Objective:To investigate the efficacy and safety of daratumumab (Dara) - combination regimens for newly diagnosed multiple myeloma (NDMM).Methods:A retrospective case series study was conducted. The clinical data of 34 patients with NDMM receiving treatment regimen including Dara from Qilu Hospital of Shandong University, Yantai Yuhuangding Hospital, Huangdao Branch of Affiliated Hospital of Qingdao University and Taian City Central Hospital between April 2020 and March 2022 were retrospectively collected. The efficacy, survival and adverse reactions of patients were analyzed. Cox proportional risk model was used to analyze the factors affecting overall survival (OS) and minimal residual disease (MRD) turning negative.Results:Among 34 patients with NDMM, there were 19 males and 15 females, with 21 cases aged < 65 years and 13 cases aged ≥65 years. The median follow-up duration [ M ( Q1, Q3)] was 22 months (19 months, 26 months), the median of Dara treatment cycles was 7 (5, 11), and the overall response rate (ORR) reached 97.1% (33/34). There were statistically significant differences in the optimal efficacy of patients stratified by receiving hematopoietic stem cell transplantation or not and receiving different treatment cycles (all P ≤ 0.05), while there were no statistically significant differences in patients stratified by other clinical features (all P > 0.05). The 1-year progression-free survival rate was 79.4% and the 1-year OS rate was 94.1%. Multivariate Cox regression analysis showed that the cycle number of treatment regimens containing Dara was an independent influencing factor of MRD turning negative (6 cycles vs. 2 cycles, HR = 0.267, 95% CI: 0.076-0.935, P = 0.039); age ≥ 65 years was an independent risk factor for OS ( HR = 35.313, 95% CI: 1.709-729.669, P = 0.021). The incidence of hematological adverse reactions grade 3 or above was 20.6% (7/34), and the non-hematological adverse reactions primarily included infection [44.1% (15/34)] and edema of extremity and trunk [41.2% (14/34)]. Conclusions:The Dara-based regimens for NDMM exhibit a high ORR. The remission depth accelerated with the increasing number of treatment cycle, and the adverse reactions are mild.

Objective To investigate the effect of the monoamine oxidase A(MAOA),Maoa c.1409 T＞C synonymous mutation on anxiety,fear,and other emotional behaviors in mice.Methods In this study,CRISPR/Cas9 technology was used to construct a mouse model of a single nucleotide polymorphism(SNP)synonymous mutation.We evaluated the differential effect of this gene between males and females through animal behavior and gene expression studies in animal models.In terms of animal behavior,an open field test,elevated plus maze test,defensive burial experiment,forced swimming test,and 3D behavioral analysis were used.Other method were used to evaluate behavioral differences between male and female mice with polymorphisms in Maoa synonymous mutant genes.Results The result of the open field experiment showed that the residence time of female SNP mice in the central area was significantly higher than that of male SNP mice(P＜0.001).In the elevated cross maze experiment,the EPM result showed that the time and frequency of male SNP mice entering the open arm were higher than those of female SNP mice,but there was no significant difference.The defensive burial test showed that the number and duration of excavations by female SNP mice in response to rat urine were significantly reduced(P＜0.01).The FST showed that SNP females had shorter immobility time and longer swimming time(P＜0.05),and thus their depression was lower than males.3D-AI fine behavior analysis showed no significant male and female differences,except for the movement trajectory and climbing behavior of mice.The MAOA enzyme content of female SNP mice was significantly lower than that of male SNP mice(P＜0.001),but there was no significant difference in enzyme activity between male and female SNP mice.Conclusions The synonymous mutation of Maoa c.1409 T＞C acts by affecting the expression of MAOA and may have different fear,anxiety,and mood effects in male and female SNP mice.

