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Objective:To explore the effectiveness of blood glucose monitoring at different frequencies on the control of blood glucose in overweight/obese prediabetes population on the basis of health education, and to provide a basis for blood glucose monitoring and management in prediabetes population.Methods:A randomized controlled study was used. 90 prediabetes patients from the Physical Examination Center/Endocrine Clinic/Endocrine Ward of the First Affiliated Hospital of China Medical University from January to March 2021 were selected by continuous sampling method, and were randomly divided into the group A, B and C by lottery method, with 30 patients in each group, and the study period was 12 months. Group A, B and C received unified health education guidance at enrollment, 6-month follow-up, and 12-month follow-up. Group A underwent blood glucose monitoring every 6 months, group B underwent blood glucose monitoring every 3 months, group C underwent blood glucose monitoring every month. Recorded and compared the levels of glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-hour post-load blood glucose (2 hPG), and body mass index (BMI) of three groups at the time points of enrollment, 6-month follow-up, and 12-month follow-up.Results:There were 15 males and 15 females in the group A, 14 males and 16 females in the group B, 12 males and 18 females in the group C. The ages in the group A, B and C were (48.37 ± 10.80), (49.20 ± 9.25) and (44.77 ± 12.28) years old respectively. At the time point of 12-month follow-up, the HbA1c in the group A, B and C were (6.01 ± 0.36)%, (5.82 ± 0.35)% and (5.64 ± 0.27)%, the difference was significant ( F=9.72, P<0.05); the FPG in the group A, B and C were (5.64 ± 0.88), (5.05 ± 0.53) and (4.98 ± 0.48)mmol/L, the difference was significant ( F=9.23, P<0.05); the 2 hPG in the group A, B and C were (9.38 ± 1.23), (8.23 ± 0.72) and (7.71 ± 0.86) mmol/L, the difference was significant ( F=23.89, P<0.05); the BMI in the group A, B and C were (28.52 ± 4.24), (27.02 ± 2.67) and (25.56 ± 1.34) kg/m 2, the difference was significant ( F=7.37, P<0.05). Conclusions:On the basis of health education, compared with the routine blood glucose monitoring once every six months, blood glucose monitoring once every three months and once every month can improve the blood glucose control and BMI level of overweight/obese young and middle-aged people with prediabetes, and provide a basis for seeking an effective and economic blood glucose monitoring mode in clinical practice.
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Mutation breeding is a significant means of increasing breeding efficiency and accelerating breeding process. In present study, we explored a new method for mutations inducing in rice (Oryza sativa L.) by using direct current electrophoresis bath (DCEB). The results showed that 20 mM NaCl solution is the optimal buffer, and the mortality of rice seeds followed an upward trend with increasing voltage and processing time of DCEB. By exploring the mutagenic effects of γ-irradiation and DCEB on seed vigor and physiological damages, we found that the physiological damages induced by DCEB on seed vigor were significant compared with that by γ-irradiation. We screened two mutants with low filled grain percentage and one mutant with abnormal hull from the M2 generations. These three mutants were confirmed to be authentic mutants based on 48 SSR markers followed by the protocol NY/T 1433-2014. Whole-genome resequencing detected a total of 503 and 537 polymorphisms in the two mutants, respectively, and the DCEB mutagenesis induced mainly InDel variants, while the exon region of mutant genes occupied a large proportion, especially the SNP variants, which occupied about 20% of the mutation sites in the exon region.
