Objective·To establish various in vitro screening systems for the discovery of peptide inhibitors targeting the interaction between small ubiquitin-like modifier(SUMO)-activating enzyme subunit 1(SAE1)and subunit 2(SAE2),as well as to evaluate their advantages,disadvantages,and applicability to this research.Methods·The DNA fragments encoding human SAE1 and SAE2 were cloned into vector pET-28a,respectively,to generate protein SAE1 and SAE2.Purified proteins were used to establish screening assays,including isothermal calorimetry(ITC),fluorescence polarization(FP),surface plasmon resonance(SPR)and a fluorescence assay based on the SAE enzyme activity.The inhibitory activity of peptide candidates in different screening systems was examined,and their performance in terms of sensitivity,robustness,throughput and cost was evaluated.Results·The dissociation constant(Kd)of in vitro SAE1 and SAE2 interaction was determined to be 0.96 μmol/L by ITC,and PEPT7 was identified as the most potent peptide.However,the tracer of FP,which was derived from PEPT7,was not up to snuff due to its low affinity with SAE2.In the SPR assay,the Kd value(=1.13 μmol/L)of SAE1 and SAE2 interaction was in line with the results from ITC.The SAE enzyme activity-based screening assay revealed that HP1B,the most effective peptide,inhibited SAE with an half-maximal inhibitory concentration(IC50)of 15.72 μmol/L.The affinity of HP1B for SAE1 was determined to be 34.4 μmol/L by SPR.Conclusion·Several common screening systems for protein-protein interation(PPI)inhibitors are established and compared.Among them,ITC does not allow for high-throughput screening and it is difficult to accurately evaluate the low-affinity polypeptides with insignificant binding heat.The feasibility of FP relies heavily on the strong affinity between a tracer peptide and the protein target,making it unsuitable for the screening and optimization of low-affinity peptides.SPR is highly sensitive but the cost is high.The SAE enzyme activity-based assay stands out because it is a combination of high sensitivity,robustness,throughput and acceptable cost.

Objective:To explore any effect of combining robot-assisted virtual scenario training of the upper limbs with scalp acupuncture on post-stroke cognitive impairment.Methods:Ninety patients with post-stroke cognitive impairment (PSCI) were divided at random into a control group, a scalp acupuncture group and a comprehensive group, each of 30. In addition to routine health education and rehabilitation training, the scalp acupuncture group was given scalp acupuncture, while the comprehensive group was treated with scalp acupuncture and virtual scenario training with an upper limb robot. Before and after 4 weeks of the treatment, the subjects′ cognitive functioning was assessed using the Mini-mental State Examination (MMSE) and the Montreal Cognitive Assessment scale (MoCA). Ability in the activities of daily living (ADL) was quantified using the Modified Barthel Index (MBI).Results:After the intervention, significant improvement was observed in the average MMSE, MoCA and MBI scores of all three groups. The average MMSE and MBI scores of the scalp acupuncture group were then significantly higher than the control group′s averages, while the average MMSE, MoCA and MBI scores of the comprehensive group were all significantly better than those of the other two groups.Conclusion:Robot-assisted virtual scenario upper limb training combined with scalp acupuncture can significantly improve the cognition and ADL ability of PSCI patients.

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

Objective:To investigate the status quo of sexual function and marital adjustment of postpartum women and their spouses, so as to analyze the subject-object effects of sexual function and marital adjustment.Methods:This was a cross-sectional study. A total of 240 postpartum women and their spouses who gave birth in PLA Rocket Force Characteristic Medical Center from October 2022 to February 2023 were selected as the research objects by the convenient sampling method. The general data questionnaire, Female Sexual Function Index (FSFI), Male Sexual Function Index (MSFI) and Locke-Wallace Marital Adjustment Test were used to investigate them. Pearson correlation analysis and actor-partner interdependence model (APIM) were used to explore the relationship between sexual function and marital adjustment of postpartum women and their spouses.Results:In this study, 480 questionnaires were distributed to 240 couples, and 450 valid questionnaires were collected, with an effective recovery rate of 93.75% (450/480). The sexual function index score of 225 postpartum women was (24.89±4.97), and that of their spouses was (49.64±7.99). The marital adjustment scores of postpartum women was (96.42±22.64) and that of their spouses was (103.38±23.93). The results of APIM showed that the sexual function of postpartum women and their spouses could predict their own marital adjustment (β-values of 0.765 and 0.176, P<0.01). In terms of object effect, the sexual function of postpartum women could predict the marital adjustment of their spouses (β=0.632, P<0.01), but the sexual function of their spouses could not predict the marital adjustment of postpartum women ( P>0.05) . Conclusions:Postpartum women and their spouses have sexual dysfunction and marital disorder, their own sexual function is closely related to marital adjustment, and women's sexual function can also positively affect their spouses' marital adjustment. Medical staff should take postpartum women and their spouses as a whole to formulate intervention measures to promote the recovery of postpartum women's sexual function, balance family relations, enhance the satisfaction of sexual life between husband and wife and improve the level of marital adjustment.

