Modeling human pregastrulation development by 3D culture of blastoids generated from primed-to-naïve transitioning intermediates

Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro. Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates. However, whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown. Here, we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast, trophectoderm, and primitive endoderm signatures of the primed-to-naïve conversion process, which resemble natural blastocysts in morphological architecture, composition of cell lineages, transcriptome, and lineage differentiation potential. In addition, these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system. In summary, our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri- and postimplantation development in vitro.

Generating universal chimeric antigen receptor expressing cell products from induced pluripotent stem cells: beyond the autologous CAR-T cells / 中华医学杂志(英文版)

Adoptive therapeutic immune cells, such as chimeric antigen receptor (CAR)-T cells and natural killer cells, have established a new generation of precision medicine based on which dramatic breakthroughs have been achieved in intractable lymphoma treatments. Currently, well-explored approaches focus on autologous cells due to their low immunogenicity, but they are highly restricted by the high costs, time consumption of processing, and the insufficiency of primary cells in some patients. Induced pluripotent stem cells (iPSCs) are cell sources that can theoretically produce indefinite well-differentiated immune cells. Based on the above facts, it may be reasonable to combine the iPSC technology and the CAR design to produce a series of highly controllable and economical "live" drugs. Manufacturing hypoimmunogenic iPSCs by inactivation or over-expression at the genetic level and then arming the derived cells with CAR have emerged as a form of "off-the-shelf" strategy to eliminate tumor cells efficiently and safely in a broader range of patients. This review describes the reasonability, feasibility, superiority, and drawbacks of such approaches, summarizes the current practices and relevant research progress, and provides insights into the possible new paths for personalized cell-based therapies.

Application of Linear Accelerator on Boarding Kilovolt Fan Beam CT and Megavolt Cone Beam CT System on Set-up Errors During Radiation Treatment / 肿瘤防治研究

Objective To quantify the setup errors for the different anatomical sites of patients who received intensity-modulated radiotherapy (IMRT) with linear accelerator on-board kilovolt fan beam CT(kV-FBCT) as non-isocenter IGRT and megavolt cone beam CT (MV-CBCT) as isocenter IGRT. Methods A retrospective analysis was performedon 70 patients who underwent radiotherapy, kV-FBCT, and/or MV-CBCT scans after each routine setup prior to IMRT. The average displacement (M), systematic error (Σ), and random error (б) at different treatment sites in the left-right, anterior-posterior, and cranial-caudal directions were calculated according to the individual displacements. The formula 2.5Σ+0.7б was used to estimate the PTV margin in respective direction. For each single patient, the root mean square in three directions was used as 3D displacement. Results A total of 1130 displacements were recorded in the 70 patients. The PTV margin was estimated to be 1.9-3.1 mm in head and neck cancer, 2.8-5.1 mm in thoracic cancer, 4.6-5.1 mm in breast cancer, 3.0-5.5 mm in upper abdominal cancer, and 3.5-6.8 mm in pelvic tumor. For the 3D mean displacements, the head and neck, thoracic, breast, upper abdominal, and pelvic cancer were 2.4±1.0, 4.0±1.6, 4.1±2.0, 4.6±2.1, and 4.6±2.1 mm, respectively. The average 3D displacement obtained by kV-FBCT and MV-CBCT were 4.1 and 3.4 mm, respectively (P=0.212). Conclusion The quantitative setup-error data can be obtained using linear accelerator on-board FBCT, and the non-isocenter IGRT induced set-up error cannot be negligible.

Application of indocyanine green fluorescence imaging technique for hepatoblastoma resection in 13 children / 中华肝胆外科杂志

