Objective To observe the effects of Xixin Decoction on the blood-brain barrier permeability and the expressions of P-glycoprotein(P-gp),cannabinoid receptor 1(CB1)and cannabinoid receptor 2(CB2)in hippocampal tissue of rapidly aging mice(SAMP8);To explore the possible mechanism of Xixin Decoction in the treatment of Alzheimer disease(AD).Methods Totally 60 SAMP8 mice were randomly divided into model group,probiotics group,and Xixin Decoction high-,medium-and low-dosage groups,with 12 mice in each group,another 12 SAMR1 mice were set as control group.The medicated groups received corresponding drugs by gavage for 10 weeks respectively,while the control group and model group were gavaged with equal volume of distilled water.Morris water maze test was used to detect the learning and memory ability of mice,the blood-brain barrier permeability was detected by Evans blue method,the contents of matrix metalloproteinase 9(MMP9),nuclear factor(NF)-κB and tumor necrosis factor-α(TNF-α)in serum were determined by ELISA,the expressions of P-gp,CB1 and CB2 in hippocampal tissue were detected by Western blot,P-gp expression in hippocampal tissue was detected by immunofluorescence staining.Results Compared with the control group,the learning and memory ability of mice in model group significantly decreased,Evans blue exudation in brain tissue significantly increased,the contents of MMP9,TNF-α and NF-κB in serum significantly increased,the expressions of P-gp and CB2 protein significantly decreased,the expression of CB1 protein significantly increased,with statistical significance(P<0.01,P<0.05).Compared with the model group,the learning and memory ability of mice in Xixin Decoction high-dosage group significantly increased,the Evans blue exudation in brain tissue significantly decreased,the contents of MMP9,TNF-α and NF-κB in serum significantly decreased,the protein expressions of P-gp and CB2 significantly increased,and the protein expression of CB1 significantly decreased,with statistical significance(P<0.01,P<0.05).Conclusion Xixin Decoction can improve the spatial learning and memory ability of AD model mice,and its mechanism is related to regulating the permeability of the blood-brain barrier and related protein expression,and inhibiting neuroinflammation.

ObjectiveTo observe the possible mechanism of Xixin Decoction （洗心汤， XXD） in the prevention and treatment of Alzheimer 's disease（AD）. MethodsFifty rapid aging model mice （SAMP8） were randomly divided into model group， probiotic group， high-， moderate- and low-dose group of XXD， with 10 mice in each group. Another 10 homologous anti-rapid aging mice （SAMR1） were set as control group. After 10 weeks of feeding， the control group and the model group were given 10 ml·kg^-1·d^-1 of distilled water by gavage， while the probiotic group （0.39 g·kg^-1·d^-1）， the high-dose group of XXD （5.08 g·kg^-1·d^-1）， the moderate-dose group of XXD （2.54 g·kg^-1·d^-1）， and the low-dose group of XXD （1.27 g·kg^-1·d^-1） were given corresponding drugs or decoctions by gavage， once a day in all groups. After 10 weeks of intragastric administration， Morris water maze was used to detect the spatial learning and memory ability of mice in each group. HE staining was used to observe the pathological changes of hippocampal CA3 region and colon. The levels of β-amyloid 1-42 （Aβ_1-42）， lipopolysaccharide （LPS）， serum amyloid A （SAA） and acetylcholine （ACH） in hippocampus and colon were detected by ELISA.The diversity of intestinal flora in mouse feces was detected by 16S rRNA sequencing. ResultsCompared to those in the control group， the levels of Aβ_1-42，LPS， SAA increased， while the level of ACH decreased in the model group （P＜0.05 or P＜0.01）. Compared to those in the model group， the escape latency period of the probiotic group was significantly shortened on the 2nd and 5th days， while the escape latency period was shortened， and the residence time in the target platform quadrant increased in the high-dose XXD group during the 2nd to 5th days； the escape latency period was shortened significantly in the moderate-dose XXD group on the 5th day （P＜0.05 or P＜0.01）. Compared to those in the model group， the hippocampal neuron cells in the high- and moderate-dose XXD groups were arranged more closely， with decreased levels of SAA， Aβ_1-42 and LPS， increased ACH level， Simpson and Shannon index （P＜0.05 or P＜0.01）； the arrangement of hippocampal neuron cells in the probiotic group and the low-dose XXD group was relatively loose； the proportions of Bacteroidetes and Prevotella were significantly reduced in the probiotic group and the high-dose XXD group， while that of Firmicutes and Lactobacillus significantly increased （P＜0.05 or P＜0.01）. Compared to those in the probiotic group and the high-dose XXD group， the number of goblet cells in the moderate-dose XXD group decreased， and the number of glands in the low-dose XXD group decreased with atrophy. The high-dose XXD group had decreased Aβ_1-42 level in the hippocampus， increased ACH level in thehippocampus and colon tissue， and decreased SAA in the colon tissue than the moderate- and low-dose XXD groups （P＜0.05 or P＜0.01）； moreover， the SAA level in the hippocampus was significantly higher in the low-dose XXD group than the high- and moderate-dose groups （P＜0.01）. ConclusionXXD can improve the spatial learning and memory ability of SAMP8， reduce the production and deposition of LPS， SAA and Aβ_1-42 in brain and intestine， and increase the content of ACH. The mechanism of its prevention and treatment of AD maybe related to regulating intestinal microecology， affecting flora diversity and improving inflammatory response.

