[A clinical observational study on the preliminary effect of dupilumab in the treatment of severe asthma].

Objective: To investigate the effect and safety of dupilumab in the treatment of patients with severe asthma in a preliminary clinical observational study. Methods: This study retrospectively analyzed the clinical data of 20 patients with severe asthma who received dupilumab for 4-12 months between 2019 and 2022 at the First Hospital of Guangzhou Medical University, comparing pre-and post-treatment laboratory data, oral glucocorticoid dose (OCS), asthma control test (ACT) and adverse effects. The median age of the 20 patients was 48.5 (41.0-52.8) years, including 14 males and 6 females. The clinical data of 10 patients treated with other biologic agents were further analyzed to determine the reasons for switching to biologic drug treatment and the efficacy of dupilumab in these patients. Paired t-tests or Wilcoxon signed-rank tests were used for comparisons. Mann-Whitney analysis was used for inter-group comparison, and chi-square test or Fisher test was used for inter-group comparisons of count data. Results: A total of 20 patients were included in this study. All 20 severe asthma phenotypes were type 2 (T2)-high and completed at least the first 4 months of treatment, including 17 patients who completed 12 months of treatment. Among patients who completed 4 months of treatment, the asthma exacerbation score decreased from 1.0(0.3-1.0) episodes/4 months to 0.0(0.0-1.0) episodes/4 months, P<0.001, and FEV1/FVC increased from 58.4% (50.5%-69.0%) to 66.9% (59.6%-77.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 15 (75%) to 9 (45%), P<0.05. Among patients who completed 12 months of treatment, the asthma exacerbation score decreased from 1.0(0.5-1.0) episodes/4 months to 0.0 (0.0-0.0) episodes/4 months, P<0.01, and FEV1/FVC increased from 57.9% (49.6%-67.8%) to 72.7% (64.6%-78.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 13 (76%) to 6 (35%), P<0.01. In 10 patients with a history of previous biologic therapy, the most common reasons for switching to a biologic were a poor response to previous monoclonal antibodies (40%) and loss of control of asthma symptom control after discontinuation of monoclonal antibodies (30%). The remaining reasons were patients' uncontrolled symptoms of chronic rhinosinusitis (20%) and irregular or underdosed use of previous biologics (10%). After 4 months of switching to dupilumab, 10 patients experienced varying degrees of improvement in asthma control. Conclusions: The application of dupilumab for the treatment of T2-high severe asthma showed good efficacy and few adverse effects. Biologically targeted therapy is an important treatment approach to achieving better control of severe asthma.

An observational study on the safety of COVID-19 vaccination in patients with myasthenia gravis.

OBJECTIVE: There is concern that the coronavirus disease (COVID-19) vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of COVID-19 vaccination on symptom severity in patients with myasthenia gravis (MG). METHODS: A total of 106 enrolled patients with MG who were vaccinated against COVID-19 were followed up, and a questionnaire was used to document in detail the exacerbation of muscle weakness after vaccination and all other uncomfortable reactions after vaccination. Demographic, clinical characteristics, medication, and vaccination data were collected by follow-up interview. The main observation outcome was whether the MG symptoms of patients were exacerbated. The definition of exacerbation is according to the subjective feeling of the patient or a 2-point increase in daily life myasthenia gravis activity score relative to before vaccination, within 30 days after vaccination. RESULTS: Of 106 enrolled patients [median age (SD) 41.0 years, 38 (35.8%) men, 53 (50.0%) with generalized MG, 74 (69.8%) positive for acetylcholine receptor antibody, and 21 (19.8%) with accompanying thymoma], muscle weakness symptoms were stable in 102 (96.2%) patients before vaccine inoculation. Muscle weakness worsened in 10 (9.4%) people after vaccination, of which 8 patients reported slight symptom worsening that resolved quickly (within a few days). Two (1.9%) of patients showed serious symptom aggravation that required hospitalization. CONCLUSION: Our results suggest that inactivated virus vaccines against COVID-19 may be safe for patients with MG whose condition is stable. Patients with generalized MG may be more likely to develop increased muscle weakness after vaccination.

