Aggregation represents a significant challenge for the long-term formulation stability of insulin therapeutics. The supramolecular PEGylation of insulin with conjugates of cucurbit[7]uril and polyethylene glycol (CB[7]‒PEG) has been shown to stabilize insulin formulations by reducing aggregation propensity. Yet prolonged in vivo duration of action, arising from sustained complex formation in the subcutaneous depot, limits the application scope for meal-time insulin uses and could increase hypoglycemic risk several hours after a meal. Supramolecular affinity of CB[7] in binding the B1-Phe residue on insulin is central to supramolecular PEGylation using this approach. Accordingly, here we synthesized N-terminal acid-modified insulin analogs to reduce CB[7] interaction affinity at physiological pH and reduce the duration of action by decreasing the subcutaneous depot effect of the formulation. These insulin analogs show weak to no interaction with CB[7]‒PEG at physiological pH but demonstrate high formulation stability at reduced pH. Accordingly, N-terminal modified analogs have in vitro and in vivo bioactivity comparable to native insulin. Furthermore, in a rat model of diabetes, the acid-modified insulin formulated with CB[7]‒PEG offers a reduced duration of action compared to native insulin formulated with CB[7]‒PEG. This work extends the application of supramolecular PEGylation of insulin to achieve enhanced stability while reducing the risks arising from a subcutaneous depot effect prolonging in vivo duration of action.

Objective:To evaluate the long-term impact of three different outdoor activity intervention strategies on the prevalence of myopia among school-aged children in China.Methods:Cross-sectional data from the Refractive Error Study in Children (RESC) on the baseline prevalence of myopia and 10-year longitudinal data from the Guangzhou Twin Eye Study (GTES) on the baseline incidence of myopia were utilized.The effect size of outdoor activity intervention was derived from longitudinal data of the Guangzhou Outdoor Activity Longitudinal Study (GOALS). Three intervention strategies were proposed: intervention for children in grades 1 to 6 (Strategy A), intervention for children in grades 1 to 3 (Strategy B), and intervention for children from the last year of kindergarten to grade 3 (Strategy C). Outdoor activity interventions across all strategies included an extra 40 minutes of daily outdoor activity time.Simulated analyses assumed that the prevalence of myopia would decrease with declining incidence and increasing school grade, and the degree of myopia among highly myopic children would decrease with delayed myopia onset.This study was approved by the Ethics Committee of Zhongshan Ophthalmic Center (No.2006-5).Results:With prolonged intervention time, the overall prevalence of myopia in children showed a significant declining trend.After 5 years of implementation, Strategy A resulted in a decrease in myopia prevalence from 34.67% to 25.71%, which decreased to 24.89% after 10 years, with an average annual reduction of 0.98%.Strategies B and C had similar long-term effects, with myopia prevalence after 10 years being 26.00% and 26.20% respectively, with an average annual reductions of 0.87% and 0.85%.Strategy A yielded the greatest reduction in myopia severity, with a decrease of -5.94 D after 5 years and -5.88 D after 10 years in the initial 15-year-old highly myopic individuals.Strategy B followed with -6.08 D and -6.02 D after 5 and 10 years, respectively.Conclusions:Implementing intensified outdoor activity intervention among children in grades 1 to 6 may be the recommended strategy to reduce the overall prevalence of myopia in regions with high rates of myopia among school-aged children.