OBJECTIVE To study the intervention effect and metabolic mechanism of Mongolian medicine Echinops sphaerocephalus extract on D-galactose-induced osteoporosis. METHODS Thirty-six 12-week-old male Wistar rats were selected and randomly divided into blank group， model group， Gushukang group， E. sphaerocephalus high-dose， medium-dose and low- dose groups， with 6 rats in each group. Except for blank group， other groups were intraperitoneally injected with D-galactose at 120 mg/kg per day. After 8 weeks of continuous injection， E. sphaerocephalus high-dose， medium-dose and low-dose groups were given drugs intragastrically at dose of 878， 439， 219.5 mg/kg， respectively. Gushukang group was given Gushukang 105.1 mg/kg intragastrically， once a day， for consecutive 8 weeks. After last administration， blood was collected from the abdominal aorta. Enzyme-linked immunosorbent assay was used to measure the contents of bone metabolism indexes [hydroxyproline （HYP）， alkaline phosphatase （ALP）] and oxidative stress indexes [total antioxidant capacity （TAOC）， superoxide dismutase （SOD）， malondialdehyde （MDA）] in serum of rats. Positron emission tomography/computedtomography （PET/CT） was used to analyze the changes of bone microstructure in right tibia bone. Meanwhile， metabolomic technology was used to study the regulation effect of E. sphaerocephalus on osteoporosis model rats. RESULTS Compared with blank group， HYP， ALP， MDA， ratio of bone surface to bone volume （BS/BV）， and trabecular separation （Tb·Sp） in model group were significantly increased （P＜0.05）， while TAOC， SOD， bone mineral density （BMD）， bone volume fraction （BVF）， trabecular E-mail：Xpfdc153@163.com thickness （Tb·Th） and trabecular number （Tb·N） were significantly decreased （P＜0.05）. Compared with model group， above indexes of administration groups were all reversed to different extents. The results of metabonomics study showed that after intervened with the extract of E. sphaerocephalus， 18 metabolites such as arachidonic acid， phenylalanine， tyrosine， tryptophan， isoleucine and uric acid in the serum of rats changed significantly， involving 15 metabolic pathways such as arachidonic acid， phenylalanine and tyrosine， of which arachidonic acid metabolism， phenylalanine metabolism and tyrosine metabolism were the main influencing pathways. CONCLUSIONS E. sphaerocephalus extract can effectively improve D-galactose-induced oxidative stress and the deterioration of bone microstructure， which interferes with metabolic pathways such as arachidonic acid metabolism and amino acid metabolism.

Transcatheter aortic valve implantation (TAVI) has become the main treatment for elderly patients with middle and high risk aortic stenosis. However, coronary artery occlusion (CAO) related to TAVI is a very serious complication, which often leads to poor prognosis. Therefore, active preoperative prevention is particularly important. Preoperative computed tomography evaluation, bioprosthetic or native aortic scallop intentional laceration and chimney stent implantation technology can prevent TAVI-related coronary orifice obstruction. Ensuring commissural alignment during operation can reduce the occurrence of coronary occlusion, but its long-term prognosis needs further study. In addition, percutaneous coronary intervention is the main treatment, but there are problems such as difficult coronary access after TAVI. This article summarized the research progress in the mechanism, prevention and treatment of CAO related to TAVI.

