Objective: To characterize the sequence polymorphism of HLA-A, -B, and -C loci in the northern Han Chinese population and to evaluate their selection signals and phylogenetic patterns based on long-read sequencing data. Methods: A total of 408 unrelated healthy blood donors were enrolled. Long-read sequencing of HLA-A, -B, and -C loci was performed using the PacBio Sequel II platform. The Ewens-Watterson neutrality test, sliding-window nucleotide diversity (π) and Tajima′s D analyses were conducted, together with genetic distance heatmaps, principal coordinates analysis (PCoA), and maximum likelihood phylogenetic analysis to assess polymorphism distribution, selection signals, and phylogenetic structure across the three loci. Results: The analyzed sequence lengths for the HLA-A, -B, and -C loci were 3 257 bp, 3 794 bp, and 3 831 bp, respectively; the numbers of locus-specific sequence types were 44, 82, and 56, with corresponding locus-specific sequence type diversities of 0.905 2, 0.964 9, and 0.939 8, respectively. The Ewens-Watterson test showed no significant deviation from neutrality (P>0.05). Sliding-window analysis revealed elevated π and Tajima′s D values in exons 2 and 3 as well as in certain intronic regions of HLA-A and HLA-B, whereas HLA-C exhibited relatively lower overall diversity. Genetic distance heatmaps, PCoA, and phylogenetic analysis consistently showed clear clustering in HLA-A and HLA-C, while HLA-B displayed the highest phylogenetic heterogeneity. Conclusion: HLA-A, -B, and -C gene sequences in the northern Chinese Han population exhibit high levels of polymorphism and marked regional heterogeneity. HLA-B shows greater diversity, stronger signals of selection, and more complex phylogenetic structure compared with HLA-A and HLA-C.

BACKGROUND:Vertebral compression fracture is a common disease in the current orthopedic field.However,the occurrence of re-fracture in neighboring vertebrae after surgery is a problem that cannot be ignored,which has a serious impact on the normal life of patients. OBJECTIVE:The aim of this study is to establish four postoperative models with different recovery heights using computed tomography images.By using finite element analysis,we derived the stresses on the neighboring vertebrae at different recovery heights and further explored the importance of postoperative recovery of the height of the injured vertebrae. METHODS:A finite element model of the thoracolumbar spine(T11-L3)was established and validated,on the basis of which four postoperative finite element models of L1 with different recovery heights of 100%,80%,60%,and 40%were constructed,in which the cement capacity varied with the recovery height.The specific models are as follows:Model 1 was the postoperative model with normal recovery height,and the cement capacity was 8.3 mL.Model 2 was the postoperative model in which 20%of the anterior height of the L1 was removed and the posterior convexity angle became 10.41°,and the cement capacity was 6.9 mL.Model 3 was the postoperative model in which 40%of the anterior height of the L1 was removed and the posterior convexity angle became 20.17°,and the cement capacity was 4.7 mL.Model 4 was a postoperative model with 60%of the L1 anterior height removed and the posterior convexity angle changed to 28.85°,with a cement capacity of 3.6 mL.For evaluation of the postoperative model,we applied a moment of 7 Nm and an axial force of 500 N.The followings were recorded and analyzed:peak stresses in the L2 upper endplate and T12 lower endplate;peak stresses in the L2 and T12 cancellous bone. RESULTS AND CONCLUSION:(1)The highest peak stresses for each condition of the L2 upper endplate,T12 lower endplate,L2 cancellous bone,and T12 cancellous bone occurred in Model 1 and Model 4.In particular,the T12 lower endplate,except for the posterior extension condition,the anterior flexion,left and right lateral bending,and left and right rotation conditions all reached their highest peak stresses in Model 4,with stresses of 50.3,33.1,44.9,34.3,and 31.9 MPa.(2)Based on the peak stresses in the adjacent vertebral endplates and cancellous bone,after excluding Model 1 and Model 4,the minimum peak stresses for most of the conditions appeared in the Model 2,and the minimum peak stresses appeared in the Model 2 in 66.6%of the cases,especially in the upper endplates of the L2 and cancellous bone except for the posterior extension condition,the minimum peak stresses all appeared on the Model 2.(3)Therefore,controlling the recovery height at about 100%and 40%of the original height was a dangerous recovery height,which had a greater impact on the neighboring vertebrae.Controlling the recovery height at about 80%of the original height may be a more ideal choice.With a recovery height of about 80%of the original height,the adjacent vertebrae are subjected to less stress,thus reducing the risk of re-fracture of the adjacent vertebrae in the patient.

