Objective We aimed to investigate the TCM syndrome characteristics and risk factors of early death in higher-risk patients with myelodysplastic syndromes with excess blasts (HR-MDS-EB). Methods The data of 57 HR-MDS-EB patients in the hematology ward of Xiyuan Hospital, China Academy of Chinese Medical Sciences admitted between January 2013 and August 2020 were analyzed. Patients were divided into an early death group and a non-early death group according to the survival time. The basic information, clinical characteristics, specialized examination, complete blood cell counts and laboratory examination result for first diagnosis, TCM syndrome characteristics, and other data of patients were collected and analyzed to screen the risk factors of death.Results There were statistically significant differences in Charlson comorbidity index (CCI) score, Barthel index score, platelet count at first diagnosis, blast ratio in peripheral blood, lactate dehydrogenase levels, blazing pathogenic heat pattern, and constipation between the early death group and the non-early death group (P<0.05). According to the result of the above univariate analysis, logistic multivariate regression analysis was performed for significant factors P<0.05. CCI score had statistically significant effects on the risk of death (P<0.05).Conclusion Higher CCI score is an independent risk factor for early death in HR-MDS-EB patients.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Objective:To investigate the application value of CT and MRI imageomics based on machine learning method in the diagnosis of pancreatic cancer.Methods:The clinical data of 62 patients with surgically resected and pathologically confirmed pancreatic cancer, who underwent enhanced CT scan, MRI plain or enhanced scan in Shanghai General Hospital between January 2014 and December 2021 were collected. According to the chronological order of surgery, 49 patients from January 2014 to December 2020 were enrolled in the training set and 13 patients from January 2021 to December 2021 were enrolled in the validation set. 3D-slicer 4.8.1 software was used to draw the region of interest in each layer of CT and MRI images for cancerous and paracancerous tissue segment. Image features were extracted by Python and the optimal feature set from the training set data was obtained by using Lasso regression model. The machine learning decision tree model was constructed. The receiver operating characteristic curve(ROC) curve was drawn, and the area under the curve (AUC) was calculated to evaluate the value of these three kinds of imageomics models in the diagnosis of pancreatic cancer.Results:The 1 767 CT features and 1 674 MRI features were obtained from enhanced CT scan, MRI plain scan and enhanced MRI scan, respectively. For the differential diagnosis model of cancerous tissue and paracancerous tissue, the enhanced CT scan data model obtained the optimal feature set involving 6 features, the MRI plain scan model obtained the optimal feature set involving 16 features, and the enhanced MRI scan model obtained the optimal feature set involving 15 features. The diagnostic model based on enhanced CT scan had an AUC of 0.98 in the training set and 1 in the verification group. The AUC of the MRI plain scan and enhanced MRI scan models in both the training set and the validation set was 1. The specificity and sensitivity of machine learning decision tree model based on the three kinds of imageomics models in the diagnosis of cancerous tissue and paracancerous tissue were 100%. For the differential diagnosis model of splenic artery wrapping, the enhanced CT scan model didn′t obtain the optimal features and had no diagnostic efficacy. The MRI plain scan model and enhanced MRI scan model obtained the optimal feature set involving 5 and 4 features, respectively. The AUC of the MRI plain scan model in the training set and the validation set were 0.862 and 0.750, respectively, with diagnostic sensitivity of 93.8% and 50.0%, and specificity of 78.6% and 100%, respectively. The AUC of the enhanced MRI scan model in the training set and the validation set were 0.950 and 0.861, respectively, with diagnostic sensitivity of 90.0% and 93.6%, and specificity of 100% and 78.6%, respectively.Conclusions:Based on the radiomics of CT enhanced, MRI plain scan and enhanced MRI scan, the machine learning diagnostic model has an accuracy of more than 90% in differentiating pancreatic cancer from paracancerous tissue. For the differentiation of splenic artery wrapping in pancreatic cancer, the diagnostic model based on enhanced MRI scan haS the best diagnostic efficiency.

