Objective To assess the effect of quality control circle on blood pressure and metabolic syndrome in patients with newly diagnosed primary hypertension. Methods Review health examination in 132 cases of newly diagnosed patients with primary hypertension as the control group, routine health education was given. The 128 cases of patients with newly diagnosed primary hypertension as the intervention group and the prospective study was done.The quality control group of quality control circle was set up in order to improve treatment adherence for patients with newly diagnosed primary hypertension, and the nursing intervention was implied for the intervention group for 6 months. Blood pressure and metabolic syndrome were compared between the two groups. Results The compliance rate was improved from 56.3%(72/128) to 90.6%(116/128) after intervention in the intervention group. There was significant difference before and after intervention (χ2=62.57, P<0.01).The systolic blood pressure, diastolic blood pressure, triglyceride (TG), fasting blood glucose (FBG) and waist circumference were (151.6±11.3) mmHg (1 mmHg=0.133 kPa), (98.6±12.1) mmHg, (1.98±0.36) mmol/L, (6.37±1.25) mmol/L, (92.88±6.90) cm respectively before intervention in the intervention group and were (132.6±14.3) mmHg, (82.5 ± 12.5) mmHg, (1.53 ± 0.17) mmol/L, (5.34 ± 1.06) mmol/L, (83.29 ± 5.47) cm respectively after intervention. There was statistically significant difference before and after intervention in the intervention group(t=7.11-12.79, P<0.05). The systolic blood pressure, diastolic blood pressure, TG, FBG and waist circumference were (150.4 ± 10.6) mmHg, (99.4 ± 10.8) mmHg, (1.94 ± 0.39) mmol/L, (6.52 ± 0.29) mmol/L, (91.37±6.03) cm respectively before intervention in the control group and were (145.3±13.7) mmHg, (92.6± 10.9) mmHg, (1.86 ±0.31) mmol/L, (6.02±0.27) mmol/L, (93.86±6.52) cm respectively after intervention. There was significant difference in systolic blood pressure and diastolic blood pressure before and after intervention in the control group (t=3.38, 5.09, P<0.05). But the difference was not statistically significant in TG, FBG and waist circumference (t=1.85, 1.27, 1.93, P>0.05). The difference of systolic blood pressure,diastolic blood pressure,TG, FBG and waist circumference between two groups was statistically significant after the intervention (t=6.77-12.84,P<0.05). The intervention group was significantly better than the control group. Conclusions The quality control circle may improve treatment adherence and it is helpful to improve the metabolic syndrome and it has high clinical application value for the treatment of primary hypertension.

Objective To investigate the signal pathway of platelet activation in acute respiratory distress syndrome (ARDS). Methods Thirty healthy Sprague-Dawley (SD) rats were randomly divided into control group (n = 6) and model group (n = 24). The model of ARDS was reproduced by intravenous injection of oleic acid (0.25 mL/kg), and the rats in control group were injected with the same amount of normal saline. The blood of abdominal aorta was collected at 2, 6, 24, and 72 hours after model reproduction, the platelets were separated, and c-Jun N-terminal kinase phosphorylation (pJNK) levels which was one of major protein kinases in the mitogen-activated protein kinases (MAPKs) signal pathway was determined by Western Blot. The rats were sacrificed, the lung tissues were harvested, and lung coefficient (lung weight/body weight ×100%) and lung wet/dry (W/D) ratio were calculated. Pathological changes in the lung tissue were observed with hematoxylin-eosin (HE) staining in light microscope. Results Comp ared with the control group, platelet pJNK level in ARDS model group was significantly increased at 2 hours after model reproduction (gray value: 0.72±0.09 vs. 0.22±0.01), and peaked at 6 hours (gray value: 0.91±0.03 vs. 0.22±0.01), then it was decreased gradually. It was also significantly higher than that of control group till 72 hours after model reproduction (gray value: 0.39±0.06 vs. 0.22±0.01, all P < 0.05). Lung coefficient and lung W/D ratio in ARDS model group were significantly increased at 2 hours after model reproduction as compared with those of control group [(1.30±0.20)% vs. (0.60±0.10)%, 6.00±0.60 vs. 3.30±0.30], then they were decreased gradually. They were also significantly higher than those of control group till 72 hours after model reproduction [(0.90±0.10)% vs. (0.60±0.10)%, 4.80±0.70 vs. 3.30±0.30, all P < 0.05]. It was showed by light microscopy that lung tissue of rats in the control group had no significant pathological changes. At 2 hours after model reproduction in model group, clearly visible alveolar edema and interstitial edema, interstitial lung infiltration of inflammatory cells, small blood vessels dilation and congestion were found, and the re were a lot of protein exudates. The lesions of lung peaked at 24 hours. At 72 hours, absorption of most of fluid leaking in alveolar, alveolar space narrow, alveolar septum thickening, the reduction of inflammatory cells infiltration, fibrous tissue proliferation, and micro thrombosis formation were found. Conclusion In ARDS, in addition to pathological changes in the lung tissue, platelet activation occurs, and its activation process is related to the priming of JNK signal transduction pathways.

