Objective:To explore the biomarkers associated with multiple myeloma in remission phase (MM-RP) in order to provide potential indicators for disease monitoring and prognostic evaluation.Methods:Bone marrow blood samples were prospectively collected from 9 newly diagnosed multiple myeloma (NDMM) patients and 9 MM-RP patients in Beijing Chaoyang Hospital of Capital Medical University from January to October 2020. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for proteomic analysis in 3 independent experiments, each containing 3 paired NDMM and MM-RP samples. Differentially expressed proteins (DEP) consistently identified across all 3 experiments were considered potential MM-RP biomarkers. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used for enrichment analyses of the biological functions of these potential biomarkers. Protein-protein interaction (PPI) networks were constructed using the STRING 11.5 database, and α-2-macroglobulin (α2M) was identified as a hub protein. The UCSC Xena database was utilized, and the overall survival (OS) of MM patients with high or low α2M expression [stratified by the average level of α2M transcriptome sequencing (RNA-seq) data] was analyzed by using Kaplan-Meier. A multivariate Cox proportional hazards model adjusted for age, International Staging System (ISS) stage and treatment regimen was employed to analyze the impact of α2M expression on OS of MM patients. The Human Protein Atlas (HPA) database was used to examine α2M mRNA expression patterns in 33 cancer types. The correlation of drug sensitivity [50% inhibiting concentration ( IC50)] with α2M expression was assessed using pharmacogenomic data from the GSCALite platform. Results:Among 104 proteins consistently identified in 3 proteomic experiments, 34 DEP were found between NDMM and MM-RP (∣fold change∣>1.0 and P < 0.05), including 25 upregulated DEP and 9 downregulated DEP in MM-RP. GO analysis showed that the identified MM-RP potential markers were mainly involved in biological processes such as complement activation and humoral immune response, and the molecular functions mainly involved serine hydrolase activity, serine peptidase activity, etc., and were mainly distributed in secretory granules, blood particles, and other parts; KEGG enrichment analysis showed that biomarkers were mainly enriched in the complement and coagulation cascade pathways. In the human α2M PPI network constructed using data from the STRING database, there were 10 proteins that interacted with α2M, with a connectivity of 7.82, and had direct interactions with 71% of the proteins in the network, the betweenness centrality value was 0.06, and the closeness centrality value was 1, indicating significant network centrality feature of α2M. In the constructed PPI network of α2M protein and DEP screened by proteomics, there were interactions between α2M protein and 11 MM-RP markers screened by proteomics, and the betweenness centrality value of α2M reached 0.50, the closeness centrality value was 0.67, indicating that α2M was at the core position of the PPI network. UCSC Xena analysis revealed that MM patients with low α2M expression (523 cases) had worse OS than those with high expression (336 cases) ( P =0.024). Multivariate Cox regression analysis confirmed that low α2M expression was an independent risk factor for poor OS (compared with high α2M expression: HR = 0.726, 95% CI: 0.550-0.960, P = 0.024). HPA database analysis demonstrated that the α2M expression levels were variable in different types of cancer, its level in glioblastoma multiforme, clear cell renal cell carcinoma, and stomach adenocarcinoma was higher than that in normal tissues (all P < 0.05), and its level in urothelial carcinoma, breast cancer and cervical squamous cell carcinoma was lower than that in normal tissues (all P < 0.05). GSCALite analysis revealed negative correlations between α2M expression level and IC50 values of B-Raf kinase inhibitors, B-Raf V600E inhibitors and dabrafenib mesylate. Conclusions:α2M expression level in MM-RP patients is lower than that in NDMM patients, and its expression level may be related to the prognosis of patients, which is expected to become a novel biomarker reflecting the disease activity of MM.

