[Allogeneic hematopoietic stem cell transplantation in a patient with MonoMAC syndrome and hematopoietic dysplasia which was induced by GATA2 deficiency: a case report and literature review].

A retrospective analysis was conducted on a MonoMAC syndrome case admitted in October 2022 to the First Affiliated Hospital of Zhejiang University School of Medicine. The patient, a 16-year-old female with a history of persistent monocytopenia and mild anemia for several years, experienced recurrent symptoms of cough, expectoration, and fever, leading to multiple visits to the hospital. The diagnosis of MonoMAC syndrome was confirmed through comprehensive assessments including routine blood tests, pathogen metagenomic sequencing, lung and bone marrow biopsies, and next-generation sequencing of peripheral blood. The patient underwent haploidentical hematopoietic stem cell transplantation, with a smooth course of transplantation, achieving neutrophil engraftment on + 16 d and platelet engraftment on + 17 d, eventually restoring normal monocyte and NK cell counts. MonoMAC syndrome patients often initially present with infectious symptoms, and the diagnosis can be established based on significant monocytopenia in routine blood tests, history of non-tuberculous mycobacterial infections, and GATA2 germline mutations. Allogeneic hematopoietic stem cell transplantation may be required for some patients to improve their prognosis.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

[Research progress in the promotion of peri-implant soft tissue integration of dental titanium implant based on immune microenvironment regulation].

A good integration of dental implants and the surrounding soft tissue is essential to ensure the long-term effect of implant. In this review, we summarized the research progress of peri-implant soft tissue integration of dental titanium implants, with emphasis on the modification of the gingival interface of implants based on immune microenvironment regulation. This method influences the immune response around the implant by promoting the surface properties of implants, so as to enhance the peri-implant soft tissue integration. The purpose of this review is to provide reference for the related research and clinical application in the field of dental implantation.

[The effect of occupational stress on anxiety of nursing staff in a third-grade general hospital and mediating effect of job burnout].

Objective: To explore the mediating effect of job burnout of nursing staff in clinical departments on occupational stress and anxiety, and to provide scientific basis for the formulation of intervention measures to relieve anxiety. Methods: From November 2020 to January 2021, a cross-sectional survey was conducted to investigate the basic situation, occupational stress, job burnout and anxiety of 653 nursing staff in a third class A general hospital in Hebei Province. Spearman rank correlation was used to analyze the relationship between occupational stress, job burnout and anxiety, stepwise regression and mediating effect model were used to verify the mediating effect of job burnout on the relationship between occupational stress and anxiety. Results: 551 valid questionnaires were collected with effective recovery of 84.38%. The incidence of high occupational stress was 68.06% (375/551) , the incidence of job burnout was 63.70% (351/551) [high, moderate and moderate were 11.07% (61/551) and 52.63% (290/551) respectively], and the incidence of anxiety was 55.72% (307/551) [mild, moderate and severe were 38.11% (210/551) , 8.53% (47/551) and 9.08% (50/551) respectively]. Occupational stress was positively correlated with job burnout and anxiety (r=0.545, 0.479) , and job burnout was positively correlated with anxiety (r=0.542, P<0.05) . The mediating effect analysis showed that occupational stress had a statistically significant effect on anxiety (c=0.509, P<0.001) , and the mediating effect of job burnout on the relationship between occupational stress and anxiety accounted for 44.99% of the total effect. Conclusion: The anxiety level of the nursing staff in this third-class A general hospital was relatively high. Job burnout has a mediating effect between occupational stress and anxiety, and anxiety of nursing staff can be alleviated by reducing occupational stress or job burnout.

[The impact of donor-to-recipient gender compatibility on outcomes of haploid hematopoietic stem cell transplantation in patients with hematological malignancies].

Objective: To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases. Methods: From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) . Results: ① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups (P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups (P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively (P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % (P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion: The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.

[Clinical characteristics of severe pre-eclampsia in a single tertiary referral center].

