[A 10-year retrospective analysis of spectrums and treatment options of orthostatic intolerance and sitting intolerance in children].

OBJECTIVE: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options. METHODS: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed. RESULTS: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ2= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS. CONCLUSION: POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.

[Effects of estradiol on the day of human chorionic gonadotropin administration on adverse perinatal outcomes].

Objective: To investigate the association between estradiol on the day of human chorionic gonadotropin (HCG) administration and birth outcomes among singleton live births following fresh embryo transfers. Methods: Based on the clinical reproduction medicine management system of the First Affiliated Hospital of Nanjing Medical University, this retrospective cohort study collected data of fresh embryo transfer cycles during January 2013 and December 2016, including pregnant women's age, body mass index (BMI), type and cause of infertility, assisted reproductive therapy indicators (fertilization mode, ovulation stimulation protocol, estradiol levels on HCG administration day), adverse birth outcomes[small for gestational age (SGA), premature and low birth weight (LBW)], etc.. A total of 2 060 women with singleton pregnancy (2 061 fresh embryo transfer cycles) were enrolled. Multivariate logistic regression was used to analyze the association between estradiol on HCG administration day and singletons' adverse birth outcomes. Results: The age and BMI of the 2 060 pregnant women were (29.63±3.92) years old and (22.29±2.86) kg/m2. Incidences of SGA, premature and LBW were 9.8% (201/2 061), 6.9% (143/2 061) and 3.5% (73/2 061), respectively. After adjusting for confounders, the risk of LBW in 4 000-4 499 pg/ml group was significantly elevated when compared to estradiol<1 500 pg/ml group [OR (95%CI): 4.42 (1.13-17.24)]. A protective effect of premature was observed in estradiol≥4 500 pg/ml group [OR (95%CI): 0.50 (0.25-0.97)]. Conclusion: The high level of estradiol on HCG administration day might be a risk factor for LBW, but a protective factor for premature.

The role of ancillary features for diagnosing hepatocellular carcinoma on CT: based on the Liver Imaging Reporting and Data System version 2017 algorithm.

AIM: To investigate the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) version 2017 for diagnosing hepatocellular carcinoma (HCC), by using major features only and combined major and ancillary features on computed tomography (CT). MATERIALS AND METHODS: A total of 147 HCC, 35 non-HCC malignancy, and 37 benign lesions in 205 patients at high risk of HCC were evaluated retrospectively, and the diagnostic performance of LI-RADS for diagnosing HCC were compared between using major features only and adopting major and ancillary features in combination. RESULTS: When using LR-5 as a predictor for diagnosing HCC, the diagnostic specificity (90.3% versus 91.7%), positive predictive value (92.3% versus 93.3%), and accuracy (68% versus 68.8%) were increased based on major and ancillary features in combination than just using major features on CT. When using LR-4/5 as a predictor for diagnosing HCC, the diagnostic sensitivity (78.9% versus 85.7%), negative predictive value (64.4% versus 72%), and accuracy (78.5% versus 82.2%) were increased while preserving a high specificity (77.8% versus 75%), according to major and ancillary features in combination rather than just using major features on CT. The LI-RADS categories of 8.7% (19/219) lesions were adjusted by adding the ancillary features on CT. CONCLUSION: Adding the ancillary features visible on CT can improve the diagnostic performance of the LI-RADS v2017 algorithm for diagnosing HCC, especially for LR-3 lesions.

[Progress in diagnosis and management of syncope in children].

