Diabetic retinopathy, a prevalent and vision-threatening microvascular complication of diabetes mellitus, is the leading cause of blindness among middle-aged and elderly individuals. Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties. This study aimed to identify novel bioactive diterpenoids from S. pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy, both in vitro and in vivo. Three new ent-pimarane-type diterpenoids (1-3) and six known compounds (4-9) were isolated from the aerial parts of S. pubescens. Their structures were elucidated through spectroscopic data interpretation, and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism (ECD) spectra. Among these compounds, 14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene (5) exhibited the most potent protective effect against high glucose and interleukin-1β (IL-1β)-stimulated human retinal endothelial cells. Mechanistically, compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy, both in vivo and in vitro. These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S. pubescens, but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.
Diabetic Retinopathy/metabolism* ; Humans ; Oxidative Stress/drug effects* ; Animals ; Diterpenes, Kaurane/administration & dosage* ; Asteraceae/chemistry* ; Male ; Endothelial Cells/drug effects* ; Abietanes/administration & dosage* ; Molecular Structure ; Mice ; Anti-Inflammatory Agents/chemistry* ; Plant Extracts/chemistry* ; Mice, Inbred C57BL

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

2,6-dimethylbenzenamine was determined as a genotoxic impurity in lidocaine hydrochloride injection, and 2-chloro-N-(2,6- dimethylphenyl) acetamide was determined as potential genotoxic impurity. An LC-MS/MS method was established to research the profiling of genotoxic impurities in active pharmaceutical ingredients (API), homemade preparation and reference preparation on column Agilent ZORBAX Eclipse Plus C18(4.6 mm250 mm，5 μm). The results show that in the homemade preparation the 2,6-dimethylbenzenamine and the 2-chloro-N-(2,6-dimethylphenyl) acetamide may be degraded under oxidation condition and alkaline condition in addition to the introduction from API preparation process. This study provides guidance for genotoxic risk assessment and prescription process optimization of lidocaine hydrochloride.

Objective:To evaluate the accuracy of pRIFLE criterion and KDIGO criterion for the diagnosis of acute kidney injury (AKI) after radical operations for tetralogy of Fallot in children from the perspective of postoperative outcomes.Methods:A total of 375 children, aged<8 yr, undergoing radical operations for tetralogy of Fallot, were selected continuously and retrospectively. According to the pRIFLE and KDIGO diagnostic criteria, postoperative AKI was diagnosed, and the children were classified into different AKI grades. The prognostic parameters (postoperative mechanical ventilation time, duration of intensive care unit (ICU) stay, postoperative length of hospital stay, total costs of hospitalization, and in-hospital mortality, etc.) were collected, and the differences among different AKI grades were compared. Logistic regression method was used to analyze the risk factors for prolonged postoperative length of hospital stay (≥14 days) when two different criteria were used to diagnose AKI. The children diagnosed as non-AKI by KDIGO criterion were further confirmed using pRIFLE criterion, and the prognostic parameters in the children who were diagnosed as AKI and non-AKI were compared.Results:When two different criteria were used to diagnose AKI after radical resection for tetralogy of Fallot, the incidence was 56.8% (pRIFLE criterion) and 40.0% (KDIGO criterion). AKI diagnosed according to the two criteria was the independent risk factor for prolonged postoperative length of hospital stay, and the levels of all the prognostic parameters (postoperative mechanical ventilation time, duration of ICU stay, postoperative length of hospital stay, total costs of hospitalization, and in-hospital mortality) were significantly higher in AKI children than in non-AKI (AKI grade 0) children ( P<0.01). Among the 225 children diagnosed as non-AKI according to the KDIGO criterion, 63 cases were diagnosed as AKI and 162 cases as non-AKI according to the pRIFLE criterion, however, there was no significant difference in each prognostic parameter between children with AKI and non-AKI ( P>0.05). Conclusion:The pRIFLE criterion has a higher sensitivity, while the KDIGO criterion produces better accuracy when used to evaluate the diagnosis of AKI after radical operation for tetralogy of Fallot in children from the perspective of postoperative outcomes.

