[Genotype and epidemiological characteristics of human metapneumovirus among hospitalized cases of acute respiratory infection in children in Changchun City, Jilin Province from 2019 to 2023].

Objective: To investigate the genotype and epidemiological characteristics of human metapneumovirus (HMPV) among hospitalized cases with acute respiratory infections (ARI) in children in Changchun City, Jilin Province, China. Methods: From June 2019 to June 2023, throat swabs of ARI inpatients in Changchun Children's Hospital were collected, and their epidemiological and clinical information were also collected. Quantitative reverse transcription-PCR was used to identify HMPV-positive cases, followed by the amplification of the G gene and genetic analysis in the HMPV-positive cases. Results: A total of 3 311 children hospitalized with ARI were included in this study. Their age ranged from 0 to 17 years old, and the M (Q1, Q3) of age was 2 (1, 3) years. About 1 811 (54.70%) cases were males. A total of 167 HMPV-positive cases were detected with a positive rate of 5.04%, of which 92.81% (155/167) were children under 5 years old. The positive rate of HMPV in 2019 was 6.37% (30/471), which dropped to the lowest in 2020 (2.31%, 10/432). The HMPV-positive rate was then rebounded in 2021 (4.70%, 60/1 277) and 2022 (4.56%, 21/461), which increased to 6.87% (46/670) in 2023. The difference in HMPV-positive rate among each year was statistically significant (P<0.05). The prevalence peak of HMPV varied in different years, showing either a unimodal or bimodal distribution in one year. A total of 79 HMPV G gene sequences were obtained, of which subtype A and subtype B accounted for 48.10% and 51.90%, respectively. All of the subtype A sequences were clarified as A2c duplicated variants, and subtype B was mainly B2 genotype. Besides, subtypes A and B were prevalent alone or co-circulated in different years, and there was a subtype replacement pattern in HMPV. Conclusion: The positive rate of HMPV in hospitalized ARI cases in children is significantly different from 2019 to 2023 in Changchun City. Notably, there are certain switch patterns of HMPV subtypes A and B in different years.

[Infection status and Molecular types of Rhinovirus among Cases of Acute Respiratory Tract Infections in Luohe City, Henan Province, from 2017 to 2022].

Objective: To understand the infection status and molecular types of rhinovirus (RV) among cases of Acute Respiratory Infections (ARIs) in Luohe City, Henan Province, from 2017 to 2022. Methods: From October 2017 to June 2022, clinical and epidemiological data were collected from 2 270 cases of ARIs at Luohe Central Hospital in Henan Province. Throat swab specimens were obtained from these cases. Real-time quantitative polymerase chain reaction (qPCR) was used to screen for RV-positive specimens. Subsequently, the positive samples were subjected to nested reverse transcription polymerase chain reaction (nested RT-PCR) to amplify the full-length VP1 region. Using the MEGA software, along with 169 RV reference strains recommended by the International Committee on Taxonomy of Viruses, a phylogenetic tree was constructed to determine RV types. Results: Among the 2 270 cases of ARIs, there were 1 283 male cases (56.52%). The median age (Q1, Q3) was 3 (1, 6) years, with the population under 5 years old accounting for 68.59% (1 557/2 270). RV was detected in 137 cases (6.04%), of which 68 cases (49.64%) showed co-detection with other viruses, with the most common being co-detection with enterovirus, accounting for 14.60% (20/137). The RV detection rates in the age groups of 0~4 years, 5~14 years, 15~59 years, and≥60 years were 6.42% (100/1 557), 4.69% (21/448), 3.80% (6/158), and 9.35% (10/107), respectively, with no statistically significant differences (χ2=5.310, P=0.150). The overall detection rates of RV before (2017-2019) and during (2020-2022) the COVID-19 pandemic showed no statistically significant difference (χ2=1.823, P=0.177). A total of 109 VP1 sequences were obtained, including 62 types. Among them, RV-A, RV-B, and RV-C had 42, 3, and 17 types respectively. Conclusion: RV is one of the predominant pathogens in ARIs cases in Luohe City, Henan Province, from 2017 to 2022. Multiple types of RV co-circulate without any apparent dominant type.

[The current situation and influencing factors of depersonalization in clinical nurses].

