Objective To study on the application of biological variation total allowable error in quality management of serum lipid detection .Methods The σ score ,quality goal index (QGI) ,priority improvement measures and performance evaluation of lipid accuracy criteria were evaluated ,including cholesterol (CHOL) ,triglyceride (TG) ,high density lipoprotein (HDL‐C) ,low density lipoprotein (LDL‐C) ,which included in the standard of accuracy of the Ministry of Health in 2015 .The reason for unsatisfactory re‐sults of cholesterol (CHOL) test were analyzed .Results Based on the three levels of quality specifications derived in biological var‐iation ,when the total allowable error was located at an appropriate level ,the σ score of TG ,HDL‐C ,LDL‐C reached 6 ,it was not re‐quired for improvement .While the score of CHOL performance analysis was poor ,accuracy was required to give priority to impro‐ving .When the total allowable error reached the best level ,only the σ score of TG achieved “good” in the four items ,improvement of precision was needed .When the total allowable error was located at the lowest level ,the σ score of TG ,HDL‐C ,LDL‐C was grea‐ter than 6 ,the score of performance analysis reached the “excellent” .The σ score of CHOL (2 .9) had been closen to 3σ ,accuracy was required to be corrected .Conclusion The biological variation derived total allowable error is easy to meet the requirements of the quality management in serum lipid determination by current technologies and methods .The theory of 6σ quality can reflect the performance of detection indexes ,and improve the quality of analysis effectively .

[ ABSTRACT] AIM: To investigate the underlying genetic changes of a Chinese patient with infantile malignant osteopetrosis ( IMO) .IMO is a monogenic disease, mostly caused by mutations of TCIRG1 and CLCN7 genes.The former is believed a homozygous gene and only cause the disease in homozygous or compound heterozygous status.However, it has been reported that heterozygous mutations also cause the disease in 6 non-Chinese cases.METHODS:Genomic DNA was extracted from peripheral blood of the patient and his parents.All exons and splice sites of TCIRG1 and CLCN7 genes were amplified by PCR followed by Sanger sequencing.Mutation detection in the 2 genes was also investigated in the parents. Haplotypes were constructed by variations obtained in mutation detection and microsatillites flanking TCIRG1 gene in the family by Cyrillic.Chromosomal microarray analysis ( CMA) was performed to detect copy number variations ( CNV) of the patient and his mother.RESULTS:A novel mutation c.449_452delAGAG ( p.Gln149Glnfs16) was detected in the pa-tient.This mutation truncated 666 amino acids at the C terminal of the V-ATPase 116 kD isoform a3 protein.It wiped out the entire ATPase V0 complex and was predicted to result in total loss of protein function.This mutation was also detected in the patient’ s father.No pathogenic mutation was detected in CLCN7 gene.CMA did not reveal any CNV involving TCIRG1 or CLCN7 gene.CONCLUSION:We reported a novel heterozygous mutation of TCIRG1 gene causing IMO.This represents the first IMO case in China caused by heterozygous TCIRG1 gene mutation.