The Physical Resilience Instrument for Older Adults (PRIFOR) in Surgical Inpatients: Further Evidence for Its Factor Structure and Validity.

BACKGROUND: The Physical Resilience Instrument for Older Adults (PRIFOR) is a questionnaire for assessing physical resilience in older adults suffering from acute health stressors. Prior psychometric evidence of the PRIFOR showed that it has good criterion-related validity, known-group validity, predictive validity, and internal consistency. However, it is unclear whether the PRIFOR can be replicated in older adults suffering after surgical treatment. OBJECTIVES: This study aimed at evaluating whether the three-factor structure of the PRIFOR can be replicated in older adults suffering after surgical treatment. Moreover, the concurrent validity of the PRIFOR was examined using the association between the PRIFOR and measures of depression, cognition, activities of daily living, and frailty. DESIGN AND SETTING: A longitudinal study was adopted in a tertiary-care medical center in Taiwan. PARTICIPANTS: A total of 207 patients aged 65 years old and older who underwent surgery and if they were able to communicate independently. MEASUREMENTS: The PRIFOR, the 5-item Geriatric Depression Scale, the Short Portable Mental Status Questionnaire, the Katz Index of Independence in Activities of Daily Living and Clinical Frailty Scale were all assessed after surgery. RESULTS: The three-factor structure (positive thinking, cope and adjust lifestyle, and belief and hopeful mindset) was supported by the CFA results in the present sample. In addition, the PRIFOR showed good concurrent validity with depression (r = -0.470 to -0.542), cognition (r = 0.358 to 0.409), activities of daily living (r = 0.209 to 0.310), and frailty (r =-0.161 to -0.237). CONCLUSION: The PRIFOR can be recommended to measure physical resilience in older adults suffering after surgical treatment. For the adequate estimation of older adults' level of physical resilience postoperatively and to guide the implementation of individualized interventions, it is important to provide appropriate care for older adults to recover after surgery.

Applying machine learning methods to predict the hospital re-admission within 30 days of total hip arthroplasty and hemiarthroplasty.

BACKGROUND: Total hip arthroplasty (THA) and hemiarthroplasty are common treatments for severe hip joint disease. To predict the probability of re-admission after discharge when patients are hospitalized will support providing appropriate health education and guidance. METHODS: The research aims to use logistic regression (LR), decision trees (DT), random forests (RF), and artificial neural networks (ANN) to establish predictive models and compare their performances on re-admissions within 30 days after THA or hemiarthroplasty. The data of this study includes patient demographics, physiological measurements, disease history, and clinical laboratory test results. RESULTS: There were 508 and 309 patients in the THA and hemiarthroplasty studies respectively from September 2016 to December 2018. The accuracies of the four models LR, DT, RF, and ANN in the THA experiment are 94.3%, 93.2%, 97.3%, and 93.9%, respectively. In the hemiarthroplasty experiment, the accuracies of the four models are 92.4%, 86.1%, 94.2%, and 94.8%, respectively. Among these, we found that the RF model has the best sensitivity and ANN model has the best area under the receiver operating characteristic (AUROC) score in both experiments. CONCLUSIONS: The THA experiment confirmed that the performance of the RF model is better than the other models. The key factors affecting the prognosis after THA surgery are creatinine, sodium, anesthesia duration, and dialysis. In the hemiarthroplasty experiment, the ANN model showed more accurate results. Poor kidney function increases the risk of hospital re-admission. This research highlights that RF and ANN model perform well on the hip replacement surgery outcome prediction.

[Efficacy of omalizumab in the treatment of eosinophilic granulomatous polyangiitis with asthma as the first symptom].

