[Infectious complications following chimeric antigen receptor T-cell therapy for a hematologic malignancy within 28 days].

Objective: To explore the incidence, clinical and microbiological characteristics and risk factors of infection in patients with acute lymphoblastic (ALL) , non-Hodgkin lymphoma (NHL) , and multiple myeloma (MM) within 28 days after CAR-T cell infusion. It provides data support for early identification of infection and the rational use of antibacterial drugs in these patients. Methods: We retrospectively analyzed the baseline data of 170 patients with ALL, NHL and MM who received chimeric antigen receptor-modified T (CAR-T) -cell treatment in the Department of Hematology of Wuhan Union Hospital from January 2016 to December 2020, and the clinical characteristics of infection within 28 days after infusion, including 72 patients with ALL, 56 patients with NHL, and 42 patients with MM; we used Poisson regression and Cox proportional hazard regression models to assess high-risk factors for infection before and after infusion, respectively. Results: Among 170 patients, 119 infections occurred in 99 patients within 28 days, with a cumulative infection rate of 58.2%. Seventy-eight patients had 98 bacterial infections and the cumulative incidence of bacterial infection was 45.9%. The infection density was 2.01, and the median time for the first infection was about 12 days after infusion. The adjusted baseline characteristic model showed that ALL patients, previous 30 days of infection history, refractory disease, absolute neutrophil count (ANC) <0.5×10(9)/L before infusion and ≥4 prior antitumor treatment regimens had a higher infection density within 28 days; grade 3 or 4 CRS was the only high-risk factor related to infection after infusion in the multivariate analysis. Conclusion: Infection is a common complication of CAR-T cell therapy in patients with hematologic malignancy. Bacterial infections occur in most patients regardless of the type of disease. ALL patients, previous 30 days of infection history, refractory disease, ANC<0.5×10(9)/L before infusion and grade 3 or 4 CRS are risk factors for infection. Chinese Clinical Trial Register:: ChiCTR-OIC-17011180, ChiCTR1800018143.

[Gene analysis and clinical features of MYH9-related disease].

Objective: To identify gene variants and investigate clinical features of nonmuscle myosin heavy chain 9-related disease (MYH9-RD). Methods: In this retrospective study, the data of patients with MYH9-RD admitted to Shenzhen Children's Hospital from July 2017 to September 2020 were extracted. The gene variants, clinical features and laboratory tests results were summarized. Results: Among the 6 children, 4 were males and 2 were females, aged 4.0 (0.5-7.6) years. Main clinical manifestations included thrombocytopenia (6 cases), epistaxis (3 cases), petechias (2 cases), traumatic hematoma (1 case), and abnormal liver enzymes (1 case). One patient had no family history, and the other 5 cases were pedigrees. Two pedigrees (2 cases) had long-term microscopic hematuria, one pedigree (2 cases) had history of early cataract, and three pedigrees (5 cases) had chronic mild elevation of liver enzymes. Four MYH9 gene variants were found in 12 patients, including c.2104C>T(p.R702C) in exon 17, c.4270G>A(p.D1424N) in exon 31, c.5521G>A (p.E1841K) in exon 39, and c.5797C>T (p.R1933X) in exon 41. According to the family pedigrees analysis, except for the case of variant in exon 17 which was spontaneous mutation with no family history, the other variants were from their father or mother. The complete blood count results showed a decreased platelet number in these patients, and the counting results of the automated hematology analyzer were significantly lower than that of manual counting method ((33.4±17.2) × 109 vs. (60.4±21.0) × 109/L,t=-5.83, P<0.05). The examination of the peripheral blood smear revealed the presence of thrombocytopenia with giant platelets and granulocyte inclusion bodies. The MYH9 gene variant (R702C) located at the N-terminus head domain of non-muscle myosin heavy chain ⅡA (NMMHC-ⅡA), which has ATPase activity, led to severe reduction of platelet number (<20×109/L) and obscure granulocyte inclusion bodies. However, higher platelet numbers (40×109-80×109/L) and obvious granulocyte inclusion bodies were observed in patients with tail-position mutations at C-terminus. Conclusions: The clinical phenotypes of MYH9-RD were variable. The mutations in certain regions of MYH9 gene were related to platelet count and granulocyte inclusion bodies. MYH9-RD should be considered in individuals with unknown etiology and persistent thrombocytopenia which is non-responsive to conventional treatment, regardless of family history. Complete blood count and blood smear morphology examinations are the first steps to screen and diagnose the disease. The laboratory should pay attention to the morphological review rules and standardized reports.

[Clinicopathological characteristics and prognosis of patients with sporadic multiple primary gastrointestinal stromal tumors].

