1.Mechanism of Shenshuai Xiezhuo Decoction in Intervention of Chronic Kidney Disease Combined with Atherosclerosis Based on Regulation of PI3K/Akt/mTOR Signaling Pathway by miRNA126
Gengxin LIU ; Gedi ZHANG ; Wenqi YUAN ; Fusheng LI ; Min GUO ; Fuli LUO ; Ziyou YAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):48-55
ObjectiveExploring the role of microRNA126 (miRNA126) in chronic kidney disease combined with atherosclerosis (CKD AS) by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway and the mechanism of Shenshuai Xiezhuo decoction in the intervention of CKD AS rats with 5/6 nephrectomy combined with high-fat feeding. MethodA total of 60 SD rats were randomly divided into sham operation group, model group, losartan group, and low, medium, and high dose groups of Shenshuai Xiezhuo decoction. The CKD AS rat model was established by 5/6 nephrectomy combined with high-fat feeding for 10 weeks. The low, medium, and high dose groups (6.0, 12.0, 24.0 g·kg-1·d-1) of Shenshuai Xiezhuo decoction and the losartan group (20 mg·kg-1·d-1) were gavaged, and the corresponding intervention was carried out for eight weeks. Then, the rats were killed, and samples were collected for corresponding detection. Fully automated biochemical analyzers were used to detect kidney function and blood lipids in rats: blood creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels. Hematoxylin-eosin (HE) and Masson staining of aortic tissue and pathological observation under a light microscope were carried out, and autophagosomes and autophagy lysosomes were observed by transmission electron microscopy. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to determine the mRNA levels of miRNA126, PI3K, Akt, and mTOR in rats, and Western blot was used to determine the protein expression levels of phosphorylated (p)-PI3K, PI3K, p-Akt, Akt, p -mTOR, mTOR, benzyl chloride 1 (Beclin-1), and microtubule-associated protein light chain 3Ⅱ/Ⅰ (LC3Ⅱ/LC3Ⅰ). ResultCompared with the sham operation group, the serum SCr, BUN, TC, TG, and LDL-C in the model group were significantly increased (P<0.01). Compared with the model group, the SCr, BUN, TC, TG, and LDL-C were decreased in the losartan group and low, medium, and high dose groups of Shenshuai Xiezhuo decoction (P<0.05). Compared with the sham operation group, thickening plaques, infiltration of mononuclear macrophages, a small number of foam cells, disordered arrangement of smooth muscle fibers in the tunica media, and increased collagen fibers were observed in the model group, and the lesions in the losartan group and Shenshuai Xiezhuo decoction groups were alleviated compared with those in the model group. Compared with the model group, the number of autophagosomes and autophagy lysosomes increased in the medium and high dose groups of Shenshuai Xiezhuo decoction. Compared with the sham operation group, the expression of miRNA126 in the aortic tissue of the model group was significantly decreased (P<0.01), and the mRNA expressions of PI3K, Akt, and mTOR were significantly increased (P<0.01). Compared with the model group, the expression of miRNA126 in the aortic tissue of rats in high, medium, and low dose groups of Shenshuai Xiezhuo decoction and losartan group was significantly increased (P<0.01), while the mRNA expressions of PI3K, Akt, and mTOR were significantly decreased (P<0.01). Compared with the sham operation group, the protein expressions of p-PI3K, PI3K, p-Akt, Akt, p-mTOR, and mTOR in the model group were significantly increased (P<0.01), while the protein levels of Beclin-1, LC3Ⅰ, and LC3Ⅱ were significantly decreased (P<0.01). Compared with the model group, the protein expressions of p-PI3K, PI3K, p-Akt, Akt, p-mTOR, and mTOR in the losartan group and low, medium, and high dose groups of Shenshuai Xiezhuo decoction were decreased (P<0.05), while the protein levels of Beclin-1 and LC3Ⅱ/LC3Ⅰ were increased (P<0.05). ConclusionThe expression of miRNA126 is decreased in the aortic tissue of CKD AS rats, and the PI3K/Akt/mTOR pathway is activated to inhibit autophagy flux. Shenshuai Xiezhuo decoction regulates the PI3K/Akt/mTOR signaling pathway through miRNA126, restores the autophagy of aortic endothelial cells, protects the damage of CKD vessels, reduces the formation of As plaques, and slows the development of cardiovascular complications.