Objective:To evaluate the assistant role of manifestations under tracheoscopy in the diagnosis of invasive pulmonary aspergillosis (IPA) in severe patients.Methods:A retrospective study was conducted. The patients with suspected IPA admitted to intensive care unit (ICU) of Affiliated Hospital of Binzhou Medical College from January 2015 to December 2019 were enrolled. The diagnosis, clinical diagnosis and suspected diagnosis were made according to the grading criteria of Guidelines for the diagnosis and treatment of invasive fungal infection in severe patients (2007). Those who met the criteria were enrolled in the IPA group, and those who did not meet the criteria or other pathogens were enrolled in the non-IPA group. The general data of the patients were collected, and the changes of tracheal and bronchial mucosa under tracheal microscope before and after treatment were recorded, as well as the results of galactomannan (GM) test and aetiology culture of bronchoalveolar lavage fluid (BALF). The baseline, bronchoscopy and pulmonary CT manifestations and their dynamic changes were compared in each group. Results:A total of 142 patients with suspected IPA were finally enrolled. Among them, 12 were pathologically proven IPA, 77 were probable IPA, 22 were possible IPA, and 31 were undefined IPA. Of the 142 patients, 60 had typical manifestations of mucosal injury under bronchoscopy, including 7 proven IPA patients (58.3%), 52 probable IPA patients (67.5%), and 1 possible IPA patient (4.5%), but none undefined IPA patient. The patients undergoing lung CT scan were 12 proven IPA patients (100%), 73 probable IPA patients (94.8%), and 21 possible IPA patients (95.5%), respectively. Most of the Chest CT showed patchy or strip density increasing and other non-specific manifestations. There were 3 proven IPA patients (25.0%), 7 probable IPA patients (9.0%), and 0 possible IPA patient (0%) who had typical IPA CT manifestations (halo sign and cavity or crescent sign). Among the patients of proven IPA and probable IPA (89 cases), there were a total of 35 cases with endoscopic airway mucosal injury and tracheoscopy reexamination ≥ 3 times. All the 35 patients received anti-aspergillus treatment, among which 16 survived and 19 died. Among the 16 patients who survived, the microscopic appearance of mucosal injury was gradually reduced and the clinical manifestations were gradually improved. Of the 19 patients who died, 16 had deteriorated endoscopic airway mucosal injury.Conclusions:The specific manifestations of severe patients with bronchial mucosal injury are of great significance in the diagnosis of IPA. In the case of severe patients who cannot receive pathological examination or chest CT in time, dynamic observation of the changes of airway mucosal injury is a simple auxiliary method to discover the changes of patients' condition in time, evaluate the effect of antifungal therapy and the prognosis of IPA.

