Predictive value of deep learning-based coronary artery calcification score for coronary artery disease in type 2 diabetes mellitus / 中华放射学杂志

Objective:To explore the predictive value of deep learning (DL)-based coronary artery calcification score (CACS) for obstructive coronary artery disease (CAD) and noncalcified plaque/mixed plaque in type 2 diabetes mellitus (T2DM).Methods:Forty hundred and twenty-four consecutive T2DM patients who accepted CACS scan and coronary CT angiography (CCTA) from December 2012 to December 2019 were included retrospectively, with clinical risk factors and plaque features collected. Plaque composition was classified as calcified, non-calcified or mixed plaque. Obstructive CAD was defined as maximum diameter stenosis≥50%. CACS was calculated with a fully automated method based on DL. Univariate and multivariate logistic regressions were applied to select statistically significant factors and the odds ratios(ORs) were measured. Receiver operating characteristic (ROC) curve was evaluated to assess the predictive performance.Results:Increased CACS was associated with a significantly higher odds of obstructive CAD in CCTA (adjusted ORs were 2.22, 6.18 and 16.98 for CACS=1-99, 100-299, 300-999 vs. CACS=0, and P values were 0.009,<0.001,<0.001 respectively). The area under ROC curve (AUC) of CACS to predict obstructive CAD was 0.764. Compared with 0, increased CACS was associated with increased risk of non-calcified/mixed plaque (adjusted ORs were 2.75, 4.76, 5.29 for CACS=1-99, 100-299, 300-999 respectively and P values were 0.001,<0.001,<0.001 respectively). The AUC of CACS to predict non-calcified/mixed plaque was 0.688. It took 1.17 min to perform automated measurement of CACS based on DL in total, which was significantly less than manual measurement of 1.73 min ( P<0.001). Conclusion:DL-based CACS can predict obstructive CAD and non-calcified plaque/mixed plaque in T2DM, which is economical and efficient, and has important value for clinical diagnosis and treatment.

Awareness of HPV and HPV vaccine and willingness to be vaccinated among parents of children aged 9-14 / 公共卫生与预防医学

Objective To investigate the HPV vaccination status of children aged 9-14 years, parents’ vaccine-related cognition, willingness to vaccinate children and their influencing factors. Methods From January to April 2021, the convenience sampling method was used to collect data based on the online platform and the Department of Pediatrics and Adolescent Gynecology of the Children's Hospital of Zhejiang University School of Medicine. The data were analyzed by descriptive analysis, Chi-square test, and logistic regression. Results A total of 864 questionnaires were collected, and 846 valid questionnaires were obtained after screening, with an effective rate of 97.9%. 13.57% of mothers and 3.09% of girls were vaccinated, and the vaccine awareness rate was 68.43%. 87.22% of parents were willing to bring their children for vaccination. Risk perception (OR=4.79, 95% CI: 2.22-10.35), willingness to vaccinate themselves (OR =29.01, 95% CI: 12.62-66.69), awareness of sex education (OR =3.73, 95% CI: 1.08-12.83) and whether the vaccines were free (P<0.001) were related to whether parents were willing to vaccinate their children. Conclusion Parents of children aged 9-14 have high awareness of HPV and HPV vaccine and are willing to vaccinate their children with HPV vaccine , but the vaccination rate in children is low. Disease perception, willingness to vaccinate, awareness of sex education, and whether vaccines are free are all the factors influencing parents' willingness to vaccinate children.

Network meta-analysis comparing the clinical outcomes and safety of robotic, laparoscopic, and transanal total rectal mesenteric resection for rectal cancer / 中华胃肠外科杂志

Objective: To methodically assess the clinical effectiveness and safety of robot-assisted total rectal mesenteric resection (RTME), laparoscopic-assisted total rectal mesenteric resection (laTME), and transanal total rectal mesenteric resection (taTME). Methods: A computer search was conducted on PubMed, Embase, Cochrane Library, and Ovid databases to identify English-language reports published between January 2017 and January 2022 that compared the clinical efficacy of the three surgical procedures of RTME, laTME, and taTME. The quality of the studies was evaluated using the NOS and JADAD scales for retrospective cohort studies and randomized controlled trials, respectively. Direct meta-analysis and reticulated meta-analysis were performed using Review Manager software and R software, respectively. Results: Twenty-nine publications comprising 8,339 patients with rectal cancer were ultimately included. The direct meta-analysis indicated that the length of hospital stay was longer after RTME than after taTME, whereas according to the reticulated meta-analysis the length of hospital stay was shorter after taTME than after laTME (MD=-0.86, 95%CI: -1.70 to -0.096, P=0.036). Moreover, the incidence of anastomotic leak was lower after taTME than after RTME (OR=0.60, 95%CI: 0.39 to 0.91, P=0.018). The incidence of intestinal obstruction was also lower after taTME than after RTME (OR=0.55, 95%CI: 0.31 to 0.94, P=0.037). All of these differences were statistically significant (all P<0.05). There were no statistically significant differences between the three surgical procedures regarding the number of lymph nodes cleared, length of the inferior rectal margin, or rate of positive circumferential margins (all P>0.05). An inconsistency test using nodal analysis revealed no statistically significant differences between the results of direct and indirect comparisons of the six outcome indicators (all P>0.05). Furthermore, we detected no significant overall inconsistency between direct and indirect evidence. Conclusion: taTME has advantages over RTME and laTME, in terms of radical and surgical short-term outcomes in patients with rectal cancer.