2.Retrospective analysis of serum protein electrophoresis screening for monoclonal gammopathy in 533 989 cases
Ruojian SHEN ; Wenqi SHAO ; Jing ZHU ; Yifeng SHEN ; Baishen PAN ; Beili WANG ; Wei GUO
Chinese Journal of Laboratory Medicine 2024;47(1):65-71
Objective:To compare the distribution differences of serum protein electrophoresis (SPE) among different gender and age individuals, and to explore the clinical application of SPE screening monoclonal gammopathy.Methods:A retrospective analysis was conducted based on the SPE results obtained from 533 989 cases enrolled from January 2018 to December 2019 at Zhongshan Hospital Affiliated to Fudan University. Among these patients, 435 479 inpatients were from departments of hematology, nephrology, spinal surgery, endocrinology, and rheumatology and immunology; and 98 510 were apparently healthy individuals. The distributions of albumin, α1 globulin, α2 globulin, β1 globulin, β2 globulin and γ globulin in different gender and age groups (≤20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, ≥91 years old) were compared. A total of 10 014 cases were selected by immunofixation electrophoresis (IFE). The positive detection rates of different SPE bands and IFE bands were analyzed. The sensitivity and specificity of SPE methods were determined according to IFE results as the gold standard.Results:No significant difference was examined in the proportion of SPE bands between different genders ( P>0.05). There were statistically significant differences in the proportion of albumin bands between apparently healthy individuals and hospitalized patients at different ages (apparently healthy individuals: F=5.12, P<0.05, inpatients: F=4.18, P<0.05), and all of them decreased with the increase of age. The proportion of γ globulin bands increased with age (apparently healthy individuals: F=1.34, P<0.05; inpatients: F=1.24, P<0.05). The sensitivity of SPE was 69% (2 098/3 051), and the specificity was 97% (6 721/6 963). Compared with IFE method, the positive detection rate of monoclonal gammopathy was significantly different (χ2=5 049.94, P<0.05). The positive rate of monoclonal gammopathy in γ globulin region (21.11%, 2 114/10 014) was higher than that in β globulin region (3.28%, 328/10 014) (χ2=90.74, P<0.05) and β-γ globulin region (1.63%, 163/10 014) (χ2=44.34, P<0.05). IgG and IgM bands are common in γ globulin region. Among them, IgG-κ type accounted for 94.1% (995/1 058), IgG-λ type accounted for 94.8% (690/728), IgM-κ type accounted for 89.2% (222/249), IgM-λ accounted for 83.8% (62/74). IgA bands are common in β region, of which IgA-κ accounted for 49.8% (103/207) and IgA-λ accounted for 51.6% (149/289). The positive rate of monoclonal gammopathy of IgG-κ type was the highest (10.57%, 1 058/10 014), and the positive rate of monoclonal gammopathy of IgM-λ type was the lowest (0.74%, 74/10 014). Conclusions:With increasing age, the proportion of albumin band in SPE decreased and the proportion of γ globulin band increased. IgG and IgM type monoclonal gammopathy is mostly found in the gamma region, with a higher detection rate in IgG type. IgA type monoclonal gammopathy is mostly found in the β region, with a lower detection rate.