Objective To study the distribution characteristics and drug resistance of non-fermenting bacterial infection in intensive care unit (ICU) at a tertiary hospital during seven consecutive years,and to provide evidence for rational use of antibiotics in ICU.Methods A retrospective analysis was conducted.The related data about non-fermentative bacteria obtained from clinical specimens,collected from lower respiratory tract,blood,urine,bile and other secretions of ICU patients admitted to Binzhou Medical University Hospital from January 2009 to December 2015 were retrospectively analyzed.The distribution characteristics and drug resistance of non-fermentative bacteria,and isolation rate of multiple drug resistance (MDR) strains were analyzed.Results 2 672 strains of nonfermentative bacteria were isolated during seven consecutive years,accounting for 57.9％ gram negative (G-) bacilli (2 672/4 613),and 35.2％ of all bacteria (2 672/7 587).The top five were Acinetobacter baumannii (38.4％),Pseudomonas aeruginosa (34.6％),Onion burkholderia cepacia (9.9％),Stenotrophomonas maltophilia (6.2％),and Pseudomonas fluorescens (5.6％).Non-fermentative bacteria were mainly isolated from the lower respiratory tract (60.9％).Isolation of the non-fermentative bacteria accounted for over 50％ of G-bacilli during seven consecutive years,and the isolation rate of the top five types of bacteria showed no obvious change,while positive rate of Acinetobacter baumannii showed a tendency to increase (obviously from 26.5％ in 2009 to 50.2％ in 2015),and a lowering trend of positive rate of Onion burkholderia cepacia,Stenotrophomonas maltophilia,and Pseudomonas fluorescens was obvious (from 15.6％,10.6％,13.0％ in 2009 to 5.6％,7.4％,1.4％ in 2015 respectively) was observed.The isolation rate of Pseudomonas aeruginosa was stable (about 30％) during seven consecutive years.The drug susceptibility results showed that the resistant rates of Acinetobacter baumannii against imipenem,meropenem,aminoglycosides and third-generation cephalmsporins were all higher than 70％,while its resistant rate to cefoperazone-sulbactam was relatively lower (40.2％-68.1％)with relatively higher sensitivity rate (23.6％-46.0％).In contrast,the resistant rates of Pseudomonas aeruginosa against antibiotics were low,while the sensitivity rate to fourth-generation cephalmsporins cefepime (58.3％-87.7％)and third-generation cephalmsporins was high (ceftazidime:55.6％-79.3％,piperacillin-tazobactam:62.5％-86.2％,cefoperazone-sulbactam:46.0％-89.8％).From 2009 to 2015,the incidence of MDR strains of Acinetobacter baumannii showed an obvious increasing tendency (from 68.0％ to 84.1％);in contrast,the incidence of MDR strains of Pseudomonas aeruginosa did not show an obviously increase in incidence from 2009 to 2012,on the other hand,it showed a decreasing tendency from a peak 68.6％ in 2012 to 23.5％ in 2015.Conclusions The isolation rate of non-fermentative bacteria was high and the drug resistance situation was serious.Therefore,it is important to grasp the knowledge regarding distribution characteristics,drug resistance and variation of non-fermentative bacteria in ICU.It is not only beneficial for both rational use of antibiotics,improve efficacy but also helpful in reducing the emergence of drug resistance stains.

OBJECTIVE:To optimize the technology of supercritical CO2 extraction from Zingiberis rhizoma. METHODS:With the comprehensive score of the contents of 6-ginger phenol,8-ginger phenol and 10-ginger phenol and the extraction rate of the oil from Z. rhizoma as the index,uniform design method was adopted to investigate the effects of extraction pressure,extrac-tion temperature and extraction duration on the extraction result;verification tests were conducted. RESULTS:The optimal condi-tions were as follows as the extraction pressure of 25 MPa,extraction temperature of 30 ℃ and extraction duration of 2 h. In the verification tests,the average extraction rate of the oil from Z. rhizoma was 3.2%(n=3),and the comprehensive score was 1.874 2 (RSD=0.65%,n=3),with the relative deviation of 0.6% between the measured value and the predicted value. CONCLUSIONS:The optimal extraction technology is stable and feasible,with the advantages of low temperature,short duration.