Subject(s)
Oryza , Oryza/genetics , Oryza/radiation effects , Mutagens , Plant Breeding , Mutation , Mutagenesis/genetics , Seeds/geneticsABSTRACT
ObjectiveTo investigate the individual factors of postural adjustment reaction time and movement time during adaptive equilibrium. MethodsFrom March to December, 2021, 126 healthy adults aged 18 to 80 years were recruited at the First Medical Center of the General Hospital of the Chinese PLA. The DE-A somatosensory balance detection system was used to detect their postural adjustment reaction time (RT) and movement time (MT) as the platform tilting in multiple directions during standing (static) or walking (dynamic). The ages, genders, body mass index (BMI) and physical activity level of them were investigated. ResultsThe age was the only factor independently associated with dynamic RT and MT in all the directions (β > 0.632, P < 0.05). For static MT, as the platform tilting forward, physical activity level (β = -0.143, P < 0.05), BMI (β = 0.154, P < 0.05) and age (β = 0.663, P < 0.05) were the independently associated factors; as the platform tilting leftward, gender (β = -0.173, P < 0.05) and age (β = 0.647, P < 0.05) were the independently associated factors; and age was the only independently associated factor for other directions (β > 0.571, P < 0.05). For the static RT, age was the only independently associated factor for all the directions (β > 0.615, P < 0.05). ConclusionAge is the most important independently factor related to postural adjustment during adaptive equilibrium, and aging may delay the postural adjustment after instability.
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AIM:To observe the toxic effects of zinc oxide nanoparticles(ZnO NPs)on cornea by constructing intoxicated model in vivo and in vitro.METHODS:Human corneal epithelial cells(HCEpiC)were cultured in vitro and exposed to different concentrations(0.5, 5, 12.5, 25, 50, 100, 250 μg/mL)of ZnO NPs for 24h. The cell culture medium without nano-solution was used as the blank control group. The viability of the cells was assessed by MTT assay. Three different concentrations(25, 50 and 100 μg/mL)of ZnONPs dispersions were exposed to the conjunctival sac of anesthetized mice three times a day for 7d consecutively. The phosphate buffered saline(PBS)eye group was the PBS control group. Corneal morphology was observed on 1, 3, 5 and 7d, and the eyes were removed on 8d for various laboratory examinations, including corneal pathological changes and expression levels of inflammatory factors(TNF-α, IL-6).RESULTS:After treatment of HCEpiC cells with different concentrations of ZnO NPs for 24h, the MTT results showed that Zno NPs cause damage to cells at 0.5 μg/mL, and the cell survival rate was about 80%(P<0.05). Half of the cells were killed at a dose of 5 μg/mL, the damaging effect on cells in the concentration range of 5~250 μg/mL was concentration-dependent(P<0.0001). After 7d of conjunctival capsule spotting in mice, dot-like staining of fluorescein was seen in the 25 μg/mL ZnO NPs and 50 μg/mL ZnO NPs groups. Localized circular fluorescein stained areas were seen in the corneas of the 100 μg/mL ZnO NPs group. HE staining showed that the corneal epithelial layer, stromal layer thickness and stromal layer immune cell number did not change significantly in the 25 μg/mL and 50 μg/mL ZnO NPs groups(all P>0.05), while the corneal epithelial layer thinned, the corneal stromal layer thickened and the stromal layer immune cells increased significantly in the 100 μg/mL ZnO NPs group(all P<0.05). Immunohistochemical staining showed that the number of corneal stromal immune cells producing TNF-α and IL-6 and the mean integral optical density(IOD)values of TNF-α and IL-6 were significantly higher in the 100 μg/mL ZnO NPs group than in the PBS control group(P<0.05), and the degree of inflammation response was concentration-dependent. Compared with the PBS control group, no significant increase in immune cell count and IOD values in the 25 μg/mL ZnO NPs and 50 μg/mL ZnO NPs groups(P>0.05).CONCLUSION:The toxic damaging effect of ZnO NPs on the cornea was confirmed from both in vitro and in vivo, which provided a theoretical basis for the ocular safety evaluation of ZnO NPs.