Objective: To investigate the depersonalization status and to analyze the effect of workplace incivility perception, intrusive rumination and fear of negative evaluation on depersonalization in clinical nurses. Methods: In May 2019, 10 cities were selected as sampling cities by the method of grabbing random ball in Henan Province and Fujian Province. Using the stratified sampling, clinical nurses were selected as the research objects for a questionnaire survey in 22 tertiary hospitals and 23 secondary hospitals, included 1200 nurses. A total of 1200 questionnaires were issued and collected, and 1159 valid questionnaires were collected with effective recovery of 96.6%. Clinical nurses were investigated by Workplace Incivility Scale, Event Related Rumination Inventory, Fear of Negative Evaluation Scale, Maslach Burnout Inventory-General Survey. The demographic characteristics of nurses' depersonalization were compared and analyzed with t test and single factor analysis of variance. The influence mechanism of workplace incivility perception, intrusive rumination and fear of negative evaluation on depersonalization was analyzed with Bootstrap. Results: Depersonalization scores were (9.3±2.6) points, 467 of those had depersonalization symptoms in clinical nurses (40.3%). The scores of depersonalization of those with <3 years of service [ (10.5±2.9) points] was higher than those with 3-10 years [ (9.1±2.8) points] and 11-31 years [ (9.0±2.9) points]. The scores of depersonalization of those with monthly earning of <3000 yuan [ (10.1±2.8) points] was higher than those with 3000-7999 yuan [ (8.4±2.7) points] and 8000-12000 yuan [ (8.0±2.9) points]. The scores of depersonalization of clinical nurses in surgical departments [ (10.0±2.9) points] was higher than those in non-surgical departments [ (8.7±2.6) points]. The scores of depersonalization of clinical nurses in tertiary hospitals [ (10.0±2.7) points] was higher than those in secondary hospitals [ (8.6±2.8) points]. The differences were statistically significant (P<0.05). Workplace incivility perception affected depersonalization through the single mediating role of intrusive rumination, fear of negative evaluation and the chain mediating role of intrusive rumination and fear of negative evaluation (ß=0.16, 0.17, 0.07, 95%CI: 0.15-0.20, 0.15-0.21, 0.03-0.09, P<0.05) . Conclusion: Workplace incivility perception directly or through the independent mediating effects of intrusive rumination or fear of negative evaluation, and the chain mediating effects of intrusive rumination and fear of negative evaluation influences the depersonalization of clinical nurses.

[Analysis of the clinical predictive value of lactate on the prognosis of patients with acute-on-chronic liver failure combined with infection].

Objective: To explore the predictive value of lactic acid for the adverse prognostic outcomes in patients with acute-on-chronic liver failure combined with infection. Methods: A retrospective analysis was conducted on the clinical data of 208 cases of ACLF combined with infection who were hospitalized from January 2014 to March 2016. Patients were divided into a survival group (n = 83) and a mortality group (n = 125) according to the results of a 90-day follow-up. The clinical data were statistically analyzed between the two groups. Multivariate logistic regression with two categorical variables was used to analyze the independent risk factors for 90-day disease mortality and establish a new prediction model. The receiver operating characteristic curve (ROC curve) was used to evaluate the predictive value of lactic acid, the MELD score, the MELD-Na score, lactic acid combined with the MELD score, lactic acid combined with the MELD-Na score, and the new model. Results: The 90-day mortality rate of 208 cases of ACLF combined with infection was 60.1%. There were statistically significant differences in white blood cell count, neutrophil count, total bilirubin (TBil), serum creatinine (Cr), blood urea nitrogen (BUN), blood ammonia, the international normalized ratio (INR), lactic acid (LAC), procalcitonin, the MELD score, the MELD-Na score, hepatic encephalopathy (HE), acute kidney injury (AKI), and bleeding between the two groups. Multivariate logistic regression analysis showed that TBil, INR, LAC, HE, and bleeding were independent risk factors for 90-day mortality in patients with ACLF combined with infection. After the establishment of MELD-LAC, MELD-Na-LAC, and a new prediction model, the ROC curve revealed that the AUC (95% confidence interval) of MELD-LAC and MELD-Na LAC were 0.819 (0.759 ~ 0.870) and 0.838 (0.780 ~ 0.886), respectively, and was superior than the MELD score [0.766 (0.702 ~ 0.823)] and MELD-Na score [0.788 (0.726 ~ 0.843)], with P < 0.05, while the new model had an AUC of 0.924, the sensitivity of 83.9%, specificity of 89.9%, and accuracy of 87.8%, which was higher than LAC, MELD score, MELD-Na score, MELD-LAC, and MELD-Na-LAC (P < 0.01). Conclusion: Lactic acid is an independent risk factor for mortality in patients with ACLF combined with infection, and it improves the clinical predictive value of MELD and MELD-Na for the prognosis of mortality.

[Computer simulation of molecular docking between methylene blue and some proteins of Porphyromonas gingivalis].

