Objective:To explore the characteristics of systemic immune microenvironment during the progression of dextran sulfate sodium(DSS)-induced acute ulcerative colitis(UC)induced in mice by Mass cytometry(CyTOF).Methods:Male C57BL/6 mice were randomly divided into control group and model group.The control group was given normal drinking water for 15 d.The mouse in the model group were given 5%DSS in drinking water,which was changed to normal drinking water after 7 days.In the model group,peripheral blood was collected on days 4,9 and 15,respectively.CyTOF was used to detect the expressions of 33 immune cell markers and changes in cell subsets in peripheral blood of mice,and the characteristics of systemic immune microenvironment in mice with acute UC were analyzed.Results:The cluster analysis of 33 kinds of immune cell markers showed that CD45+cells in peripheral blood of mice with DSS induced acute UC were divided into 23 fine subgroups,among which the proportions of B cell subgroup,T cell subgroup and neutrophil subgroup showed significant changes.A further dimensional reduction cluster analysis of T cell subsets found significant differences in the composition and proportion of the 10 identified T cell subsets.Conclusion:The systemic immune micro-environment map of mice with acute UC induced by DSS has been successfully constructed,and heterogeneity has been found in the systemic immune microenvironment of mice with acute UC.The changes and activation degree of T cell subpopulations are closely re-lated to disease progression and inflammation level.The results of this study provide theoretical basis for assisting the diagnosis,moni-toring the risk,progression,treatment and prognosis of acute UC.

Objective To develop a deep learning method for small sample multi-omics data using attention mechanism and Meta-learning for the establishment of autism diagnosis model.Methods MLAN(Meta-learning based attentive network)consisting of the omics feature pre-reduction module,the multi-omics data fusion and feature learning module,and the parameter optimization module was designed.Firstly,differential expression analysis was performed on high-dimensional multi-omics data to preliminarily screen out unimportant features.Secondly,a multi-channel attention mechanism was used to learn the importances of every set of omics data and to realize data fusion,and a two-layer fully connected network was constructed to further extract latent features and realize the diagnosis task.Finally,the Meta-learning algorithm Reptile was used to optimize the initial parameters of the above model to obtain the optimal parameters.A total of 58 children's saliva samples were collected,including 21 children diagnosed with autism,12 children with social disorders,and 25 healthy controls,and the protein and metabolomics data were detected by mass spectrometry.All data were randomly divided into training set and test set by 4∶1,and the training set was divided into training data and validation data in the same way for model training and validation.The test set was used for the final evaluation of the model effect.Five baseline models and three ablated models were constructed and evaluated along with MLAN based on metrics including multi-classification accuracy,F1-macro and F1-weighted scores.Results The constructed multi-classification autism diagnosis model MLAN achieved multi-classification accuracy,F1-macro and F1-weighted scores of 0.850±0.066,0.817±0.103 and 0.834±0.087.The values of all three indicators were better than those of baseline models and the ablated models.Conclusion The proposed MLAN can effectively deal with heterogeneous multi-omics data with small samples and achieve good results,which is expected to provide assistance for the clinical diagnosis of autism.

BACKGROUND:At present,the surgical treatment of atlantoaxial dislocation mainly adopts the posterior atlantoaxial screw-rod internal fixation system for lifting and reduction.During the operation,the curvature of the connecting rod is often increased to increase the drop between the atlantoaxial vertebrae to improve the reduction effect,but it increases the difficulty and risk of surgery.The axis pivot screw directly increases the reduction drop between the atlantoaxial vertebrae,but the extent to which it increases the reduction capacity is unclear.OBJECTIVE:To test the reduction ability of axis pivot screw and compare it with ordinary screw.METHODS:Six fresh human craniocervical specimens were used in study.The joint capsules of two lateral mass joints and atlanto-odontoid joint and transverse ligament were removed to make an atlantoaxial instability model.Three kinds of internal fixation were performed successively on both sides of the axis of each specimen:uniaxial axis pivot screws(group A),multi-axial axis pivot screws(group B)and ordinary screws(group C).Flexible ultra-thin film pressure sensors were placed in the anterior atlanto-odontoid space.Two connecting rods with the same curvature were placed to simulate the lifting and reduction,and the pressure of the anterior atlanto-odontoid space was obtained.Comparative analysis was conducted among the three groups.RESULTS AND CONCLUSION:(1)The anterior atlanto-odontoid space pressure of groups A-C was(97.59±8.58),(60.43±5.09),and(22.74±0.81)N,respectively.There were significant differences among the three groups(F=251.603,P=0.000).The pairwise comparison among the three groups showed significant differences(P=0.000).(2)The axis pivot screw applied to the posterior atlantoaxial screw-rod internal fixation system can improve the reduction capacity compared with the common cervical posterior screw,and the uniaxial axis pivot screw has more reduction capacity than the multi-axis uniaxial axis pivot screw to improve the posterior atlantoaxial screw-rod internal fixation system.

