Clinical Analysis of Infants with Acute Lymphoblastic Leukemia (18 cases) / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL).@*METHODS@#The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed.@*RESULTS@#Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×109/L ［(3.92-470)×109/L］ at initial diagnosis, including 2 patients with WBC≥300×109/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%.@*CONCLUSION@#B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.

Correlation Analysis between Cerebrospinal Fluid Status and Prognosis in Childhood with Acute Lymphoblastic Leukemia by Flow Cytometry / 中国实验血液学杂志

OBJECTIVE@#To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM).@*METHODS@#The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed.@*RESULTS@#Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI- ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI- and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status.@*CONCLUSION@#Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.

Clinical Study on the Relationship between Gene Mutation Profile and Prognosis in Pediatric Acute Lymphocyte Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene mutation profile in children with acute lymphocyte leukemia (ALL) and to explore its prognostic significance.@*METHODS@#Clinical data of 249 primary pediatric ALL patients diagnosed and treated in the Department of Hematological Oncology of Wuhan Children's Hospital from January 2018 to December 2021 were analyzed retrospectively. Next-generation sequencing (NGS) was used to obtain gene mutation data and analyze the correlation between it and the prognosis of children with ALL.@*RESULTS@#227 (91.2%) were B-ALL, 22 (8.8%) were T-ALL among the 249 cases, and 178 (71.5%) were found to have gene mutations, of which 85 (34.1%) had ≥3 gene mutations. NRAS(23.7%), KRAS (22.9%),FLT3(11.2%), PTPN11(8.8%), CREBBP (7.2%), NOTCH1(6.4%) were the most frequently mutated genes, the mutations of KRAS, FLT3, PTPN11, CREBBP were mainly found in B-ALL, the mutations of NOTCH1 and FBXW7 were mainly found in T-ALL. The gene mutation incidence of T-ALL was significantly higher than that of B-ALL (χ2= 5.573，P＜0.05) and were more likely to have co-mutations (P＜0.05). The predicted 4-year EFS rate (47.9% vs 88.5%, P＜0.001) and OS rate (53.8% vs 94.1%, P＜0.001) in children with tp53 mutations were significantly lower than those of patients without tp53 mutations. Patients with NOTCH1 mutations had higher initial white blood cell count （128.64×109/L vs 8.23×109/L，P＜0.001）, and children with NOTCH1 mutations had a lower 4-year EFS rate than those of without mutations (71.5% vs 87.2%, P＝0.037).@*CONCLUSION@#Genetic mutations are prevalent in childhood ALL and mutations in tp53 and NOTCH1 are strong predictors of adverse outcomes in childhood ALL, with NGS contributing to the discovery of genetic mutations and timely adjustment of treatment regimens.

Clinical Study of Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation in Children / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical characteristics, treatment and prognosis of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and futher evaluate the occurring risk factors.@*METHODS@#The clinical data of 136 patients undergoing allo-HSCT in Wuhan Children's Hospital Affiliated to Tongji Medical College from August 2016 to August 2020 were retrospectively analyzed, clinical characteristics of children with intestinal aGVHD were observed. The risk factors of intestinal aGVHD were assessed by logistic regression while cumulative survival were analyzed by Kaplan-Meier method.@*RESULTS@#Among 136 patients intestinal aGVHD occurred in 24 (17.6%) cases, with 4 cases of grade II, 20 cases of grade III-IV, and the median occurrence time was 28(10-63) days. The clinical manifestations were diarrhea with intermittent abdominal pain, 17 cases with nausea and vomiting, 11 cases with fresh bloody stool, and 8 cases with skin rash before intestinal aGVHD. The average time for treatment was 33(11-100) days. 18 cases received electronic colonoscopy and histopathology examination. 20 out of 24 cases achieved remission after treatment, and the total effective rate was 83.3%. Finally, 9 out of 24 cases died during the follow-up time. Survival analysis showed that the cumulative survival rate of patients with intestinal aGVHD (15/24, 62.5%) were significantly lower than those without intestinal aGVHD (101/112, 90.2%) (Log-rank test, P=0.001). Univariate analysis showed that recipient age, sex, primary disease, donor age, donor sex, donor-recipient blood type, conditioning regimen, prophylaxis of GVHD, dosage of ATG, engraft time of blood platelet and neutrophils, and number of MNC/CD34+ were not risk factors for intestinal aGVHD (P>0.05). Only the type of HSCT (χ2=16.020, P=0.001) and matched degree of HLA (χ2=15.502, P=0.001) had statistical significance with intestinal aGVHD (P<0.05). Multivariate analysis showed that only HLA-mismatched unrelated donor was the risk factor for intestinal aGVHD for children (P=0.014，OR=16，95%CI 1.735-147.543).@*CONCLUSION@#Intestinal aGVHD is a risk factor for cumulative survial of patients who received allo-HSCT in children and HLA-mismatched unrelated donor is its independent risk factor.