Objective:To investigate the effect of oroxylin A (OrA) on macrophage pyroptosis induced by Mycobacterium tuberculosis ( Mtb) infection and the underlying molecular mechanism. Methods:An in vitro infection model was constructed by infecting J774A.1 cells with Mtb. The MTT method was used to detect the effect of OrA on the viability of J774A.1 cells. Lactate dehydrogenase (LDH) assay kit was used to detect the release of LDH by J774A.1 cells. Western blot was used to detect the protein levels of pyroptosis-related proteins such as NOD-like receptor thermal protein domain associated protein 3 (NLRP3), GSDMD-N, caspase1-p20, apoptosis-associated speck-like protein containing a CARD (ASC), and α7 nicotinic acetylcholine receptor (α7nAChR) as well as the phosphorylation of NF-κB p65. ELISA was used to detect the levels of IL-1β in each group. Immunofluorescence was performed to detect the expression and localization of α7nAChR. Results:MTT results showed that OrA had no cytotoxicity to J774A.1 cells at concentrations below 80 μmol/L. OrA reduced the release of IL-1β, down-regulated the expression of NLRP3, GSDMD-N and caspase1-p20 at protein level, inhibited ASC oligomerization, promoted the expression of α7nAChR at protein level, and inhibited the phosphorylation of NF-κB p65. In the presence of α7nAChR agonist PNU282987, the protein levels of GSDMD-N decreased and the phosphorylation of NF-κB p65 was inhibited.Conclusions:OrA may inhibits Mtb infection-induced macrophage pyroptosis through regulating cholinergic anti-inflammatory pathway.

Shegan Mahuang Decoction is a classic formula for the treatment of asthma, which has the efficacy of dissipating cold and reducing phlegm, relieving cough and relieving asthma, and can be used clinically alone to control acute attacks, or to assist Western medical methods to improve the efficacy, and can also to combine with other classical prescriptions for the pathogenesis, which can improve the symptoms of cough and asthma, expectoration, and lung function indexes. The mechanism of Shegan Mahuang Decoction in the treatment of asthma is mainly related to reducing inflammatory response and inhibiting airway remodeling, and it mainly regulates immune inflammatory pathways to play a role.

Objective:To explore the mediating effect of self-directed learning ability between feedback-seeking behavior and caring ability of nursing students in school.Methods:In September 2019, convenience sampling was used to select undergraduate nursing students from grades 1 to 3 in a medical university in Liaoning Province as the research object. The Feedback Seeking Behavior Scale, Self-regulated Learning Ability Scale and the Caring Ability Inventory were used to conduct a cross-sectional survey. A total of 184 questionnaires were distributed and 172 valid questionnaires were returned.Results:The caring ability score of 172 school nursing students was (184.45±18.34) . Among nursing students in school, caring ability was positively correlated with feedback-seeking behavior and self-directed learning ability with a statistical difference ( P<0.01) , and feedback-seeking behavior was positively correlated with self-directed learning ability also with a statistical difference ( P<0.01) . The self-directed learning ability played a part of mediating role between feedback-seeking behavior and caring ability, and the difference was statistically significant ( P<0.01) , and the mediating effect was 61.18%. Conclusions:The caring ability of school nursing students is at an intermediate level and needs to be further improved. The feedback-seeking behavior of nursing students in school can directly affect the caring ability, and can also indirectly affect the caring ability through self-directed learning ability. Educators can guide and cultivate the feedback-seeking behavior and self-directed learning ability of nursing students at school, promote their self-regulation, and improve their caring abilities.