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Cr/Fe-bearing sludge is a hazardous solid waste, produced at mass production in smelting, plating and surface finishing industries. Such waste is commonly treated by chemical detoxification and safety landfill, whereas only a few Cr-rich sludge is recycled as a tanning reagent. In this study, a novel route was developed to recycle Cr/Fe-bearing sludge as erdite-bearing flocculant for wastewater treatment. Results showed that two sludges were irregular aggregates, one of which contained 1.6 wt.% Cr (short for LS) and the other contained 4.2 wt.% Cr (HS). After hydrothermal treatment, stable Cr(III)/S-bearing product was formed from the Cr(VI) reduction in the sludges. Conversely, erdite was generated in nanorod form with diameter and length of 200 nm and 0.5-1 µm from LS, respectively, whereas grew radially to 1.5-2.5 µm for HS. The two erdite-bearing products were spontaneously hydrolysed to Fe/S-bearing flocs and showed similar performance in the treatment of real electroplating effluent with 91.55, 1.94 and 0.25 mg/L of Zn, Ni and Cr, respectively. For instance, by adding 1 g/L product of LS, the release of Cr from the products did not occur, and the residual Zn, Ni and Cr in the effluent was 0.25, 0.65 and 0.17 mg/L, respectively, which met the discharge standard of the electroplating industry. With the two converted products, the residual Zn/Ni/Cr concentrations were apparently lower than those of the raw sludges and other common reagents (e.g. polymeric ferric sulphate, activated carbon and diatomite). Thus, such erdite-bearing products could serve as a flocculant and then be applied in electroplating wastewater treatment.
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SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials in subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP in how it activates the GIPR, it differs markedly from GLP-1 in its activation of the GLP-1R, resulting in less agonist-induced receptor desensitization. We report how cryogenic electron microscopy and molecular dynamics simulations inform the structural basis for the unique pharmacology of tirzepatide. These studies reveal the extent to which fatty acid modification, combined with amino acid sequence, determines the mode of action of a multireceptor agonist.
Subject(s)
Diabetes Mellitus, Type 2 , Receptors, Gastrointestinal Hormone , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Gastric Inhibitory Polypeptide/metabolism , Gastric Inhibitory Polypeptide/pharmacology , Gastric Inhibitory Polypeptide/therapeutic use , Glucagon-Like Peptide-1 Receptor/metabolism , Humans , Incretins/pharmacology , Receptors, Gastrointestinal Hormone/agonists , Receptors, Gastrointestinal Hormone/metabolism , Receptors, Gastrointestinal Hormone/therapeutic useABSTRACT
Objective: To analyze the changes in tobacco use and exposure in primary school students in Shandong province in 2012 and 2019. Methods: A multi-stage stratified cluster random sampling method was used in the survey. In 2012 and 2019, 5 861 and 4 021 students from 3 different cities of Shandong province were selected as the study population. The questionnaire was filled anonymously by the subjects. χ2 test was conducted to compare the difference of groups. Results: In 2012 and 2019, the rate of attempting smoking among pupils under this study in Shandong province were 6.0%and 6.3%, respectively, while the current smoking rate were 1.2%and 2.3%, respectively. The sex ratio of male and female students attempting to smoke was 2.56∶1 in 2012 and 1.31∶1 in 2019. The sex ratio of current smoking rate was 2.43∶1 and 2.00∶1, respectively in 2012 and in 2019. The rate of tobacco exposure in the public places was 50.5%and 41.4%, respectively. The rate of tobacco exposure in family was 49.7% and 46.4%, respectively. Two rates of tobacco exposure decreased, but the reduction in family (3.3%) was far less than that in public places (9.1%). In 2019, the rate of tobacco exposure in family was higher than that in public places. Conclusions: The tobacco exposure rate declined in senior pupils in Shandong province. However, the situation is still grim for the current smoking rate, growth trend of girls tobacco use, and tobacco exposure in family.
