Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

ObjectiveTo investigate protective effect of Arctium lappa root aqueous extract （ALR-AE） on hydrochloric acid/ethanol （HCl/EtOH）-induced acute gastric ulcer in rats based on protein kinase B/nuclear transcription factor-κB （Akt/NF-κB） signaling pathway. MethodRats were randomly divided into 5 groups， namely normal group， model group， ranitidine group （35 mg·kg^-1）， ALR-AE low dose group （50 mg·kg^-1， ALR-AE-L group） and ALR-AE high dose group （100 mg·kg^-1， ALR-AE-H group）. Different doses of ALR-AE were orally administered twice daily for three consecutive days before the animals were subjected to HCl/EtOH （60% ethanol in 150 mmol·L^-1 HCl） to induce acute gastric ulcer. For the gastric tissue samples， the ulcer surface was recorded by electronic imaging technique， and then the ulcer inhibition rate was calculated using ImageJ 1.8.0， hematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining were used to observe the pathological changes and mucoprotein distribution， respectively. The levels of oxidative stress factors of malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in rat gastric tissues were determined by colorimetric method， the levels of pro-inflammatory mediators of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β were determined by enzyme linked immunosorbent assay （ELISA）， protein levels of phosphorylation and non-phosphorylation of Akt， NF-κB p65， NF-κB inhibitor protein α （IκBα） and IκB kinase α （IKKα） were evaluated by Western blot. ResultCompared with the normal group， the gastric tissue of the model group was severely damaged， and the area of gastric ulcer were significantly enlarged （P<0.01）， the levels of MDA， TNF-α， IL-6 and IL-1β in gastric tissue were significantly increased （P<0.01）， levels of GSH-Px and SOD were significantly decreased （P<0.01）， and phosphorylation levels of Akt， NF-κB p65， IKKα and IκBα in gastric tissue were significantly increased （P<0.01）. Compared with the model group， ALR-AE significantly attenuated HCl/EtOH-induced gastric tissue damage， significantly increased ulcer inhibition rate （P<0.01）， and dose-dependently reduced the levels of MDA， TNF-α， IL-6 and IL-1β （P<0.05， P<0.01）， and elevated GSH-Px and SOD levels （P<0.01）， ALR-AE-L group could significantly inhibit the phosphorylation levels of Akt （P<0.05）， and ALR-AE-H group could significantly inhibit phosphorylation levels of Akt， NF-κB p65， IKKα and IκBα （P<0.05， P<0.01）. ConclusionALR-AE has a significant protective effect on HCl/EtOH-induced acute gastric ulcers in rats， and its mechanism may be related to the inhibition of inflammatory mediator expression and reduction of oxidative stress levels mediated by Akt/NF-κB signaling pathway.

ObjectiveTo establish a quantitative analysis multi-components by single marker method （QAMS） for five main components （aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin） in Eucommiae Folium， to verify its feasibility and applicability in the determination of Eucommiae Folium， so as to provide a scientific basis for the development of quality standard of this herb. MethodHigh performance liquid chromatography was performed on a Welch Boltmatetm™ C₁₈ column （4.6 mm×100 mm， 2.7 μm） with methanol （A）-0.2% phosphoric acid aqueous solution （B） as the mobile phase for gradient elution （0-8 min， 3%A； 8-10 min， 3%-11%A； 10-26 min， 11%A； 26-27 min， 11%-25%A； 27-60 min， 25%-32%A）， the column temperature was set at 30 ℃， the flow rate was 0.6 mL·min^-1， the detection wavelengths were at 210 nm and 254 nm. Chlorogenic acid was used as an internal reference to establish the relative correction factors （f） between it and the other four components， and the contents of the five components in 14 batches of Eucommiae Folium were determined by QAMS and external standard method （ESM）， respectively. ResultThe f values of chlorogenic acid to aucubin， geniposidic acid， asperuloside and rutin were 3.13， 1.45， 2.64 and 0.56， respectively. Repeatability was good under different experimental conditions， relative standard deviation （RSD） was <5.0%. The contents of aucubin， geniposidic acid， chlorogenic acid， asperuloside and rutin in 14 batches of Eucommiae Folium were 1.340-28.975， 0.252-36.086， 10.016-27.443， 1.396-8.646， 0.533-1.766 mg·g^-1， respectively. There were no significant difference between content results of QAMS and that of ESM （RSD<5.0%）. ConclusionQAMS established with chlorogenic acid as the internal reference can be used to determine the contents of five components in Eucommiae Folium， and this method is simple and accurate. After comprehensive evaluation， the quality standard of Eucommiae Folium in subsequent editions of Chinese Pharmacopoeia is suggested that three main active components， chlorogenic acid， aucubin and geniposidic acid， are selected as quality markers， and their content limits are recommended not less than 1.5%， 1.0% and 1.0%， respectively. This quality standard draft can avoid the potential quality risk due to poor specificity and low content limit of the index component （chlorogenic acid） in the previous editions of Chinese Pharmacopoeia.

