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.

Objective To investigate the anti-inflammatory protective effects of remimazolam on microglial cells and elucidates the potential molecular mechanisms underlying these effects. Methods The mouse microglial cell line (BV2) was selected as the research object. The following groups were set up:the control group (complete medium),the Rema group (200 μg/mL remimazolam),the model group (1 μg/mL lipopolysaccharide,LPS),and different-concentration administration groups (1 μg/mL LPS+50,100,200 μg/mL remimazolam). In the Rema group,cells were treated with 200 μg/mL remimazolam alone for 26 h. In the model group,cells were treated with LPS for 24 h. In the different-concentration administration groups,cells were pre-treated with different concentrations of remimazolam for 2 h,and then treated with LPS for 24 h. The effects of LPS and remimazolam on the morphology of BV2 cells were observed and evaluated using an optical microscope. Cell viability was determined using the CCK-8 assay,while the expression and secretion of inflammatory cytokines were quantified by quantitative real-time PCR and ELISA. Reactive oxygen species (ROS) levels were measured using a fluorescent probe. Additionally,malondial-dehyde (MDA) content,superoxide dismutase (SOD) activity,and glutathione peroxidase (GSH) activity were evaluated using respective assay kits. Western blot analysis was conducted to examine the protein expression levels of Bax,Bcl-2,IL-1β,RAGE,NF-κB,p-NF-κB,IκBα,p-IκBα,iNOS,and Arg-1. Immunofluorescence staining was employed to visualize NF-κB nuclear translocation and M1/M2 polarization in the cells. Results Compared to the control group,LPS-treated BV2 cells demonstrated significantly reduced cell viability,elevated expression and se-cretion of inflammatory cytokines (TNF-α,IL-6,IL-1β),decreased activities of SOD and GSH,and increased in-tracellular levels of MDA and ROS. Additionally,RAGE protein levels were upregulated,along with enhanced phos-phorylation of IκBα and NF-κB,leading to observable NF-κB nuclear translocation. The expression of the M1 marker iNOS was upregulated,while that of the M2 marker Arg-1 was downregulated. In contrast,in the LPS+Rema group,cell viability was restored,expression and secretion of inflammatory cytokines were attenuated,SOD and GSH activities were improved,and levels of MDA and ROS were reduced compared to the LPS group. Furthermore,RAGE protein expression and phosphorylation levels of IκBα and NF-κB were diminished,inhibiting NF-κB nuclear translocation. The expression of the M1 marker iNOS was downregulated,while that of the M2 marker Arg-1 was up-regulated. Conclusion Remimazolam mitigates LPS-induced inflammation by facilitating the transition of microglial cells from the M1 to the M2 phenotype via modulation of the NF-κB pathway and reduction of ROS production.

Objective To compare the therapeutic effects of laparoscopic transabdominal preperitoneal repair(TAPP)and Bassini herniorrhaphy in the treatment of inguinal hernia.Methods 107 patients with inguinal hernia from January 2021 to December 2024 were selected and divided into the Bassini group(53 cases were repaired by Bassini herniorrhaphy)and the TAPP group(54 cases were repaired by TAPP)by random number table method.The surgical-related indicators,pain degree,stress index levels,quality of life,rehabilitation effect and incidence of complications of the two groups of patients were compared.Results The operation time of the Bassini group was significantly shorter than that of the TAPP group,the intraoperative blood loss was significantly more than that in the TAPP group,and the hospital stay was significantly longer than that in the TAPP group,the differences were statistically significant(P<0.05).The visual analogue scale(VAS)score of the two groups of patients after surgery showed a trend of first increasing and then decreasing.The VAS scores of the TAPP group at 3 and 7 days after surgery were significantly lower than those of the Bassini group,and the differences were statistically significant(P<0.05).The levels of cortisol and norepinephrine in both groups of patients 3 days after the operation were significantly higher than those before the operation,and the Bassini group was significantly higher than the TAPP group,the differences were statistically significant(P<0.05).The total effective rate of the TAPP group was 98.15%,significantly higher than that of the Bassini group(83.02%),and the difference was statistically significant(P<0.05).The Short Form 36(SF-36)score of the two groups of patients one month after the operation was significantly higher than that before the operation,and the TAPP group was significantly higher than the Bassini group,the differences were statistically significant(P<0.05).The incidence of complications in the TAPP group was 3.70%,significantly lower than 18.87%in the Bassini group,and the difference was statistically significant(P<0.05).Conclusion Compared with Bassini herniorrhaphy,TAPP can effectively shorten the hospital stay,reduce intraoperative blood loss,lower postoperative pain and stress response,improve the postoperative quality of life of patients,enhance rehabilitation effect and reduce the incidence of complications.It is worthy of clinical promotion and application.

