Community-acquired respiratory infection is the commonest cause of sepsis presenting to emergency departments. Yet current experimental animal models simulate peritoneal sepsis with intraperitoneal (I.P.) injection of lipopolysaccharide (LPS) as the predominant route. We aimed to compare the progression of organ injury between I.P. LPS and intranasal (I.N.) LPS in order to establish a better endotoxemia murine model of respiratory sepsis. Eight weeks old male BALB/c mice received LPS-Escherichia coli doses at 0.15, 1, 10, 20, 40 and 100 mg per kg body weight (e.g. LPS-10 is a dose of 10 mg/kg body weight). Disease severity was monitored by a modified Mouse Clinical Assessment Score for Sepsis (M-CASS; range 0–21). A M-CASS score ≥ 10 or a weight reduction of ≥ 20%, was used as a criterion for euthanasia. The primary outcome was the survival rate (either no death or no need for euthanasia). The progression of disease was specified as M-CASS, body weight, blood glucose, histopathological changes to lung, liver, spleen, kidney, brain and heart tissues. Survival rate in I.P. LPS-20 mice was 0% (2/3 died; 1/3 euthanized with M-CASS > 10) at 24 h. Survival rate in all doses of I.N. LPS was 100% (20/20; 3–4 per group) at 96 h. 24 h mean M-CASS post-I.P. LPS-10 was 6.4/21 significantly higher than I.N. LPS-10 of 1.7/21 (Unpaired t test, P < 0.05). Organ injury was present at 96 h in the I.P. LPS-10 group: lung (3/3; 100%), spleen (3/3; 100%) and liver (1/3; 33%). At 24 h in the I.P. LPS-20 group, kidney injury was observed in the euthanized mouse. At 96 h in the post-I.N. LPS-20 group, only lung injury was observed in 2/3 (67%) mice (Kruskal-Wallis test with Dunn’s, P < 0.01). At 24 h in the post-I.N. LPS-100 group all (4/4) mice had evidence of lung injury. Variable doses of I.N. LPS in mice produced lung injury but did not produce sepsis. Higher doses of I.P. LPS induced multi-organ injury but not respiratory sepsis. Lethal models of respiratory virus, e.g., influenza A, might provide alternative avenues that can be explored in future research.

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

OBJECTIVE: To investigate the prevalence of comorbid depression and anxiety and to evaluate the effect of psychological interventions among schistosomiasis patients in China, so as to provide insights into improvements of psychological health among schistosomiasis patients. METHODS: Publications pertaining to comorbid depression and anxiety and psychological interventions among Chinese schistosomiasis patients were retrieved in electronic databases, including CNKI, Wanfang Data, PubMed, Web of Science, and Embase. The prevalence of comorbidity, psychological interventions, and scores for the Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) before and after psychological interventions among Chinese schistosomiasis patients were extracted. The prevalence of comorbid depression and anxiety was investigated among Chinese schistosomiasis patients using a meta-analysis, and the effect of psychological interventions for depression and anxiety was evaluated. RESULTS: A total of 231 publications were retrieved, and 14 publications that met the inclusion and exclusion criteria were included in the final analysis, including 2 English publications and 12 Chinese publications. Meta-analysis showed that the prevalence rates of comorbid depression and anxiety were 61% [95% confidential interval (CI): (48%, 72%)] and 64% [95% CI: (42%, 81%)] among Chinese schistosomiasis patients. Both the SDS [1.45 points, 95% CI: (1.30, 1.60) points] and SAS scores [2.21 points, 95% CI: (2.05, 2.38) points] reduced among Chinese schistosomiasis patients after psychological interventions than before psychological interventions, and the SDS [-0.47 points, 95% CI: (-6.90, -0.25) points] and SAS scores [-1.30 points, 95% CI: (-1.52, -1.09) points] reduced among Chinese schistosomiasis patients in the case group than in the control group. CONCLUSIONS The comorbid anxiety and depression are common among Chinese schistosomiasis patients, and conventional psychological interventions facilitate the improvements of anxiety and depression among schistosomiasis patients.
Humans ; Depression/therapy* ; Psychosocial Intervention ; Prevalence ; Anxiety/therapy* ; Comorbidity ; Schistosomiasis/therapy*

