Objective To investigate the extraction process of Yuchang granules .Methods The extraction process was optimized by orthogonal experiment based on the content of berberine ,atractylodes lactone Ⅰ and the extraction yield .Results Through the visual analysis of orthogonal experiment ,the analysis of variance and the verification experiments ,the optimum extraction process was obtained as follows :extracting 1 h for twice with 10 times water of medicinal herbs and the 70％ ethanol depositing concentration .Conclusion This process is consistent and feasible .It is a simple and convenient method to extract Yuchang granules .

We report a case of a fetus with rhizomelic chondrodysplasia punctata type Ⅰ. Ultrasound examination of the pregnant women at 23 weeks of gestation showed multiple fractures in bilateral femurs, thick metaphysis, severely short, thickened and curved bilateral humerus with multiple fracture images, some of which were callu formation after fracture. The pregnancy was terminated at 23 +2 gestational weeks, samples of fetal skin tissue were taken after birth, and parental peripheral blood was collected for whole exome sequencing, which revealed a frameshift mutation c.179delT (p.F61Lfs*13) in the PEX7 gene of chromosome 6, and the heterozygous deletion (141 kb) occurred in the region of chromosome 6 137105182-137245871, covering the pathogenic gene PEX7. The analysis of parental samples suggested that the mutations were compound heterozygous mutations, none of which had been previously reported and were determined to be pathogenic mutations. The severe clinical phenotype of this case may be caused by severe damage of PEX7 gene contributed by the frameshift mutation and large fragment deletion mutations.

Objective To investigate the learning curve of contrast-enhanced ultrasonography ( CEUS) in sentinel lymph node( SLN ) of breast cancer and provide a theoretical basis for leaners to learn SLN CEUS . Methods The multi-center study of SLN CEUS in breast cancer" was planned by Sichuan Cancer Hospital . According to the uniform inclusion and exclusion criteria , 511 patients with complete clinical data and follow-up results from 9 hospitals in Multi-center were included in this study . According to the inspection time ,the patients were divided into 3 groups named as group A ( 170 patients) ,group B ( 170 patients) and group C ( 171 patients ) ,respectively . The basic clinical data ,ultrasound imaging data , intraoperative and postoperative pathological findings of all patients were recorded . With the accumulation of cases examined ,analysis was performed to find the learning curve of the SLN CEUS examination time , SLN CEUS detection rate ,SLN CEUS surface marking accuracy rate and SLN CEUS diagnosis rate ,the learning curve was analyzed . Results ① There was no statistical significant difference in patients ages , tumors sizes ,tumors locations ,SLNs numbers and LCs numbers among the three groups( all P > 0 .05) . ②As the number of cases examined increases ,the examination time was reduced gradually ,but SLN detection rate ,surface marking accuracy and SLN diagnostic coincidence rate were increased gradually( F = 151 .75 , 1 .96 ,7 .49 ,5 .50 ; P = 0 .000 ,0 .143 ,0 .001 ,0 .005 ) . Conclusions The skill of the doctor is improved gradually when learning SLN CEUS . With the number of the cases increase ,the operating time of SLN CEUS is shorted ,and the SLN detection rate ,surface marking accuracy and SLN diagnostic coincidence rate of SLN-CEUS are gradually increased . It has an important clinical significance for beginners to learn the SLN CEUS technology .

