[Analysis of efficacy and prognosis of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors. Methods: In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children's Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors. Results: Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% vs. (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis (HR=2.55, 95%CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant (HR=2.96, 95%CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions: Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.

[Associations of blood pressure change with change in foods' intake among adults with mild to moderate hypertension].

Objective: To explore the association between the intake and changes in various types of food and the changes in blood pressure in patients with mild to moderate hypertension. Methods: Mild to moderate hypertension participants with complete baseline and outcome data were included from DECIDE-Diet study, a multicenter, randomized controlled trial. Dietary records and blood pressure measurements at both 7-day run-in (baseline) and 28-day intervention phases were collected for enrolled participants. Blood pressure change was defined as the difference between blood pressure at the end of trial and the baseline blood pressure. Baseline intake of food was the average daily intake during the run-in period, and the intake increment was defined as the difference between the average intake during the trial period and the average intake during the run-in period. After adjusting for age, sex, study center, intervention groups, baseline body mass index (kg/m2), antihypertension medication use, and baseline total calorie intake, a linear regression model was used to analyze the associations of the before-after-intervention change in blood pressure with baseline intake and intake increment of foods. Results: A total of 258 patients with mild to moderate hypertension were included, including 133 males, aged (56.5±9.9) years. (1) After adjusting for confounding factors, there was no significant association between baseline intake of food and baseline blood pressure (all P>0.05). The blood pressure change was negatively associated with baseline intakes of tubers, vegetables, and vegetable oils but positively with baseline intake of meats; and was negatively associated with intake increment of whole grains and fish (all P<0.05). (2) The multiple linear regression analysis showed that baseline intake of vegetables (ß=-0.021, P=0.004), vegetable oils (ß=-0.260, P=0.002), and increment in intake of fish (ß=-0.128, P=0.026) were all significantly associated with changes in systolic blood pressure; baseline intake of vegetables (ß=-0.017, P=0.002), vegetable oils (ß=-0.182, P=0.001), dairy products (ß=0.021, P=0.022), and increment in intake of fish (ß=-0.092, P=0.010) were all significantly associated with changes in diastolic blood pressure. Conclusion: Increasing the intake of whole grains, vegetables, vegetable oils, and fish and decreasing the intake of meat may be beneficial for blood pressure control in patients with mild to moderate hypertension.

[Unrelated umbilical cord blood stem cell transplantation in the treatment of hyper-IgM syndrome caused by CD40 ligand gene mutation: a report of three cases and literature review].

Objective: To evaluate the efficacy and safety of unrelated umbilical cord blood stem cell transplantation (UCBT) with reduced-intensity conditioning regimens in the treatment of hyper-IgM syndrome (HIGM) caused by CD40 ligand gene (CD40LG) mutation. Methods: Clinical features, laboratory data and treatment prognosis of 3 patients with HIGM caused by CD40LG mutation treated with UCBT in Children's Hospital of Fudan University from May 2018 to August 2019 were analyzed retrospectively. The literature search was conducted with "CD40 ligand deficiency" and "hematopoietic stem cell transplantation" as keywords at China National Knowledge Infrastructure, Wanfang, Weipu and Pubmed databases (up to February 2021) to summarize donor selection, stem cell source, conditioning regimen and prognostic factors of this disease. Results: Three boys with recurrent respiratory tract infection were diagnosed as HIGM with CD40LG mutation. The age of UCBT was 1.0, 1.4 and 0.5 years respectively. Reduced-intensity conditioning regimen including busulifan, fludarabine and cyclophosphamide were used in all patients. Human leucocyte antigen matching of patients and umbilical cord blood was 8/10, 10/10 and 9/10 respectively. All patients achieved complete donor chimerism 14 days after UCBT. All patient suffered grade Ⅰ acute skin graft-versus-host disease without other severe complications. Up to the last follow-up, their disease-free survival time were 33, 18, 18 months after transplantation respectively. No reports were found in Chinese journals, while 24 publications were found in English journals. According to the literature, 258 HIGM patients with CD40LG mutation were treated with hematopoietic stem cell transplantation (HSCT). Matched sibling donors (30.6%(79/258)) and unrelated donors (40.3% (104/258)) were main donor types. Bone marrow (50.8%(131/258)) was the main source of grafts, myeloablative conditioning (66.7% (172/258)) was the main conditioning regimen, and the overall survival rate after transplantation was 70.9% (183/258). Lung injury and liver complications before transplantation were adverse factors affecting prognosis. Among the 14 patients who received UCBT, 2 patients suffered from engraftment failure, 2 patients had mixed chimerism and 3 patients died after transplantation. Conclusions: UCBT is safe and effective in the treatment of HIGM caused by CD40LG mutation. Reduced-intensity conditioning regimen is worthy of further study.