OBJECTIVE: To study the binding target of photosensitizer and bacteria in antimicrobial photodynamic therapy with computer-simulated target prediction and molecular docking research methods and to calculate the binding energy. METHODS: The protein names of Porphyromonas gingivalis (Pg) were obtained and summarized in Uniprot database and RCSB PDB database; the structure diagrams of methy-lene blue were screened in SciFinder database, PubChem database, ChemSpider database, and Chemical Book, and ChemBioDraw software was used to draw and confirm the three-dimensional structure for target prediction and Cytoscape software was used to build a visual network diagram; a protein interaction network was searched and built between the methylene blue target and the common target of Pg in the String database; then we selected FimA, Mfa4, RgpB, and Kgp K1 proteins, used AutoDock software to calculate the docking energy of methylene blue and the above-mentioned proteins and performed molecular docking. RESULTS: The target prediction results showed that there were 19 common targets between the 268 potential targets of methylene blue and 1 865 Pg proteins. The 19 targets were: groS, radA, rplA, dps, fabH, pyrG, thyA, panC, RHO, frdA, ileS, bioA, def, ddl, TPR, murA, lepB, cobT, and gyrB. The results of the molecular docking showed that methylene blue could bind to 9 sites of FimA protein, with a binding energy of -6.26 kcal/mol; with 4 sites of Mfa4 protein and hydrogen bond formation site GLU47, and the binding energy of -5.91 kcal/mol, the binding energy of LYS80, the hydrogen bond forming site of RgpB protein, was -5.14 kcal/mol, and the binding energy of 6 sites of Kgp K1 protein and the hydrogen bond forming site GLY1114 of -5.07 kcal/mol. CONCLUSION: Computer simulation of target prediction and molecular docking technology can initially reveal the binding, degree of binding and binding sites of methylene blue and Pg proteins. This method provides a reference for future research on the screening of binding sites of photosensitizers to cells and bacteria.

Efficacy and safety of endothelin receptor antagonists in type 2 diabetic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

AIM: To analyse the efficacy and safety of endothelin receptor antagonists for people with diabetic kidney disease. METHODS: Randomized controlled trials comparing endothelin receptor antagonists with placebo in people with diabetic kidney disease were identified through PubMed, Embase and the Cochrane Library. We used a random-effect model to calculate the mean difference or risk ratio with the 95% CI. RESULTS: Seven studies with a total of 4730 participants were included. Overall, endothelin receptor antagonists significantly reduced albuminuria compared with placebo (standardized mean difference -0.48, 95% CI -0.64 to -0.33). Atrasentan, in particular, effectively reduced albuminuria (standardized mean difference -0.58, 95% CI -1.00 to -0.17) and the risk of composite renal endpoints (risk ratio 0.65; 95% CI 0.49 to 0.88), with insignificant change in the rate of congestive heart failure (risk ratio 1.40, 95% CI 0.76 to 2.56) and mortality (risk ratio 1.11, 95% CI 0.77 to 1.61). In contrast, although avosentan reduced albuminuria (standardized mean difference -0.47, 95% CI -0.57 to -0.36) and the risk of composite renal endpoints (risk ratio 0.63, 95% CI 0.42 to 0.94), it was associated with a significant increase in congestive heart failure risk (risk ratio 2.61, 95% CI 1.36 to 5.00) and an insignificant increase in mortality risk (risk ratio 1.50, 95% CI 0.81, 2.78). No significant change in efficacy or safety outcomes with bosentan was detected. Dose-response analysis indicated that 0.75 mg/day atrasentan is expected to be optimal for renoprotection, with maximal albuminuria reduction and minimal fluid retention events. CONCLUSIONS: Among the endothelin receptor antagonists, atrasentan and avosentan, but not bosentan, are effective for renoprotection in people with diabetic kidney disease. Compared with other types and doses, atrasentan 0.75 mg/day is the most promising, with maximal albuminuria reduction and minimal fluid retention. Vigilant monitoring of congestive heart failure risk is needed in future clinical practice. (PROSPERO registration no. CRD42020169840).

Lesion-aware convolutional neural network for chest radiograph classification.

AIM: To investigate the performance of a deep-learning approach termed lesion-aware convolutional neural network (LACNN) to identify 14 different thoracic diseases on chest X-rays (CXRs). MATERIALS AND METHODS: In total, 10,738 CXRs of 3,526 patients were collected retrospectively. Of these, 1,937 CXRs of 598 patients were selected for training and optimising the lesion-detection network (LDN) of LACNN. The remaining 8,801 CXRs from 2,928 patients were used to train and test the classification network of LACNN. The discriminative performance of the deep-learning approach was compared with that obtained by the radiologists. In addition, its generalisation was validated on the independent public dataset, ChestX-ray14. The decision-making process of the model was visualised by occlusion testing, and the effect of the integration of CXRs and non-image data on model performance was also investigated. In a systematic evaluation, F1 score, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) metrics were calculated. RESULTS: The model generated statistically significantly higher AUC performance compared with radiologists on atelectasis, mass, and nodule, with AUC values of 0.831 (95% confidence interval [CI]: 0.807-0.855), 0.959 (95% CI: 0.944-0.974), and 0.928 (95% CI: 0.906-0.950), respectively. For the other 11 pathologies, there were no statistically significant differences. The average time to complete each CXR classification in the testing dataset was substantially longer for the radiologists (∼35 seconds) than for the LACNN (∼0.197 seconds). In the ChestX-ray14 dataset, the present model also showed competitive performance in comparison with other state-of-the-art deep-learning approaches. Model performance was slightly improved when introducing non-image data. CONCLUSION: The proposed LACNN achieved radiologist-level performance in identifying thoracic diseases on CXRs, and could potentially expand patient access to CXR diagnostics.