Objective:To analyse the application of indocyanine green (ICG) fluorescence contrast technique for resection of hepatoblastoma in children and to study its value in the application.Methods:The data of 13 children with pediatric hepatoblastoma who underwent open liver resection by using the ICG real-time image guided system were collected from June 2020 to October 2021 at the Children's Hospital of Nanjing Medical University. There were 10 males and 3 females. Their ages ranged from 5 days to 63 months, with a median of 22 months. The characteristics of the ICG imaging, surgical excision and postoperative pathology were analysed.Results:The tumors showed bright fluorescence in 13 patients. The border between the tumor and normal liver tissues was clear in 12 patients, and there was no difference between the background fluorescence of the liver and fluorescence of the tumor in one patient. Regular hepatic resection was performed in 6 patients and irregular hepatic resection in 7 patients under ICG fluorescence navigation. In one patient, the left half of the liver was resected, and there was no fluorescence on the transected surface of the liver remnant. The surface of the liver remnant was scattered with fluorescence showing multiple tumors, which were then locally enucleated. Twelve specimens which were fluorescently visualized were bisected with 8 specimens showing partial fluorescence visualization of the nodules within the tumor + annular visualization at the margins, and 4 patients showing annular fluorescence visualization at the tumor margins only. In 12 children, histopathological examination of the tissues at the site with circumferential imaging showed distorted, vacuolated and densely arranged hepatocytes resembling pseudo-envelope changes due to compression, but there were no tumor cells.Conclusion:The ICG fluorescence contrast technique was very effective for resection of childhood hepatoblastoma, and the ring fluorescence contrast of the tumor edge indicated the border for tumor resection. The ICG contrast plays an important role in navigating tumor resection, especially in patients with multiple tumor nodules.

Targeted therapy and immunotherapy of esophageal cancer / 国际肿瘤学杂志

Esophageal cancer is a complex digestive tract cancer. Currently, the study of radiotherapy and chemotherapy for non-surgical esophageal cancer has reached the bottleneck. In recent years, with the in-depth study of tumor signal pathway related targets and immunotherapy, tumor treatment methods are becoming more and more diversified. At present, research shows that a variety of gene targets and immune receptors are related to esophageal cancer, including epidermal growth factor receptor, vascular endothelial growth factor, human epidermal growth factor receptor 2, programmed death-1/programmed death ligand-1, etc. In addition, tumor vaccine and adoptive cell therapy are also being studied. These factors contribute to the individualized and accurate treatment of esophageal cancer and improve survival rate and local control rate.

Diagnosis of splenic marginal zone lymphoma / 白血病·淋巴瘤

Objective:To explore the clinical features, diagnosis and differential diagnosis of splenic marginal zone lymphoma.Methods:The clinical diagnosis and differential diagnosis processes of 3 cases of CD5 - CD10 - B cell non-Hodgkin lymphoma with splenomegaly and cytopenia who were admitted to Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology in 2019 were retrospectively analyzed, and the relevant literature was reviewed. Results:The 3 cases were all elderly patients with varying degrees of splenomegaly and cytopenia. CD5 - CD10 - monoclonal B lymphocytes were found in the bone marrow or lymph nodes. Based on the patient's clinical characteristics, peripheral blood and bone marrow morphology, immunophenotype and genetic characteristics, 2 patients were diagnosed as splenic marginal zone lymphoma, and 1 patient was diagnosed as diffuse large B-cell lymphoma. Conclusions:The diagnosis of splenic marginal zone lymphoma requires comprehensive analysis of clinical characteristics, peripheral blood and bone marrow morphology, immunophenotype and genetic characteristics. Careful differentiation from other CD5 - CD10 - small B-cell lymphomas is also needed. The next-generation gene mutation high-throughput sequencing and mutational spectrum analysis will help the accurate diagnosis of atypical and difficult cases.

Application values of multiple detection methods of bone marrow in newly diagnosed multiple myeloma / 白血病·淋巴瘤

