A number of biosimilars will be soon marketing due to the expiration of patent protection of their originators.Unlike classical chemical drugs,biotherapeutics are proteins with large and complex molecules produced by biological high-tech with sophisticated manufactural procedures.This leads to the difficulties of the copy of biosimilars from their originators,and the almost inevitable distinctions between the two products.Thus biosimilars are only similar but not identical to their reference drugs in terms of stracture,action,and safety.It is important for physicians to understand these differences before using biosimilars.Optimal management by a national regulatory authority with rigorous standards is very important in all aspects of authorization of the development,production,marketing,and postmarketing surveillances for biosimilars.

Objective:To prepare a pig model of obstructive sleep apnea-hypopnea syndrome(OSAHS) and to observe the hemodynamics and pathological characteristics of common carotid artery,so as to lay a foundation for further studying the effect of OSAHS on cardiovascular system.Methods: Twelve male small-type pigs were randomly divided into model group and control group(n=6).Animals in the model group were housed in a negative pressure chamber for 6 months to establish OSAHS model and those in the normal control group were fed routinely.After pigs in the model group presented the symptoms of OSAHS,the changes in hemodynamics of carotid artery were detected with color Doppler ultrasound.The morphological changes of common carotid artery were analyzed under light microscope and electron microscope.Results: Animal model of OSAHS was successfully created.The internal diameter of carotid artery of pigs in the model group was decreased,the intima was increased,and the peak-systolic mean velocity(S) and the resistance index(RI) were both increased compared with those of the control group(P

Objective To perfect the prescription knowledge discovery methods; To discover the key factors affecting the robustness of prescription therapeutic model as well as improve its recognition capability.Methods Expanded knowledge base and improved design of Chinese Medicine Prescriptions Intelligence Analytic System (CPIAS) were proposed, such as the establishment of the heuristic filtering rules of efficacy-syndrome relationship, knowledge table of efficacy-syndrome element relationship, identification of efficacy-syndrome element relationship, and syndrome element-syndrome relationship. In addition, quantitative data were calculated by CPIAS. Prescription therapeutic modeling experiments on the Chinese medicine prescriptions system were conducted based on support vector machine (CPSVM), which was also used to analyze the learning outcomes.Results Using expanded knowledge base and improved calculation results can significantly promote learning abilities of CPSVM.Conclusion Screening of efficacies, sorting of symptoms, and collection of syndrome elements are the key factors affecting the quality of prescription therapeutic model.

OBJECTIVE: To analyze the curative effect of CI in children with GJB2-associated NSSNHL. METHOD: The evaluations of curative effect with CI include auditory threshold, IT-MAIS/MAIS, CAP, SIR. MESP. The outcomes of 40 cases with GJB2-associated NSSNHI, were compared 80 patients with negative results of screening of gene mutation (control group). RESULT: In comparison with control group the auditory threshold in children with GJB2-associated NSSNIL is better, however had no significant difference in other tests (P > 0.05). CONCLUSION CI could he performed on children with GJB2-associated NSSNHL. Postoperative outcomes of hearing and speech were satisfied.
Child ; Child, Preschool ; Cochlear Implantation ; Connexin 26 ; Connexins ; genetics ; Female ; Hearing Loss, Sensorineural ; genetics ; surgery ; Humans ; Infant ; Male ; Mutation ; Treatment Outcome

Objective To investigate the efficacy and safety of domestic exenatide injection versus imported exenatide injection in type 2 diabetic patients with inadequate glycemic control on monotherapy or combination therapy of metformin and insulin secretagogues. Methods A multicenter, randomized, parallel-controlled, and non-inferiority trial was carried out. A total of 240 subjects were randomized at a 1:1 ratio to add domestic exenatide injection (trial group) or imported exenatide injection (control group) on the background therapies. The primary endpoint of efficacy was HbA1C change from baseline to week 16. The secondary endpoints of efficacy were the proportion of HbA1C<7.0%, and the changes in fasting plasma glucose (FPG), 2 h plasma glucose after standard meal (2hPG), 7-point self monitoring of blood glucose (7P-SMBG), and body weight from baseline to week 16. Results Among subjects of per-protocol sets, adjusted mean HbA1C reduction was -1.07% in the trial group versus -1.06% in the control group after 16 weeks of treatment. The lower boundary of the two-sided 95% confidence intervals of the mean HbA1C reduction difference between the trial and control groups was -0.29%, which was more than -0.35%, suggesting that the predefined statistical criterion for non-inferiority was achieved. The proportions of subjects achieving HbA1C<7.0% at the end of the 16-week treatment were 56.19% and 54.08% in the trial and control groups, respectively (P>0.05). The changes in FPG, 2hPG, 7P-SMBG and body weight from baseline to week 16 were comparable between the two groups (all P>0.05). Moreover, the incidences of hypoglycemia and adverse events were similar between the two groups (both P>0.05). Conclusion In type 2 diabetic patients inadequately controlled by monotherapy or combination therapy of metformin and insulin secretagogues, the efficacy of cotreatment with domestic exenatide injection is not inferior to that of imported product ones, with a similar safety profile.