[The application of Voriconazole in 76 patients with cirrhosis at Child-Pugh C stage complicated by invasive fungal infection].

Objective: To investigate the safety and efficacy of voriconazole in the patients with cirrhosis at Child-Pugh C stage complicated by invasive fungal infection(IFI). Methods: A retrospective collection of medical records of 76 patients with cirrhosis at Child-Pugh C stage complicated by IFI who were admitted to our hospital, from August 2014 to August 2017 was carried out. All the 76 patients who used voriconazole to treat IFI were divided into recommended dose group for hepatic insufficiency(56 cases) and routine dose group(20cases). The two groups were observed and compared in terms of the voriconazole's plasma concentrations, the outcomes of IFI and the rate of untoward reactions. The liver functional indicators were also compared between before and after treatment each group. We used Student's t test, Z test, chi-square test, or Fisher's exact test, as appropriate, for statistical analysis. Results: Both groups had good performance and low frequencies of side effects in the treatment of IFI, but there were also significant differences in the plasma concentrations of voriconazole and the incidence of untoward reactions between the two groups(P = 0.008 and P = 0.022). There commended dose group for hepatic insufficiency had lower adverse effect rate. The levels of direct bilirubin, alanine aminotransferase and aspartate aminotransferase were significantly lower after treatment of IFI in the recommended dose group for hepatic insufficiency(P < 0.05). Conclusion: In our research, it is relatively safe and effective to use voriconazole to treat IFI in the patients with cirrhosis at Child-Pugh C stage if according to the recommended dose regimen for cirrhosis at Child-Pugh A,B stage.

[Bilateral superior cervical ganglionectomy attenuates cardiac remodeling and improves cardiac function in pressure-overloaded heart failure mice].

Objective: To investigate the effect of bilateral superior cervical ganglionectomy on cardiac remodeling and function in pressure-overloaded heart failure (HF) mice. Methods: Pressure-overloaded HF mouse model was produced by severe thoracic aorta banding (sTAB). Bilateral superior cervical ganglionectomy (SCGx) was performed 2 weeks after sTAB. Twenty four 6-week-old male C57BL/6 mice were randomized divided into 4 groups (n=6 each): control group: sham sTAB+sham SCGx; denervated group: sham sTAB+SCGx; HF group: sTAB+sham SCGx; denervated HF group: sTAB+SCGx. Cardiac function was measured by echocardiography at week 0, 1, 2, and 4 after sTAB, respectively. All mice were sacrificed at the end of week 4 and heart tissues were harvested. HE and Masson staining were performed. Immunohistochemical staining (IHC) for tyrosine hydroxylase (TH), adrenergic receptor ß1 (AR-ß1) and CD68 was performed. Western blot was used to determine the protein expression level of TH, B type natriuretic peptide (BNP), and AR-ß1. Results: Left ventricular ejection fraction (LVEF) declined continuously in HF group. LVEF was similar between denervated HF group and control group at various time points (P>0.05). LVEF was significantly higher in denervated HF group than in HF group at the end of week 4 (P<0.05). HE staining showed that cross sectional cardiomyocyte area was significantly larger in HF group than in control group and denervated HF group (P<0.05), which was similar between denervated HF group and control group (P>0.05). Masson staining showed that fibrosis level was significantly lower in denervated HF group than in HF group (P<0.05). IHC showed that TH+nerves and CD68+ macrophages were significantly increased in HF mice as compared to control mice (P<0.05), whereas this change was abolished in denervated HF group. AR-ß1 was significantly down-regulated in HF group compared with control group (P<0.05), which was not affected by denervation (P>0.05). Western blot demonstrated that the expression level of TH and BNP was significantly higher in HF group compared with the control group (P<0.05), whereas this difference was diminished in denervated HF group (P>0.05). Conclusion: Bilateral superior cervical ganglionectomy can reduce sympathetic innervation and macrophage infiltration in pressure overloaded failure heart, thus attenuate cardiac remodeling and improve cardiac function.

[Analysis of magnetic resonance imaging characteristics in Chinese patients with myelin oligodendrocyte glycoprotein antibody associated disorders].

