[Correlation between heart rate index, SBPpeak-to-SBPrest ratio and peak oxygen consumption in patients with chronic heart failure].

Objective: To investigate the correlation between heart rate index (HRI), systolic blood pressure(SBP) peak-to-SBPrest ratio (SBPR) and peak oxygen consumption (peakVO2) in patients with chronic heart failure (CHF), and discuss the possibility of using HRI and SBPR collected during exercise to assess the exercise tolerance of CHF patients in the absence of gas analysis. Methods: In this cross-sectional study, a total of 547 patients with CHF who underwent cardiopulmonary exercise test(CPET) in Tongji Hospital Heart Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were collected retrospectively, focusing on their clinical data including age, gender, type of heart failure,BMI as well as data collected during their CPETs, such as peakVO2, HRI and SBPR. Spearman univariate correlation analysis was used for statistical analysis, to unveil the correlations between peakVO2 and those parameters, and multiple linear regression analysis was also conducted. Results: A total of 547 CHF patients conducting CPET were included in this research, of which 447 were male, at age of 63(56, 69). Univariate analysis indicates that HRI, SBPR and peakVO2 showed significant positive correlation (r=0.323, 0.263, respectively, all P<0.001); Age and peak VO2 showed significant negative correlation(r=-0.207, P<0.001); Male patients showed peakVO2 higher than female(r=-0.229, P<0.001); PeakVO2 of heart failure with reduced ejection fraction(HFrEF) was lower than heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF) (r=0.181, P<0.001). Body mass index (BMI) had no significant correlation with peakVO2 (P>0.05). Multivariate linear regression analysis showed that the HRI, SBPR were positively correlated with peakVO2(t=7.68, 5.08, respectively, all P<0.05), while age and BMI showed negative correlation with peakVO2(t=-5.43, -0.31, respectively, all P<0.05). PeakVO2 of male was higher than female(t=-6.03, P<0.05), and peakVO2 of HFrEF was lower than those of HFmrEF and HFpEF(t=3.17, 4.48, respectively, all P<0.05). A linear equation (F=33.52, adjusted R2=0.29) could be constructed: peakVO2=10.65(male) or 8.53(female)+4.26HRI+3.31SBPR-0.07age-0.13BMI+0(HFrEF) or 1.05 (HFmrEF) or 1.62(HFpEF). Conclusion: HRI and SBPR are positively correlated with peakVO2. In the absence of gas analysis, it is possible to apply HRI and SBPR during exercise to predict exercise tolerance in patients with CHF.

KRT15 overexpression predicts poor prognosis in colorectal cancer.

Keratin-15 (KRT15) is a type I keratin lacking a defined type II partner and plays a key role in maintaining cytoplasmic stability. Recently, studies have reported that KRT15 was correlated with tumor formation and progression. However, the clinical significance of KRT15 in colorectal cancer is unclear. In this study, we aimed to investigate the expression of KRT15 and its clinical significance in colorectal cancer. KRT15 expression was examined in 98 cases of colorectal cancer and matched adjacent normal tissues by quantificational real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively. Then, the clinical significance of KRT15 expression was evaluated in colorectal cancer. QRT-PCR results revealed that the mRNA levels of KRT15 in colorectal cancer tissues were significantly higher compared with those in normal tissues (p<0.0001). The rates of KRT15 high-expression in colorectal cancer and normal tissues were 57.1% and 8.9%, respectively, and the difference was statistically significant (p<0.0001). KRT15 high-expression correlated with differentiation, T stage, lymph node metastasis and clinical stage in colorectal cancer (p<0.05). Meanwhile, KRT15 overexpression predicted poor prognosis and could be used as an independent prognostic factor. These data indicate KRT15 is highly expressed in colorectal cancer and may serve as a prognostic biomarker.

[Clinical value of intact parathyroid hormone levels on the first day after total thyroidectomy on prediction for permanent hypoparathyroidism].

Objective: To examine the value serum calcium and intact parathyroid hormone (iPTH) levels measured on the first day after total thyroidectomy on prediction for permanent hypoparathyroidism. Methods: Totally 546 patients with thyroid cancer and benign thyroid lesions who underwent total thyroidectomy at Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University from February 2008 to December 2018 were analyzed retrospectively. There were 158 males and 388 females aging (50.9±13.2) years (range: 19.0 to 79.2 years). Serum calcium and iPTH levels were collected before surgery, on the first day and 6 months after surgery. Logistic regression was used to analyze the correlation between each data and the occurrence of permanent hypoparathyroidism after surgery.The area under the receiver operating characteristic curve was used to evaluate the predictive power of iPTH for postoperative occurrence of permanent hypoparathyroidism. Results: Among the 546 cases of total thyroidectomy, 22 cases of permanent hypoparathyroidism occurred, with an incidence of 4.0% (22/546). Multivariate analysis showed that iPTH levels on the first day after total thyroidectomy (OR=2.932, 95%CI: 1.129 to 7.616, P=0.027) and serum calcium levels (OR=2.584, 95%CI: 1.017 to 6.567, P=0.046) were independent prognosis factors for postoperative permanent hypoparathyroidism. When the threshold value of iPTH at 24 hours after total thyroidectomy was 5.51 ng/L, the AUC was 0.956 (95%CI: 0.936 to 0.972, P=0.000), sensitivity was 100%, specificity was 85.1%, positive predictive value was 22%, negative predictive value was 100%. When the threshold value of serum calcium at 24 hours after total thyroidectomy was 1.93 mmol/L, the AUC was 0.733 (95%CI: 0.694 to 0.770, P=0.000), sensitivity was 63.6%, specificity was 78.1%, positive predictive value of 10.8% and negative predictive value of 98.1%. Conclusions: Serum iPTH and calcium levels on the first day after total thyroidectomy were related to the occurrence of permanent hypoparathyroidism postoperatively. The predictive value of iPTH level is higher than that of serum calcium level.