Objective:To evaluate the value of endogenous digitalis-like factor (EDLF) dynamic changes in predicting myocardial injury and prognosis in patients with sepsis.Methods:A total of 160 sepsis patients admitted to the emergency department of Beijing Friendship Hospital Affiliated to Capital Medical University from July 2017 to January 2019 were selected and divided into the myocardial injury(MI) group ( n=75) and the non-myocardial injury (NMI) group ( n=85) according to whether there was myocardial injury. The plasma EDLF concentration was tested on the 1 st, 3 rd and 7 th day after admission. The predictive factors of MI and 90-days outcome were evaluated by logistics regression analysis. Cox proportional hazards regression model was used to estimate the prognostic value of EDLF concentration on the 90 days after admission for sepsis. Results:Septic patients with MI had increased levels of myocardial enzymes, decreased left ventricular fractional shortening index (FS) and interventricular septum (IVS) amplitude and abnormal wall motion, when compared to NMI patients (all P<0.05). EDLF concentration on the 7 th day in the MI group was significantly lower than in the NMI group ( P=0.019). Logistic regression showed that EDLF 7 th was an independent protective factor for MI and 90-day mortality in sepsis respectively ( OR=0.964, 95% CI: 0.934-0.994, P=0.021; OR=0.931, 95% CI: 0.871-0.995, P=0.036). Cox proportional hazards regression analysis suggested that EDLF 7 th concentration <26.7 pmol/L was an independent predictor of 90-day mortality in patients with sepsis ( HR=4.601, 95% CI: 1.030-20.563, P=0.046). Conclusions:EDLF 7 th may serve as a protective factor for sepsis-induced MI and adverse outcome. The exogenous supplement of cardiotonic drugs at one week after MI may be a potential treatment to improve the survival rate of septic patients.

Objective:To investigate the effect of irinotecan combined with XELOX regimen on serum CD cells, miR-34a and let-7i in patients with advanced gastric cancer.Methods:A total of 72 patients with advanced gastric cancer treated in the Affiliated Hospital of Hubei University of Arts And Science from January 2015 to January 2020 were prospectively selected, and they were divided into control group and observation group with 36 cases in each group by random number table method. The control group was treated with XELOX regimen, while the observation group was treated with irinotecan on the basis of the control group. The efficacy, serum immune level, serum miR-34a and let-7i contents, incidence of toxic and side effects and life cycle of the two groups were compared.Results:The objective response rate (ORR) of the observation group was 33.33% , which were significantly higher than that of the control group (13.89%, χ 2=3.770, P>0.05). There was no significant difference in serum immune level, miR-34a and let-7i between the two groups before treatment (all P>0.05). After treatment, the levels of CD3 + , CD4 + and CD8 + in the two groups were significantly increased (all P<0.05), and the improvement of CD3 + , CD4 + and CD8 + in observation group was significantly better than that in control group (all P<0.05). After treatment, the serum miR-34a level increased significantly and serum let-7i level decreased significantly in the two groups (all P<0.05), and the serum miR-34a level in the observation group was higher than that in the control group, and the serum let-7i level was significantly lower than that in the control group (all P<0.05). Among the grade Ⅰ-Ⅱ adverse reactions, nausea and vomiting and leukocyte decline were the most common; The incidence of grade Ⅲ-Ⅳ leukopenia in the control group and the observation group were 5.56%(2/36) and 5.56%(2/36), respectively; The incidence of grade Ⅲ-Ⅳ thrombocytopenia was 5.56%(2/36) and 2.78%(1/36), respectively; One patient in the control group had grade Ⅲ-Ⅳ abnormal liver function, and one patient in the observation group had grade Ⅲ-Ⅳ nausea and vomiting. All patients with adverse reactions were effectively relieved after symptomatic treatment, and there were no treatment-related deaths. The progression free survival (PFS) of the observation group was 24.90 months (95% CI: 0.469-1.955), and that of the control group was 21.85 months (95% CI: 0.512-2.131). The PFS of the observation group was significantly longer than that of the control group (log rank=1.357, P=0.007). Conclusions:Irinotecan combined with XELOX regimen in the treatment of advanced gastric cancer can effectively improve the level of serum miR-34a and immune function, reduce the content of let-7i, and has good safety.