Objective: To investigate the efficacy, and safety of omalizumab in the treatment of eosinophilic granulomatous with polyangiitis (EGPA) with asthma as the first symptom. Method: The clinical characteristics of 22 EGPA patients with asthma as the first symptom treated with omalizumab in the First Affiliated Hospital of Guangzhou Medical University from March 2018 to December 2020 were retrospectively analyzed. The asthma control test (ACT) score, the frequency of asthma exacerbation (AE), the Birmingham Vasculitis Activity Score (BVAS), the variation rate of peak expiratory flow (PEF), the percentage of PEF to predicted value of PEF (PEFpred%), the percentage of forced expiratory volume in first second (FEV1) to predicted value of FEV1 (FEV1pred%), the dosage of oral corticosteroid (OCS) and other clinical data [M(Q1, Q3)] were collected before and after treatment, to observe the efficacy and adverse reactions of omalizumab. Results: There were 22 subjects recruited in this study. The median age was 42 (22-70) years. Eleven of the patients were males. After treated with omalizumab for 4 months, there were 68.2%(15/21) of patients who responded to the treatment. In the response group (n=15), the patients' ACT score increased from 19.0 (16.5, 21.0) to 23.0 (21.5, 24.0) (P=0.001). The frequency of AE decreased from 0.7 (0.3, 1.0) to 0 (0, 0.7) per four mouths (P<0.001). The BVAS decreased from 4.0 (2.0, 6.0) to 2.0 (2.0, 4.0) (P=0.007). The variation rate of PEF decreased from 18.8% (14.0%, 27.7%) to 9.2% (6.8%, 11.9%) (P=0.007). The PEFpred% increased from 80.8% (73.5%, 90.7%) to 100.5% (79.4%, 114.0%) (P=0.005). The maintenance dosage of OCS reduced from 15.0 (10.0, 20.0) mg/d to 8.8 (5.0, 10.0) mg/d (P=0.005). The level of baseline eosinophil in peripheral blood of patients in non-response group was higher than that in response group [11.4% (9.2%, 22.6%) vs 3.4% (1.1%, 6.5%), P<0.05]. A total of 190 injections were performed in 22 patients, and only 4 patients (2.1%) had adverse reactions after a single injection of omalizumab, such as dizziness, swelling of injection site and pruritus. The adverse reactions were tolerable. Conclusions: Omalizumab has certain curative effect on EGPA, can reduce asthmatic symptoms and OCS maintenance dosage, and has a good safety profile. The rate of response to the treatment is higher in patients with mild eosinophilic inflammation.

[Analysis of clinical characteristics and related genetic variation of juvenile myasthenia gravis].

Objective: To analyze the clinical characteristics and related genetic variation of juvenile myasthenia gravis (MG) patients. Methods: We collected the clinical data of adolescent MG patients who were treated in the Department of Neurology of the First Affiliated Hospital of Sun Yat-sen University from June 2019 to May 2020. After obtaining the patient's informed consent, the blood samples were collected. The Whole Exome Sequencing (WES) was performed on peripheral blood samples. And use biological information software and SPSS 22.0 for data processing and result analysis. Results: According to the inclusion and exclusion criteria, 54 patients with juvenile MG were included, 28 males and 26 females. And the average age of onset was (3.79±0.89) years. Among the enrolled patients, there were 52 (96.3%) patients with ocular MG, the MG-ADL scores of 54 patients were (3.44±0.44) points, and the titer of AChR antibody was (5.88±2.45) nmol/L. Two patients had thymic hyperplasia, and 5 patients had a family history of MG.A total of 169 variant genes were found in 54 patients, of which TTN gene variants had the largest number, with a total of 17 variants (31.5%). In the TTN gene variant group, 7(41.2%) patients had eye fixation symptoms, and 4 (10.8%) patients in the non-mutation group had eye fixation symptoms. And The difference between the two groups was statistically significant (P=0.016). In addition, the synaptic nucleus envelope protein-1 (SYNE1) and the ryanodine receptor-1 (RYR1) gene variations were also found in 7 cases (13.2%), and no clear relationship between these gene variations and clinical manifestations of MG was found. Conclusions: The incidence of juvenile MG was preschoolers with no gender difference, and ocular MG was more common. The proportion of TTN gene variation in adolescent MG was higher, suggesting that this gene may be a potential therapeutic target for juvenile MG patients.