Proteomic analysis reveals the mechanisms of Mycena dendrobii promoting transplantation survival and growth of tissue culture seedlings of Dendrobium officinale.

AIMS: Dendrobium officinale is an important traditional Chinese medicinal herb. Its seedlings generally show low survival and growth when transferred from in vitro tissue culture to a greenhouse or field environment. In this study, the effect of Mycena dendrobii on the survival and growth of D. officinale tissue culture seedlings and the mechanisms involved was explored. METHODS AND RESULTS: Mycena dendrobii were applied underneath the roots of D. officinale tissue culture seedlings. The seedling survival and growth were analysed. The root proteins induced by M. dendrobii were identified using two-dimensional (2-D) electrophoresis and matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF-MS). Mycena dendrobii treatment significantly enhanced survival and growth of D. officinale seedlings. Forty-one proteins induced by M. dendrobii were identified. Among them, 10 were involved in defence and stress response, two were involved in the formation of root or mycorrhizae, and three were related to the biosynthesis of bioactive constituents. CONCLUSIONS: These results suggest that enhancing stress tolerance and promoting new root formation induced by M. dendrobii may improve the survival and growth of D. officinale tissue culture seedlings. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a foundation for future use of M. dendrobii in the large-scale cultivation of Dendrobiums.

Expression profiling analysis of hypoxic pulmonary disease.

Exposure of humans to low levels of environmental oxygen results in alveolar hypoxia and normally causes chronic pulmonary hypertension and morphological alterations of precapillary pulmonary vessels. In this study, the microarray dataset GSE11341 was used to identify potential differentially expressed genes related with human lung microvascular endothelial cell hypoxia. In addition, gene ontology term enrichment analysis was performed to explore their underlying functions. In addition, we also investigated the small molecules by comparing with the Connectivity Map. We found that hypoxia samples of 3, 24, and 48 h relative to 0 h displayed 22, 21, and 29 differentially expressed genes, respectively. Among them, six genes (ADM, HMOX1, VEGFA, EGLN3, APOLD1, and ANGPTL4) were closely related to pulmonary microvascular endothelial cell hypoxia response. Three drugs (pindolol, sulfapyridine, and ciclopirox) were selected as candidates to treat hypoxia-related pulmonary diseases. In conclusion, our results provide some underlying drug targets for treatment of hypoxic pulmonary patients.

[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.

[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.

[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 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 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.

[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.

[A report of clinical characteristics of 2 Chinese pedigrees with haploinsufficiency of A20 and literature review].

Objective: To summarize the clinical characteristics of patients with haploinsufficiency of A20 (HA20). Methods: The clinical manifestations, laboratory examinations, treatment, outcome and genetic analysis of 4 cases with HA20 hospitalized in Peking Union Medical College Hospital were analysed.Further literature review was done after searching articles in PubMed and Wangfang databases with the key words "HA20" "A20 haploinsufficiency" "TNFAIP3" up to the date of September 2019. Results: The 4 patients were a father and a daughter, as well as a mother and a daughter. Their phenotypes were quite variable, but all of them have been suffering from recurrent oral ulcer since childhood. Elevation of C-reactive protein (13-33 mg/L) and erythrocyte sedimentation rate (21-60 mm/1h) were found in these 4 patients, and there was positive antinuclear antibody in proband 1.The father in pedigree 1 and the 2 patients in pedigrees 2 have been diagnosed with Behçet disease and the proband 1 with undifferentiated connective tissue disease. The 2 patients in pedigree 1 have developed Hashimoto's thyroiditis. After gene sequencing analysis, it was found that all the 4 patients have heterozygous nonsense mutations in TNFAIP3 gene, that is, c.811C>T, p.R271X in pedigree 1 and c.133C>T, p.R45X in pedigree 2.The diagnosis of HA20 was eventually established when sequencing results and their clinical manifestations were both compatible with this disease.A total of 21 articles were retrieved, all in English, with a total of 91 cases from 39 families (including the 4 cases reported in this paper). HA20 was reported more often in female (57, 64.8%). Most patients develop symptoms from childhood, but as many as 53.4% (47 cases) are not correctly diagnosed until adulthood. Oral ulcers, genital ulcers, periodic fever, gastrointestinal symptoms, rashes, and arthritis are the primary manifestations.Hashimoto's thyroiditis is the most common autoimmune diseases that HA20 patients coexist with. Laboratory tests were characterized by significantly elevated inflammatory markers and low to moderate titers of autoantibodies in some patients.Most HA20 patients were reported to have nonsense mutations or shift mutations of TNFAIP3 gene, which leads to truncation of A20 protein, and only a small number of patients have missense mutation. In terms of treatment, anti-TNF treatment and anti-interleukin 1 is believed to be an effective and the most optimal therapy. The treatment effect is variable and requires long term observations. Conclusions: The clinical phenotypes of HA20 are complex. For patients with both autoinflammatory and autoimmune characteristics, family history should be inquired in detail and gene sequencing should be performed if necessary.