BACKGROUND:The elastic modulus of traditional bone implants is large and does not match the elastic modulus of human bone,which will cause a stress shielding effect and lead to bone resorption.The trabecular scaffold of the triply periodic minimal surface with radial gradient has elastic modulus matching with human cancellous bone,and its yield strength is greater than that of human cortical bone,which provides a new choice for the design of bone scaffold. OBJECTIVE:Triply periodic minimal surface structure with radial gradient was constructed by the implicit surface method.The sample was manufactured by laser selective melting technology,and the quasi-static compression test was carried out to obtain trabecular scaffolds with mechanical properties matching human bones. METHODS:Four types of the trabecular scaffolds of the triply periodic minimal surface with a radial gradient of G,I,P and D were established by the implicit surface method.Samples were manufactured by laser selective melting technology.We observed the surface morphology of the molded sample,evaluated the molding quality,conducted a quasi-static compression test,and evaluated the mechanical properties of the samples. RESULTS AND CONCLUSION:The quasi-static compression test results showed that compared with the four triply periodic minimal surface scaffolds,the platform stress of the G scaffold had less fluctuation and no failure or fracture,indicating that the G scaffold had the best plasticity.The mechanical properties of the G scaffolds with 45%,55%and 65%porosities were analyzed.It was found that the elastic modulus of G scaffolds with 55%porosity was within the range of elastic modulus of human cancellous bone(0.022-3.7 GPa),and the yield strength was close to the maximum yield strength of human cortical bone(187.7-222.3 MPa).In conclusion,G triply periodic minimal surface scaffold with 55%porosity can reduce the stress shielding effect,bear a higher body load,improve the stability of the implant,and prolong the service life of the implant.

Objective: To observe the effects of electroacupuncture (EA) at Neiguan (PC6) on arrhythmia during acute myocardial ischemia-reperfusion and the expression of connexin 43 (Cx43) in rats. Methods: A total of 40 Sprague-Dawley male rats were used. Ten rats were randomly selected as the blank group, and the remaining 30 rats were randomly divided into a model group and an EA group, with 15 rats in each group. Before modeling, rats in the EA group received one session of EA intervention at bilateral Neiguan (PC6) for 30 min; the other groups were treated with the same grasping and anesthesia for 30 min without intervention. PowerLab physiological recorder was used to record electrocardiograph within 30 min of infarction. After the experiment, cardiac tissue and serum were collected from rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of myocardial tissue in the ventricular infarction area of rats in each group. The expression of Cx43 protein in the myocardium of each group was detected by Western blotting (WB). Enzyme-linked immunosorbent assay (ELISA) was used to determine the activity of Na+-K+-ATPase in myocardial tissue and the serum content of endogenous digitalis-like factor (EDLF) in rats. Results: There was no statistical difference in arrhythmia score between the EA group and the model group, but the total duration and average duration of arrhythmia in the EA group were decreased (P<0.01). HE staining showed that compared with the blank group, myocardial cells in the model group were disorganized and seriously damaged. The pathological changes in the EA group were similar to those in the model group, but the damage was relatively minor. The results of WB showed that compared with the blank group, the Cx43 expression in myocardial tissue of the model group was decreased (P<0.01); compared with the model group, the Cx43 expression in the EA group was increased (P<0.01); compared with the blank group, the Na+-K+-ATPase activity in myocardial tissue of the model group was significantly decreased (P<0.01); compared with the model group, the Na+-K+-ATPase activity in the EA group was increased (P<0.01). ELISA results showed that compared with the blank group, the serum EDLF content in the model group was significantly increased (P<0.01); compared with the model group, the EDLF content in the EA group was decreased (P<0.01). Conclusion: EA at Neiguan (PC6) can delay and reduce the onset of arrhythmia during myocardial infarction in the rat model of myocardial ischemia-reperfusion. Its mechanism of action may be related to the regulation of the Cx43 expression in myocardial tissue, improvement of the activity of Na+-K+-ATPase in myocardial tissue, and increase in the content of serum EDLF.

Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.

Objective To explore the independent risk factors of the prolonged time of retention ICU after type A aortic dissection operation,to establish a corresponding perioperative risk assessment system.Methods A total of 509 consecutive patients with type A aortic dissection were enrolled in the study from September 2011 to May 2016,among which,418 patients received emergency operation.The prolonged retention time of ICU was considered as endpoint event.A perioperative assessment system was established through the analysis of related risk factors of the most common complications after type A aortic dissection operation.The possible risk factors of prolonged retention time of ICU were introduced into a single factor analysis.The meaningful variables in the single factor analysis were introduced into logistic regression analysis.The independent risk factors which were obtained from logistic regression analysis were used to establish risk prediction modeL,and the ROC curve and Hosmer-Lemeshow goodness of fit test were used to evaluate the model.Results The perioperative mortality rate was 8.64％,the prolonged retention time of ICU was 5.06 days,and 98 cases exceeded 7 days.The results of logistic regression analysis showed that age,the history of stroke,obesity,emergency operation,cardiopulmonary bypass time,deep hypothermic circulatory arrest time,renal inadequacy,massive transfusion,hypoxemia,and pulmonary infection were the independent risk factors for prolonged retention time of ICU.Accordingly,a mathematical model was established.The area under ROC cure for prediction model(AUC) =0.761,Hosmer-Lemeshow goodness of fit test P =0.512.Conclusion The logistic model estabhshed in this study can successfully predict ICU retention time after type A aortic dissection operation,and the efficacy was predicted satisfactorily.

Results showed that its action was satisfactory.Theclinical effects of all three kinds of disease were betterthan that of the control group,especially on the im-provement of deficiency of blood and Qi(P