Humans ; Anemia, Aplastic ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Immunophenotyping

Objective: To reveal the compensatory features of bone marrow (BM) erythropoiesis in hereditary spherocytosis (HS) and to explore the effect of diferent hemoglobin levels on this compensation. Methods: Clinical and laboratory data of patients with HS were collected, and the peripheral blood absolute reticulocytes counts value was taken as the surrogate parameter to evaluate the ability of erythropoiesis compensation. BM erythropoiesis compensation in HS with diferent degrees of anemia were evaluated. Results: ①Three hundred and two patients were enrolled, including 115 with compensated hemolytic disease, 74 with mild anemia, 90 with moderate anemia, and 23 with severe anemia. ②Hemoglobin (HGB) was negatively correlated with serum erythropoietin in the decompensated hemolytic anemia group (EPO; rs=-0.585, P<0.001) . ③The median absolute reticulocyte count (ARC) of HS patients was 0.34 (0.27, 0.44) ×10(12)/L, up to 4.25 times that of normal people. The maximum ARC was 0.81×10(12)/L, about 10 times that of normal people. The median ARC of patients with compensated hemolytic disease was 0.29 (0.22, 0.38) ×10(12)/L, up to 3.63 times that of normal people. The median ARC of patients with hemolytic anemia was 0.38 (0.30, 0.46) ×10(12)/L, which was significantly higher than the patients with compensated hemolytic disease, up to 4.75 times that of normal people (z=4.999, P=0.003) . ④ ARC was negatively correlated with HGB in the compensated hemolytic disease group (rs=-0.177, P=0.002) and positively correlated with HGB in the decompensated hemolytic anemia group (rs=0.191, P=0.009) . There was no significant difference in the ARC among patients with mild, moderate, and severe anemia (χ(2)=4.588, P=0.101) . ⑤The median immature reticulocyte production index of the mild, moderate, and severe anemia groups was 13.1% (9.1%, 18.4%) , 17.0% (13.4%, 20.8%) , and 17.8% (14.6%, 21.8%) , respectively; the mild anemia group had lower index values than the moderate and severe anemia groups (P(adj) values were both<0.05) , but there was no significant difference between the latter groups (P(adj)=1.000) . The median immature reticulocyte count of patients in the mild, moderate, and severe groups was 5.09 (2.60, 7.74) ×10(10)/L, 6.24 (4.34, 8.83) ×10(10)/L, and 7.00 (3.07, 8.22) ×10(10)/L, respectively; there was no significant difference among the groups (χ(2)=3.081, P=0.214) . Conclusion: HGB can be maintained at a normal level through bone marrow erythropoiesis, while red blood cells are reduced in HS. However, once anemia develops, the bone marrow exerts its maximum erythropoiesis capacity and does not increase, regardless of anemia aggravation or serum EPO increase.
Bone Marrow ; Erythropoiesis ; Humans ; Reticulocyte Count ; Reticulocytes ; Spherocytosis, Hereditary

Objective: To study the metabolic characteristics of anti-human T-cell porcine immunoglobulin (p-ATG) in patients with severe aplastic anemia (SAA) . Methods: For patients with SAA treated with p-ATG combined cyclosporine A (CsA) immunosuppressants between February 2017 and December 2017, the p-ATG dose was 20 mg·kg(-1)·d(-1) over 12 h of intravenous administration for 5 consecutive days. The blood concentration of p-ATG was detected by the three-antibody sandwich ELISA method, the pharmacokinetic analysis software was fitted, and the second-chamber model method was used to calculate the pharmacokinetic parameters and plot the pharmacokinetic curve. Adverse events were recorded and the hematologic reactions were determined at 6 months after treatment. Results: Sixteen patients with SAA treated with p-ATG were enrolled, including 8 females and 8 males, with a median age of 22 years (range, 12 to 49 years) and a median weight of 62.5 kg (range, 37.5 to 82.0 kg) . The pharmacokinetics of p-ATG could be evaluated in 14 cases. p-ATG is distributed in vivo as a two-chamber model, with an average drug concentration peak (T(max)) of (5.786±2.486) days, a peak concentration (C(max)) of (616±452) mg/L, and a half-life of (10.479±8.242) days. The area under the drug time curve (AUC) was (5.807±3.236) mg/L·d. Six months after treatment, 8 of 14 patients received a hematologic response; the AUC (0-t) of the effective group and ineffective groups was (7.50±3.26) mg/L·d vs (4.50±2.18) mg/L·d, and the C(max) was (627±476) mg/L vs (584±382) mg/L, respectively. Conclusion: The plasma concentration of p-ATG reached a peak after 5 days of continuous infusion, and then decreased slowly, with a half-life of 10.479 days, and the residual drug concentration was detected in the body 60 days after administration. A relationship between drug metabolism and efficacy and adverse reactions could not be determined.
Anemia, Aplastic/drug therapy* ; Animals ; Antilymphocyte Serum/therapeutic use* ; Cyclosporine/therapeutic use* ; Female ; Humans ; Immunoglobulins/therapeutic use* ; Immunosuppression Therapy ; Immunosuppressive Agents/therapeutic use* ; Male ; Swine ; T-Lymphocytes ; Treatment Outcome