Objective To observe Hedgehog signaling pathways of liver cancer cell growth and the influence of the metastatic potential targeted inhibit Hedgehog.Methods Construction of Smo shRNA plasmid,The stable and low-expressed Smo-expressing HCC QGY-7701 cell line was screened after lipofection.The stable and low-expressed Smo-expressing HCC QGY-7701 cell line was screened,The cell cycle,apoptosis,invasion and metastasis of QGY-7701 cells were detected by Western blot,flow cytometry,CCK8 and transwell assay.Subcutaneous implantation of hepatocarcinoma cells in nude mice.Study on the growth and metastasis of hepatocarcinoma cells with low expression of Smo in.The ultrastructural changes of hepatoma cells with low expression of Smo were observed under electron microscope.Results RT-PCR and Western blot showed stable shR-Smo cell line was successfully constructed.Cell cycle test showed that compared with the control group,G0/G1 cells increased in shR-Smo,cells in S phase decreased;apoptosis,CCK8 and Transwell tests showed that Smo-gene silencing could significantly increase the apoptosis percentage of the hepatic cancer cells to (5.46％ ± 1.46％),proliferation activity decreasedand and the migration rates reduced to (7.82％ ±2.14)％;nude mice model showed that Smo-gene silencing could inhibit the growth of hepatocellular carcinoma cells in vivo,electron microscopy revealed that lysosomes increased significantly in Smo-gene silence cells.Conclusions Blocking Hh signaling pathways,liver cancer cells in vitro malignant degree of decline.Hedgehog in treating liver cancer have hidden meaning.

Objective This study was conducted to evaluate treatment-related toxicities,the patterns of failure,overall survival(OS)and progression-free survival(PFS)by comparing IFI with ENI in combination with chemotherapy. Methods Eligible patients were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. The primary end points wereacute treatment-related toxicities. The secondary end points were patterns of failure,OS and PFS. Kaplan?Meier survival rate of the method for calculating the Logrank test difference method. Results Between April 2012 and October 2016,a total of 228 patients were enrolled from nine centers in china. Grade≥3,Grade≥2 radiation esophagitis and pneumonitis in the IFI arm were significantly lower than that of the ENI arm(P=0.018,0.027).No significant differences were observed in overall failure rates,loco-regional failure,distant failure rates,in-field and out-field lymph node failure between the two arms(P=0.401,0.561,0.510,0.561,0.681).The 1-,2-, 3-,4-yearand median OS in the ENI arm and IFI arm were 84.1%,57.3%,39.4%,31.6%,28 months and 83.6%,62.1%,44.5%,31.5%,32 months(P=0.654),respectively. The 1-,2-,3-yearand median PFS in the ENI arm and IFI arm were 71.9%,42.3%,32.7%,20 months and 70.1%,45.0%,35.9%,22 months (P=0.885),respectively. Conclusions Compared to ENI,IFI resulted in decreased radiation pneumonitis and esophagitis without sacrificing loco-regional lymph nodal control,PFS and OS in thoracic ESCC. Clinical Trial Registry Chinese Clinical trail registry,registration number:NCT01551589.