Objective: To explore the feasibility and key point of improvement in preventing and postponing the onset of severe pre-eclampsia (SPE) and its severe complications in the tertiary referral system by analyzing the clinical characteristics of SPE in a single tertiary referral center. Methods: The clinical data of 217 patients with SPE who were hospitalized and terminated pregnancy in Peking University Third Hospital from January 2020 to December 2020 were retrospectively analyzed. The risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the characteristics and perinatal outcome. Results: (1) Clinical characteristics: among the 217 cases of SPE, 84 cases were in the referral group and 133 cases were in the central group. The gestational ages at SPE clinical diagnosis [31.5 weeks (28.1-34.6 weeks) vs 35.6 weeks (33.3-37.2 weeks); Z=-6.547, P<0.01], termination of pregnancy [32.3 weeks (29.5- 35.1 weeks) vs 36.3 weeks (34.4-37.5 weeks); Z=-6.554, P<0.01] and onset of SPE severe complications [30.6 weeks (26.4-32.7 weeks) vs 34.9 weeks (32.7-36.5 weeks); Z=-4.040, P<0.01] in the referral group were significantly earlier than those in the central group, the rates of ICU [10.7% (9/84) vs 3.8% (5/133); χ²=4.126, P=0.042] and neonatal ICU hospitalization [72.9% (51/70) vs 54.7% (70/128); χ²=6.286, P=0.012] were higher than those in the central group, while the live birth rate [83.3% (70/84) vs 96.2% (128/133); χ²=10.736, P=0.001] was lower than that of the central group. (2) Analysis of risk factors: for the patient whose risk factors were obesity, advanced age or pre-eclampsia history, the gestational ages at SPE clinical diagnosis and termination of pregnancy in the referral group were significantly earlier than those in the central group (P<0.05). For those with chronic hypertension, the gestational ages at severe complications onset in the referral group were significantly later than those in the central group (P<0.05). For those without obvious risk factors, the gestational ages at SPE clinical diagnosis, termination of pregnancy and onset of SPE severe complications in the referral group were earlier than those in the central group (P<0.05). (3) Analysis of severe complications: the top three severe complications in the referral group and the central group were hypertensive encephalopathy/cerebrovascular accident [20.2% (17/84) vs 7.5% (10/133)], HELLP syndrome [7.1% (6/84) vs 8.3% (11/133)] and placental abruption [8.3% (7/84) vs 7.5% (10/133)]. The rate of hypertensive encephalopathy/cerebrovascular accident in the referral group was significantly higher than that in the central group (χ²=7.645,P=0.006). (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (8.3%, 7/84), referral after onset of SPE (67.9%, 57/84), referral after detection of SPE early warning signs (14.3%, 12/84) and referral after detection of SPE risk factors in the 2nd and 3rd trimester (9.5%, 8/84). The earlier the referral, the longer the interval from clinical diagnosis to onset of severe complications, from referral to termination of pregnancy, and from referral to severe complications onset (P<0.05). The earlier the referral, the lower the NICU hospitalization rates, the higher the live birth rates. The ICU hospitalization rate of referrals after severe complications onset was significantly higher than those of the other three referral timing groups (P<0.05). Conclusions: SPE occurs in hospitals of different levels. Although tertiary referral center may postpone the onset of SPE and its severe complications, reduce the severity of SPE and prolong the gestational age, its awareness of prevention and control still needs to be further improved. Early identification of the risk of SPE and timely referral are important parts of improving SPE adverse outcomes in primary medical institutions. The significance and value of referral system need to be brought into full play.

[Spatial autocorrelation and its application in public health field].

The prevalence and distribution of infectious diseases and occupational diseases in specific time and space is the result of the interaction between natural environment, social economy and other factors, its distribution pattern has spatial properties. Based on the assumption of independence, the traditional statistical methods ignore the spatial attributes of diseases and cannot analyze the spatial characteristics of diseases. On the basis of geographic information system, the spatial autocorrelation analysis can simultaneously analyze the spatial relationship and attribute value of diseases, explore the spatial dependence of disease data in different spatial units, and provide decision-making basis for the prediction and early warning of diseases such as occupational and infectious diseases, and the formulation and evaluation of prevention and control measures.

[The characteristics of spatial-temporal evolvement of pneumoconiosis in Hebei Province from 2009 to 2018].