Objective:To investigate differences in intestinal microbiome between adult patients with psoriasis vulgaris and healthy individuals.Methods:Fecal samples were collected from 22 patients with confirmed psoriasis vulgaris and 23 healthy controls in Hospital for Skin Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College from September 2017 to February 2018. The total DNA of intestinal flora was extracted and amplified, and the next-generation 16S rRNA gene-targeted sequencing was performed to analyze the diversity and distribution of intestinal flora. Species annotation and classification were performed according to Silva database, and rank sum test was used to analyze species differences among samples at different taxonomic ranks; QIIME software (Version 1.9.1) was used to calculate the number of operational taxonomic units (OTUs) and main indices of α diversity (Chao1 index, Shannon index and Simpson index) , and t test to analyze differences in indices; PCoA analysis was performed to analyze the difference in β diversity, and differences in microbial community composition structure were analyzed between the two groups by using permutational multivariate analysis of variance; rank sum test and linear discriminant analysis effect size (LEfSe) analysis were used to evaluate the species difference. Results:No significant difference in the number of OTUs was observed between the psoriasis group (147.55 ± 57.07) and healthy control group (148.96 ± 50.45, t = 0.088, P = 0.930) . In addition, there were no significant differences in the Shannon index, Chao1 index or Simpson index between the psoriasis group (4.08 ± 0.80, 169.52 ± 63.17, 0.87 ± 0.07, respectively) and healthy control group (4.11 ± 0.94, 175.36 ± 53.59, 0.86 ± 0.90, respectively; t = 0.12, 0.34, 0.27, all P > 0.05) . PCoA analysis showed that the first and second principal components explained 49.8% and 15.62%, respectively, of the total variance between the psoriasis group and healthy control group, and permutational multivariate analysis of variance revealed that the β diversity significantly differed between the two groups ( P = 0.011) . Different microbes between the psoriasis group and healthy control group included Firmicutes, Clostridia, Clostridiales, Erysipelotrichales and Erysipelotrichaceae, whose abundance significantly increased in the psoriasis group, as well as Epsilonproteobacteria, Campylobacterales, Campylobacteraceae, Campylobacter, Bacteroidales and Bacteroidaceae, whose abundance significantly increased in the healthy control group. Conclusion:The intestinal microbiome differs between patients with psoriasis vulgaris and healthy individuals, which may serve as potential biomarkers for psoriasis vulgaris.

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ² test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ²=288.60,P<0.01),N stage(χ²=68.10, P<0.01), vascular invasion(χ²=128.70, P<0.01)and neural invasion(χ²=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ²=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

OBJECTIVE: To investigate the effect of treatment time on the outcome of patients with ischemic stroke undergoing reperfusion therapy. METHODS: The clinical data of 3229 ischemic stroke patients who received intravenous thrombolysis with or without arterial thrombolysis from 71 hospitals in Zhejiang province from June 2017 to September 2018 were retrospectively reviewed. The good outcome was defined as modified Rankin Scale (mRS) ≤ 2. Binary logistic regression analysis was used to investigate the association of door to needle time (DNT), or door to reperfusion time (DRT) with the outcomes in patients treated by intravenous thrombolysis or bridging arterial thrombolysis, respectively. RESULTS: Binary logistic regression showed that DNT (=0.994, 95%:0.991-0.997, <0.01) or DRT (=0.989, 95%:0.983-0.995, <0.01) were independently associated with good outcomes, respectively. Every hour decreases in DNT resulted in a 4.7%increased probability of functional independence (mRS 0-2) in patients treated by intravenous thrombolysis; Every hour decreases in DRT was associated with a 11.4%increased probability of functional independence in patients treated by intravenous thrombolysis with arterial thrombolysis. CONCLUSIONS Good outcomes are associated with lower DNT in ischemic stroke patients treated by intravenous thrombolysis or lower DRT in patients treated by intravenous thrombolysis bridging arterial thrombolysis.
Brain Ischemia ; drug therapy ; Fibrinolytic Agents ; therapeutic use ; Humans ; Reperfusion ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; Time Factors ; Treatment Outcome