Objective:To investigate the effects of docetaxel for postoperative chemotherapy of advanced gastric cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 311 patients with advanced gastric cancer who were admitted to Lanzhou University Second Hospital from January 2013 to December 2018 were collected. There were 224 males and 87 females, aged from 26 to 82 years, with a median age of 58 years. Of 311 patients, 204 cases undergoing chemotherapy with the FOLFOX regimen (oxaliplatin, calcium folinate, 5-fluorouracil) were allocated into the FOLFOX group, and 107 cases undergoing chemotherapy with the FLOT regimen (docetaxel, oxaliplatin, calcium folinate, 5-fluorouracil) were allocated into the FLOT group. Observation indicators: (1) the propensity score matching conditions and comparison of general data between the two groups of patients after matching; (2) follow-up; (3) analysis of survival factors; (4) subgroup analysis; (5) adverse reactions. Follow-up was performed using a combination of outpatient examination, hospitalization review and telephone interview to detect situations of patients chemotherapy, postoperative survival, tumor recurrence and metastasis up to February 2019. The propensity score matching was realized using the nearest neighbor method with 1: 1 ratio and caliper setting as 0.02. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability method. Rank data was analyzed using non parametric Rank sum test. The survival curve and rate were respectively drawn and calculated using the Kaplan-Meier method. The survival analysis was done using the Log-rank test. Univariate analysis and multivariate analysis were conducted using the COX regression model. Subgroup analysis was done using interaction test. Results:(1) The propensity score matching conditions and comparison of general data between the two groups of patients after matching: 198 of 311 patients had successful matching, including 99 in each group. Cases with tumor differentiated as poorly differentiation or well differentiation, cases with CA19-9 <27 U/mL or ≥27 U/mL, cases with CA125 <35 U/mL or ≥35 U/mL before propensity score matching were 109, 95, 156, 48, 186, 18 in the FOLFOX group, and 42, 65, 93, 14, 104, 3 in the FLOT group, respectively, showing significant differences in the above indicators between the two groups ( χ2=5.649, 4.798, 4.039, P<0.05). After propensity score matching, the above indicators were 44, 55, 85, 14, 96, 3 in the FOLFOX group, and 42, 57, 85, 14, 96, 3 in the FLOT group, respectively, showing no significant difference in the above indicators between the two groups ( χ2=0.082, 0.000, 0.000, P>0.05). (2) Follow-up: 198 patients of the two groups after matching were followed up for 2 to 69 months, with a median follow-up time of 38 months. During the follow-up, 92 cases survived without tumor, 2 cases underwent tumor recurrence or metastasis, and 104 cases died including 103 with tumor related death and 1 case with non-tumor related death. The courses of chemotherapy were 5.6±0.7 and 5.4±0.8 for the FOLFOX group and FLOT group, respectively, showing no significant difference between the two groups ( t=1.651, P>0.05). The 1, 3, and 5-year cumulative survival rates of patients were 72.2%, 31.5%, 27.7% and 83.2%, 42.8%, 38.2% for the FOLFOX group and FLOT group, respectively. The median overall survival time were 21 months and 34 months for the FOLFOX group and FLOT group, respectively, showing significant difference between the two groups ( χ2=4.473, P<0.05). (3) Analysis of survival factors: results of univariate analysis showed that cases undergoing chemotherapy with the FLOT regimen, cases with tumor as diffuse type of Lauren classification, cases with tumor as mixed type of Lauren classification, cases with tumor differentiated as well differentiation, cases with tumor diameter≥5 cm, cases with CA19-9≥27 U/mL, cases with carcinoembryonic antigen (CEA)≥3.4 μg/L, cases with tumor as T4 stage of T staging, cases with tumor as N2 stage of N staging, cases with tumor as N3 stage of N staging, cases undergoing distal gastrectomy and cases undergoing total gastrectomy were related factors influencing postoperative survival of patients ( hazard ratio=0.659, 1.617, 1.798, 0.672, 1.726, 1.655, 1.942, 2.036, 2.536, 4.085, 1.810, 2.310, 95% confidence interval: 0.444-0.978, 1.024-2.556, 1.105-2.926, 0.457-0.990, 1.159-2.569, 1.006-2.723, 1.295-2.912, 1.190-3.484, 1.409-4.564, 2.491-6.697, 1.020-3.211, 1.261-4.233, P<0.05). Results of multivariate analysis showed that cases undergoing chemotherapy with the FLOT regimen, cases with CEA≥3.4 μg/L, cases with tumor as N2 stage of N staging and cases with tumor as N3 stage of N staging were independent risk factors influencing postoperative survival of patients ( hazard ratio=0.622, 1.732, 2.217, 4.039, 95% confidence interval: 0.418-0.926, 1.124-2.670, 1.200-4.097, 2.448-6.662, P<0.05). (4) Subgroup analysis: results of subgroup analysis showed that of the different subgroups using gender, age, tumor Lauren classification, tumor differentiation degree, tumor location, tumor diameter, tumor markers, tumor T staging, tumor N staging and surgical procedures as subgrouping index, the efficacy difference between the FLOT group and the FOLFOX group was the same (interaction P>0.05). (5) Adverse reactions: the incidence of grade Ⅲ-Ⅳ adverse reactions of leukopenia, anemia, thrombocytopenia, nausea, vomiting and liver and kidney dysfunction were 11.1%(11/99), 2.0%(2/99), 3.0%(3/99), 12.1%(12/99), 4.0%(4/99), 1.0%(1/99) and 34.3%(34/99), 1.0%(1/99), 9.1%(9/99), 24.2%(24/99), 4.0%(4/99), 0 in the FOLFOX group and the FLOT group, respectively. There were significant differences of the incidence of leukopenia and nausea between the two groups ( χ2=15.213, 4.889, P<0.05). There was no significant difference of the incidence of thrombocytopenia between the two groups ( χ2=3.194, P>0.05) and there was no significant difference of the incidence of anemia, vomiting and liver and kidney dysfunction between the two groups ( P>0.05). There was no patient in the two group withdrawal from chemotherapy as no tolerance to toxic reactions. All patients were treated with glucocorticoids, proton pump inhibitors and serotonin receptor antagonists during chemotherapy. Patients undergoing leukopenia were treated with granulocyte stimulating factor. Conclusions:Compared with FOLFOX regimen, FLOT regimen which adds docetaxel significantly prolongs the postoperative median overall survival time of patients with advanced gastric cancer. However, FLOT regimen increases the incidence of grade Ⅲ-Ⅳ adverse reactions of leukopenia and nausea.

