Objective:To explore the differential efficacies of conventional chemotherapy, autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for T lymphoblastic lymphoma (T-LBL) .Method:From January 2012 to December 2022, the relevant clinical data were retrospectively reviewed for 82 T-LBL patients hospitalized at Affiliated Tongji Hospital. According to different treatments, they were assigned into two groups of non-transplantation (49 cases) and transplantation (33 cases). The transplantation group was divided further into two groups of allo-HSCT (22 cases) and auto-HSCT (11 cases) according to different transplantation modes. In non-transplantation group, remission was induced mostly by cyclophosphamide+messosodium+doxorubicin+dexamethasone+vincrine/methotrexate+Hyper CAVD A/B. Six patients achieved remission based upon cyclophosphamide+cytarabine+6-mercaptopurine (CAT), etoposide+vincristine+doxorubicin+cyclophosphamide+cyclophosphamide+ prednisone (EPOCH), high-dose methotrexate+dexamethasone and vincristine+pirubicin+ cyclophosphamide+ pemasase+prednisone (VDCLP). The transplantation group underwent HSCT after multi-drug combination intensive induction therapy. Efficacy and survival were analyzed by observing the rates of overall survival (OS) and progression-free survival (PFS) .Result:There were 64 males and 18 females with a median age of 23 (11~74) year. Among them, 62 cases (75.61%) had clinical stage Ⅲ~Ⅳ. And 43 cases (53.44%) had systemic symptoms (B symptom) of fever, night sweats and weight loss at an onset of disease. Fifty cases (61.00%) had an involvement of bone marrow and 33 cases (80.5%) belonged to Ann Arbor stage Ⅲ and above. There were 65 cases (79.27%) with Eastern Cooperative Oncology Group (ECOG) score ≤2 and 17 cases (20.73%) with ECOG score >2. International Prognostic Index (IPI) was ≤3 (63 cases, 76.83%) and >3 (19 cases, 23.17%). Follow-up period was 27.5 (5~118) month. And 3-year OS and PFS were 53.64% (95% CI: 42.35%~64.62%) and 47.56% (95% CI: 36.53%~58.82%). Significant inter-group difference existed in 3-year OS[42.86% (95% CI: 29.12%~57.71%) vs 69.70% (95% CI: 51.13%~83.79%), P=0.014]and 3-year PFS was 38.76% (95% CI: 25.54%~53.76%) and 60.61% (95% CI: 42.24%~76.57%). And the difference was statistically significant ( P=0.032) . Conclusion:As a consolidation therapy, HSCT may improve the long-term outcomes of T-LBL patients as compared with chemotherapy alone.

Objective:To preliminarily investigate the applicability of a poliovirus pseudovirus-based neutralization assay in evaluating the immunogenicity of recombinant poliovirus vaccines and their in vivo potency in rats. Methods:Serum samples from rats immunized with recombinant poliovirus vaccines were tested using both the pseudovirus neutralization assay and the live-virus neutralization assay with Sabin strain. The consistency and correlation of the two methods were analyzed using the Kappa test and Spearman′s rank correlation.Results:For the neutralizing antibodies against typeⅠ, Ⅱ, and Ⅲ polioviruses, the Kappa values for consistency analysis of the two methods were 0.914, 1.000, and 0.751, respectively ( P<0.001), and the correlation coefficients ( R values) were 0.833, 0.927, and 0.859, respectively ( P<0.001). Conclusions:The test results of the two methods are consistent and show a good correlation, indicating that the pseudovirus neutralization assay can be applied to evaluating the immunogenicity of poliovirus vaccines and also can be used in rat potency tests.

