[Deciphering Hypoplastic Myelodysplastic Syndrome and Aplastic Anemia via In-Depth Analysis of Lymphocyte Subsets].

OBJECTIVE: To explore the difference of lymphocyte subsets in peripheral blood (PB) between aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (hypo-MDS) patients, meanwhile to compare the clinical parameters obtained from PB and bone marrow (BM). METHODS: The lymphocyte subsets in hypo-MDS (n=25) and AA (n=33) patients were investigated by flow cytometry. Meanwhile, the differences in PB cell counts, biochemical indicators, BM cell counts and abnormal chromosomes between the two groups were analyzed. RESULTS: The percentage of CD8+T cells in AA group was significantly higher than that in hypo-MDS group (P=0.001), while the percentage of CD4+ T cells and the CD4+/CD8+ ratio in AA group were obviously lower than those in hypo-MDS group (P=0.015 and 0.001, respectively). Furthermore, the proportion of CD4+ and CD8+ activated T (TA) cells, and memory Tregs in AA group was distinctly lower than those in hypo-MDS group (P=0.043, 0.015 and 0.024, respectively). Nevertheless, the percentage of CD8+ naive T (TN) cells in AA patients was remarkably higher (P=0.044). And hypo-MDS patients had declined lymphocyte counts (P=0.025), increased levels of total bilirubin (TBil), lactate dehydrogenase (LDH), vitamin B12 and proportion of BM blasts than AA patients (P=0.019, 0.023, 0.027 and 0.045, respectively). CONCLUSION: In this study it was confirmed that the percentages of CD4+ and CD8+ TA cells, memory Tregs and CD8+ TN cells were significantly different between AA and hypo-MDS patients, which provide an essential basis for the identification of these two diseases.

Plasma thymidylate synthase and dihydrofolate reductase mRNA levels as potential predictive biomarkers of pemetrexed sensitivity in patients with advanced non-small cell lung cancer.

BACKGROUND: High levels of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) expression in tumour tissues are an indicator of ineffective responses to pemetrexed-based chemotherapy in various tumours, including non-small cell lung cancer (NSCLC). However, tumour tissues are highly heterogeneous, so a single biopsy may not reflect genetic alterations during disease progression. This study investigated the potential use of plasma TS and DHFR mRNA levels as biomarkers for predicting sensitivity to pemetrexed-based chemotherapy. METHODS: Plasma samples were obtained from 245 patients with advanced NSCLC and 30 healthy donors. Total RNA was extracted from the plasma samples, and TS and DHFR mRNA levels were determined via real-time PCR. TS and DHFR mRNA levels between cancer patients and healthy controls were compared. The association between plasma TS and DHFR mRNA levels and tumour response to pemetrexed/cisplatin chemotherapy was analysed. RESULTS: The plasma TS and DHFR mRNA levels decreased in patients with advanced NSCLC compared with healthy controls. Moreover, plasma TS and DHFR mRNA levels negatively correlated with tumour response to pemetrexed/cisplatin chemotherapy in patients with advanced NSCLC. Overall survival time was prolonged in patients with low TS mRNA expression compared with those with high TS mRNA expression, although the difference was not statistically significant. CONCLUSIONS: Low expression levels of plasma TS and DHFR mRNA confer increased tumour sensitivity to pemetrexed/cisplatin chemotherapy in patients with advanced NSCLC. The results suggested that plasma TS and DHFR mRNA levels are promising biomarkers for choosing patients who are likely to respond and benefit the most from pemetrexed-based chemotherapy.

[Differential Expression Profiles of MicroRNAs between de novo and Complete Response Severe Aplastic Anemia].

OBJECTIVE: To detect the expression of miRNA in de novo and complete response SAA patients and predict the targets of the miRNAs. METHODS: The expression profiles of miRNA from bone marrow mononuclear cells of the SAA patients with de novo and CR were detected by miRNA microarray. RESULTS: Totally 35 up-regulated and 37 down-regulated miRNA were identified in CR SAA patients in comparison with de novo SAA patients. Furthermore, by predicting the targets of the differentlly expressed miRNA, it was found that some targets associated with T cell receptor signaling pathway and cell adhesion molecules. CONCLUSION: Some miRNA may be involved in the pathogenesis of SAA.

[Long-term Follow-up of Patients with Hepatitis-Associated Aplastic Anemia].