Objective:To evaluate the application effect of the vertical and horizontal step-by-step teaching mode in clinical nursing students.Methods:Using the convenient sampling method, the nursing students who were internship in the nursing college of Dalian Medical University were selected as the research objects. 27 nurses from July 9, 2016 to April 12, 2017 were the control group, and 29 nursing students from July 2017 to April 2018 were experimental groups. The control group adopts the traditional teaching mode, and the experimental group adopts the vertical and horizontal ladder teaching mode to complete the 40-week internship, and each round (four weeks) conducts theoretical and skill assessment.Results:The experimental group of nursing students in the experimental group had a score of (91.52 ± 1.75) points on the theoretical theory, a score of (90.99 ± 1.44) points on the staged skills examination, and a score of (699.34 ± 8.85) points on the national nursing qualification examination. The comprehensive quality evaluation score of the phased internship nursing students was (92.58 ± 1.17) points, which were higher than the control group's (88.89 ± 2.82), (88.27 ± 2.04), (694.26 ± 7.61), (89.44 ± 0.62) points, and the difference was statistically significant ( t values were -4.21,-5.79, -2.30, -7.50, P <0.05). Conclusion:The vertical and horizontal step-by-step teaching mode is conducive to improving the efficiency of clinical teaching, improving the learning effect of students, and playing a positive guiding role in the development of internship plans with teaching departments, and improving the overall level of nursing teaching.

Objective:To understand the factors that affect the self-management behavior of patients with cardiac resynchronization therapy (CRT) and to provide reference for the development of patients' self-management behavior nursing measures and personalized nursing programs.Methods:The convenient sampling method was used to select 15 chronic heart failure patients who underwent CRT in the cardiology department in a ClassⅢ Grade A general hospital in Dalian from June to December 2019 as the research objects. The phenomenological research method in qualitative research was used to conduct semi-structured interviews with patients, and the data was analyzed by the Colaizzi 7-step analysis method.Results:The two themes of hindering factors and promoting factors of self-management behavior of patients after the first operation of CRT were summarized. Hindering factors included the misunderstanding of health outcomes after CRT, the ignorance of the ability to recognize postoperative symptoms, postoperative learned helplessness and decreased postoperative social connectedness. Promoting factors included perceived postoperative benefit, positive self-adjustment of emotions and rebuilding confidence in future life.Conclusions:The self-management behavior of patients after CRT is affected by multiple factors, and comprehensive evaluation should be made from the aspects of symptoms, physiology, psychology and society to improve the self-management ability of patients after CRT for the first time.

Objective This study aims to investigate the frequency and characteristics of vascular involvement in Beh(c)et's disease (BD).Methods We enrolled patients who were hospitalized at Changhai Hospital affiliated Naval Medical University and who had been diagnosed with BD at discharge from January 1999 to July 2017.Patientswere divided into two groups,Vascular Beh(c)et's disease (VBD) group and non-VBD group,according to vascular involvement or not.We recorded and compared the demographicinformation,disease activity scores Beh(c)et’s Disease Current Activity Form (BDCAF),other systemic involvement and laboratory test results between the two groups.The clinical features of vascular involvement were analyzed.The measureddata were statistically analyzed with Student's t/t’ test or Mann-Whitney U test.The numerical data were statistically analyzed with x2 test or continuity correction x2 test.Results The total numbers of BD patients were 224,including 120 males and 104 females.Vascular involvements were found in 41 (18.3％) cases,including 34 males and 7 females.VBD was more common in males (28.3％ vs 6.7％,x2=17.388,P＜0.01).Of 41 VBD patients,11 cases (26.8％) had single vascular lesions,and 30 cases (73.2％) had multiple vascular lesions.Moreover,24 cases (58.5％) had arterial lesions,and 25 cases (61.0％) had venous lesions.Eight (19.5％) patients had both arterial and venous lesions.Compared to the non-VBD group,the VBD group had a higher frequency of cardiac involvement (22.0％ vs 3.8％,x2=16.592,P＜0.01),a higher disease activity index score (BDCAF) [3.0(2.0,4.0) score vs 2.0(2.0,3.0) score,U=2 609.5,P=0.001],higher levels of C-reactiveprotein (CRP) (14.45(4.97,64.08) mg/L vs 9.02(3.16,26.53) mg/L,U=2 809,P=0.046) and plasma homocysteine (Hcy) [(17.6±7.7) μmol/L vs (7.1±2.1) μmol/L,t'=7.894,P＜0.01].Conclusion VBD mainly affectsmales.It mainly presentsas multiple lesions.Moreover,patients in the VBD group havehigher frequency of cardiac complications,higher disease activity index scores (BDCAF),higher levels of CRP and Hcy than the non-VBD group.These results may have great valueto predict and diagnoseof VBD.