Objective:To investigate the application values of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH) and cytogenetic testing in newly diagnosed multiple myeloma.Methods:A total of 280 patients with multiple myeloma who were newly diagnosed in Tianjin KingMed Diagnosis Center from September 2018 to August 2019 were collected. The bone marrow biopsy was carried out according to the routine method, and bone marrow morphology, bone marrow immunohistochemistry, flow cytometry immunophenotyping, FISH and cytogenetic testing were performed. The detection results of each method were compared.Results:In 280 patients, the bone marrow immunohistochemistry results showed that the median ratio of plasma cells was higher than those of bone marrow morphology (20 cases, 0.675 vs. 0.300) and flow cytometry (47 cases, 0.650 vs. 0.147), and the differences were statistically significant ( Z = -3.883, P < 0.01; Z = -5.947, P < 0.01). Flow cytometry results showed that the positive rates of CD38, CD138, κ, λ, CD56 and CD19 were 100.0% (280/280), 100.0% (280/280), 57.5% (161/280), 42.5% (119/280), 62.1% (174/280) and 19.3% (54/280); bone marrow immunohistochemistry results showed that the positive rates of CD38, CD138, κ, λ and CD56 were 98.9% (277/280), 98.2% (275/280), 57.5% (161/280), 42.5% (119/280) and 62.1% (174/280); there was no statistical difference between the two detection methods in the detection coincidence rate of the same detection index (all P > 0.05). Among patients who underwent FISH detection, the detection rate of gene abnormalities was 69.9% (93/133); the detection rate of abnormalities by direct fluorescence in situ hybridization (D-FISH) was 42.9% (57/133); the detection rate of abnormalities by CD138 immunomagnetic sorting myeloma cells (MACS)-FISH was 82.7% (110/133). Among patients who underwent G-band karyotyping, the detection rate of abnormal karyotype was 38.5% (85/221). FSIH, especially MACS-FISH, had a higher detection rate of cytogenetic abnormalities than G-band karyotyping, and the difference was statistically significant ( χ2 = 65.697, P < 0.05). Conclusion:The comprehensive application of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, FISH (especially MACS-FISH), cytogenetic testing and other detection methods is more helpful for the diagnosis of multiple myeloma, and may be useful for prognostic judgment.

A case of Ⅴ-type hyperlipidemia pancreatitis in children / 中华实用儿科临床杂志

Hyperlipidemia pancreatitis in children is mostly genetic metabolic disease.The incidence of acute pancreatitis in children is only (3-13)/100 000, and pancreatitis caused by hyperlipidemia accounts for 9% of acute pancreatitis.A child suffering from V-type hyperlipidemia pancreatitis was admitted to the Children′s Hospital Affiliated to Nanjing Medical University in July 2019.The missense mutation at position c. 2770G>A of CFTR gene (nucleotide 2770 in coding region changed from guanine to adenine) in children was detected by gene sequencing, thus resulting in amino acid change p. D924N.It is extremely rare to report that CFTR gene mutation causes hereditary pancreatitis, and there is no literature report on c. 2770G>A site.This case is reported as follows, hoping to provide reference and inspiration for pediatricians.

CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies / 医学前沿

The current standard of care in hematological malignancies has brought considerable clinical benefits to patients. However, important bottlenecks still limit optimal achievements following a current medical practice. The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders. Consequently, new treatment strategies are necessary to improve clinical outcomes. Chimeric antigen receptor T-cell (CAR T) immunotherapy opens a new path for targeted therapy of hematological malignancies. In this review, through a representative case study, we summarize the current experience of CAR T-cell therapy, the management of common side effects, the causative mechanisms of therapy resistance, and new strategies to improve the efficacy of CAR T-cell therapy.

Prediction of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation by the level of galectin-9 in peripheral blood / 中华血液学杂志

Objective@#To evaluate possible effects of Gelctin-9 on acute graft versus host disease (aGVHD) development and clinical outcomes in patients before and afer allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#Peripheral blood samples were obtained from 29 patients and 15 healthy volunteers with heparin anticoagulant tubes. Samples were analyzed using ELISA kits to measure the serum concentrations of Galectin-9.@*Results@#Patients developing aGVHD had significantly lower level of Galectin-9 [ (7.96±1.18) μg/L] before allo-HSCT compared with those not developing aGVHD [ (12.37±0.97) μg/L, P<0.001]. And after allo-HSCT, the consentration of Galectin-9 increased markedly in patients developing aGVHD [ (17.78±1.78) μg/L] compared with those not developing aGVHD [ (9.45±0.80) μg/L, P<0.001]. Patients developing 3-4 grade aGVHD had significantly higher level of Galectin-9 [ (23.25±2.59) μg/L] compared with those developing 1-2 grade aGVHD [ (14.37±1.45) μg/L, P=0.008] and those without aGVHD [ (9.45±0.80) μg/L, P<0.001]. The patients with lower level of Galectin-9 after allo-HSCT (<13.61 μg/L) showed more favorable clinical outcomes compared with those with higher level of Galectin-9 (≥13.61 μg/L) . The 3-year overall survival rates were (100.00±6.05) % and (69.23±12.80) %, respectively (P=0.009) . The cumulative incidence of non-relapse mortality was significantly higher in high Galectin-9 group [ (23.08±11.69) %] in comparison with low Gaelctin-9 group [ (0.00±7.39) %] (P=0.023) . There was no significant difference between the two groups in terms of the cumulative incidence of relapse. The cumulative incidence of relapse at 3 years were (8.33±7.98) % and (12.50±8.27) % in high and low Galectin-9 groups, respectively (P=0.708) .@*Conclusions@#The serum concentration of Galectin-9 at the time of engraftment after allo-HSCT may be used as a predictor for the development and severity of aGVHD. Galectin-9 might be considered as a potential new approach to regulate transplant rejection to achieve desirable survival.