Background Due to the prominent particularity of medical work,nurses are prone to developing depression,which not only poses a considerable threat to the physical and mental health of nurses,but also affects the quality of nursing to some extent.Occupational stress is a known contributor to depression in nurses,whereas relatively little research has been done to investigate the underlying mediation path.Objective To explore the mediation effect of perceived organizational support and psychological capital on the relationship between occupational stress and depression among nurses,and to provide theoretical references for the prevention and treatment of occupational stress-induced depression in nurses.Methods From March to August 2019,a stratified random sampling method was utilized to select a sample size of 720 nurses in each department of a grade A tertiary hospital in Shandong Province.All subjects were assessed using Effort-Reward Imbalance Questionnaire(ERI),Perceived Organization Support Questionnaire(POS),Psychological Capital Questionnaire(PCQ)and Center for Epidemiologic Studies Depression Scale(CES-D).Pearson correlation was adopted to examine the correlation among above scales,and multilevel mediation analyses were conducted with model 6 in Process macro(version 3.3)for SPSS 26.0 using Bootstrap re-sampling method.Results A total of 658 nurses(91.39%)completed the effective questionnaire survey.ERI score was positively correlated with CES-D score(r=0.499,P<0.01),and negatively correlated with POS and PCQ scores(r=-0.318,-0.275,P<0.01).POS score was positively correlated with PCQ score(r=0.455,P<0.01),and negatively correlated with CES-D score(r=-0.401,P<0.01).PCQ score was negatively correlated with CES-D score(r=-0.567,P<0.01).The total effect value of occupational stress on depression was 0.466(95%CI:0.399～0.534).Perceived organizational support(indirect effect value of 0.027,95%CI:0.006～0.057)and psychological capital(indirect effect value of 0.059,95%CI:0.013～0.120),separately from each other,mediated the relationship between occupational stress and depression,and a chained mediation effect of perceived organizational support and psychological capital was also demonstrated(indirect effect value of 0.051,95%CI:0.031～0.082),accounting for 10.94%of the total effect.Conclusion Occupational stress is a influencing factor of nurses' depression,which can affect the occurrence of depression both directly and indirectly through either separate or chained mediation of perceived organizational support and psychological capital.

Objective:To study the effects of the combined application of NaF and Nisin on Streptococcus mutans(S.mutans).Meth-ods:The minimum inhibitory concentration(MIC)of Nisin and NaF against S.mutans was determined by microdilution method respec-tively.The fractional inhibitory concentration(FIC)was calculated by checkerboard method.The inhibition effect of the combination of NaF and Nisin at(NF)the same MIC concentration on acid production and acid resistance of S.mutans was detected.Crystal violet staining was used to detect the effects of NF in the inhibition of the biofilm formation,and the damage and dispersion of the established biofilms.The changes of the biofilms were observed by CLSM.Results:The MIC of NaF and Nisin was 0.6 mg/mL and 20 mg/mL re-spectively.The FIC was 0.75.The 1/8×MIC NF showed significantly higher inhibition on acid production and biofilm formation than 1/4×MIC NaF or Nisin(P＜0.05),but it has no obvious dispersion effect on established biofilms.The 1/2×MIC NF showed stronger in-hibition effect on the acid resistance of S.mutans in the membrane than 1×MIC NaF or Nisin(P＜0.05).At the concentration of 2x MIC,any component didn't cause obvious damage on the established biofilm structure.Conclusion:Nisin and NaF have synergistic in-hibitory effects on the proliferation,acid production,acid resistance and biofilm formation of S.mutans.

Objective To study the mechanical response of tibial prostheses and the distal tibial cancellous bone after implantation of radial and axial functionally graded materials(FGM)into the ankle joint.Methods Three FGM were used:titanium alloy-bioactive glass composite FGM(FGM-Ⅰ),titanium(Ti)alloy-ideal bone elastic composite FGM(FGM-Ⅱ),and Ti alloy-hydroxylapatite composite FGM(FGM-Ⅲ).A three-dimensional finite element model of total ankle arthroplasty(TAA)was established,and the simulation software ABAQUS was used for secondary development based on Fortra.By changing the volume fraction,the mechanical properties of the FGM tibial prosthesis can be adjusted both axially and radially.The stress distributions of the tibial prosthesis and cancellous bone after FGM axial and radial tibial component implantation in the standing position were analyzed.Results Compared with Ti alloy tibial prosthesis,three kinds of FGM could effectively reduce the stress concentration on the tibial prosthesis,and the overall effect of FGM-Ⅲ tibial prosthesis was better than that of FGM-Ⅰ and FGM-Ⅱ tibial prosthesis;the radial distribution of FGM could effectively reduce the maximum von Mises stress of the prosthesis.For the tibial cancellous bone,the three types of FGM radial tibial prostheses and FGM-Ⅲ axial tibial prostheses could effectively increase the distal stress,thus,relieving the stress shielding on the cancellous bone;the FGM-Ⅲ radial tibial prosthesis was the most effective in improving the stress level of the cancellous bone.Conclusions FGM-Ⅲ radial ankle prosthesis can effectively reduce the stress concentration phenomenon and the stress shielding effect on the prosthesis to prolong its life,with potential application prospects.