[Clinical characteristics and outcomes of myasthenia gravis patients with double positive antibodies against acetylcholine receptor and muscle-specific tyrosine kinase].

Objective: To investigate the clinical manifestations, treatment characteristics and outcomes of myasthenia gravis (MG) dually positive for anti-acetylcholine receptor antibody (AChR-Ab) and anti-muscle-specific tyrosine kinase antibody (MuSK-Ab). Method: MG patients hospitalized in the First Affiliated Hospital of Sun Yat-sen University from August 2017 to November 2020 were retrospectively collected. Thirty-four MuSK-Ab positive MG (MuSK-MG) patients, 11 double-antibodies positive MG (DP-MG) patients, and 80 AChR-Ab positive MG (AChR-MG) patients were included and allocated to three different groups. The clinical data of patients in the three groups were collected, and the differences of demographic characteristics, clinical manifestations and treatment outcomes between DP-MG patients and AChR-MG and MuSK-MG patients were analyzed. Result: The proportion of female and male patients in DP-MG group was 7/11 and 4/11 respectively, and the onset age of DP-MG was (41±27) years.The difference in gender distribution between DP-MG and AChR-MG groups was statistically significant (P<0.05). The proportion of extraocular muscle involvement in the DP-MG and MuSK-MG groups (8/11 and 52.9%) was lower than that in the AChR-MG group (83.8%), and the difference was statistically significant (P<0.05). The incidence of myasthenia crisis in DP-MG and MuSK-MG groups (54.5% and 61.8%) were higher than that in AChR-MG group (20.0%), with astatistically significant difference(P<0.05). The positive rate of neostigmine test in DP-MG and MuSK-MG groups(8/11 and 74.2%) were lower than that of AChR-MG group (96.8%), and the positive rate of low frequency repetitive nerve stimulation (RNS) in DP-MG group (5/10) was lower than that in AChR-MG group (85.1%), with statistically significant differences (all P<0.05). MuSK-Ab titer was positively correlated with the course of disease (r=0.466, P<0.05), and antibody titer decreased after symptom improvement (P<0.05). The response of patients in DP-MG and MuSK-MG groups to cholinesterase inhibitors (2/11 and 9.1%) was worse than that in the AChR-MG group (66.3%), and the incidence of side effects in the two groups (5/11 and 39.4%) was higher than that in the AChR-MG group (15.0%), with statistically significant differences (all P<0.05). There were 4 DP-MG patients underwent thymectomy, and the pathological results detected two cases of thymoma and two cases of thymic hyperplasia. Subsequent follow-up showed that 5 (5/11) DP-MG patients achieved minimal manifestation status or better status. Conclusion: The gender distribution, age of onset, pharmacological characteristics and electrophysiological examination of DP-MG patients were similar to those of MuSK-MG patients, but the severity of DP-MG patients was between that of AChR-MG and MuSK-MG patients.

[Preliminary clinical observation of omalizumab therapy for moderate to severe asthma].