Objective To sum up the clinical manifestations and laboratory features for the diagnosis of pediatric tuberculous pleurisy,and to improve the recognition of this disease in early stage.Methods A retrospective study of 113 children diagnosed as tuberculous pleurisy from August 2006 to September 2014 in the Second Department of Respiratory Medicine,Beijing Children's Hospital Affiliated to Capital Medical University was conducted.Meanwhile,another 113 cases of children with mycoplasma pneumoniae pneumonia complicated with pleurisy were selected as control group.The general information,clinical symptoms,pleural effusion and imaging features between 2 groups were analyzed and compared by using SPSS 16.0 statistical software.Results The proportion of patients with cough in tuberculous pleurisy group and control group was 47.79％ (54/113 cases) and 99.12％ (112/113 cases) (x2 =76.33,P ＜ 0.01) respectively,and the proportion with severe cough was 3.70％ (2/54 cases) and 97.32％ (109/112 cases) (x2 =144.10,P ＜0.01),while the disease duration was 15.00 (10.00,30.00) days and 10.00 (8.00,14.50) days (W =8 668.00,P ＜ 0.01),respectively,and all the differences between 2 groups were significant.The proportion of patients with low fever,moderate fever,high fever and hyper fever was 8.65％ (9/104 cases),47.12％ (49/104 cases),44.23 ％ (46/104 cases) and 0,respectively in tuberculous pleurisy group,while the proportion was 0.90％ (1/111 cases),18.92％ (21/111 cases),79.28％ (88/111 cases) and0.90％ (1/111 cases) respectively in control group,and the difference between 2 groups was significant(W =9 064.00,P ＜ 0.01).The unilateral effusion ratio in tuberculous pleurisy group and the control group was 94.69％ (107/113 cases) and 71.68％ (81/113 cases),respectively (x2 =21.39,P ＜ 0.01).The monocyte ratio was higher in tuberculous pleurisy group [0.89 (0.76,0.93)] than that in the controlgroup [0.60 (0.30,0.78)] (W =888.50,P ＜ 0.01) and the level of protein in 2 groups was [51.00 (47.35,54.20) g/L] and [42.10 (37.85,46.15) g/L],respectively (W =842.50,P ＜ 0.01).The level of lactate dehydrogenase (LDH) in tuberculous pleurisy group[553.50 (358.00,749.25) U/L] was lower than that in the control group[1 189.10 (670.95,1 820.00) U/L] (W =2 186.00,P ＜ 0.01),and the differences were significant between 2 groups.In addition to pleural effusion,the high density was the main feature of imaging examination in 2 groups.The proportion of patients with atelectasis was 77.88％ (88/113 cases) and 4.42％ (5/113 cases) (x2 =125.90,P ＜ 0.01),while the proportion of patients with consolidation was 4.42％ (5/113 cases) and 72.57 ％ (82/113 cases),respectively (x2=110.80,P ＜ 0.01).All the differences between 2 groups were significant.The sputum culture-positive rate of mycobacterium tuberculosis was only 1.77％ (2/113 cases) and the other pathogen examinations were negative in tuberculous pleurisy group.Conclusions For patients with unilateral pleural effusion,when the onset only has fever (moderate-high fever),and respiratory symptoms are not clear or symptoms are not proportional to radiographic severity,or when high monocytes proportion (＞ 0.70) in pleural effusion and radiographic evidence of compression atelectasis are observed,tuberculous pleurisy should be considered and further questioning of the predisposing factors,purified protein derivative test should be taken so as to diagnose the tuberculous pleurisy at early stage.

Tissue-resident lymphocytes constitute the first line of defense against diseases and are important for maintaining body homeostasis.During inflammation,virus infection and carcinogenesis,tissue-resident lymphocytes will immediately response and exert effector functions.However,these processes are regulated by multiple factors in the local microenvironment such as ATP,which accumulates in damaged tissues,and regulates disease progression via activating P2X purinergic receptors on immune cells.Among the P2X purinergic receptor family,P2RX7 is well studied and participates in broad immune responses.P2RX7 is expressed on nearly all immune cells,with particularly high levels of expression on tissue-resident lymphocytes.Multiple tumor models have con-firmed that targeting R2RX7 is a very promising therapeutic strategy in the treatment of cancer but its relationship with tissue-resident lymphocytes is unclear.In this review,we mainly discuss the effects of P2RX7 on tissue-resident lymphocyte populations and how it further affects the development of diseases such as inflammation,virus infection or cancer development.

Objective:To explore the early clinical clues for diagnosis of chronic granulomatous disease (CGD).Methods:One hundred and thirty-nine children with CGD seen in Beijing Children′s Hospital from January 2007 to October 2020 were included in this study. The clinical features including age of onset, first presentations, reason for being hospitalized, etiology, imaging features, clues for early diagnosis of all patients were evaluated retrospectively. According to the time of diagnosis, the patients were divided into two groups, cases diagnosed before 2015 and after 2015 and 2015. The time of diagnosis, the length of stay and the hospital charges were compared between the two groups. T test and χ 2 test were used for statistical analyses. Results:One hundred and nineteen of the cases were males and 20 were females. The age of onset was 4 months (8 d to 14 years), and 103 cases (74.1%) had onset before 1 year of age. The age at diagnosis was 1.8 years (21 d to 14.7 years), and the time of diagnosis delay was 1 year (7 d to 13.7 years). One hundred and thirty-five cases (97.1%) had pulmonary infection as the main reason for hospitalization, of whom 76 cases (56.3%) had positive pulmonary etiology. One hundred and thirty-six patients (97.8%) were referred cases, of whom 5 were suspected of CGD before referral, and the misdiagnosis rate was as high as 96.3% (131/136). Eight early clues for diagnosis were found, the frequency from high to low, large bacillus Callmette-Guer scar in 99 cases (70.5%), left axillary lymphadenopathy or calcification in 73 cases (52.5%), skin or other lymph node infections in 58 cases (41.7%), skin scars in 50 cases (36.0%), multiple lung nodules in 42 cases (30.2%), perianal abscess in 35 cases (25.2%), pulmonary Aspergillus infection in 26 cases (18.7%) and pulmonary Burkholderia infection in 15 cases (10.8%). A total of 120 cases of CGD were diagnosed by respiratory burst test during hospitalization, including 55 cases diagnosed before 2015 and 65 cases diagnosed after 2015. After using these 8 early diagnosis clues, the cases diagnosed after 2015 had shorter time of diagnosis and the length of stay and lower hospitalization charge than cases diagnosed before 2014, and the difference was statistically significant ((25±7) vs. (10±5) d, (29±7) vs. (18±6) d, (3.7×10 4±1.2×10 4) vs. (3.2×10 4±1.2×10 4) Yuan, t=13.763, 9.262, 2.381, all P<0.05). Conclusions:Patients with CGD are younger at onset and the diagnosis is delayed. Pulmonary infections are the most common. Large BCG scar, left axillary lymphadenopathy or calcification, skin or other lymph node infections, skin scars, multiple lung nodules, perianal abscesses, pulmonary Aspergillus infection and Burkholderia infection can help early diagnosis of CGD.