OBJECTIVE： To establish the fingerprint of Maizao yishen granules， and to provide scientific basis for its further development. METHODS： HPLC method was adopted to establish the fingerprint by using 10 batches of Maizao yishen granules sa samples. The determination was performed on Venusil XBP C18（L） column with mobile phase consisted of acetonitrile-0.2％ phosphoric acid （gradient elution） at the flow rate of 1→0.7 mL/min at 7-10 min， 0.7→1 mL/min at 10-15 min and 1 mL/min at the rest of time. The detection wavelengths were set at 284 nm （0-7 min）， 330 nm （7-32 min） and 360 nm （32-45 min）. The column temperature was 25 ℃， and sample size was 10 μL. The fingerprint of Maizao yishen granules was established， and the similarity evaluation was performed by using “Similarity Evaluation System of TCM Chromatographic Fingerprints” （2004 A edition） software. Then， the common peaks were assigned and identified by comparing reference substance and control medicinal materials. RESULTS： The precision， stability （24 h） and repeatability of the methodological investigation were all good [RSD values of relative retention time and relative peak area of each chromatographic peak were less than 3％ （n＝6）]. The similarity of 10 batches of samples were all above 0.900. Seventeen common peaks were identified， of which common peak 1 and 6 came from Semen Raphani； common peak 7， 9， 14， 15 and 16 from Citrus reticulata； common peak 5， 10， 11， 12 and 13 came from Glycyrrhiza uralensis； common peak 2 came from C. reticulata， G. uralensis and Ziziphus jujuba； peak 3 came from G. uralensis and Semen Raphani； peak 8 came from Hordeum vulgare and Semen Raphani； peak 4 and 17 came from C. reticulata and G. uralensis. Peak 1 was identified as hesperidin and the peak 9 was identified as sinapine. CONCLUSIONS： Established fingerprint of Maizao yishen granules is accurate and reliable， and can be used for quality control of Maizao yishen granules.

Objective:To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis.Methods:Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn.Results:There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [μg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [μg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95% CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (β value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 μg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly. Conclusions:PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 μg/L, the 28-day survival rate decreased significantly.

Objective:To study the role of SUMOylation in the process of therapeutic hypothermia on neural stem cells (NSCs) in neonatal hypoxic-ischemic encephalopathy.Methods:SUMOylation is an essential post-translational modification involving small ubiquitin-like modifiers (SUMOs). Primary-cultured NSCs from mice were assigned into four groups: control group, hypoxia group, hypothermia group and hypoxia+hypothermia group. Western Blot was used to detect the protein levels of SUMO2/3, hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator factor 1α (PGC-1α) and octamer binding transcription factor 4 (Oct4). The diameters of NSCs were compared. ELISA was used to detect lactate dehydrogenase (LDH) level. Apoptosis was examined using flow cytometry. Immunofluorescence method was used to measure the differentiation of NSCs into neuronal cells.Results:Compared with the control group, the levels of SUMO2/3, HIF-1αand PGC-1α in NSCs of the hypoxia group increased 33%, 126% and 140%, respectively ( P<0.05). Compared with the control group, the levels of SUMO2/3 and PGC-1α in NSCs of the hypothermia group increased 52% and 536%, respectively ( P<0.05). Compared with the hypoxia group, the levels of SUMO2/3, HIF-1α, PGC-1α and Oct4 in the hypoxia+hypothermia group increased 44%, 40%, 230% and 59%, respectively ( P<0.05). The diameters of NSCs in hypoxia group, hypothermia group and hypoxia+hypothermia group were smaller than control group, and hypoxia+hypothermia group smaller than hypoxia group ( P<0.05). No significant differences existed in LDH levels between hypothermia group and control group ( P>0.05). LDH level in hypoxia+hypothermia group were significantly lower than hypoxia group ( P<0.05). No significant differences existed in the cell death rates between hypothermia group and control group ( P>0.05). The cell death rate in hypoxia+hypothermia group was significantly lower than hypoxia group ( P<0.05). Compared with the control group, the expressions of Nestin in both hypoxia group and hypothermia group were increased, but neuron specific enolase (NSE) were decreased ( P<0.05). Compared with hypoxia group and hypothermia group, the level of Nestin in hypoxia+hypothermia group was further increased, while NSE was further decreased ( P<0.05). Conclusions:Therapeutic hypothermia may increase the tolerance of NSCs to hypoxia by enhancing SUMO modification of proteins, providing theoretical basis for the treatment of hypoxic-ischemic encephalopathy with therapeutic hypothermia.