The clinical data of 4 patients with acute eosinophilic pneumonia (AEP) diagnosed in the Department of Respiratory and Critical Care Medicine, Peking University Third Hospital were retrospectively analyzed. All 4 patients were males, aged 28, 34, 43 and 68 years respectively. The main manifestations were fever, cough and dyspnea. Three cases had a history of smoking and 1 case had a history of ulcerative colitis. The proportion of eosinophils in bronchoalveolar lavage fluid (BALF) was 85%, 93%, 41% and 50%, respectively. The proportion of eosinophils in peripheral blood was 53.3% (16.29×10 9/L), 25.1% (1.29×10 9/L), 4.8% (0.4×10 9/L) and 13.7% (1.55×10 9/L), respectively. Blood gas analysis (without supplemental oxygen) showed type I respiratory failure in 1 case, hypoxemia in 3 cases. The total IgE (normal range ≤ 100.0 KU/L) in peripheral blood of the 4 cases was>2 500.0 KU/L, 60.3 KU/L, 379.4 KU/L and 407.0 KU/L, respectively. HRCT showed diffuse distribution of lesions in both lungs, including ground glass opacity, patchy consolidation and centrilobular nodules. After diagnosis, all patients were treated with systemic glucocorticoids. Fever, cough and dyspnea, as well as the chest CT lesions were significantly improved after treatment. The patients were followed up for 29 months, 16 months, 18 months and 24 months respectively, without recurrence. AEP is a rare disease which is easy to be misdiagnosed as severe pneumonia and/or ARDS. Eosinophilia in peripheral blood is suggestive of the disease, and timely BALF cell differentials is important for early diagnosis.

Micheliolide is a kind of guaiacane sesquiterpene lactone from natural plants. It distributs in the root bark of Cephalantheropsis gracilis and Michelia compressa . Modern pharmacological studies show that ，micheliolide can play an anti-tumor role by inhibiting the proliferation of tumor cells ，regulating the apoptosis of tumor cells ，inducing autophagy of tumor cells ，and inhibiting invasion and metastasis of tumor cells. It can reduce the expression of inflammatory cytokines by regulating several related signaling pathways ，such as nuclear factor κB and phosphatidylinositol-3-hydroxykinase/protein kinase B ；it can play an immunomodulatory role by restoring the expression of immune-related factors in the body ；it can play a neuroprotective effect by reducing the accumulation of amyloid β-protein and inhibiting microglial activation ；it can play a liver protective role by reducing the inflammatory response and steatosis of hepatocytes ；its nephroprotective mechanism is related to the relief of the inflammatory response by regulating multiple pathways ；the mechanisms of its cardioprotective action include alleviating the inflammatory response and reducing the level of oxidative stress ，etc. In conclusion ，micheliolide is a compound of great development value.