Objective: To observe the effectiveness, safety and management of omalizumab therapy for moderate to severe asthma in real-world clinical practice in China. Methods: This retrospective analysis involved 79 patients with moderate to severe asthma who received omalizumab therapy for at least 4 months in the First Affiliated Hospital of Guangzhou Medical University from March 2018 to April 2020. All participants were between 14 to 76 years old(median 50 years),including 30 males and 49 females. Data regarding the patients' clinical manifestations, eosinophil count, fractional exhaled nitric oxide (FeNO), lung function, oral corticosteroid dosage, and adverse reactions were collected before and after treatment. Paired t-test or non-parametric paired Wilcoxon analysis was used for pairwise comparison, Mann Whitney analysis for inter-group comparison, and Chi square test or Fisher test for inter-group comparison of count data. Results: The following changes were noted after 4 months of omalizumab thearpy. The patients' Asthma Control Test (ACT) scores increased from 17.0 (13.0-19.0) to 20.0 (18.0-24.0) points (P<0.001). The frequency of acute exacerbations(AE) decreased from 1.0 (0-1.0) to 0 (0-1.0) episodes every 4 months (P<0.001). The variation rate of the peak expiratory flow (PEF) decreased from 16.5 (13.8-27.3)% to 10.4 (6.0-16.2)% (P<0.001). The percent predicted value of PEF (PEFpred%) increased from 71.7 (51.4-91.6)% to 87.5 (65.2-105.5)% (P<0.001). The percent predicted value of the forced expiratory volume in 1 second(FEV1%pred) increased from 73.6 (53.9-90.8)% to 80.6 (68.7-91.8)% (P=0.007). The maintenance dose of oral corticosteroids (OCS) decreased from 12.0 (10.0-20.0) to 5.0 (0-17.5) mg/day (P=0.001). After 4 months of treatment, the response rate of the 79 patients with asthma was 74.7%. The response rate of patients with allergic asthma (77.3%) was higher than that of patients with non-allergic asthma (25.0%) (P=0.019). Among 5 patients who completed 1 year of treatment, the ACT score, frequency of AE, PEFpred%, variation rate of PEF and OCS maintenance dose were still improved after 1 year of treatment. Adverse reactions occurred in 3 patients (3.8%), for a total of 3 (0.6%) times. Stratified analysis showed that after 4 months of treatment, the improvement in the ACT score and the decrease in the PEF variation rate among patients who reached the recommended treatment dose (full dose) [3.0 (1.0-8.0) points, 6.5 (3.5-15.8) %] were significantly higher than those among patients who did not reach the recommended treatment dose (insufficient dose) [1.0 (-0.3-3.0) points, 2.9 (1.5-5.0) %] (P<0.05). Additionally, the treatment response rate in patients with a sufficient dose (80.0%) was higher than that in patients with an insufficient dose (50.0%) (P=0.019).The main factors associated with stopping treatment within 1 year despite a response to omalizumab was economic burden (70.3%), followed by satisfactory improvement by self-evaluation (21.9%) and less improvement in symptoms than expected (7.8%). Conclusion: Omalizumab was an effective treatment for moderate to severe allergic asthma with few adverse effects. The response rate was higher when the recommended injection dose was achieved. Financial difficulty was the main reason for stopping treatment within 1 year despite a good therapeutic response.

[Characteristics of electromyography in 111 patients with generalized myasthenia gravis: a retrospective study].

Objective: To retrospectively analyze the characteristics of the electromyography (EMG) study in generalized myasthenia gravis (gMG) patients. Methods: A total of 111 gMG patients were enrolled. Patients were divided into two groups: 36 severe patients discontinuing pyridostigmine bromide (PB) for 8 hours were included in 8 h group, and 75 g MG patients discontinuing PB for at least 18 hours were included in>18 h group. The clinical information and EMG study data were collected and analyzed. Results: There were statistically significant differences in the initial location of the myasthenia muscle (P=0.027), the affected muscle detected by the EMG (P=0.015) and quantitative myasthenia gravis (QMG) score (P<0.01) between the two groups. Comparisons in each group revealed that the highest positive rate of low-frequency repetitive nerve stimulation (RNS) of facial in 8 h group and>18 h group was 94.4% and 60.0%, respectively. Comparisons between the two groups showed that the positive rate of low-frequency RNS in 8 h group was significantly higher than that in>18 h group (94.4% vs 70.7%, χ(2)=8.115, P=0.004). In particular, the positive rate of RNS in facial nerves and the extent of the amplitude decrease under different electrical stimulations (1 Hz, 3 Hz, and 5 Hz) were dramatically higher in the 8 h group (P<0.01). Conclusions: For gMG patients, the facial and accessory nerve detection can improve the positive rate of RNS. Different muscles had various sensitivity to PB, and orbicularis oculi muscle seemed the least sensitive muscle to PB. For suspect MG patients in severe condition, only discontinuing PB medication for 8 h before low-frequency RNS testing can avoid the deterioration and also obtain similar positive rate.