Objective To investigate the differences in central hemodynamic indices between hypertensive and normotensive subjects and identify the blood pressure index that the most strongly correlate with arterial stiffness and vascular damage markers. Methods A cohort of 820 hypertensive patients and 820 normotensive individuals matched for age and gender were enrolled in this study. We measured carotid-femoral and carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and central blood pressures using pulse wave analysis and applanation tonometry. Plasma homocysteine (HCY), high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also tested in these subjects. Results In both hypertensive and normotensive subjects, the central systolic blood pressure (SBP) and pulse pressure (PP) were significantly lower than brachial SBP and PP; this PP amplification was significantly lower in the normotensives (9.85 ± 6.55 mmHg) than in the hypertensives (12.64 ± 6.69 mmHg), but the amplification ratios were comparable between the two groups. Blood pressure and age were closely related with aortic arterial stiffness. Compared with normotensive subjects, hypertensive subjects had higher carotid-femoral PWV and AIx, and showed significantly lowered PP amplification ratio with age. Central PP was more strongly related to arterial stiffness and vascular damage markers than the other pressure indices. Multivariate analyses revealed that carotid-femoral PWV and aortic AIx were strongly influenced by central PP but not by the mean blood pressure or brachial PP. Conclusion The central PP is a more direct indicator of central arterial stiffness and a better marker of vascular aging than other blood pressure variables. These findings support the use of central blood pressure as a treatment target in future trials.

Objective To investigate the differences in central hemodynamic indices between hypertensive and normotensive subjects and identify the blood pressure index that the most strongly correlate with arterial stiffness and vascular damage markers. Methods A cohort of 820 hypertensive patients and 820 normotensive individuals matched for age and gender were enrolled in this study. We measured carotid-femoral and carotid-radial pulse wave velocity (PWV), aortic augmentation index (AIx) and central blood pressures using pulse wave analysis and applanation tonometry. Plasma homocysteine (HCY), high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also tested in these subjects. Results In both hypertensive and normotensive subjects, the central systolic blood pressure (SBP) and pulse pressure (PP) were significantly lower than brachial SBP and PP; this PP amplification was significantly lower in the normotensives (9.85 ± 6.55 mmHg) than in the hypertensives (12.64 ± 6.69 mmHg), but the amplification ratios were comparable between the two groups. Blood pressure and age were closely related with aortic arterial stiffness. Compared with normotensive subjects, hypertensive subjects had higher carotid-femoral PWV and AIx, and showed significantly lowered PP amplification ratio with age. Central PP was more strongly related to arterial stiffness and vascular damage markers than the other pressure indices. Multivariate analyses revealed that carotid-femoral PWV and aortic AIx were strongly influenced by central PP but not by the mean blood pressure or brachial PP. Conclusion The central PP is a more direct indicator of central arterial stiffness and a better marker of vascular aging than other blood pressure variables. These findings support the use of central blood pressure as a treatment target in future trials.

Objective To investigate the morbidity, diagnostic profile and perinatal outcome of pregestational diabetes mellitus (PGDM) in 15 hospitals in Guangdong province. Methods A total of 41338 women delivered in the 15 hospitals during the 6 months,195 women with PGDM(PGDM group) and 195 women with normal glucose test result(control group)were recruited from these tertiary hospitals in Guangdong province from January 2016 to June 2016. The morbidity and diagnostic profile of PGDM were analyzed. The complications during pregnancy and perinatal outcomes were compared between the two groups. In the PGDM group, pregnancy outcomes were analyzed in women who used insulin treatment (n=91) and women who did not (n=104). Results (1)The incidence of PGDM was 0.472%(195/41338). Diabetes mellitus were diagnosed in 59 women (30.3%, 59/195) before pregnancy, and 136 women (69.7%,136/195) were diagnosed as PGDM after conceptions. Forty-six women (33.8%) were diagnosed by fasting glucose and glycohemoglobin (HbA1c) screening. (2) The maternal age, pre-pregnancy body mass index (BMI), prenatal BMI, percentage of family history of diabetes, incidence of macrosomia, concentration of low density lipoprotein were significantly higher in PGDM group than those in control group (all P<0.05). Women in PGDM group had significantly higher HbA1c concentration((6.3±1.3)% vs (5.2±0.4)%), fasting glucose [(6.3±2.3) vs (4.8±1.1) mmol/L], oral glucose tolerance test(OGTT)-1 h glucose((12.6±2.9) vs (7.1± 1.3) mmol/L)and OGTT-2 h glucose [(12.0±3.0) vs (6.4±1.0) mmol/L] than those in control group (P<0.01). (3)The morbidity of preterm births was significantly higher (11.3% vs 1.0%, P<0.01), and the gestational age at delivery in PGDM group was significantly smaller [(37.6±2.3) vs (39.2±1.2) weeks, P<0.01]. Cesarean delivery rate in the PGDM group (70.8% vs 29.7%) was significantly higher than the control group (P<0.01). There was significantly difference between PGDM group and control in the neonatal male/female ratio (98/97 vs 111/84, P=0.033). The neonatal birth weight in PGDM group was significantly higher((3159±700) vs (3451±423) g, P<0.01). And the incidence of neonatal hypoglycemia in the PGDM group was higher than the control group (7.7% vs 2.6%, P=0.036).(4)In the PGDM group, women who were treated with insulin had a smaller gestational age at delivery [(36.9±2.9) vs (37.9±2.5) weeks, P<0.01], and the neonates had a higher neonatal ICU(NICU)admission rate (24.2% vs 9.6% , P<0.01). Conclusions The morbidity of PGDM in the 15 hospitals in Guangdong province is 0.472%. The majority of PGDM was diagnosed during pregnancy; HbA1c and fasting glucose are reliable parameters for PGDM screening. Women with PGDM have obvious family history of diabetes and repeated pregnancy may accelerate the process of diabetes mellitus. Women with PGDM have higher risk for preterm delivery and neonatal hypoglycemia. Unsatisfied glucose control followed by insulin treatment may increase the need for NICU admission.