Neutron emission and fast ion simulation for high performance long pulses at EAST.

Neutron emission spectroscopy and neutron yield measurements are important for high neutral beam injection (NBI) power heating at the Experimental Advanced Superconducting Tokamak (EAST). The neutron yields mainly depend on the deposition from NBI to the deuterium plasmas in the EAST. We have recently used TRANSP with time dependent diagnostic results to simulate the transport process of 30 s long pulse deuterium plasma discharges in the EAST, obtaining the time dependent fast ion distribution, neutron emission spectrum, and total neutron emission rate. Combined with the time trace of the result measured by a standard 235U fission chamber, the effects of different configurations of NBI heating in EAST fusion plasmas have been evaluated.

A compact stilbene crystal neutron spectrometer for NBI-heated plasma neutron diagnostics at EAST.

Stilbene crystal detectors are widely used as fast neutron measurement tools based on recoil proton detection, such as liquid scintillators. A compact stilbene crystal neutron spectrometer (CSCNS) has been installed at the Experimental Advanced Superconducting Tokamak (EAST) to obtain information on fuel ions produced in the plasma core because of its merits of good n/γ discrimination capability, high detection efficiency, and fast response. For the first time, CSCNS has been used for neutron emission spectroscopy measurements in EAST plasmas with neutral beam injection (NBI) heating. The CSCNS has the same horizontal line of sight as the time-of-flight enhanced diagnostics neutron spectrometer. Under NBI heating scenarios, the time trace of the neutron yield monitored by the CSCNS is similar to the one monitored by a standard 235U fission chamber. The experimental pulse height spectra are also similar to the simulated ones generated by folding the simulated neutron energy spectrum with the detector response functions. These results demonstrate the capability of the CSCNS for neutron diagnostics and the study of fast-ion physics in EAST.

Lactate augments intramuscular triglyceride accumulation and mitochondrial biogenesis in rats.

Regular exercise induces intramuscular triglyceride accumulation with improved mitochondrial ability, but the mechanism remains unknown. The glycolytic product of exercise, lactate, has long been rec-ognized to suppress lipolysis and promote lipogenesis in adipocytes through inhibition of the cAMP-PKA pathway by activation of the G protein-coupled receptor (GPR81). However, whether lactate results in a similar process in skeletal muscle is unclear. Here, by using intramuscular injection of lactate to the gastrocnemius, the lipid metabolism effects were investigated in rat skeletal muscle. Firstly, the lactate-injection effect was verified by comparing changes in blood lactate levels from injection and exercise (30 min, 31 m/min, treadmill running). After five weeks of lactate intervention, intramuscular triglyceride levels in the gastrocnemius and the proportion of epididymis adipose mass to body weight increased. Chronic intramuscular injection of lactate elevated lactate receptor, GPR81, and reduced cAMP response element-binding (CREB) and P-CREB abundance in the gastrocnemius. Additionally, there was a significant decline in lipolytic-related proteins (AMPK, P-AMPK, P-HSL, CPT-1B, TGF-ß2, SDHA) and a significant increase in fat synthesis proteins (SREBP-1C, PPAR-γ). Surprisingly, mitochondrial biomarkers (PGC-1α, CS) were also increased in the gastrocnemius, suggesting that chronic lactate might promote mitochondria biogenesis. Together, these results demonstrated that lactate may play a crucial role in triglyceride storage and mitochondria biogenesis in the skeletal muscle of rat.

[Nutritional risk screening and related factors of cancer patients in community of Shanghai, 2018-2019].