Relationship between blood uric acid levels and body composition in patients with polycystic ovary syndrome / 中华妇产科杂志

Objective: To analyze the difference in blood uric acid levels between patients with polycystic ovary syndrome (PCOS) and healthy women of childbearing age, and to investigate the correlation between body composition and blood uric acid levels. Methods: A total of 153 eligible childbearing age patients with PCOS treated at Tianjin Medical University General Hospital from January 2018 to March 2022 were selected, and 153 healthy women with normal menstruation were selected as the control group. Fasting blood uric acid levels were measured by venous blood test, and body composition was measured by a body composition analyzer. Group comparisons were made to analyze the correlation between body composition and blood uric acid levels. Results: The incidence of hyperuricemia was higher in patients with PCOS than that in the control group [30.1% (46/153) vs 2.0% (3/153)], with a statistically significant difference (χ2=44.429, P<0.001). Blood uric acid level was also significantly higher in patients with PCOS than that in the control group [(371±98) vs (265±67) μmol/L; t=11.170, P<0.001]. Among PCOS patients, there were statistically significant differences in weight, body mass index (BMI), body fat mass, skeletal muscle mass, percent body fat, lean body weight, fat mass/lean body weight, percent skeletal muscle, and visceral fat level between the hyperuricemia group and the normal blood uric acid group (all P<0.001), but no significant difference was observed in waist-hip ratio (P=0.348). The following body composition indicators: weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, visceral fat level, lean body weight, and fat mass/lean body weight in all subjects, the PCOS patients and the control group, were positively correlated with blood uric acid levels (all P<0.01). The blood uric acid level in PCOS obese patients was higher than that in non-obese PCOS patients, and the difference was statistically significant [(425±83) vs (336±91) μmol/L; t=6.133, P<0.001]. The blood uric acid level in central obesity PCOS patients was also higher than that in non-central obesity PCOS patients [(385±95) vs (299±79) μmol/L], the difference was statistically significant (t=4.261, P<0.001). The blood uric acid level in normal-weight obese PCOS patients was higher than that in normal-weight non-obese PCOS patients [(333±73) vs (277±54) μmol/L], and the difference was statistically significant (t=2.848, P=0.006). Blood uric acid levels in normal-weight [(315±74) vs (255±67) μmol/L], overweight [(362±102) vs (276±57) μmol/L], and obese PCOS patients [(425±83) vs (303±74) μmol/L] were all higher than those in the corresponding control groups, with statistically significant differences (all P<0.001). Conclusions: PCOS patients have a higher incidence of hyperuricemia than healthy women of childbearing age. Blood uric acid levels are closely correlated with body composition indicators, such as weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, and visceral fat level. Body composition analysis of women with PCOS could help identify potentially obese people more accurately and carry out individualized treatment, thereby reducing the risk of metabolic abnormalities.

Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.@*METHODS@#This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence.@*RESULTS@#All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)].@*CONCLUSION@#A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

The fat attenuation index around coronary artery measurement on coronary calcium score images and coronary CT angiography images: a comparison study / 中华放射学杂志