Objective: To investigate the clinicopathological characteristics and prognosis of sporadic multiple primary gastrointestinal stromal tumor (GIST). Methods: A retrospective cohort study was conducted. Case inclusion criteria: (1) postoperative pathological diagnosis of GIST; (2) primary GIST with single lesion or sporadic multiple primary GIST (sporadic GIST was defined as primary GIST other than familial and syndrome-related GIST, and multiple primary GIST was defined as the number of primary GISTs in the same patient ≥ 2); (3) patients with complete clinicopathological data. Those with tumor recurrence or distant metastasis, and with other malignancies were excluded. Medical records of patients with primary GIST who underwent surgical resection in the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2010 to December 2020 were collected. Patients were divided into sporadic multiple primary GIST group and single primary GIST group according to the number of primary GIST lesions. The clinicopathological data and prognosis of the two groups were observed and compared. Results: A total of 1200 patients with primary GIST were enrolled in this study, including 628 males (52.3%) and 572 females (47.7%), with a median onset age of 58 (19-93) years. Among them, 1165 cases (97.1%) were sporadic primary GIST with single lesion; 35 cases (2.9%) were sporadic multiple primary GIST. Among 35 cases of sporadic multiple primary GIST, 3 cases (8.6%) had acid reflux as the first symptom, which was higher than the single primary GIST group (22/1165, 1.9%) (χ(2)=7.437, P=0.006). There were no significant differences in other clinical characteristics between the two groups (all P>0.05). Patients in the sporadic multiple primary GIST group contained a total of 80 primary tumors. Compared with the single primary GIST group, the sporadic multiple primary GIST group had a higher proportion of tumors originating in the stomach [87.5% (70/80) vs. 59.1% (689/1165)], lower proportion of spindle cell in histology [85.0% (68/80) vs. 93.7% (1092/1165)], higher proportion of positive CD34 [97.5% (78/80) vs. 87.6% (1021/1165)], smaller maximum diameter [maximum diameter ≤2.0 cm: 61.2% (49/80) vs. 28.8% (335/1165)], lower mitotic rate [≤5/50 high-power fields (HPF): 93.8% (75/80) vs. 74.5% (868/1165)], lower risk of recurrence [60.0% (48/80) vs. 23.3% (271/1165)], and the differences were all statistically significant (all P<0.05). The 3-year recurrence-free survival rate in the sporadic multiple primary group and the single primary GIST group was 96.6% and 89.3% respectively (P=0.160), and the 3-year overall survival rate was 100.0% and 92.8%, respectively (P=0.088). Conclusions: The most common type of sporadic multiple primary GIST is multiple tumors originating in the stomach at the same time. Compared with primary GIST with single lesion, sporadic multiple primary GIST presents smaller maximum diameter and lower mitotic rate. The prognosis of patients between two groups is not significantly different.

[Plasma differentially expressed genes and bioinformatics analysis of workers occupationally exposed to mercury].

Objective: To screen and identify plasma differentially expressed genes and related signal pathway by human gene expression profile array and fluorescent quantitative PCR. Methods: From September 2018 to October 2019, 291 workers from a Mercury-in-glass thermometer factory in Jiangsu Province were selected for an occupational health examination, a total of 60 persons were divided into two groups: high and low mercury exposure groups (30 persons in each group) . Plasma total RNA samples from the high exposure group and the low exposure group (10 cases each) were detected by gene expression microarray, and differentially expressed genes (DEGs) with fold change >2 were selected. DEGs were submitted to David and Metascape for gene function clustering, pathway and protein interaction network analysis. Finally, fluorescence quantitative PCR was performed to verify the changes in the expression levels of key DEGs in the high exposure group and the low exposure group (another 20 cases in each group) . Results: A total of 269 DEGs, of which 203 up regulated and 66 down regulated were identified in the differential expression analysis of gene expression microarray. Bioinformatics analysis suggested that, DEGs were involved in forebrain development, glial cell fate determinants of GO biological process and PID NF-KB, PTEN signal pathway. NFE2L1, SOX8, SOX6 and RNF2 (P<0.05) were confirmed down regulated in high level group by fluorescent quantitative PCR compared with the low level group (fold changes were 2.10, 11.52, 2.19, and 4.38 respectively) . Conclusion: The plasma NFE2L1, SOX8, SOX6 and RNF2 gene expressions are significantly altered in occupa tional high mercury exposure population. PTEN signaling pathway and fate of glia cells determines the biological process may be closely related to the body injury caused by mercury exposure.

