantly increased, the time spent in the target quadrant was prolonged, the apoptosis rate of neurons was decreased, and the expression of NLRP3 and Bax was down-regulated, and the expression of Bcl-2 was up-regulated in CU group ( P<0.05). Compared with CU group, the frequency of crossing the original platform was significantly reduced, the time spent in the target quadrant was shortened, the apoptosis rate of neurons was increased, and the expression of NLRP3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in CN group ( P<0.05). Conclusions:The NLRP3 inflammasome is involved in curcumin-induced reduction of postoperative cognitive dysfunction in sevoflurane-anesthetized rats.

ObjectiveTo explore the impact of Gegen Qinliantang（GQT） on the fecal short-chain fatty acids（SCFAs） metabolism in antibiotic-associated diarrhea（AAD） through targeted metabolomics. MethodA total of 240 SD rats were randomly divided into six groups（n=40， half male and half female）， including blank group， model group， bifidobiogen group（0.15 g·kg^-1）， and GQT high-， medium-， and low-dose groups（10.08， 5.04， 2.52 g·kg^-1）， except for the blank group， clindamycin（250 mg·kg^-1） was given to all groups by gavage for modeling every day for 7 d. After successful modeling， each administered group was gavaged with the corresponding dose of the drug， and the blank and model groups were gavaged with an equal volume of normal saline solution， 1 time/d， for 14 d. At 0， 3， 7， 14 d after the drug intervention， eight rats were randomly selected from each group， respectively. Gas chromatography-time-of-flight mass spectrometry（GC-TOF-MS） was used to perform targeted metabolomic analysis of SCFAs in the feces of rats， and partial least squares-discriminant analysis（PLS-DA） was applied to compare the differences in metabolic profiles between groups at different treatment times， and to compare the changes in the contents of SCFAs in rat feces between groups. ResultPLS-DA results showed that the blank group could be clearly distinguishable from the model group， with GQT exhibiting a closer proximity to the blank group after 7 d of treatment. After further analyzing the composition of SCFAs， it was found that the proportion of acetic acid increased and the proportions of butyric acid， valeric acid， hexanoic acid and isovaleric acid decreased in the model group compared with the blank group. After the treatment with GQT， the proportions of butyric acid， isobutyric acid， valeric acid， and isovaleric acid increased， and the proportions of acetic acid， propionic acid and caproic acid decreased. Subsequent differential analysis revealed that GQT could significantly improve the content of butyric acid， and had a certain retrogressive effect on the contents of valeric acid and hexanoic acid. ConclusionThe medium dose group of GQT can improve the contents of SCFAs in AAD feces after 7 days of treatment， which may be related to the improvement of the composition ratio of SCFAs and the contents of butyric acid， valeric acid and caproic acid.

BackgroundThe occurrence rate of dangerous behaviors in patients with severe mental disorders is higher than that of the general population. In China， there is limited research on the prediction of dangerous behaviors in community-dwelling patients with severe mental disorders， particularly in terms of predicting models using data mining techniques other than traditional methods. ObjectiveTo explore the influencing factors of dangerous behaviors in community-dwelling patients with severe mental disorders and testing whether the classification decision tree model is superior to the Logistic regression model. MethodsA total of 11 484 community-dwelling patients with severe mental disorders who had complete follow-up records from 2013 to 2022 were selected on December 2023. The data were divided into a training set （n=9 186） and a testing set （n=2 298） in an 8∶2 ratio. Logistic regression and classification decision trees were separately used to establish predictive models in the training set. Model discrimination and calibration were evaluated in the testing set. ResultsDuring the follow-up period， 1 115 cases （9.71%） exhibited dangerous behaviors. Logistic regression results showed that urban residence， poverty， guardianship， intellectual disability， history of dangerous behaviors， impaired insight and positive symptoms were risk factors for dangerous behaviors （OR=1.778， 1.459， 2.719， 1.483， 3.890， 1.423， 2.528， 2.124， P<0.01）. Being aged ≥60 years， educated， not requiring prescribed medication and having normal social functioning were protective factors for dangerous behaviors （OR=0.594， 0.824， 0.422， 0.719， P<0.05 or 0.01）. The predictive effect in the testing set showed an area under curve （AUC） of 0.729 （95% CI： 0.692~0.766）， accuracy of 70.97%， sensitivity of 59.71%， and specificity of 72.05%. The classification decision tree results showed that past dangerous situations， positive symptoms， overall social functioning score， economic status， insight， household registration， disability status and age were the influencing factors for dangerous behaviors. The predictive effect in the testing set showed an AUC of 0.721 （95% CI： 0.705~0.737）， accuracy of 68.28%， sensitivity of 64.46%， and specificity of 68.60%. ConclusionThe classification decision tree does not have a greater advantage over the logistic regression model in predicting the risk of dangerous behaviors in patients with severe mental disorders in the community. ［Funded by Chengdu Medical Research Project （number， 2020052）］