Objective:To investigate the difference in the peri-coronary fat attenuation index (FAI) between using coronary calcium score (CCS) images and coronary CT angiography (CCTA) images, and to explore the feasibility and befitting threshold of FAI measured on CCS images.Methods:The clinical and imaging data of patients who underwent CCTA examination from August 2019 to August 2020 were retrospectively analyzed in the First Affiliated Hospital of Soochow University. According to the inclusion and exclusion criteria, there were 122 cases in non-calcified plaque group (144 coronary arteries) and 97 cases in none-plaque group (186 coronary arteries). The coronary arteries were delineated both on CCS and CCTA images with Perivascular Fat Analysis Tool; the regions of interest of peri-coronary adipose tissue were generated automatically after setting the threshold of fat tissue. Then the FAI value was calculated. The thresholds were set in four levels (-190--30, -185--25, -180--20 and -175--15 HU) for CCS images and one level (-190--30 HU) for CCTA images. The intra-class correlation coefficient (ICC) was used to evaluate the consistency of the measurements of FAI values on CCS and CCTA images between the two physicians. Paired t test was used to compare the differences of FAI values between CCS and CCTA images, and Pearson correlation coefficient was used to evaluate the correlation between CCS-FAI and CCTA-FAI. Results:(1) FAI values measured on CCS and CCTA images by 2 physicians showed good consistency; (2) At the threshold of -185--25 HU, there was no significant difference in FAI values between the CCS and CCTA images for non-calcified plaque group [(-84.15±5.99)HU vs. (-83.83±5.98)HU, t=0.79, P=0.429], as well as for the none-plaque group [(-83.41±5.75)HU vs.(-83.84±6.25)HU, t=-1.08, P=0.280]; (3) There were significant differences on FAI values between the CCS images and CCTA images at the threshold of -190--30、-180--20 and -175--15 HU (all P<0.05); (4) There were moderate correlations on FAI values between the CCS images and CCTA images under different thresholds both in non-calcified plaque group and none-plaque group. Conclusion:It is feasible to measure FAI on CCS images, and the befitting threshold is -185--25 HU.

Impact of bicuspid aortic valve or tricuspid aortic valve on hemodynamics and left ventricular reverse remodeling in patients after transcatheter aortic valve replacement / 中华心血管病杂志

Objective: To compare the impact of bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) on hemodynamics and left ventricular reverse remodeling after transcatheter aortic valve replacement (TAVR). Methods: We retrospectively analyzed the clinical data of patients who underwent TAVR in our hospital from January 2019 to March 2021. Patients were divided into BAV group and TAV group according to aortic contrast-enhanced CT. Each patient was followed up by N-terminal pro B-type natriuretic peptide (NT-proBNP) and echocardiography at four time points, namely before TAVR, 24 hours, 1 month and 6 months after TAVR. Echocardiographic data, including mean pressure gradient (MPG), aortic valve area (AVA), left ventricular ejection fraction (LVEF), left ventricle mass (LVM) and LV mass index (LVMi) were evaluated. Results: A total of 41 patients were included. The age was (75.0±8.6) years, and male patients accounted for 53.7%. There were 19 BAV patients and 22 TAV patients in this cohort. All patients undergoing TAVR using a self-expandable prosthesis Venus-A valve. MPG was (54.16±21.22) mmHg(1 mmHg=0.133 kPa) before TAVR, (21.11±9.04) mmHg at 24 hours after TAVR, (18.84±7.37) mmHg at 1 month after TAVR, (17.68±6.04) mmHg at 6 months after TAVR in BAV group. LVEF was (50.42±13.30)% before TAVR, (53.84±10.59)% at 24 hours after TAVR, (55.68±8.71)% at 1 month after TAVR and (57.42±7.78)% at 6 months after TAVR in BAV group. MPG and LVEF substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05) in BAV group. MPG in TAV group improved at each time point after operation, and the difference was statistically significant (all P<0.05). LVMi was (164.13±49.53), (156.37±39.11), (146.65±38.84) and (134.13±39.83) g/m2 at the 4 time points and the value was significantly reduced at 1 and 6 months post TAVR compared to preoperative level(both P<0.05). LVEF in the TAV group remained unchanged at 24 hours after operation, but it was improved at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). LVMi in TAV group substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05). NT-proBNP in both two groups improved after operation, at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). MPG in TAV group improved better than in BAV group during the postoperative follow-up (24 hours after TAVR: (11.68±5.09) mmHg vs. (21.11±9.04) mmHg, P<0.001, 1 month after TAVR: (10.82±3.71) mmHg vs. (18.84±7.37) mmHg, P<0.001, 6 months after TAVR: (12.36±4.42) mmHg vs. (17.68±6.04) mmHg, P=0.003). There was no significant difference in NT-proBNP between BAV group and TAV group at each time point after operation (all P>0.05). There was no significant difference in paravalvular regurgitation and second prosthesis implantation between the two groups (all P>0.05). Conclusions: AS patients with BAV or TAV experience hemodynamic improvement and obvious left ventricular reverse remodeling after TAVR, and the therapeutic effects of TAVR are similar between BAV and TAV AS patients in the short-term post TAVR.