Objective: This study aimed to determine the independent and joint associations of sedentary time (ST) and physical activity (PA) with metabolic syndrome (MetS) and its components among Chinese adults. Methods: The study analyzed data from 4,865 adults aged ≥ 18 years who participated in the 2009 and 2015 China Health and Nutrition Surveys (CHNS). Four types of leisure ST and three types of PA self-reported at baseline were collected. Multivariable logistic regressions were used to determine the independent and joint associations of ST and PA with the odds of MetS or its components. Results: For independent effects, higher levels of television time and total leisure ST was associated with higher MetS risk [odds ratio ( Conclusions MVPA and total PA have independent preventive effects, and sedentary behavior (mainly watching TV) has an unsafe effect on MetS and its components. Strengthening the participation of MVPA and combining the LPA to replace the TV-based ST to increase the total PA may be necessary to reduce the prevalence of MetS in Chinese adults.
Adult ; Aged ; Aged, 80 and over ; China/epidemiology* ; Exercise/statistics & numerical data* ; Female ; Humans ; Male ; Metabolic Syndrome/etiology* ; Middle Aged ; Nutrition Surveys ; Risk Factors ; Sedentary Behavior ; Young Adult

Guizhi Fuling capsule (GFC), a traditional Chinese medicine (TCM) with effects of promoting blood circulation and dissipating blood stasis, has been widely used in the clinic. Because of the complex matrix and various chemical structure types, quality control of GFC remains great challenge. In the present study, an ultra performance liquid chromatography hybrid triple-quadrupole mass spectrometry (UPLC-QQQ MS) method with ultrafast positive/negative ionization switching was developed for simultaneous determination of 18 bioactive components in GFC, including methyl gallate, ethyl gallate, oxypaeoniflorin, benzoic acid, albiflorin, paeonolide, paeoniflorin, 1, 2, 3, 4, 6-pentagalloylglucose, mudanpioside C, benzoyloxypaeoniflorin, benzoylpaeoniflorin, pachymic acid, amygdalin, cinnamaldehyde, paeonol, cinnamic acid, 4-hydroxybenzoic acid, and gallic acid. Separation was performed on an Agilent Zorbax Extend-C18 column (2.1 mm × 50 mm, 1.8 μm), using a gradient elution with acetonitrile and water containing 0.1% formic acid. Cholic acid was selected as the internal standard. This newly developed method was fully validated for linearity, precision, accuracy, and stability, and then applied to quality assessment of GFC. Finally, the batch-to-batch reproducibility of GFC samples was evaluated by the cosine ration and Euclidean distance method, which showed high quality consistency. The results demonstrated that the developed method pro vided a reasonable and powerful manner for quality control of GFC.
Chemical Fractionation ; methods ; Cholic Acid ; standards ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Drugs, Chinese Herbal ; analysis ; chemistry ; Quality Control ; Reference Standards ; Reproducibility of Results ; Tandem Mass Spectrometry

Overexpressing of ATP-binding cassette (ABC) transporters is the essential cause of multidrug resistance (MDR), which is a significant hurdle to the success of chemotherapy in many cancers. Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR. Olmutinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has been approved in South Korea for advanced EGFR T790M-positive non-small cell lung cancer (NSCLC). Here, we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABC transporter subfamily G member 2 (ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [I]-iodoarylazidoprazosin (IAAP). However, olmutinib neither altered ABCG2 expression at protein and mRNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly, olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.

Objective: To analyze the spatial distribution and identify the high risk areas of pulmonary tuberculosis at the township level in Beijing during 2005-2015. Methods: Data on pulmonary tuberculosis cases was collected from the tuberculosis information management system. Global autocorrelation analysis, local indicators of spatial association and Kulldorff's Scan Statistics were applied to map the spatial distribution and detect the space-time clusters of the pulmonary tuberculosis cases during 2005-2015. Results: Spatial analysis on the incidence of pulmonary tuberculosis at the township level demonstrated that the spatial autocorrelation was positive during the study period. The values of Moran's I ranged from 0.224 3 to 0.291 8 with all the P values less than 0.05. Hotspots were primarily distributed in 8 towns/streets as follows: Junzhuang, Wangping, Yongding and Tanzhesi in Mentougou district, Yancun in Fangshan district, Wangzuo town in Fengtai district, Tianqiao street in Xicheng district and Tianzhu town in Shunyi district. Spatiotemporal clusters across the entire study period were identified by using Kulldorff's spatiotemporal scan statistic. The primary cluster was located in Chaoyang and Shunyi districts, including 17 towns/streets, as follows: Cuigezhuang, Maizidian, Dongfeng, Taiyanggong, Zuojiazhuang, Hepingjie, Xiaoguan, Xiangheyuan, Dongba, Jiangtai, Wangjing, Jinzhan, Jiuxianqiao, Laiguangying, Sunhe towns/streets in Chaoyang district, Houshayu and Tianzhu town in Shunyi district, during January to December 2005. Conclusion: Incidence rates of pulmonary tuberculosis displayed spatial and temporal clusterings at the township level in Beijing during 2005-2015, with high risk areas relatively concentrated in the central and southern parts of Beijing.
Beijing ; China ; Cluster Analysis ; Humans ; Incidence ; Spatial Analysis ; Spatio-Temporal Analysis ; Tuberculosis ; Tuberculosis, Pulmonary/ethnology*