Syncope is a common emergency of children and adolescents, which has serious influence on the quality of life. Neurally-mediated syncope, including postural tachycardia syndrome, vasovagal syncope, orthostatic hypotension and orthostatic hypertension, is the main cause of syncope in children and adolescents. The main manifestations of neurally-mediated syncope are diverse, such as dizziness, headache, chest tightness, chest pain, pale complexion, fatigue, pre-syncope and syncope. Although the clinical manifestations are similar, each subtype of syncope has its hemodynamic feature and optimal treatment option. The diagnosis rate of syncope in children has been greatly improved on account of the development of the diagnostic procedures and methods. In recent years, with the promotion of head-up tilt test and drug-provocated head-up tilt test, the hemodynamic classification of neurally-mediated syncope gets continually refined. In recent years, with the effort of clinicians, an appropriate diagnostic protocol for children with syncope has been established. The initial evaluation consists of history taking, physical examination, standing test and standard electrocardiography. After the initial evaluation, some patients could be diagnosed definitely, such as postural tachycardia syndrome, orthostatic hypotension, and situational syncope. Those with a specific entity causing syncope need selective clinical and laboratory investigations. Patients for whom the cause of syncope remained undetermined should undergo head-up tilt test. The precise pathogenesis of neurally-mediated syncope is not entirely clear. In recent years, studies have shown that neurally-mediated syncope may be related to several factors, including hypovolemia, high catecholamine status, abnormal local vascular tension, decreased skeletal muscle pump activity and abnormal neurohumoral factors. Currently based on the possible pathogenesis, the individualized treatment of neurally-mediated syncope has also been studied in-depth. Generally, the management of neurally-mediated syncope includes non-pharmacological and pharmacological interventions. Patient education is the fundamental part above all. In addition to exercise training, the first-line treatments mainly include oral rehydration salts, beta adrenoreceptor blockers, and alpha adrenoreceptor agonists. By analyzing the patient's physiological indexes and biomarkers before treatment, the efficacy of medication could be well predicted. The individualized treatment will become the main direction in the future researches.

[Co-morbidity of vasovagal syncope and postural tachycardia syndrome with allergic diseases in children].

OBJECTIVE: To explore the clinical characteristics of the co-morbidity of vasovagal syncope (VVS) and postural tachycardia syndrome (POTS) with allergic diseases in children. METHODS: A re-trospective analysis was launched to summarize the clinical data of children with VVS and POTS. They were divided into allergic group and non-allergic group according to the history of allergic diseases. The participants' clinical characteristics were compared between allergic group and non-allergic group using independent sample t test or rank sum test; composition comparisons were completed by Chi-square test. Bi-variate correlation analysis was used to explore the association between eosinophil percentage/count and symptom scores/frequency of syncope episodes. A P value <0.05 was defined as statistically significant. RESULTS: Sixty-seven children complaining of orthostatic intolerance (43 patients diagnosed as VVS and 24 cases diagnosed as POTS) were enrolled. Totally 21 cases (31%) had allergic diseases, including allergic rhinitis, atopic eczema, asthma, as well as food allergy. And allergic rhinitis is the most common co-morbidity. There were no significant differences between the two groups in age, gender ratio, height, body weight and basement blood pressure. Compared with the non-allergic group, the allergic group showed later onset age (year) (11±2 vs. 9±3, P<0.05) of orthostatic intolerance and shorter course of the diseases (month) [8.0 (0.1, 0.1) vs. 24.0 (0.1, 144.0), P<0.05]. The frequency of syncope episodes in the allergic group among VVS children (times per month) [2.50 (0.08, 30.00) vs. 0.25 (0.03, 5.00), P<0.05] was much higher than that in the non-allergic group. Additionally, the eosinophil percentage (%) [3.50 (0.70, 0.59) vs. 1.65 (0.30, 6.20), P<0.001] and eosinophil count (×109) [0.18 (0.05, 0.71) vs. 0.10 (0.02, 0.38), P<0.001] were increased in the allergic group. However, there were no remarkable differences in the results of head-up tilt test in children with VVS or in the maximum change of heart rate during standing test in children with POTS were involved. CONCLUSION: Allergic diseases are common co-morbidities in children with both VVS and POTS. Allergic rhinitis is the most common co-morbidity. Children with co-morbidity of VVS/POTS and allergic diseases had a later onset of symptoms of orthostatic intolerance, and were more likely to be hospitalized for intensive attacks of symptoms during a short period when compared with those without allergic diseases. Children diagnosed as VVS combined with allergic diseases had more frequent episodes of syncope.

[Relationship between blood routine test parameters and syncopal recurrence of vasovagal syncope in children].

