Clinical study on factor Ⅷ inhibitor in children with hemophilia A / 中华血液学杂志

Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.

Analysis of the management measures and effects in prevention and control of COVID-19 in outpatient service of a general hospital / 医学研究生学报

To preliminarily analyze the prevention and control of COVID-19, a general hospital outpatient service took six management measures, including setting up a leading group, building rules and regulations, infection control and supervision, special training, humanized service, public opinion propaganda. After nearly two months, the rates of both body temperature monitoring and epidemiological history screening are 100%, the medical staff infection rate is zero, and no cross infection between the patients due to adopting outpatient service comprehensive management measures which had strong organization and leadership, effective targeted training, effective control of all links in epidemic prevention and control work. During the fight against COVID-19, outpatient management played an important role in hospital management. The above approaches provide valuable experience for preventing the spread of infectious diseases effectively and winning the biological weapon wars in the future.

The application of WeChat applet and integrity propaganda and education in outpatient pre-examination during the prevalence of COVID-19 / 医学研究生学报

ObjectiveDuring the prevention and control of COVID-19, it is a difficult problem to obtain the individual epidemiological status of outpatients efficiently and accurately in a large comprehensive third-grade class-A hospital. To discuss the application and effect of WeChat applet and integrity propaganda and education in outpatient pre-examination during the prevention and control of COVID-19.MethodsFirstly, the outpatients were treated with integrity propaganda and education (like informing the law and regulations, recording the personal credit) at the outpatient pre-examination office. Secondly, let them take real-name authentication in the hospital self-developed WeChat applet. Thirdly, the outpatients filled in the epidemiological questionnaire related to COVID-19 by WeChat. The differences between before using the application (8,186 patients) and after using (7,361 patients) were compared in pre-examination time and concealing the incidence of an individual's epidemiological history.ResultsAfter the application of WeChat applet and integrity propaganda and education, the pre-examination time after using application [(1.07±0.23)min] was shorter than that before using[(2.15±0.37) min] (P<0.05). The concealment rate of epidemiological history was 0.05% before using application and zero after using.ConclusionWeChat applet and integrity propaganda and education can shorten the pre-examination time of covid-19 and reduce the occurrence of concealing personal epidemiological history.

Treament of CRRT combined with low-flow ECMO for canines with ARDS / 医学研究生学报

Objective Single mechanical ventilation for curing severe acute respiratory distress syndrome (ARDS) is sometimes not effective in improving oxygenation and removing excess CO2 in the blood. The purpose of this study is to observe the effect of continuous renal replacement therapy（CRRT）combined with low-flow extracorporeal membrane oxygenation （ECMO）of V-V mode on clearance of inflammatory mediators，improving oxygenation and reducing PaCO2 in canines with ARDS and hypercapnia. Methods 30 healthy adult canines were divided into 3 groups (n=10 each) using a random number table method sham group, ECMO (EC) group and CRRT+ECMO（CR+EC）group. A canine model of ARDS with hypercapnia were prepared by injected intravenously oleic acid. Sham group was only treated with invasive mechanical ventilation. EC group was treated with invasive mechanical ventilation and ECMO. CR+EC group was treated with CRRT combined with low-flow ECMO of V-V mode besides invasive mechanical ventilation. The heart rate(HR)，mean artery pressure (MAP)，cardiac output(CO) and concentration of serum TNF-α and IL-6 were examined at the beginning of modeling(T0)，after 1，3，6 and 9 (T1, T3, T6, T9) hours of mechanical treatment respectively. Oxygenation index（OI），PaCO2, temperature（T）were examined at the beginning of modeling，after 3, 6, 9 hours of mechanical treatment，and at the time point of 3 hours(T12) after ECMO treatment (EC group) and CRRT+ECMO treatment(CR+EC group)，respectively. The differences were compared between groups involved in above-mentioned indexes at different time points. Results Compared with the sham group, the HR decreased at T6 and T9 in the EC group and CR+EC group (P<0.05), and the concentration of IL-6 and TNF-α decreased at T3, T6 and T9 in the CR+EC group (P<0.05). Compared with T0, HR decreased at T6 and T9 in the EC group (P<0.05). Compared with T0, the concentration of IL-6 and TNF-α decreased at T3, T6 and T9 in the CR+EC group (P<0.05). Compared with the EC group, the HR decreased at T6 and T9 in the CR+EC group (P<0.05). Compared with the EC group, the concentration of IL-6 and TNF-α decreased at T3, T6 and T9 in the CR+EC group (P<0.05). Compared with the sham group, the OI decreased at T9 and T12 in the CR+EC group (P<0.05). Compared with the sham group, PaCO2 decreased at T3, T6 and T9 in the EC group and CR+EC group (P<0.05). Compared with the EC group, the OI decreased at T9 and T12 in the CR+EC group (P<0.05). Compared with T0, the OI decreased at T6 and T12 in the CR+EC group (P<0.05). Conclusion The CRRT combined with low-flow ECMO of V-V mode has positive effects on clearance of inflammatory mediators，reducing hypercapnia and improving oxygenation in the canines with ARDS and hypercapnia.

