Electrophysiological evidence for the characteristics of implicit self-schema and other-schema in patients with major depressive disorder: An event-related potential study.

Background: The significance of implicit self-schema and other-schema in major depressive disorder (MDD) is highlighted by both cognitive theory and attachment theory. The purpose of the current study was to investigate the behavioral and event-related potential (ERP) characteristics of implicit schemas in MDD patients. Methods: The current study recruited 40 patients with MDD and 33 healthy controls (HCs). The participants were screened for mental disorders using the Mini-International Neuropsychiatric Interview. Hamilton Depression Rating Scale-17 and Hamilton Anxiety Rating Scale-14 were employed to assess the clinical symptoms. Extrinsic Affective Simon Task (EAST) was conducted to measure the characteristics of implicit schemas. Meanwhile, reaction time and electroencephalogram data were recorded. Results: Behavioral indexes showed that HCs responded faster to positive self and positive others than negative self (t = -3.304, p = 0.002, Cohen's d = 0.575) and negative others (t = -3.155, p = 0.003, Cohen's d = 0.549), respectively. However, MDD did not show this pattern (p > 0.05). The difference in other-EAST effect between HCs and MDD was significant (t = 2.937, p = 0.004, Cohen's d = 0.691). The ERP indicators of self-schema showed that under the condition of positive self, the mean amplitude of LPP in MDD was significantly smaller than that in HCs (t = -2.180, p = 0.034, Cohen's d = 0.902). The ERP indexes of other-schema showed that HCs had a larger absolute value of N200 peak amplitude for negative others (t = 2.950, p = 0.005, Cohen's d = 0.584) and a larger P300 peak amplitude for positive others (t = 2.185, p = 0.033, Cohen's d = 0.433). The above patterns were not shown in MDD (p > 0.05). The comparison between groups found that under the condition of negative others, the absolute value of N200 peak amplitude in HCs was larger than that in MDD (t = 2.833, p = 0.006, Cohen's d = 1.404); under the condition of positive others, the P300 peak amplitude (t = -2.906, p = 0.005, Cohen's d = 1.602) and LPP amplitude (t = -2.367, p = 0.022, Cohen's d = 1.100) in MDD were smaller than that in HCs. Conclusion: Patients with MDD lack positive self-schema and positive other-schema. Implicit other-schema might be related to abnormalities in both the early automatic processing stage and the late elaborate processing stage, while the implicit self-schema might be related only to the abnormality in the late elaborate processing stage.

Effects of the salbutamol bronchodilator response on measurements of fractional exhaled nitric oxide in children with asthma: a prospective, observational study.

Background: Salbutamol bronchodilator response (BDR) test and fractional exhaled nitric oxide (FeNO) have been recommended for the diagnosis of asthma in children, but FeNO levels is affected by many factors. Nonetheless, data of the effect on the FeNO values throughout the bronchodilator test and the differences in FeNO values between BDR positive (BDR+) and negative (BDR-) children with asthma are still limited. We aimed to evaluate the effect of the BDR test on FeNO and the differences in FeNO levels between BDR+ and BDR- children with asthma. Methods: This was a prospective, observational study performed over a 5-month period (December 2018 to April 2019) and involved 57 children with asthma. The FeNO levels at pre-spirometry, post-spirometry, and post-salbutamol BDR testing were estimated. Finally, the children were divided into two groups i.e., BDR+ and BDR-, and differences in the FeNO levels were compared between the two groups. Results: The spirometry results were normal in 2 patients (3.5%). There were 53 (93%) patients with obstructive lung disease, including 40 (70.2%), 11 (19.3%), and 2 (3.5%) patients with mild, moderate, and severe obstruction, respectively. The remaining two patients had mixed lesions (3.5%), none of which were restrictive. The baseline median FeNO levels were significantly higher in the BDR+ group than in the BDR- group [33.00 (23.78, 46.73) vs. 23.00 (9.80, 37.80), (P=0.048)]. Following spirometry, there was a statistically significant decrease in median FeNO levels from baseline to post-spirometry (P=0.002). However, there was no significant difference between the median FeNO levels at baseline and following the BDR test (P=0.976). The impact of spirometry on FeNO was not statistically different in BDR+ versus BDR- children (Z=-0.186, P=0.853); however, the impact of bronchodilators on FeNO exhibited a statistically significant difference between the two groups (Z=3.160, P=0.002). Conclusions: This study revealed dynamic changes in the FeNO levels during the BDR test. The use of a bronchodilator results in a statistically significant difference in FeNO levels between BDR+ and BDR- children with asthma. Moreover, spirometry leads to a marked decrease in the FeNO levels. Our results will allow clinicians to better interpret FeNO, BDR and pulmonary function outcomes and better develop clinical protocols.