Objective:To explore the characteristics of systemic immune microenvironment during the progression of dextran sulfate sodium(DSS)-induced acute ulcerative colitis(UC)induced in mice by Mass cytometry(CyTOF).Methods:Male C57BL/6 mice were randomly divided into control group and model group.The control group was given normal drinking water for 15 d.The mouse in the model group were given 5%DSS in drinking water,which was changed to normal drinking water after 7 days.In the model group,peripheral blood was collected on days 4,9 and 15,respectively.CyTOF was used to detect the expressions of 33 immune cell markers and changes in cell subsets in peripheral blood of mice,and the characteristics of systemic immune microenvironment in mice with acute UC were analyzed.Results:The cluster analysis of 33 kinds of immune cell markers showed that CD45+cells in peripheral blood of mice with DSS induced acute UC were divided into 23 fine subgroups,among which the proportions of B cell subgroup,T cell subgroup and neutrophil subgroup showed significant changes.A further dimensional reduction cluster analysis of T cell subsets found significant differences in the composition and proportion of the 10 identified T cell subsets.Conclusion:The systemic immune micro-environment map of mice with acute UC induced by DSS has been successfully constructed,and heterogeneity has been found in the systemic immune microenvironment of mice with acute UC.The changes and activation degree of T cell subpopulations are closely re-lated to disease progression and inflammation level.The results of this study provide theoretical basis for assisting the diagnosis,moni-toring the risk,progression,treatment and prognosis of acute UC.

Objective To develop a deep learning method for small sample multi-omics data using attention mechanism and Meta-learning for the establishment of autism diagnosis model.Methods MLAN(Meta-learning based attentive network)consisting of the omics feature pre-reduction module,the multi-omics data fusion and feature learning module,and the parameter optimization module was designed.Firstly,differential expression analysis was performed on high-dimensional multi-omics data to preliminarily screen out unimportant features.Secondly,a multi-channel attention mechanism was used to learn the importances of every set of omics data and to realize data fusion,and a two-layer fully connected network was constructed to further extract latent features and realize the diagnosis task.Finally,the Meta-learning algorithm Reptile was used to optimize the initial parameters of the above model to obtain the optimal parameters.A total of 58 children's saliva samples were collected,including 21 children diagnosed with autism,12 children with social disorders,and 25 healthy controls,and the protein and metabolomics data were detected by mass spectrometry.All data were randomly divided into training set and test set by 4∶1,and the training set was divided into training data and validation data in the same way for model training and validation.The test set was used for the final evaluation of the model effect.Five baseline models and three ablated models were constructed and evaluated along with MLAN based on metrics including multi-classification accuracy,F1-macro and F1-weighted scores.Results The constructed multi-classification autism diagnosis model MLAN achieved multi-classification accuracy,F1-macro and F1-weighted scores of 0.850±0.066,0.817±0.103 and 0.834±0.087.The values of all three indicators were better than those of baseline models and the ablated models.Conclusion The proposed MLAN can effectively deal with heterogeneous multi-omics data with small samples and achieve good results,which is expected to provide assistance for the clinical diagnosis of autism.

