Aim To investigate the protective effect of ginsenoside Rb1 against apoptosis induced by H_2O_2. Methods H_2O_2 was used to build an oxidative stress-induced injury model in neonatal rat cardiomyocytes. After treated with gensenoside Rb1(20, 40, 80 mg?L -1),the apoptosis rate, the content of malondialdehyde (MDA), and the activity of superoxide dimutase (SOD) of the cardiomyocytes were examined. The intracellular calcium indicated by the fluorescence in cells were measured by the laser confocal microscope. Results Compared with the model group, the apoptosis rate and the content of MDA of the cardiomyocytes decreased greatly (P

Objective: To investigate the relationship between miRNA-196b-5p and miRNA-99a-5p expression and autophagy and apoptosis in multiple myeloma cells. Methods: Human myeloma cell line U266 and normal CD138+ plasma cells were selected as the research objects. The subjects were divided into 45 cases of multiple myeloma patients and 40 healthy controls. The expression of miRNA-196b-5p and miRNA-99a-5p was measured by real-time quantitative PCR, and Western blot was used to determine the expression of autophagy related protein LC3-Ⅱ, LC3-Ⅰ, P62, Beclin-1 expression, apoptosis related protein CL caspase3, CL caspase7, Bcl-2, Bax, and TGF-β/Smad pathway associated proteins TGF-β1, Smad2/3, p-Smad3 and Smad7. The cell apoptosis rate was determined by flow cytometry. The correlation between miRNA expression level and clinical characteristics of multiple myeloma patients was analyzed. Results: Compared with normal plasma cells, the expression of miRNA-196b-5p in myeloma cells increased significantly (0.43±0.15 vs 2.44±0.63 or 2.02±0.85, all P<0.001), the expression of miRNA-99a-5p was significantly decreased (1.87±0.61 vs 0.62±0.15 or 0.80±0.33, P<0.001), LC3-Ⅱ/LC3-Ⅰ increased significantly (P<0.05), Beclin-1 expression increased significantly (P<0.05), P62 expression decreased significantly (P<0.05). The expression of Bax, CL caspase3 and CL caspase7 decreased significantly (P<0.05), and the expression of Bcl-2 increased significantly (P<0.05) and apoptosis rate significantly decreased (P<0.05). After transfected with miRNA-196b-5p mimic or miRNA-99a-5p inhibitor, the LC3-Ⅱ/LC3-Ⅰ of CD138+ plasma cells increased significantly (P<0.05), the expression of Beclin-1 increased significantly (P<0.05), P62 expression decreased significantly (P<0.05), and the apoptosis rate significantly decreased (P<0.05). However, after autophagy inhibitor of 3-MA was administered, the apoptotic rate of the above reaction system did not change significantly (P>0.05). The expression of miRNA-196b-5p and miRNA-99a-5p was significantly correlated with DS and ISS stage in multiple myeloma patients (P<0.05). Conclusion miRNA-196b-5p and miRNA-99a-5p are closely related to the clinical characteristics of patients with multiple myeloma. The overexpression of miRNA-196b-5p and down regulation of miRNA-99a-5p could inhibit the apoptosis of myeloma cells by up regulation of autophagy, and the mechanism is related to the activation of the TGF-β/Smad signaling pathway.

Objective To investigate the effect and mechanism of IL-17 on heart failure(HF)in hy-pertensive rats based on NF-κB/sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)signa-ling pathway.Methods Thirty SPF male spontaneously hypertensive rats(SHR)aged 6-8 weeks were divided into control group,model group,phosphate buffer salt(PBS)solution injec-tion group(PBS group),IL-17 protein injection group(IL-17 group)and IL-17 and antibody injec-tion group(IL-17+IgG group),with 6 animals in each group.Hypertensive HF model was estab-lished,and corresponding agents were applied to the PBS group,IL-17 group and IL-17+IgG group intraperitoneally,respectively.The role of IL-17,NF-κB and SERCA2 in hypertensive HF was studied with HE staining,immunohistochemical assay,Western blotting,RT-qPCR and ELISA.Results Significantly higher serum levels of NT-proBNP and IL-17,enhanced myocardial expression of IL-17 mRNA and NF-κB protein,lower serum VEGF level,and down-regulated pro-tein level of SERCA2 in heart tissue were observed in the model group and the PBS group when compared with the control group(P＜0.01).The IL-17 group had obviously higher serum NT-proBNP and IL-17 levels and myocardial expression of IL-17 mRNA and NF-κB protein,and reduced serum VEGF level and SERCA2 protein level in heart tissue than the model group(P＜0.01).IL-17+IgG treatment resulted in notably lower serum IL-17 level and myocardial NF-κB protein level when compared with those of model group(8.98±1.20 vs 11.19±1.22,0.88±0.03 vs 0.93±0.03,P＜0.01),and also resulted in remarkably reduced serum levels of NT-proBNP and IL-17 and myocardial expression of IL-17 mRNA and NF-κB protein but increased serum VEGF level and SERCA2 protein level in heart tissue when compared with the IL-17 group(P＜0.01).The heart rate,SBP,IVSd,LVPWd,LVEDD and LVESD were significantly lower,while LVFS was notably higher in the IL-17+IgG group than the model group and IL-17 group(P＜0.01).The IL-17+IgG group had obviously higher LVEF than the IL-17 group[(70.81±6.50)％vs(62.77±5.43)％,P＜0.01].Conclusion IL-17/NF-κB/SERCA2 signaling pathway is involved in the regulation of inflammatory response after hypertensive HF,and inhibiting IL-17 can effective-ly improve the cardiac dysfunction caused by hypertensive HF.