OBJECTIVE: To explore the clinical characteristic, therapeutic efficacy and prognosis of patients with hepatitis-associated aplasitc anemia (HAAA). METHODS: the clinical data and labrotatory examination results of 30 cases of HAAA were analyzed retrospectively, the 6-month response ratio and overall survival (OS) were assessed. RESULTS: HAAA most commonly occured in males, with the occurence rate of males and females was 4:1, the median onset age was 16 (4-43) years old, HAAA oriented focus on sever aplastic anemia (SAA)(4 cases,13%) and very sever aplastic anemia (VSAA)(22 cases,73%). Aplastic anemia (AA) could be seen on occurence of hepatitis (accompanied aplastic anemia) (7 cases,23%), or after the onset of hepatits (delayed aplastic anemia) (23 cases,77%), but more often occured in the latter. Statistical analysis showed that when compared with the patients of delayed aplastic anemia, patients accompanied aplastic anemia possesses lower levels of glutamic-pyruvic transaminase(ALT), aspertate aminotransferase (AST) and total bilirubin (TBIL)(P=0.042,0.012,0.001), and possessed a more obvious lymphoid cell disorder when AA occured, with more lower peripheral blood CD19+ B cells proportion (P=0.046) and more obvious imbalance of CD4+/CD8+ ratio, but the difference was no statistical significant (P=0538). Factors affecting the 6-month respose were the severity of AA (P=0.044), the peak level of bilirubin of hepatitis (P=0.006) and the propotion of mature monocyte in bone marrow (P=0.034). The long-term follow-up showed that the 2-year OS of HAAA was 64.3±9.2%, the 6-month curative efficacy significantly affect the prognosis (P<0.001). CONCLUSION: HAAA more often occur in young male, HAAA is mainly SAA and VSAA and mostly non-A-C hepatitis associated aplastic anemia, patients usually have a high incidence of early infection. Patients acompanied with aplastic anemia possess more obvious immunological derangement; the treatment efficacy for HAAA is poor, patients who haven't obtained 6-month response indicate a sinister prognosis, allogeneic hematopoietic stem cell transplantion is a better choice for these patients.

[Clinical Characteristics and Gene Mutations of Gilbert Syndrome Complicated with Myeloproliferative Neoplasm].

OBJECTIVE: To investigate the clinical characteristics and gene mutations of patients with Gilbert syndrome complicated with myeloproliferative neoplasms (MPN). METHODS: Peripheral blood samples from 1 patient with Gilbert syndrome complicated with MPN and his son were collected to analyse all exon mutations of UGT1A1 gene. RESULTS: The patient with leukocytosis, thrombocythemia, mild anemia and positive JAK2/V617F mutation was initially diagnosed as MPN. The hyperbilirubinemia suggested concurrent disease. Further gene evaluation disclosed a insertion mutation in the (TA)6TAA box, and a missense mutation(G→A) at 211 bp of exon 1, corresponding to the deficiency in the bilirubin-conjugating enzyme uridine-diphosphoglucuronosyl transferase1A1 (UGT1A1). His son only carried some polymorphism mutation without manifestation of this disease. CONCLUSION: It is a first report case of MPN complicated with Gilbert syndrome that can highlight the differential diagnosis for hyperbilirubinemia.

Uniportal versus three-port video-assisted thoracoscopic surgery for spontaneous pneumothorax: a meta-analysis.

BACKGROUND: Whether or not uniportal video-assisted thoracoscopic surgery (VATS) is beneficial for spontaneous pneumothorax remains inconclusive. This meta-analysis aimed to summarize the available evidence to assess the feasibility and advantages of uniportal VATS for the treatment of spontaneous pneumothorax compared with three-port VATS. METHODS: Eligible publications were identified by searching the Cochrane Library, PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data databases and CQVIP. Odds ratios (OR) and standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated to compare dichotomous and continuous variables, respectively. RESULTS: This meta-analysis was based on 17 studies and included a total of 988 patients with spontaneous pneumothorax. No death was reported during the perioperative period. Compared with three-port VATS groups, there was a statistically significant difference in uniportal VATS groups regarding postoperative hospital stay (SMD= -0.58; 95% CI: -1.04 to -0.12; P=0.01), paresthesia (OR=0.13; 95% CI: 0.07 to 0.24; P<0.00001), visual analogue pain score (VAS) at 24 hours (h) (SMD= -0.87; 95% CI: -1.07 to -0.68; P<0.00001), VAS at 72 h (SMD= -0.49; 95% CI: -0.68 to -0.30; P<0.00001), and patients satisfaction scale (PSS) at 24 h (SMD= -0.81; 95% CI: -1.21 to -0.41; P<0.0001), PSS at 48 h (SMD= -0.69; 95% CI: -1.08 to -0.29; P=0.0007). However there was no statistically significant difference on the recurrence (OR=0.79; 95% CI: 0.42 to 1.46; P=0.45), operative time (SMD= -0.23; 95% CI: -0.21 to 0.67; P=0.31), length of postoperative drainage (SMD= -0.17; 95% CI: -0.40 to -0.07; P=0.16), VAS at 48 h (SMD= -0.40; 95% CI: -1.47 to 0.67; P=0.46), and PSS at 72 h (SMD= -0.13; 95% CI: -0.52 to -0.25; P=0.50). CONCLUSIONS: The results for mortality, recurrence, operative time, and length of postoperative drainage were similar between uniportal and three-port VATS. Uniportal VATS resulted in reduction in postoperative pain and paresthesia as well as an improvement in patients' satisfaction. This meta-analysis indicated that using uniportal VATS to treat spontaneous pneumothorax was safe and feasible, and it may be a better alternative procedure because of its advantage in reducing postoperative pain and paresthesia.