OBJECTIVE: To investigate enterovirus 71 (EV71)-induced of autophagy, apoptosis and the related signaling pathways in THP-1 macrophages. METHODS: THP-1 macrophages were infected with EV71 at the multiplicity of infection (MOI) of 0.1 for 2, 8 or 16 h, and the cell proliferation and toxicity were analyzed using CCK-8 kit. The intracellular viral nucleic acid in THP-1 macrophages were detected by fluorescence quantitative PCR, and the ultrastructural changes of the cells were observed using transmission electron microscopy. Cell apoptosis induced by EV71 infection was detected using Hoechst 33342 staining and AnnexinV/PI double staining. Western blotting was performed for analysis of changes in autophagy and apoptosis of the cells and in the expressions of the related proteins. The effect of EV71 infection on apoptosis of THP-1 macrophages incubated with 3-MA and Ac-DEVD-CHO inhibitor for 2 h was assessed using Western blotting. RESULTS: EV71 infection significantly lowered the cell survival rate of THP-1 macrophages at 2, 8 h and 16 h after the infection ( < 0.05). The total copy number of viral nucleic acid in THP-1 macrophages incubated with EV71 increased significantly and progressively over time ( < 0.01). Intracellular autophagosomes and virions could be seen in EV71-infected THP-1 macrophages. The total apoptotic rate of the infected cell also increased significantly over time ( < 0.01). EV71 infection significantly increased LC3 conversion (LC3-Ⅱ/ LC3-I) and the expression of cleaved caspase 3 protein and decreased the protein expressions of p62, Bcl-2 and caspase-3 ( < 0.01) without causing obvious changes in cleaved caspase-8 (>0.05). 3-MA significantly inhibited the EV71-induced autophagy of THP-1 macrophages and reduced LC3 conversion (LC3-Ⅱ/LC3-I) and p62 protein expression at 8 h after EV71 infection ( < 0.01). Compared with DMSO, Ac-DEVD-CHO significantly inhibited EV71-induced apoptosis of THP-1 macrophages (15.5% 7.7%, < 0.01). CONCLUSIONS EV71 not only can infect and replicate in THP-1 macrophages, but also induces autophagy and cell apoptosis possibly by activating LC3/p62 autophagy pathway and caspase apoptosis pathway.
Apoptosis ; Autophagy ; Cell Line ; Enterovirus A, Human ; Humans ; Macrophages

Objective We utilized a joint independent component analysis (Joint ICA), a novel method that combined rs?fMRI and DTI information, to describe comprehensive characteristics of brain functional activities and microstructural changes in the continuum of AD. Methods We employed a Joint ICA to calculate ALFF maps of fMRI data and FA maps of DTI data and fuse them in healthy controls (n=68), SCD (n=35), amnesic MCI (n=47) and AD (n=31). Besides, we applied one way ANOVA to detect the significant differences of joint components among groups, while controlling the age, gender, education, head motion, volumes of gray matter, white matter and CSF. Partial correlation analysis was used to test the relationships between joint ICs and cognitive measures. Results The results showed that there was no inner?group difference in HC and SCD groups (F=14.16, P<0.05). Compared to HC, SCD and AD groups, the ALFF component of aMCI group showed higher values in the bilateral cerebellum, bilateral precuneus, bilateral angular gyrus, bilateral frontal gyrus, bilateral temporal areas, thalamus and left insula. And in these regions, the ALFF of AD group was lower than HC. For the FA component map, same differences were found in the corpus callosum and limbic system. Furthermore, positive partial correlation between the IC weights and Mini?Mental State Examination (MMSE) scores was also found (r=0.29, P<0.01). Conclusions Multi?modal evaluation of AD has been implemented by using Joint ICA analysis of fMRI?DTI, which would contribute to early prediction, diagnosis, and even effective intervention in AD. These findings could help to explain the underlying mechanism of the disease progression.

Objective To evaluate the clinical efficacy of autologous whole blood injections (AWBI) combined with antihistamines for the treatment of patients with refractory chronic spontaneous urticaria and positive autologous serum skin test (ASST),to evaluate its effect on the expression of the high-affinity IgE receptor (FcεR Ⅰ) and CD63 on basophils,and to analyze the possible mechanism underlying the treatment of ASST-positive chronic urticaria with AWBI.Methods Eighty patients with ASST-positive chronic intractable urticaria were enrolled from Department of Dermatology,The First Hospital Affiliated to Army Medical University between November 2017 and June 2018,and randomly and equally divided into two groups by a random number table:AWBI group and control group were both conventionally treated with oral loratadine and ebastine,and AWBI group were additionally treated with AWBI once a week for 12 sessions.Before the treatment and after 12-week treatment,urticaria activity score of 7 days (UAS7) and dermatology life quality index (DLQI) in the two groups were evaluated.Among 30 patients in the AWBI group,flow cytometry was performed to determine the expression of FcεRⅠ and CD63 on the basophils in the peripheral blood at the baseline,weeks 4,8 and 12 after the initial treatment.Statistical analysis was carried out with GraphPad Prism 7.00 software by t test for the comparison of UAS7 or DLQI scores,Mann-Whitney U test for the comparison of FcεR Ⅰ α expression,paired Wilcoxon signed rank test for comparing FceR Ⅰ α or CD63 expression between two different time points,and Spearman correlation analysis for analyzing the correlation between FcεR Ⅰ α and CD63 expression.Results Before the treatment,no significant differences in UAS7 or DLQI scores were observed between the AWBI group and control group (UAS7:27.15 ± 4.53 vs.26.90 ± 5.22;DLQI:16.88 ± 6.01 vs.17.08 ± 6.79;both P ＞ 0.05).After 12-week treatment,UAS7 and DLQI scores both significantly decreased in the two groups compared with those before the treatment (all P ＜ 0.01),and were significantly lower in the AWBI group than in the control group (UAS7:14.25 ± 7.56 vs.19.93 ± 6.32;DLQI:8.48 ± 4.15 vs.13.93 ± 5.43;both P ＜ 0.01).At the baseline,weeks 4,8 and 12 after the initial treatment,the fluorescence intensities of FcεR Ⅰα on basophils (M [P25,P75]) in the AWBI group were 22 532 (16 740,29 220),16 911 (10 240,21 816),13 282 (7 600,16 848) and 11 466 (7 161,14 578) respectively,and the proportions of CD63+ basophils induced by ASST-positive serum (M [P25,P75]) in the AWBI group were 35.25％ (26.75％,49.13％),25.95％ (19.37％,37.54％),13.57％ (7.79％,19.57％) and 9.87％ (6.43％,16.52％) respectively.At week 4 after the initial treatment,the expression of FcεR Ⅰα and CD63 on basophils in the AWBI group both significantly decreased compared with those at the baseline (both P ＜ 0.01),but significantly increased compared with those at week 8 (both P ＜ 0.01).The changes in FcεR Ⅰ α expression from baseline to week 4,from week 4 to week 8,and from week 8 to week 12 were positively correlated with the changes in CD63 expression induced by ASST-positive serum (r =0.364,0.422,0.455,respectively,all P ＜ 0.05).Conclusion AWBI combined with antihistamines can improve the clinical symptoms of ASST-positive refractory chronic urticaria,likely by affecting the expression of FcεR Ⅰ and CD63 on basophils.