Subject(s)
Female , Humans , Male , Cities , Environment , Prevalence , Students , Surveys and Questionnaires , Tobacco Smoke Pollution , Tobacco Use/epidemiologyABSTRACT
Objective:To investigate clinical characteristics of bullous pemphigoid (BP) developing after the treatment with dipeptidyl peptidase-Ⅳ inhibitors (DPP4i) in patients with diabetes mellitus.Methods:A total of 116 inpatients with BP complicated by diabetes mellitus were collected from the Seventh People′s Hospital of Shenyang between January 2014 and December 2020, and divided into 2 groups: DPP4i-BP group treated with DPP4i before the onset of BP, and general BP group receiving no treatment with DPP4i. General clinical data, skin lesion area, laboratory indicators, treatment regimens, and prognosis were analyzed and compared between the above 2 groups, the time interval from the administration of DPP4i to the diagnosis of BP was recorded in the DPP4i-BP group. One-way analysis of variance was used to compare measurement data among multiple groups, two-independent-sample t test was used for comparisons between two groups, and paired t-test for intra-group comparisons before and after treatment; chi-square test was used to compare enumeration data between groups. Results:There were 32 patients aged 77.17 ± 15.32 years in the DPP4i-BP group, with a male-to-female ratio being 15∶17; there were 84 patients aged 76.65 ± 19.32 years in the general BP group, with a male-to-female ratio being 43∶41. The time interval from the administration of DPP4i to the diagnosis of BP was 14.61 ± 3.93 months in the DPP4i-BP group. The time interval for vildagliptin was the shortest (5.42 ± 2.84 months) , and there was a significant difference in the time interval among vildagliptin, sitagliptin, linagliptin and saxagliptin ( F= 8.93, P < 0.001) . The proportion of patients with severe BP was significantly higher in the DPP4i-BP group (16 cases, 50%) than in the general BP group (25 cases, 29.76%; Z= 2.63, P= 0.008) . There was no significant difference in the positivity rate of anti-BP180 antibody between the two groups ( χ2= 0.03, P= 0.870) . However, the level of anti-BP180 antibody was significantly higher in the DPP4i-BP group than in the general BP group before and after treatment ( P= 0.015, < 0.001, respectively) , and the decrease in the level of anti-BP180 antibody was significantly less in the DPP4i-BP group than in the general BP group after treatment ( t= 5.11, P < 0.001) . There was no significant difference in the average effective dose of glucocorticoids required to control the disease between the two groups ( t= 1.00, P= 0.322) . However, the DPP4i-BP group showed a significant increase in the average time required to control the disease and in the proportion of patients requiring combined treatment with immunosuppressants or other drugs compared with the general BP group ( t= 6.72, 10.05, P < 0.001,= 0.002, respectively) . Within 6 months after the start of systemic treatment, the recurrence rate was significantly higher in the general BP group (17 cases, 27.86%) than in the DPP4i-BP group (2 cases, 7.69%; χ2= 4.35, P= 0.037) ; at 6 months, the average dose of glucocorticoids was also significantly higher in the general BP group than in the DPP4i-BP group ( t= 7.04, P < 0.001) . Conclusions:Among the DPP4i hypoglycemic drugs, vildagliptin was the most common drug administrated by patients before the onset of BP, with the shortest interval from the administration to the onset of BP. DPP4i-BP may be difficult to control at the early stage, but the prognosis is good.
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The common pathogens of neonatal respiratory viruses include respiratory syncytial virus, influenza virus, parainfluenza virus, adenovirus and rhinovirus, among which respiratory syncytial virus is the most common.Neonates infected with respiratory viruses can not only show respiratory symptoms such as cough, nasal obstruction and rhinorrhea, but also lead to multiple organ injury in severe cases.It is one of the causes of neonatal death.In the past, more attention has been paid to the harm caused by bacterial infection in the neonatal period.However, with the constant mutation of previous virus and the emergence of new virus, there are also some reports about the outbreaks of respiratory tract virus infection in neonatal wards.Neonatal immune system is immature.Newborns are susceptible to respiratory virus infection.Therefore, clinicians should pay more attention to the harm caused by respiratory infection in neonatal period.