Management experiences of hematopoietic stem cell transplantation center under the pandemic of COVID-19 / 中华器官移植杂志

With a global pandemic trend, coronavirus disease-2019 (COVID-19), starting a breakout in December 2019, has posed a great threat to people's lives, health and safety. Regarding how to manage hematopoietic stem cell transplantation (HSCT) center, treat non-COVID-19 HSCT patients, follow up patients after HSCT and resume the orderly treatment of transplant patients, our transplantation center has accumulated a wealth of practical experience and formulated a series of standard processes. This article was intended to summarize the management experiences of HSCT center under the pandemic of COVID-19 epidemic, provide references for effectively managing HSCT center in future public health crises and treat noncommunicable disease transplant patients in a timely and effective manner.

Expressions of plasma D-dimer, von Willebrand factor antigen and blood coagulation factor Ⅶ in lymphoma and their clinical significances / 白血病·淋巴瘤

Objective@#To investigate the clinical value of blood coagulation and fibrinolysis index detection in lymphoma patients.@*Methods@#A total of 115 lymphoma patients hospitalized at Zhongshan Hospital of Xiamen University from January 2013 to September 2017 were retrospectively analyzed. According to the diagnostic and therapeutic criteria of lymphoma from World Health Organization (2008), these patients were divided into chemotherapy remission group (76 cases) and chemotherapy non-remission group (39 cases). A total of 138 healthy examination subjects at the same period were selected as the control group. Coagulation factor Ⅶ (FⅦ), D-dimer (D-D), von Willebrand factor antigen (vWF: Ag) and serum lactate dehydrogenase (LDH) levels were measured in all subjects. Kruskal-Wallis test was used to compare the differences of blood coagulation and fibrinolysis indicators in patients with different lymphoma staging and stratified treatment outcomes. Correlation test of D-D and LDH and disease staging was performed by using Spearman correlation analysis. The receiver operating characteristics (ROC) curve was used to analyze the efficacy of D-D in the assisted diagnosis of lymphoma with thrombosis.@*Results@#The plasma D-D, vWF: Ag levels and FⅦ activity [the median (interquartile range)] in lymphoma patients were higher than those in healthy controls [1 240 ng/ml (1 610 ng/ml) vs. 250 ng/ml (43 ng/ml), Z = -10.728, P < 0.01; 170 ng/ml (113 ng/ml) vs. 105 ng/ml (28 ng/ml), Z = -6.425, P < 0.01; 120% (26%) vs. 96% (26%), Z = -4.602, P < 0.01]. With the increase of Ann Arbor stage, plasma D-D, vWF: Ag levels and FⅦ activity were also increased gradually (all P < 0.05); plasma D-D, vWF: Ag levels and FⅦ activity in lymphoma with thrombosis group were higher than those in the group without thrombosis (all P < 0.01), D-D and vWF: Ag levels in the chemotherapy remission group were lower than those in the chemotherapy non-remission group (all P < 0.01). Plasma D-D levels were positively correlated with LDH level and Ann Arbor stage (r values were 0.414 and 0.530, respectively, all P < 0.01). When the plasma D-D level was 1 735 ng/ml, the sensitivity of diagnosis of thrombosis in patients with lymphoma was 81.8%, the specificity was 85.7%, the area under the ROC curve was 0.894, and the Youden index was the highest (0.675).@*Conclusions@#Clinically, blood coagulation and fibrinolysis in patients with lymphoma can be evaluated by detecting blood coagulation and fibrinolysis indexes such as plasma D-D. Real-time monitoring of plasma D-D level can determine the thrombosis trend of lymphoma patients, and it may play an important role in evaluating the efficacy and prognosis.