Objective: To explore the characteristics of the default memory network (DMN) and working memory network (WMN) at resting state brain functional network of exercise addiction people. Methods: Twenty-nine sports addicts and 26 non-sports addicts matched by sex, age, average education level and sports dependence were screened by the exercise addiction index (EAI). Resting status brain scanning was performed with 3.0T magnetic resonance scanner.Sparse approximation coefficients independent component analysis (SACICA) model was used to analyze the independent components of brain networks. Results: Compared with the DMN template, four features were extracted, including " basic conformity" , " less frontal lobe" , " more frontal lobe" and " less occipitoparietal lobe" . Compared with the parameters of " basic conformity" , the proportion of exercise addiction group (33.3%, 9/27) was higher than that of control group (18.2%, 4/22). In the other three parameters, the proportion of exercise addiction group (37.0%, 10/27; 3.7%, 1/27; 22.2%, 6/27) was lower than those of control group (45.5%, 10/22; 22.7%, 5/22; 27.3%, 6/22). But Chi-square test showed that there was no significant difference between the two groups(all P>0.05). Compared with the WMN template, six features were extracted, including " basic conformity" , " more frontal and parietal lobes" , " more parietal lobes" , " more frontal lobes" , " less frontal lobes" and " less parietal lobes" . The percentages of the first three features in exercise addiction group (22.2%, 6/27; 7.4%, 2/27; 7.4%, 2/27) were less than those in the control group (45.5%, 10/22; 22.7%, 5/22; 9.1%, 2/22), while the percentages of the last three features in the exercise addiction group (7.4%, 2/27; 37.0%, 10/27; 14.8%, 4/27) were higher than those in the control group (4.5%, 1/22; 13.6%, 3/22; 0, 0). Chi-square test showed that there was no significant difference in all features between the two groups was statistically(P>0.05). Conclusion No significant characteristic changes are found in DMN and WMN networks of exercise addiction population.

Mitophagy is an essential intracellular process that eliminates dysfunctional mitochondria and maintains cellular homeostasis. Mitophagy is regulated by the post-translational modification of mitophagy receptors. Fun14 domain-containing protein 1 (FUNDC1) was reported to be a new receptor for hypoxia-induced mitophagy in mammalian cells and interact with microtubule-associated protein light chain 3 beta (LC3B) through its LC3 interaction region (LIR). Moreover, the phosphorylation modification of FUNDC1 affects its binding affinity for LC3B and regulates selective mitophagy. However, the structural basis of this regulation mechanism remains unclear. Here, we present the crystal structure of LC3B in complex with a FUNDC1 LIR peptide phosphorylated at Ser17 (pS), demonstrating the key residues of LC3B for the specific recognition of the phosphorylated or dephosphorylated FUNDC1. Intriguingly, the side chain of LC3B Lys49 shifts remarkably and forms a hydrogen bond and electrostatic interaction with the phosphate group of FUNDC1 pS. Alternatively, phosphorylated Tyr18 (pY) and Ser13 (pS) in FUNDC1 significantly obstruct their interaction with the hydrophobic pocket and Arg10 of LC3B, respectively. Structural observations are further validated by mutation and isothermal titration calorimetry (ITC) assays. Therefore, our structural and biochemical results reveal a working model for the specific recognition of FUNDC1 by LC3B and imply that the reversible phosphorylation modification of mitophagy receptors may be a switch for selective mitophagy.
Crystallography, X-Ray ; Membrane Proteins ; chemistry ; metabolism ; Microtubule-Associated Proteins ; chemistry ; metabolism ; Mitochondrial Degradation ; Mitochondrial Proteins ; chemistry ; metabolism ; Peptides ; chemistry ; metabolism ; Phosphorylation ; Protein Structure, Quaternary

Objective To summarize the therapeutic effect of combined treatment for children hemifacial microsomia.Methods From Aug 2008 to May 2016, 108 children with hemifacial microsomia underwent combined treatment at an early age .Digital simultation technology was used for design of the guiding model during osteotomy .The mandibular distraction osteogenesis , auricular reconstruction and orthodontic treatment were also adopted .The maxillary development and post-distraction relapse were analyzed during the follow-up period.Results The distractor fell off in 3 cases.All other patients got obvious improvement in facial symmetry , auricular deformity and occlusion .During the follow-up period of 6 -39 months, the development of maxilla on the affected side increased significantly .Though the distracted mandible showed some certain relapse , but the facial asymmetry and occlusion improved a lot . Conclusions The children hemifacial microsomia should receive a combined treatment at an early age to achieve a goodresult .

Objective To summarize the therapeutic effect of combined treatment for children hemifacial microsomia.Methods From Aug 2008 to May 2016, 108 children with hemifacial microsomia underwent combined treatment at an early age .Digital simultation technology was used for design of the guiding model during osteotomy .The mandibular distraction osteogenesis , auricular reconstruction and orthodontic treatment were also adopted .The maxillary development and post-distraction relapse were analyzed during the follow-up period.Results The distractor fell off in 3 cases.All other patients got obvious improvement in facial symmetry , auricular deformity and occlusion .During the follow-up period of 6 -39 months, the development of maxilla on the affected side increased significantly .Though the distracted mandible showed some certain relapse , but the facial asymmetry and occlusion improved a lot . Conclusions The children hemifacial microsomia should receive a combined treatment at an early age to achieve a goodresult .