Objective: To investigate the magnetic resonance imaging (MRI) characteristics in the brain and spinal cord of Chinese patients with myelin oligodendrocyte glycoprotein antibodies associated diseases (MOGAD). Methods: Forty nine MOGAD patients with seropositive MOG-IgG and 58 AQP4-IgG positive patients were enrolled in this study. The characteristics of brain and spinal cord MRI were retrospectively analyzed. Results: There was no significant difference in the proportion of abnormal brain MRI of the two groups (69.4% vs 65.5%, P=0.177) , while the proportion of abnormal spinal cord MRI of the AQP4-IgG positive group was significantly higher than that in the MOG-IgG positive group (84.5% vs 36.7%, P=0.001) . The proportion of MOG-IgG positive patients with subcortical white matter lesions and large lesions in the brain MRI was significantly higher than that in AQP4-IgG positive group (48.9% vs 13.8%, P=0.003, 46.9% vs 12.1%, P=0.000) . The longitudinally extensive transverse myelitis in spinal cord MRI of AQP4-IgG positive group was significantly higher than that in the MOG-IgG group (70.7% vs 24.5%, P=0.002) . In addition, the proportion of MOG-IgG positive child patients with large lesions in the brain was significantly higher than that in AQP4-IgG positive child patients (76.9% vs 20.0%, P=0.047) . Conclusion: Demyelinating MRI lesions caused by MOG-IgG are heterogeneous, and could lead to a wide range of clinical phenotypes which is significantly different from those with AQP4-IgG.

[Clinical analysis of mediastinal lymph node dissection through sternotomy approach in the treatment of papillary thyroid carcinoma with mediastinal lymph node metastasis].

Objective: To investigate the rule of mediastinal lymph node metastasis of papillary thyroid carcinoma and the application of therapeutic mediastinal lymph node dissection through the sternotomy approach in the treatment of mediastinal lymph node metastasis of papillary thyroid carcinoma. Methods: All cases of papillary thyroid carcinoma with mediastinal lymph node metastasis treated through sternotomy cooperated by thoracic surgeons and head and neck surgeons from January 2006 to January 2017 in Cancer Hospital of Chinese Academy of Medical Sciences were included in this study. The distribution, metastasis rate, metastasis degree, surgical method, surgical complications and postoperative survival of patients with mediastinal lymph node metastasis were retrospectively analyzed. Results: A total of 31 patients (16 males and 15 females) with papillary thyroid cancer with mediastinal lymph node metastasis, with a median age of 46 (19-65) years, were enrolled in the group. Partial upper sternotomy was used in 28 cases, and total sternotomy was used in 3 cases. The mediastinal lymph nodes of papillary thyroid carcinoma metastasized farthest to the station 6, and the lymph node metastasis rate of each group from high to low was: 2R (61%), 1R (39%), 3A (39%), 1L (16%), 2L (10%), 4R (10%), 5 (3%) and 6 (3%). No metastasis was observed in station 3P, 4L and 7. In addition, the degree of lymph node metastasis at station 2R was the highest, reaching 35% (77/219). Extra-nodal invasion of mediastinal metastatic lymph nodes in thyroid papillary carcinoma is common (23%), easily fuses into masses (23%) and invades peripheral vascular nerves (26%). Up to 29% of blood transfusions are required during or after surgery due to oozing or bleeding (9/31). The 1-, 3-, 5-and 10-year survival rates of patients undergoing surgical treatment were 94%, 94%, 87% and 81%, respectively. Conclusion: Papillary thyroid carcinoma can metastasize to almost all mediastinal lymph nodes except station 3P, 4L and 7. Radical mediastinal lymph node dissection through sternotomy is an effective method for the treatment of mediastinal lymph node metastasis of thyroid papillary carcinoma.

[The pathological characteristics and outcomes of 40 surgically treated stage M1b non-small cell lung cancer patients].

Objective: Clinical evidences of surgically treated stage M1b non-small cell lung cancer (NSCLC) patients were limited. This study aimed to summarize the clinical data of these patients to explore the prognostic factors of this population. Methods: From January 1999 to December 2012, the clinical data of 40 stage M1b NSCLC patients, including 24 males and 16 females, who underwent surgery were collected by Cancer Hospital, Chinese Academy of Medical Sciences. Kaplan-Meier method, log rank test and Cox risk regression model were used to analyze the prognose of these patients and their influence factors. Results: A total of 40 patients were available for survival analysis. The Survival rates of the whole population at 1, 3 and 5 years were 70.0%, 40.0% and 22.5%, respectively. The median survival time (MST) was 31.5 months. The outcomes of 23 patients underwent primary tumor resection and local treatment of metastatic site (MST: 41.5 months) were significantly better than those of 13 patients with only primary tumor resection (MST: 15.5 months) and 4 patients with thoracic exploration (MST: 14.5 months) (P<0.05). Multivariate analysis showed that patients without pleural effusion, brain metastasis, chemotherapy and targeted therapy had a statistically better survival (P<0.05). Conclusions: The overall survivals of surgically treated stage M1b NSCLC patients appear encouraging, and some selected patients may even achieve a long-time survival. Multimodality treatment including surgical lung resection and radical treatment of metastasis should be considered for these patients.

[Effect of liraglutide on glucagon secretion in obese type 2 diabetic patients].