Recurrent and Refractory Langerhans Cell Histiocytosis in Children Treated with the Combination of Cladribine and Cytarabine / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children.@*METHODS@#Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae.@*RESULTS@#Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus.@*CONCLUSION@#2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.

The Relationship between Plasma sST2/Reg3α Levels and Acute Graft-Versus-Host Disease in Children After Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To explore the relationship between plasma sST2/Reg3α levels and acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 29 pediatric patients received allo-HSCT treatment in Department of Hematology and Oncology of Wuhan Children's Hospital from January 2019 to January 2020 were collected. Peripheral blood samples were collected at 14 and 28 day after allo-HSCT. The plasma concentrations of sST2 and Reg3α were detected by Luminex assay.@*RESULTS@#Among 29 patients there were 15 males and 14 females with a median age of 53 (29-117) months. After allo-HSCT, 18 patients developed grade 0-I aGVHD; while 11 patients developed grade II-IV aGVHD. These included skin aGVHD in 6 cases, gastrointestinal aGVHD (GI-aGVHD) in 3 cases and gastrointestinal/skin aGVHD in 5 cases. Plasma sST2 level in II-IV aGVHD group showed significantly higher than that in 0-I aGVHD group at 28 days after allo-HSCT [101.81 (73.94-150.77) ng/ml vs 48.97 (28.82-56.69) ng/ml, P=0.021]. Also, the plasma sST2 level was significantly higher in GI-aGVHD group than that in no-aGVHD group at 28 days after allo-HSCT [118.74 (87.00-243.36) ng/ml vs 48.97 (23.55-61.40) ng/ml, P=0.004]. Plasma sST2 level ≥65.34 ng/ml at 28 days after allo-HSCT showed a sensitivity of 85.7% and a specificity of 87.5% in predicting II-IV aGVHD. And the patients with a plasma sST2 level ≥65.34 ng/ml showed a significantly higher incidence of II-IV aGVHD than those with plasma sST2 level of < 65.34 ng/ml after allo-HSCT (P=0.021). There was no significant difference in plasma Reg3α level between the patients with II-IV aGVHD and the non-aGVHD ones.@*CONCLUSION@#The increasing plasma sST2 level after allo-HSCT in children indicates the development of II-IV aGVHD, so sST2 is promising as a biomarker for predicting II-IV aGVHD.

Upregulation of long non-coding RNA XIST has anticancer effects on epithelial ovarian cancer cells through inverse downregulation of hsa-miR-214-3p / 부인종양

OBJECTIVE: The present study is to evaluate the biological functions of long non-coding RNA (lncRNA), X-inactive specific transcript, X-inactive specific transcript (XIST) in human epithelial ovarian cancer (EOC). METHODS: XIST was upregulated in EOC cell lines, CAOV3 and OVCAR3 cells by lentiviral transduction. The effects of XIST overexpression on cancer cell proliferation, invasion, chemosensitivity and in vivo tumor growth were investigated, respectively. Possible sponging interaction between XIST and human microRNA hsa-miR-214-3p was further evaluated. Furthermore, hsa-miR-214-3p was overexpressed in XIST-upregulated CAOV3 and OVCAR3 cells to evaluate its effect on XIST-mediated EOC regulation. RESULTS: Lentivirus-mediated XIST upregulation had significant anticancer effects in CAOV3 and OVCAR3 cells by suppressing cancer cell proliferation, invasion, increasing cisplatin chemosensitivity and inhibiting in vivo tumor growth. Hsa-miR-214-3p was confirmed to directly bind XIST, and inversely downregulated in XIST-upregulated EOC cells. In EOC cells with XIST upregulation, secondary lentiviral transduction successfully upregulated hsa-miR-214-3p expression. Subsequently, hsa-miR-214-3p upregulation functionally reversed the anticancer effects of XIST-upregulation in EOC. CONCLUSION: Upregulation of lncRNA XIST may suppress EOC development, possibly through sponging effect to induce hsa-miR-214-3p downregulation.