[Comparison of modeling effects of two different 7, 12-dimethylbenz[a] anthracene induced breast cancer models in tree shrew].

Objective: To explore the feasibility of 7, 12-dimethylbenz[a] anthracene (DMBA) induced tree shrew breast cancer model, and compare the effects of two administration modes by gavage and mammary gland injection. Methods: A total of 40 tree shrews were randomly divided into two groups (20 animals per group): DMBA gavage group and mammary gland injection group. DMBA was dissolved in edible vegetable oil. For gavage group, tree shrews were administered with DMBA solutions (15 mg/kg) by gavage once a day. For mammary gland injection group, DMBA solution (10 mg/kg) was injected into the mammary fat pad of tree shrews, and the injection was performed for a total of 3 times. From the first administration of DMBA, medroxyprogesterone acetate (MPA, 100 mg/kg) was intramuscularly injected into the muscles of the lateral thighs of tree shrews at the same time, for a total of 5 times. The tumorigenesis and survival of tree shrews were monitored. The tumor histological morphology was observed by HE staining. The expression of estrogen receptor (ER), progesterone receptor (PR), cytokeratin5/6 (CK5/6) and human epidermal factor receptor-2 (HER-2) was detected by immunohistochemical staining. Results: In the gavage group, there were 10 deaths, and 4 tree shrews developed mammary tumors with 20.0% (4/20) tumor formation rate. The success rate of mammary cancer modeling was 10.0% (2/20), and the tumor formation time was 197.3±15.1 days. In the mammary gland injection group, there were 8 tree shrews died, and 9 tree shrews formed tumors with 45.0% (9/20) tumor formation rate. The success rate of mammary cancer modeling was 40.0% (8/20), and the tumor formation time was 71.8±19.0 days. There was no significant difference in mortality and tumor formation rate (P>0.05) between the two groups (all P>0.05). However, in the mammary gland injection group, the success rate of mammary cancer modeling was significantly higher than that in the gavage group (P<0.05), whereas the tumor formation time was markedly shorter than that in the gavage group (P<0.01). The pathological types in the gavage group included ductal hyperplasia, intraductal papilloma and ductal carcinoma in situ, while those in the breast injection group included intraductal papilloma and ductal carcinoma in situ. In both groups, immunohistochemical staining showed the negative expression of HER-2 but positive expression of ER, PR and CK5/6 with varying degrees. Conclusion: Both the DMBA gavage and mammary gland injection can successfully establish the tree shrew breast cancer model, and the modeling effect of mammary gland injection is better than gavage.

Effects of IBDV infection on expression of ghrelin and ghrelin-related genes in chicken.