Objective To investigate the effects of inclined axial compressive force and flexion moment on the anterior and posterior shear stiffness of the lumbosacral segment.Methods Six fresh-frozen human cadaveric L5-S1 segments were tested under intact and two progressively impaired structural conditions:intact,a 4-mm bilateral facet joint gap,and anterior discectomy with nucleus pulposus removal plus circumferential release of the inner annular fibers(disc injury).A 300 N axial compressive force was applied either vertically downward or with a 10° or 20° anterior inclination through the disc's shear center.Anterior(0 N to 250 N)and posterior(-50 N to 0 N)shear tests were conducted using a material testing machine.These tests were repeated under a 5 N-m flexion moment.The relative motion between L5 and Si was measured using a three-dimensional motion capture system.Results In the intact state,the inclination of the axial compressive force did not significantly alter anterior or posterior shear stiffness.However,the application of a flexion moment increased anterior shear stiffness by 49.3％.Progressive structural damage resulted in incremental increases in anteroposterior shear translation and corresponding reductions in stiffness.Notably,under combined loading with axial compression and flexion moment,anterior stiffness decreased from 939 N/mm(intact)to 224 N/mm(disc injury),while posterior stiffness decreased from 572 N/mm to 217 N/mm.Within the low-load range,no significant differences in shear stiffness were observed across any structural conditions,regardless of axial force inclination or combined with a flexion moment.Conclusions This study supports the clinical view that retro-inclination of the pelvis serves as a compensatory mechanism to enhance segmental shear stability.However,this compensatory capacity gradually diminishes and ultimately fails as spinal degeneration progresses.

Objective To compare the therapeutic effects of laparoscopic transabdominal preperitoneal repair(TAPP)and Bassini herniorrhaphy in the treatment of inguinal hernia.Methods 107 patients with inguinal hernia from January 2021 to December 2024 were selected and divided into the Bassini group(53 cases were repaired by Bassini herniorrhaphy)and the TAPP group(54 cases were repaired by TAPP)by random number table method.The surgical-related indicators,pain degree,stress index levels,quality of life,rehabilitation effect and incidence of complications of the two groups of patients were compared.Results The operation time of the Bassini group was significantly shorter than that of the TAPP group,the intraoperative blood loss was significantly more than that in the TAPP group,and the hospital stay was significantly longer than that in the TAPP group,the differences were statistically significant(P<0.05).The visual analogue scale(VAS)score of the two groups of patients after surgery showed a trend of first increasing and then decreasing.The VAS scores of the TAPP group at 3 and 7 days after surgery were significantly lower than those of the Bassini group,and the differences were statistically significant(P<0.05).The levels of cortisol and norepinephrine in both groups of patients 3 days after the operation were significantly higher than those before the operation,and the Bassini group was significantly higher than the TAPP group,the differences were statistically significant(P<0.05).The total effective rate of the TAPP group was 98.15%,significantly higher than that of the Bassini group(83.02%),and the difference was statistically significant(P<0.05).The Short Form 36(SF-36)score of the two groups of patients one month after the operation was significantly higher than that before the operation,and the TAPP group was significantly higher than the Bassini group,the differences were statistically significant(P<0.05).The incidence of complications in the TAPP group was 3.70%,significantly lower than 18.87%in the Bassini group,and the difference was statistically significant(P<0.05).Conclusion Compared with Bassini herniorrhaphy,TAPP can effectively shorten the hospital stay,reduce intraoperative blood loss,lower postoperative pain and stress response,improve the postoperative quality of life of patients,enhance rehabilitation effect and reduce the incidence of complications.It is worthy of clinical promotion and application.