Objective: To investigate the effect of liraglutide on glucagon release in obese type 2 diabetes (T2DM). Methods: A multi-center, prospective, and self-comparison study was conducted in four hospitals in Qingdao. Twenty-four patients with T2DM were selected and treated with liraglutide for 12 weeks. Glucagon levels before and after treatment were detected before and 30 min, 60 min and 120 min after meals. Results: After 12 weeks of treatment, the overall level of glucagon decreased, in which the differences in glucagon levels at 30 min [(220±79) ng/L vs. (203±77) ng/L, P<0.05] and 60 min [(248±119) ng/L vs. (203±82)ng/L, P<0.05] reached significance, respectively, comparing to those before treatment. The area under the curve of glucagon after treatment was significantly lower than that before treatment (438±190 vs. 389±153, P<0.05). In contrast, after treatment, the overall level of C-peptide increased, especially the levels at 30 min [(1.53±1.02) nmol/L vs.(2.03±1.29) nmol/L], 60 min [(1.93±1.19) nmol/L vs. (2.48±1.75) nmol/L] and 120 min [(2.36±1.47) nmol/L vs. (2.96±1.84) nmol/L], all P<0.05. The area under C-peptide curve increased significantly (3.6±2.2 vs. 4.6±2.9, P<0.05). Fasting plasma glucose, postprandial 2 h plasma glucose and glycosylated hemoglobin A1c were all lower than before, and the differences were statistically significant (P<0.05). Waist circumference and body mass index were significantly lower than before (P<0.05). The amount of insulin used for the treatment decreased by approximately 55.1% compared with that before liraglutide, and the difference was statistically significant (P<0.05). Conclusions: Liraglutide inhibits glucagon secretion and lowers blood glucose. It can also reduce body weight, improve islet cell function and reduce insulin use in T2DM.

[Study on analgesic effect and mechanism of cinobufagin on rats with bone cancer pain].

Objective: To evaluate the analgesic effects of cinobufagin (CBG) on cancer-induced bone pain in rat and study the role of the muscarinic receptor M4 subtype (M4 mAChR) in its involvement. Methods: A total of 100 Female Sprague-Dawley rats were randomly divided into 5 groups (n=20): Sham group (group S), Cancer group (group A), Normal saline + CBG vehicle solution group (group ANS), Normal saline + 1 mg/kg CBG group (group ANC) and Tropicamide + 1 mg/kg CBG group (group ATC). Rats in group S were injected 10 µl Hank's solution into the left tibia medullar cavity, while rats in group A, ANS, ANC, and ATC were injected Walker 256 mammary cancer cells (10 µl, 2×10(7) cells/ml) into the same place. On day 9 post-inoculation rats in group ANS, ANC, and ATC were respectively received Saline (0.9%, 15 µl, i.t.), Saline (0.9%, 15 µl, i.t.)and 10 nmol of M4 mAChR blocker Tropicamide. After 10 min, ANS group, ANC group and ATC group were intraperitoneally injected with CBG vehicle solution, 1 mg/kg CBG and 1 mg/kg CBG. Model rats in each group were tested three times average as its basis pain threshold before injection cancer cells (T(0)). Mechanical withdrawal thresholds were measured on left hind paws, before 20 min (T(1)) and after 10 min (T(2)), 30 min (T(3)), 60 min (T(4)), 90 min (T(5)) and 120 min (T(6)) intrathecal injection. Left L4-L6 spinal dorsal horn and DRG were removed for determination of the expression of CaM-dependent kinaseⅡa (CaMKⅡa) and pCaMKⅡa by Western Blot after 60 min drug delivery. Results: At each time point from T(1) to T(6), the mechanical pain thresholds of group S were (8.69±0.45), (8.63±0.44), (8.65±0.39), (8.84±0.23), (8.80±0.14), (8.75±0.14) g, respectively, and the mechanical pain thresholds of group A were (6.37±0.30), (6.42±0.13), (6.29±0.17), (6.25±0.22), (6.34±0.33), (6.36±0.34) g, the difference was statistically significant (t=-16.41, -23.47, -30.25, -17.35, -19.52, -22.56, all P<0.01). At each time point from T(3) to T(5), the mechanical pain thresholds of the ANS group were (6.42±0.32), (6.39±0.34), (6.26±0.32) g, respectively, and the mechanical pain thresholds of the ANC group were (7.29±0.34), (7.81±0.15), (7.54±0.19) g, the difference was statistically significant (t=13.52, 14.22, 17.33, all P<0.01). At each time point from T(3) to T(5), compared with the ANC group, the mechanical pain threshold of the ATC group decreased (6.55±0.23), (6.84±0.46), (6.80±0.43) g, and the difference was statistically significant (t=-12.69, -11.26, -10.33, all P<0.01). At the time of T(4), the expressions of pCaMKⅡa in the spinal dorsal horn of each group were (0.67±0.05), (1.64±0.12), (1.57±0.14), (0.78±0.09), (1.39±0.11), respectively, and the expressions of pCaMKⅡa in DRG of each group were (1.65±0.39), (3.59±0.17), (3.43±0.32), (2.17±0.34), (2.95±0.23). The differences were statistically significant (F=179.89, 198.76, both P<0.01). Compared with the S group, the expression of pCaMⅡa was up-regulated in group A. Compared with ANS group, the expression of pCaMKⅡ a was down-regulated in ANC group. Compared with ANC group, the expression of pCaMK Ⅱ a was up-regulated in ATC group. The expression of CaMKⅡa in spinal dorsal horn and DRG was not statistically significant (F=1.25, 2.79, both P>0.05). Conclusions: These results demonstrated that M4mAChR participated in mediating the alleviation of hyperalgesia by cinobufagin in rats with bone cancer pain, and its mechanism may be related to pCaMKⅡa/CaMKⅡa signaling pathway.