Objective To summarize the brain protection application experiences of combined internal and external blood shunt technologies for the in-situ three-fenestration revascularization of aortic arch.Methods From Feb 2017 to Jun 2018,8 patients with aortic arch leisons were treated by the in-situ three-fenestration techniques,including 3 aortic dissection,2 aortic aneurysm,3 postoperative TEVAR patients.We adopt the method of internal and external blood shunt technologies for brain protection using the vascular sheath for fenestration combined with carotid shunt tube skills,and using TCD to monitor the blood flow of brain.Results All operations completed successfully,and TCD showed no significant cerebral ischemia when aortic stent was used to cover the three branches of the aorta.The mean time of brain protection was (17.62 ± 6.87) minutes.One patient developed transient cerebral ischemia after surgery,and another one developed cerebral infarction.Conclusions The brain protection strategy of internal bypass combined with external converter technology maintain the brain blood flow,while is simple and feasible,it cannot completely avoid neurological complications.

Objective To verify the mental health status and methods to regulate emotion as well as identify the associated factors among Northwest University students during the lockdown period of the COVID-19 outbreak in Xi'an.Methods A questionnaire survey using the random sampling was conducted among the college students in Xi'an,using Self-Control Scale(SCS),Perceived Social Support Scale(PSSS),the Depression-Anxiety-Stress Scale Lite(DASS-21),and Self-Rating Scale of Sleep(SRSS).Results A total of 512 valid questionnaires for college students were collected.The statistical results showed that during the lockdown period after the COVID-19 epidemic outbreak in Xi'an,there were gender and discipline differences in self-control and understanding of social support among college students.That is,compared with boys,girls were more likely to receive social support(P=0.031),friend support(P=0.008),and other support(P=0.029).Compared to liberal arts majors,college students majoring in science and engineering were more likely to engage in self-control,especially in healthy habits(P=0.001),moderate entertainment(P=0.002),and impulse control(P=0.001).However,there was no significant difference in the influence of students'age or whether they came from rural or urban areas on their self-control and understanding of social support abilities.The statistical results also found that the age of college students was significantly correlated with their level of stress and sleep status.Their self-control ability and ability to comprehend social support also had correlation with their mental health status and sleep status during the lockdown period of the epidemic.Conclusion College students were prone to have negative emotions and sleep disorders during the lockdown period of sudden epidemic,which were more common in senior grades,male college students,and liberal arts majors.Active self-control and seeking social support can effectively moderate negative emotions and sleep disturbances.

Objective To assess the diagnostic value of sweat conductivity testing in Chinese children with cystic fibrosis (CF). Methods This is a retrospective study. Sweat conductivity tests were conducted in 45 CF children (CF group) and 200 non‐CF children (non‐CF group) diagnosed with other chronic pulmonary diseases at the No. 2 Department of Respiratory Medicine, Beijing Children′s Hospital from May 2014 to June 2018. Pearson′s chi‐square test was used to assess the differences between CF and non‐CF groups. A receiver operating characteristic curve was constructed to calculate the best cut‐off value to diagnose or rule out CF. The pulmonary function parameters (forced expiratory volume in the first second, forced vital capacity,forced expiratory flows at 75% of exhaled vital capacity) of CF children over 6 years old were analyzed. The relationship between sweat conductivity and pulmonary function was compared between the two groups (80‐120mmol/L vs.>120mmol/L). Results The age of CF group was 9 (7, 12) years old, 19 males (42%) and 26 females(58%); the age of non‐CF group was 8 (5,11) years old, 106 males (53%) and 94 females(47%). The results of sweat conductivity test showed that sweat conductivity in CF group 108(99, 122) mmol/L was significantly higher than that in non‐CF group 43(36, 52) mmol/L (χ2=207, P<0.01). A cut‐off value of 80 mmol/L for CF diagnosis showed a sensitivity of 93.3% and a specificity of 98.5%. The receiver operating characteristic curve analysis suggested the best conductivity cut‐off value for the diagnosis of CF was at 83.5 mmol/L,with a sensitivity of 93.3% and a specificity of 100%,and an area under the curve of 0.993 (95% confidence interval 0.985-1.000). The best conductivity cut‐off value to rule out CF diagnosis was at 63.5 mmol/L,with a sensitivity of 97.8% and a specificity of 90.5%. There was no correlation between the level of sweat conductivity and the extent of pulmonary function decline. Conclusions Sweat conductivity testing can be used for the screening of CF in Chinese children. A diagnosis of CF should be considered if the value is greater than 80 mmol/L.