Analysis of clinical characteristics and prognostic factors in patients with non-Hodgkin lymphoma and HBV infection / 中华血液学杂志

Objective: To explore the clinical characteristics and prognostic factors of the patients with non-Hodgkin's Lymphoma (NHL) complicated with HBV infection, so as to provide a basis for clinical accurate diagnosis and prognosis evaluation. Methods: The data of 313 newly diagnosed NHL patients from August 2012 to July 2016 were collected. The HBV serological markers were detected by ELISA, and HBV DNA was quantified by full automatic microparticle chemiluminescence immunoassay (≥1×10(5) copies/ml as high copy group, 1×10(3)-<1×10(5) copies/ml as low copy group). The relationship between HBV infection and prognosis was analyzed combined with the clinical features of the patients, and the HBV detection rate was compared with that of the common population (from the national HBV sero epidemiological data). Results: ①The positive rate of HBsAg in NHL patients was 12.5% (39/313), which was higher than 7.2% in the general population (χ(2)=14.596, P<0.001). HBV infection in the past (HBsAg negative but HBcAb positive) in 114 cases (36.4%), the incidence was slightly higher than that in the general population (34.1%). ②Compared HBsAg positive group with the negative group, the proportion of B cell type (87.2% vs 70.3%, P=0.027), Ann Arbor stage Ⅲ-Ⅳ(69.2% vs 34.6%, P<0.001), IPI score 3-5 (74.4% vs 50%, P=0.004), LDH level (79.5% vs 47.8%, P<0.001) and liver involvement (45.5% vs 31.7%, P=0.006) were all higher. The difference was statistically significant. ③Compared the HBV infected group (114 cases) with the non-infected group (160 cases), the difference had statistical significance in the proportion of Ann Arbor stage Ⅲ-Ⅳ (P=0.023) and IPI score 3-5 scores P=0.035). ④Compared HBV DNA positive group (30 cases) with negative group (71 cases), Ann Arbor stage Ⅲ-Ⅳ (P=0.011), IPI score 3-5 score (P=0.030), LDH level (P=0.025) and liver involvement (P<0.001) in the proportion of patients had statistical significance. The positive patients were divided into HBV DNA high and low copy groups with 1×10(5) copies of /ml as the boundary. The results showed that there was no statistical difference between the two groups (P>0.05). Conclusions: The HBV infection rate of NHL patients is significantly higher than that of the general population, and HBV infection is more closely related to B cell type NHL. Patients with HBV infection and HBV DNA positive had late Ann Arbor stage, high IPI score, high LDH level and liver involvement, and the prognosis is poor.

Comparison of different styles of allogeneic hematopoietic stem cell transplantation as first-line treatment treated with severe aplastic anemia in children and adolescents / 中华血液学杂志

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) . Methods: The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT). Results: The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ2=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ2=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ2=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ2=0.230, P=0.891; χ2=2.628, P=0.269; χ2=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ2=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade Ⅲ/Ⅳ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS. Conclusion: The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.