Ghrelin is a peptide hormone that plays a modulatory role in the immune system. Studies have demonstrated that mammal ghrelin level is influenced by pathological status. However, it has not been reported whether chicken ghrelin level changes during pathogen infection. This study was designed to investigate changes of ghrelin levels in chickens infected with infectious bursal disease virus (IBDV) and to explore the relationship between ghrelin changes and bursal damage, and inflammatory cells infiltration induced by IBDV. The results showed that (1) plasma ghrelin concentration increased after IBDV infection. It reached a peak at 10443.6 ± 2612.9 pg/mL on 2 dpi, which was about 100-fold as high as that of the control. Then it decreased sharply on 3 dpi, which was only 31.7% as that of 2 dpi, and remained stable until 5 dpi. Meanwhile, ghrelin and ghrelin-related gene, ghrelin-o-acyltransferase (GOAT), and growth hormone secretagogue receptor (GHSR) mRNA expression levels in bursa were also increased after IBDV infection, and reached the peak on 2 dpi at 149, 28.8, and 117.2-fold higher than that of the control, respectively. Then they decreased and remained at a higher status. Correlation analysis showed that plasma ghrelin concentration and ghrelin, GOAT, and GHSR mRNA expressions in bursa were strongly associated with IBDV VP2 mRNA expression in bursa. (2) The damage of bursa was the most severe on 5 dpi with a histopathological score of 12. It had no direct correlation with plasma ghrelin level and ghrelin, GOAT, and GHSR mRNA expressions in bursa. However, the number of inflammatory cells infiltrating into bursa, which was the highest on 2 and 3 dpi, showed significant a positive correlation with the ghrelin and GHSR mRNA expression. Presumably chicken ghrelin may function as an anti-inflammatory factor. In conclusion, IBDV infection upregulates the expression of ghrelin and ghrelin-related gene in chickens, and chicken ghrelin may play an important regulatory role during pathogen infection.

The effect of structural change on the digestibility of sarcoplasmic proteins in Nanjing dry-cured duck during processing.

To evaluate the effect of structural change on the digestibility of sarcoplasmic proteins in Nanjing dry-cured duck during processing, carbonyl content, sulfhydryl (SH) group, disulfide (S-S) group, surface hydrophobicity, particle size, secondary structures, and in vitro digestibility were determined. During processing, carbonyl content increased; SH groups turned into S-S groups; α-helix turned into ß-sheet. From marinating to early dry-ripening stage, surface hydrophobicity increased but particle size decreased, whereas these had opposite tendencies at the late dry-ripening stage. The in vitro digestibility of pepsin decreased at drying-curing and drying-ripening stages, whereas the one of pancreatic proteases kept stable until late drying-ripening stage. We concluded that salting, drying, and protein oxidation caused the denaturation and aggregation during processing. The oxidation and aggregation of sarcoplasmic proteins of Nanjing dry-cured duck resulted in a loss of nutritional quality during drying-ripening stage.

[Correlation factors of 127 times pre-crisis state in patients with myasthenia gravis].

Objective: To investigate the clinical features of the Pre-Crisis State and analyze the correlated risk factors of Pre-Crisis State of myasthenia crisis. Methods: We included 93 patients with myasthenia gravis (MG) who experienced 127 times Pre-Crisis State between October 2007 and July 2016. Those patients were hospitalized in the MG specialize center, Department of Neurological Science, first Affiliated Hospital of Sun Yat-sen University. The information of the general situation, the clinical manifestations and the blood gas analysis in those patients were collected using our innovated clinical research form. Statistic methods were applied including descriptive analysis, univariate logistic analysis, multivariate correlation logistic analysis, etc. Results: (1)The typical features of MG Pre-Crisis State included: dyspnea (127 times, 100% not requiring intubation or non-invasive ventilation), bulbar-muscle weakness (121 times, 95.28%), the increased blood partial pressure of carbon dioxide (PCO(2)) (94 times, 85.45%), expectoration weakness (99 times, 77.95%), sleep disorders (107 times, 84.25%) and the infection (99 times, 77.95%). The occurrence of dyspnea in combination with bulbar-muscle weakness (P=0.002) or the increased blood PCO(2) (P=0.042) often indicated the tendency of crisis. (2) The MG symptoms which were proportion to the occurrence of crisis includes: bulbar-muscle weakness (P=0.028), fever (P=0.028), malnutrition (P=0.066), complications (P=0.071), excess oropharyngeal secretions (P=0.005) and the increased blood PCO(2) (P=0.007). The perioperative period of thymectomy would not increase the risk of crisis. Conclusions: Dyspnea indicates the occurrence of the Pre-Crisis State of MG. In order to significantly reduce the morbidity of myasthenia crisis, the bulbar-muscle weakness, the increased blood PCO(2), expectoration weakness, sleep disorders, infection & fever and excess oropharyngeal secretions should be treated timely.