Objective: To study the risk of malnutrition and related factors of cancer patients in community of Shanghai. Methods: From October 2018 to January 2019, four communities, Pengpu New Village Street, Pengpu Town, Jiangning Road Street, and Caojiadu Street, from 14 communities in Jing 'an District, Shanghai City, were selected by using a random cluster sampling method based on the Shanghai Cancer Registration and reporting system. All cases of malignant tumors and benign tumors of the central nervous system were included. A total of 4 396 questionnaires were distributed. After the exclusion of 9 invalid questionnaires, 3 310 valid questionnaires were included with a rate of 99.73%. A self-designed questionnaire was used to collect data including basic demographic characteristics, history of malignant, physical and psychological pain, nutritional demands and cognitive status. Malnutrition Universal Screening Tools (MUST) was used to analyze the nutritional risk of cancer patients in the community. Multivariate logistic regression model was applied to analyze potential factors. Results: Among the 3 310 cancer patients who completed the survey, the average age of study participants was (64.05±13.02), and 1 467 cases (44.32%) were males. The incidence rate of nutritional risk was 12.84% (425/3 310). The result of logistic regression analysis showed that compared with male, other cancer patients and no physical pain, the risk factors of the occurrence of nutritional included: female (OR=1.53,95%CI:1.23-1.92), head and neck malignant tumors (OR=1.42,95%CI:1.07-1.90), bronchus/lung malignant tumors (OR=1.93,95%CI:1.43-2.61), liver, biliary/pancreatic malignant tumors (OR=2.11,95%CI:1.21-3.65) and upper gastrointestinal malignant tumors (OR=6.04,95%CI:4.31-8.46), patients with physical pain (OR=1.39,95%CI:1.02-1.89). Conclusion: Nutritional risk of cancer patients is higher in community of Shanghai. Gender, location of tumors and physical pain are associated with the occurrence of nutritional risk.

[Targeted-knockdown of Yes-associated protein inhibits the Warburg effect and the invasion of laryngeal cancer cells].

Objective: To investigate the migration and invasion behaviors of Hep-2 after the targeted knockdown of yes-associated protein (YAP). Methods: Hep-2 cells were knock-downed for YAP by shRNA as YAP-shRNA group, Hep-2 treated with non-specific shRNA as YAP-NC group, and Hep-2 with no treatment as control. Glucose uptake and lactate production in the cells were examined to assess Warburg effect. The migration and invasion behaviors of cells in three groups were observed. The expressions of vimentin and E-cadherin were detected by RT-PCR and Western Blot. The statistical software GraphPad Prism 7.0 was used to analyze significance of data. Two tailed Student' s t-tests was used to determine significance when only two groups were compared. P values of less than 0.05 was considered statistically significant. Results: Downregulation of YAP led to a obvious decrease in glucose uptake [(18.51±1.72)%] and lactate production [103.40±8.32] in Hep-2 cells compared with control [(41.20±1.11)% and 743.69±19.49, t=19.20 and 52.33, respectively, both P<0.01] and YAP-NC group [(39.60±0.78)% and 705.22±17.20, t=19.34 and 54.56, respectively, both P<0.01]. Compared with the control group (78.32±4.04) and YAP-NC group (77.28±3.11), the scratch healing ability of Hep-2 cells was significantly decreased in YAP-shRNA group (44.71±4.68). The P value was less than 0.01 (t=9.42 and 10.04). The number of cells with YAP-shRNA (33.30±4.19) passing through compartments was remarkable fewer than the control group (133.71±6.72) and YAP-NC group (126.32±4.21). The P value was less than 0.01 (t=21.96 and 27.13). The expression of E-cadherin protein in cells of YAP-shRNA group (6.16±0.11) was up-regulated compared with control (0.97±0.10, t=35.70, P<0.01) and YAP-NC group (1.13±0.09, t=36.28, P<0.01), while the expression of vimentin protein in cells of YAP-shRNA group (1.08±0.09) was down-regulated compared with control (5.67±0.12, t=29.91, P<0.01) and YAP-NC group (5.51±0.12, t=29.04, P<0.01). Conclusions: The down-regulation of YAP in Hep-2 inhibits the migration and invasion of cells via suppressing Warburg and EMT program.