[Expression of HLA-DP in patients with neuromyelitis optica spectrum disorders].

Objective: To investigate the effect of HLA-DP gene expression on the susceptibility and disease status of neuromyelitis optica spectrum disorders (NMOSD). Methods: A total of 86 NMOSD patients (52 in acute phase and 34 in remission phase), 52 multiple sclerosis (MS) patients (20 in acute phase and 32 in remission phase) diagnosed in Department of Neurology, the Third Affiliated Hospital of Sun Yat-sen University and 29 healthy controls were enrolled prospectively. Genotyping of HLA-DP was performed. The expression levels of HLA-DP molecules in peripheral blood B cells and monocytes were measured by flow cytometry. The transcription levels of HLA-DPB1 mRNA in peripheral blood mononuclear cells (PBMC) were measured by real time-PCR. The results were compared among different groups Results: There was no statistically significant difference of the distributions of HLA-DPB1*0501/HLA-DPB1*0501, HLA-DPB1*0501/X and X/X genotypes and the frequencies of allele of HLA-DPB1*0501 among NMOSD, MS patients and healthy controls (P=0.96 and 0.71, respectively). The expression levels of HLA-DP on the surface of B cells in NMOSD patients, especially in remission phase patients, were significantly higher than those in healthy controls(212±328 and 374±394 vs 55±57, P=0.049 and 0.002, respectively). The expression levels of HLA-DP on the surface of monocytes in NMOSD patients in acute phase were significantly higher than those in healthy controls(158±175 vs 65±90, P=0.025). The transcription levels of PMBC HLA-DPB1 mRNA in acute phase and remission phase of NMOSD patients were significantly higher than those in healthy controls (3.0±1.4 and 2.9±1.3 vs 1.5±1.4, P=0.000 and 0.003, respectively). The expression levels of HLA-DP molecules on the surface of peripheral blood B cells and monocytes and the transcription levels of PMBC HLA-DPB1 mRNA in MS patients at the acute and remission stages were not significantly different from those in healthy controls. The expression levels of HLA-DP molecules on the surface of B cells in patients with HLA-DPB1*0501/HLA-DPB1*0501, HLA-DPB1*0501/X and X/X genotypes were statistically different (P=0.017). Conclusion: HLA-DP gene transcription and molecular expression levels in antigen presenting cells may affect the susceptibility and disease status of NMOSD patients, while HLA-DPB1*0501 allele may affect the transcription and molecular expression levels of HLA-DP gene in antigen presenting cells.

[Role of vitamin K-dependent protein Gas6 in the expression of endothelial cell adhesion molecule-1 and chemokines induced by Porphyromonas gingivalis lipopolysaccharide].

OBJECTIVE: Growth-arrest-specific protein 6 (Gas6) is a vitamin K-dependent protein and involved in cell proliferation, survival, adhesion and migration . Also it has been shown to play an important role in the inflammatory response .The aim of present study was to investigate the role of Gas6 in the process of the expression of adhesion molecules and chemokines of human umbilical vein endothelial cells (HUVECs) induced by Porphyromonas gingivalis lipopolysaccharide(P.g-LPS). METHODS: After up-regulation and down-regulation of the expression of Gas6, the vascular endothelial cells were stimulated with 1 mg/L P.g-LPS for 3 h and 24 h. Real-time quantitative polymerase chain reaction(real-time PCR) was taken to detect the expression of the cell adhesion molecules:intercellular adhesion molecule-1 (ICAM-1) and E-selectin, as well as chemokines:interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1). Wound healing assay was taken to observe the migration ability of endothelium cells in different groups. RESULTS: After 3 h of P.g-LPS stimulation, the expression of adhesion molecules and chemokine in the down-regulation group was not significantly different from that in the control group,while in the up-regulation group the decrease of E-selectin, ICAM-1, IL-8 and MCP-1 was 81%±0%, 47%±3%, 76% ± 3%, 26% ± 6% respectively. After 24 h of P.g-LPS stimulation, the expression of adhesion molecules and chemokine in down-regulation group was significantly higher than that in control group (2.06±0.07, 1.99±0.11, 3.14±0.15, 1.84±0.03 flod), while these molecules in the down-regulation group was significantly lower than in the control group (29%±1%, 62%±3%, 69%±1%, 41%±2%). Differences were statistically significant (P<0.01). Wounding healing assay showed that down-regulation of Gas6 enhanced migration ability of endothelial cells while up-regulation of Gas6 weakened this ability,which was consistent with the trend of real-time PCR result. CONCLUSION: Down-regulation of the Gas6 gene enhanced the expression of ICAM-1, E-selectin, IL-8 and MCP-1 in HUVECs after P.g- LPS stimulating, while up-regulaiton of the Gas6 gene weakened the expression of ICAM-1, E-selectin, IL-8 and MCP-1 in HUVECs after P.g-LPS stimulating,suggesting that Gas6 may play a role in the process of endothelial cell adhesion.