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Objective: To investigate the correlation between CLOCK and BMAL1 genes and MEN2 medullary thyroid carcinoma (MTC). Methods: Thirteen cases with MEN2 MTC and thirteen cases with non-MEN2 MTC were selected who were treated in the Yantai Yuhuangding Hospital between January 2013 and September 2021. Clinical indicators such as blood calcitonin level, tumor diameter and metastatic lymph node of patients were collected. The expression differences of CLOCK and BMAL1 between MEN2 MTC and para-carcinoma tissue as well as between MEN2 MTC and non-MEN2 MTC were detected by immunohistochemistry and qPCR. The correlation between lymph node metastasis and CLOCK or BMAL1 expression was analyzed. Protein-protein interaction (PPI) network analysis combined with qPCR and correlation analysis was used to explore the expression regulation relationship between RET and circadian clock genes. The rhythm disorder of MEN2 cells was verified by lipopolysaccharide cell stimulation experiment after dexamethasone rhythm synchronization. Results: MEN2 MTC exhibited typical RET gene mutation. The mean blood calcitonin level, the tumor diameter and the number of metastatic lymph nodes of patients with MEN2 MTC were higher than those of patients with non-MEN2 MTC (t value was 2.76, 2.53, 2.26, all P<0.05). Immunohistochemical results showed that the expression levels of CLOCK and BMAL1 in MEN2 MTC were higher than those in non-MEN2 MTC, while negatively expressed in para-cancerous thyroid follicle. qPCR displayed that the expression of CLOCK gene in cancer tissues was higher than that in non-MEN2 MTC and para-cancerous tissues (t value was 2.68 and 2.86, all P<0.05); the expression of BMAL1 gene in MEN2 MTC was higher than that in non-MEN2 MTC and para-cancerous tissues (t value was 2.21 and 2.35, all P<0.05). Correlation analysis showed that the expression levels of CLOCK and BMAL1 genes were positively correlated with the number of lymph node metastases in patients with MEN2 MTC (r=0.65, P<0.001; r=0.52, P=0.005). PPI network analysis indicated that the expression of CLOCK gene was positively correlated with the abnormal expression of RET gene (r=0.96, P<0.001). With lipopolysaccharide to stimulate cultured cells in vitro after dexamethasone rhythm synchronization, the expressions of CLOCK and BMAL1 in MEN2 MTC cells (0.47±0.22 and 2.60±1.48) at 12 hours of synchronization were significantly lower than those in para-cancerous tissues (1.70±1.62 and 8.23±2.52), the difference was statistically significant(t=5.04, P=0.007; t=3.34, P=0.029). Conclusion: CLOCK and BMAL1 are correlated with the occurrence and development of MEN2 MTC, and may be potential targets for the development of new therapeutic strategies for MEN2 MTC.
ARNTL Transcription Factors/genetics* ; CLOCK Proteins/genetics* ; Calcitonin ; Carcinoma, Neuroendocrine/genetics* ; Dexamethasone ; Humans ; Lipopolysaccharides ; Lymphatic Metastasis ; Multiple Endocrine Neoplasia Type 2a/genetics* ; Thyroid Neoplasms/surgery*

OBJECTIVE: To explore the relationship between the change of lymphocyte subsets before and after immunosuppressive therapy (IST) with disease severity of severe aplastic anemia (SAA) and hematologic response to IST. METHODS: The clinical data of 94 patients with SAA/VSAA treated by r-ATG and CsA in our hospital from December 2009 to October 2011 was analyzed retrospectively. Among them, 26 patients who had sequential data of lymphocyte subsets and cytokines before and after treatment were enrolled. The relationship between lymphocyte subsets, cytokine level before IST and disease severity, as well as the relationship between changes if lymphocyte subsets, changes of cytokine and the HR after IST for 6 months was analyzed. RESULTS: There were no statistical differences in the ratio and absolute count of lymphocyte, the ratio and absolute count of each lymphocyte subsets, including CD3 CONCLUSION The hematopoietic recovery and early hematologic remission may be affected by the intensity of immune suppression reflected from the changes of lymphocyte subsets and the immune reconstruction reflected from the recovery of lymphocyte subsets. The immune reconstruction is most significant within 3 months after IST.
Anemia, Aplastic ; Humans ; Immunosuppression ; Immunosuppressive Agents/therapeutic use* ; Lymphocyte Subsets ; Retrospective Studies