Objective: To explore the temporal and spatial characteristics of pneumoconiosis in Hebei Province from 2009 to 2018, and to provide evidence for the policy development of pneumoconiosis prevention and control. Methods: In February 2019, a database of pneumoconiosis incidence from 2009 to 2018 in Hebei Province was built. The spatial-temporal distribution of pneumoconiosis in Hebei Province was displayed based on barycenter migration technology and spatial autocorrelation analysis. Results: A total of 6099 cases of pneumoconiosis were reported in Hebei Province from 2009 to 2018, the top 5 pneumoconiosis were silicosis(4399, 72.13%) , coal worker pneumoconiosis (1298 , 21.28%) , ceramics pneumoconiosis (224, 3.67%) , welding worker's pneumoconiosis(76, 1.25%) , and casting worker's pneumoconiosis(48, 0.79%). The focus of pneumoconiosis from 2009 to 2014 moved from Tangshan in the northeast to Zhangjiakou in the northwest, and moved to Chengde in the north from 2015 to 2017, and moved back to Tangshan in 2018. The incidence of pneumoconiosis was globally autocorrelation (P <0.05) from 2009 to 2011 and 2014 to 2018. The high-high gathering areas were located in Zhangjiakou, Chengde and other areas. Conclusion: The barycenter of pneumo- coniosis in hebei province from 2009 to 2018 is relatively stable, mainly locates in the northern part of Hebei Province over the years. There is an obvious regional aggregation, and the aggregation type is mainly high-high aggregation, which indicates that relevant departments should focus on strengthening the prevention and treat- ment of aggregation areas on the basis of overall planning.

[Preliminary study of human serum albumin level in early warning onset of preeclampsia].

Objective: To observe the dynamic changes of human serum albumin (HSA) level during pregnancy and study the early warning significance of HSA level on the onset of preeclampsia (PE) . Methods: Totally 369 PE pregnant women (PE group) and 309 normal pregnant women (control group) without PE who admitted in Haidian Maternal and Child Health Hospital from January 2013 to December 2017 were selected. HSA levels were tested before meeting the criterion of PE in the first trimester, the early-third trimester and the late-third trimester, the difference between the two groups were compared. The relationship between the HSA level and the incidence of complications in PE patients was analyzed. Results: (1)The mean values of HSA level in PE group and control group were (41.9±3.1) versus (40.0±2.2) g/L, (34.2±2.7) versus (35.4±2.7) g/L and (33.7±2.9) versus (36.7±3.3) g/L in the first trimester,the early-third trimester and the late-third trimester respectively,the difference in the first trimester was no significance (P>0.05), while the differences in the early-third trimester and the late-third trimester were both significant (all P<0.05). (2) The HSA level during pregnancy of PE group showed a continuous downward trend, while the control group was V-shaped trend. The receiver operating characteristic (ROC) curve analysis showed that PE could be early warned by the decrease of HSA level in PE group [area under curve (AUC)=0.742, cut-off value=5.97 g/L, sensitivity 70.8%, specificity 62.8%], the same result was in severe PE (AUC=0.756, cut-off value=6.85 g/L, sensitivity 70.8%, specificity 72.0%). The level of HSA was negatively correlated with the incidence of complications (r=-0.19, P<0.01). Conclusions: Excessive decrease of HSA level is an early warning factor for PE onset. The higher the baseline of HSA level and the greater the extent of pregnancy decline, the risk of PE in pregnant women is higher. The lower of HSA level in PE, the incidence of complications is higher. The excessive decrease of HSA level may be the first clinical manifestation before the onset of clinical symptoms of PE, so it may be the warning factor and one of the laboratory indicators in the PE sub-clinical stage.

Carfilzomib combined with ex vivo-expanded patient autologous natural killer cells for myeloma immunotherapy.

Natural killer (NK) cell-based immunotherapy is promising, as NK cells are in the first line of defense against cancer and capital of lysing tumor cells without pre-stimulation. However, NK cells from multiple myeloma (MM) patients are always deficient in numbers and the expression of certain activating receptors, disabling them in cytotoxicity against the cancer. Therefore, effective strategies to expand NK cells and increase NK cell-mediated cytotoxicity against MM are significant. Here, NK cells were efficiently expanded from peripheral blood mononuclear cells (PBMCs) of newly diagnosed MM patients after co-culture with irradiated K562 cells transfected with 41BBL and membrane-bound interleukin (IL)-15 (K562-mb15-41BBL) in the presence of 200 IU/ml human IL-2. The ex vivo-expanded NK cells were demonstrated to vigorously kill both MM cells and autologous primary MM cells without significant lysis of patient normal cells. Further exploration revealed a significant increase in cell surface expression of most activating receptors of NK cells and indicated that expanded NK (exp-NK) cell killing of MM cells was mediated by perforin/granzyme. NK cells are capital of lysing human leukocyte antigen (HLA) I-deficient tumor cells and carfizomib, a selective proteasome inhibitor approved for the treatment of relapsed/refractory MM patient, down-regulates the expression of HLA class I, thus enhancing NK cell-mediated lysis in MM. Here, we found for the first time that carfizomib dramatically augmented ex vivo exp-NK cell cytotoxicity against patient autologous MM cells, suggesting the use of exp-NK alone or in combination with the drug to treat MM patient.