Objective: To investigate the association between people who were under lack of care in childhood and the development of cognitive impairment in their middle-aged and elderly life spans. Methods: Based on the baseline survey data of the third phase of "Guangzhou Biobank Cohort study" conducted from January 2007 to January 2008, 9 223 residents aged ≥50 years with records on Mini Mental State Examination (MMSE) were included in a retrospective survey on received childhood care of their early lives. Questions would include: feelings of care and support from their close relatives during childhood, the status of separation from their mothers for ≥1 year, and the current status of their parents. Linear regression, unconditional and multinomial logistic regression models were used to analyze the associations between the received childhood care and cognitive function (i.e., MMSE scores and cognitive impairment) in middle and old age, of this population under study. Results: After adjusting for age, gender, education, place of residence, marital status, physical activity, smoking, drinking, occupation, personal income, childhood socioeconomic position and depressive symptoms etc., factors as feeling lack of concern and support from close relatives (LC), status of separation from the mother for ≥1 year (SM), and the current status of their parents etc., were all negatively associated with the MMSE score when in middle and old age, with partial regression coefficient β (95%CI) as -0.44 (-0.65- -0.23), -0.26 (-0.38- -0.14) and -0.61 (-0.96- -0.27), respectively. The presence of LC, SM or PD were associated with the increased risks of cognitive impairment, and the adjusted odds ratio OR (95%CI) appeared as 1.43 (1.15-1.78), 1.26 (1.08-1.47) and 1.64 (1.16-2.31) respectively in all the participants, but 1.27 (1.01-1.62), 1.29 (1.09-1.55) and 1.75 (1.19-2.55) respectively, in those with education level of primary school or below. In those with secondary school education or above, only the presence of item A was associated with an increased risk of cognitive impairment (OR=2.26, 95%CI: 1.41-3.50). Conclusion: We noticed that 'lack of care' in childhood was associated with cognitive impairment during middle and old age, mainly in those population with lower education.
Aged ; Cognition/physiology* ; Cognition Disorders/physiopathology* ; Cognitive Dysfunction/physiopathology* ; Humans ; Linear Models ; Middle Aged ; Odds Ratio ; Retrospective Studies ; Surveys and Questionnaires

Objective To investigate the clinical characteristics and risk factors of intra- and post-operative reperfusion injury following surgical evacuation of epidural hematoma. Methods Clinical and radiographic data of 206 patients with cerebral herniation presented with an epidural hematoma and underwent surgical evacuation in our hospital from June 2009 to June 2015, were retrospectively analyzed; risk factors of intra- and post-operative reperfusion injury were analyzed by multi-factor and non-conditional Logistic regression analyses. Results A total of 12 patients with acute epidural hematoma and concurrent cerebral herniation developed reperfusion injury after hematoma evacuation; 7 patients (58.3%) were within 15-30 min after surgical evacuation intraoperatively and 5 patients (41.7%) were at an early stage within 6 h after operation. Local vascular cerebral edema, effusion, or even spot and patchy hemorrhage in the compressed cerebral parenchyma underneath the epidural hematoma were depicted by craniocerebral CT/MR imaging examination and further CT perfusion examination confirmed the local hyperperfusion-induced lesions. These 12 patients had an unsatisfactory clinical outcome with a high ratio of bad prognosis (58.3%, 7/12). Regression analyses indicated that the described surgical complication was significantly associated with duration of preoperative cerebral herniation (≥120 min, odds ratio [OR]=61.617, P=0.001), hematoma thickness (≥40 mm, OR=10.051, P=0.018). Conclusions Cerebral herniation longer than 120 min and hematoma thickness greater than 40 mm are high-risk factors associated with intra- and post-operative reperfusion injury. Controlled decompressive surgical strategy is helpful for a good recovery of cerebrovascular autoregulation function and thereby reduces the occurrence of reperfusion injury.