[Analysis of clinical characteristics and prognosis of neuromyelitis optic spectrum disease complicated with malignant tumor].

Objective: To investigate the clinical features of patients involved with both malignant tumors and neuromyelitis optica spectrum disorders (NMOSD). Methods: The clinical data of 473 patients with NMOSD admitted into the Third Affiliated Hospital of Sun Yat-sen University and the Department of Neurology, Affiliated Hospital of Guizhou Medical University from June 2012 to March 2017 were retrospectively analyzed. Eleven NMOSD patients complicated with malignant tumors were screened out (3 with breast cancer, 2 with cervical cancer, 2 with rectal cancer, 2 with leukemia, 1 with nasopharyngeal carcinoma, 1 with thyroid cancer). Fifty patients without NMOSD were included as controls. Results: Most of the NMOSD patients were complicated by low-moderately differentiated squamous cell carcinoma/adenocarcinoma, mainly seen in breast, reproductive system, digestive system and hematological system. In terms of sex ratio and autoantibodies, the NMOSD patients with and without malignant tumors showed no significant difference. However, comparing to the patients without malignant tumor, the ones with malignant tumor showed a tendency of lower rate of initial brain symptoms and relapse rate, while with older onset age, higher initial EDSS score, protein content in cerebrospinal fluid (CSF), higher rates of initial symptom resulted from the focus of posterior region of the medulla and of significant image focus. Of the 8 NMOSD patients who diagnosed as malignant tumors in our hospital, 2 with breast cancer and 1 with cervical cancer had a good prognosis (follow-up EDSS score <3). All the 3 patients received aggressive surgery and chemotherapy treatment. However, the other 5 patients had poor prognosis (follow-up EDSS score ≥3 points). All the 11 patients received anti-tumor therapy, 4 patients had first NMOSD attack after anti-tumor treatment and no relapse. Only one case from the remaining 7 patients had relapse; Among the 9 patients received immunosuppressive therapy, 7 patients had no relapse, and 8 cases maintained stable; while, among all the 9 patients received immunosuppressive agents and anti-tumor therapy, only one case had relapse. Conclusions: There are some differences in the clinical features between the NMOSD patients with malignant tumors and the NMOSD patients without malignant tumors. Immunosuppressive therapy can improve the prognosis of patients with NMOSD and tumor, without increasing the risk of malignant tumor. The pathological type, staging and antitumor therapy may influence the prognosis of NMOSD. NMOSD patients with malignant tumor could be treated with anti-tumor and immunosuppressive agents if needed.

[Efficacy and safety of mycophenolate mofetil in treating neuromyelitis optica spectrum disorder: a multicenter, prospective, self-control study in Guangzhou City].

Objective: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in neuromyelitis optica spectrum disorder (NMOSD). Method: From September 2014 to February 2017, NMOSD patients with seropositive aquaporin4-IgG was enrolled through a multicenter, prospective study, and the annual recurrence rate (ARR), Expanded Disability Status Scale (EDSS) and MMF-related side effects before and after MMF treatment were compared. Results: Ninety patients were enrolled in the study. After being treated for a median of 12 months (1-30 months), the median ARR decreased from 1.1 pre-MMF to 0 post-MMF (P<0.001), and the median EDSS score decreased from 4.0 pre-MMF to 3.0 post-MMF (P<0.001). The EDSS score reduced significantly after 90 days' treatment (P<0.05). The main adverse events included the deranged liver enzymes (19%, 17/90), respiratory infection (11%, 10/90), urinary tract infection (6%, 5/90), varicella-zoster infection (6%, 5/90), anemia (6%, 5/90), leucopenia (6%, 5/90), diarrhea (2%, 2/90), hair loss (1%, 1/90); 11% (10/90) patients experienced severe adverse events, and 6% (5/90) patients discontinued MMF. Conclusions: MMF could significantly reduce the ARR and EDSS score of NMOSD. However, awareness on side effects should be raised.