Extracorporeal Membrane Oxygenation Improving Survival and Alleviating Kidney Injury in a Swine Model of Cardiac Arrest Compared to Conventional Cardiopulmonary Resuscitation / 中华医学杂志(英文版)

Background@#Acute kidney injury (AKI) frequently occurs in cardiopulmonary resuscitation patients. Studies comparing the effects of extracorporeal membrane oxygenation (ECMO) with conventional cardiopulmonary resuscitation (CCPR) on AKI were rare. This study aimed to compare the effects of ECMO with those of CCPR on survival rate and AKI and explore the underlying mechanisms in a swine model of cardiac arrest (CA).@*Methods@#Sixteen male pigs were treated with ventricular fibrillation to establish CA model and then underwent CCPR (CCPR group, n = 8) or ECMO during cardiopulmonary resuscitation (ECPR group, n = 8). The study endpoints were 6 h after return of spontaneous circulation (ROSC) or death. Serum and urine samples were collected at baseline and during the 6 h after ROSC. The biomarkers of AKI were detected by enzyme-linked immunosorbent assay. The apoptosis of renal tubular epithelial cells was discovered by transmission electron microscope (TEM) and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Apoptosis-related genes were detected by immune-staining and Western blotting. Data were compared by Student's t-test.@*Results@#All pigs in ECPR group were successfully resuscitated with a higher 6-h survival rate (8/8) compared to CCPR group (6/8). The expressions of AKI biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinase2 (TIMP2), insulin-like growth factor-binding protein 7 (IGFBP7), liver fatty acid-binding protein (LFABP), and kidney injury molecule1 (Kim-1) were all increased along with the time after ROSC in both groups and lower in ECPR group compared with CCPR group. Especially, products of urinary TIMP and IGFBP levels (TIMP*IGFBP) were significantly lower at ROSC4 (0.58 ± 0.10 ng/ml vs. 1.18 ± 0.38 ng/ml, t = 4.33, P = 0.003) and ROSC6 (1.79 ± 0.45 ng/ml vs. 3.00 ± 0.44 ng/ml, t = 5.49, P < 0.001); urinary LFABP was significantly lower at ROSC6 (0.74 ± 0.06 pg/ml vs. 0.85 ± 0.11 pg/ml, t = 2.41, P = 0.033); and urinary Kim-1 was significantly lower at ROSC4 (0.66 ± 0.09 pg/ml vs. 0.83 ± 0.06 pg/ml, t = 3.99, P = 0.002) and ROSC6 (0.73 ± 0.12 pg/ml vs. 0.89 ± 0.08 pg/ml, t = 2.82, P = 0.016). Under light microscope and TEM, the morphological injures in renal tissues were found to be improved in ECPR group. Moreover, apoptosis was also alleviated in ECPR group.@*Conclusions@#Compared with CCPR, ECMO improves survival rate and alleviates AKI in a swine model of CA. The mechanism of which might be via downregulating AKI biomarkers and apoptosis in kidney.

AsO Up-Regulates the Proportion of CD4CD25CD127 Tregs in Peripheral Blood of Patients with Severe Aplastic Anemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of ATO on the proportion of Treg in the peripheral blood of patients with severe aplastic anemia (SAA) in vitro.</p><p><b>METHODS</b>The peripheral blood of 20 newlydiagnosed patients were collected, and the peripheral blood monomuclear cells (PBMNC) were extracted. After the PBMNC were treated with ATO of different concentrotions (0, 1, 2.5 and 5 µmol/L) for 96 hours, the proportion of CD44 CD25CD127 regulatatory T cells (Treg) were detected by flow cytometry. The expression levels of Foxp3 mRNA were detected by RT-PCR, and the levels of IFN-γ,IL-4,IL-17 and TGF-β1 were detected by ELTSA to verify the results of flow cytomery.</p><p><b>RESULTS</b>ATO significantly increased the proportion of Treg (P<0.01) at the concentration of 2.5 and 5 µmol/L, and the rising degree of Treg proportion improved with the increasing ATO concentration(r= 0.524). Treg proportion increased at a concentration of 1 µmol/L, but without statistical significance (P>0.05). At 1(P<0.05), 2.5(P<0.01) and 5 µmol/L(P<0.01), ATO significantly up-regulated the expression of Foxp3 mRNA, and the increase of Foxp3 mRNA positively and linearly correlated with the increase of Treg cell-frequency(r=0.523). ATO significantly reduced the levels of IFN-γ (at ATO 1,2.5 and 5 µmol/L, P<0.01), IL-4 (at ATO 2.5 µmol/L, P<0.01; at ATO 5 µmol/L, P<0.01) and IL-17(at ATO 2.5 µmol/L, P<0.05; at ATO 5 µmol/L, P<0.01). ATO had no significant effect on TGF-β1 at 1(P>0.05) and 2.5 µmol/L (P>0.05), but significantly reduced TGF-β1 level at 5 µmol/L (P<0.05).</p><p><b>CONCLUSION</b>ATO can mediate the immune regulation through up-regulating the proportion of Treg in peripheral blood of patients with SAA and reducing the levels of IFN-γ, IL-4 and IL-17.</p>