LINC00968 accelerates the progression of epithelial ovarian cancer via mediating the cell cycle progression.

OBJECTIVE: The aim of this study was to clarify the potential role of LINC00968 in the progression of epithelial ovarian cancer (EOC) and the underlying mechanism. PATIENTS AND METHODS: The relative expression level of LINC00968 in EOC tissues (n=40) and normal ovarian tissues (n=40) was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). LINC00968 expression in human-derived ovarian cancer cell lines was examined by qRT-PCR as well. After transfection of LINC00968 small-interfering RNA (siRNA) in ovarian cancer cells, cell cycle progression and cell proliferation were evaluated through flow cytometry, Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Tumor xenograft was conducted in nude mice to elucidate the function of LINC00968 in EOC tumorigenesis in vivo. Furthermore, the relative expression levels of cell cycle factors and protein kinase B/extracellular-signal-regulated kinase (AKT/ERK) in ovarian cancer cells influenced by LINC00968 were detected by Western blot. RESULTS: LINC00968 was significantly up-regulated in EOC tissues when compared with normal control tissues. Meanwhile, LINC00968 expression was positively correlated with the prognosis of EOC. Transfection of LINC00968 siRNA in HEY and HO8910 cells markedly attenuated proliferative ability and arrested cell cycle in the G1 phase. Knockdown of LINC00968 remarkably suppressed tumor growth of EOC in nude mice. The silence of LINC00968 significantly downregulated Cyclin D, Cyclin E and CDK4, whereas upregulated p16 and p21. In addition, AKT and ERK pathways were inhibited by knockdown of LINC00968 in ovarian cancer cells. CONCLUSIONS: LINC00968 expression is markedly upregulated in EOC. Meanwhile, it arrests the cell cycle in the G1 phase by inhibiting the ERK and AKT pathways, thus accelerating EOC progression.

[Genetic screening in early diagnosis of neonatal WAS gene-related disorders].

Objective: To explore the clinical value of genetic screening for early identification of WAS gene-related disorders in newborns. Methods: This was a retrospective study. Neonatal Genome Project from Children's Hospital of Fudan University collected 5 800 high-risk newborns in the neonatal intensive care unit to study the patients' genetic causes using high-throughput sequencing from January 2016 to December 2017. Eleven newborns (all were boys) with pathogenic or likely pathogenic variants in WAS gene were enrolled. Data of clinical characteristics,gene variants and genotype-phenotype correlation were collected and summarized. Results: Eleven patients included 5 cases with Wiskott-Aldrich syndrome (WAS) and 6 cases with X-linked thrombocytopenia (XLT).Two patients with WAS developed clinical manifestations in the early neonatal period,and 3 patients in 5-8 weeks after birth. Three neonates with XLT were hospitalized for other diseases in the first place.Their platelet count was found to be reduced after admission to hospital, and diagnosis was made after genetic testing. Eleven pathogenic or likely pathogenic variants in WAS gene were identified. Among them, 7 were first reported in this study, including 2 frame shift variants c.138delG and c.388_390del, 4 splicing variants c.1453+1G>A,c.734+1G>C,c.135G>A and c.1453+3G>C, and 1 missense variant c.1118C>T. The other 4 reported variants were c.777+1G>A,c.107_108delTT, c.436delC and c.1509_*3delAGTG. Conclusions: The clinical features of WAS gene-related disorders in neonatal period lack specificity. Genetic screening in newborns plays an important role in the early diagnosis of diseases and provides providing evidence for the early intervention.

[Anatomy and function of the Eustachian tube influence the development of chronic suppurative otitis media].