Objective: To explore the clinical application of individualized design of facial artery perforator flap for the repair of midfacial defect caused by tumor resection. Methods: From January 2015 to January 2018, a total of 36 cases of midfacial defect were repaired by individualized designed facial artery. Flaps were designed and harvested according to the location and size of the midfacial defect resulted from tumor resection, including propeller flaps, droplet flaps and swallowtail-shape flaps. Flap size was between 1.3 cm × 1.6 cm and 2.0 cm × 4.2 cm with the donor site being sutured in the first stage. Results: During the 6 months to 3 years of postoperative follow-up, no tumor recurred. All the 36 cases of individualized designed facial artery perforator flaps survived well. Furthermore, flaps being designed according to the wound defect had a good appearance, the flaps matched the color and texture of the surrounding skin and had a favorable appearance. Besides, flaps had a certain degree of sensory recovery while there was no obvious scarring presented in the donor area. Conclusions Individualized design of facial artery perforator flap has great advantages of simple and flexible, easy manipulation, reliable flap blood flow and minimal donor injury, which render it valuable for clinical application.

Objective To evaluate the immunogenicity and safety of a split-virion influenza vac-cine after its manufacturing process was improved. Methods The immunological non-inferiority of trial to control vaccines was evaluated in 240 subjects aged 3-<18 years. Another 360 subjects aged 18-<60 years were randomly divided into three groups that were respectively given three consecutive lots of trail vaccine to assess the consistency of immunogenicity. Results There were 4. 17% of the subjects aged 3-<18 years showed adverse reactions following immunization with trail vaccine and it was not significantly different from that of the control group (P>0. 05). No significant difference in seroconversion rate, geometric mean titer (GMT) of haemagglutination inhibition antibodies(HIAb) or protection rate was found between trial and control groups (P>0. 05). No significant difference in seroconversion rate or HIAb GMT was found among the three lots (P>0. 05). Conclusion The trial influenza vaccine has good safety, immunogenicity and lot-to-lot consistency after the manufacturing process was improved.

Gastric cancer is one of the most common malignant gastrointestinal tumors.Docetaxel alone or combination with other drugs can attenuate the progress of disease,prolong the overall response rate and the median overall survival rate in advanced gastric cancer.However,the incidence of toxicities is high.Moreover,there is no uniform standard for dosage and course for docetaxel treatment.Currently,its efficacy is not definite.

Objective:To explore therapeutic effect of esmolol hydrochloride combined amlodipine on patients with hyper-tension complicated aortic dissection (AD) and its influence on patient's blood pressure (BP) and heart rate (HR) .Meth-ods:A total of 110 patients with hypertension complicated AD were randomly and equally divided into amlodipine group and combined treatment group (received amlodipine and esmolol) .Results:Compared with before treatment , after treat-ment 0. 5 ,1. 5 and 7h ,there were significant reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both groups ,P<0.01 ,on 7h after treatment ,SBP level of combined treatment group significantly reduced than that of amlodipine group [(101.5 ± 7.8) mmHg vs .(123.4 ± 10.2) mmHg ,P<0.01];on 0.5 ,1.5 and 7h after treatment ,HR and rate pressure product (RPP) of combined treatment group significantly reduced than those of amlodipine group , P<0. 01 all. Compared with amlodipine group after treatment , there were significant rise in standard-reaching rates of BP (56.36% vs .87.27% ) ,HR (38.18% vs .92.73% ) and BP+HR (25.45% vs .81.82% ) in combined treatment group , P<0.01 all. Conclusion:Esmolol combined amlodipine can control blood pressure and heart rate rapidly ,safely and effec-tively in patients with hypertension complicated aortic dissection .