Objective To investigate the relationship between nutritional risk status and implementation of nutrition therapy in mechanical ventilated (MV) chronic obstructive pulmonary disease (COPD) patients, so as to provide evidence for individualized nutrition therapy. Methods A prospective multicenter observational study was conducted. MV COPD patients admitted to Department of Intensive Care Units (ICU) of 10 County Hospitals in Zhejiang Province from January 2015 to January 2016 were enrolled, and according to nutrition risk screening 2002 (NRS2002) score, they were divided into nutritional high risk group (NRS2002 3-5) and nutritional extremely high risk group (NRS2002 6-7). Nutrition therapy situation and hospital mortality were compared between the two groups; multivariate Cox regression analysis was used to analyze the risk factors affecting the prognosis of patients with COPD under mechanical ventilation. Kaplan-Meier curve was used to analyze the prognosis at 30 days; receiver operating characteristic (ROC) curve was used to test the robustness of multivariable regression analysis. Results ① One hundred and six COPD patients with MV were analyzed; among them, 90 patients were in the nutritional high risk group, and 16 were in the nutritional extremely high risk group. There were no significant differences in age, gender and body mass index (BMI) between the two groups (all P > 0.05); the acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, NRS2002 score in patients of nutrition risk extremely high group were obviously higher than that in patients with nutrition high risk group (APACHEⅡ: 24.9±6.1 vs. 20.3±5.8, NRS2002 score: 6.3±0.5 vs. 4.2±0.8, both P < 0.05). ② Patients in both groups received early enteral nutrition (EN) therapy, the proportion of patients in nutritional extremely high risk group received early EN was lower than that of patients in the nutritional high risk group [12.5% (2/16) vs. 17.7% (16/90)], along with the prolongation of hospital stay, the proportions of patients beginning to receive the EN were gradually increased in the nutrition extremely high risk group and high risk group, after 2 days the EN increased significantly, and reached the highest value on day 6 after entering ICU [100.0% (16/16), 98.9% (89/90), respectively]; within 3 days after admission into ICU, the proportion of EN in nutrition extremely high risk group was obviously lower than that in nutrition high risk group, and from day 4, there was no statistical significant difference in proportion of EN between the two groups (all P > 0.05). The time to start parenteral nutrition (PN) treatment was relatively early admission to the ICU on day 1 and the proportion of this therapy was high in the two groups [56.2% (9/16), 27.7% (25/90), respectively], the PN proportion did not decrease with the length of hospitalization and the increase of EN. The proportion of patients in the nutrition extremely high risk group who started PN treatment was higher, which reached 56.2% admission to the ICU on day 1.③ With extension of hospital stay, the calories of EN were gradually increased in the nutritional high risk group, the highest calories in nutritional high risk groups was 4 318 (3 912, 4 812) kJ/d at day 7; while the highest calories in nutritional extremely high risk groups was 3 602 (2 167, 4 615) kJ/d at day 6 and a slight decreased at day 7; the difference of calories within the first week between the two groups had no significance (all P > 0.05). The calorific value of PN therapy remained at a constant level during hospitalization within 7 days, and after admission into ICU for 4-5 days, the target range of calories was achieved. ④ Kaplan-Meier survival curve analysis showed that the mortality at 30 days in the extremely high risk group was significantly higher than that in the high risk group [62.5% (10/16) vs. 11.1% (10/90), χ2 = 15.4, P < 0.01]. ⑤ Multiple cox-regression analysis showed that NRS2002 scoring was the independent risk factor affecting the mortality of patients in hospital [odds ratio (OR) = 2.08, 95% confidence interval (95%CI) = 1.39-3.12, P = 0.005]. ⑥ ROC curve analysis: according to ROC curve analysis of the effectiveness of multi-factor regression model, area under ROC curve (AUC) was 0.79, sensitivity was 70.00%, specificity was 74.42%, positive likelihood ratio was 2.74, negative likelihood ratio was 0.40, 95% confidence interval (95%CI) was 0.702-0.864, P = 0.001, and it showed that the regression model had a good prediction effect. Conclusions MV COPD patients have significant nutritional risk and all receive early EN therapy. The proportion of beginning to use PN treatment in patients with nutritional extremely high risk is relatively high. Initial nutritional status is the independent risk factor of poor prognosis in MV patients with COPD.

ObjectiveThe genotoxicity of zinc oxide nanoparticles （ZnO NPs） in rats was determined by Pig⁃a mutation assay in vivo. MethodsCombined with 28-day oral toxicity test， male SD rats were given ZnO NPs by oral administration for 28 days， at doses of 0， 14， 70 and 350 mg‧kg^-1 （maximum concentration of nanoscale dispersion state）. Rats in control groups received 350 mg‧kg^-1 of normal size ZnO， 40 mg‧kg^-1 N-ethyl-N⁃nitrosourea（ENU）or 0 mg·kg^-1 ZnO NPs（solvent control group） Changes of body weight were recorded. At 0， 15， 28 d and 28 d of recovery observation period， 200 μL of tail venous blood was collected from each group， which was labeled by APC mouse anti-rat erythroid cells and FITC mouse anti-rat CD59. The information of 1×10⁶ red blood cells（RBC） from each sample were collected by flow cytometry， and the mutation rate of RBC^CD59- was calculated. ResultsCompared with the solvent control group， after 15 days of intragastric administration， the mutation rate of RBC ^CD59- in peripheral blood of in 350 mg‧kg^-1 ZnO NPs group and 40 mg‧kg^-1 ENU group was significantly increased while that of in 70 mg‧kg^-1 ZnO NPs group was also significantly increased after 28 days of intragastric administration.with time-response and dose-response relationship. All groups except 40 mg‧kg^-1 ENU group showed no significant difference in the mutation rate of RBC^CD59- in peripheral blood in comparison with the solvent control group after 28-days recovery observation. Conclusion70 and 350 mg‧kg^-1 ZnO NPs can increase the mutation rate of Pig⁃a gene in peripheral blood of SD rats.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.