[Clinical analysis of 10 cases of multi-center tumor necrosis factor receptor-associated periodic syndrome].

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.

[Short-term efficacy of empagliflozin in children with glycogen storage disease type â b].

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.

[An investigation on the nutritional status and support of in-patients with common variable immunodeficiency].

The study aimed to reveal for the first time the clinical characteristics, nutritional and metabolic status and support of hospitalized patients with common variant immunodeficiency disease (CVID), and provide reference to improve the long-term nutritional management for such patients. This is a retrospective cross-sectional study. Through searching the electronic medical record system of Peking Union Medical College Hospital, the study included 33 consecutive in-patients with CVID diagnosed in Jan 2016 to Jun 2021, with the male to female ratio of 16∶17. All their medical data, nutritional assessment and intervention retrospectively summarized and analyzed. Data with normal distribution were described using (x¯±s), and analyzed with independent sample t-test. Data with non-normal distribution were compared with non-parametric test. The results showed that the median onset-age of the included patients was 22 (10.0,36.5) years old, and the median duration was 9.0 (2.0,16.0) years. All patients had recurrent infections involving various systems (33/33), with development of autoimmune diseases (8/33) and lymphoproliferative disease or malignancy (9/33) in some cases among them. The nutritional risk screening 2002 (NRS 2002) scores revealed that 85.19% of adults had an NRS 2002≥3 points, and 33.33% of children had a BMI-for-age z score<-2. Weight loss occurred in 66.67% of patients (22/33), while 87.88% (29/33), 69.70% (23/33) and 81.82% (27/33) of patients respectively had anemia, hypoalbuminemia and decreased prealbumin. Among 22 patients with micronutrients status evaluated, 77.27% (17/22), 22.73% (5/22) and 31.82% (7/22) of patients respectively had lowered serum iron, folate deficiency and vitamin B12 insufficiency. Six patients underwent 25-OH-VD3 measurement, and were all testified to have vitamin D deficiency. Among all patients with nutritional risk, 56.00% of them underwent nutritional support: oral nutritional supplements (14 cases), enteral feeding (4 cases) and parenteral nutrition (5 cases). In conclusion, the condition of malnutrition was prevalent in patients with CVID, but was under-recognized and undertreated to some degree.

[Clinical analysis of 49 cases of non-inflammasome related conditions].

Objective: To summarize the clinical characteristics and provide clues for early identification of non-inflammasome related conditions. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 49 children with non-inflammasome related conditions in Peking Union Medical College Hospital from January 2006 to February 2022 were retrospectively analyzed. Results: A total of 49 children, 29 of them were boys and 20 were girls. The age of onset was 0.8 (0.3, 1.6) years, the age at diagnosis was 5.7 (2.8, 8.8) years, and the time from onset to diagnosis was 3.6 (1.9, 6.3) years. Combined with genetic testing results, 49 children with non-inflammasome related conditions were found, including 34 cases (69%) of Blau syndrome, 4 cases (8%) of tumour necrosis factor receptor-associated periodic syndrome, 4 cases (8%) of haploinsufficiency of A20, 2 cases (4%) of Majeed syndrome, 2 cases (4%) of pyogenic sterile arthritis, pyoderma gangrenosum, acne syndrome and 3 cases (6%) of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome. There were 22 cases (45%) with a positive family history. The clinical manifestations included 37 cases (76%) cases with rash, 38 cases (78%) with joint involvement, 33 cases (67%) with eye involvement, 17 cases (35%) with recurrent fever. In addition, 11 cases (22%) were complicated with digestive system involvement. Thirty cases (61%) presented as elevated inflammatory indexes (erythrocyte sedimentation rate and (or) C-reactive protein), positive autoantibodies were noticed in 3 cases (6%). The patients were treated with glucocorticoid in 23 cases (47%), immunosuppressive agents in 43 cases (88%) and biologic agents in 37 cases (76%). During the follow-up of 5.8 (2.9, 8.9) years, 3 cases (6%) died. Conclusions: The symptoms of non-inflammasome related conditions include recurrent fever, rash, joint and ocular involvement with increased inflammatory indexes and negative autoantibodies. Up to now, glucocorticoids, immunosuppressants and biologic agents are the most popular medications for the non-inflammasome related conditions.