Minimal residual disease positive acute B lymphocytic leukemia: immunophenotyping analyses of 106 cases / 白血病·淋巴瘤

Objective To analyze the immunophenotypic characteristics of the patients with minimal residual disease (MRD) positive acute B lymphocytic leukemia (B-ALL). Methods The leukemia-associated immunophenotype (LAIP) of 106 cases with MRD positive B-ALL from Department of Hematology, Tianjin KingMed Diagnois Center between June 2014 and January 2016 were retrospectively analyzed. CD10, CD13/CD33, CD19, CD38, CD58, CD45 and other antibodies were used to analyze the MRD of B-ALL. Results All the patients were positive for CD19. CD34 was negatively or weakly positive expressed in 27 cases (25.4％). CD10 was negatively or weakly positive expressed in 23 cases (21.7％). CD10 was strongly positive in 24 cases (22.6％). Totally, CD10 was weakly or strongly expressed in 47 cases (44.3％). CD58 was strongly positive in 98 cases (92.5％). CD13/CD33 was positively or weakly positive expressed in 64 cases (60.4％). CD38 was negative or weakly expressed in 33 cases (31.1％). CD45 was negative in 21 cases (19.8％). 15 cases (14.1％) were positive for 6 types of LAIP; 30 (28.3％) cases were positive for 5 types of LAIP; 42 (39.6％) cases were positive for 4 types of LAIP; 13 (12.3％) cases were positive for 3 types of LAIP;5 cases (4.7％) were positive for 2 types of LAIP; only one case (0.9％) was positive for 1 type of LAIP. Conclusion The combination of CD58, CD13/CD33, CD10, CD38 and CD34 antibodies can distinguish the neoplastic blast/immature B lymphocytes from progenitor B cells. This strategy has a high accuracy for the judgement of MRD in B-ALL.

Preliminary clinical study of C-arm CT assisted transjugular intrahepatic portosystemic shunt for the treatment of portal hypertension / 中华放射学杂志

Objective To explore the value of C-arm CT in transjugular intrahepatic portosystemic shunt (TIPS).Methods Between June 2015 and October 2017,a total of 16 patients with cirrhosis complicated by upper gastrointestinal bleeding or massive ascites due to portal hypertention in our center were retrospectively enrolled in the study.Abdominal enhanced CT was routinely performed before surgery.Postprocessing images of portal vein were used as a guidance of TIPS in real time after integrated with intraoperative c-arm CT images during selective operations.Results The success rate of C-arm CT-guided TIPS was 100％.Portal vein angiography showed the position basically consistent with CT matched images reference position.No obvious abdominal hemorrhage,injury of biliary tract and other complications occurred in all patients.The mean number of needle passes was 2.1 ±0.9 passes(range of 1.0-4.0 passes),the mean time of portal vein entry was 4.3 ± 1.9 min (range of 2.0-8.0 min),the mean fluoroscopy period was 22.6 ± 4.8 min (range of 17.0-32.0 min),DAP was (256.2± 96.7)mGy/cm2.Conclusion C-arm CT-guided TIPS is technically feasible and safe.