Objective To establish an intelligent detection algorithm model for acute promyelocytic leukemia(M3 model)based on a contrast large model using machine learning statistical software and validate its effectiveness.Methods The data from 8 256 outpa-tients and inpatients who underwent complete blood cell analysis at Peking Union Medical College Hospital were retrieved and analyzed using the laboratory information system(LIS)and hospital information system(HIS).A M3 screening model was established and vali-dated using the data from outpatients and inpatients who underwent complete blood cell analysis at our hospital from July to October 2023.Results The M3 model demonstrated potential application value in screening for M3 disease in complete blood cell analysis,which showed certain efficacy in screening for neutrophil toxicity changes,particularly in identifying two cases of blue-green inclusion bodies in neutrophils.Conclusion The M3 model exhibited low specificity for M3 diagnosis.Future research should focus on increas-ing the number of M3-positive cases to optimize the model,ensuring high sensitivity while improving specificity.This model will provide assistance for the intelligent review of complete blood cell analysis.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

【Objective:】 To understand the current situation and influencing factors of ethical knowledge, attitude, and practice (KAP) among clinical researchers, enhance their ethical awareness, and improve the quality of clinical researches. 【Methods:】 A self-designed questionnaire was used to conduct a convenient sampling survey of medical staff who have participated in clinical study. 【Results:】 A total of 6,021 subjects were investigated, with males accounting for 28.46% and females accounting for 71.53%. The average age of them was (37.47±11.46) years old. The total score of ethics and the mean scores of the three dimensions of knowledge, attitude and practice were (70.62±12.99), (59.63±12.50), (79.55±19.62) and (74.92±18.29), respectively. Multiple linear regression analysis showed that researchers with male, tertiary hospitals, doctors, ethics-related part-time jobs, postgraduate education, associate senior title or above, and training experience scored higher (P<0.05). 【Conclusion:】 Ethical attitudes have a significant mediating effect between knowledge and practice, accounting for 62.72% of the total effect. Researchers recognize the importance of ethics, but it is urgent to strengthen their knowledge learning and practical application.

ObjectiveTo investigate the effects of Huashi Runzao prescription （HRP） on the histopathological injury and function of submandibular gland in naive non-obese diabetic （NOD/Ltj） mouse model of Sjögren's syndrome （SS） and its regulatory effect on aquaporin 5 （AQP5） expression in submandibular gland cells. MethodThe SS model was induced in NOD/Ltj mice. The NOD/Ltj female mice aged nine weeks were selected and randomly assigned into model group，HRP group （7.15 g·kg^-1·d^-1），and hydroxychloroquine （HCQ） group （1.30 g·kg^-1·d^-1）， and female BALB/c mice in the same age were selected and assigned into the normal group， with six mice in each group. Drug intervention lasted eight weeks. The water consumption and salivary flow rate （SFR） of each group were recorded. The pathological staining results of the submandibular gland of mice in each group were observed and scored. AQP5 expression was determined by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed increased water consumption （P<0.05） and reduced SFR （P<0.05）. Compared with the model group， the HRP group showed decreased water consumption （P<0.05） and increased SFR （P<0.05）， and the HCQ group showed increased SFR （P<0.05）. In terms of histopathological results of the submandibular gland，compared with the normal group，the model group showed increased pathological score， number of lymphocyte infiltration foci，and percentage of lymphatic infiltration area （P<0.05）. Compared with the model group， the HRP group showed reduced pathological scores and number of lymphocyte infiltration foci （P<0.05）， and the HRP group and the HCQ group showed reduced percentage of lymphatic infiltration area（P<0.05）. The results of IHC and Western blot showed that compared with the normal group，the model group showed down-regulated expression level of AQP5 protein （P<0.05）， and compared with the model group and the HCQ group，the HRP group showed up-regulated expression level of AQP5 protein （P<0.05）. ConclusionHRP can improve the secretion function of submandibular gland acinous cells and glandular structure injury in SS model mice， and its mechanism may be related to the up-regulation of AQP5 protein expression level in submandibular gland cells.