Expressions and prognostic significance of PTEN and PD-1 protein in patients with classical Hodgkin's lymphoma / 中华血液学杂志

Objective: To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin's lymphoma (CHL) to further determine their clinical role and prognostic significance. Methods: The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed. Results: This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL. Conclusions: This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.

Influence of probucol combined atorvastatin on hemodynamics and blood lipids in patients with large artery cerebral infarction / 心血管康复医学杂志

Objective :To analyze influence of probucol combined atorvastatin on hemodynamics and blood lipids in patients with large artery cerebral infarction (LACI).Methods :A total of 92 LACI patients were randomly and e-qually divided into atorvastatin group and combined treatment group (received atorvastatin combined probucol ) , both groups were treated for six months .Therapeutic effect etc indexes before and after treatment were compared between two groups .Results :Compared with atorvastatin group after six-month treatment ,there were significant reductions in levels of TC [ (4.57 ± 0.82) mmol/L vs.(3.23 ± 0.71) mmol/L] ,TG [ (1.37 ± 0.45) mmol/L vs. (1.02 ± 0.34) mmol/L] ,LDL-C [ (2.52 ± 0.83) mmol/L vs .(1.50 ± 0.54) mmol/L] ,oxidized low density lipo-protein [ox-LDL ,(78.36 ± 14.05) mg/L vs.(58.37 ± 12.00) mg/L] ,left and right middle cerebral artery pulsatili-ty index (PI) [left :(0.84 ± 0.25) vs.(0.74 ± 0.14) ,right :(0.84 ± 0.23) vs.(0.74 ± 0.16)] and inflammatory factors ,and significant rise in total effective rate (69.57% vs.89.13% P＝0.020) ,left and right middle cerebral systolic blood flow velocity (Vs) [left :(87.45 ± 15.58) cm/s vs.(95.48 ± 18.34) cm/s ,right :(89.27 ± 14.36) cm/s vs.(96.18 ± 14.03) cm/s] and mean blood flow velocity (Vm) [left :(60.90 ± 16.19) cm/s vs .(76.19 ± 17.40) cm/s ,right :(62.08 ± 17.23) cm/s vs .(91.38 ± 19.26) cm/s] in combined treatment group ,P＜0.05 or ＜0.01. There was no significant difference in drug adverse reactions incidence rate between two groups , P＝1. 000 .Conclu-sion :Therapeutic effect of probucol combined atorvastatin is significantly better than that of pure atorvastatin on large artery cerebral infarction .It can more significantly improve blood lipids and intracranial artery hemodynamics with anti-inflammatory effects .

Clinical study on the serum peroxisome proliferater-activated receptor γlevels in patients with rheumatoid arthritis associated with osteoporosis / 中华风湿病学杂志

Objective To investigate the value of serum levels of peroxisome proliferater-activated receptor (PPAR)γin patients with rheumatoid arthritis (RA) and to explore the associations between serum PPARγwith disease activity of RA and RA-associated osteoporosis (OP).Methods One hundred and one cases of hospitalized patients with RA were enrolled.A total of 88 normal subjects during the same period were recruited as the control group.Levels of serum PPARγwere detected by enzyme linked immunosorbent assay (ELISA).Bone mineral density (BMD) was measured by dual energy X-ray absortiometry.All the clinical and laboratory indexes of RA patients were recorded in detail.T-test (or t'-test) was used for comparison of measurement data between the two groups,non-parametric test was applied for skewed distribution data.Comparison of incidence was analyzed with x2 test,correlation analysis was represented ascorrelation coefficient (r).Results Binary logistic regression analysis was used for multivariate regression analysis.Serum levels of PPARγ(3.38/4.00 ng/ml) in RA patients were higher than thosein normal subjects (2.63/1.76) ng/ml (Z=3.204,P=0.001).The positive rate of serum levels of PPARγin RA was 35.6％ (36/101),while the positive rate in the controls was (2.3％,2/88,x2=32.602,P＜0.01).The incidence of OP in RA was 34.7％(35/101;while the levels of serum PPARγ in RA without OP at femur area (femoral neck,total hip) and lumbar spine (L1,L1-4) were higher than that in RA with OP (P＜0.05).Serum levels of PPARγ between groups with different disease activity had no significant difference (P＞0.05).Serum levels of PPARγ in RA with negative RF or negative anti-CCP were higher than thosetin the RA group with positive RF or positive anti-CCP(P＜0.05).Serum levels of PPARγ in RA were negatively correlated with serum RF,anti-CCP,hemoglobin (P ＜0.05-0.001),and positively correlated with erythrocyte sedimentation rate,platelet,BMD at sites of femur neck andWard (P＜0.05-0.001).Results of binary logistic regression analysis showed that levels of serum PPARγwere protective factors in RA for OP at femurneck [OR=0.577,P=0.005,95％CI (0.394-0.846)],and total hip [OR=0.754,P=0.033,95％CI (0.581-0.978)].Condusion Serum levels of PPARγ in patients with RA are significantly increased,and negatively correlate with autoantibodies.Serum levels of PPARγare protective factors for OP in RA.