Influence of the timing of bronchoscopic alveolar lavage on children with adenovirus pneumonia: a comparative study.

BACKGROUND: Adenovirus pneumonia is prone to severe clinical and imaging manifestations in children. Bronchoscopic alveolar lavage (BAL) is an important adjunctive therapy for patients with severe imaging findings. The study aimed to evaluate the effect of the timing on the efficacy of bronchoalveolar lavage in children with adenovirus pneumonia. METHODS: This study included 134 patients with adenovirus pneumonia treated with BAL at Guangzhou Women and Children's Medical Center from January 2019 to January 2020.They were classified into the severe and mild groups. Based on the timing of BAL, each group was divided into the early BAL layer (received BAL within 1-9 days of the illness course) and the late BAL layer (received BAL within 10-14 days of the illness course). The clinical data of patients with different BAL timings were analyzed in two groups. RESULTS: Among the 134 patients, 70 were categorized into the mild group and 64 were categorized into the severe group. Of the 134 patients, 42 patients received BAL early (mild group: n = 21 and severe group: n = 21) and 92 patients received BAL later (mild group: n = 49 and severe group: n = 43). In the mild group, the fever and hospital duration were shorter in patients who received BAL early than in those who received BAL later (p < 0.05). However, in the severe group, there were no statistically significant differences in the fever and hospital duration between patients who received BAL early and those who received BAL later. However, the need for mechanical ventilation and the incidence of BAL complications, such as new need for oxygen, were higher in patients who received BAL early than in those who received BAL later in the severe group (p < 0.05). CONCLUSION: For mild adenovirus pneumonia, early BAL may shorten the fever and hospital duration. However, early BAL in severe cases might not shorten the course of the disease or improve prognosis and may even increase the risks of mechanical ventilation and BAL complications.

Two novel mutations in TCIRG1 induced infantile malignant osteopetrosis: a case report.

BACKGROUND: Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by a higher bone density in bone marrow caused by the dysfunction of bone resorption. Clinically, IMO can be diagnosed with medical examination, bone mineral density test and whole genome sequencing. CASE PRESENTATION: We present the case of a 4-month-old male infant with abnormal skull development, hypocalcemia and premature closure of the cranial sutures. Due to the hyper bone density showed by his radiographic examination, which are characteristic patterns of IMO, we speculated that he might be an IMO patient. In order to confirm this diagnosis, a high-precision whole exome sequencing of the infant and his parents was performed. The analysis of high-precision whole exome sequencing results lead to the identification of two novel heterozygous mutations c.504-1G > C (a splicing site mutation) and c.1371delC (p.G458Afs*70, a frameshift mutation) in gene TCIRG1 derived from his parents. Therefore, we propose that there is a close association between these two mutations and the onset of IMO. CONCLUSIONS: To date, these two novel mutations in gene TCIRG1 have not been reported in the reference gene database of Chinese population. These variants have likewise not been reported outside of China in the Genome Aggregation Database (gnomAD). Our case suggests that the use of whole exome sequencing to detect these two mutations will improve the identification and early diagnosis of IMO, and more specifically, the identification of homozygous individuals with TCIRG1 gene mutation. We propose that these mutations in gene TCIRG1 could be a novel therapeutic target for the IMO in the future.

Differential proteomic analysis of children infected with respiratory syncytial virus.

Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.

Differential proteomic analysis of children infected with respiratory syncytial virus

Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.

Clinical manifestations and risk factors of adenovirus respiratory infection in hospitalized children in Guangzhou, China during the 2011-2014 period.