[The effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation in acute leukemia].

Objective: To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) . Methods: Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression. Results: The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ(2)=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ(2)=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) . Conclusion: High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.

[A multicenter, retrospective study of pathogenic bacteria distribution and drug resistance in febrile neutropenic patients with hematological diseases in Shanghai].

Objective: To investigate the pathogen spectrum distribution and drug resistance of febrile neutropenic patients with hematological diseases in Shanghai. Methods: A retrospective study was conducted on the clinical isolates from the febrile neutropenic patients hospitalized in the departments of hematology in 12 general hospitals in Shanghai from January 2012 to December 2014. The drug susceptibility test was carried out by Kirby-Bauer method. WHONET 5.6 software was used to analyze pathogenic bacteria and drug susceptibility data. Results: A total of 1 260 clinical isolates were collected from the febrile neutropenic patients. Gram-positive bacteria accounted for 33.3% and Gram-negative bacteria accounted for 66.7%. Klebsiella pneumoniae (12.5%) , Stenotrophomonas maltophilia (9.5%) , Escherichia coli (9.1%) , Pseudomonas aeruginosa (8.7%) , Acinetobacter baumannii (6.6%) , Staphylococcus aureus (5.6%) and Enterococcus faecium (5.0%) were ranked in the first 7 of all pathogens. In the respiratory tract secretions specimens, non-fermented strains accounted for 56.2%. Stenotrophomonas maltophilia accounted for 15.2%. Enterobacteriaceae and coagulase-negative Staphylococci accounted for 42.3% (104/246) and 32.6% (85/246) respectively in blood samples. Enterobacteriaceae and Enterococcus bacteria accounted for 39.4% (76/193) and 28.5% (55/193) respectively in pus specimens. The detection rates of methicillin resistant Staphylococcus aureus (MRSA) and methicillin resistant coagulase negative Staphylococci (MRCNS) were 54.3% and 82.5%, respectively. Staphylococcus bacterial strain was not found to be resistant to linezolid, vancomycin and teicoplanin. The detection rate of Enterococcus vancomycin-resistant strains was 8.9%. Enterococcus was not detected resistance to oxazolidinone strains. Enterobacteriaceae bacteria were highly sensitive to carbapenems. The resistance rate of Pseudomonas aeruginosa to imipenem and meropenem was 34.1% and 15.8%, respectively. Stenotrophomonas maltophilia was more sensitive to minocycline hydrochloride, levofloxacin and sulfamethoxazole. The resistance rate of Acinetobacter baumannii only to cefoperazone-sulbactam was less than 10.0%. The antibiotic resistance rate of Klebsiella pneumoniae, Stenotrophomonas maltophilia, Pseudomonas aeruginosa and Acinetobacter baumanii to most of common antibiotics was lower than that of the CHINET surveillance. Conclusions: The pathogenic strain distribution in common infection sites of febrile neutropenic patients was characterized. Bacterial resistance surveillance was better than the CHINET nationwide large sample surveillance in China.

Quantitative candidate gene association studies of metabolic traits in Han Chinese type 2 diabetes patients.