The radial migration of cortical pyramidal neurons (PNs) during corticogenesis is necessary for establishing a multilayered cerebral cortex. Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia, epilepsy, and intellectual disability (ID). TRIO is a high-risk candidate gene for ASDs and ID. However, its role in embryonic radial migration and the etiology of ASDs and ID are not fully understood. In this study, we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born PNs. Further investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin (N-cadherin). Also, independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent locomotion. Taken together, our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 domain. These results suggest the vital roles of the guanine nucleotide exchange factor 1 (GEF1) and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners, which might be associated with the abnormal phenotypes in neurodevelopmental disorders.
Autism Spectrum Disorder/metabolism* ; Cell Movement/genetics* ; Humans ; Interneurons/metabolism* ; Neurodevelopmental Disorders/genetics* ; Neurons/metabolism* ; Rho Guanine Nucleotide Exchange Factors/genetics*

Objective:To analyze the clinical characteristics of Group A Streptococcal(GAS) toxic shock syndrome (STSS) in children. Methods:The clinical data of 10 STSS children hospitalized in Shenzhen Children′s Hospital from January 2015 to March 2022 were downloaded from the electronic medical record system.The clinical manifestations were analyzed and treatment experience was summarized respectively.Results:There were 5 males and 5 females, with an average age of (5.29±2.87) years.All the patients were healthy in the past.The diagnoses were confirmed by blood culture in 2 cases, pus culture in 5 cases, and blood metagenomics next generation sequencing in 3 cases.The rapid detection of GAS antigen was positive in 7 cases.All cases had fever, and 9 cases of them developed fever after viral infection, including pneumonia in 7 cases, skin and soft tissue infections in 6 cases, necrotizing fasciitis in 3 cases, and purulent meningitis in 1 case.All cases also presented with shock.Six cases had liver function injury, and 4 cases suffered from acute kindey injury.Four cases had infection-related encephalopathy, and 7 cases were afflicted with disseminated intravascular coagulation.Two cases had respiratory failure, and 2 cases had rhabdomyolysis.There were 3 cases with a decreased white blood cell (WBC) count and 7 cases with an increased WBC count on admission.Seven cases were found to have thrombocytopenia, but their platelet levels were all elevated after recovery.C-reactive protein and procalcitonin and the proportion of neutrophils were markedly increased in all cases.All cases suffered from hypoalbuminemia, hyponatremia and hypocalcemia.All the 10 positive strains were sensitive to Penicillin, Ceftriaxone/Cefotaxime and Vancomycin.Eight cases were treated with combined antibiotics after admission.Eight patients received intravenous immunoglobulin.All cases were cured and discharged.Conclusions:The STSS progresses rapidly in children, so pediatricians should pay great attention to the disease.Early identification, diagnosis of infection sources, infusion of antibiotics and surgical treatment are the keys to disease management.

Objective:To retrospectively analyze clinical characteristics, flora distribution characteristics, and antimicrobial sensitivity of type 2 diabetic patients with back abscess.Methods:The clinical data of patients with type 2 diabetes mellitus and back abscess were collected from Endocrinology Department of Henan Provincial People′s Hospital from October 2017 to April 2020. The results of bacterial culture and drug sensitivity test were analyzed, antibiotics were given to treat infection, incision and debridement of abscess were performed according to the situation of abscess, drainage of abscess cavity or continuous negative pressure suction was given when necessary, and the clinical outcome was recorded.Results:A total of 12 type 2 diabetic patients with back abscess were included. The average size of their abscess was(150.3±101.2)cm 2, with over 100 cm 2 in 8 cases(66.7%). Among the 12 patients, 11 patients underwent bacterial culture and drug sensitivity analysis. The positive rate of culture was 100%, and all of them were Staphylococcus aureus, with 10 cases of methicillin-susceptible Staphylococcus aureus(MSSA)and 1 case of methicillin-resistant Staphylococcus aureus(MRSA). MSSA strains were 100% sensitive to oxacillin, vancomycin, linezolid, levofloxacin, moxifloxacin, tetracycline, tegecycline, rifampicin, amoxicillin/clavulanic acid, amikacin, and teicoplanin. Both MSSA and MRSA strains were sensitive to vancomycin, linezolid, rifampin, amikacin, and teicoplanin. The wound of all patients was healed, with 100% cure rate and(35.8±34.0)days of average healing time. Conclusion:The back abscess in type 2 diabetic patients is characteristic of rapid progress, huge abscess, and difficult to treat, which should be treated early, incised and debrided timely. Staphylococcus aureus is its single pathogen and it is helpful to select the antibiotics empirically.