To evaluate epidemiology and risk factors of severe adenovirus respiratory infection in hospitalized children in Guangzhou, China.A retrospective review study was conducted, and 542 children hospitalized for adenovirus respiratory infection, were included from January 2011 to December 2014. Patients were younger than 14 years. Disease severity was classified into severe and mild. Laboratory tests and clinical characteristics were analyzed for risk factors of adenovirus respiratory infection by multivariable logistic regression.Among these 542 children, 92.1% were aged < 6 years. Clinical diagnoses were upper respiratory infections in 11.6%, bronchiolitis in 16%, and mild pneumonia in 62.0% of children. Severe pneumonia rate was 10.3% (56/542) with a mortality rate of 0.9% (5/542). The cohort comprised 542 patients; 486 patients with mild adenovirus respiratory infection and 56 patients with severe adenovirus respiratory infection. Multivariable logistic regression was used to confirm associations between variables and adenovirus respiratory infection, after age and gender adjustment. Hospital stay, still significantly associated with adenovirus respiratory infection. Patients with longer hospital stay (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.13-1.28, P < .001), lower LYMPH (OR = 0.73 95% CI: 0.55-0.99, P = .039), and increased LDH (OR = 1.002, 95% CI: 1.001-1.003, P =  .001) had a higher risk of severe adenovirus respiratory infection.Adenovirus is a major pathogen in hospitalized children with respiratory infection. High serum LDH level and low lymphocyte count could be used as predictors of adenovirus respiratory infection severity in children.

Impaired visual, working, and verbal memory in first-episode, drug-naive patients with major depressive disorder in a Chinese population.

Cognitive impairment has been observed in patients with major depressive disorder (MDD). However, it remains unclear whether the deficits in specific cognitive domains are present in first-episode, drug-naïve patients or medicated patients. In the present study, using the CogState battery (CSB) Chinese language version, we evaluated the visual, working, and verbal memory in first-episode drug-naive patients and medicated patients with MDD in a Chinese population. We measured the cognitive function in first-episode drug-naïve patients (n = 36), medicated MDD patients (n = 71), and age- and sex-matched healthy control subjects (n = 59) in a Chinese population. The CSB composite scores in both first-episode drug-naive patients and medicated patients were significantly poorer than those in the healthy control subjects. The CSB sub-scores, including visual, working, and verbal memory were also significantly poorer in both patient groups than those in the healthy control subjects. In contrast, processing speed, attention/vigilance, executive function, spatial working memory, and social cognition were no different from healthy controls, whereas the executive function was significantly better in the medicated patients than in the healthy control subjects and first-episode drug-naïve patients. These findings suggest an impairment in the visual, working, and verbal memory in first-episode, drug-naive MDD patients in a Chinese population.

A 2-year step-down withdrawal from inhaled corticosteroids in asthmatic children receiving immunotherapy.

BACKGROUND: Inhaled corticosteroids (ICSs) for treating asthma are controversial because of their negative effects on the growth of asthmatic children and without clearly defined withdrawal strategy. A 2-year ICS step-down and withdrawal strategy has been developed for asthmatic children receiving 3-year subcutaneous immunotherapy (SCIT). METHODS: Eleven children were included into the SCIT group and 13 children into the ICS group. ICSs were discontinued when children met the following criteria: requiring only 1 puffper day, with good control, for at least 6 months; having a forced expiratory volume in 1 second (FEV1)/forced vital capacity ≥80%; and SCIT discontinued for ≥24 months. The main endpoints were the results of both the childhood asthma control test (C-CAT) and the methacholine bronchial provocation test. RESULTS: In the SCIT group, all the 11 children had ICS discontinued, with one child developed asthma attack after pneumonia and received ICS again after completion of SCIT. In the ICS group, five children discontinued ICS and developed asthma attacks later and received ICS again; the other eight children developed severe symptoms during ICS step-down. Thus, the discontinuation of ICS was only achieved in the SCIT group. The dose of methacholine that caused a decrease of 20% in FEV1 continued to improve after discontinuation of ICS for the SCIT group and presented better results than the ICS group (P=0.050). After completion of SCIT, the C-CAT had improved significantly after 30 months of treatment compared with the ICS group (P<0.05). CONCLUSIONS: In the present study, we developed a 2-year step-down and withdrawal strategy from ICSs strategy for allergic asthma children receiving SCIT; the strategy was efficacious and safe.

Absence of PTHrP nuclear localization and C-terminus sequences leads to abnormal development of T cells.