Objective:To explore the influence of anatomy and function of the Eustachian tube（ET） on the development of chronic suppurative otitis media. Method:We retrospectively enrolled 92 cases（184 ears） of adult patients with chronic suppurative otitis media（CSOM）, in whom 118 CSOM ears, 25 atelectasis ears and 41 normal ears were included. All patients underwent endoscopy, tympanometry, pure tone average, temporal bone computerized tomography scans and ET function test. Patients with pars flaccida retraction, cholesteatoma, ET obstruction or maxillofacial deformity were excluded. The length, angle and function of ET were analyzed. Result:The ET angle was （23.1±2.4） ° in CSOM ears, was （22.9±2.9） ° in atelectasis ears and was （25.1±3.0） ° in normal ears. The ETs were more horizontal in ears with CSOM and atelectasis（P<0.01）. The ET length was （39.2±4.3） mm in CSOM ears, was （41.7±5.8） mm in atelectasis ears and was （43.0±5.9） mm in normal ears. The ETs in CSOM ears were shorter compared to the ETs normal ears（P<0.01）. No significant difference was detected between the length of ETs of atelectasis ears and normal ears（P>0.05）. The ET dysfunction rate was 62% in CSOM ears, was 68% in atelectasis ears, which were both significantly higher than the dysfunction rate in normal ears（22%）（P<0.05）. Conclusion:The anatomical and functional changes of ETs contribute to the development of CSOM. For patients with more horizontal and shorter ETs as well as ETs dysfunction, more progressive treatment should be considered.

Velocity-space sensitivity of time-of-flight neutron spectrometer at EAST in deuterium plasma.

The Time-Of-Flight Enhanced Diagnostics (TOFED) neutron spectrometer with a double-ring structure has been installed at the Experimental Advanced Superconducting Tokamak (EAST) to perform advanced neutron emission spectroscopy diagnosis for deuterium plasma. In order to reduce the random coincidence from the background neutrons and gamma-rays, TOFED was moved outside the experimental hall and placed in the newly-built nuclear diagnostics laboratory in 2017. In this paper, the instrument-specific weight functions of TOFED are derived by taking the instrument response matrix and the radial line of sight in this new layout into consideration. The results show that the instrument is predominantly sensitive to counter-passing particles in the region where time-of-flights < 69.4 ns, while events at higher time-of-flights (corresponding lower neutron energies) are mostly representative of co-passing ions. The instrument-specific weight functions express the relationship between data in a given channel of the spectrum and the velocity space region that contributes to that. The results can be applied for energetic particle physics studies at EAST, in particular to compare data from different diagnostic techniques.

Velocity-space sensitivity of the compact neutron emission spectrometers at EAST.

Several compact neutron spectrometers are now installed at EAST (Experimental Advanced Superconducting Tokamak) to obtain information on fuel ions produced in the core of the plasma. In this paper, a stilbene crystal neutron spectrometer and an EJ301 liquid scintillator neutron spectrometer with n-γ discrimination capability will be discussed. Both spectrometers have a horizontal line of sight, while at different positions. In the last few experiment campaigns at EAST, they all proved to be reliable diagnostics for auxiliary heated D-D plasmas. Taking the response function simulated by dedicated Geant4 models into consideration, the velocity-space sensitivities given by the instrument-specific weight function of the beam-thermal part of neutron energy spectra in D-D plasmas are derived for both spectrometers with the Genesis code. This method makes it possible to directly relate the contribution of different deuteron velocity space regions to events in each channel of the neutron spectrum measured by the two instruments: http://rsi-htpd.peerx-press.org/.

[Dynamic investigation of nutritional risk in patients with malignant tumor during hospitalization].