[The correlation between serum uric acid levels in the third trimester of pregnancy and adverse pregnancy outcomes].

Objective: To investigate the associations between serum uric acid levels during the third trimester of pregnancy and risks of adverse pregnancy outcomes. Methods: In this retrospective study, a cohort of 7 995 pregnant women who were hospitalized for childbirth from January 2014 to January 2019 were collected to compare pregnancy outcomes between subjects with or without hyperuricemia (HUA). A smooth curve analysis was used to evaluate the relationship between uric acid levels and preterm delivery, low birth weight and smaller than gestational age. Logistic regression analyses were performed to identify risk factors for adverse pregnancy outcomes, and the interaction of the factors. Results: During the third trimester of pregnancy, the uric acid levels of about 10% pregnant women were over 420 µmol/L. In those with HUA, the median neonatal birth weight was 2 590 (1 790, 3 410) g, the probability of premature birth was 49.81%, and the incidence of small than gestational age was 20.41%. These were significantly different from the women without HUA (the median neonatal birth weight: 3300 (2850, 3640) g; the probability of premature birth 23.09%; the incidence of small than gestational age 6.55%, respectively) (All P<0.001). Maternal uric acid levels were negatively correlated with neonatal birth weight, and positively correlated with the risk of smaller than gestational age. It has a U-shaped association with the probability of premature birth, and the lowest probability of premature birth was at 200-400 µmol/L of the uric acid. Risks of low birth weight (adjusted ß=-5.22, 95%CI-6.46--3.99) and smaller than gestational age (adjusted OR=1.03, 95%CI 1.02-1.04) were increased in the function of uric acid levels. High uric acid, hypertension, oligoamnios and preeclampsia were important risk factors for the adverse pregnancy outcomes. The risk of preterm delivery and low birth weight enhanced when hyperuricemia combined with hypertension and preeclampsia. Conclusions: Serum uric acid level can be used as one of reliable markers for predicting adverse pregnancy outcomes, which might provide theoretical basis for clinical intervention in practice.

CircRNA_0048211 protects postmenopausal osteoporosis through targeting miRNA-93-5p to regulate BMP2.

OBJECTIVE: The purpose of this study was to elucidate the potential influence of circular RNA (circRNA)_0048211/miRNA-93-5p/BMP2 regulatory loop in the progression of postmenopausal osteoporosis (PMOP). PATIENTS AND METHODS: Bone marrow samples were collected from PMOP patients (n=30) and healthy subjects (n=30) for isolating hBMSCs. Relative levels of circRNA_0048211, miRNA-93-5p, and BMP2 in hBMSCs isolated from PMOP patients and healthy controls were detected. In addition, their dynamic expressions in hBMSCs isolated from PMOP patients undergoing osteogenesis for 0, 7, 14, and 21 days were examined. Then, the interaction in the circRNA_0048211/miRNA-93-5p/BMP2 regulatory loop was verified by Dual-Luciferase reporter gene assay. Next, the potential influences of circRNA_0048211/miRNA-93-5p/BMP2 regulatory loop on osteogenesis-associated gene expressions, ALP activity, and mineralization ability were assessed. RESULTS: CircRNA_0048211 and BMP2 were downregulated, while miRNA-93-5p was upregulated in hBMSCs isolated from PMOP patients. In hBMSCs undergoing osteogenesis, circRNA_0048211, miRNA-93-5p and BMP2 were time-dependently changed. Overexpression of circRNA_0048211 upregulated RUNX2, OPN, and OCN, which also stimulated ALP activity and mineralization ability. CircRNA_0048211 could bind to miRNA-93-5p, and BMP2 was a direct target of miRNA-93-5p. In the meantime, circRNA_0048211 was negatively correlated with miRNA-93-5p, and positively correlated with BMP2. Besides, CircRNA_0048211/miRNA-93-5p/BMP2 regulatory loop was responsible for regulating osteogenesis-associated gene expressions, ALP activity, and mineralization ability in hBMSCs. CONCLUSIONS: CircRNA_0048211 negatively targets miRNA-93-5p to upregulate BMP2, thus alleviating the progression of PMOP.

MicroRNA-760 inhibits the biological progression of colorectal carcinoma by directly targeting FOXA1 and regulating epithelial-to-mesenchymal transition and PI3K/AKT signaling pathway.