[A monogenic lupus family caused by homozygous deletions of DNASE1L3 gene and literature review].

Objective: To report the clinical features and genetic variations of monogenic lupus caused by DNASE1L3 deficiency and to introduce preliminary experience on diagnosis and treatment for this disease. Methods: Clinical data of 3 children from the same pedigree were collected who were diagnosed with DNASE1L3 defect-associated monogenic lupus in August 2020 by Department of Pediatrics, Peking Union Medical College Hospital referred from Department of Pediatrics, Boai Hospital of Zhongshan. DNA was extracted from the peripheral blood of the patients and their parients to perform genetic analysis and confirmation. Six interferon-stimulated genes were relatively quantified to examine the activation of the type I interferon signaling. "DNASE1L3" "systemic lupus erythematosus" and "SLE" were searched in PubMed, Wangfang Data, CNKI databases for related reports from database established date to June 2022. Spectrum of genetic variations and clinical phenotypes were analyzed in combination with this pedigree. Results: Case 1, a 14-year-old girl with edema, hematuria, and heavy proteinuria, presented with membranous nephropathy. Case 2, the 12-year-old younger brother of case 1 with hematologic, cardiac, pulmonary, renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody and low complement C3, manifested with systemic lupus erythematosus. Case 3, the 8-year-old younger sister of case 1 with hematologic, cardiac, pulmonary and renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody, and low complement C3 and C4, manifested with systemic lupus erythematosus. Genetic testing revealed that all 3 patients carried homozygous deletions in exons 3 and 4 on DNASE1L3 gene. Interferon scores were elevated in case 1, 2 and their parents but normal in case 3. All 3 patients were diagnosed with monogenic lupus caused by DNASE1L3 defects. Literature searching identified 10 relevant publications in English and 0 publication in Chinese, involving 42 patients from 18 pedigrees (including the 3 cases from this pedigree). Nine variants were found: c.289_290delAC (p.T97Ifs*2), c.643delT (p.W215Gfs*2), c.320+4delAGTA, c.321-1G>A, Ex5 del, c.433G>A, c.581G>A (p.C194Y), c.537G>A (p.W179X), and Ex3-4 del. The hotspot variants were c.643delT (43% (36/84)) and c.289_290delAC (36% (30/84)). Kidney was affected in 31 cases (74%) of the 42 cases. Among the 25 patients, joints were affected in 16 cases (64%), fever were reported in 13 cases (52%) hematologic system was involved 13 cases (52%), rash was present in 10 cases (40%), intestinal tract was involved in 8 cases (32%), lungs were involved in 6 cases (24%), eyes were involved in 4 cases (16%), and the heart was involved in 4 cases (16%). The 2 cardiopulmonary affected patients from literature showed poor prognosis, with 1 died, and 1 right heart failure. Conclusions: The clinical manifestations of monogenic lupus caused by DNASE1L3 defect are highly heterogenous, primarily with renal, blood, joint, intestinal, and cardiopulmonary involvement. There is no correlation between the genotype and the phenotype. DNASE1L3 defects were predominantly mediated by null varations including nonsense, splicing, frameshift and exon deletions. The hotspot variants are c.643delT and c.289_290delAC. DNASE1L3 defects should be cautioned in early-onset lupus-like patients with renal, joint and hematologic involvement. Cardiopulmonary involved patients require close monitoring for poor prognosis. Copy number variations should be carefully analyzed after negative whole exome sequencing.

[Analysis of clinical characteristics of 35 inflammasomopathies cases].