Recent genome-wide association studies have identified many loci associated with type 2 diabetes mellitus (T2DM), hyperuricemia, and obesity in various ethnic populations. However, quantitative traits have been less well investigated in Han Chinese T2DM populations. We investigated the association between candidate gene single nucleotide polymorphisms (SNPs) and metabolic syndrome-related quantitative traits in Han Chinese T2DM subjects. Unrelated Han Chinese T2DM patients (1975) were recruited. Eighty-six SNPs were genotyped and tested for association with quantitative traits including lipid profiles, blood pressure, body mass index (BMI), serum uric acid (SUA), glycated hemoglobin (HbA1c), plasma glucose [fasting plasma glucose (FPG)], plasma glucose 120 min post-OGTT (P2PG; OGTT = oral glucose tolerance test), and insulin resistance-related traits. We found that CAMTA1, ABI2, VHL, KAT2B, PKHD1, ESR1, TOX, SLC30A8, SFI1, and MYH9 polymorphisms were associated with HbA1c, FPG, and/or P2PG; GCK, HHEX, TCF7L2, KCNQ1, and TBX5 polymorphisms were associated with insulin resistance-related traits; ABCG2, SLC2A9, and PKHD1 polymorphisms were associated with SUA; CAMTA1, VHL, KAT2B, PON1, NUB1, SLITRK5, SMAD3, FTO, FANCA, and PCSK2 polymorphisms were associated with blood lipid traits; CAMTA1, SPAG16, TOX, KCNQ1, ACACB, and MYH9 polymorphisms were associated with blood pressure; and UBE2E3, SPAG16, SLC2A9, CDKAL1, CDKN2A/B, TCF7L2, SMAD3, and PNPLA3 polymorphisms were associated with BMI (all P values <0.05). Some of the candidate genes were associated with metabolic and anthropometric traits in T2DM in Han Chinese. Although none of these associations reached genome-wide significance (P < 5 x 10(-8)), genes and loci identified in this study are worthy of further replication and investigation.

Effects of acrylonitrile on lymphocyte lipid rafts and RAS/RAF/MAPK/ERK signaling pathways.

Acrylonitrile (ACN) is a widely used chemical in the production of plastics, resins, nitriles, acrylic fibers, and synthetic rubber. Previous epidemiological investigations and animal studies have confirmed that ACN affects the lymphocytes and spleen. However, the immune toxicity mechanism is unknown. Lipid rafts are cell membrane structures that are rich in cholesterol and involved in cell signal transduction. The B cell lymophoma-10 (Bcl10) protein is a joint protein that is important in lymphocyte development and signal pathways. This study was conducted to examine the in vitro effects of ACN. We separated lipid rafts, and analyzed Bcl10 protein and caveolin. Western blotting was used to detect mitogen-activated protein kinase (MAPK) and phosphorylated MAPK levels. The results indicated that with increasing ACN concentration, the total amount of Bcl10 remained stable, but was concentrated mainly in part 4 to part 11 in electrophoretic band district which is high density in gradient centrifugation. Caveolin-1 was evaluated as a lipid raft marker protein; caveolin-1 content and position were relatively unchanged. Western blotting showed that in a certain range, MAPK protein was secreted at a higher level. At some ACN exposure levels, MAPK protein secretion was significantly decreased compared to the control group (P < 0.05). These results indicate that ACN can cause immune toxicity by damaging lipid raft structures, causing Bcl10 protein and lipid raft separation and restraining Ras-Raf-MAPK-extracellular signal-regulated kinase signaling pathways.

Donor TLR9 gene tagSNPs influence susceptibility to aGVHD and CMV reactivation in the allo-HSCT setting without polymorphisms in the TLR4 and NOD2 genes.

Owing to ethnicity of the population, those best confirmed polymorphisms in the TLR (toll-like receptor)4 and NOD2 genes with significantly prognostic impact on allogeneic hematopoietic SCT (allo-HSCT) seem to be more applicable to Europeans and are nonpolymorphic in the Asian population. The influence of innate immunity gene polymorphisms on the outcomes of allo-HSCT in those populations has been questioned. We evaluated the influence of 10 candidate single nucleotide polymorphisms (SNPs) in the TLR1, TLR2, TLR3, TLR8 and TLR9 genes on the outcomes of allo-HSCT in a Chinese population including 138 pairs of patients and unrelated donors and a second cohort of 102 pairs of patients and HLA-identical sibling donors. We found that two tagSNPs in the TLR9 gene in the donor side, +1174 A/G (rs352139) and +1635 C/T (rs352140), influenced the risk of acute GVHD (aGVHD) and CMV reactivation. Furthermore, the presence of the susceptible haplotype (A-C) in donor may be an informative predicator of worse OS at 5 years compared with those with the G-C and G-T haplotypes (58% vs 82.9%, P=0.024). Our data suggested an unrecognized association between donor TLR9 tagSNPs and the risk of HSCT-related complications in a population without polymorphisms in the TLR4 and NOD2 genes.