OBJECTIVE: Colorectal carcinoma (CRC) is one of the most common factors for tumor-associated mortalities globally. In recent years, microRNAs (miRNAs) have been identified as novel therapeutic biomarkers for cancer treatment. The purpose of the current study was to unravel the clinical significance and underlying molecular mechanisms of miR-760 in CRC progression. PATIENTS AND METHODS: Fifty-four pairs of CRC tissue samples and adjacent para-carcinoma tissue samples were collected from CRC patients who underwent surgical resection. We measured miR-760 expressions in CRC using quantitative Real-time polymerase chain reaction (qRT-PCR) analysis. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and transwell assays were performed to determine the functions of miR-760 in CRC cell proliferation, invasion and migration. Dual-luciferase reporter assays and Western blots were used to investigate the underlying molecular mechanisms. Moreover, the association between miR-760 expressions and clinicopathological features was analyzed. RESULTS: In this study, the results showed that the down-regulated miR-760 expressions were related to the poor prognosis and malignant clinicopathologic features of CRC patients. Furthermore, functional assays revealed that miR-760 restoration obviously suppressed CRC cell proliferation, migration and invasion through modulating phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) pathway and epithelial-mesenchymal transition (EMT). FOXA1 was also considered as a functional target of miR-760 in CRC cells. Furthermore, miR-760 up-regulation also significantly repressed tumorigenesis in vivo. CONCLUSIONS: These results suggested that miR-760 exerted cancer-suppressive functions in CRC, providing a therapeutic strategy for CRC treatment.

Proton Shell Evolution below

The ß-delayed γ-ray spectroscopy of neutron-rich ^{123,125}Ag isotopes is investigated at the Radioactive Isotope Beam Factory of RIKEN, and the long-predicted 1/2^{-} ß-emitting isomers in ^{123,125}Ag are identified for the first time. With the new experimental results, the systematic trend of energy spacing between the lowest 9/2^{+} and 1/2^{-} levels is extended in Ag isotopes up to N=78, providing a clear signal for the reduction of the Z=40 subshell gap in Ag towards N=82. Shell-model calculations with the state-of-the-art V_{MU} plus M3Y spin-orbit interaction give a satisfactory description of the low-lying states in ^{123,125}Ag. The tensor force is found to play a crucial role in the evolution of the size of the Z=40 subshell gap. The observed inversion of the single-particle levels around ^{123}Ag can be well interpreted in terms of the monopole shift of the π1g_{9/2} orbitals mainly caused by the increasing occupation of ν1h_{11/2} orbitals.

[Quantitative evaluation of image quality of megavoltage computed tomography for guiding helical tomotherapy].

OBJECTIVE: To quantitatively analyze image quality of two sets of phantom (CatPhan504 and Cheese) Megavoltage computed tomography (MVCT) images acquired by Helical Tomotherapy with three scanning modes (Fine, Normal and Coarse), and to explore and validate a semi-automatic quality assurance procedure for MVCT images of Helical Tomotherapy. METHODS: On Helical Tomotherapy, CatPan504 and Cheese phantoms were scanned with three pitch levels (Fine, Normal, Coarse: 4 mm, 8 mm, 12 mm/circle) respectively. Pylinac, Matlab and Eclipse were used to calculate and compare spatial resolution, noise level and low contrast resolution of images obtained under three scanning modes respectively. The spatial resolution can be evaluated by the blurring of line-pair CT value in the images of CatPhan504's CTP528 module. The noise level can be evaluated by the integral non-uniformity in the images of Cheese's uniformity module. the low contrast resolution can be evaluated by contrast-to-noise ratio of both phantoms' plug-in module, or visibility of the region of interest (Supra-Slice) in the images of CatPhan504's CTP515 module. RESULTS: Analyses on CatPhan504's line pair module(CTP528 module) showed that the first three line pairs(the gap size are 0.500 cm, 0.250 cm and 0.167 cm respectively) could be clearly observed but blurring began to occur from the fourth line pair(the gap size is 0.125 cm) under Coarse mode. Meanwhile, the first four line pairs were all observable under the Normal and Fine modes. Integral non-integrity index(the value negatively correlated with the noise level) were 0.155 7, 0.136 8 and 0.122 9 for Coarse, Normal and Fine modes respectively. None of the Supra-Slice in CatPhan504's CTP515 module could be observed under three imaging modes. Low contrast contrast-to-noise ratio of Cheese phantom was similar under three modes and the insert visibility exhibited nearly linear growth with the increasing difference between CT average value of the insert material and background. CONCLUSION: Superiority and inferiority of three image modes in terms of the three image quality index was not consistent. Evaluation results above could provide reference for more rational decision on scanning modes selection of helical tomotherapy, which was based on image visualization demands in clinical practice. The proposed method could also provide guidance for similar image quality assessment and periodic quality assurance.

MiR-203 is essential for the shift from osteogenic differentiation to adipogenic differentiation of mesenchymal stem cells in postmenopausal osteoporosis.