Objective:To compare the differences in lung function between sanitation workers and the general population undergoing routine physical examinations, and to analyze the risk factors for restricted airflow and severity of the condition in sanitation workers.Methods:This study is a large cross-sectional study called "Shanxin Respiratory Health Screening for Ten Thousand People". A total of 1 036 sanitation workers (sanitation group) and 6 701 individuals from the general population undergoing routine physical examinations (control group) were selected as the original study subjects from June 2021 to April 2022 (before matching). Both groups underwent pre-bronchodilator lung function tests, and the differences in lung function characteristics between the two groups were compared. The sanitation group also completed a questionnaire survey. Multivariate and ordinal multinomial logistic regression analysis were used to analyze the risk factors for airflow limitation and its severity.Results:A total of 1 027 individuals from the sanitation group and 999 individuals from the control group were included in the study. There were no significant differences in age, gender, height, weight, and body mass index (BMI) between the two groups (all P>0.05). The rate of airflow restriction was significantly higher in the sanitation group compared to the control group (22.88% vs 8.81%, P<0.001). In the sanitation group, there was no statistically significant difference in a self-assessment test for chronic obstructive pulmonary disease (CAT) scores between individuals with airflow restriction (235 cases) and those without airflow restriction (792 cases) [(1.50±2.50) vs (1.15±2.03) points, P=0.084]. There were no statistically significant differences in forced vital capacity (FVC) as a percentage of predicted value (FVC%pred) between the two groups. However, the sanitation group had significantly lower %pred for forced expiratory volume in one second (FEV 1%pred), FVC/FEV 1 ratio (FEV 1/FVC%pred), forced expiratory flow at 50% of FVC (FEF 50%%pred), forced expiratory flow at 75% of FVC (FEF 75%%pred), and maximal mid-expiratory flow (MMEF%pred) compared to the control group (all P<0.05). The rates of abnormal FEF 50%%pred, FEF 75%%pred, and MMEF%pred were significantly higher in the sanitation group compared to the control group (17.62% vs 10.31%, 17.04% vs 10.01%, 27.26% vs 18.41%, all P<0.001). Small airway parameters and the rate of airflow restriction were significantly higher in past and current smokers of the sanitation group compared to never smokers (all P<0.05). Multifactorial analysis showed that high BMI ( OR=0.929, 95% CI: 0.885-0.974) was a protective factor for airflow restriction, while high smoking index was a risk factor ( OR=1.020, 95% CI: 1.011-1.030). Ordered multinomial logistic regression analysis showed that high BMI ( OR=0.925, 95% CI: 0.882-0.971) was a protective factor for the severity of airflow restriction, while high smoking index ( OR=1.020, 95% CI: 1.011-1.029) was a risk factor for the severity of airflow restriction. Conclusions:The incidences of airflow limitation and small airway abnormalities in sanitation workers are higher than that in general physical examination population. High smoking index and low BMI are independent risk factors for airflow limitation and its severity.

Steroid saponins are secondary metabolites with multiple medicinal values that are found in large quantities in natural medicines, especially Vernonia amygdalina, a famous nature medicine for the treatment of tonsillitis, diabetes, pneumonia. The current study was designed to combine molecular networking (MN) with diagnostic ions for rapid identification of Δ^7,9(11) stigmastane-type saponins which were the α-glucosidase inhibitory active substances in V. amygdalina. First, the α-glucosidase inhibitory activities of five Δ^7,9(11) stigmastane-type steroid saponins that were previously isolated were screened, which indicated that the Δ^7,9(11) stigmastane-type steroid saponin was one of the active constituents responsible for ameliorating diabetes. Furthermore, a strategy was proposed to identify stigmastane-type steroid saponins and verify the plausibility of derived fragmentation pathways by applying MN, MolNetEnhancer and unsupervised substructure annotation (MS2LDA). Based on this strategy, other seven Δ^7,9(11) stigmastane-type steroid saponins were identified from this plant. Our research provide scientific evidence for the antidiabetic potential of the steroid saponin-rich extract of V. amygdalina leaf.
alpha-Glucosidases/metabolism* ; Vernonia/chemistry* ; Plant Extracts/chemistry* ; Plant Leaves/chemistry* ; Saponins/chemistry* ; Steroids/chemistry* ; Diabetes Mellitus