Association between balance and fails with spinal osteoporotic fractures in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the prevalence of balance deficiency and falls in patients with rheumatoid arthritis (RA),and to explore the effect of above factors on osteoporotic fracture (OPF).Methods A total of 386 patients with RA and 158 age,gender-matched normal subjects from Jan 2013 to Oct.2015 were recruited.Antero-posterior and lateral X-rays scanning of vertebral column (T5-L5) were conducted for each individual,and semi-quantity method was used as the standard for determining vertebral OPF.Falls in 296 RA were recorded in details.The balance ability of 263 cases were measured by Berg balance scale.Statistical analysis was performed with ttest and Chi-square text and logistic regression analysis.Results ① The prevalence of vertebral OPF in RA was 17.4％(67/386),which was 4.5 times the prevalence of the control group (6/158,3.8％) (x2=17.743,P＜0.01).The occurrence rate of falls in RA was 20.3％ during the last year (60/296).② Compared to RA without OPF,patients with OPF had lower Berg balance score (43±14 vs 33±15,t=4.150,P＜0.01).Patients with falls also had lower Berg balance scale scorethan that in RA without falls (31± 16 vs 41±14,t=4.373,P＜0.01).③ The prevalence of falls during the last year in RA with vertebral OPF was 39.2％ (20/51),which was higher than that in RA without OPF (15.7％,22/140) (x2=12.036,P=0.01).The prevalence of falls during the last year in RA with Berg balance scale score ＜40 was 32.5％,which was higher than that in patients with Berg balance scale score≥40 (P＜0.01).Incidence of Berg balance scale score ＜40 in patients with OPF (68.8％,33/48) was higher than that in group without OPF (29.7％,35/118) (x2=21.558,P＜0.01).④ Logistic regression analysis found that age [OR=1.064,P=0.001,95％CI (1.025,1.103)] and falls [OR=2.735,P=0.021,95％CI(1.168,6.407)] were risk factors for OPF in RA patients,while Berg balance scale score [OR=0.957,P=0.016,95％CI (0.924,0.992)] was negatively correlated with spinal OPF in RA patients.Conclusion Falls and decreased balance capacity in RA are closely correlated with OPF in RA.

Comparison of clinical and laboratory features between patients with ankylosing spondylitis and non-radiolographic axial spondyloarthritis / 中华风湿病学杂志