Study on the diagnostic value of lung biopsy in hematologic patients with lung infection / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the diagnostic value and safety of percutaneous lung biopsy in hematologic patients with lung infection.</p><p><b>METHODS</b>28 cases hematologic patients received CT-guided percutaneous lung biopsy when they developed a fever associated with pulmonary nodules or lumps in CT scan whose clinical diagnosis were unclear during or after chemotherapy. Sample of each lesion were drawn twice. The lung tissue was re-scanned after lung biopsy to check up in order to discover bleeding and pneumothorax. Biopsy tissue was examined by bacteria culture, acid-fast staining and pathology. Pathological examination contained HE staining, acid-fast stain, PAS stain, TB-DNA, methenamine silver and others.</p><p><b>RESULTS</b>28 cases contain 24 males and 4 females. Median age was 40 15 - 77 years old. Blood tests were as follows: 3 cases with HGB > 110 g/L, 9 with HGB 90 - 110 g/L, 12 with HGB 60 - 89 g/L, 4 with HGB < 60 g/L. 8 with WBC > 10×10(9)/L, 6 with WBC (4 - 10)×10(9)/L, 13 with WBC < 4×10(9)/L, 1 with WBC < 2×10(9)/L; 14 with PLT > 100×10(9)/L, 5 with PLT (50 - 100)×10(9)/L, 5 with PLT < 50×10(9)/L, 4 with PLT < 30×10(9)/L. 4 cases had mild extended PT, 3 mild extended APTT, 3 FIB lower than normal. Lung CT scans were as follows: 4 cases with simply lesion in right lung, 4 with simply lesion in left lung, 20 with lesions in bilateral lung. 8 cases were diagnosed as fungal infection, 3 as tuberculosis infection, 1 as lung cancer, 1 as pulmonary infiltration of lymphoma, 1 as pulmonary infiltration of leukemia, and 14 as inflammatory changes with no specific diagnosis. 4 cases came with pneumothorax during lung biopsy, mild to moderate in 3 cases and severe in 1 case. Severe patient turned better after CT-guided suction. 3 cases with mild hemoptysis turned better after treatment.</p><p><b>CONCLUSION</b>When hematopathy patients are with pulmonary nodules or lumps in CT scan whose clinical diagnosis is unclear, CT-guided percutaneous lung biopsy is safe and conducive to early diagnosis and conducive to early rehabilitation of patients if the coagulation function is basically normal and platelet count is not too low.</p>

Retrospective analysis of 54 patients with high risk aggressive T-cell non-Hodgkin lymphomas / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the clinical characteristics, treatments and prognosis of patients with T-cell non-Hodgkins lymphoma (NHL) in intermediate-high and high risk.</p><p><b>METHODS</b>Fifty-four patients with T-cell NHL classified intermediate-high and high risk were retrospectively analyzed.</p><p><b>RESULTS</b>According to WHO classification criteria, there were 12 cases of T-lymphoblastic lymphoma (TLBL), 31 peripheral T-cell lymphoma unspecified (PTCL-U), and 11 hepatosplenic T-cell lymphoma (HSTCL). The IPI were 12 cases of intermediate-high risk and 42 high risk. Of them, 49 cases were bone marrow affected and 7 CNS affected. The response rate (RR) for the whole group was 86.5%, complete remission (CR) rate 67.3%, and 3-year survival rate 16.0%. The 3-year survival rates for haematopoietic stem cell transplantation and chemotherapy groups were 44.4% and 8.3%, respectively. Multi-factor analysis showed that choice of therapy modality, and achievement of remission were significant factors for overall survival.</p><p><b>CONCLUSION</b>T-NHL is a group of heterogeneous malignancies. The response rate of intermediate-high and high risk T- NHL, especially PTCL-U and LTBL, is not low, but its long-term outcome is poor. New treatment modality needs to be explored for these patients, and autologous HSCT is perhaps a good choice.</p>