Objective: To prospectively investigate the changes in nutritional status of patients with malignant tumors during hospitalization by using nutritional risk screening (NRS2002), and to analyze the correlation between the nutritional status and clinical outcomes . Methods: This was a prospective and parallel research done by multi-center collaboration from 34 hospitals in China from June to September 2014.Hospitalized patients with malignant tumors inthese departments (Department of Gastroenterology, respiratory medicine, oncology, general surgery, thoracic surgery and geriatrics)were investigated. Only the patients with age≥ 18 years and hospitalization time between 7-30 days were included. During hospitalization, the physical indexes of human bodywere measured, and the NRS 2002 scores, and monitored the nutritional support at the time points of admission and 24 hours before discharge were recorded.And whether there was a nutritional risk in hospitalized patients and its association with clinical outcomes were investigated. Results: A total of 2 402 patients with malignancies were enrolled in this study. Seventy fourpatients who did not complete NRS2002 were eliminated, and 2 328 patients were included. The number of the main diseases was the top five, including 587 cases of colorectal cancer, 567 cases of lung cancer, 564 cases of gastric cancer, 146 cases of esophageal cancer, and 119 cases of liver tumor. At the time of discharge, compared with admission, the BMI, body weight, grip and calf circumferences of patients with malignant tumor were significantly decreased (P<0.05). The total protein, albumin, prealbumin and hemoglobin were significantly lower than those at admission (P<0.05). In 2 328 patients who were completed nutritional risk screening, the rate of malnutrition at admission was 11.1% (BMI =18.5, 258/2 328) and the rate of malnutrition at discharge was 10.9% (BMI =18.5, 254/2 328), there were no significant differences (χ(2)=0.019 7, P=0.888). There were 1 204 patients with nutritional risk at admission (51.7%, NRS2002 score≥3)and 1 352 patients with nutritional risk at discharge (58.1%, NRS2002 score≥3), with significant differences (χ(2)=49.9, P<0.001). The incidence of nutritional risk in patients with colorectal, stomach, and lung tumors at discharge was significantly higher than that at admission (P<0.05). The infective complications and other complications of patients with nutritional risk were significantly greater than those without nutritional risk at admission and at discharge.ICU hospitalization stay of patients with nutritional risk was increased significantly than those without nutritional risk at admission(P=0.042). Hospitalization expenses of patients with nutritional risk was increased significantly than those of patients without nutritional risk at discharge(P<0.01). Conclusion: The patients with malignant tumor have a higher incidence rate of malnutrition at both admission and discharge and malnutritionhas correlation with adverse clinical outcomes.The aboveindicators did not improve significantly at discharge.Doctors should pay more attention to the nutritional status (screening and evaluation)of patients before discharge and use appropriate and adequate nutrition support in order to prevent the weight loss and improve the life quality of patients.

[Clinical characteristics of human recombination activating gene 1 mutations in 8 immunodeficiency patients with diverse phenotypes].

Objective: To investigate the clinical characteristics of 8 immunodeficiency cases caused by human recombination activating gene 1 (RAG1) mutations, and to explore the relationship among genotypes, clinical manifestations and immunophenotypes. Methods: Clinical data were collected and analyzed from patients with RAG1 mutations who visited the Department of Clinical Immunology, Children's Hospital of Fudan University between October 2013 and June 2017. The data included clinical manifestations, immunophenotypes and genotypes. Results: A total of 8 patients were diagnosed with RAG1 deficiency (6 boys and 2 girls). The minimum age of onset was 2 months, and the maximum age was 4 months. The minimum age of diagnosis was 2 months, and the maximum age was 13 years. Four patients had a family history of infant death due to severe infections. Two cases were born to the same consanguineous parents. All cases had recurrent infections, including involvement of respiratory tract (8 cases), digestive tract (6 cases), urinary tract (1 case), and central nervous system (1 case). The pathogens of infection included bacteria, viruses and fungi. Rotavirus was found in 3 cases, cytomegalovirus (CMV) in 5 cases, bacillus Calmette-Guérin adverse reaction in 2 cases (1 of whom had a positive acid-fast smear from lymph node puncture fluid), fungal infection in 3 cases. One case had multiple nodular space-occupying lesions in lungs and abdominal cavity complicated with multiple bone destruction. The peripheral blood lymphocyte counts of all patients ranged between 0.1 ×10(9)/L and 3.3×10(9)/L (median, 0.65×10(9)/L). Eosinophilia was found in 3 cases (range, (0.48-1.69) ×10(9)/L). The patients were classified according to immunophenotype as severe combined immunodeficiency phenotype (4 cases), leaky severe combined immunodeficiency (2 cases), Omenn syndrome (1 case) and combined immunodeficiency (1 case) . Decreased serum IgG levels were found in 3 cases, increased serum IgM levels in 3 cases, increased serum IgE levels in 5 cases. RAG1 homozygous mutations were detected in 5 cases and RAG1 compound heterozygous mutations in 3 cases. Two novel mutations and six previously reported mutations were identified. Three cases were successfully treated with hematopoietic stem cell transplantation. Four cases died due to infections, and the 13 year-old patient was still under follow-up in the outpatient clinic. Conclusions: Different RAG1 gene mutations can lead to diverse clinical presentations and immune phenotypes. Clinicians should pay attention to the family history of infant death with severe infection. In that situation, immunological evaluation and gene detection should be performed as early as possible.