ObjectiveTo observe the efficacy and safety of Huashi Runzao prescription for patients with primary Sjögren's syndrome （pSS） of combined dryness and dampness pattern. MethodA total of 105 eligible patients were randomized into the experimental group （65 cases） and control group （40 cases）， and they were respectively treated with Huashi Runzao prescription and hydroxychloroquine for 12 weeks. Visual Analogue Scale （VAS） was employed to assess the symptoms. The symptoms of dryness， fatigue， and pain， European League Against Rheumatism （EULAR） Sjögren's Syndrome Patient Reported Index （ESSPRI）， EULAR Sjögren's syndrome disease activity index （ESSDAI）， and immune inflammatory indicators before and after treatment were compared between the two groups， and adverse reactions were observed. ResultAfter treatment， the ESSPRI score was lower than that before treatment in the experimental groups （P<0.01） and was lower in the experimental group than in the control group （P<0.05）. The VAS scores of dry mouth， dry eyes， overall dryness， fatigue， and pain in the experimental group decreased compared with those before treatment （P<0.01）， and the experimental group had lower VAS scores of dry mouth and overall dryness than the control group （P<0.01）. After treatment， the ESSDAI score of both groups decreased compared with that before treatment （P<0.05， P<0.01）， but there was no significant difference between the groups. After treatment， the level of immunoglobulin M （IgM） decreased （P<0.01） and the level of complement C3 increased （P<0.01） in the experimental group， while the level of complement C3 decreased in the control group （P<0.05）. There was no significant difference in the laboratory indexes between groups. During the treatment， stomachache occurred to one case in the experimental group， which was alleviated after the treatment， and no adverse reaction was observed in the control group. According to the chi-square test， the occurrence of adverse reactions was insignificantly different between the two groups. ConclusionHuashi Runzao prescription can alleviate the symptoms of dryness， fatigue， and pain， and reduce disease activity without associated side effects in pSS patients with combined dampness and dryness pattern.

ObjectiveTo explore the characteristics of tongue manifestations and traditional Chinese medicine （TCM） syndromes in patients with primary Sjogren's syndrome （pSS） of different time. MethodpSS patients who visited TCM Department of Rheumatism in China-Japan Friendship Hospital from December 2018 to October 2021 were included and grouped according to the disease courses （short<5 years， medium 5-10 years， long > 10 years）. Chi-square test was used for comparison between three groups and Bonferroni method for multiple comparisons. In the pairwise comparison， P<0.017 indicated significant difference. Chi-square test was performed on the syndrome and specific tongue manifestations with inter-group differences to analyze the trend of tongue manifestations and TCM syndromes over time （interval： two years）. ResultA total of 193 pSS patients were enrolled， with 85 （44.0%） of short disease course， 69 （35.8%） of medium disease course， and 39 （20.2%） of long disease course. The common tongue manifestations were crimson tongue， fissured tongue， thin tongue， lack of fluid， and dry coating， which showed no significant difference among the three groups. Higher proportion of patients with light red tongue was observed in the group with short disease course than in group with medium disease course （χ²=6.407， P<0.017）. Higher proportions of patients with thick coating （χ²=6.784， P<0.017） and phlegm-dampness syndrome （χ²=11.545， P<0.017） and lower proportion of patients with Qi deficiency syndrome （χ²=12.706， P<0.017） were found in the group with short disease course than in the group with long disease course. Patients with medium （χ²=6.358， P<0.017） and long （χ²=8.279， P<0.017） disease course tended to have exfoliated coating compared with those with short disease course， and the proportion of patients with exfoliated coating rose and the proportion of patients with thick greasy coating decreased over time （P_trend<0.05）. In addition， the proportion of patients with phlegm-dampness syndrome decreased and that with Qi deficiency syndrome increased over time （P_trend<0.05）. ConclusionIn the early stage， patients with pSS often show both dryness and dampness， as manifested by the thick greasy coating and phlegm-dampness syndrome. In the medium and late stage， patients often have Qi-Yin deficiency， as evidenced by exfoliated coating and Qi deficiency. In the clinical practice， medicines should be prescribed based on tongue manifestations and TCM syndrome of patients.