Objective To investigate the effect of stress-related hyperglycemia on myocardial function of patients with cardiac disorder after non-cardiac surgery.Methods The clinical data of 211 patients having undergone thoracic or abdominal operations in Department of Critical Care Medicine of Sun Yat-sen University Cancer Center were retrospectively analyzed. According to the postoperative average blood glucose level in the following 3 days after surgery and the patients' history of cardiac disorder, they were divided into four groups: without hyperglycemia (blood glucose ≤ 10 mmol/L) and cardiac disorder group (HG0CV0 group), without hyperglycemia but with cardiac disorder group (HG0CV1 group), with hyperglycemia (blood glucose > 10 mmol/L) but without cardiac disorder group (HG1CV0 group) and with hyperglycemia and cardiac disorder group (HG1CV1 group). The correlations between the blood glucose and each level of the following items: high-sensitivity cardiac troponin I (hs-cTnI), brain natriuretic peptide (BNP), myocardial zymogram aspartate aminotransferase (AST), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB), lactic dehydrogenase (LDH), lactic dehydrogenase isoenzyme (LDH-1), myoglobin (MYO), α- hydroxybutyrate dehydrogenase (HBDH) in each group were analyzed.Results The postoperative blood glucose levels of all 211 patients were significantly higher than those before operation (mmol/L: 8.7±0.2 vs. 5.7±0.2,P < 0.05), and the blood glucose level more than 6.1 mmol/L in postoperative 179 patients accounted for 84.8% of the total. In HG0CV0 group, the postoperative blood glucose level was positively correlated with MYO and AST [r values were 0.193, 0.307; 95% confidence intervals (95%CI) were 0.010 - 0.362, 0.096 - 0.479;P values were 0.038, 0.003]. There were no correlations between postoperative blood glucose level and hs-cTnI, BNP, LDH, LDH-1, HBDH, CK and CK-MB (allP > 0.05). In HG0CV1 group, the postoperative blood glucose level was negatively correlated with hs-cTnI level (r = -0.609, 95%CI = -0.810 to -0.264,P = 0.001). There were no correlations between postoperative blood glucose level and the levels of BNP, MYO, AST, LDH, LDH-1, HBDH, CK and CK-MB (allP > 0.05). In HG1CV0 group, there were no correlations between postoperative blood glucoselevel and hs-cTnI, BNP, MYO, AST, LDH, LDH-1, HBDH, CK and CK-MB (allP > 0.05). In HG1CV1 group, the postoperative blood glucose level was positively correlated with hs-TnI level (r = 0.837, 95%CI = 0.476 - 0.984,P = 0.001). There were no correlations between postoperative blood glucose level and the levels of BNP, MYO, AST, LDH, LDH-1, HBDH, CK and CK-MB (allP > 0.05).Conclusion The early stress-related hyperglycemia after non-cardiac surgery may have a protective effect on myocardial function of patients with cardiac disorder.

Obgective To investigate the impact of different ways and doses of recombinant human interferon o1b(rhIFN-α1b) on antiviral effect on respiratory syncytial virus(RSV)-effected mice and signal pathway of JAK/ STAT.Methods Forty-eight mice were divided randomly into 6 groups,negative control group,RSV-infection model group,12.5,25.0,50.0 μg rhIFN-α1 b atomization inhalation of intervention group,and 12.5 μg rhIFN-α 1 b injection of intervention group.After continuous drug therapy for 5 days,the left lung tissues of mice were aseptically dissected in the sixth day.Then it were observed lung tissue pathology changes by optical microscope,and expression of STAT1 and STAT2 protein with laser scanning confocal microscopy.Results It was observed that RSV-infection model mice's lungs had significant inflammatory injury under light microscope.After treatments of rhIFN-α 1b,it showed that the mice lung tissue had recovery of inflammation on different degrees.The group of inhaled rhIFN-o1b 50.0 μg was damaged on lightest degree.There were statistically significant differences between each group (all P ＜ 0.05).The expression of STAT1 and STAT2 protein in RSV-infection model mice's lungs decreased remarkably under fluorescene microscopy.Treatments of rhIFN-α 1b increased the expression of STAT1 and STAT2 inhibited by RSV-infection.The expression of STAT1 and STAT2 protein of the inhaled rhIFN-α1b 50.0 μg group increased significantly.The differences between groups were statistically significant(all P ＜ 0.05).Conclusions rhIFN-α 1 b played an important role in anti-RSV effects,simultaneously,it could improve the activity of JAK/STAT signal pathway inhibited by RSV-infection.The treatment effect of rhIFN-α 1b deliveried by atomization inhalation was better than that of intraperitoneal injection.And curative effect is proportional to the atomization inhalation dose within a certain range.

Objective To explore the clinical value of virtual touch quantification technique(VTQ)and fibroscan technique for the diagnosis of hepatic fibrosis.Methods A total of 1 02 patients with chronic liver disease and 78 normal individuals were enrolled in the study.They were all examined with VTQ and fibroscan technique.Pathological results were used as standard criterion.Results The liver tissue riqidity was associated with pathological results.The coefficient of relativity was 0.43309(VTQ)and 0.35840(Fibroscan).ROC curve displayed that VTQ value of 1.4 m/s and fibroscan value of 7.75 kPa can be used to differential diagnose the lowgrade liver fibrosis and high-grade liver fibrosis.The probability of success was 100 0A(102/102)and 100%(78/78)by VTQ,but 88%(90/102)and 100%(78/78)by fibroscan technique.Conclusions VTQ and fibroscan technique are useful in the diagnosis of hepatic fibrosis.Compared with fibroscan technique,VTQ has more advantages in sensitivity practicability and convenience.