Measurement and simulation of the response function of time of flight enhanced diagnostics neutron spectrometer for beam ion studies at EAST tokamak.

The 2.5 MeV TOFED (Time-Of-Flight Enhanced Diagnostics) neutron spectrometer with a double-ring structure has been installed at Experimental Advanced Superconducting Tokamak (EAST) to perform advanced neutron emission spectroscopy diagnosis of deuterium plasmas. This work describes the response function of the TOFED spectrometer, which is evaluated for the fully assembled instrument in its final layout. Results from Monte Carlo simulations and dedicated experiments with pulsed light sources are presented and used to determine properties of light transport from the scintillator. A GEANT4 model of the TOFED spectrometer was developed to calculate the instrument response matrix. The simulated TOFED response function was successfully benchmarked against measurements of the time-of-flight spectra for quasi-monoenergetic neutrons in the energy range of 1-4 MeV. The results are discussed in relation to the capability of TOFED to perform beam ion studies on EAST.

[Laboratory diagnosis of chronic granulomatous disease].

OBJECTIVE: To evaluate the methods of flow cytometric-dihydrorhodamine 123 (DHR) analysis, gp91 protein detection, gene mutation analysis for the precise diagnosis of chronic granulomatous disease (CGD). METHOD: Clinical and laboratory data of patients with CGD confirmed by gene mutation analysis from 2008 to 2015 in Children's Hospital of Fudan University were retrospectively reviewed.The results of respiratory burst, gp91 protein level, and gene mutations were analyzed.The relationships among these three methods were explored. RESULT: A total of 138 patients of CGD with confirmed gene mutation were included in this study, of them, 123 cases(89.1%) had CYBB gene mutation, 4 cases(2.9%) had CYBA mutation, 5 cases(3.6%) had NCF1 mutation and 6 cases(4.4%) had NCF2 mutation.The range of stimulatory index (SI) was 0.8-60.5, the 25 th, 50 th, 75th percent was 1.7, 2.7, 4.7; 112 cases had the results of gp91, of them, 100 with gp91(0,) 2 with gp91(-), and 10 with gp91(+) . Six mutations, which were not reported before, were c. 76-77delTT, c. 343-344delCA, c. 481A>T, c. 1152G>C, c. 1613G>A for CYBB gene, and c. 137T>G for NCF2 gene. Among CGD patients with CYBB mutation, SI of patients with gp91(+) was higher than patients with gp91(0) 14.6 vs. 2.5(t=44.21, P=0.004). Patients of NCF1 mutation had higher SI than patients with CYBB mutation, 17.7 vs. 2.5 (t=60.8, P=0.003). CONCLUSION: Flow cytometric-DHR analysis and gp91 protein detection are important diagnostic methods for CGD, they could help the precise diagnosis of CGD.Different mutation types, different mutation genes could have impact on the results of respiratory burst and gp91 level.The application of diagnostic technology from function, protein to gene analysis could help precise diagnosis of CGD.

Extreme ultraviolet imaging of three-dimensional magnetic reconnection in a solar eruption.

Magnetic reconnection, a change of magnetic field connectivity, is a fundamental physical process in which magnetic energy is released explosively, and it is responsible for various eruptive phenomena in the universe. However, this process is difficult to observe directly. Here, the magnetic topology associated with a solar reconnection event is studied in three dimensions using the combined perspectives of two spacecraft. The sequence of extreme ultraviolet images clearly shows that two groups of oppositely directed and non-coplanar magnetic loops gradually approach each other, forming a separator or quasi-separator and then reconnecting. The plasma near the reconnection site is subsequently heated from ∼1 to ≥5 MK. Shortly afterwards, warm flare loops (∼3 MK) appear underneath the hot plasma. Other observational signatures of reconnection, including plasma inflows and downflows, are unambiguously revealed and quantitatively measured. These observations provide direct evidence of magnetic reconnection in a three-dimensional configuration and reveal its origin.