Preparation and application of DNA hydrogels: a review / 生物工程学报

Deoxyribonucleic acid (DNA) not only serves as the material basis of biological inheritance, but also shows great potential in the development of novel biological materials due to its programmability, functional diversity, biocompatibility and biodegradability. DNA hydrogel is a three-dimensional mesh polymer material mainly formed by DNA. It has become one of the most interesting emerging functional polymer materials in recent years because of the perfect combination of the DNA biological properties that it retained and the mechanical properties of its own skeleton. At present, single- or multi-component DNA hydrogels developed based on various functional nucleic acid sequences or by combining different functional materials have been widely used in the field of biomedicine, molecular detection, and environmental protection. In this paper, the development of preparation methods and classification strategies of DNA hydrogels are summarized, and the applications of DNA hydrogels in drug delivery, biosensing and cell culture are also reviewed. Finally, the future development direction and potential challenges of DNA hydrogels are prospected.

Study on endpoint determination method of tablet coating based on 3σ criteria and logic regression / 中国中药杂志

This paper explores the statistical distribution characteristics of coating film thickness, so as to present a new method for determining coating endpoint based on 3σ criterion and logic regression. Firstly, the spectrum and thickness of 4 batch samples were collected. Secondly, the spectral range of normal products was obtained by 3σ criterion, with the spectral feature NI as the number of test spectrum in the above range. Then, the model based on 3σ criterion and logic regression was built according to the best condition in K-fold cross-validation and the determined threshold of qualified rate in the coating endpoint. Finally, the qualified rate of test set samples at different time points was calculated by the above model, and the above change trend and the threshold value were combined to determine the coating endpoint. The results of KS analysis showed the distribution of thickness of the qualified products followed the normal distribution(P=0.081>0.05). The accuracy of the coating endpoint determination was as high as 100% by the model based on 3σ criterion and logic regression when the determined threshold of qualified rate was 90%. Therefore, the 3σ criterion was feasible to the research of coating eligibility. This paper reveals certain random phenomena in the coating process, and the method features a high accuracy, quick analysis and a good interpretability, which provides a reference for online detection and qualify evaluation in future.

Perioperative management strategy of severe traumatic brain injury during the outbreak of COVID-19 / 中华创伤杂志(英文版)

Since December 2019, a pneumonia caused by a new coronavirus, i.e. COVID-19 occurred in Wuhan, Hubei Province, China. Although the epidemic in China has been bought under control, the global COVID-19 situation is still grim. Severe traumatic brain injury (TBI), as one of critical conditions in the department of neurosurgery, requires an early and effective treatment, especially surgery. There were currently no reliable guidelines on how to perform perioperative protection in TBI patients with suspected or confirmed coronavirus infection. According to the corresponding treatment regulations and guidelines issued by the authorities, we summarized the management strategy of TBI patients in perioperative period during the COVID-19 outbreak based on medical and nursing practice, in order to provide a reference for clinicians.

Preliminary study on the value of pericoronary adipose tissue histogram parameters for the differentiation of acute coronary syndrome and stable coronary artery disease / 中华放射学杂志

Objective:To investigate the value of pericoronary adipose tissue histogram parameters based on coronary CT angiography (CTA) images for the differentiation of acute coronary syndrome and stable coronary artery disease.Methods:The clinical data and CTA images of 93 patients with coronary CTA examination in Suzhou Kowloon Hospital from 2013 to 2018 were analyzed retrospectively. There were 39 patients with acute coronary syndrome (acute coronary syndrome group) and 54 patients with stable coronary artery disease (stable coronary artery disease group). A region of interest (ROI) was drawn around the stenosis of the coronary arteries, with CT attenuation ranging from-190 to -30 HU to exclude non-adipose tissue. The CT attenuation of ROI excluding non-adipose were measured and histogram analysis was performed. The obtained parameters included the mean value, median value and the 5th, 10th, 45th, 55th, 70th and 95th percentiles. The differences in histogram parameters between the two groups were compared, and then the value of each parameter in differentiating acute coronary syndrome and stable coronary artery disease was evaluated based on receiver operating characteristic (ROC) analysis. The stepwise regression of multivariate logistic regression analysis was used to identify the useful features and establish the final prediction model. The ROC curve of the final model was calculated and its value was analyzed.Results:The mean, median and the 5th, 10th, 45th, 55th,70th and 95th percentile differences between the acute coronary syndrome group and the stable coronary artery disease group were statistically significant (all P<0.05). The ROC curve for the median and the 95th percentile had the same area under curve (AUC) of 0.73. The sensitivity, specificity and AUC of the diagnostic model established by multiple logistic regression were 82.1%, 89.1% and 0.90 respectively. Conclusion:CT attenuation histogram of pericoronary adipose tissue is of high value in differentiating acute coronary syndrome from stable coronary artery disease.