Objective:To preliminarily observe the clinical efficacy of microwave hyperthermia combined with intensity-modulated radiotherapy (IMRT) and chemotherapy for patients with locally advanced gastric cancer.Methods:Forty patients who could not been operated or refused operation were enrolled in this clinical trial, who were confirmed as locally advanced proximal or distal gastric cancer by gastroscopy pathology and imaging. Radiotherapy was delivered by IMRT technology for 5 times per week with a total dose of 46 to 56 Gy (median dose of 50 Gy) in 25 to 28 fractions. Synchronous hyperthermia was given at 42 to 44℃ twice a week, 45 min/time. S-1 or capecitabine-based synchronous chemotherapy was performed, d1-14/3 weeks. The symptom remission rate, adverse reactions, objective remission rate (complete and partial remission) and survival were observed.Results:A total of 40 patients, aged between 56 and 83 years (median age of 71 years), were enrolled in this study. The male-to-female ratio was 7: 1. Among them, 38 cases (95%) showed symptom remission. The most common adverse reactions were grade 1-2 gastrointestinal reactions and leukopenia. The objective remission rate was 87.5%, the 2-year progression-free survival and overall survival rates were 68.6% and 70.5%, respectively.Conclusion:Preliminary findings demonstrate that microwave hyperthermia combined with chemoradiotherapy achieve satisfactory outcomes and yield tolerable toxicity in patients with locally advanced gastric cancer.

Objective:To explore the application value of enhanced recovery after surgery (ERAS) in colorectal cancer patients.Methods:From January 2017 to December 2018, 60 patients with colorectal cancer who admitted to the Second People′s Hospital of Lianyungang were selected and divided into ERAS group and control group according to the random digital table method, with 30 patients in each group.The inflammation, nutritional indicators, immune indicators and clinical manifestations before and after surgery in the two groups were compared.Results:At 1 d and 3 d after surgery, the C-reactive protein (CRP) levels in the ERAS group were (70.2±10.3)mg/L, (82.5±8.2)mg/L, respectively, which were lower than those in the control group [(81.5±9.9)mg/L, (110.2±12.9)mg/L] ( t=4.324, 9.911, all P<0.05). On the third day after operation, the levels of albumin and prealbumin in the ERAS group were (31.6±4.8)g/L, (196.8±40.6)g/L, respectively, which were higher than those in the control group [(28.0±5.8)g/L, (172.1±38.8)g/L]( t=2.621, 2.409, all P<0.05). The immune parameters(IgA, IgM, IgG, CD 4+, CD 4+ /CD 8+) in the ERAS group were higher than those in the control group( t=2.132, 2.223, 6.063, 4.253, 2.828, all P<0.05). The number of cases with thirsty and hunger on the day of surgery in the ERAS group was 3 cases and 7 cases, respectively, which were less than 21 cases and 25 cases of the control group(χ 2=22.500, 21.696, all P<0.05). The first exhaust time, defecation time and hospital stay time in the ERAS group were (36.2±12.1)h, (63.4±13.4)h and (9.5±3.2)d, respectively, which were shorter than those in the control group [(54.7±13.8)h, (96.5±18.8)h and (12.1±4.0)d] ( t=5.513, 7.845, 2.761, all P<0.05). The incidence of complications between the two groups had no statistically significant difference ( P>0.05). Conclusion:ERAS can significantly reduce the physical and psychological traumatic stress of patients with colorectal cancer, achieve rapid recovery, improve the treatment effect, shorten the length of hospital stay, reduce social and family burden, and provide a basis for the choice of clinical treatment program.