BACKGROUND:At present,the surgical treatment of atlantoaxial dislocation mainly adopts the posterior atlantoaxial screw-rod internal fixation system for lifting and reduction.During the operation,the curvature of the connecting rod is often increased to increase the drop between the atlantoaxial vertebrae to improve the reduction effect,but it increases the difficulty and risk of surgery.The axis pivot screw directly increases the reduction drop between the atlantoaxial vertebrae,but the extent to which it increases the reduction capacity is unclear.OBJECTIVE:To test the reduction ability of axis pivot screw and compare it with ordinary screw.METHODS:Six fresh human craniocervical specimens were used in study.The joint capsules of two lateral mass joints and atlanto-odontoid joint and transverse ligament were removed to make an atlantoaxial instability model.Three kinds of internal fixation were performed successively on both sides of the axis of each specimen:uniaxial axis pivot screws(group A),multi-axial axis pivot screws(group B)and ordinary screws(group C).Flexible ultra-thin film pressure sensors were placed in the anterior atlanto-odontoid space.Two connecting rods with the same curvature were placed to simulate the lifting and reduction,and the pressure of the anterior atlanto-odontoid space was obtained.Comparative analysis was conducted among the three groups.RESULTS AND CONCLUSION:(1)The anterior atlanto-odontoid space pressure of groups A-C was(97.59±8.58),(60.43±5.09),and(22.74±0.81)N,respectively.There were significant differences among the three groups(F=251.603,P=0.000).The pairwise comparison among the three groups showed significant differences(P=0.000).(2)The axis pivot screw applied to the posterior atlantoaxial screw-rod internal fixation system can improve the reduction capacity compared with the common cervical posterior screw,and the uniaxial axis pivot screw has more reduction capacity than the multi-axis uniaxial axis pivot screw to improve the posterior atlantoaxial screw-rod internal fixation system.

The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.
Humans ; Consensus ; Prone Position ; Wakefulness ; China ; Dyspnea