Objective To analyze and compare the clinical and laboratory features between patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA).Methods One hundred and forty-one patients with AS and 73 cases with nr-axSpA were recruited.Clinical and laboratory indexes of individuals were recorded in detail,Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) crp were calculated.Spondyloarthritis research consortium of Canada (SPARCC) score standard was used to evaluate the degree of bone marrow edema in sacr-oiliac joint under magnetic resonance imaging scanning.T test,rank test and x2 test were used for statistical analysis.Results The average age of patients with AS was obviously higher than that of patients with nr-axSpA (t=4.962,P＜0.01).Patients with AS were more often male,and those with nr-axSpA were more often female (82.0％ of the AS patients were men and 49.3％ of the nr-axSpA patients were men (x2=24.079,P＜0.01).Disease duration of AS was significantly longer than that of the nr-axSpA (Z=6.396,P＜0.01).The incidence of human leukocyte antigen (HLA)-B27 positive in AS was 89.4％,which was similar to that in patients with nr-axSpA (84.9％) (x2=0.884,P＞0.05).21.6％ (21 cases) of patients with AS had peripheral swollen joints,which was higher than that in nr-axSpA (2.2％,x2=8.861,P=0.003).Forty cases in AS had tender joints (41.2％),only 6 patients in nr-axSpA had tender joints (13.3％,x2=11.458,P＜0.01).Serum erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) levels in patients with AS were clearly higher than those in nr-axSpA (P＜0.01) patients.In AS,the patient global assessment (PGA),BASDAI and ASDAScrp value was significantly higher than that in nr-axSpA (P＜0.01).There were no differences in SPARCC score or incidence of bone marrow edema in sacroiliac joint in magnetic resonance imaging scanning between AS and nr-axSpA (P＞0.05).Percentage of patients with occipit-to-wall distance higher than 0 cm in AS was higher than that in nr-axSpA,and the mean distance of fingers to ground in AS was also higher than that in nr-axSpA (x2=19.844,P＜0.01;Z=5.724,P＜0.01).Chest expansion degree and Schboer's test in AS was much lower than that in nr-axSpA,respectively (Z=3.083,P=0.002;Z=5.103,P＜0.01).BASFI in AS was higher than that in nr-axSpA (Z=5.840,P＜0.01).The ratio of joint function in AS was obviously worse than that in nr-axSpA (x2=1 1.369,P=0.01).Conclusion Compared to patients with nr-axSpA,AS patients are male predominant,and have severer inflammation in clinical and laboratory findings and are worse in functional status.

Clinical research of sarcopenia and vitamin D deficiency in rheumatoid arthritis patients with osteoporosis / 中华风湿病学杂志

Objective To investigate the effect of sarcopenia and vitamin D deficiency on osteoporosis (OP) in patients with rheumatoid arthritis (RA).Methods Six hundred and forty-eight patients with RA were enrolled into the study,while 158 normal subjects were recruited as the control group.Bone mineral density (BMD) at total hip and lumbar vertebra 2-4 were measured by dual energy X-ray absorptiometry (DEXA),limbs skeletal muscle mass was determined in 267 patients with RA and 156 normal subjects by bioelectrical impedance method.Serum 25-hydroxy vitamin D [25(OH)D] levels were determined by electrochemiluminescence in 234 RA patients and 68 normal subjects.Clinical and laboratory features,daily dosage and duration of glucocorticoid (GC) were recorded.Numerical data and categorical data comparisons were analyzed using t test,x2 test,linear correlation analysis,single factor analysis of variance test and Logistic regression analysis test.Results ① Incidence of OP in RA (37.8％,245/648) was significantly higher than that in the controls (13.9％,22/158)(x2=32.712,P＜0.01).Incidence of sarcopenia was evidently higher in RA,compared with normal subjects [55.8％(149/267),9.0％(14/156),x2=91.176,P＜0.01].Percentage of sarcopenia was higher in RA with OP compared with RA without OP group [76.6％(49/64),39.3％(35/89),x2=20.848,P＜0.01].②Compared to control group,serum 25 (OH)D levels were significantly lower in RA group [(13.4±9.7) ng/ml,(22.4±6.3) ng/ml,t=9.063,P＜0.01].Rate of vitamin D deficiency iu RA was also higher than that in controls [80.8％(189/234),36.8％(25/68),x2=49.412,P＜0.01].③The differences of serum 25 (OH)D levels among different bone metabolic state groups at lumbar vertebra in RA (normal bone mass,osteopenia,OP) were statistically significant (F=6.263,P=0.003),whichrepresented a clearly decreasing trend along with the decreasing of serum 25 (OH)D levels (P=0.001).④Linear correlation analysis found that skeletal muscle mass indexes at limbs in RA were positively correlated with BMD and serum 25 (OH)D levels (P＜0.05).⑥Logistic Regression analysis revealed that sarcopenia (OR=4.373,P=0.002),age (OR=1.083,P=0.001) and duration of disease (OR=1.074,P=0.029) were the risk factors for occurrence of OP in patients with RA.Conclusion Sarcopenia generally exists in patients with RA,which is correlated with decreasing of serum 25 (OH)D levels,and also is the risk factor for the occurring of OP in RA.