Application of fusion imaging combined Xper-CT with CTPV in transjugular intrahepatic portosystemic stent shunt / 中国医学影像技术

Objective To explore the feasibility of fusion image of Xper-CT and CT portal venography (CTPV) as DSA 3D-roadmap in operation of transjugular intrahepatic portosystemic stent shunt (TIPS).Methods Thirty-seven patients with portal hypertension were enrolled in this study,among them 21 underwent conventional TIPS retrospectively,16 underwent Xper-CT and CTPV imaging to obtain fusion image in the workstation with the software of Multi-Modality Matching for hepatic portal vein without contrast medium administration.Then the fusion image was used as the 3D-roadmap in the process of real-time fluoroscopy.Results In the fusion process of Xper-CT and CTPV,osseous registration error was ＜ 2.00 mm,while error of the portal vein fusion image and the real-time X-ray image displacement were ＞2.00 mm between up and down in 15 patients,＞5.00 mm between left and right in 1 patient.Conclusion Xper-CT with CTPV fusion image can be used as 3D-roadmap of TIPS to observe the relationship between puncture needle and the portal vein without administration of contrast medium,improving the accuracy and safety of puncture and reducing operation time.

The effects of nutritional treatment in patients with AIDS / 重庆医学

Objective To investigate the effects of nutritional treatment in patients with AIDS.Methods A total of 104 HIV/AIDS patients with a total score of nutritional risk screening≥3 were divided into two groups:observation group (n =50) who were treated with nutritional therapy,control group(n =54) who refused nutritional treatment.The changes of parameters in two groups were observed before(I0) and 1 month after (I1)treatment and 3 months after treatment (I2).Results Compare with thecontrol group,the weight,BMI and ALB in observation group were higher at the time of I1 and I2 (P＜0.05);Except for Hb and ALB,the other indexes had significant difference between the time of I0,I1,I2 in control group.While all the indexes had significant differencebetween the time of I0,I1,I2 in observation group.Conclusion Long-term comprehensive nutritional therapy can improve the nutritional status of AIDS patients,which provides patients with a good basis for anti-viral treatment.

A prospective multi-center trial of non-interventional and observational study of lenalidomide in Chinese patients with multiple myeloma / 中华内科杂志

Objective To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM).Methods It was a prospective,multi-center,observational study.A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015.Relevant information was recorded,such as baseline clinical data,cytogenetic abnormalities,treatment regimens,and duration of treatment,safety,and survival.Results (1)There were 126 relapsed and refractory MM (RRMM) patients,25 newly diagnosed patients and 19 maintenance patients.The evaluable RRMM patients accounted for 120 cases,among which 74 cases(61.7％) reached the partial response (PR) or above,and a very good partial response (VGPR) in 16 patients (13.3％),a complete response (CR) in 14 cases (11.7％),a strictly complete response (sCR) in 4 cases (3.3％).Thus,a VGPR or above in 34 patients accounted for 28.3％.(2)The median follow-up was 13 months,the median time to progression 12 months.The median survival after receiving lenalidomide was 19 months,and the median overall survival (OS) was 62 months.(3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype,international staging system (ISS) Ⅰ-Ⅱ,t(4;14) negative (detected by fluorescence in situ hybridization),non-bortezomib resistance and response to previous regimens.As to OS,nonbortezomib resistance,response to previous regimens and non-primary refractoriness were positive factors.Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival (PFS),non-bortezomib resistance and non-primary refractoriness for OS.(4) Grade 3 or 4 adverse events that occurred in more than 10％ of all enrolled patients were neutropenia (12.7％),leukocytosis (11.5％) and thrombocytopenia (12.7％).Owing to intolerance of toxic side effects,7 cases withdrew lenalidomide.Conclusions No matter what combination,regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7％,a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable.In addition,the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS,non-bortezomib resistance and non-primary refractoriness for OS.Clinical trail registration Clinicaltrials.gov,NCT01947309

Differences in expression of Ras1, Rac1 and Rho1 genes between yeast and hyphal phases of Trichosporon asahii / 中华皮肤科杂志

Objective To investigate differences in the expression of Ras 1,Rac1 and Rho1 genes between yeast and hyphal phases of Trichosporon asahii (T.asahii),and to explore their roles in the formation of hyphae.Methods The yeast phase and hyphal phase of T.asahii were cultured and served as yeast phase group and hyphal phase group respectively.Total RNA was extracted from the 2 groups,and real -time fluorescence-based quantitative PCR (RT-PCR) was performed to measure the mRNA expression of Ras1,Rac1 and Rho1.Results The hyphal formation rate was significantly lower in the yeast phase group than in the hyphal phase group (0.40％ ± 0.53％ vs.99.33％ ± 0.57％,t =13.93,P ＜ 0.05).When the mRNA expression of Ras1,Rac1 and Rho1 in the yeast phase group was all set as 1,that in the hyphal phase group was 25.17 ± 10.99,16.81 ± 7.80,42.61 ± 18.50,respectively,with significant differences between the two groups in the three parameters (t =3.81,3.51,3.90,respectively,all P ＜ 0.05).Conclusion Ras1,Rac1 and Rho1 genes may participate in the regulation of hyphal formation in T.asahii.