3.Characteristics and distribution of monoclonal gammopathy in clinical patients: a single-center study
Lina ZHU ; Wenqi SHAO ; Jing ZHU ; Ruojian SHEN ; Qun WU ; Baishen PAN ; Beili WANG ; Wei GUO
Chinese Journal of Laboratory Medicine 2024;47(1):72-77
Objective:To investigate the characteristics and distribution of monoclonal gammopathy in clinical patients.Methods:A total of 936 171 patients (508 449 males and 427 722 females) who received capillary zone electrophoresis in Zhongshan Hospital Affiliated to Fudan University from January 2012 to December 2021 were selected, from which 14 945 patients with abnormal bands were screened as the study subjects, including 10 173 males and 4 772 females and the age 21-102 (65±13) years old. According to the age, patients were divided into 8 groups: 21-30 years old (168 cases), 31-40 years old (405 cases), 41-50 years old (1 326 cases), 51-60 years old (3 068 cases), 61-70 years old (4 985 cases), 71-80 years old (3 288 cases), 81-90 years old (1 519 cases), and≥91 years old (186 cases). The diagnostic results of the 14 945 patients with abnormal bands were collected and were divided into tumor group (5 196 cases) and non-tumor disease group (9 749 cases) according to the presence of tumor. The distribution of abnormal bands in different gender, age, and disease groups were retrospectively analyzed. Among the 14 945 patients, 4 988 cases underwent immunofixation electrophoresis, excluding 336 negative cases and 412 cases of double clonal bands reaction, and 4 240 patients with monoclonal immunoglobulin (M protein) reaction were selected as the study subjects, including 2 794 males and 1 446 females aged 21-102 (67±12) years old. They were divided into 8 groups according to the age: 21-30 years old (18 cases), 31-40 years old (91 cases), 41-50 years old (364 cases), 51-60 years old (862 cases), 61-70 years old (1 455 cases), 71-80 years old (904 cases), 81-90 years old (486 cases), and≥91 years old (60 cases). The diagnostic results and immunoglobin subtypes (IgA-κ, IgA-λ, IgG-κ, IgG-λ, IgM-κ, IgM-λ, κ, λ) of patients were collected, and the distribution of monoclonal gammopathy in different gender, age and disease groups were retrospectively analyzed.Results:Among 936 171 patients, 14 945 cases showed abnormal bands in electropherograms with a detection rate of 1.60%; the detection rates of abnormal bands in males and females were 2.00% (10 173/508 449) and 1.12% (4 772/427 722), respectively, with a statistically significant difference ( P<0.01). There was a significant difference in the detection rate of abnormal bands among different age groups ( P<0.01); among them, the highest detection rate of abnormal band in group of ≥91 years old was 5.98%, and the ratio of male to female was 1.67∶1. Among the 14 945 cases of abnormal bands, patients aged 51-60, 61-70 and 71-80 accounted for 20.53% (3 068 cases), 33.36% (4 985 cases) and 22.00% (3 288 cases), respectively, and the differences among the age groups were statistically significant (χ 2=115.82, P<0.01). In the tumor group, the top 3 tumors with abnormal bands were plasmacytoma with 1 123 cases, lymphoma with 289 cases, and leukemia with 49 cases. The detection rate of abnormal bands in electropherograms of plasmacytoma was 89.92% (1 123/1 249), which was higher than that in lymphoma and leukemia [6.73% (289/4 296) and 6.40% (49/766), respectively, P<0.01]. Among 4 240 patients with positive M protein, the proportion of 51-60, 61-70 and 71-80 years old patients were 20.33% (862/4 240), 34.32% (1 455/4 240) and 21.32% (904/4 240), respectively, and the differences among age groups were statistically significant ( P<0.01). The results of M protein types showed that the proportion of IgG-κ type was the highest in both genders, with 32.28% (902/2 794) in males and 34.30% (496/1 446) in females. In the 21-30, 31-40, and 41-50 age groups, the proportion of IgG-λ was the highest, which were 38.89% (7/18), 36.26% (33/91) and 34.07% (124/364) in these groups respectively. However, the proportions of IgG-κ were the highest in either of the 51-60, 61-70, 71-80, 81-90 and ≥91 years old groups, which were 33.87% (292/862), 34.16% (497/1 455), 31.53% (285/904), 34.57% (168/486), 28.33% (17/60), respectively, and the differences among all age groups and gender groups had statistical significance ( P<0.01). Among patients with positive M protein in the tumor group, plasmacytoma accounted for 14.22% (603/4 240), followed by lymphoma 6.30% (267/4 240); among non-tumor diseases, M proteinemia accounted for the highest proportion (7.24%, 307/4 240), followed by pulmonary infection (5.47%, 232/4 240). Conclusions:The detection rate of abnormal bands in capillary zone electrophoresis may increase with age, and is higher in males than in females in the same age group; different malignant tumor diseases can also show abnormal bands in capillary zone electrophoresis, but they are still mainly hematological tumors. Among the positive results of M protein, 61-70 years old group accounts for the highest proportion; the most common type of monoclonal gammopathy is IgG type; in the age group of 21-50 years, the proportion of IgG-λ type is the highest; in the group of >50 years old, the proportion of IgG-κ type is the highest; in the diagnosis of positive monoclonal gammopathy, the top 3 diseases are all hematological diseases, including plasmacytoma, monoclonal gammopathies and lymphoma.