Objective To invkstigatk thk kffkcts of intkrlkucin-6(IF-6)on mitochondrial biogknksis in ac-tivatkd astrocetks(LS)and thk rolk of adknosink monophosphatk protkin cinask( LMPK)in this prockss. Methods Thk LS isolatkd from nkonatal rat ckrkbral codkx wkrk purifikd and culturkd. Thk LS was randomle dividkd into 5 groups:control group,lipopolesaccharidk(FPS)+intkrfkron-γ(IPN-γ)group( IPN-γ group),FPS+IPN-γ+IF-6 group(IF-6 group),FPS+IPN-γ+IF-6A siANL+IF-6 group(siANL group),and FPS+IPN-γ+nkga-tivk control(NC)+IF-6 group(NC group),thkn,LS in kach group was trkatkd for 6 h. Tumor nkcrosis factor-α (TNP-α)mANL and intkrlkucin-1β(IF-1β)mANL kxprkssion wkrk dktkctkd be adopting rkvkrsk transcription-polemkrask chain rkaction(AT-PCA). Thk lkvkls of rkactivk oxegkn spkciks(AOS)wkrk dktkctkd be fluorksknt probk mkthod and thk lkvkls of adknosink triphosphatk(LTP)wkrk dktkctkd be lucifkrask mkthod. Ckll viabilite was kvaluatkd be using ckll count Kit-8. Pkroxisomk prolifkrator-activatkd rkckptor gamma coactivator-1α(PGC-1α),nuclkar rk-spiratore factor-1(NAP-1),mitochondrial transcription factor L( TPLM)and phospho-adknosink monophosphatk activatkd protkin cinask(p-LMPK)protkin kxprkssion wkrk dktkctkd be using Zkstkrn blotting. ResuIts (1)Com-parkd with thk control group,thk mANL kxprkssions of TNP-α and IF-1β(2. 548 ± 0. 154 vs. 1. 000 ± 0. 001,P﹦ 0. 000;2. 912 ± 0. 102 vs. 1. 000 ± 0. 001,P﹦0. 000),thk lkvkls of AOS[(245. 307 ± 13. 379)APR vs.(69. 460 ± 7. 257)APR,P﹦0. 000]and LTP[(1. 558 ± 0. 008)nmol╱mg protkin vs.(1. 016 ± 0. 025)nmol╱mg protkin,P﹦0. 000]significantle klkvatkd,and thk ckll viabilite(0. 840 ± 0. 013 vs. 1. 000 ± 0. 001,P﹦0. 000)dkcrkaskd,whilk thk protkin kxprkssion of NAP-1(0. 406 ± 0. 045 vs. 0. 157 ± 0. 016,P﹦0. 017),TPLM(0. 605 ± 0. 025 vs. 0. 416 ± 0. 013,P﹦0. 005)klkvatkd in FPS+IPN-γ group,and thk diffkrkncks wkrk significant(all P＜0. 05).(2)Comparkd with FPS+IPN-γ group,thk lkvkls of LTP[(1. 763 ± 0. 028)nmol╱mg protkin vs.(1. 558 ± 0. 008)nmol╱mg pro-tkin,P﹦0. 000],thk ckll viabilite(0. 910 ± 0. 024 vs. 0. 840 ± 0. 013,P﹦0. 008)wkrk klkvatkd,whilk thk protkin kx-prkssion of PGC-1α(0. 724 ± 0. 027 vs. 0. 586 ± 0. 039,P﹦0. 000),NAP-1(1. 036 ± 0. 211 vs. 0. 406 ± 0. 045,P﹦0. 000),TPLM(0. 786 ± 0. 058 vs. 0. 605 ± 0. 025,P﹦0. 002)and p-LMPK(1. 094 ± 0. 223 vs. 0. 755 ± 0. 084,P﹦0. 014)wkrk klkvatkd in IF-6 group,and thk diffkrkncks wkrk significant( all P＜0. 05).(3)Comparkd with IF-6 group,LTP[(1. 187 ± 0. 005)nmol╱mg protkin vs.(1. 763 ± 0. 028)nmol╱mg protkin,P﹦0. 000]and thk ckll viabili-te(0. 680 ± 0. 040 vs. 0. 910 ± 0. 024,P ﹦0. 000)all dkcrkaskd in siANL group,whilk thk protkin kxprkssion of PGC-1α(0. 631 ± 0. 022 vs. 0. 724 ± 0. 027,P﹦0. 020),NAP-1(0. 386 ± 0. 066 vs. 1. 036 ± 0. 211,P﹦0. 000), TPLM(0. 593 ± 0. 022 vs. 0. 786 ± 0. 058,P﹦0. 009)and p-LMPK(0. 365 ± 0. 063 vs. 1. 094 ± 0. 223,P﹦0. 002) significantle dkcrkaskd in siANL group,and thk diffkrkncks wkrk significant(all P＜0. 05). ConcIusions IF-6 can incrkask mitochondrial biogknksis in activatkd LS,which is probable mkdiatkd through up-rkgulating thk kxprkssion of LMPK.