Associations between balance ca pacity declining and sarcopenia with spinal osteoporotic fracture in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the prevalence of balance capacity declining and sarcopenia in patients with rheumatoid arthritis (RA),and to explore the effect of balance capacity declining and sarcopenia on spinal osteoporotic fracture (OPF)in RA. Methods A total of 963 hospitalized patients with RA and 158 age, gender-matched normal subjects from Jan. 2013 to Oct. 2015 were recruited from department of Rheumatology and Immunology, the first affiliated hospital of Anhui Medical University. Anteroposterior and lateral X-ray scanning of vertebral column(T5-L5)was conducted for every individual and semi-quantity method were used as the standard for determining vertebral OPF. Two hundred and sixty-seven RA patients and 156 control individuals were measured by bioelectrical impedance method for detecting skeletal muscle mass. Berg balance scale method was used to determine the balance capacity in RA patients. Statistical analyses were performed using statistical product and service solutions (SPSS) software (Version 17.0). Comparison of frequency among different groups was used by x2test. Ranksum test was used to compare the median of measurement data in different groups when the data were skewed in distribution. Linear correlation between two indicators was represented with correlation coefficient. Multivariate regression was analyzed by binary logistic Regression(Backward LR). Results ①The prevalence of vertebral OPF in RA was 15.1%(141/936), which was higher than that in the control group (6/158, 3.8%) ( x2=18.658, P<0.01). The incidence of sarcopenia in RA patients was 55.8%(149/267), which was significantly higher than that in control group (9.0%, 14/156) ( x2=91.176, P<0.01).②Compared to RA without spinal OPF, skeletal muscle mass of general body and every part of extremities were apparently decreased in RA with spinal OPF (P<0.05). Berg balance scale score in RA with spinal OPF (33±15) was lower than that in RA without spinal OPF (43 ±14) (t=4.150, P<0.01). ③Berg balance scale score in RA patients with sarcopenia was lower than that in RA without sarcopenia (37±14 vs 43±13, t=3.524, P=0.001) and the proportion of Berg balance scale score ≤40 in RA with sarcopenia was higher than that in RA without sarcopenia (50.8%,65/128 vs 29.9%,32/107, x2=10.477, P=0.001).Skeletal muscle mass of general body(18±4 vs 20±5,t=3.563,P<0.01)and every part of extremities in RA patients with Berg balance scale score ≤40 also were significantly reduced than that in RA group with Berg balance scale score >40(P<0.05). ④ Linear correlation analysis found that Berg balance scale score was positively correlated with skeletal muscle index (SMI)(r=0.299, P<0.01), skeletal muscle mass of general body (r=0.251, P<0.01), muscle mass of right upper limb (r=0.225, P<0.01), muscle mass of left upper limb (r=0.221,P<0.01).muscle mass of trunk(r=0.230,P<0.01),muscle mass of right lower limb(r=0.228, P<0.01), muscle mass of left lower limb (r=0.245, P<0.01) in RA. ⑤Logistic regression analysis (LR Backward) discovered that age (OR=1.075, P=0.002, 95%CI (1.028,1.124)] was the risk factor for spinal OPF in RA patients, while skeletal muscle mass index (SMI) [OR=0.649, P=0.020, 95% CI (0.451, 0.933)] and Berg balance scale score [OR=0.957, P=0.016, 95%CI (0.924, 0.992)] were protective factors for the occurrence of spinal OPF in RA. Conclusion Sarcopeniaand balance capacity declining are probably correlated with spinal OPF in RA.

Clinical Value of Serum 14-3-3η protein levels in patients with Rheumatoid Arthritis and Secondary Osteo-porosis / 实用医学杂志

Objective To investigate the clinical value of serum 14-3-3η protein levels in patients with rheumatoid arthritis (RA) and secondary osteoporosis (OP). Methods 259 RA patients and 80 healthy controls were recruited. Serum 14-3-3η levels were determined by ELISA and bone mineral density (BMD) were detected by the DEXA. Results Firstly, the levels and the positive rate of serum 14-3-3η protein were significantly high-er in RA patients than healthy controls (P < 0.000 1). Secondly, ROC curve revealed that the sensitivity of 14-3-3η protein for diagnosis of early RA was 91.7% and its specificity was 99.6% when the cut-off point was 0.879 ng/mL (AUC = 0.917, P < 0.000 1). Finally, 14-3-3η protein concentrations revealed significant differ-ence among the groups of bone mass normal, osteopenia and osteoporosis in early RA (χ2=7.974, P = 0.019). Conclusion Serum 14-3-3η protein levels increase significantly in RA , especially in early RA , which is relat-ed to clinical symptoms and osteoporosis.