ObjectiveTo observe the effect of Gualou Xiebai Banxiatang on mitochondrial dysfunction and adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK）/peroxlsome proliferator-activated receptor-γ coactlvator-1α （PGC-1α） signaling pathway in rats with ischemic myocardial injury. MethodSeventy male SD rats were used in this experiment. Six rats from them were randomly selected as the control （CON） group， and the others were given high fat diet combined with isoproterenol injection （5 mg·kg^-1·d^-1， 7 d） to induce the rat model of ischemic heart disease based on hyperlipidemia. Successfully modeled rats were then randomly divided into model （MOD） group， high-dose Gualou Xiebai Banxiatang （GXBD-H） group， medium-dose Gualou Xiebai Banxiatang （GXBD-M） group， low-dose Gualou Xiebai Banxiatang （GXBD-L） group， and metoprolol （MET） group. Rats in the GXBD-H， GXBD-M， and GXBD-L groups were given 11.2， 5.6， 2.8 g·kg^-1·d^-1 Gualou Xiebai Banxiatang， those in the MET group were given 2.6 mg·kg^-1·d^-1 metoprolol， and those in the CON and MOD groups were given equal volume of pure water for 28 d. Hemodynamics were measured in rats by cardiac catheterization. Transmission electron microscopy was used to analyze myocardial mitochondria. Serum brain natriuretic peptide （BNP） and cardiac troponin T （cTnT） levels were detected by enzyme-linked immunosorbent assay （ELISA）. Mitochondrial membrane potential assay kit （JC-1 method） was applied for detecting mitochondrial membrane potential. The changes in the mitochondrial DNA copy number were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. The content of adenosine triphosphate （ATP） in myocardial tissues was determined by spectrophotometer. The expression levels of p-AMPK， AMPK， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM） in myocardium was detected by Western blot. ResultAs compared with the CON group， left ventricular end-systolic pressure （LVESP） and left ventricular end-diastole pressure （LVEDP） in the MOD group were significantly increased （P<0.05， P<0.01）， and +dp/dt_max and -dp/dt_max were significantly decreased （P<0.01）. In the MOD group， cardiac index and myocardial interstitial fibrosis area were significantly increased （P<0.01）， accompanied by mitochondrial damage， serum BNP， cTnT， and malondialdehyde （MDA） were significantly increased （P<0.01）， and serum superoxide dismutase （SOD） level was significantly decreased （P<0.01）. The myocardial mitochondrial membrane potential， DNA copy number， and ATP level were significantly decreased （P<0.01）， and the protein expression levels of p-AMPK/AMPK， PGC-1α， NRF1， and TFAM in myocardial tissues were significantly decreased in the MOD group （P<0.01）. Compared with the MOD group， the GXBD-H and GXBD-M groups significantly improved LVESP， LVEDP， +dp/dt_max， and -dp/dt_max （P<0.05， P<0.01）， significantly decreased heart index and myocardial interstitial fibrosis area （P<0.05， P<0.01）， and alleviated mitochondrial damage. In the GXBD-H and GXBD-M groups， serum BNP， cTnT， and MDA were decreased significantly （P<0.05， P<0.01）， serum SOD level was increased significantly （P<0.05）， and myocardial mitochondrial membrane potential， DNA copy number， and ATP level were significantly increased （P<0.05， P<0.01）. The protein levels of p-AMPK/AMPK， PGC-1α， NRF1， and TFAM in myocardial tissues were significantly increased in the GXBD-H and GXBD-M groups （P<0.05， P<0.01）. ConclusionGualou Xiebai Banxiatang has the effects of reducing the changes in cardiac function and myocardial pathology of rats with myocardial injury， inhibiting mitochondrial dysfunction， and up-regulating the protein expression levels of p-AMPK/AMPK， PGC-1α， NRF1， and TFAM in myocardial tissues. This study provides new laboratory evidence for in-depth exploration of the mechanism of this classical compound in preventing and treating myocardial injury.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Objective:To explore the regulatory mechanism of α-synuclein in the degradation of autophagy-lysosome pathway(ALP) in Parkinson disease(PD) model cells after interference or overexpression of dynein heavy chain(Dynhc) gene.Methods:SH-SY5Y cells were divided into control group, PD group, Dynhc interference group, Dynhc overexpression group, and Dynhc interference+ rapamycin group according to experimental requirements.Using Western blot to detect Dynhc, α-synuclein, microtubule-associated protein l light chain 3 (LC3), lysosome-associated membrane protein 2 (LAMP2), tubulin, dynein activator protein p150, and kinesin KIF5B.Flow cytometry was used to detect the level of cell apoptosis.Immunoconfocal microscopy was used to observe the structure of tubulin and the co-localization of LC3 and LAMP.SPSS 23.0 software was used for statistical analysis.One-way ANOVA was used for inter group comparisons, and further pairwise comparisons were conducted by LSD- t test. Results:There were statistically significant differences in the expression of α-synuclein, autophagy-related proteins, microtubules, and microtubule-related proteins among cells in the 5 groups(all P<0.001). The protein expression levels of Dynhc, α-synuclein, LC3, LAMP2, p150, and KIF5B in the PD group were higher than those in the control group (all P<0.05). The protein levels of Dynhc, LAMP2, tubulin and p150 in the Dynhc interference group were lower than those in the PD group (all P<0.05), while the protein levels of α-synuclein, LC3 and KIF5B were higher than those in the PD group (all P<0.05). The protein levels of α-synuclein, LC3, and KIF5B in the Dynhc overexpression group were lower than those in the PD group (all P<0.05), while the protein levels of Dynhc, LAMP2 and p150 were higher than those in the PD group (all P<0.05). The protein level of LC3 in the Dynhc interference+ rapamycin group was higher than that in the Dynhc interference group ( P<0.05). There were no statistically significant differences in the protein levels of Dynhc, α-synuclein, LAMP2, microtubule protein, p150 and KIF5B compared to the Dynhc interference group (all P>0.05). Compared with the control group, the cell apoptosis rate in PD group increased((12.77±1.66)%, (7.64±1.45)%), the microtubule morphology remained unchanged, and autophagosomes fused more with lysosomes. Compared with the PD group, the cell apoptosis rate of Dynhc overexpression group decreased, and there was no significant change in microtubule structure, and there was more fusion between autophagosomes and lysosomes.Compared with the PD group, the cell apoptosis rat of Dynhc interference group increased((18.45±1.91)%), and the microtubule morphology was sparse, and there was less fusion between autophagosomes and lysosomes. Compared with the PD group, the Dynhc overexpression group showed a decrease in cell apoptosis rate ((9.95±1.56)%), no significant changes in microtubule structure, and more fusion between autophagosomes and lysosomes.Compared with the Dynhc interference group, the Dynhc interference+ rapamycin group showed no significant changes in cell apoptosis rate ((19.05±2.46)%), microtubule morphology, and fusion of autophagosomes and lysosomes. Conclusion:Dynhc can reduce cell apoptosis by enhancing cell ALP function, increasing the degradation of α-synuclein and maintaining of microtubule structure integrity.