OBJECTIVE: The purpose of this study was to investigate how miR-203 promotes osteogenic differentiation of bone marrow mesenchymal cells (BMSCs) by regulating its target gene DKK1, thereby inhibiting the occurrence of osteoporosis. PATIENTS AND METHODS: A total of 60 cases with postmenopausal osteoporosis and 40 cases of normal individuals were recruited. The expression of miR-203 in serum of all cases was detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The capacity of osteogenesis and adipogenic differentiation of MSCs was determined by alizarin red staining and oil red staining, respectively. Transfection of miR-203 mimics and miR-203 inhibitor were mediated by Liposomes, and then the MSCs were induced osteogenic and adipogenic differentiation. MiR-203 mimic was co-transfected with wild-type or mutant DKK1 for luciferase reporter gene detection. In the osteoporosis model of rats, the tibia was taken for micro-CT examination of bone mineral density (BMD) and bone volume/structural parameters (BV/TV), while the femur was taken for the measurement of absorption parameters (Ob.S)./BS) and the number of osteoclasts per circumference of bone (N.Oc/B.Pm). RESULTS: The expression level of miR-203 was significantly lower in patients with postmenopausal osteoporosis than that in normal individuals. The osteogenic capacity of BMSCs in these patients was reduced, while their adipogenic capacity was enhanced. MiR-203 promoted the expression of osteogenic genes and inhibited that of adipogenic genes. Knockdown of miR-203 decreased the level of osteogenic related genes but increased that of adipogenic related genes, while overexpression of miR-203 led to the opposite results. Furthermore, miR-203 inhibited the protein expression of DKK1. In addition, bone density and bone volume/structural parameters were lower in ovariectomized rats than those in normal rats. Meanwhile, bone resorption parameters and the number of osteoclasts per bone circumference in ovariectomized rats were higher than those in normal rats. CONCLUSIONS: MiR-203 can promote osteogenic differentiation of mesenchymal stem cells by downregulating the gene expression of DKK1.

[Safety and efficacy of rotational atherectomy in the interventional treatment of coronary chronic total occlusion lesions].

Objective: To investigate the safety and efficacy of rotational atherectomy in the interventional treatment of coronary chronic total occlusion lesions. Methods: In this retrospective study,a total of 31 consecutive patients with coronary chronic total occlusion(CTO) lesions underwent rotational atherectomy in our hospital from February 2004 to December 2016 were enrolled,and the clinical features were analyzed. Coronary atherectomy was performed if balloon failed to cross the CTO lesions or balloon could not be fully dilated in the CTO lesions after wire crossing. The definition of procedure success was defined as residual stenosis less than 20% after implantation of drug eluting stent and rotational atherectomy. After the procedure, the patients were followed up to observe major adverse cardiac and cerebral vascular events which including cardiogenic death, myocardial infarction, cerebrovascular accident, and target lesion revascularization. Results: The 1.25 mm diameter burr was firstly selected in 80.6% (25/31) patients,and 96.8%(30/31) patients used only 1 burr to complete the rotational atherectomy procedure. The complication rate was 9.8% (3/31) including 1 patient with coronary dissection and 3 patients with slow flow or no flow. There was 1 patent with both coronary dissection and slow flow. The procedure success rate was 96.8%(30/31). Interventional treatment related myocardial infarction occurred in 3 patients during hospitalization.The 30 patients with procedure success were followed up 36(11, 96) months. The incidence rate of major adverse cardiac and cerebral vascular events was 13.3% (4/30), of which the cardiogenic death rate was 3.3% (1/30), the myocardial infarction rate was 6.7% (2/30), cerebrovascular accident rate was 3.3%(1/30),and the target lesion revascularization rate was 6.7% (2/30). Conclusion: Rotational atherectomy is safe and effective in the interventional treatment of coronary CTO lesions.

[X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia: report of a family and literature review].