[Study on abnormal iron metabolism and iron overload in patients with aplastic anemia].

OBJECTIVE: To investigate the abnormalities of iron metabolism, the prevalence and risk factors of iron overload and clinical characteristics of patients with aplastic anemia (AA). METHODS: A cross-sectional study was conducted on 520 newly diagnosed AA patients. RESULTS: Iron overload was observed in 66(13%) of 520 AA patients,in which a higher prevalence of iron overload was seen not only in patients with infections(19/86, 22%)than those without infections (47/434, 11%, P<0.01), but also in patients with hepatitis associated AA(HAAA) (6/22, 19%) than the idiopathic cases (60/488, 12%, P>0.05). Excluded the patients with infections and/or HAAA, 43 of 405(11%)cases had iron overload, including 14 of 248(6%) cases without history of blood transfusion and 29 of 157 patients (18%, P<0.01) with transfusion. In univariate analysis, higher levels of serum ferritin (SF), serum iron (SI) and transferrin saturation (TS) were mainly observed in adult male patients with severe AA (SAA) and significantly upward with increasing blood transfusion (P<0.01). No differences of soluble transferrin receptor (sTfR) were observed between adults and children, males and females, hepatitis and idiopathic AA. However, patients with infections had significantly lower level of sTfR (0.50 mg/L) than cases without infections (0.79 mg/L, P<0.01). The level of sTfR in SAA patients (0.70 mg/L) was only half of that in non-SAA (NSAA) (1.36 mg/L, P<0.01). Patients with increasing blood transfusion had significantly downward levels of sTfR (P<0.01). In multivariate analysis, more than 8 U blood transfusion (OR=10.52, P<0.01), adults (OR=3.48, P<0.01), males (OR=3.32, P<0.01) and infections (OR=2.09, P<0.01) were independent risk factors. CONCLUSION: AA patients had higher iron burden and were high-risk populations occurring iron overload. The iron overload occurred in 18% of patients with blood transfusion and in 6% of patients without transfusion.

[The clinical study of myelodysplastic syndromes with PNH clones].

OBJECTIVE: To analyze the clinical characteristics and risk factors on responses and survival of myelodysplastic syndromes (MDS) patients with paroxysmal nocturnal hemoglobinuria (PNH) clones. METHODS: The clinical data of 31 MDS cases with PNH clones from October 2004 to June 2012 were retrospectively analyzed to reveal the influence of PNH clone size on responses and survival. RESULTS: ①The chromosome karyotypes were analyzed in all patients, 23 patients with normal karyotype, 7 patients with abnormal karyotype [including 3 patients with +8, 2 -Y, 1 del(7q) and 1 Xp+] and 1 patient with no mitosis. 1 patient belonged to low-risk, 27 intermediate-1 risk, 2 intermediate-2 risk and 1 high-risk groups, respectively, according to IPSS. There were significantly statistical differences between responders and nonresponders in terms of infection, ANC, Reticulocyte count and IPSS (P values were 0.049, 0.006, 0.031 and 0.043, respectively). ②The overall responsive rate was 67.7%, no patients progressed to acute leukemia (AL) during median follow-up of 19 months after immunosuppressive therapy (IST). The 3-year and 5-year overall survival rates were 82.7% and 55.1%,respectively. ③According to univariate analysis,age, infection and ANC had significant influence on survival (P values were 0.050, 0.031 and 0.026, respectively). ④The PNH clone size had no significant influence on survival through univariate and COX analyses (P=0.393). CONCLUSION: MDS patients with PNH clone had less cytogenetic abnormalities, higher probability of response to IST and lower probability of progression to AL; Furthermore, the PNH clone size had no significant influence on response and survival.