4.Effects of kinesio taping on the biomechanical characteristics of the lower limbs during side-step cutting
Jing YOU ; Wenqi HUANG ; Wei ZHENG ; Jieming LU ; Yanhua GUO ; Yuan GAO ; Zheyu XIONG
Chinese Journal of Tissue Engineering Research 2024;28(27):4383-4389
BACKGROUND:Kinesio taping has been widely used as a means of sports protection,but its role as a means to correct abnormal biomechanical changes of the lower limbs during side-step cutting remains unclear. OBJECTIVE:To analyze and compare the changes in lower limb kinematics and dynamics when the subjects complete the side-step cutting of the knee joint under the conditions of kinesio taping,placebo taping and blank control. METHODS:Thirty-nine male college students majoring in basketball were recruited as subjects.Each subject was tested with kinesio taping,placebo taping or no taping.The mechanical correction method was used to patch the dominant knee joint of each subject.The run-up speed of 4.5-5.5 m/s was selected to complete the 45° side-step cutting motion,and the kinematics and kinetics data were collected synchronously by the three-dimensional dynamic capture system and the force measuring platform.The kinematics and kinetics parameters at the moment of initial touchdown and peak ground reaction force were selected for data analysis.SPSS 27.0 software was used for statistical analysis of the test data. RESULTS AND CONCLUSION:Kinematic indexes:compared with no taping and placebo taping,the hip abduction and knee valgus angles at the initial touchdown moment were significantly decreased when kinesio taping was used(P<0.05);at the moment of peak lateral ground reaction force,the angles of hip abduction,knee valgus and ankle plantar flexion decreased significantly(P<0.05),and the knee flexion angle was significantly increased(P<0.05).Kinetic indexes:Compared with no taping,both kinesio taping and placebo taping significantly reduced hip abduction and external rotation torque,knee valgus and external rotation torque at the moment of initial touchdown(P<0.05),and significantly reduced peak vertical ground reaction force and peak horizontal backward ground reaction force(P<0.05);in addition,kinesio taping significantly reduced peak lateral ground reaction force compared with no taping and placebo taping(P<0.05).These results indicate that kinesio taping of the knee joint may improve some kinematic and kinetic indexes associated with lower limb injury risk factors during the completion of the side-step cutting in basketball specialized college students to some extent,and may have a positive effect on the prevention of injury during the side-step cutting.In addition,the trends in the effects of placebo taping and kinesio taping on the knee joint are more consistent in terms of changes in some indexes,suggesting that there may be a placebo effect on the mechanism of action of kinesio taping.