Objective: To summarize the clinical characteristics of inflammasomopathies, enhance the recognition of those diseases, and help to establish the early diagnosis. Methods: The clinical manifestations including fever, rash, systems involvement as well as laboratory results and genotypic characteristics of 35 children with inflammasomopathies diagnosed by the Department of Pediatrics, Peking Union Medical College Hospital, from January 1, 2008 to December 31, 2020 were analyzed retrospectively. Results: A total of 35 cases of inflammasomopathies were diagnosed, and 20 of them were boys while 15 were girls. Inflammasomopathies patients have early onset, the age of onset as well as diagnostic age were 1 (0,7) and 7 (3,12), respectively. Among those patients, 10 had familial mediterranean fever, 3 had mevalonate kinase deficiency, 15 cases had NLRP3 gene associated autoinflammatory disease, 4 cases had NLRP12-associated autoinflammatory disease, 2 cases had familial cold autoinflammatory syndrome 3, and 1 case had familial cold autoinflammatory syndrome 4. A total of 34 cases (97%) showed recurrent fever, 27 cases (77%) had skin rashes, while 11 cases (31%), 10 cases (29%), and 8 cases (23%) were presented with lymphadenopathy, hepatosplenomegaly and growth retardation, respectively. In terms of systemic involvement, there were 18 cases (51%), 12 cases (34%), 8 cases (23%), and 5 cases (14%) with skeletal, neurological, auditory, and renal involvement, respectively. Central nervous system involvement was seen only in NLRP3 gene associtated autoinflammatory diseases (12 cases), sensorineural deafness was seen in NLRP3 gene associtated autoinflammatory diseases (6 cases) and NLRP12 gene associated autoinflammatory diseases (2 cases), and abdominal pain was observed in familial Mediterranean fever (5 cases), mevalonate kinase deficiency (1 case) and NLRP12 gene related autoinflammatory diseases (1 case). In the acute inflammatory phase, the acute phase reactants (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) of 35 cases (100%) were significantly increased. There were 21 cases received ferritin examination, and only 4 cases (19%) showed an increase of it. In terms of autoantibodies, among all 35 patients, 4 cases (11%) were positive for antinuclear antibodies (ANA). Conclusions: Fever, skin rash, and skeletal manifestations are the most common clinical features, accompanied with increased CRP and ESR, and negative results of autoantibodies such as ANA. The clinical manifestations of those diseases are complex and diverse, and it is prone to delayed diagnosis and treatment.

[Clinical characteristics of 25 patients with type â interferonopathies].

Objective: To summarize the clinical characteristics of type I interferonopathies and provide clues for early identification and diagnosis. Methods: Clinical data of 20 patients admitted to Department of Pediatrics, Peking Union Medical College Hospital and 5 patients admitted to Department of Rheumatology and Immunology, Shenzhen Children's Hospital from January 2016 to September 2021 were retrospectively analyzed. The data included gene results, clinical manifestations and auxiliary examination results. Results: Of the 25 cases, 12 were males and 13 were females. Age of onset ranged from 1 day to 11 years. And 84% of them had the onset before the age of 3 years. The cases consisted of 14 cases of Aicardi-Goutières syndrome (AGS), 6 cases of adenosine deaminase 2 deficiency (DADA2), 3 cases of stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI), and 2 cases of Spondyloenchondrodysplasia with immune dysregulation (SPENCDI). Eighteen patients (72%) experienced neurologic disorder, among whom 16 (64%) showed intracranial calcification, 11 (44%) had dystonia, 10 (40%) had leukodystrophy, 6 (24%) had epilepsy, 5 (20%) had brain atrophy and 5 (20%) had early-onset cerebrovascular events. Skin involvement occurred in 15 cases (60%), among whom 8 cases (32%) had chilblain-like rash, 4 cases (16%) had livedo reticularis, 3 cases (12%) had erythema, 2 cases (8%) had erythema nodosum and 2 cases (8%) had Raynaud's phenomenon. In addition, 12 cases (48%) had positive autoimmune antibodies, 10 cases (40%) manifested as developmental retardation, 8 cases (32%) experienced lung interstitial lesions, and 7 cases (28%) demonstrated thyroid dysfunction. And 1 died (4%) at 11 years of age. Conclusions: Type Ⅰinterferonopathies can involve multiple organs, and share the characteristics of systemic inflammatory and autoimmune diseases. The early-onset neurological symptoms (early-onset cerebrovascular events, intracranial calcification, leukodystrophy and cerebral atrophy), rashes (chilblain-like rash, livedo reticularis and erythema), positive autoimmune antibodies, developmental delay, interstitial lung disease and thyroid dysfunction may indicate type Ⅰ interferonopathies.