Objective To investigate the effects of inclined axial compressive force and flexion moment on the anterior and posterior shear stiffness of the lumbosacral segment.Methods Six fresh-frozen human cadaveric L5-S1 segments were tested under intact and two progressively impaired structural conditions:intact,a 4-mm bilateral facet joint gap,and anterior discectomy with nucleus pulposus removal plus circumferential release of the inner annular fibers(disc injury).A 300 N axial compressive force was applied either vertically downward or with a 10° or 20° anterior inclination through the disc's shear center.Anterior(0 N to 250 N)and posterior(-50 N to 0 N)shear tests were conducted using a material testing machine.These tests were repeated under a 5 N-m flexion moment.The relative motion between L5 and Si was measured using a three-dimensional motion capture system.Results In the intact state,the inclination of the axial compressive force did not significantly alter anterior or posterior shear stiffness.However,the application of a flexion moment increased anterior shear stiffness by 49.3％.Progressive structural damage resulted in incremental increases in anteroposterior shear translation and corresponding reductions in stiffness.Notably,under combined loading with axial compression and flexion moment,anterior stiffness decreased from 939 N/mm(intact)to 224 N/mm(disc injury),while posterior stiffness decreased from 572 N/mm to 217 N/mm.Within the low-load range,no significant differences in shear stiffness were observed across any structural conditions,regardless of axial force inclination or combined with a flexion moment.Conclusions This study supports the clinical view that retro-inclination of the pelvis serves as a compensatory mechanism to enhance segmental shear stability.However,this compensatory capacity gradually diminishes and ultimately fails as spinal degeneration progresses.

Objective To investigate the lung protection effect of remazolam under lung protection ventilation strategy in elderly patients undergoing laparoscopic upper abdominal surgery.Methods A prospective randomized controlled study was conducted on 60 patients aged 60 years or older who were scheduled to undergo laparoscopic upper abdominal surgery,including cholecystectomy,common bile duct choledocholithotomy,partial hepatectomy,and subtotal gastrectomy from October 2023 to October 2024.The patients were divided into 2 groups by random number table method:30 patients in the observation group received lung protective ventilation strategy and remazolam administration,and 30 patients in the control group received lung protective ventilation strategy and propofol administration.The inflammatory response indexes(TNF-α,IL-6,and hs-CRP),stress indexes(SOD,NE,and Cor),anesthesia quality(VAS score and Ramsay score),lung function(FVC,FEV1,and MVV％),blood gas indexes(pH,Lac,PaO2,and PaCO2),recovery quality(tracheal tube extubation time,respiratory recovery time,and awakening time),and pulmonary complications were compared between the two groups.Results In the observation group,the serum levels of inflammatory markers of TNF-α,IL-6,and hs-CRP at 2,12,and 24 h postoperatively were all lower than those in the control group(all P=0.000).Regarding stress response indicators,the serum SOD levels in the observation group were higher than those in the control group at 2,12,and 24 h postoperatively,while the NE and Cor levels were lower(all P=0.000).The VAS scores at 24 h postoperatively,and the Ramsay scores at 2 and 24 h postoperatively in the observation group were lower than those in the control group(all P=0.000).In the observation group,the FVC,FEV1,and MVV％were all higher than those in the control group at 48 h postoperatively(P＜0.05).The PaO2 level in the observation group was higher than that in the control group at 24 h postoperatively,and the Lac level was lower(P＜0.05).The respiratory recovery time and awakening time in the observation group were both shorter than those in the control group(P＜0.05).There were no significant differences between the two groups in extubation time and pulmonary complications(P＞0.05).Conclusions The lung protection effect of remazolam under lung protection ventilation strategy is better than that of propofol in elderly patients undergoing laparoscopic upper abdominal surgery.The lung protective effects may be achieved by alleviating perioperative stress response,improving oxygenation function,effective sedation,and reducing inflammatory response.