5.Effect of Qinji Liangxue mixture on animal models of hemorrhoids
Mengen ZHOU ; Peng LI ; Wenqi JIN ; Ruolin WANG ; Xiutian GUO
Acta Laboratorium Animalis Scientia Sinica 2024;32(1):33-39
Objective To explore the mechanism underlying the anti-hemorrhoid effects of Qingji Liangxue mixture(QLM).Methods Models of acute hemorrhoid in rats were established using a croton oil preparation(COP)and glacial acetic acid.A total of 80 SD female rats were randomly divided into two major groups:the COP group and the glacial acetic acid group,each consisting of 40 rats.In the COP group,rats were further randomly assigned to the following subgroups:control group 1(group CA),model group 1(group CB),low-dose QLM group 1-1(group CC),high-dose QLM group 1-2(group CD),and diosmin group 1(group CE),with eight rats in each subgroup.In the glacial acetic acid group,rats were randomly divided into the following subgroups:control group 2(group GA),model group 2(group GB),low-dose QLM group 2-1(group GC),high-dose QLM group 2-2(group GD),and diosmin group 2(group GE),with eight rats in each subgroup.Except for the control groups,all other subgroups were treated with COP or glacial acetic acid then treated with various drugs for 7 days.HE staining was used to observe anorectal histomorphology induced by COP and glacial acetic acid.ELIS As were used to measure serum levels of IL-6 and TNF-α induced by COP.Additionally,the area of perianal ulcers induced by glacial acetic acid was recorded.Twenty-four C57 mice were randomly divided into a control group(group A),low-dose QLM group(group B),high-dose QLM group(group C),and adrenal chromazone tablet group(group D).Results QLM significantly improved the pathological injury of animal models with similar hemorrhoids,reduced the score of pathological changes induced by COP(P<0.05),reduced the serum levels of IL-6 and TNF-α(P<0.05),reduced the area of perianal ulcers induced by glacial acetic acid(P<0.05),and shortened the time of coagulation and bleeding(P<0.05).Conclusions QLM has a good anti-hemorrhoid activity,which may be achieved by anti-inflammatory effects,hemostasis,and reducing tissue damage.
6.Impact of Baseline Non-high-density Lipoprotein Cholesterol Level on New-onset Cardiovascular Disease Among Postmenopausal Women
Lisha ZHANG ; Shouling WU ; Zhiqiang SHAO ; Jia GUO ; Jian WANG ; Wenqi XU ; Lu GUO ; Wenjuan LI ; Shuohua CHEN ; Yijun GAO
Chinese Circulation Journal 2024;39(1):61-67
Objectives:To investigate the impact of baseline non-high-density lipoprotein cholesterol(non-HDL-C)levels on new-onset cardiovascular disease(CVD)in postmenopausal women. Methods:This prospective cohort study selected 8 893 postmenopausal women who participated from 2006 to 2018 employee health examination of Kailuan Group and had complete total cholesterol(TC)and HDL-C data and no history of CVD.Participants were followed up to 31 December,2021.The primary endpoint was the occurrence of CVD or death.According to the Chinese Lipid Management Guidelines(2023),the participants were divided into non-HDL-C<4.1 mmol/L group(n=6 079),4.1 mmol/L≤non-HDL-C<4.9 mmol/L group(n=1 824)and non-HDL-C≥4.9 mmol/L group(n=990).The cumulative incidence of CVD in different groups of non-HDL-C levels was calculated using the Kaplan-Meier method and tested by log-rank analysis.Multivariate Cox regression model was used to analyze the effects of different non-HDL-C levels on CVD. Results:The mean follow-up time was(10.78±4.48)years,the cumulative incidence of CVD in different non-HDL-C level groups was 1.82%,3.24%and 2.89%,respectively.Kaplan-Meier survival curve showed a statistically significant difference in cumulative incidence among the three groups(log-rank P<0.0001).The results of Cox regression analysis showed that after adjusting for confounding factors such as age and sex,the HR(95%CI)values for CVD in the 4.1≤non-HDL-C<4.9 mmol/L group and the non-HDL-C≥4.9 mmol/L group were 1.40(1.13-1.74)and 1.35(1.03-1.78),respectively. Conclusions:High non-HDL-C levels are an independent risk factor for new-onset CVD in postmenopausal women.