Objective:To compare the clinical outcomes and safety of haploidentical donor (HID)and HLA-matched sibling donor(MSD)hematopoietic stem cell transplantation(HSCT)for severe aplastic anemia(SAA).Methods:From January 1, 2012 to December 31, 2019, retrospective review of clinical data was performed for 75 SAA patients undergoing HSCT at Department of Hematology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.Based upon donor sources, they were divided into two groups of MSD(49 cases)and HID (26 cases). And two groups were compared with regards to hematopoietic recovery, graft-versus-host disease(GVHD)infection and overall survival(OS).Results:Time of platelet and neutrophil engraftment of two groups was comparable(11 d vs.11 d, P=0.84; 11 d vs.12 d, P=0.08). Compared with HID group, MSD group had a lower incidence of acute GVHD(46.2% vs.18.4%, P=0.01)with a comparable incidence of grade Ⅱ-Ⅳ acute GVHD(26.9% vs.14.3%, P=0.24), grade Ⅲ-Ⅳ acute GVHD(15.4% vs.4.1%, P=0.09)and chronic GVHD(23.9% vs.23.1 %, P=0.71). A reactivation of CMV occurred in 27(55.1%)MSD and 22(84.6%)HID recipients( P=0.01). And the incidence of EB viremia was 69.4% and 61.5% respectively.After a median follow-up period of 54.0 and 18.5 months, the estimated 3-year OS rate of MSD and HID groups were 94.0% and 88.0% respectively ( P=0.35). Conclusions:HID HSCT is an effective and relatively safe option for SAA patients, especially for those in urgent need of treatment without MSD or refractory/relapse to immunosuppressive therapy.

Objective:To explore the clinical application value of group A Streptococcus (GAS) antigen rapid detection method in children suffering from GAS infection.Methods:A total of 44 733 children with suspected GAS infection who were admitted to the Outpatient and Inpatient Departments of Shenzhen Children′s Hospital from January 2015 to December 2019.Throat swab specimens from all children were collected, and BinaxNOW Strep A Test reagent was used for GAS antigen rapid detection.Among them, the throat swabs of 346 children were inoculated with blood culture medium for traditional bacterial culture, and then the GAS antigen rapid detection was tested.The sensitivity and specificity of the two methods were compared, and according to the result of the GAS antigen rapid detection, its age, gender and seasonal trends were analyzed.SPSS 19.0 software was applied for statistical analysis of the data.Results:Among the 346 children tested by both methods, the results of bacterial culture were adopted as the reference method, the sensitivity of the rapid detection method for GAS antigen was 89.41%(152/170 cases), and the specificity was 94.32%(166/176 cases) compared with culture methods.A total of 44 733 cases GAS antigen were tested in children in Shenzhen, of which 10 024 cases were positive, with the positive detection rate of 22.41%.The trend of GAS antigen rapid detection was consistent with the five-year trend, with the high positive rate of 3-8 years, of which 4-6 years of positive rate was the highest.The two seasonal peaks were evident each year, with peaks occurring in April-June, and November and January of next year.The detection rate ratio of male and female was 1.74∶1, and the gender difference was significant ( χ2=27.93, P<0.000 1). GAS antigen rapid detection rate in different clinical departments from high to low in order are as follows: dermatology outpatient (52.34%), emergency clinic (47.74%), internal medicine outpatient (37.36%), infectious disease area (19.71%), five-level disease area (10.27%), internal medicine area (8.63%), surgical areas (7.34%) and neonatal areas (0). Conclusions:GAS antigen rapid detection method and bacterial culture method have high coincidence rate, and high sensitivity and specificity, and can be popularized and applied in the diagnosis of GAS infectious diseases in children.GAS detection rate is higher in outpatient emergency department and dermatology clinics.There are obvious differences from seasonal and population (age and gender) in the positive detection of GAS antigen.No neonates were found.