Objective To investigate the anti-inflammatory protective effects of remimazolam on microglial cells and elucidates the potential molecular mechanisms underlying these effects. Methods The mouse microglial cell line (BV2) was selected as the research object. The following groups were set up:the control group (complete medium),the Rema group (200 μg/mL remimazolam),the model group (1 μg/mL lipopolysaccharide,LPS),and different-concentration administration groups (1 μg/mL LPS+50,100,200 μg/mL remimazolam). In the Rema group,cells were treated with 200 μg/mL remimazolam alone for 26 h. In the model group,cells were treated with LPS for 24 h. In the different-concentration administration groups,cells were pre-treated with different concentrations of remimazolam for 2 h,and then treated with LPS for 24 h. The effects of LPS and remimazolam on the morphology of BV2 cells were observed and evaluated using an optical microscope. Cell viability was determined using the CCK-8 assay,while the expression and secretion of inflammatory cytokines were quantified by quantitative real-time PCR and ELISA. Reactive oxygen species (ROS) levels were measured using a fluorescent probe. Additionally,malondial-dehyde (MDA) content,superoxide dismutase (SOD) activity,and glutathione peroxidase (GSH) activity were evaluated using respective assay kits. Western blot analysis was conducted to examine the protein expression levels of Bax,Bcl-2,IL-1β,RAGE,NF-κB,p-NF-κB,IκBα,p-IκBα,iNOS,and Arg-1. Immunofluorescence staining was employed to visualize NF-κB nuclear translocation and M1/M2 polarization in the cells. Results Compared to the control group,LPS-treated BV2 cells demonstrated significantly reduced cell viability,elevated expression and se-cretion of inflammatory cytokines (TNF-α,IL-6,IL-1β),decreased activities of SOD and GSH,and increased in-tracellular levels of MDA and ROS. Additionally,RAGE protein levels were upregulated,along with enhanced phos-phorylation of IκBα and NF-κB,leading to observable NF-κB nuclear translocation. The expression of the M1 marker iNOS was upregulated,while that of the M2 marker Arg-1 was downregulated. In contrast,in the LPS+Rema group,cell viability was restored,expression and secretion of inflammatory cytokines were attenuated,SOD and GSH activities were improved,and levels of MDA and ROS were reduced compared to the LPS group. Furthermore,RAGE protein expression and phosphorylation levels of IκBα and NF-κB were diminished,inhibiting NF-κB nuclear translocation. The expression of the M1 marker iNOS was downregulated,while that of the M2 marker Arg-1 was up-regulated. Conclusion Remimazolam mitigates LPS-induced inflammation by facilitating the transition of microglial cells from the M1 to the M2 phenotype via modulation of the NF-κB pathway and reduction of ROS production.

Objective To investigate the lung protection effect of remazolam under lung protection ventilation strategy in elderly patients undergoing laparoscopic upper abdominal surgery.Methods A prospective randomized controlled study was conducted on 60 patients aged 60 years or older who were scheduled to undergo laparoscopic upper abdominal surgery,including cholecystectomy,common bile duct choledocholithotomy,partial hepatectomy,and subtotal gastrectomy from October 2023 to October 2024.The patients were divided into 2 groups by random number table method:30 patients in the observation group received lung protective ventilation strategy and remazolam administration,and 30 patients in the control group received lung protective ventilation strategy and propofol administration.The inflammatory response indexes(TNF-α,IL-6,and hs-CRP),stress indexes(SOD,NE,and Cor),anesthesia quality(VAS score and Ramsay score),lung function(FVC,FEV1,and MVV％),blood gas indexes(pH,Lac,PaO2,and PaCO2),recovery quality(tracheal tube extubation time,respiratory recovery time,and awakening time),and pulmonary complications were compared between the two groups.Results In the observation group,the serum levels of inflammatory markers of TNF-α,IL-6,and hs-CRP at 2,12,and 24 h postoperatively were all lower than those in the control group(all P=0.000).Regarding stress response indicators,the serum SOD levels in the observation group were higher than those in the control group at 2,12,and 24 h postoperatively,while the NE and Cor levels were lower(all P=0.000).The VAS scores at 24 h postoperatively,and the Ramsay scores at 2 and 24 h postoperatively in the observation group were lower than those in the control group(all P=0.000).In the observation group,the FVC,FEV1,and MVV％were all higher than those in the control group at 48 h postoperatively(P＜0.05).The PaO2 level in the observation group was higher than that in the control group at 24 h postoperatively,and the Lac level was lower(P＜0.05).The respiratory recovery time and awakening time in the observation group were both shorter than those in the control group(P＜0.05).There were no significant differences between the two groups in extubation time and pulmonary complications(P＞0.05).Conclusions The lung protection effect of remazolam under lung protection ventilation strategy is better than that of propofol in elderly patients undergoing laparoscopic upper abdominal surgery.The lung protective effects may be achieved by alleviating perioperative stress response,improving oxygenation function,effective sedation,and reducing inflammatory response.

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.