Objective: To analyze the clinical efficacy of thalidomide combined with TP regimen (taxol+cisplatin) in treatment of advanced gastric cancer. Methods: A total of 60 patients with advanced gastric cancer in the Affiliated Cancer Hospital of Zhengzhou University from February 2016 to March 2018 were enrolled. The patients were divided into two groups by using random number table method: the observation group (32 cases) taking thalidomide, oral administration 100 mg based on TP regimen before going to bed; the control group (28 cases) taking TP regimen chemotherapy only. Both groups received 75 mg/m² doses of cisplatin, intravenous infusion, 25 mg/m² per day, for 3 d. Paclitaxel dose was 150 mg/m², intravenous infusion for 1 day, 3-week was one course, and the efficacy was evaluated after at least 2 course of treatment. Results: The incidence of gastrointestinal adverse reactions including nausea and vomiting was 21.8% (7/32) in the observation group, and was 64.3% (18/28) in the control group, and the difference was statistically significant (χ ² = 11.051, P = 0.001), but there were no statistically significant differences in the incidence of morning faint, constipation, bone marrow suppression, liver and kidney injury and other adverse reactions between the two groups (all P > 0.05). The effective rates in the observation group and the control group were 43.8% (14/32) and 39.3% (11/28), respectively, and the disease control rates in the observation group and the control group were 84.4% (27/32) and 78.6% (22/28), respectively. There were no significant differences in the effective rates and the disease control rates between the two groups (χ ² = 0.122, P = 0.726; χ² = 0.336, P = 0.562). The improvement and significant improvement rate of sleeping quality, pain, Eastern Cooperative Oncology Group (ECOG) score was 71.9% (23/32), 53.1% (17/32), 56.2% (18/32), respectively in the observation group, and 17.9% (5/28), 14.3% (4/28), 21.4% (6/28), respectively in the control group, and the difference between the two groups was statistically significant (all P < 0.05). Conclusions Thalidomide combined with TP regimen in treatment of advanced gastric cancer patients can improve the efficacy of chemotherapy and the quality of life. It also has a good tolerance to side effects.

Objective: To explore the clinical characteristics, treatment strategy and prognosis of adenoid cystic carcinoma of the head and neck (ACCHN). Methods: A retrospective analysis of the clinical and follow-up treatment of 79 patients with ACCHN from June 2008 to July 2017 was conducted in the Cancer Hospital of Zhengzhou University. Results: A total of 79 ACCHN cases, including 31 males and 48 females. The age ranged from 19 to 77 (median, 52). The clinical manifestations of ACC were related to the locations of primary tumor.The mean size of the tumor was 2.6 cm (range from 1.5 to 7.7 cm). 50 of 79 patients with a definitive pathological diagnosis received surgical resection. 59 cases received chemotherapy and 62 cases received radiotherapy. With a median follow-up of 55 months, the 5-year, 10-year survival rate of these patients were 69.6% and 54.4%, respectively. Conclusions ACCHN is an uncommon neoplasm with the characteristics of epithelial nerve growth, being inclined to distant metastasis, and high early misdiagnosis rate. The clinical manifestation, imaging and pathological result are need to be combined together to diagnose ACCHN.