Parathyroid hormone-related protein (PTHrP), a ubiquitously expressed protein, is composed of four functional domains including N-terminus, mid region, nuclear localization signal (NLS) and C-terminus. Under the direction of NLS, PTHrP can enter cell nucleus from cytoplasm and stimulate mitogenesis. Although PTHrP is considered to have important developmental roles, the role of PTHrP NLS and C-terminus in developmental process remains unknown, especially in T-cell development. Here, we used a knock-in mouse model, which expresses a truncated form of PTHrP missing the NLS (87-107) and C-terminus (108-139) of the protein, to examine the role of PTHrP NLS and C-terminus in T-cell development. Our results showed that the truncated PTHrP (1-84) led to abnormal subpopulations, impaired proliferation and increased apoptosis in the thymus, indicating that PTHrP is involved in the development of T cells, and the NLS and C-terminus part is necessary for the normal role of PTHrP in T-cell development.

iTRAQ-based Quantitative Proteomics Study in Patients with Refractory Mycoplasma pneumoniae Pneumonia.

Mycoplasma pneumoniae (MP) is a leading cause of community-acquired pneumonia in children and young adults. Although MP pneumonia is usually benign and self-limited, in some cases it can develop into life-threating refractory MP pneumonia (RMPP). However, the pathogenesis of RMPP is poorly understood. The identification and characterization of proteins related to RMPP could provide a proof of principle to facilitate appropriate diagnostic and therapeutic strategies for treating paients with MP. In this study, we used a quantitative proteomic technique (iTRAQ) to analyze MP-related proteins in serum samples from 5 patients with RMPP, 5 patients with non-refractory MP pneumonia (NRMPP), and 5 healthy children. Functional classification, sub-cellular localization, and protein interaction network analysis were carried out based on protein annotation through evolutionary relationship (PANTHER) and Cytoscape analysis. A total of 260 differentially expressed proteins were identified in the RMPP and NRMPP groups. Compared to the control group, the NRMPP and RMPP groups showed 134 (70 up-regulated and 64 down-regulated) and 126 (63 up-regulated and 63 down-regulated) differentially expressed proteins, respectively. The complex functional classification and protein interaction network of the identified proteins reflected the complex pathogenesis of RMPP. Our study provides the first comprehensive proteome map of RMPP-related proteins from MP pneumonia. These profiles may be useful as part of a diagnostic panel, and the identified proteins provide new insights into the pathological mechanisms underlying RMPP.

Hypoxemia is an independent predictor of bronchiolitis obliterans following respiratory adenoviral infection in children.

Bronchiolitis obliterans (BO) is an uncommon and severe sequela of chronic obstructive lung disease in children that results from an insult to the lower respiratory tract. Few prognostic factors achieved worldwide acknowledgment. In the present study, we retrospectively collected the children with respiratory adenoviral infection and identified the predictive factors of BO. In the period between Jan 2011 and December 2014, the consecutive in-hospital acute respiratory infection children with positive result for adenovirus were enrolled into the present study. High resolution computerized tomography and clinical symptoms were utilized as the diagnostic technique for BO. Multivariate analysis using a Logistic proportional hazards model was used to test for independent predictors of BO. A total of 544 children were included with 14 (2.57 %) patients developed BO. Compared with children without BO, BO children presented higher LDH (523.5 vs. 348 IU/ml, p = 0.033), lower blood lymphocyte count (2.23 × 109/L vs. 3.24 × 109/L, p = 0.025) and higher incidence of hypoxemia (78.6 vs. 20.8 %, p = 0.000). They presented relatively persistent fever (15.5 vs. 7 days, p = 0.000) and needed longer treatment in hospital (19.5 vs. 7 days, p = 0.000). Concerning treatment, they were given more intravenous γ-globulin (85.7 vs. 36.8 %, p = 0.000), glucocorticoids (78.6 vs. 24.3 %, p = 0.000) and mechanical ventilation (35.7 vs. 5.5 %, p = 0.001). Multiple analyses determined that hypoxemia was the only independent predictor for BO. The present study identified hypoxemia as the independent predictive factor of BO in adenoviral infected children, which was a novel and sensitive predictor for BO.

Intranasal Delivery of Recombinant AAV Containing BDNF Fused with HA2TAT: a Potential Promising Therapy Strategy for Major Depressive Disorder.