Objective To investigate the value of modified loop ileostomy in laparoscopic low and superlow radical resection of the rectal cancer with reservation of anus.Methods The clinical data of 108 patients who received laparoscopic low and super-low radical resection of rectal cancer with preservation of anus at the Subei Hospital of Jiangsu Province from January 2010 to June 2012 were retrospectively analyzed.Fifty-three patients who received preventive ileostomy were in the ileostomy group,and 55 patients who did not receive preventive ileostomy were in the non-ileostomy group.The operation,incidence of complication and follow-up of the 2 groups were analyzed.All data were analyzed using the t test,chi-square text or Fisher exact test.Results The operation time and blood loss were (185 ± 14)minutes and (31 ± 26)ml in the ileostomy group,and (154 ± 12)minutes and (28 ± 19)ml in the non-ileostomy group,with no significant difference between the 2 groups (t =2.34,1.82,P ＞ 0.05).The time to first flatus,time to liquid diet intake,time to pelvic drainage tube removal,duration of hospital stay,hospital costs were (1.1 ± 0.3) days,(1.1 ± 0.2) days,(5.2 ± 1.0) days,(7.2 ± 1.4) days,(3.0 ± 0.2) ×104 yuan in the ileostomy group,and (4.2 ± 0.6) days,(4.3 ± 0.6) days,(8.4 ± 3.9) days,(12.9 ±4.4)days,(3.8 ±0.7) × 104 yuan in the non-ileostomy group,with significant differences between the 2 groups (t =7.25,28.12,15.34,34.01,7.83,P ＜ 0.05).The incidences of postoperative complications and anastomotic fistula were 5.7％ (3/53) and 0 in the ileostomy group,and 21.8％ (12/55) and 12.7％ (7/55) in the non-ileostomy group,with significant differences between the 2 groups (P ＜ 0.05).Conclusion Modified loop ileostomy in laparoscopic low and super-low radical resection of rectal cancer can effectively reduce the incidence of anastomotic fistula,and helps the recovery of patients.

ObjectiveTo investigate the impacts of neural stem cells (NSCs) transplantation on spinal pathology and ultrastructure after spinal cord injury (SCI) in rats and probe into the protective role of tacrolimus (FK506) on neural regeneration.MethodsCompressive SCI at T8 was induced in the adult SD rats,which were randomly assigned to the control group,FK506 group,NSCs group and NSCs + FK506 group.The differences of neural regeneration in each group were compared at days 7,14,28 and 56 after injury by motor evoked potentials ( MEP),HE staining,immunohistochemical staining,ultrastructure observation and image analysis of the myelinated fiber. ResultsThe MEP latency in the NSCs + FK506 group was significantly shorter than that in other groups at day 28 ( P ＜ 0.05 ).HE staining revealed that only local necrosis presented in the NSCs + FK506 group at day 56.More BrdU and NF-200 positive cells were detected with immunohistochemical staining in the other three groups as compared with the control group.Moreover,the positive cells in the NSCs + FK506 group also outnumbered the FK506 group and NSCs group.Electron microscope scan showed edema under the membrane of large myelin sheath in the control group,and classic new myelin sheath and neuraxis in the NSCs + FK506 group at day 56.The regeneration of the nerve fiber in the NSCs + FK506 group was better than that of other three groups (P ＜0.01 ).ConclusionAfter NSCs transplantation for SCI rats,the early combination use of FK506 can improve the pathology and ultrastructure of the regenerative nerve fiber and is conducive to nerve regeneration.

Objective To compare the complications of temporary ileostomy and temporary colostomy for colorectal anastomoses,then to evaluate which one is superior to another.Methods Studies and relevant literatures comparing temporary ileostomy with temporary colostomy for defunctioning colorectal anastomoses were searched though PubMed,Embase and the Cochrane Library.The rates of complications were pooled and compared using a meta-analysis.The risk ratios were calculated with 95％ confidence intervals to evaluate the safety and efficacy of each technique.Results Five randomized controlled trials and seven non-randomized studies were included,with 1687 patients in total.The meta-analysis of the RCTs demonstrated a lower risk of stoma prolapse ( Risk ratio 0.15) in the temporary ileostomy group.Meta-analysis of the non-randomized studies showed a lower risk of stoma prolapse ( Risk ratio 0.26) and wound infection after stoma closure ( Risk ratio 0.28 ) in the temporary ileostomy group.No other statistically significant difference was observed for complications.Conclusions Each type of defunctioning stoma has its advantages and disadvantages.The authors endorse temporary ileostomy over temporary colostomy.However,there is not a strong evidence for the superiority of one temporary stoma over another for colorectal anastomoses.Large scale RCTs and high quality studies are needed.