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@#To investigate the clinical value of transcranial Doppler ultrasound (TCD) in evaluating intracranial collateral circulation in patients with extracranial segment of unilateral internal carotid artery occlusion (ICAO). Methods A total of 145 patients with ICAO,109 in the symptomatic group and 36 in the asymptomatic group,who were diagnosed by cervical vascular ultrasonography and confirmed by digital subtraction angiography (DSA) in the Stroke Center of the First Affiliated Hospital of Soochow University from January 2018 to December 2020,were retrospectively enrolled. TCD was recorded to evaluate intracranial collateral circulation types and performed consistency test with DSA.The hemodynamic parameters of bilateral middle cerebral artery (MCA) and CT perfusion (CTP) parameters of bilateral basal ganglia and temporal lobe were recorded. According to the Collateral circulation assessment system of the American Society for Interventional and Therapeutic Neuroradiology/Society for Interventional Radiology (ASITN/SIR),patients were divided into poor collateral circulation(grade 0~2) and good collateral circulation (grade 3~4),and the differences of MCA parameters and CTP parameters were compared between the two groups. The differences in bilateral MCA blood flow parameters between the asymptomatic group and the symptomatic group and the early CT scores (ASPECTS) of the Alberta Stroke Project were compared.Results (1) Consistency analysis:The coincidence rates of anterior communicating artery (ACoA),posterior communicating artery (PCoA),ocular artery (OA) and DSA evaluated by TCD were:93.1%,91.0%,80.7%,with good consistency (Kappa value=0.84,0.78,0.66,all P<0.05).(2)Collateral circulation compensation:The mean flow rate(Vm),peak systolic flow rate (Vs),end diastolic flow rate (Vd) and pulsation index (PI)of the affected middle cerebral artery in the poor collateral circulation group were lower than those in the good group,and the differences in Vm,Vs and Vd were statistically significant (P<0.05). CBF and CBV in basal ganglia and temporal lobe were decreased,while MTT and TTP were prolonged,with statistically significant differences(all P<0.05).(3)ASPECTS in asymptomatic group were significantly higher than those in symptomatic group,and blood flow parameters in MCA of healthy side were less different than those in symptomatic group (all P<0.01).Conclusion TCD is consistent with DSA in evaluating intracranial collateral circulation in patients with intracranial extracranial occlusion of unilateral internal carotid artery.MCA blood flow parameters can reflect the perfusion in the blood supply area,and TCD is an effective tool for evaluating intracranial collateral circulation.
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Sepiolite is an efficient mineral for the immobilization of Cd in contaminated soils. Here, we conducted a 3-year field experiment to investigate the effect of sepiolite on soil aggregation and porosity, Cd availability, and organic carbon content in the bulk and aggregate soils and Cd accumulation by leafy vegetables. The sepiolite-treated soils showed a 15.4%-53.4% and 5.5%-63.0% reduction in available Cd content in the bulk soil and different particle-size aggregates, respectively. Moreover, the Cd concentrations in the edible parts of Brassica campestris, Lactuca sativa L., and Lactuca sativa var. ramosa Hort. decreased by 5.9%-26.2%, 22.8%-30.1%, and 14.4%-19.1%, respectively, compared with those of the control groups. Treatments with 0.5%-1.5% sepiolite resulted in a significant increase (P < 0.05) in the proportion of 0.25-5.0 mm aggregates, and the increase in the mean weight diameter and geometric mean weight of the soil aggregates indicated that sepiolite treatments enhanced soil aggregate stability. Furthermore, three-dimensional X-ray computed tomography imaging showed that sepiolite treatments resulted in an increase in the total area, average size, and pore perimeter of aggregates, with the maximum values being 1.63-, 1.41-, and 1.401-fold higher than those of the corresponding control groups, respectively. The highest values of soil organic carbon and particulate organic carbon were obtained in 1.5% sepiolite-treated soils and were 2.07- and 1.91-fold higher than those of the control groups, respectively. Additionally, the level of organic carbon functional groups in the bulk soil and different particle-size aggregates generally increased with increasing sepiolite application. Overall, sepiolite, as a soil amendment, not only reduced toxic element bioavailability and uptake by plants but also enhanced soil structure and function.