Objective:To investigate the predictive factors of delayed high atrioventricular block(DH-AVB) after transcatheter aortic valve replacement(TAVR) and the risk of pacemaker implantation.Methods:Patients who underwent TAVR in the heart center of Qingdao Municipal Hospital from January 2019 to October 2022 were retrospectively analyzed. A total of 85 patients who met the criteria of transcatheter aortic valve replacement were included in this study. They were divided into DH-AVB group after TAVR and non-DH-AVB group after TAVR. The data were analyzed by univariate analysis and binary logistic regression analysis. Results:The results showed that the over-rate of valve implantation( OR=3.582, 95% CI: 0.923-13.902, P=0.048), the depth of valve implantation( OR=3.727, 95% CI: 1.138-12.204, P=0.030), the new postoperative CLBBB( OR=5.958, 95% CI: 1.258-28.220, P=0.025)and the prolonged PR time limit( OR=1.036, 95% CI: 1.008-1.065, P=0.011) were independent risk factors for DH-AVB after TAVR. With the progress of conduction block, patients in DH-AVB group had a higher pacemaker implantation rate(81.82 % vs.18.18 %, P<0.001). Conclusion:The excessive rate of valve implantation, the depth of valve implantation, the new complete left bundle branch block(CLBBB) and the prolonged PR time after operation are independent predictors of delayed complete atrioventricular block after TAVR. The incidence of pacemaker implantation in patients with delayed complete atrioventricular block after operation is higher.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Objective:To observe the clinical effect of combining four-channel electrical stimulation with electroacupuncture of the antagonistic muscles in treating post-stroke spastic foot drop.Methods:Ninety stroke survivors with spastic foot drop were randomly divided into a control group, an electrical stimulation group and an observation group, each of 30. In addition to routine rehabilitation training, the electrical stimulation group was given four-channel electrical stimulation for 4 weeks, the electrical stimulation was delivered with a pulse duration of 200μs and an intensity of motor threshold at 30Hz, while the observation group also received electroacupuncture of the antagonistic muscle. Before and after the treatment, the three groups were evaluated using the clinical spasticity index (CSI). Stride frequency, stride length, and the supporting and swing phases on the affected side were also measured. Electromyography (EMG) was also conducted.Results:After the treatment, the average CSI scores of all groups had decreased significantly, with that of the observation group significantly lower than the electrical stimulation group and control group′s averages. The average gait descriptors of the three groups had also improved significantly, with significantly greater improvement in the observation group than in the other two. The average H reflex latency was significantly longer and Hmax/Mmax was significantly smaller in all three groups, but the observation group′s average values were again significantly better than those of the electrical stimulation group.Conclusion:Electroacupuncture of the antagonistic muscle enhances the effectiveness of four-channel electrical stimulation in relieving foot drop symptoms and improving gait after a stroke.

Objective:To explore the status quo of palliative care needs of patients with end-stage heart failure, and analyze its influencing factors.Methods:This study was a cross-sectional study. From December 2019 to December 2020, convenience sampling was used to select 83 patients with end-stage heart failure in a Heart Failure Treatment Center of a Class Ⅲ Grade A hospital in Qingdao as the research object. The General Information Questionnaire and the Palliative Care Needs Scale for Patients with End-stage Heart Failure were used to investigate the patients. Multiple linear regression was used to analyze the influencing factors. A total of 83 questionnaires were distributed and 76 valid questionnaires were returned with the valid response rate of 91.57%.Results:Among 76 patients with end-stage heart failure, the total score of the Palliative Care Needs Scale for Patients with End-stage Heart Failure was (110.87±20.77) , of which the information needs dimension score (29.61±6.69) was the highest. The results of multiple linear regression analysis showed that the serum sodium concentration, the number of comorbidities, and the educational background were the influencing factors of the palliative care needs of patients with end-stage heart failure ( P<0.05) , which explained 30.6% of the total variation of the palliative care needs. Conclusions:Patients with end-stage heart failure have a high demand for palliative care. Nursing staff should provide personalized palliative care for patients with end-stage heart failure according to their own characteristics.