Clinical and laboratory features, and quality of life assessment in wheat dependent exercise-induced anaphylaxis patients from central China / 华中科技大学学报（医学）（英德文版）

Wheat dependent exercise-induced anaphylaxis (WDEIA) is a rare but potentially severe food allergy caused by the combination of wheat ingestion and physical exercise. The impact of WDEIA on quality of life (QOL) is unclear. This study characterized the clinical and laboratory features and investigated the QOL in WDEIA patients from Central China. Twenty-eight WDEIA patients were analyzed, and QOL was measured by validated Chinese version Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) and Food Allergy Independent Measure (FAIM) after obtaining the diagnosis. The results showed that half of the patients were females. The median onset age was 37 years old. The symptoms occurred within 1 h after wheat ingestion (26/28). Symptoms of anaphylaxis included cutaneous (26/28), respiratory (11/28), gastro-intestinal (5/28) and cardiovascular manifestations (27/28). Skin prick tests were positive to salt soluble (89.3%) and salt insoluble wheat allergen extracts (100%). Positive rate to wheat, gluten and omega-5 gliadin specific IgE was 64.3%, 92.9% and 92.9% respectively. Specific IgE to omega-5 gliadin with a cut-off value 0.83 KU/L offered highly efficient diagnostic criterion for WDEIA (sensitivity: 89.3%; and specificity: 88.9%). The mean scores of FAQLQ-AF and FAIM were 4.70 and 4.98 respectively and level of anti-omega-5 gliadin IgE had positive correlations with FAQLQ scores. Thereby, WDEIA is commonly found in mid-age adults. In most cases, multi-organs especially skin and cardiovascular systems are involved. Salt insoluble wheat allergen skin test and serum specific IgE to gluten and omega-5 gliadin help to diagnose WDEIA. QOL in WDEIA patients is severely impaired.

Clinical research on vitamin D deficiency and falls in rheumatoid arthritis patients with spinal osteoporosis fractures / 中华风湿病学杂志

Objective To explore the effect of vitamin D deficiency and falls on osteoporotic fracture (OPF) in patients with rheumatoid arthritis (RA).Methods A total of 852 patients with RA were recruited, anteroposterior and lateral X-rays examination of vertebral column were conducted for every patient.Serum 25-hydroxy vitamin D [25(OH)D] levels and bone mineral density (BMD) of all the vertebrae of lumbar were exam-ined.Clinical and laboratory index of patients were recorded in details meanwhile.Data of 156 normal subjects during the same period were collected as the control group.Numerical data and categorical data comparisons were analyzed using t test, x2 test, single factor analysis of variance test, linear correlation and Logistic regression analysis test.Results ① The prevalence of vertebral OPF in RA was 16.1％(137/852).Compared to RA without OPF, patients with OPF had lower serum 25(OH)D levels [(14±4) ng/ml vs (18±7) ng/ml, t=2.898, P=0.004].② The occurrence rate of falls in RA patients was 19.7％(36/183).Patients with falls had lower serum 25(OH)D levels [(14±4) ng/ml vs (18±6) ng/ml, t=2.854, P=0.005].③ The prevalence of falls in RA with vertebral OPF was higher than that in RA without OPF (38.1％ vs 14.2％,x2=11.708, P=0.001).④ Linear correlation analysis found that serum levels of 25 (OH)D was positively correlated with total lumbar region BMD in RA patients.⑤ Logistic regression analysis revealed that age [OR=1.124, P=0.002, 95％CI: (1.045, 1.209)]and usage of glucocorticostroid (GC) [OR=6.724, P=0.031,95％CI: (1.196, 37.813)] were the risk factors for occurrence of OPF in RA, while serum 25 (OH) D level [OR=0.850, P=0.046, 95％CI: (0.725, 0.997)] was the protective factor.Conclusion Spinal OPF in patients with RA is clearly related with vitamin deficiency, falls and usage of GC.