Depression is a disturbing psychiatric disease with unsatisfied therapy. Not all patients are sensitive to anti-depressants currently in use, side-effects are unavoidable during therapy, and the cases with effectiveness are always accompanied with delayed onset of clinical efficacy. Delivering brain-derived neurotrophic factor (BDNF) to brain seems to be a promising therapy. However, a better approach to delivery is still rudimentary. The purpose of our present work is to look for a rapid-onset and long-lasting therapeutic strategy for major depressive disorder (MDD) by effectively delivering BDNF to brain. BDNF, fused with cell-penetrating peptides (TAT and HA2), was packaged in adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for intranasally delivering BDNF to central nervous system (CNS) via nose-brain pathway. Intranasal administration of BDNF-HA2TAT/AAV to normal mice displayed anti-depression effect in forced swimming test when the delivery lasted relatively longer. The AAV applied to mice subjected to chronic mild stress (CMS) through intranasal administration for 10 days also alleviated depression-like behaviors. Western-blotting analysis revealed that BDNF-HA2TAT/AAV nasal administration enhanced hippocampal BDNF content. These results indicate intranasal administration of constructed BDNF-HA2TAT/AAV exerts anti-depression effect in CMS mice by increasing hippocampal BDNF, suggesting that this strategy holds a promising therapeutic potential for MDD.

Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect.

The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

[Treatment of type C pelvic fracture with Stoppa approach and posterior percutaneous plate fixation].

OBJECTIVE: To explore the clinical effects of Stoppa approach and posterior percutaneous plate in treating type C pelvic fracture. METHODS: From June 2009 to July 2011,16 patients with type C pelvic fracture were treated with reconstruction plate fixation in Stoppa approach for anterior lesions combined with posterior percutaneous plate fixation for posterior lesions.There were 11 males and 5 females,with an average age of 38.8 years (ranged, 22 to 59 years). According to the Tile classification,10 cases belonged to C1,4 belonged to C2,2 belonged to C3. Tometta and Majeed score standards were used to evaluate clinical results. RESULTS: Sixteen patients were followed up from 4 to 13 months with an average of 7.3 months. Operative time was from 80 to 140 min with an average of 100 min;blood loss volume was from 200 to 500 ml with an average of 280 ml; and the healing time of fracture was from 12 to 16 months with an average of 14 months. According to the Tometta score classification, 9 cases got excellent results, 6 good, 1 fair. According to the Majeed score classification, 9 cases obtained excellent results, 5 good, 2 fair. CONCLUSION: Reconstruction plate fixation in Stoppa approach for anterior lesions combined with posterior percutaneous plate fixation for posterior lesions is an ideal minimally invasive operation in treaing type C pelvic fracture. It can early exercise and has the advandages of small trauma, safe operaton,less complication, stable fixation.

[Arthroscopic single bundle anterior cruciate ligament anatomical reconstruction with remnant preservation].

OBJECTIVE: To investigate the feasibility and clinical effects of single bundle anterior cruciate ligament anatomical reconstruction with remnant preservation. METHODS: From October 2007 to November 2009, 17 patients (10 male and 7 female, ranging in age from 28 to 62 years, with an average of 39.3 years) with posterior cruciate ligament injuries were treated with single bundle anatomical reconstruction with remnant preservation. Nine patients had the injuries caused by traffic accident; 6 patients caused by falling down; and 2 patients caused by sports injuries. The average time from injury to surgery was 8.5 days (ranging from 2 to 14 days). The international knee documentation committee knee evaluation form (IKDC) and Lysholm were used to analysis the effect of surgery. RESULTS: All the patients obtained the follow-up and the average time was 29.5 months (ranging from 24 to 39 months). There were no complications such as injuries of popliteal fossa artery, tibial nerves or peroneal nerve. Twelve patients had knee joint recovering to normal; 1 patient had stiff joints and was treated with arthroscopic surgery to release after 6 months,who had postoperative flexion lack of 20 degree and straight to normal. Three patients had flexion loss of 5 to 10 degree, and 1 patient had hyperextension limitation of 5 degree. Posterior drawer test in 17 patients and the Lachman test were negative. IKDC scores of the 17 patients achieved normal(16 patients) or near normal(1 patient). IKDC overall score normal in 16 patients (94.1%), close to normal in 1 case (5.9%). The IKDC subjective score was 94.3+/-5.1 and Lysholm score was 94.7+/-3.1 at the latest follow-up. CONCLUSION: The single bundle anterior cruciate ligament with remnant preservation anatomical reconstruction can provide good clinical results.