Objective:To analyze the clinical features of cystic fibrosis (CF) associated allergic bronchopulmonary aspergillosis (ABPA) in children.Methods:A retrospective study was performed in 22 children who were diagnosed with CF associated ABPA in Beijing Children′s Hospital affiliated to Capital Medical University from March 2010 to March 2020. The clinical features, imaging characteristics, laboratory results and the prognosis were reviewed.Results:A total of 22 cases met the diagnostic criterion, including 12 males and 10 females. The age of diagnosis was (10.4±2.8) years and the age of onset was (5.5±4.4) years. Clinical manifestations included cough and expectoration (22 cases), recurrent wheezing (15 cases), hemoptysis (7 cases), failure to thrive (12 cases), pancreatitis (10 cases), hepatomegaly (7 cases), splenomegaly (4 cases) and steatorrhea (4 cases). CT scans of all the patients showed pulmonary infiltrates and central bronchiectasis, combined with mucoid impaction in 17 cases and high density mucus plug in 12 cases. Eosinophilia was found in 18 patients. Total IgE and serum levels of A. fumigatus-specific IgE were elevated in all 22 patients. Positive culture of sputum or bronchoalvedar lauage fluid for fungus were in 15 cases, with single Aspergillus infection in 8 cases and mixed Aspergillus infection in 3 cases. The predominant bacteria found in the airways were Pseudomonas aeruginosa (17 cases), followed by staphylococcas. aureus (6 cases) and stenotrophomonas. maltophilia (5 cases). Pulmonary function revealed obstructive ventilation dysfunction in 4 cases, mixed dysfunction in 11 cases, and small airway dysfunction in 4 cases. Regarding the treatment, 3 were treated only with systemic corticosteroid, while the remaining 19 cases also received antifungal agents.The follow up continued for 1-7 years, and 6 maintained remission, 10 had recurrent episodes, 1 died, and 5 lost to follow up. Conclusions:CF associated ABPA is extremely rare in China. The overlapping clinical, radiographic, and immunologic features of these two diseases make the diagnosis challenging. Systemic corticosteroids are considered the first-line therapy for these patients, and adjuvant antifungal agents may be helpful. Recurrence rate in our center is high.

Objective To understand the frequency distribution of CYP2C9 and VKORC1 gene single nucleotide polymor-phisms in Yunnan Han population.Methods CYP2C9(430C> T,1075A>C and 1080C> G)locus and VKORC1(-1639G> A and 1173C> T)locus gene polymorphisms in 202 samples were detected by adopting electrochemical gene sensor method,and the allele frequencies and genotype frequencies were performed the statistics and the gene polymorphism in relevant populations was an-alyzed.Results Among 202 samples,202 cases(100.0%)were genotype C/C at CYP2C9 * 2 locus,C allele frequency was 100.0%;185 cases(91.6%)were genotype A/A at CYP2C9*3 locus,15 cases(7.4%)were A/C genotype,2 cases(1.0%)were C/C genotype,A allele frequency was 95.3%,C allele frequency was 4.7%;CYP2C9*5 locus genotype C/C was in 202 cases (100.0%),C allele frequency was 100%;VKORC1 -1639G > A locus genotype A/A was in 145 cases(71.8%),57 cases (28.2%)were G/A genotype,A allele frequency was 85.9%,G was 14.1%;1173C> T locus genotype T/T was in 145 cases (71.8%),C/T gene type in 57 cases(28.2%),T allele frequency was 85.9%,and C was 14.1%.Conclusion The distribution of CYP2C9 gene in Yunnan Han population is similar to that in other regions of our country.The VKORC1 gene is different from the foreign population,Chinese Han nationality and partial minority nationalities.