Objective:To investigate the relationship between serum matrix metalloproteinase-9 (MMP-9) level and the location and severity of bleeding in patients with cerebral microbleeds(CMBs).Methods:A total of 60 CMBs patients admitted to the Department of Neurology of the First Affiliated Hospital of the Xinxiang Medical University from January 2019 to August 2020 were selected as subjects as the CMBs group, and 60 healthy controls without nervous system diseases in outpatient physical examination during the same period were selected as the control group. The clinical data and biochemical indicators of the two groups were collected. Serum MMP-9 levels were measured by enzyme linked immunosorbent assay (ELISA). According to susceptibility weighted imaging (SWI), CMBs patients were divided into grade 1 group ( n=24), grade 2 group ( n=19) and grade 3 group ( n=17), and according to the micro analytical rating scale (MARS), the CMBs patients were divided into the lobar group ( n=19), the deep or infratentorial group ( n=17) and the mixed group ( n=24).The relationship between serum MMP-9 level and the location and severity of CMBs was analyzed. SPSS 19.0 software was used for data statistical analysis.One-way ANOVA, t-test and rank sum test were used for comparison. Logistic regression analysis was used to analyze the influencing factors. Pearson correlation analysis and Spearman correlation analysis were used for correlation analysis. Results:The level of MMP-9 in CMBs group was significantly higher than that in control group (208.13(142.25, 285.88) μg/L, 149.50(93.40, 186.51)μg/L), and the difference was statistically significant ( P<0.05). Serum MMP-9 level was a risk factor of CMBs ( β=1.322, OR=3.750, 95% CI=2.038-7.997, P=0.002). The difference of level of MMP-9 in different severity of CMBs was statistically significant (147.55(109.25, 266.47)μg/L, 242.12(147.55, 288.80)μg/L, 270.42(203.43, 364.27)μg/L, P=0.017). Serum MMP-9 level was positively correlated with the number of CMBs ( r=0.371, P=0.003). The difference of MMP-9 level of CMBs in different locations were statistically significant (249.77(158.43, 338.46)μg/L, 188.83(138.52, 243.15)μg/L, 210.65(144.25, 255.78)μg/L, P=0.013). The increased serum MMP-9 level was a risk factor for CMBs( β=0.401, OR=1.122, 95% CI=1.004-1.204, P=0.036). Conclusion:The increased level of serum MMP-9 may be a risk factor of CMBs, especially for CMBs in cerebral lobesand, and the level of MMP-9 is positively correlated with the severity of CMBs.

Objective:To investigate the relationship between serum matrix metalloproteinase-9(MMP-9) level and vascular cognitive impairment with no dementia (VCIND) in patients with cerebral small vessel diseases (CSVD).Methods:A total of 374 patients with CSVD treated in the First Affiliated Hospital of Xinxiang Medical University from January 2016 to January 2020 were collected and 150 healthy subjects in the same period were used as general data of the control group. All subjects were detected for serum MMP-9 level using enzyme linked immunosorbent assay and received cognitive function scoring using Montreal cognitive assessment (MoCA). The 374 patients with CSVD were divided into the Group A(186 cases with vascular cognitive impairment with no dementia) and the Group B(188 cases without cognitive impairment). The general data, serum MMP-9 level and cognitive function score were compared among the three groups and the correlation between MMP-9 level and cognitive function was analyzed.Results:The MMP-9 levels of Groups A and B ( (335.10±105.10)μg/L, (261.62±80.32)μg/L) were higher than those of the control group ( (168.23±48.85)μg/L), and the MMP-9 level of Group A was higher than that of Group B ( P<0.05). The MoCA scores of Groups A and B ( (18.45±5.24), (28.31±1.52) ) were lower than those of the control group (29.49±0.90), and the MoCA scores of Group A were lower than those of Group B ( P<0.05). The serum MMP-9 level, a risk factor for VCIND in patients with CSVD ( β=1.505, OR=1.323, 95% CI=1.149-1.527, P<0.05), was negatively correlated with total score of MoCA scale, visual-spatial and executive function, naming, language, abstract thinking, delayed recall, and directive force factor score ( r=-0.299, r=-0.155, r=-0.383, r=-0.358, r=-0.192, r=-0.259, r=-0.246 respectively, all P<0.05). Conclusion:The increased level of MMP-9 may be a risk factor of VCIND in CSVD patients, and it is closely related to cognitive impairment.

Genome editing is a novel targeted genome modification biotechnology, which could successfully mutate specific loci as well as generate gene replacement and insertion in various organisms. So far, genome editing technology has been widely applied in investigating gene function and developing valuable traits in both model plants and major crops. In this review, we briefly survey the historical development of genome editing technology, summarize recent progress using the CRISPR/Cas9 system for plant genome editing and explore the potential of the CRISPR/Cas technology in improving forage legumes.