Objective:To construct the expression vector of the fusion protein of human serum albumin (HSA) and thymopentin (TP5) and to express it in Pichia pastoris,and to elucidate the biological activity of fusion protein.Methods:The HSA-TP5 fusion gene was constructed by gene recombination and transfected into Pichia pastoris to construct the eukaryotic expression system of HSA-TP5.The recombinant eukaryotic expression plasmid of PPICZα-HSA-TP5 was obtained by agarose gel electrophoresis and purification reagent.The two step fermentation method was used to ferment gene engineering bacteria of HSA-TP5 in high density,and the fermentation supernatant protein was precipitated and concentrated;the purified fusion protein was obtained by cation exchange chromatography and hydrophobic chromatography and analyzed by SDS-polyacrylamide gel electrophoresis.The effect of the fusion protein on the proliferation of lymphocytes was detected by MTT assay.Results:The HSA target gene fragment with length of 1 845 bp was achieved by PCR method.The HSA-TP5-pPICZαC fusion plasmid was identified by restriction endonuclease digestion,and the fragment length was 707 bp.The sequence analysis showed that the HSA and TP5 sequences of the target genes were identical with the gene sequences reported in GenBank and were fused by forward fusion.PCR method confirmed that the eukaryotic recombinant plasmid PPICZ αC-HSA-TP5 was integrated into the yeast genome,and compared with control group,the target gene PCR product length was found to be 1 860 bp.SDS-PAGE analysis showed that the expression level of HSA-TP5 fusion protein was gradually increased with the induction time within 72 h.HSA-TP5 fusion protein was purified by cation exchange chromatography and AKTA multifunctional protein purification system.The MTT assay results showed that HSA-TP5 fusion protein was consistent with TP5 protein in promoting lymphocyte proliferation activity.Conclusion:HSA-TP5 fusion protein can be obtained by constructing the eukaryotic expression system of Pichia pastoris and owns the biological activity.

Objective To validate the value of Simplified Renal Index Score(SRI) in predicting acute renal injury requiring renal replacement therapy(RRT-AKI) after cardiac valve surgery in Chinese adult patients.Methods An analysis was conducted for all the adult patients who underwent cardiac valve surgery from January 2010 to December 2014 in Changhai Hospital,Shanghai.A total of 3 183 adult patients were included.Based on SRI Score,the patients were divided into 3 risk stages:0 to 1 point,2 to 3 point,and 4 to 8 point.The incidence of RRT-AKI was compared between different stages.And the prediction value of the SRI model was assessed by area under the receiver operating characteristic curve (AU-ROC) and the model calibration was assessed with the Hosmer-Lemeshow (H-L) test.Results After surgery 52 (1.6％) patients developed acute kidney impairment and subsequently underwent renal replacement therapy.Patients with low values of simplified renal index (0-1),medium(2-3) and high values (4 and more) were found to have increasingly higher risk for renal replacement therapy of 0.8％ (95％ CI:0.005-0.012) 、3.8％ (95％ CI:0.026-0.052) 、20％ (95％ CI:0.010-0.720),respectively.TheAU-ROCwas0.68(95％ CI:0.610-0.760,P＜0.01).The H-L test was x2 =2.45,P=0.29.Conclusion SRI model gives a certain clinical significance,suggesting that high-values patients may occur RRT-AKI with a significantly higher risk than low-values patients.However,SRI model cannot give an accurate prediction value for RRT-AKI in Chinese adult patients after cardiac valve surgery.Direct clinical use of the model should be considered cautiously.