[Analysis of the clinical perinatal characteristics of 226 patients with Prader-Willi syndrome in China].

Objective: To enhance the early recognition of Prader-Willi syndrome by summarizing the clinical characteristics of Prader-Willi syndrome (PWS) during perinatal period. Methods: Through a nationwide cross-sectional study in the Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences,226 children diagnosed as PWS by molecular genetics were recruited from September 2019 to March 2020. Clinical data including fetuses Age, birth weight, fetal movement, fetal position, amniotic fluid, mode of bith, crying, muscle tension, feeding, and cryptorchidism were collected to analyze the clinical characteristics of Chinese PWS patients in the perinatal period, and according to the mode of birty, birth weight and genotypes to perform subgroup analysis. The clinical manifestations of different subtypes were statistically analyzed by t test, χ2 test or Mann-Whitney U test. Results: Among the 226 PWS patients, 120 were males, and 106 were females. Among them, 100 (44.2%) patients were small for gestational age. Decreased fetal movement was the most common manifestation 202 cases (89.4%) during pregnancy, and other manifestations included polyhydramnios 71 cases (31.4%) and abnormal fetal position 58 cases (25.7%). One hundred and eighty-five (81.9%) patients were delivered by cesarean section and the frequency of abnormal fetal position was significantly higher (30.8%(57/185) vs. 2.4%(1/41),χ²=14.161,P<0.01). As for abnormal manifestations after birth included hypotonia 221 cases (97.8%),220 cases (97.3%) showing weak crying, 116 cases among the total 120 males patients (96.7%) wanifested with cryptordnildism and 206 feeding difficulties (91.2%). In terms of genetic subtype, most of them (184/226, 81.4%) had a paternal deletion, while maternal age (35±5 vs. 29±5, t=-6.591, P<0.01) and the frequency of polyhydramnios (47.6% (20/42) vs. 27.7% (51/185), χ²=6.286, P=0.012) were significantly higher in the non-deletion group. Conclusions: The main manifestations of PWS patients during the perinatal period are hypotonia, weak crying, feeding difficulties, decreased fetal movement, cryptorchidism and those patients are more likely to be born by cesarean section. In newborns with these characteristics, pediatricians should be aware of the possibility of PWS. In terms of the relationship between genotypes and phenotypes, polyhydramnios is more frequently observed in the non-deletion group.

Lipid status and linear relationship between total cholesterol and triglycerides in glycogen storage disease type I.