Objective:To investigate the basic knowledge of chronic obstructive pulmonary disease (COPD) among physicians in primary hospitals (county and township hospitals) in Shanxi province.Methods:A electronic questionnaire survey that included questions on basic knowledge, epidemiology, diagnosis and management of COPD was conducted. The questionnaire was distributed through Wechat communication by convenient sampling among physicians and respiratory specialists in primary hospitals in Shanxi province.Results:A total of 1 162 questionnaires were collected, among which 1 100 were valid (882 from county hospitals and 218 from township hospitals). The results showed that 768 (69.8%) considered that smoking and biomass fuel exposure were the main risk factors of COPD, while 639 (58.1%) thought that COPD patients needed to quit smoking. Only 334 respondents (30.4%) indicated that their COPD knowledge was derived from guidelines; 764 respondents (69.5%) considered pulmonary function tests as the gold standard for diagnosing COPD, but only 407 (37.0%) provided correct answers for the specific criteria of pulmonary function, and only 98 respondents (8.9%) correctly identified the diagnostic criteria for severe COPD. In comparison with the county hospital group, fewer doctors in the township hospitals received their COPD knowledge from guidelines [23.9%(52/218) vs.32.0%(282/882), χ 2=5.450, P<0.05]; more doctors in the township hospitals experienced difficulties in the diagnosis and treatment of COPD, including inadequate spirometers in their hospitals [59.6%(130/218) vs. 45.2% (399/882), χ 2=14.509, P<0.01] and significantly inadequate COPD medications [42.7%(93/218) vs.34.2%(302/882), χ 2=5.385, P<0.05]. Significantly lower proportions of general physicians performed pulmonary function tests for COPD patients (χ 2=12.638, P<0.01) and provided correct answers for the diagnostic criteria for severe COPD [6.6%(46/692) vs. 12.7%(52/408), χ 2=11.760, P<0.01] in comparison with respiratory specialists. Conclusions:Doctors in primary hospitals in Shanxi have an inadequate knowledge of COPD. Strengthening COPD-related education and promoting the use of guidelines among doctors remain important issues for successful management of COPD.

Objective To explore the influence of cucurbitacin E (CuE) on autophagy in human bladder cancer cell line T24 and further study its impacts on cell proliferation. Methods MTT assay was used to determine the proliferation inhibition capacity of CuE on T24 and western blot to check the impacts of CuE treatment on the expression of classic autophagy markers LC3A/B and p62. LC3 turnover assay and GFP-RFP-LC3 fluorescent assay were performed to determine autophagy flux. Western-blot was used to check the autophagy inhibition ability of 3-MA on CuE treatment and MTT assay and cell counting assay were used to check the influence of CuE-induced autophagy on cell proliferation with/without autophagy inhibition. Results CuE inhibited the proliferation of T24 and the IC50 in 24 h was about 0.75 μmol/L. CuE treatment increased the expression of LC3A/B Ⅱ and LC3A/B Ⅱ/Ⅰ ratio (P < 0.05) , but decreased the expression of p62 (P < 0.05) , indicating the induction of autophagy. Autophagy flux was induced because of positive LC3 turnover assay and the increase of yellow and red dots in GFP-RFP-LC3 fluorescent assay (P < 0.05). CuE-induced autophagy was inhibited by 3-MA (P < 0.05). With autophagy inhibition, CuE's proliferation suppression ability on T24 was attenuated (P <0.05). Conclusion CuE induces autophagy in bladder cancer cell line T24 and the induced autophagy positively contributes to the inhibitation of cell proliferation.