Objective To compare the effects of using three different filling appliances,CompothixoTM resin filler,conventional resin filler,and SonicFill sonic handpiece,on marginal microleakage after auxiliary resin filling of class Ⅱ cavities.Methods A total of 40 permanent molars extracted from the Department of Stomatology,Affiliated Hospital of Shandong Second Medical University(Weifang Medical University Affiliated Hospital)from October 2020 to February 2021 were collected and randomly divided into four groups:A,B,C,and D.Standard class Ⅱ cavities were prepared in the proximal and distal middle of the isolated teeth,filled according to the standard filling requirements of the instruments in each grouping,dissected after temperature cycling and methylene blue staining,and the dye penetration depths of the dental tissues and restorative axial and gingival walls were observed and graded under the body-view microscope to calculate the microleakage degree scores.Results Microleakage occurred in four groups,and tested by the Mann-Whitney U test,the microleakage scores of group A was higher than those of the other three groups(P<0.05);There was no statistically significant difference between groups B and C(P>0.05);The scores of groups B and C were higher than those of group D(P<0.05).Group A had higher microleakage scores than group D(P<0.05),and there was no statistically significant difference between the remaining groups(P>0.05).Conclusion The use of the CompothixoTM resin filler is beneficial in reducing microleakage between the resin and the tooth tissue when compared to conventional filling appliances;Compare with the SonicFill handpiece,the use of the CompothixoTM resin filler is not conducive to the reduction of microleakage between the SonicFill ultrasonic resin and the tooth tissue.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective:To investigate the topological properties of whole-brain functional networks in first-episode drug-na?ve adolescents with major depressive disorder (MDD).Methods:Seventy-six first-episode drug-na?ve adolescents with MDD admitted to Department of Neurology, Xiangyang No.1 Hospital Affilated to Hubei University of Medicince from January 2022 to January 2023 were selected as study subjects; 66 gender- and age-matched healthy controls (HCs) were recruited via advertisement. All subjects underwent resting-state functional MRI. The whole-brain functional networks were constructed for each subject; and then, the global topological metrics (global efficiency, local efficiency, clustering coefficient, characteristic path length, normalized clustering coefficient, normalized characteristic path length, and small-worldness properties) and local topological metrics (nodal degree centrality, nodal efficiency and nodal betweenness centrality) of the functional brain networks were analyzed between the two groups using graph-theory methods. Network-based statistics were used to examine between-group differences in functional connectivity strength of whole brain networks. Results:Small-worldness properties were demonstrated in both MDD group and HC group. MDD patients showed significantly higher global efficiency (0.129[0.124, 0.132] vs. 0.131[0.128, 0.133]), significantly lower clustering coefficient and characteristic path length (0.143[0.139, 0.146] vs. 0.139[0.135, 0.144]; 0.457[0.446, 0.734] vs. 0.451[0.440, 0.463]), and significantly increased nodal centralities in the right inferior parietal lobule, bilateral caudate nucleus and bilateral thalamus of brain functional networks compared with HCs ( P<0.05, FDR-corrected). Compared with HCs, MDD patients exhibited obviously lower functional connectivity strength in the orbitofrontal-temporal and anterior cingulate-limbic-temporal circuits. Conclusion:Abnormal alterations of topological properties of the brain functional networks are found in adolescents with MDD, which may be the underlying neuropathologic basis for MDD.

ObjectiveTo investigate the mechanism of Gegen Qinliantang（GQT） on the intestinal flora of antibiotic-associated diarrhea（AAD） by 16S rRNA sequencing and network pharmacology. MethodSixty SD rats were randomly divided into six groups（n=10）， including blank group， model group， GQT high-， medium- and low-dose groups（10.08， 5.04， 2.52 g·kg^-1） as well as Lizhu Changle group（0.15 g·kg^-1）， except for the blank group， each group was given clindamycin（250 mg·kg^-1） by gavage once a day for 7 consecutive days. After successful modeling， the blank group and the model group were given equal volumes of normal saline by gavage. The other groups were given corresponding doses of drugs by gavage for 14 days. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） was used to screen the active components and targets of GQT， GeneCards， Online Mendelian Inheritance in Man（OMIM） database， Pharmacogenetics and Pharmacogenomics Knowledge Base（PharmGKB）， DrugBank and DisGeNET were used to search for AAD disease targets. The drug-disease common targets were obtained by R software. STRING was applied to analyze the target protein-protein interaction， and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis was performed. Then hematoxylin-eosin（HE） staining was used to observe the pathological changes of the colon， and 16S rRNA sequencing of AAD colon content flora structure further verified the results of network pharmacology. ResultThrough network pharmacology， it was found that 238 active components were screened from GQT and acted on 276 component targets， among which quercetin， puerarin， wogonin and apigenin were the main core components of GQT， 1 097 AAD disease targets and 127 drug-disease intersection targets. The protein-protein interaction network mainly included core targets such as protein kinase B1（Akt1）， interleukin（IL）-6 and IL-1β， which were mainly enriched in the IL-17 signaling pathway. It was verified through animal experiments that compared with the blank group， the colon structure of the model group was seriously abnormal， the intestinal epithelial columnar cells were damaged， the goblet cells were reduced， and a large number of inflammatory cells were infiltrated. Compared with the model group， the colon structure of the GQT high-dose group improved， but there were still abnormalities， the colon structure of GQT medium- and low- dose groups and Lizhu Changle group improved significantly and reached the normal level. GQT could improve the structural diversity of AAD intestinal flora. At the phylum level， the abundance of Firmicutes was increased and the abundance of Bacteroidetes was decreased. At the genus level， the abundance of Lactobacillus was increased， and the abundances of Prevotella and Bacteroides were decreased. Among them， Lactococcus could be used as a biomarker for AAD treatment with GQT， and the prediction of functional metabolism of intestinal flora revealed that GQT could promote acetate and lactate metabolic pathways in the intestine. ConclusionGQT may activate IL-17 signaling pathway by acting on the targets of Akt1 and IL-6 through key components such as quercetin and wogonin， and improve the abundance of Lactococcus in the intestinal tract as well as acetate and lactate metabolic pathways， so as to play a role in repairing the intestinal barrier for the treatment of AAD.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.