Objective: To explore the relationship between venous blood routine test parameters and syncopal recurrence of children with vasovagal syncope (VVS). Method: Sixty-three children (male 32, female 31) diagnosed as VVS in Department of Pediatrics, Peking University First Hospital from November 2010 to October 2015 were included in a case observational study.Their mean age was (11.2±2.7) years and basic treatment such as predisposing causes avoiding, standing training, autonomic nervous function exercise and oral rehydration salts were advised to them.The clinical data were obtained by out-patient visit and over telephone from December 2015 to January 2016, with a median follow-up period of 10 (4, 26) months. The effects of baseline venous blood routine test parameters, gender, age, and body mass index (BMI) on syncopal recurrence were studied via univariate and multivariate Cox regression analysis.Kaplan-Meier curve was used to evaluate the long-term prognosis. Result: Among the 63 VVS children in this study, 31 cases were diagnosed as VVS vasodepressor type, 4 cases as VVS cardioinhibitory type and 28 cases as VVS mixed type, 16 cases (25%) had experienced recurrence of syncope while 47 cases (75%) had not.The result of univariate analysis of Cox regression showed that baseline platelet count (PLT) (HR=1.012, 95%CI: 1.003-1.022) had a marked impact on the survival rate.And the result of multivariate analysis of Cox regression showed that baseline hemoglobin concentration (HGB) (HR=1.055, 95%CI: 1.007-1.105), mean corpuscular hemoglobin (MCH) (HR=0.612, 95%CI: 0.423-0.884) and PLT(HR=1.015, 95%CI: 1.006-1.024) had significant effects on survival rate of VVS children.In this study, the one-year, two-year, and three-year survival rate were 83% (52/63), 79% (50/63) and 75% (47/63), respectively. Conclusion: The baseline venous blood routine test parameters HGB, MCH and PLT might be the influencing factors of the syncopal recurrence of VVS children.

[DNA damage associated genetic variants contribute to lung cancer susceptibility in a Han Chinese population].

OBJECTIVE: To explore the association between DNA damage-related genetic variants and lung cancer susceptibility in a Han Chinese population. METHODS: This case-control study enrolled patients from the Cancer Hospital of Jiangsu Province and Jiangsu Province Hospital from 2003 to 2009. Controls were randomly selected from individuals who visited the same hospital or a community-based health examination program during the same time period. A 5 ml venous blood sample was obtained from each participant and epidemiological information was collected on a standard questionnaire. Illumina Infinium(®) BeadChip was used for genotyping of 35 DNA damage-related single nucleotide variations (SNVs), which were identified in our previous study. Multivariate and binary logistic regressions were used to calculate the OR and 95%CI for lung cancer risk. HaploReg V4.1 and Regulome DB were used to understand functional annotation on important SNV. RESULTS: The distributions of age (61.06±10.15) vs. (61.32±11.07) years; t=-0.72, P=0.473) and sex (χ(2)=1.81, P=0.179) were similar between cases and controls. However, the case group had a higher frequency of smokers (61.08% vs. 48.54%; χ(2)=50.04, P<0.001) and heavy smokers (42.28% vs. 24.07%; χ(2)=122.32, P<0.001). Among the 34 SNVs that passed quality control, two SNVs were significantly associated with lung cancer risk after adjustments for age, sex and cumulative smoking dose: rs9267576 C>A (CA genotype/CC genotype, OR=1.56, 95% CI: 1.01-2.40) and rs3130683 A>G (AG genotype/AA genotype, OR=1.87, 95%CI: 1.13-3.09). After step-wise logistic regression analysis, only the rs3130683 SNV was retained in the model, indicating that the association between rs9267576 and lung cancer may be due to the effect of rs3130683. Functional annotation indicated that rs3130683 was located in the promoter and enhancer regions, and was an expression quantitative trait loci of HLA. The Cancer Genome Atlas indicated that expression of HLA-C, DQB1, DRB1 and DRB5 in lung cancer tissue was significantly lower than in paired normal tumor-adjacent tissue, with down-regulation of the four respective genes in 81.3%, 88.8%, 90.7% and 90.7% of lung cancer tissues (P-values were 6.68×10(-15), 2.21×10(-13), 2.20×10(-16), 2.58×10(-13), respectively). CONCLUSIONS: The SNV rs3130683 (A>G) was associated with the risk of lung cancer in a Han Chinese population. This SNV may affect the risk of lung cancer by regulating HLA expression.