Objective: To analyze the prognostic factors of transfusion-dependent non-severe aplastic anemia (TD-NSAA) patients treated with cyclosporine A (CsA) and androgen. Methods: Clinical data of 77 consecutive TD-NSAA patients treated with CsA and androgen were retrospectively analyzed between 2010 and 2013. We obtained clinical manifestations and baseline parameters of routine blood test from responders, and compared those with non-responders. All data were analyzed by univariate analysis and multivariate analysis. Results: In 77 patients, there were 43 (55.8%) patients achieved hematological response after 6 months'treatment, and 53 (68.8%) patients got response after 12 months. Univariate analysis showed that platelets baseline was the only factor related to hematological response [19 (6-61) ×10(9)/L vs 13.5 (5-45) ×10(9)/L, P=0.001] after 6 months therapy. After 12 months, the statistical differences were maintained, which were platelets baseline [18 (6-61) ×10(9)/L vs 10.5 (5-45) ×10(9)/L, P<0.001], absolute reticulocytes [0.03 (0.01-0.06) ×10(12)/L vs 0.029 (0.02-0.06) ×10(12)/L, P=0.043], transfusion-dependent of platelet (P=0.007) , transfusion-dependent of platelet and erythrocyte (P=0.012) . Multivariate analysis showed that platelets baseline could be an independent prognostic factor of hematological response (P=0.010 or 0.009) . Cutoff value of platelets by receiver operating characteristic curve was 15.5×10(9)/L. Conclusion: Baseline of higher platelets, higher reticulocyte, and no transfusion dependence of platelet are favorable prognostic factors. When platelets baseline is higher than 15.5×10(9)/L, CsA and androgen regimen is rational.
Androgens/therapeutic use* ; Anemia, Aplastic/drug therapy* ; Antilymphocyte Serum ; Cyclosporine/therapeutic use* ; Drug Combinations ; Humans ; Immunosuppressive Agents ; Prognosis ; Retrospective Studies ; Treatment Outcome

Anemia, Hemolytic, Congenital ; Humans ; Ion Channels/genetics* ; Mutation

Objective: To explore the life span of red blood cells (RBC) in patients with severe/very severe aplastic anemia (SAA/VSAA). Methods: Clinical data of 128 SAA/VSAA patients from November 2016 to April 2017 were retrospectively analyzed, and 13 healthy volunteers in the same period was used as normal control. The endogenous Breath Carbon Monoxide (CO) test was used to detect the life span of RBC in SAA/VSAA patients, and the effect of immunosuppressive therapy (IST) on the life span of RBC in these patients was explored. Results: The mean life span of RBC in 51 untreated SAA/VSAA patients was (50.69±21.43) d, which was significantly shorter than that in normal controls[(111.85±31.55) d](t=-6.611, P<0.001). The mean life span of RBC in 77 patients treated with IST was (87.14±39.28) d. The mean life span of RBC in complete responses (CR), hematologic response (HR) and non-response (NR) patients were (106.15±32.12) d, (92.00±38.60) d and (50.44±21.56) d, respectively. The life span of RBC in patients with HR was significantly longer than that in newly diagnosed and NR patients (t=7.430, P<0.001; t=4.846, P=0.002), which was similar to that in the normal controls (t=-1.743,P=0.085). There was no statistical significance between CR patients and the normal controls in the mean life span of RBC (t=-0.558, P=0.579). No factor affecting the RBC life span was found in univariate logistical regression analyses in the newly diagnosed SAA/VSAA patients. The serum levels of IL-2R and IL-6 were much lower in HR patients than NR patients[IL-2R: 4.3×10⁵ U/L vs 6.5×10⁵ U/L, z=-2.733, P=0.006; IL-6: 2.6 (2.0-17.7) ng/L vs 6.1 (2.0-14.4) ng/L, z=-2.968, P=0.003]. Of the 51 newly diagnosed patients, 38 received IST and their 3-month curative effect was evaluated. Receiver operator characteristics (ROC) curve was used to analyze the predictive effect of RBC life span of untreated patients on the efficacy of IST before treatment. The cut-off point was 60 days with sensitivity of 37.5% and specificity of 86.4%. In 9 cases with life span of RBC>60 d before IST, 6 cases acquired HR, while in 29 cases with life span of RBC ≤ 60 d before IST, 10 cases acquired HR, the difference was not statistically significant (P=0.128). Conclusion: The life span of RBC in SAA/VSAA patients was shortened, which can be improved even recovered to the normal after IST. Elevated cytokines might play a role in the pathophysiology of the shortened RBC life span in SAA/VSAA.
Anemia, Aplastic ; Erythrocytes ; Humans ; Immunosuppressive Agents ; Longevity ; Retrospective Studies ; Treatment Outcome