Application of single port laparoscopy in classification and treatment of Meckel's diverticulum in children / 重庆医学

Objective To explore the feasibility of single port laparoscopy in classification and treatment of Meckel's diverticulum in children and its guiding treatment.Methods The clinical data in 75 children cases of Meckel's diverticulum with symptoms treated in our hospital from Aug.2011 to Aug.2015 were retrospectively analyzed.Meckel's diverticulum was classified under single port laparoscopy.The operation modes were selected according to different classifications.The excised materials were submitted to the pathologic examination.Results Among 75 children cases,50 cases were the simple type of Meckel's diverticulum and 25 cases were complex type of Meckel's diverticulum.The average operative time in the simple type and complex type was (38.93±8.75) min and(55.64 ± 13.27) min respectively,average bleeding amounts were (46.58 ± 15.81) mL and (50.12 [16.90) mL respectively,average postoperative hospitalization time was (7.33±1.41)d and (7.52 ± 1.68)d respectively,the operative time in the simple type was less than that in the complex type(P＜0.05),the other two indexes had no statistical difference between the two groups(P＞0.05).The ectopic gastric mucosal pathological change was only seen in the simple type,while the inflammatory manifestation in the complex type had higher proportion.The main clinical manifestations were lower gestational tract bleeding and infection.The two groups all obtained follow up.One case of simple type appeared the symptoms of abdominal pain and hematochezia and was cured after the second operation.Conclusion Meckel's diverticulum can be divided into the simple type and complex type under single port laparoscopy.The operation mode can be selected according to different types.This method is safe and reliable and is worthy of being clinically promoted.

Expression of FGFR3 in acute lymphoblastic leukemia patients and its contribution to proliferation of circulating endothelial cells / 中国病理生理杂志

AIM: To evaluate the expression of fibroblast growth factor receptor 3 (FGFR3) in acute lymphocytic leukemia (ALL) patients and its contribution to the proliferation of circulating endothelial cells (CECs).METHODS: The mRNA expression levels of FGFR3 in 44 patients with ALL were assayed by RT-PCR.Overall survival (OS) rates of the patients in FGFR3+ group and FGFR3-group were estimated by Kaplan-Meier analysis.The CECs were sorted from peripheral blood by magnetic-activated cell sorting and then counted by 3-color flow cytometry.The cell counts, antigen expression, growth curve and colony forming rate of the CECs in the 2 groups were determined.The FGFR3 expression of CECs was identified by immunofluorescence staining.RESULTS: The positive rate of FGFR3 mRNA expression was 43.2% in 44 ALL patients with normal karyotype.T-ALL expressed higher level of FGFR3 than B-ALL (P<0.05).FGFR3 was over-expressed in ALL patients with bone marrow blast proportion ≥5% (P<0.05).The probability of OS was significantly lower in FGFR3+ group than that in FGFR3-group (P<0.05).The sorted CECs highly expressed CD31, CD144, VEGFR-2 and CD146, and rarely expressed CD45.The counts of CECs and expression level of CD133 significantly increased in FGFR3+ group compared with FGFR3-group.The same result of the amount of colony formation was observed (P<0.05).There was significant difference at 3 time points of cultured CECs count in vitro between FGFR3+ group and FGFR3-group (P<0.05).The positive rate of FGFR3 expression of CECs from 19 ALL-FGFR3+ patients was (29.00±15.71)%.CONCLUSION: The over-expression of FGFR3 gene in ALL may be helpful to evaluate the prolife-ration of CECs, and become a double target with anti-tumor and anti-angiogenesis effects to offer more choice for molecular therapy in the future.