[Hydrogen sulfide in cartilage and its inhibitory effect on matrix metalloproteinase 13 expression in chondrocytes induced by interlukin-1ß].

OBJECTIVE: To investigate whether endogenous hydrogen sulfide (H2S) was involved in the pathogenesis of osteoarthritis (OA) and its underlying mechanism, to detect H2S and its synthases expression in knee cartilage in patients diagnosed with different severity of OA, and to explore the transcription and expression of gene MMP-13 in chondrocytes treated with IL-1ß or H2S. METHODS: Synovial fluids of the in-patients with different severity of OA hospitalized in Peking University First Hospital were collected for measurement of H2S content using methylene blue assay. Articular cartilages of the patients who underwent knee arthroplasty were collected for the cell culture of relatively normal chondrocytes. The chondrocytes were cultured to the P3 generation and H2S molecular probes were used for detection of endogenous H2S generation in the chondrocytes. Immunocytochemistry was used to detect the localization of H2S synthases including cystathionine ß-synthase (CBS), cystathionine-γ-lyase (CSE), and mercaptopyruvate sulfurtransferase (MPST) in OA chondrocytes. Western blot was used to quantify the protein expressions of CSE, MPST, and CBS in cartilage tissues of the patients who were diagnosed with OA and underwent knee arthroplasty. The relatively normal human chondrocytes were cultured to passage 3 and then divided into 4 groups for different treatments: (1)the normal control group, no reagent was added; (2)the IL-1ß group, 5 µg/L of IL-1ß was added; (3)the IL-1ß+H2S group, 200 µmol/L of NaHS was added 30 min before adding 5 µg/L of IL-1ß;(4)the H2S group, 200 µmol/L of NaHS was added. The transcription and expression of gene MMP-13 in chondrocytes of each group were determined with Real-time PCR and Western blot, respectively. And the total NF-κB p65 and phosphorylated NF-κB p65 in chondrocytes were detected with Western blot. RESULTS: The content of H2S in the synovial fluid of degenerative knee was (14.3±3.3) µmol/L. Expressions of endogenous H2S and its synthases including CBS, CSE and MPST were present in the cytoplasm of chondrocytes.CSE protein expression in Grade 3 (defined by outerbridge grading) cartilage tissues was significantly increased as compared with that of Grade 1 cartilage tissues (1.67±0.09 vs. 1.26±0.11, P< 0.05). However, no significant difference of CBS or MPST expression among the different groups was observed. The expression of MMP-13 protein in the IL-1ßgroup was significantly higher than that in the normal chondrocytes (1.87±0.67 vs. 0.22±0.10, P<0.05), and that in the IL-1ß+H2S group was significantly decreased than that in the IL-1ß group (0.55±0.11 vs. 1.87±0.67, P< 0.05), and that in the H2S group had no significant difference compared with that in the normal control group. The transcription of MMP-13 protein in the IL-1ß group was significantly higher than that in the normal chondrocytes (31.40±0.31 vs. 1.00±0.00, P<0.05), and that in the IL-1ß+H2S group was significantly decreased than that in the IL-1ß group (24.41±1.28 vs. 31.40±0.31, P<0.05), and that in the H2S group had no significant difference compared with that in the normal control group. The total NF-κB p65 in the IL-1ß group was significantly higher than that in the normal chondrocytes (2.13±0.08 vs. 0.73±0.08, P< 0.05), and that in the IL-1ß+H2S group was significantly decreased than that in the IL-1ß group (1.24±0.13 vs. 2.13±0.08, P<0.05), and that in the H2S group had no significant difference compared with that in the normal control group. The phosphorylated NF-κB p65 in IL-1ß group was significantly higher than that in the normal chondrocytes (1.30±0.13 vs. 0.19±0.04, P<0.05), and that in IL-1ß+H2S group was significantly decreased than that in the IL-1ß group (0.92±0.26 vs. 1.30±0.13, P<0.05), and that in the H2S group had no significant difference compared with that in the normal control group. CONCLUSION: H2S affected the cartilage degeneration by partly inhibiting the degradation of extracellular matrix.