7.Dissection of triple-negative breast cancer microenvironment and identification of potential therapeutic drugs using single-cell RNA sequencing analysis
Cheng WEILUN ; Mi WANQI ; Wang SHIYUAN ; Wang XINRAN ; Jiang HUI ; Chen JING ; Yang KAIYUE ; Jiang WENQI ; Ye JUN ; Guo BAOLIANG ; Zhang YUNPENG
Journal of Pharmaceutical Analysis 2024;14(8):1140-1157
Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.
8.Clinical evaluation of 2021 CKD-EPI equation and EKFC equation for estimated glomerular filtration rate
Yifeng SHEN ; Jing ZHU ; Jing YANG ; Wenqi SHAO ; Baishen PAN ; Beili WANG ; Wei GUO
Chinese Journal of Laboratory Medicine 2024;47(8):879-887
Objective:To retrospectively compare the clinical effects of the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the European Kidney Function Consortium (EKFC) equation based on creatinine to estimate glomerular filtration rate (eGFRcr) in a Chinese population.Methods:Patients and healthy individuals who visited the Zhongshan Hospital, Fudan University, between January 1, 2023, and December 31, 2023, were enrolled. The exclusion criteria were age<18 years, amputees, pregnant women, patients with muscle-related diseases, and patients who had undergone ultrafiltration or dialysis. The final study population included 660 078 individuals with a median age of 58 years (44, 68), 56.51% (372 987/660 078) of them were men. eGFRcr was calculated using the 2021 CKD-EPI, EKFC equations and initial 2009 CKD-EPI equation. Results were compared by differences (P 10), charges in population distribution and impact on staging of chronic kidney disease (CKD) by gender, age and creatinine results. Results:Compared with the results of 2009 and 2021 CKD-EPI eGFRcr, the P 10was 99.99% ( R 2=0.997). When applying the 2021 CKD-EPI eGFRcr equation, there was a slight overestimation of 3.77 (2.92, 4.47) ml/(min×1.73 m 2). 86.42% (570 455/660 078)participants had higher eGFRcr owing to the utilization of the 2021 CKD-EPI equation, which did not cause CKD stage change. A total of 12.35% (81 514/660 078) of subjects had different CKD stage with the higher 2021 CKD-EPI eGFRcr. 1.23% (8 109/660 078) had lower eGFRcr but no change in the CKD stage with the 2021 equation. Compared to the 2009 CKD-EPI eGFRcr results, the EKFC eGFRcr demonstrates P 10 values of 89.79%, with a correlation coefficient of R 2=0.976. The overall eGFRcr values using the EKFC equation were decreased by 4.63(-2.22, -7.04) ml/(min×1.73 m 2). There were 75.14% (495 992/660 078) individuals whose eGFRcr results were lower in EKFC equation, which did not cause CKD stage change. There were 15.63% (103 161/660 078) leading to a different CKD stage. Additionally, 8.80% (58 077/660 078) individuals with a higer eGFRcr result did not change CKD stage, while 0.43% (2 848/660 078) experienced a change in CKD staging due to the overestimation. Conclusions:Compared with the 2009 CKD-EPI eGFRcr results, the 2021 CKD-EPI eGFRcr results were slightly higher and had good consistency in different genders and ages. However, the EKFC eGFRcr was generally lower than 2009 CKD-EPI eGFRcr, showing poor consistency. The differences between eGFR equations should be considered when judging the CKD stage of patients.