From November 2014 to July 2017,637 patients with acute coronary syndrome (ACS) were included in the analysis,among whom there were 48 cases with prior ischemic stroke (7.5％).The risk factors,history,severity of coronary artery disease,medication status,and incidence of adverse cardiovascular and cerebrovascular events (cardiac death,re-infarction,heart failure,stroke) were analyzed.Compare with patients without prior ischemic stroke (control group) patients with prior ischemic stroke (study group) had lower rates in administration of beta blockers [50.00％(24/28) vs.69.78％(411/589),x2=8.02,P＜0.05]and interventional therapy[56.67％(17/30) vs.81.86％(334/408),x2=11.15,P＜0.05].However,there were no significant differences in medication of dual antiplatelet,statins and angiotensin converting enzyme inhibitors or angiotensin receptor blocker between two groups (P＞0.05);and there was no significant difference in major adverse cardiovascular events between two groups (P＞0.05).In the future,more studies are needed for clinical management of this group of patients.

Objective: To investigate the clinical value of Bayesian network in predicting survival of patients with advanced gallbladder cancer(GBC)who underwent curative intent surgery. Methods: The clinical data of patients with advanced GBC who underwent curative intent surgery in 9 institutions from January 2010 to December 2015 were analyzed retrospectively.A median survival time model based on a tree augmented naïve Bayes algorithm was established by Bayesia Lab software.The survival time, number of metastatic lymph nodes(NMLN), T stage, pathological grade, margin, jaundice, liver invasion, age, sex and tumor morphology were included in this model.Confusion matrix, the receiver operating characteristic curve and area under the curve were used to evaluate the accuracy of the model.A priori statistical analysis of these 10 variables and a posterior analysis(survival time as the target variable, the remaining factors as the attribute variables)was performed.The importance rankings of each variable was calculated with the polymorphic Birnbaum importance calculation based on the posterior analysis results.The survival probability forecast table was constructed based on the top 4 prognosis factors. The survival curve was drawn by the Kaplan-Meier method, and differences in survival curves were compared using the Log-rank test. Results: A total of 316 patients were enrolled, including 109 males and 207 females.The ratio of male to female was 1.0∶1.9, the age was (62.0±10.8)years.There was 298 cases(94.3%) R0 resection and 18 cases(5.7%) R1 resection.T staging: 287 cases(90.8%) T3 and 29 cases(9.2%) T4.The median survival time(MST) was 23.77 months, and the 1, 3, 5-year survival rates were 67.4%, 40.8%, 32.0%, respectively.For the Bayesian model, the number of correctly predicted cases was 121(≤23.77 months) and 115(>23.77 months) respectively, leading to a 74.86% accuracy of this model.The prior probability of survival time was 0.503 2(≤23.77 months) and 0.496 8(>23.77 months), the importance ranking showed that NMLN(0.366 6), margin(0.350 1), T stage(0.319 2) and pathological grade(0.258 9) were the top 4 prognosis factors influencing the postoperative MST.These four factors were taken as observation variables to get the probability of patients in different survival periods.Basing on these results, a survival prediction score system including NMLN, margin, T stage and pathological grade was designed, the median survival time(month) of 4-9 points were 66.8, 42.4, 26.0, 9.0, 7.5 and 2.3, respectively, there was a statistically significant difference in the different points(P<0.01). Conclusions The survival prediction model of GBC based on Bayesian network has high accuracy.NMLN, margin, T staging and pathological grade are the top 4 risk factors affecting the survival of patients with advanced GBC who underwent curative resection.The survival prediction score system based on these four factors could be used to predict the survival and to guide the decision making of patients with advanced GBC.