Development and validation of radiomics model built by incorporating machine learning for identifying liver fibrosis and early-stage cirrhosis / 中华医学杂志(英文版)

BACKGROUND@#Liver fibrosis (LF) continues to develop and eventually progresses to cirrhosis. However, LF and early-stage cirrhosis (ESC) can be reversed in some cases, while advanced cirrhosis is almost impossible to cure. Advances in quantitative imaging techniques have made it possible to replace the gold standard biopsy method with non-invasive imaging, such as radiomics. Therefore, the purpose of this study is to develop a radiomics model to identify LF and ESC.@*METHODS@#Patients with LF (n = 108) and ESC (n = 116) were enrolled in this study. As a control, patients with healthy livers were involved in the study (n = 145). Diffusion-weighted imaging (DWI) data sets with three b-values (0, 400, and 800 s/mm) of enrolled cases were collected in this study. Then, radiomics features were extracted from manually delineated volumes of interest. Two modeling strategies were performed after univariate analysis and feature selection. Finally, an optimal model was determined by the receiver operating characteristic area under the curve (AUC).@*RESULTS@#The optimal models were built in plan 1. For model 1 in plan 1, the AUCs of the training and validation cohorts were 0.973 (95% confidence interval [CI] 0.946-1.000) and 0.948 (95% CI 0.903-0.993), respectively. For model 2 in plan 1, the AUCs of the training and validation cohorts were 0.944, 95% CI 0.905 to 0.983, and 0.968, 95% CI 0.940 to 0.996, respectively.@*CONCLUSIONS@#Radiomics analysis of DWI images allows for accurate identification of LF and ESC, and the non-invasive biomarkers extracted from the functional DWI images can serve as a better alternative to biopsy.

Role of adiponectin in diabetes myocardial ischemia-reperfusion injury and ischemic postconditioning

Abstract Purpose Patients with diabetes are vulnerable to myocardial I/R (ischaemia/reperfusion) injury, but are not responsive to IPO (ischaemic post-conditioning). We hypothesized that decreased cardiac Adiponectin (APN) is responsible for the loss of diabetic heart sensitivity to IPO cardioprotecton. Methods Diabetic rats were subjected to I/R injury (30 min of LAD occlusion followed by 120 min of reperfusion). Myocardial infarct area was determined by TTC staining. Cardiac function was monitored by a microcatheter. ANP, 15-F2t-isoprostane, nitrotyrosine and MDA were measured by assay kits. Levels of p-Akt, total-Akt and GAPDH were determined by Western Blot. Results Diabetic rats subjected to myocardial IR exhibited severe myocardial infarction and oxidative stress injury, lower APN in the plasma and cardiac p-Akt expression ( P <0.05). IPO significantly attenuated myocardial injury and up-regulated plasma APN content and cardiac p-Akt expression in non-diabetic rats but not in diabetic rats. Linear correlation analysis showed that the expression of adiponectin was positively correlated with p-Akt and negatively correlated with myocardial infarction area ( P <0.01). Conclusion Protective effect of IPO was tightly correlated with the expression of adiponectin, exacerbation of I/R injury and ineffectiveness of IPO was partially due to the decline of adiponectin and inactivation of Akt in diabetes mellitus.

Simultaneous and Rapid Detection of Concentrated Liquid of Compound Dahuang Decoction Based on Near Infrared Spectroscopy / 中国实验方剂学杂志

Objective::Near infrared spectroscopy was used to detect the concentration density (25 ℃), solid-containing content, rhein content and glycyrrhizic acid content of compound Dahuang decoction. Method::The concentrated liquid of compound Dahuang decoction was determined by near infrared optical fiber transmission spectrometry. The contents of rhein and glycyrrhizic acid were determined by HPLC. Fifty-one samples were used for internal cross-validation, and partial least square regression was used to establish correction models between near-infrared spectrum and density, solid-containing content, rhein content and glycyrrhizic acid content, respectively. Ten unknown concentrated liquid samples were collected for external validation and prediction. Result::The external validation complex correlation coefficients between near-infrared spectra and density, solid-containing content, rhein content and glycyrrhizic acid content of the concentrated liquid of compound Dahuang decoction were 0.995 9, 0.999 6, 0.997 0 and 0.992 2, and the root mean square error of prediction (RMSEP) values were 2.50×10-3, 0.17, 7.57 and 67.10, respectively. Conclusion::The near infrared spectroscopy is suitable for the determination of evaluation indexes of the concentrated liquid index of compound Dahuang decoction, and has the characteristics of rapid, simple, stable and reliable.