Removal of a metallic foreign body embedded in the external nose via open rhinoplasty approach.

Most metallic foreign bodies are inert, but they can cause chronic inflammatory reactions and be a source of infection. Identification and removal of foreign bodies from wounds is often necessary. The present report describes two cases of a foreign body embedded in the external nose. Each case was successfully treated by an open rhinoplasty approach. This approach is an effective and safe method for removal of foreign bodies in the external nose. It provides a good surgical field and a better cosmetic outcome than a conventional incision.

Endoscopic transnasal reduction of an anterior table frontal sinus fracture: technical note.

Repair of an isolated anterior table frontal sinus fracture traditionally requires a coronal incision, which results in a large scar, alopecia and paresthesias, because of these problems, endoscopic approaches have been attempted. These approaches still involve small incisions at the forehead or behind the hairline so might be better described as endoscopy-assisted surgery. This report describes the reduction of an isolated anterior table frontal sinus fracture in a 14-year-old boy using an endoscopic procedure that involves a transnasal approach with no external incisions. Endoscopic instruments were used under 25 and 70 degrees endoscope guidance. A custom-made latex glove balloon was inserted into the frontal sinus, and then expanded and maintained for 20 days to support the reduced bony fragments. Postoperatively, the reduction was successful. The cosmetic deformity was repaired and there was no postoperative morbidity. This case indicates that endoscopic reduction may be a valuable treatment option for certain types of frontal sinus fractures.

[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.

[Spondyloenchondrodysplasia with immune dysregulation: a case report and literature review].

Objective: To analyze the clinical characteristics of spondyloenchondrodysplasia with immune dysregulation (SPENCDI). Methods: The clinical manifestations, laboratory examinations, treatment and genetic analysis of a patient diagnosed with SPENCDI who was admitted to the Department of Pediatrics in Peking Union Medical College Hospital in October 2016 were analyzed. Then literature review was done after searching articles in PubMed and several Chinese databases with the key words "spondyloenchondrodysplasia with immune dysregulation" up to the date of November 2017. Results: A 12-year-old girl was admitted to local hospital for complaint of "recurrent fever over one month" in October 2016. She was diagnosed with type Ⅱ autoimmune hepatitis for abnormal liver function, elevated immunoglobulin G, positive anti-liver-kidney microsomal antibody and medium to severe interface hepatitis verified by liver biopsy. Systemic lupus erythematosus was also suspected based on positive antinuclear antibody and anti-dsDNA antibody, decreased complements, reduced white blood cells and hemoglobin. Methylprednisolone and azathioprine were started based on the diagnosis. However, she experienced mycoplasma pneumoniae and suspected fungal infections during the treatment. Detailed history revealed the history of developmental retardation since birth, and cerebral palsy diagnosed when she was 2 years old. She also underwent surgery at the age of eight for eversion of her right foot. Based on the abnormal findings of immune system, skeleton and nervous system, certain primary immunodeficiency disease was speculated. Gene sequencing was performed, which revealed compound heterozygous mutations in ACP5 gene (NM_001111035.2) (c.798dupC, p. S267Lfs*20, paternal; c.716G>A, p. G239D, maternal). With X-ray of the vertebrae showed multiple platyspondyly, the diagnosis was corrected as SPENCDI and type Ⅱ autoimmune hepatitis. Then she was treated with prednisone (60 mg/d) and mycophenolate mofetil (1.5 g/d). All symptoms resolved on 3-month follow-up, with normalized activity indexes of autoimmune hepatitis and systemic lupus erythematosus. A total of 25 articles (1 Chinese, 24 English) were reviewed, with 74 SPENCDI patients reported. The most common manifestations were skeletal abnormalities (74/74, 100%), autoimmune diseases (47/74, 63.5%), dwarfism (45/74, 60.8%), and nervous system symptoms (25/74, 33.8%). A few patients with simple spondyloenchondrodysplasia were treated with growth hormone, and those who with autoimmune diseases were treated with immunosuppressants, all of whom were improved to certain extent. Conclusions: Vertebral and metaphyseal dysplasia, nervous system symptoms, and strong predisposition to autoimmune diseases are the hallmarks of SPENCDI. SPENCDI should be considered in dwarf with or without autoimmune diseases or nervous system symptoms.

[A multicenter study of reference intervals for 15 laboratory parameters in Chinese children].

Objective: To establish comprehensive laboratory reference intervals for Chinese children. Methods: This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex. Results: In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old. Conclusion: This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.