OBJECTIVE: Glycogen storage disease type Ia (GSDIa) is a glucose metabolic disorder. GSDIa patients are characterized by hypoglycemia, hepatomegaly, hyperlipidemia, and hyperlactacidemia. This retrospective study aimed to review the lipid status, explore lipid treatment targets, and assess preferable lipid-lowering drugs. PATIENTS AND METHODS: Clinical data on GSDIa patients' characteristics were collected. Most patients were followed-up once a year. Diet control and raw cornstarch treatment were used to maintain normal blood glucose and lipid levels. Some patients were given lipid-lowering drugs. We compared the lipid levels before and after each treatment. RESULTS: A total of 163 GSDIa patients were enrolled in this study. After treatment with raw cornstarch, the total triglycerides (TG) level has significantly decreased by 30±50% (8.37±7.23 to 5.39±5.29 mmol/L, p<0.001). There was no change in the total cholesterol (TC) level. Fifteen patients regularly took atorvastatin, and 15 took fibrates for more than one year. The therapeutic effect of atorvastatin was better than fibrates. The TC was positively correlated with TG after treatment, resulting in the following linear equation: TG=1.63×TC-2.86. Using this equation and Chinese children's normal TC level of 5.18 mmol/L, we aimed to maintain the patients at TG < 5.58 mmol/L. CONCLUSIONS: Patients with GSDIa have significant abnormalities in lipid metabolism. Because the complications of hyperlipidemia are caused mainly by TC, thereby, by maintaining it at a normal level, we could set a TG target by the linear equation that allowed a certain degree of hypertriglyceridemia. This study found that the therapeutic effect of atorvastatin was better than fibrates.

[Stimulator of interferon genes-associated vasculopathy with onset in infancy: first case report in China].

Objective: To summarize the clinical characteristics and treatment efficacy of the first reported case of a Chinese boy with stimulator of interferon genes (STING) associated vasculopathy with onset in infancy (SAVI). Methods: Sanger sequencing of the gene TMEM173 was performed based on systemic evaluation and clinical analysis of a highly suspected SAVI child admitted to Peking Union Medical College Hospital. A literature search (search terms included 'STING''SAVI''autoinflammatory diseases' and 'interferonopathy') was conducted using Chinese literature database, EMBASE and PubMed to include recently published SAVI studies (searched from January 2010 to December 2017). Results: A 14-year-old boy who had a history of chronic dry cough along with decreased activity tolerance after birth presented with growth retardation, chilblain lesions on the ear, telangiectasia of multiple skin areas and long clubbed fingers. His C-reactive protein was 21 mg/L, erythrocyte sedimentation rate was 78 mm/1h, and IgG was 22.16 g/L. The high-resolution computed tomography (HRCT) revealed interstitial lung diseases and echocardiography showed pulmonary artery hypertension, with a level of 61 mmHg (1 mmHg=0.133 kPa). Genetic mutation of TMEM173 (c.463G>A, p.V155M) was confirmed by Sanger sequencing. His activity tolerance increased to some extent after treatment with tofacitinib at a dose of 5 mg twice a day. Our review yielded 8 publications (8 English and 0 Chinese) . To date 20 cases have been reported worldwide, who mostly presented with skin and lung involvement as well as growth retardation. Conclusions: SAVI has been included within the spectrum of interferonopathy, which is a kind of autoinflammatory diseases as well. Typical clinical features include chilblain skin lesions, interstitial lung disease, growth retardation, elevated IgG levels, and increased inflammation markers. Janus kinase (JAK) inhibitors may offer benefit for SAVI patients.

[Clinical and immunological analysis of patients with activated phosphoinositide 3-kinase δ syndrome resulting from PIK3CD mutation].

Objective: To explore the clinical and immunological features, gene mutations, treatment and prognosis in patients with activated phosphoinositide 3-kinase δ syndrome (APDS) caused by PIK3CD gene heterozygous germline mutation. Method: The data of clinical, immunological phenotype, treatment, and prognosis of 15 patients with APDS, who visited Children's Hospital of Chongqing Medical University, Peking Union Medical College Hospital, and Shenzhen Children's Hospital from June 2014 to November 2016, were collected and analyzed. Result: Of the 15 patients, 11 were males, remaining 4 patients were females. The median age of disease onset was 1 year, and median age at diagnosis was 4 years and 4 months. All patients had the de novo heterozygous germline mutation in PIK3CD (c. 3061G>A, p. E1021K). The common initial symptoms were respiratory infections, including pneumonia (12 cases) , bronchiectasis (5 cases). Other common clinical manifestations were recurrent and chronic diarrhea (11 cases), Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV) viremia (10 cases), hepatosplenomegaly (13 cases), and lymphadenopathy (10 cases). The main immunological features were increased IgM (11 cases), decreased IgG (6 cases), decreased numbers of CD4+ T cell (7 cases) especially naïve CD4+ T cell (9 cases), reduced numbers of B cells (11 cases) particularly naïve B cells (9 cases), increased numbers of transitional B cells (5 cases) and CD8+ terminally differentiated effector memory T cells (5 cases). After 1-29 months follow up, 13 of the 15 cases remain survived, of whom 5 cases received regular intravenous immunoglobulin (IVIG) therapy, with reduced frequency of infections and improved severity of infections; of whom 3 cases received oral rapamycin therapy at the dosage of 1 mg/ (m2·d) and with a decrease in nonneoplastic lymphoproliferation. Conclusion: E1021K is a hotspot for mutation in the PIK3CD gene in patients with APDS. Regular IVIG can improve their quality of life. Targetel treatment with rapamycin could mitigate hepatosplenomegaly.