Dexmedetomidine preconditioning protects against lung injury in hemorrhagic shock rats / Pré-condicionamento com dexmedetomidina protege contra lesão pulmonar em ratos com choque hemorrágico

Abstract Background and objectives: Dexmedetomidine has demonstrated protective effects against lung injury in vitro. Here, we investigated whether dexmedetomidine preconditioning protected against lung injury in hemorrhagic shock rats. Methods: Male Sprague-Dawley rats were randomly divided into four groups (n = 8): control group, hemorrhagic shock group, 5 ug.kg-1 dexmedetomidine (DEX1) group, and 10 ug.kg-1 dexmedetomidine (DEX2) group. Saline or dexmedetomidine were administered over 20 min. 30 min after injection, hemorrhage was initiated in the hemorrhagic shock, DEX1 and DEX2 group. Four hours after resuscitation, protein and cellular content in bronchoalveolar lavage fluid, and the lung histopathology were measured. The malondialdehyde, superoxide dismutase, Bcl-2, Bax and caspase-3 were also tested in the lung tissue. Results: Compare with hemorrhagic shock group, 5 ug.kg-1 dexmedetomidine pretreatment reduced the apoptosis (2.25 ± 0.24 vs. 4.12 ± 0.42%, p < 0.05), histological score (1.06 ± 0.12 vs. 1.68 ± 0.15, p < 0.05) and protein (1.92 ± 0.38 vs. 3.95 ± 0.42 mg.mL-1, p < 0.05) and WBC (0.42 ± 0.11 vs. 0.92 ± 0.13 × 109/L, p < 0.05) in bronchoalveolar lavage fluid. Which is correlated with increased superoxide dismutase activity (8.35 ± 0.68 vs. 4.73 ± 0.44 U.mg-1 protein, p < 0.05) and decreased malondialdehyde (2.18 ± 0.19 vs. 3.28 ± 0.27 nmoL.mg-1 protein, p < 0.05). Dexmedetomidine preconditioning also increased the Bcl-2 level (0.55 ± 0.04 vs. 0.34 ± 0.05, p < 0.05) and decreased the level of Bax (0.46 ± 0.03 vs. 0.68 ± 0.04, p < 0.05), caspase-3 (0.49 ± 0.03 vs. 0.69 ± 0.04, p < 0.05). However, we did not observe any difference between the DEX1 and DEX2 groups for these (p > 0.05). Conclusion: Dexmedetomidine preconditioning has a protective effect against lung injury caused by hemorrhagic shock in rats. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation. But did not show a dose-dependent effect.

Resumo Justificativa e objetivos: Dexmedetomidina demonstrou efeitos protetores contra a lesão pulmonar in vitro. Neste estudo, investigamos se o pré-condicionamento com dexmedetomidina protege contra a lesão pulmonar em ratos com choque hemorrágico. Métodos: Ratos machos, Sprague-Dawley, foram aleatoriamente divididos em quatro grupos (n = 8): grupo controle, grupo com choque hemorrágico, grupo com 5 µg.kg-1 de dexmedetomidina (DEX1) e grupo com 10 µg.kg-1 de dexmedetomidina (DEX2). Solução salina ou dexmedetomidina foi administrada durante 20 minutos. Trinta minutos após a injeção, a hemorragia foi iniciada nos grupos choque hemorrágico, DEX1 e DEX2. Quatro horas após a ressuscitação, a proteína e o conteúdo celular no lavado broncoalveolar e a histopatologia pulmonar foram medidos. Malondialdeído, superóxido dismutase, Bcl-2, Bax e caspase-3 também foram testados no tecido pulmonar. Resultados: Na comparação com o grupo choque hemorrágico, o pré-tratamento com 5 ug.kg-1 de dexmedetomidina reduziu a apoptose (2,25 ± 0,24 vs. 4,12 ± 0,42%, p < 0,05), escore histológico (1,06 ± 0,12 vs. 1,68 ± 0,15, p < 0,05) e proteína (1,92 ± 0,38 vs. 3,95 ± 0,42 mg.mL-1, p < 0,05) e leucócitos (0,42 ± 0,11 vs. 0,92 ± 0,13 × 109/L, p < 0,05) no lavado broncoalveolar; o que está correlacionado com o aumento da atividade da superóxido dismutase (8,35 ± 0,68 vs. 4,73 ± 0,44 U.mg-1 de proteína, p < 0,05) e diminuição do malondialdeído (2,18 ± 0,19 vs. 3,28 ± 0,27 nmoL.mg-1 de proteína, p < 0,05). O pré-condicionamento com dexmedetomidina também aumentou o nível de Bcl-2 (0,55 ± 0,04 vs. 0,34 ± 0,05, p < 0,05) e diminuiu o nível de Bax (0,46 ± 0,03 vs. 0,68 ± 0,04, p < 0,05), caspase-3 (0,49 ± 0,03 vs. 0,69 ± 0,04, p < 0,05). No entanto, não houve diferença entre os grupos DEX1 e DEX2 para essas proteínas (p > 0,05). Conclusão: O pré-condicionamento com dexmedetomidina tem um efeito protetor contra a lesão pulmonar causada por choque hemorrágico em ratos. Os potenciais mecanismos envolvidos são a inibição da morte celular e a melhora da antioxidação. Porém, não mostrou um efeito dose-dependente.