Objective: To investigate the clinical features and genetic characteristics of cases with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN). Methods: Characteristics of clinical material, immunological data and gene mutation of two cases with XMEN in the same family in China were retrospectively analyzed. The related reports literature were searched by using search terms'MAGT1 gene'or'XMEN'. Results: The proband, a 2-year-eight-month old boy, was admitted due to 'Urine with deepened color for two days and yellow stained skin for one day'. He had suffered from recurrent upper respiratory tract infection and sinusitis previously. Hemoglobin level was 38 g/L. The absolute count of reticulocytes was 223.2×10(9)/L. Urobilinogen level was 38 µmol/L (3-16 µmol/L). Coomb's test was positive. Both total (77.2 µmol/L) and indirect bilirubin (66 µmol/L) levels were elevated. There was an inverted CD4(+)/CD8(+)T cell ratio (0.89). The gene sequencing results showed MAGT1 gene c.472delG, p.D158Mfs*6 mutation. His 1-year-6-month old brother, was also identified to have MAGT1 gene c.472delG, p.D158Mfs*6 mutation.The younger brother mainly suffered from recurrent upper respiratory tract infection, accompanied by an inverted CD4(+)/CD8(+)T cell ratio (0.45), an elevated ratio and number of total B cells (45.7%). A total of 7 reports were retrieved including 11 male cases caused by MAGT1 gene mutation. These 11 cases were characterized by EBV viremia (11 cases), recurrent upper respiratory tract infection, otitis media or sinusitis (10 cases), secondary neoplasia diseases (8 cases), reduction of CD4(+)/CD8(+) T cell ratio (7 cases),and autoimmune thrombocytopenia or hemolytic anemia (2 cases). Conclusion: XMEN often manifests as male onset, recurrent upper respiratory tract infection, otitis media or sinusitis, EBV viremia, lymphoproliferative disease or lymphoma, autoimmune diseases and reduction of CD4(+)/CD8 (+)T cell ratio. NKG2D expression in NK cells is significantly reduced, and gene sequencing analysis shows a pathogenic mutation in MAGT1 gene.

[Comparing the immunogenicity and safety of sequential inoculation of sIPV followed by bOPV (â +â ¢) in different dosage forms].

Objective: To compare the safety and immunogenicity of two different sequential schedules of inactivated poliomyelitis vaccine made from Sabin strain (sIPV) followed by typeⅠ+Ⅲ bivalent oral poliovirus vaccine (bOPV) in Drug Candy (DC) form or liquid dosage form). Methods: This randomized, blinded, single center, parallel-group controlled trial was done from September 2015 to June 2016 in Liuzhou, Guangxi province. Healthy infants aged ≥2 months were eligible for enrollment and divided into 1sIPV+2bOPV or 2sIPV+1bOPV sequential schedules. According to the bOPV dosage form each sequential schedules, the subjects again were divided into drug candy(DC) form or liquid dosage form group, being 1sIPV+bOPV (DC)/1sIPV+2bOPV(liquid)/2sIPV+1bOPV(DC)/2sIPV+1bOPV(liquid). According to 0, 28, 56 d immunization schedule, Each group were given 3 doses. We recorded adverse events during the clinical trial (399 participants who receive at least one dose). 28 days post-Dose 3, we receive a total of 350 blood samples (excluding the quitters or subjects against trial plan), using cell culture trace against polio virus neutralization test Ⅰ, Ⅱ, Ⅲ neutralizing antibody (GMT), calculating the antibody positive rate.PolioⅠ,Ⅱand Ⅲ antibody titers were assessed by virus-neutralizing antibody assay and the seroconversion (4-fold increase in titer) from pre-Dose 1 to 28 days post-Dose 3 was calculated (total 350 samples) . Results: During the vaccination, the incidence of AEs in 1sIPV+2bOPV(DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV(DC), 2sIPV+1bOPV (liquid) group were 79%, 76%, 80% and 74% (χ(2)=1.23, P=0.747) , respectively. The severe AEs in groups were 6%, 5%, 6% and 4% (χ(2)=0.57, P=0.903) , respectively, and none was considered to be vaccination related. 28 days after 3(rd) vaccination, the seroconversion rates in 1sIPV+2bOPV (DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV (DC), 2sIPV+1bOPV (liquid) group, were 99%, 100%, 99% and 99% (χ(2)=0.94, P=0.815) , respectively, for type Ⅰ poliovirus; and 47%, 57%, 80%, 79% (χ(2)=31.56, P<0.001) , respectively, for type Ⅱ; and were 100%, 99%, 100%, 99% (χ(2)=2.02, P=0.568) , respectively, for type Ⅲ. In each group, the GMT of antibody against poliovirus typeⅠ were 4 539.68, 6 243.43, 6 819.53 and 7 916.29 (F=25.87, P<0.001) , respectively; Type Ⅱ were 12.98, 10.54, 63.75 and 84.21 (F=8.68, P=0.034) , respectively; Type Ⅲ were 1 172.55, 1 416.03, 2 648.89 and 3 250.75 (F=14.50, P=0.002) , respectively. Conclusion: On the same sequential schedules, there was no significant difference between the dosage forms, all of them showed good safety and immunogenicity. In the same dosage forms with different sequential schedules, the seroconversion rate was higher in 2 dose sIPV group than the 1 dose sIPV group, especially at the neutralizing antibody GMT level against polio type Ⅱ and Ⅲ after vaccination.