[A major histocompatibility complex class â ¡ deficiency case report and literature review].

OBJECTIVE: To summarize and report the clinical characteristics and laboratory results of a case and those reported in literature with MHC class Ⅱ deficiency. METHOD: The clinical features, laboratory results and gene mutation analysis of an infant with MHC class Ⅱ deficiency, who was diagnosed and treated in Peking Union Medical College Hospital since December 2013, were retrospectively analyzed."Major histocompatibility complex class Ⅱ deficiency"or"bare lymphocyte syndrome"were used as keywords in order to retrieve reports from CNKI (from its establishment to October 2015) and Wanfang Database (from its establishment to October 2015), PubMed Database (from its establishment to October 2015) was searched. The characteristics, diagnosis, treatment and prognosis were summarized by reviewing related articles. RESULT: The patient was a 8-month-old boy. Since the fourth month of life, he started to have repeated fever, susceptible to a variety of pathogens, immune hemolytic anemia, severe malnutrition, and finally diagnosed as MHC class Ⅱ deficiency disease when he was 20-month-old.No related reports were retrieved from CNKI and Wanfang database, there were 20 articles and 179 patients were reported worldwide in the past 10 years. Patients exhibit an extreme vulnerability to infections(resptratory infection(82%, 146/178), inpection of gastroin testinal(76%, 135/178)). The common laboratory examinations showed hypogammaglobulinemia, CD4(+) lymphopenia(93%, 107/115) etc. Diagnosis relies on the flow-cytometric analysis and genetic analysis. CONCLUSION: It is considered necessary for patients with young onset age, manifestation of clinically opportunistic infection as immune deficient disease, including the MHC class Ⅱ deficiency disease, especially long-term diarrhea, poor development and cryptosporidium infection. This disease could coexist with autoimmune disorders.

[Identification and significance of myeloid-derived suppressor cells in peripheral blood of breast cancer patients].

OBJECTIVE: To investigate the presence, biological features, and clinical significance of myeloid-derived suppressor cells (MDSCs) in breast cancer patients. METHODS: Eighty-four cases of breast cancer, 37 cases of benign breast tumor and 21 cases of healthy individuals were included in this study. Samples of peripheral blood (2 ml) were collected, and in the breast cancer patients, blood samples were taken both before and after treatment. Flow cytometry using anti-CD11b, CD33, CD14 and HLA-DR antibody was conducted to identify the unique membrane markers of MDSCs, and statistical analysis was performed to explore the relationship between MDSCs and clinical factors. Cell isolation and in vitro assay were used to test T cell function. RESULTS: CD11b(+) CD33(+) CD14(-) MDSCs were present in the blood of breast cancer patients, and these MDSCs were histologically of mononuclear cells. Cell proliferation assay confirmed that MDSCs inhibited proliferation of homologous T cells in vitro. MDSCs levels in patients with breast cancer, benign disease and the health control were (15.93±3.17)%, (8.92±4.42)% and (5.02±2.75)%, respectively, with a statistically significant difference (P<0.001) between breast cancer patients and the other subjects (patients with benign lesions and healthy controls). The expression level of MDSCs in patients with breast cancer was associated with surgical treatment, but not with age, disease stage, lymph node metastasis, ER or PR expression. MDSCs levels were significantly lower in post-operative patients[(7.83±3.78) %] than the (15.37±2.49) % in patients before surgery (P<0.001). CONCLUSIONS: The results of this study demonstrate that MDSCs are present in the peripheral blood of breast cancer patients and the level of MDSCs is associated with surgical treatment. Our findings suggest that CD11b(+) CD33(+) CD14(-) MDSCs are likely involved in breast cancer initiation and development, and may become a novel biomarker to facilitate diagnosis and to predict clinical outcomes of breast cancer.