9.Performance and clinical evaluation of two serum free light chain detection platforms in the diagnosis of multiple myeloma
Wen XU ; Yuyi HU ; Wenqi SHAO ; Jing ZHU ; Baishen PAN ; Beili WANG ; Wei GUO
Chinese Journal of Laboratory Medicine 2023;46(10):1026-1034
Objective:To compare the detection performance of serum free light chain (sFLC) in two platforms and evaluate the comparability of serum free light chain results in patients with multiple myeloma (MM).Methods:To evaluate the detection performance (repeatability, accuracy, linear range, reference range, interfering substances, etc.) of sFLC kit based on polyclonal antibodies. Spearman correlation analysis and Bland-Altman were used to analyze 214 sFLC results obtained on two detection platforms at the same time to evaluate the correlation between the results of the two methods and analyze the causes of methodological bias. 119 cases with aMM and 23 cases of disease control group (AL, WM, POEMS syndrome, MGUS, diffuse large B-cell lymphoma) initially diagnosed in the hematology department of Zhongshan Hospital of Fudan University from March 2020 to March 2021 were all included. A retrospective analysis was conducted to calculate the area under the curve of receiver operating characteristic (AUC-ROC) and obtain the optimal sensitivity and specificity cut-off points for the diagnosis of MM patients on monoclonal antibody platform.Results:Repeatability, accuracy, linear range, reference interval and anti-interfering capacity of the detection platform based on polyclonal antibodies were verified to meet clinical needs. The overall consistency of FLC/κ, FLC/λ and κ/λ ratios in two methods was 89.3%, 84.1% and 77.1% respectively; but the correlation results were highly heterogeneous. The correlation coefficient of FLC/κ R 2 was 0.922( P<0.001), while the correlation coefficients R 2of the FLC/λ and κ/λ ratios were only 0.349 and 0.441( P<0.001). After segment analysis, it was found that the correlation of FLC/λ was improved within the linear range and R 2 could rise to 0.78( P<0.001). Compared with monoclonal antibody platform, the vast majority points of FLC/κ fell within the 95% limit by Bland Altman analysis. While the results of FLC/λ on polyclonal antibody platform showed significant positive bias. The AUC of MM diagnosis on monoclonal antibody platform was 0.751 ( P=0.001), and the optimal cutoff value was 24.67. Conclusion:The overall consistency between the two platforms was good, but there were significant differences between the results, so they were not comparable and could not be interchanged. For monitoring the prognosis of patients with multiple myeloma, the same platform should be selected for testing.
10.Association Between Different Blood Pressure Levels at Baseline and Early-onset Heart Disease Among Young Population Under 40 Years Old
Wenjuan LI ; Yongchao WAN ; Lu GUO ; Wenqi XU ; Ping GU ; Shuohua CHEN ; Shouling WU ; Aijun XING
Chinese Circulation Journal 2023;38(12):1267-1273
Objectives:To explore the association between different blood pressure levels at baseline and early-onset heart disease among young adults under 40 years in China. Methods:This prospective cohort study included 35 993 subjects who participated in the physical examination of the employees of Kailuan Group for the first time from 2006 to 2012 and were younger than 40 years,with complete blood pressure data and had no history of heart disease.Participants were followed up to the end of 2021.The primary endpoint was early-onset heart disease(including coronary heart disease,atrial fibrillation,and heart failure).According to 2018 Chinese guidelines for the management of hypertension,the participants were divided into four groups:normal blood pressure group(n=13 208),elevated blood pressure group(n=16 576),stage 1 hypertension group(n=4 357),and stage 2-3 hypertension group(n=1 852).The cumulative incidence of heart disease among participants with different blood pressure levels at baseline was compared using log-rank test.Multivariate Cox proportional hazard regression model was used to analyze the impact of different blood pressure levels at baseline on early-onset heart disease in this cohort. Results:After a mean follow-up of(12.5±2.6)years,the cumulative incidence of early-onset heart disease in normal blood pressure group,elevated blood pressure group,stage 1 hypertension group,stage 2-3 hypertension group were 0.47%,0.97%,3.56%and 4.42%respectively(log-rank P<0.01).After adjusting for confounding factors such as age and sex,Cox regression analysis showed that the HR(95%CI)of heart disease in the elevated blood pressure group,hypertension grade 1 group and hypertension grade 2-3 group were 1.59(1.12-2.24),2.08(1.41-3.08)and 3.20(2.11-4.85)(all P<0.01),respectively,compared with the normal blood pressure group. Conclusions:Elevated blood pressure is a risk factor for early-onset heart disease among young Chinese population.

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