Objective To investigate the target achievement of serum trough concentration of vancomycin in elderly patients routinely treated with vancomycin,and to analyze the influencing factors for vancomycin-associated acute kidney injury(VA-AKI).Methods A single-center retrospective study was conducted by collecting clinical data of elderly inpatients from January 2016 to July 2017 who received intravenous vancomycin therapy and serum vancomycin trough concentration test.Logistic regression was used to analyze the risk factors for VA-AKI.Results A total of 141 patients were enrolled,including 74 males (52.5 ％) and 67 females (47.5 ％).The median (interquartile range)age was 77.0(13.5) years old.Patients with serum vancomycin trough concentrations within 10～ 20 mg/L accounted for 48.9 ％ (69 cases),while those lower than the target value accounted for 23.4 ％ (33 cases),and those higher than the target value accounted for 27.7％ (39 cases).Patients were divided into three groups according to the vancomycin serum trough concentration:＜10 mg/L group,10～20 mg/L group,and ＞20 mg/L group.There were statistically significant differences among the three groups in median(interquartile range) age[74.0 (14.0) years old,76.0 (11.5) years old vs.80.0 (14.0) years old,H =9.506,P =0.009] and the median (interquartile range) vancomycin daily dose [1.5(0.5) g/d,1.5 (0.8) g/d vs.1.5 (0.5) g/d,H =6.131,P =0.047].VA-AKI occurred in 23 patients(16.3 ％).Logistic regression analysis showed that the baseline serum creatinine levels (OR =1.022,95 ％CI:1.001 ～ 1.042,P =0.035)and vancomycin trough concentration(OR =1.058,95 ％CI:1.011～1.106,P=0.015)were influencing factors for VA-AKI.Conclusions The elderly patients with infection who received clinical vancomycin therapy have a low target achievement rate of serum trough concentration.Baseline serum creatinine level and serum vancomycin trough concentration are influencing factors for VA-AKI.

Objective: To investigate the role of midkine(MK)in the pathogenesis of Henoch-Schonlein purpura(HSP) and Henoch-Schonlein purpura nephritis(HSPN). Methods: In the case group, 35 cases were hospitalized in the pediatric kidney rheumatism immunology ward of Shengjing hospital affiliated to China Medical University from December 2016 to January 2018.Among them, 10 cases were HSP, 25 were HSPN.According to quantitative level of 24-hour urine protein, HSPN group was divided into HSPN(nephrotic level of proteinuria)group of 15 cases and HSPN(non-nephrotic level of proteinuria)group of 10 cases.The control group consisted of 12 healthy cases who underwent physical examination at outpatient department in the same period in the developmental pediatric clinic of our hospital.Blood samples were collected to detect MK.The other clinical datas including renal function, 24-hour urine protein quantitative, immunoglobulin, etc were collected.The serum MK and renal function indexes were compared among groups.The correlation between MK and various clinical indicators was analyzed, and the receiver operating characteristic(ROC) curve was used to analyze the diagnostic significance of MK for HSP and HSPN. Results: MK level of case group was higher than that of healthy control group[(289.34±160.70)pg/ml vs.(100.03±56.75)pg/ml, P<0.05]. Moreover, the difference of MK concentration among the HSPN(nephrotic proteinuria)group, the HSPN(non-nephrotic proteinuria)group and the HSP group was still statistically significant[(449.91±141.91)pg/ml vs.(244.04±89.15)pg/ml vs.(175.94±46.30)pg/ml, P<0.05]. MK was positively correlated with urine microalbumin(r=0.54), IgA(r=0.132), IgE(r=0.304), urine β2 microglobulin(r=0.483), 24-hour urine protein /body weight(r=0.503), and urine transferrin level(r=0.509)in the case group(P<0.05). According to the ROC curve, the area under ROC of MK for predicting the diagnosis of HSP was 0.908(95%CI 0.828-0.988). The optimal value in predicting the diagnosis of HSP was 182.762 pg/ml, with sensitivity and specificity of 81.4% and 91.7%.The area under ROC of MK in predicting HSPN was 0.947(95%CI 0.888-1.000), and the optimal value of predicting HSPN was 218.186 pg/ml, with sensitivity and specificity of 84.0% and 95.5%. Conclusion MK may be involved in the pathogenesis of HSP and HSPN.It can provide the basis for clinical diagnosis of HSP and HSPN, and has significance in evaluating the degree of renal damage of HSPN.