Objective:To compare the clinical features, clinical efficacy, and prognosis of patients with double-hit and non-double-hit high-risk multiple myeloma (MM) and explored the clinical significance of high-risk cell karyotype in MM development.Methods:The clinical data of 73 high-risk MM patients admitted to the Department of Hematology of Fujian Provincial Hospital from January 2011 to February 2019 were retrospectively analyzed. Interphase fluorescence in situ hybridization was used to detect their karyotypes. Based on mSMART 3.0 risk stratification, we divided the patients into a double-hit group (28 cases) and a non-double-hit group (45 cases).Results:Fifteen patients in the double-hit group and 26 in the non-double-hit group received bortezomib-based chemotherapy. The median progression-free survival (PFS) in the double-hit and the non-double-hit groups was 8.0 months and 22.0 months, and the median overall survival (OS) was 10.0 months and not reached, respectively. Ten patients in the double-hit group and 12 in the non-double-hit group received bortezomib combined with lenalidomide (RVD) chemotherapy. The median PFS in the double-hit group and the non-double-hit group was 12.0 months and 24.0 months, and the median OS was 14.0 months and not reached, correspondingly. Both the PFS and OS of the double-hit group were significantly shorter than those of the non-double-hit group ( P<0.05). Univariate analysis results indicated that cytogenetic abnormalities, revised-international staging system (R-ISS), β2 microglobulin, and calcium had significant effects on PFS in high-risk MM patients ( P<0.05). The cytogenetic abnormalities, R-ISS, and β2 microglobulin were associated with OS in high-risk MM patients ( P=0.001). Multivariate Cox regression analysis showed that the cytogenetic grouping was an independent prognostic factor for OS and PFS in high-risk MM patients. The risk of disease progression was 3.160 times (95% CI: 1.364-7.318) and the risk of death was 2.966 times higher (95% CI: 1.205-7.306) in the double-hit group than those in the non-double-hit group. Calcium was an independent risk factor for PFS in the high-risk MM patients. Notably, the risk of disease progression in patients with calcium levels≥ 2.75 mmol/L was 2.667 times higher than that in patients with calcium<2.75 mmol/L (95% CI: 1.209-5.883). Conclusions:Double-hit patients are a highly specific group with worse high-risk MM prognosis. In such patients, the relapse is more common, the disease progression is faster, and the survival time is shorter than those in the non-double-hit patients.