Describing the quality of life of boys with haemophilia in China: Results of a multicentre study using the CHO-KLAT.

INTRODUCTION: The treatment of haemophilia varies across countries and across regions within some countries. Similar variation has been observed in health-related quality of life (HR-QoL). Relatively little is known about the HR-QoL of boys with haemophilia in China. AIM: The aim of this study was to describe the HR-QoL of boys with haemophilia in China using the Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT). METHODS: Boys (4-18 years of age) with haemophilia and their parents were enroled in a cross-sectional study. All parents/guardians of study subjects were requested to complete a CHO-KLAT questionnaire during a clinic visit, and report on several other clinical and socioeconomic factors in the past year. Boys who were > 7 years also completed the CHO-KLAT. RESULTS: A total of 269 parents of boys with haemophilia, from 13 hospitals in 12 provinces, were enroled during 2014. The boys ranged from 4.0 to 17.9 years of age; 91% had haemophilia A, most had moderate (52%) or severe (36%) disease, and most were receiving sub-optimal on-demand therapy or low-dose prophylactic therapy. Child self-report CHO-KLAT scores were available for 171 boys ≥7 years of age and ranged from 24.2 to 85.3 with a mean of 57.6 (n = 171). Parent proxy-reported CHO-KLAT scores ranged from 25.0 to 88.7 with a mean of 55.1 (n = 269). CONCLUSION: HR-QoL scores in boys with haemophilia in China were substantially lower than reported from Canadian and European boys with haemophilia. Longer term prospective studies are required to examine the factors impacting the HR-QoL for boys with haemophilia in China.

[Clinical characteristics in gout patients with different body mass index].

Objective: Obesity is one of the risk factors for gout. The aim of the present study was to evaluate clinical characteristics of gout patients with different BMI. Methods: A total of 5 104 patients with gout were enrolled and divided into three groups according to the BMI. The clinical information was collected and relevant biochemical indices were detected. SPSS software was applied for the statistical analyses. Results: There were significant differences in the ratios of gender, regular exercise, hypertension, tophus, renal insufficiency, hyperlipidemia, impaired glucose metabolism, liver dysfunction among the three groups (all P<0.01). The onset age in overweight [45(36, 55) years] and obese subjects [40(31, 50) years] were earlier than that of the normal weight subjects [50(38, 61) years]. Moreover, waist circumstances [103(99, 108) cm and 94 (90, 98) cm vs 87 (82, 91) cm], systolic pressure [130 (120, 145) mmHg (1 mmHg=0.133 kPa)and 130(120, 140)mmHg vs 128(115, 140) mmHg], diastolic pressure [90 (80, 100) mmHg and 85 (80, 92) mmHg vs 80 (79, 90) mmHg], fasting blood glucose [5.77 (5.30, 6.44) mmol/L and 5.65 (5.19, 6.26) mmol/L vs 5.55 (5.10, 6.15) mmol/L], TG [2.10 (1.46, 3.04) mmol/L and 1.88 (1.35, 2.78) mmol/L vs 1.52 (1.07, 2.39) mmol/L], TC [5.20 (4.55, 5.93) mmol/L and 5.07 (4.46, 5.75) mmol/L vs 4.95 (4.27, 5.65) mmol/L], serum uric acid [483(418, 552) µmol/L and 461(395, 524) µmol/L vs 440 (368, 517) µmol/L], ALT [30 (21, 46) U/L and 25 (18, 36) U/L vs 21 (14, 29) U/L], AST [21(17, 28) U/L and 20 (17, 26) U/L vs 20 (6, 25) U/L], the number of joints involved [2(1, 3)joints and 2(1, 2) joints vs 1(1, 2) joints] in the overweight and obese groups were higher than those in the normal weight group ( all P<0.01). There were no statistical differences in family history, involvement of upper limb joints, kidney stones and coronary heart disease among the three groups (all P>0.05). Conclusions: Obesity is associated with an earlier age of gout onset.With the increase of BMI, the blood pressures, glucose, lipid, serum uric acid, liver transaminase levels and the number of involved joints increased gradually. Cautions should be taken in treating patients with different BMI.

Isoflurane and sevoflurane affects Wnt/ß-catenin signaling pathways in hippocampal formation of neonatal rats.