Effect of Hei Xiaoyaosan on Expressions of Aβ1-42, GSK-3β, NEP, IDE in Hippocampus Area of Alzheimer's Dementia Mice / 中国实验方剂学杂志

Objective: To observe the effect of Hei Xiaoyaosan on expressions of β-amyloid 1-42 peptide(Aβ1-42),glycogen synthase kinase-3β(GSK-3β),neprilysin(NEP),insulin-degrading enzyme(IDE) in the hippocampus area of Alzheimer's dementia mice. Method: After weighing, 42 APP/PSI bivalent transgenic mice were randomly divided into 4 groups:10 mice in the model group, 10 mice in the positive drug control group, 11 mice in the high-dose Hei Xiaoyaosan group, and 11 mice in the low-dose Hei Xiaoyaosan group; 10 wild C57BL/6J mice of the same age and strain were used for negative control group. Drugs were administered to mice by gavage once a day for 12 weeks. Then the behavior of all the mice were detected by Morris water maze, the morphological changes in hippocampal neurons were observed by hematoxylineosin(HE) staining, the expressions of Aβ1-42, GSK-3β, NEP and IDE proteins in hippocampus were detected by immunohistochemistry. Result: After 3 months of treatment, compared with negative control groups, the average escaping latency periods prolonged significantly, and the number of cross-platform was decreased significantly in model group (Pβ1-42 and GSK-3β proteins in model mice hippocampus were significantly increased (PPPβ1-42 and GSK-3β proteins in the hippocampus of drug groups were significantly decreased (PPPConclusion: Hei Xiaoyaosan can significantly improve the learning and memory abilities of AD mice, which may be related to the reduction of cognitive impairment in AD mice by regulating abnormal deposition and degradating Aβ in the hippocampus.

Effect of Hei Xiaoyaosan on Expressions of APP，PERK in Hippocampus Area of Alzheimer's Dementia Mice / 中国实验方剂学杂志

Objective: To study the effect of Hei Xiaoyaosan on endoplasmic reticulum stress in hippocampal neurons of Alzheimer's disease (AD) model mice, including behavioral, histopathology and amyloid precursor protein (APP), protein kinase endoplasmic reticulum kinase (PERK) expressions. Method: The 42 4-month-old SPF-grade double transgenic (APP/PS1) mice were randomly divided into the high-dose group and the low-dose group, the donepezil hydrochloride group and the model group, and 10 C57BL mice of the same age were used as the blank group. Firstly, they were adapted to the environment for one week. After 2 months of treatment with different drug interventions, Morris water maze behavior was used to test the learning and memory abilities of each group of mice. After 1 month of treatment, histopathological changes in the hippocampus of each group of mice were observed by light microscopy. The expressions of APP, PERK protein and mRNA in the endoplasmic reticulum of hippocampus were detected by immunohistochemistry (IHC) and real-time fluorescent quantitative polymerase chain reaction (Real-time PCR). Result: After drug intervention, compared with the blank group, the escape latency of the AD model group was significantly prolonged (PPPPPConclusion: Hei Xiaoyaosan can significantly improve the learning and memory abilities of AD mice, which may be related to the reduction of the excessive stress response of endoplasmic reticulum to alleviate cognitive impairment in AD mice.

Pharmacokinetic-pharmacodynamic analysis of ciprofloxacin in elderly Chinese patients with lower respiratory tract infections caused by Gram-negative bacteria / 中华医学杂志(英文版)

BACKGROUND@#Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria.@*METHODS@#From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patient's renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (Cmax/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group.@*RESULTS@#Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii, and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 ± 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target Cmax/MIC value of >8. The AUC/MIC and Cmax/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7-214.9] vs. 10.4 [3.8-66.1], Z = -4.157; 9.6 [4.2-17.8] vs. 1.3 [0.4-4.7], Z = -4.018; both P  125 and Cmax/MIC > 8, cannot be reached.