Objective:To compare the clinical features, clinical efficacy, and prognosis of patients with double-hit and non-double-hit high-risk multiple myeloma (MM) and explored the clinical significance of high-risk cell karyotype in MM development.Methods:The clinical data of 73 high-risk MM patients admitted to the Department of Hematology of Fujian Provincial Hospital from January 2011 to February 2019 were retrospectively analyzed. Interphase fluorescence in situ hybridization was used to detect their karyotypes. Based on mSMART 3.0 risk stratification, we divided the patients into a double-hit group (28 cases) and a non-double-hit group (45 cases).Results:Fifteen patients in the double-hit group and 26 in the non-double-hit group received bortezomib-based chemotherapy. The median progression-free survival (PFS) in the double-hit and the non-double-hit groups was 8.0 months and 22.0 months, and the median overall survival (OS) was 10.0 months and not reached, respectively. Ten patients in the double-hit group and 12 in the non-double-hit group received bortezomib combined with lenalidomide (RVD) chemotherapy. The median PFS in the double-hit group and the non-double-hit group was 12.0 months and 24.0 months, and the median OS was 14.0 months and not reached, correspondingly. Both the PFS and OS of the double-hit group were significantly shorter than those of the non-double-hit group ( P<0.05). Univariate analysis results indicated that cytogenetic abnormalities, revised-international staging system (R-ISS), β2 microglobulin, and calcium had significant effects on PFS in high-risk MM patients ( P<0.05). The cytogenetic abnormalities, R-ISS, and β2 microglobulin were associated with OS in high-risk MM patients ( P=0.001). Multivariate Cox regression analysis showed that the cytogenetic grouping was an independent prognostic factor for OS and PFS in high-risk MM patients. The risk of disease progression was 3.160 times (95% CI: 1.364-7.318) and the risk of death was 2.966 times higher (95% CI: 1.205-7.306) in the double-hit group than those in the non-double-hit group. Calcium was an independent risk factor for PFS in the high-risk MM patients. Notably, the risk of disease progression in patients with calcium levels≥ 2.75 mmol/L was 2.667 times higher than that in patients with calcium<2.75 mmol/L (95% CI: 1.209-5.883). Conclusions:Double-hit patients are a highly specific group with worse high-risk MM prognosis. In such patients, the relapse is more common, the disease progression is faster, and the survival time is shorter than those in the non-double-hit patients.

Objective:To explore the feasibility and clinical efficacy of prone transpsoas lateral interbody fusion (PTP LIF) combined with posterior pedicle screw fixation for the treatment of lumbar degenerative diseases in the prone position.Methods:A total of 23 patients who underwent LLIF in the prone position at the First People's Hospital of Yunnan Province between March 2023 and October 2023 were retrospectively analyzed. The cohort comprised 9 males and 14 females, with a mean age of 55.5±8.8 years (range, 41-70 years). The clinical diagnoses included intervertebral disc herniation with endplate inflammation (3 cases), lumbar spinal stenosis (13 cases), lumbar spondylolisthesis (5 cases), and lumbar instability (2 cases). The surgical segments involved L 3, 4 (15 cases), L 4, 5 (6 cases), and L 3-L 5 (2 cases), with 21 cases involving a single segment and 2 cases involving double segments. The disc height and lumbar lordosis Angle before and after surgery were compared. Lower back pain was evaluated using the visual analogue scale (VAS), while lumbar spine function was assessed via the Oswestry Disability Index (ODI). Clinical efficacy was evaluated according to the modified MacNab criteria at the last follow-up. Results:All surgeries were successfully completed. The operation time was 120.2±21.4 min (range, 90-175 min), intraoperative blood loss was 131.1±40.8 ml (range, 60-200 ml), and the hospital stay was 6.2±1.6 days (range, 4-10 days). Follow-up was obtained for all 23 cases, with the follow-up time being 9.6±2.2 months (range, 6-13 months). One case of endplate damage occurred during surgery, two cases of transient psoas muscle weakness occurred postoperatively, and one case of lower limb pain and numbness was reported; no cases of wound infection or delayed healing were observed. The postoperative disc height improved compared to preoperative (6.8±1.9 mm; F=66.618, P<0.001). There was no statistically significant difference between 3 months postoperative (11.1±1.2 mm) and immediately postoperative (12.2±1.2 mm; P>0.05), but there was a statistically significant difference between the last follow-up (10.7±1.1 mm) and immediately postoperative ( P<0.05). The postoperative lumbar lordosis angle improved compared to preoperative (35.3°±5.4°; F=19.465, P<0.001), with no statistically significant difference between 3 months postoperative (44.1°±5.4°) and immediately postoperative (47.8°±6.6°; P>0.05), but there was a statistically significant difference between the last follow-up (43.2°±5.3°) and immediately postoperative ( P<0.05). The postoperative VAS score improved compared to preoperative (6.3±1.1 points; F=79.931, P<0.001), and the last follow-up (1.1±1.1 points) showed further improvement compared to 3 months postoperative (1.7±1.4 points; P<0.05). The postoperative ODI improved compared to preoperative (69.9%±7.4%; F=592.392, P<0.001), with 3 months postoperative (23.1%±3.1%) showing improvement compared to 1 month postoperative (29.2%±3.1%), and the last follow-up (17.5%±3.6%) showing further improvement compared to 3 months postoperative ( P<0.05). At the last follow-up, the modified MacNab criteria were: excellent in 16 cases, good in 5, fair in 2, with an excellent and good rate of 91% (21/23); 7 cases of cage subsidence were observed, with no cases of internal fixation loosening. Conclusion:PTP LIF combined with pedicle screw fixation for the treatment of lumbar degenerative diseases is safe and effective, with satisfactory short-term postoperative outcomes.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Proteomics ; COVID-19/prevention & control* ; Vaccination ; Antibodies ; Antibodies, Viral ; Antibodies, Neutralizing