OBJECTIVE: General anesthesia impairs spatial learning and memory in neonatal rats. The aim of this study was to investigate whether the Wnt pathway was involved in neonatal isoflurane and sevoflurane exposure-induced neurocognitive impairment. MATERIALS AND METHODS: Sprague-Dawley rats were randomly assigned to administration isoflurane or sevoflurane for 6 hours at postnatal 7 days. Wnt inhibitor XAV 939 was administrated 30 min before anesthesia. Morris water maze was used to test the learning and memory at 5-week and 10-week. Hematoxylin and Eosin (H&E) stain was performed to evaluation the neuronal death in the hippocampus. Quantitative Real-time PCR (q-PCR) and Western blot assays were used to measure mRNA and proteins expression levels of the Wnt3a, GSK 3ß and ß-catenin, respectively. RESULTS: The results showed that isoflurane or sevoflurane could significantly increase neonatal death and cell lost in the developing brain and the Wnt inhibitor could improve the cell degeneration. It demonstrated that isoflurane or sevoflurane could impair the P7 rats learning and memory capability, while these effects were reduced over time. When rats treated Wnt inhibitor at 30 min before anesthesia, the impairment of brain could relieve. q-PCR and Western blot demonstrated that isoflurane or sevoflurane affects expression levels of Wnt3a, GSK 3ß and ß-catenin. These results suggested that impairment of learning and memory in P7 rats may be related to the Wnt signaling pathway. CONCLUSIONS: The results suggested general anesthesia treatment led to increased brain cell degeneration and impaired learning and memory in P7 rats via Wnt signaling pathway.

[Clinical exploratory application of robotic resection of tumor in segment â §: a report for 7 cases].

Objective: To investigate the feasibility and security of robotic resection of tumor in segment Ⅷ primarily. Methods: The clinicopathologic data of 7 patients who underwent robotic resection of tumor in segment Ⅷ using daVinci robotic system in the Department of Hepato-pancreato-biliary Surgical Oncology, Chinese PLA General Hospital from June 2016 to December 2016 were retrospectively analyzed. The lesion size, the tumor malignance degree mean operation time, intraoperative blood loss and the rate of conversion to laparotomy, postoperative hospital stay, mobidity and motality of all the 7 patients were collected. Results: All the 7 operations were successfully performed with radical resection.The mean tumor diameter was (4.6±1.2)cm. The mean operation time, intraoperative blood loss and postoperative hospital stay were(120.7±21.7)min, (100±106.7)ml, and(7.3±1.8)days respectively.All the patients were discharged successfully with no severe complications. Conclusions: According to our experiences, as a new operationmodel of minimally invasive surgery, robotic resection of tumor in segment Ⅷ has manyadvantages in laparoscopic like less trauma, less intraoperative bleeding, light postoperative pain, shorter postoperative hospital stay and so on. There are some certain advantages in exposure of Ⅷ segment under robotic surgery system. Robotic surgery system is safe and feasible for tumorresection of segmentⅧ, andhas clinical promoting value and application prospect.

Serum carcinoembryonic antigen-related cell adhesion molecule 1 level in postmenopausal women: correlation with ß-catenin and bone mineral density.

UNLABELLED: Many epidemiological studies have shown that in some tumors carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and ß-catenin appear to be related. However, it remains to be established whether CEACAM1 is related to ß-catenin in osteoporosis. Here, we reveal that CEACAM1 might influence the canonical Wnt/ß-catenin pathway to modulate bone metabolism in postmenopausal osteoporosis. INTRODUCTION: The aim of this study is to assess the serum level of CEACAM1 in postmenopausal women and its correlation with ß-catenin and bone mineral density (BMD). METHODS: The BMD was measured at the lumbar spine (L1-L4) or the femoral neck using dual-energy X-ray absorptiometry (DXA). Serum CEACAM1, ß-catenin, receptor activator of nuclear factor kappa-B (RANKL), osteoprotegerin (OPG), ß-isomerized C-terminal crosslinking of type I collagen (ß-CTX), intact N-terminal propeptide of type I collagen (PINP), estradiol, and insulin were measured in 350 postmenopausal women. Patients were divided according to lumbar spine or femur neck T-scores into osteoporosis (group I), osteopenia (group II), and normal bone mineral density, the latter serving as control. RESULTS: Serum CEACAM1 levels were significantly lower in group I and II compared to those in control subjects (P < 0.001). Serum CEACAM1 levels correlated positively with ß-catenin and BMD, but correlated negatively to the ratio between RANKL and OPG. CONCLUSION: This study provides evidence that decreased serum CEACAM1 levels are related to low BMD in postmenopausal women, and that serum CEACAM1 levels correlated positively to ß-catenin. It suggests that CEACAM1 might influence the canonical Wnt/ß-catenin pathway to modulate bone metabolism.