Expression of multidrug resistance 1 and multidrug resistance-related protein 1 in C57BL/6 mice treated with benzene.

ATP-binding cassette super family (ABC) proteins are considered key to oncology and pharmacology studies. We examined the effect of benzene on ABC pump protein levels in C57BL/6 mouse bone marrow mononuclear cells. After a 2-week gavage (200 mg/kg, 5 days per week), the number of peripheral leukocytes, lymphocytes and basophils dropped significantly; there was also a significant decrease in MDR1 and MRP1 gene expression. A significant reduction in expression of P-gp was found; however, there was no significant decrease in the expression of MRP1 and NF-κB p65. We conclude that regulation of membrane efflux transport protein could be a factor in benzene hematotoxicity.

Determination of heterocyclic amines in braised sauce beef.

A simplified and improved analysis method to determine the content of heterocyclic amines (HAs) was developed. Samples were extracted with ethyl acetate, and macrosubstances were removed by centrifugation. The eluent used consisted of methanol/ammonia water (9:1, v/v), and the eluates were directly mixed for further HPLC analysis. A binary mobile phase consisting of 0.05 M ammonium acetate-acetic acid and acetonitrile was used for the separation of 12 HAs, and the excitation and emission wavelengths of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) were adjusted to the same 315 and 410 nm, respectively. This method was further applied to determine the content of HAs in "Jiang Niu Rou", namely braised sauce beef. Nine kinds of HAs were found in the samples and the total amounts of HAs ranged from 4.33 to 27.15 ng/g. The sterilized samples contained more HAs than un-sterilized samples.

First live offspring born in superovulated sika deer (Cervus nippon) after embryo vitrification.

The rapid growth in sika deer (Cervus nippon) farming and interest in their conservation is an impetus for development of embryo transfer (ET) procedures. However, a paucity of research has prevented widespread application of ET in this species. The objective of the present study was to establish a multiple ovulation and ET procedure with both fresh and vitrified embryos in sika deer. Multiparous weaned hinds (N = 18) were used as embryo donors during the reproductive season of 2008 at a local breeding farm in China. Estrus was synchronized in donors and recipients (N = 38) by inserting a controlled internal drug release for 12 days (insertion = Day 0). Superovulation was induced with a total of 320 mg of NIH-FSH-P1 (Folltropin-V; Bioniche, Belleville, ON, Canada) given as 40 mg im every 12 h from the afternoon of Day 9 to the morning of Day 13. After estrus was detected, donors were artificially inseminated using a transcervical technique. The embryo recovery rate was 76.8% (63/82), including 1.6% (1/63), 77.8% (49/63), and 1.6% (1/63) blastocysts, morula, and eight-cell embryos, respectively. After transfer of fresh and vitrified embryos, pregnancy rates were 85.7% and 61.6% and birth rates were 64.3% and 53.9% (P > 0.05). In conclusion, we developed a satisfactory multiple ovulation and ET procedure in farmed sika deer using vitrified embryos.

Haploidentical allogeneic haematopoietic stem cell transplantation as salvage therapy for engraftment failure after unrelated and autologous stem cell transplantation: a case report and review of the literature.

Engraftment failure is a rare but life-threatening complication of haematopoietic stem cell transplantation (HSCT) and treatment of this condition is often challenging. This case report describes a patient with acute myeloid leukaemia and engraftment failure after unrelated donor allogeneic stem cell transplantation. Rescue treatment with granulocyte-colony stimulating factor and reinfusion of autologous 'back-up' stem cells failed, but transplantation of haploidentical donor stem cells following a fludarabine and antithymocyte globulin (ATG)-based conditioning regimen resulted in haematological reconstitution and long-term disease-free survival. The use of haploidentical donor stem cell transplantation as salvage therapy after engraftment failure in adult patients has not, to the authors' knowledge, been previously reported. Additionally, a review of the relevant literature is presented. This case report and literature review suggest that reinfusion of cryopreserved 'back-up' haematopoietic stem cells is a safe and effective salvage therapy for engraftment failure after allogeneic HSCT. Haploidentical donor stem cell transplantation after a fludarabine and ATG-based conditioning regimen could provide effective second-line therapy in adult patients.