Spatiotemporal analysis of tuberculosis incidence and its associated factors in mainland China.

Spatiotemporal analysis is an important tool to monitor changes of tuberculosis (TB) epidemiology, identify high-risk regions and guide resource allocation. However, there are limited data on the contributing factors of TB incidence. This study aimed to investigate the spatiotemporal pattern of TB incidence and its associated factors in mainland China during 2005-2013. Global Moran's I test, Getis-Ord Gi index and heat maps were used to examine the spatial clustering and seasonal patterns. Generalized Linear Mixed Model was applied to identify factors associated with TB incidence. TB incidence presented high geographical variations with two main hot spots, while a generally consistent seasonal pattern was observed with a peak in late winter. Furthermore, we found province-level TB incidence increased with the proportion of the elderly but decreased with Gross Demographic Product per capita and the male:female ratio. Meteorological factors also influenced TB incidence. TB showed obvious spatial clustering in mainland China and both the demographic and socio-economic factors and meteorological measures were associated with TB incidence. These results provide the related information to identify the high-risk districts and the evidence for the government to develop corresponding control measures.

[Characteristics of distribution and quantity of dendritic cells subtypes in hyperplastic thymus in patients with myasthenia gravis].

Objective: To investigate the characteristics of the distribution and amount of different subtypes of dendritic cell (DC) in myasthenia gravis(MG). Methods: We collected the thymic specimens from 32 patients who received thymoctomy because of cardiac surgery from January 2016 to December 2016 and selected 14 of them as normal control. Meantime, 61 MG patients who combined with thymic hyperplasia and received extended thymectomy were collected and selected 8 of them as experiment group.Immunohistochemical methods were used to label the two subtype DCs: plasmacytoid dendritic cell (pDC) and classical/conventional dendritic cell (cDC), to observe the distribution of these two DC subtypes in thymus and also quantify them in different thymus structures by image analysis software.Comparing with normal thymus of the same age, we intended to demonstrate the characteristics of distribution and density of DC subtypes in patients who had MG and hyperplastic thymus. Results: (1) We labeled pDC and cDC by staining with CD123 and CD11c.The two DC subtypes distributed in both cortex and medulla, and the majority gathered in medulla, the density of pDC in thymus cortex was (34±6)/mm(2)(n=14), the density of pDC in thymus medulla was (247±35)/mm(2)(n=14), the density of cDC in thymus cortex was (21±4)/mm(2)(n=14), the density of cDC in thymus medulla was (123±16)/mm(2) (n=14). (2) The density of pDC in thymus cortex and medulla of patients with MG was lower when compared with the normal group (the density of pDC in thymus cortex, [(39±10)/mm(2) vs (29±5)/mm(2)], the density of pDC in thymus medulla, [(279±48)/mm(2) vs (236±49)/mm(2)], but with no significant difference.There was no significant difference between the density of cDC in thymus cortex of patients with MG patients and normal people, however, the amount of cDC increases in medulla and the difference was statistically significant (P<0.05). (3) The density of cDC in thymus medulla (except for germinal center) was higher than normal people (110±18) /mm(2) vs (187±29/mm(2)), though the difference was not statistically significant (P=0.059 9). The density of cDC in the ectopic germinal center (GC) of MG patients increased obviously compared with that in thymus medulla [(203±44) /mm(2) vs (439±69)/mm(2)] and the difference was statistically significant (P<0.05). Conclusions: The density of cDC increases significantly in thymus medulla of MG patients, especially gathering around or in the ectopic GC. It indicates that cDC may play an important role in the formation of ectopic GC in the hyperplasia thymus, thus involves in the disease process.