[Stevia in the fight against dental caries]. / Stevia in de strijd tegen cariës.

Stevia is a natural, non-caloric sweetener of plant origin. The sweetening power of stevia is several hundred times larger than that of table sugar (sucrose). On the basis of available research, the European Food Safety Authority concluded that stevia is safe for human consumption. Since then, stevia has been approved as a sweetener for the European market. As a substitute for sucrose, stevia can contribute to a reduced caloric intake and can play a role in the prevention and/or treatment of metabolic disorders. In addition, stevia is non-cariogenic and is, moreover, affordable. Promoting the consumption of stevia can therefore be a preventive means of fighting dental caries.

Fluorescence imaging in human identity testing.

We have investigated the use of fluorescence detection and the FluorImager S1 System (Molecular Dynamics) for analyzing a comprehensive set of human DNA typing tests. We used an alkaline phosphatase-conjugated YNH24 oligonucleotide probe to the repeat-containing D2S44 locus to detect both alleles in 50 ng of human genomic DNA (0.025 amol) by Southern hybridization using a chemifluorescent substrate. We used a similar approach to quantify human DNA using an enzyme-conjugated oligonucleotide probe to the D17Z1 locus. Both fluorescent nucleic acid gel staining and direct fluorescent labeling methods were tested to detect PCR-based D1S80 and short tandem repeat (STR) multiplex allele profiles. The fluorescent staining method sensitively detected these allelic profiles in both denaturing and non-denaturing acrylamide gels using a simple, 10-min procedure. Fluorescent primers eliminate the doublet band patterns often seen with staining methods, which label both strands of the amplified products. This complicates interpretation of STR typing tests. Only one primer for each locus is labeled, so only one strand of the DNA product is detected. Fluorescein end-labeled primers were used in multiplex PCR to amplify, detect and type STRs.

Centromere spreading and centromeric aberrations in ovarian tumors.

Centromere spreading (CS) of chromosomes and high occurrence of aberrations at centromeric region were observed in two papillary serous cystadenocarcinomas and one borderline papillary serous cystadenoma of the ovary. In the borderline tumor, CS of chromosome 12, trisomy of which had been reported as the sole abnomaly in benign ovarian tumors, was seen in three metaphases. It is suggested that CS may be an early event in the carcinogenesis of epithelial ovarian tumors. Centromeres of some chromosomes in tumor cells may be unstable and thus bring about premature centromere separations and breakages at centromeric regions, followed by some numerical and structural chromosomal aberrations.

Comparative description of Pseudomonas cocovenenans (van Damme, Johannes, Cox, and Berends 1960) NCIB 9450T and strains isolated from cases of food poisoning caused by consumption of fermented corn flour in China.

Phenotypic and genetic characteristics of Pseudomonas cocovenenans NCIB 9450T (T = type strain) and strains isolated from cases of food poisoning caused by consumption of fermented corn flour are compared. Our results show that these strains are members of the same species and conform to the description of Section II of the genus Pseudomonas. Because of small differences in substrate utilization patterns, the strains isolated in the People's Republic of China are thought to be biovars of P. cocovenenans.