Evaluation of PIMA point-of-care CD4 analyzer in Yunnan, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>CD4 count is used to determine antiretroviral therapy (ART) eligibility. In China, flow cytometers are mostly located in urban areas with limited access by patients residing in remote areas. In an attempt to address this issue, we conducted a study to validate the performance of Alere PIMA point-of-care CD4 analyzer.</p><p><b>METHODS</b>Venous and finger-prick blood specimens were collected from HIV-positive participants from two voluntary counseling and testing sites in Yunnan Province. Both venous and finger-prick blood specimens were tested with the PIMA analyzer. Venous blood specimens tested with the Becton Dickinson FACSCalibur were used as a reference.</p><p><b>RESULTS</b>Venous specimens from 396 and finger-prick specimens from 387 persons were available for analysis. CD4 counts by PIMA correlated well with those from FACSCalibur with an R2 of 0.91 for venous blood and 0.81 for finger-prick blood. Compared to FACSCalibur, the PIMA analyzer yielded lower counts with a mean bias of - 47.0 cells/μl (limit of agreement, [LOA]: -204-110 cells/μl) for venous blood and -71.0 cells/μl (LOA: -295-153 cells/μl) for finger-prick blood. For a CD4 threshold of 350 cells/μl, the positive predictive value (PPV) of PIMA was 84.2% and 75.7% and the negative predictive value (NPV) was 97.6% and 95.8% for venous and finger-prick blood, respectively. For an ART threshold of 500 cells/μl, the corresponding PPV was 90.3% and 84.0% and NPV was 94.3% and 93.4%, respectively.</p><p><b>CONCLUSIONS</b>CD4 counting using venous blood with PIMA analyzers is a feasible alternative to a large flow cytometer to determine ART eligibility.</p>

The prognostic value of serum C-reactive protein-bound serum amyloid A in early-stage lung cancer / 癌症

<p><b>BACKGROUND</b>Elevated levels of serum C-reactive protein (CRP) have been reported to have prognostic significance in lung cancer patients. This study aimed to further identify CRP-bound components as prognostic markers for lung cancer and validate their prognostic value.</p><p><b>METHODS</b>CRP-bound components obtained from the serum samples from lung cancer patients or healthy controls were analyzed by differential proteomics analysis. CRP-bound serum amyloid A (CRP-SAA) was evaluated by co-immunoprecipitation (IP). Serum samples from two independent cohorts with lung cancer (retrospective cohort, 242 patients; prospective cohort, 222 patients) and healthy controls (159 subjects) were used to evaluate the prognostic value of CRP-SAA by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>CRP-SAA was identified specifically in serum samples from lung cancer patients by proteomic analysis. CRP binding to SAA was confirmed by co-IP in serum samples from lung cancer patients and cell culture media. The level of CRP-SAA was significantly higher in patients than in healthy controls (0.37 ± 0.58 vs. 0.03 ± 0.04, P < 0.001). Elevated CRP-SAA levels were significantly associated with severe clinical features of lung cancer. The elevation of CRP-SAA was associated with lower survival rates for both the retrospective (hazard ration [HR] = 2.181, 95% confidence interval [CI] = 1.641-2.897, P < 0.001) and the prospective cohorts (HR = 2.744, 95% CI = 1.810-4.161, P < 0.001). Multivariate Cox analysis showed that CRP-SAA was an independent prognostic marker for lung cancer. Remarkably, in stages I-II patients, only CRP-SAA, not total SAA or CRP, showed significant association with overall survival in two cohorts. Moreover, univariate and multivariate Cox analyses also showed that only CRP-SAA could be used as an independent prognostic marker for early-stage lung cancer patients.</p><p><b>CONCLUSION</b>CRP-SAA could be a better prognostic marker for lung cancer than total SAA or CRP, especially in early-stage patients.</p>

Therapeutic effects of segmental resection and decompression combined with joint prosthesis on continuous knee osteoarthritis

To observe the therapeutic effects of segmental resection and decompression combined with joint prosthesis on continuous knee osteoarthritis [OA]. A total of 130 patients with knee OA were selected and randomly divided into an observation group and a control group [n=65]. The control group was treated by segmental resection in combination with joint prosthesis, and the observation group was treated by segmental resection and decompression combined with joint prosthesis. They were followed-up for three months. All patients underwent successful surgeries during which no severe complications occurred. During the follow-up period, the overall effective rates of the observation group and the control group were 93.8% and 78.5% respectively, which were not statistically significantly different [p < 0.05]. The observation group was significantly less prone to patellar instability, infection and deep vein thrombosis compared with the control group [P < 0.05]. On the same day after surgery, the knee joint scores and functional scores of the two groups were similar, which evidently increased three months later, with significant intra-group and inter-group differences [p < 0.05]. Combining segmental resection and decompression with joint prosthesis gave rise to satisfactory short-term prognosis by effectively improving the flexion and extension of injured knee and by decreasing complications, thus being worthy of promotion in clinical practice