Prokaryotic expression and purification of recombinant CARD9-MBP fusion protein / 医学研究生学报

Objective　CARD9 can activate several pathways involved in immunity, such as NF-ΚB, MAPK, etc. However the mechanism of this process has not yet been elucidated. For conducting relevant experiments in vitro, a prokaryotic expression vector of CARD9-MBP fusion protein has to been construct, and the fusion protein need to be expressed and purified.　Methods　The coding sequence of CARD9 and MBP genes were amplified by PCR and the recombinant plasmid was correctly inserted into the pET-30a(+) vector. The recombinant plasmid was transformed into E.coli DH5α competent cells and proceeded PCR identification, restriction analysis and gene sequencing. The correct recombinant plasmid was transformed into E.coli BL21(DE3) competent cells. The target protein was induced to express by IPTG under different conditions. Relative molecular weight of the target protein was detected by SDS-PAGE electrophoresis. The CARD9-MBP fusion protein was purified by MBP maltose chromatography column and gel filtration chromatography column, and identificated by MALDI-TOF mass spectrometry after MBP-tag to be removed by HRV3C enzyme.　Results　The CARD9-MBP fusion protein was successfully constructed and confirmed by PCR and restriction analysis. The result of gene sequencing was consistent with the target sequence. The SDS-PAGE electrophoresis showed that the target protein with molecular mass (MR) about 105 000 was successfully induced to express in E.coli BL21 (DE3). A quite pure CARD9-MBP fusion protein was obtained by purification of MBP maltose chromatography column. Identification by MALDI-TOF mass spectrometry demonstrated that the target protein after MBP-tag to be removed by HRV3C enzyme is CARD9 protein. In the later stage, gel filtration chromatography column was used to obtain further pure CARD9-MBP fusion protein.　Conclusion　The prokaryotic expression vector of CARD9-MBP fusion protein was successfully constructed and a large number of soluble protein expressed. The purified target protein can be obtained by purification with MBP maltose chromatography column and gel filtration chromatography column.

Effect of Fuzi Lizhong decoction in reducing liver injury of rats with non-alcoholic fatty liver via activating AMPK and suppressing NF-κBp65 pathway / 中国中药杂志

To investigate the protective effect and relevant mechanism of Fuzi Lizhong decoction (FZLZD) on liver of rats with non-alcoholic fatty liver disease (NAFLD), totally 32 male SPF Wistar rats were randomly divided into 4 groups: control group, model group, Yishanfu (YSF) group (200 mg·kg⁻¹·d⁻¹) and FZLZD group (10 g·kg⁻¹·d⁻¹), with 8 rats in each group. Rat model of NAFLD was prepared through the intragastric administration with fat emulsion for 4 weeks. After the successful modeling, rats in each administration group were continuously administered for 4 weeks. After 8 weeks, the rats in each group were put to death, and the pathological changes in liver tissue were detected by HE staining. Automatic biochemical analyzer was used to detect fasting serum lipid levels (T-Chol, TG, LDL-C, HDL-C) and liver functions (ALT, TP, ALB) of rats in each group. The rat liver index was calculated by weighing method. Enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of inflammatory cytokines TNF-α and IL-6 in liver tissue. Real-time quantitative PCR (qRT-PCR) was used to detect the mRNA expressions of fat metabolism-related factors SREBP-1c and FASN in liver tissue. Western blot was used to detect the p-AMPK and p-NF-κBp65 protein expressions in liver tissue. The results of HE staining showed that compared with the control group, the pathological changes in liver tissue in the model group rats were obvious; specifically, the outline of hepatic lobule was unclear, the hepatic cells showed diffuse steatosis of adipose tissue, and were accompanied by inflammatory infiltration, nuclear condensation, coloring deep; compared with the model group, liver lesions of all of the treatment groups were significantly alleviated; especially, the FZLZD group showed the most significant degree of remission. The results of serum test showed that the levels of serum lipids (T-Chol, TG, LDL-C, HDL-C), liver functions (ALT, TP, ALB) and liver index in model group were significantly higher than those in control group (<0.01); compared with the model group, the indexes of serum lipid and liver function of rats in each treatment group were significantly decreased (<0.01), and those in FZLZD group were significantly decreased (<0.05), while those in YSF group were not significantly changed. The results of ELISA and qRT-PCR showed that compared with the control group, the secretion levels of TNF-α, IL-6 and the mRNA levels of SREBP-1c and FASN in the liver tissue of model group rats were significantly increased (<0.01); compared with model group, the secretion levels of TNF-α, IL-6 and the mRNA levels of SREBP-1c, FASN in liver tissue of rats in each treatment group were significantly decreased (<0.01); compared with YSF group, the secretion levels of TNF-α and IL-6 and the mRNA levels of SREBP-1c and FASN in FZLZD group were significantly different (<0.01). Western blotting showed that compared with the model group, the protein expression of p-AMPK in liver tissue of rats in FZLZD group was significantly increased (<0.01), while the protein expression of p-NF-κBp65 was significantly decreased (<0.01). FZLZD can significantly improve hepatic pathological changes, reduce serum lipid levels, promote liver function and liver index in NAFLD rats, which may be associated with the activation of the AMPK pathway and thereby the inhibition of the expressions of SREBP-1c and FASN, and the inhibition of the NF-κBp65 pathway and thereby the reduction of the release of inflammatory factors.