Subject(s)
Environmental Restoration and Remediation , Oryza , Soil Pollutants , Cadmium/analysis , Carbon , Magnesium Silicates , Soil , Soil Pollutants/analysisABSTRACT
Dopamine D1 receptor (D1R) is an important drug target implicated in many psychiatric and neurological disorders. Selective agonism of D1R are sought to be the therapeutic strategy for these disorders. Most selective D1R agonists share a dopamine-like catechol moiety in their molecular structure, and their therapeutic potential is therefore limited by poor pharmacological properties in vivo. Recently, a class of non-catechol D1R selective agonists with a distinct scaffold and pharmacological properties were reported. Here, we report the crystal structure of D1R in complex with stimulatory G protein (Gs) and a non-catechol agonist Compound 1 at 3.8 Å resolution. The structure reveals the ligand bound to D1R in an extended conformation, spanning from the orthosteric site to extracellular loop 2 (ECL2). Structural analysis reveals that the unique features of D1R ligand binding pocket explains the remarkable selectivity of this scaffold for D1R over other aminergic receptors, and sheds light on the mechanism for D1R activation by the non-catechol agonist.
Subject(s)
GTP-Binding Protein alpha Subunits, Gs/chemistry , Receptors, Dopamine D1/agonists , Receptors, Dopamine D1/chemistry , Binding Sites , Crystallography, X-Ray , Humans , In Vitro Techniques , Ligands , Models, Molecular , Molecular Dynamics Simulation , Protein Binding , Protein Conformation , Protein Engineering , Protein Structure, Quaternary , Recombinant Proteins/chemistryABSTRACT
The Daqing River Basin has long been seriously threatened by floods. The construction of Xiong'an New Area has put forward higher requirements for the flood control system of the basin. Researches on the characteristics of the flood control system in the Daqing River Basin, the causes of the flood and the historical flood were conducted with the purpose to have a clear understanding of the deficiency of the existing flood control system in the Drainage Basin and figure out the countermeasures to improve the flood control capacity of the Drainage Basin by taking the development process of the flood control system in the Drainage Basin into consideration. Analysis was conducted on the causes, flood process, the process of regulation and storage of reservoirs and depressions as well as flood disaster with the flood occurred in August 1963 as the major research object. Besides, the deficiency of flood control system of the Drainage Basin in terms of flood control system and the flood occurred in August 1963 (also called 63.8 Flood). According to the research, the major problems in the current flood control system of the Daqing River Basin are mainly concentrated on Baiyang Lake with blocked internal water transmission and insufficient drainage capacity, which makes it difficult to cope with the flood exceeding the designed level. The great change of water level will also destroy the ecological balance of Baiyang Lake itself. In addition, during the construction of the New District, some flood storage and detention areas in Baiyang Lake will be deprived of the capability in regulation and storage, which will increase the difficulty of flood control in the downstream areas. Combined with the existing flood control system and aiming at the construction of Xiong'an New Area, the concepts of flood control system such as developing the Xiaoguan flood diversion way, rebuilding the new housing hub and strengthening the dredging of downstream river are put forward.
Subject(s)
Disasters , Floods , Lakes , Rivers , WaterABSTRACT
Bronchopulmonary dysplasia(BPD)is a serious complication of respiratory system in preterm infants.The etiology and pathogenesis are complex and have not been clarified yet.In recent years, studies have shown that there is a certain relationship between respiratory microecology and BPD.Before premature infants develop BPD, their respiratory tract microecology has changed, including abnormal microbial diversity and evolution pattern.Therefore, research on the colonization and evolution of neonatal respiratory tract microecology and its relationship with BPD is expected to provide new ideas for its prevention and treatment.
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Objective:To investigate the percutaneous permeability of sinomenine hydrochloride (SNH) and optimize the parameters of electroporation to achieve the best permeation enhancing effect on SNH. Method:The percutaneous permeability of SNH and the enhancement effect of electroporation were studied by <italic>in vitro</italic> diffusion cell method, and the enhancement effect of electroporation was further evaluated by <italic>in vivo</italic> study in mice. Result:Under steady-state condition, the permeation rates of SNH in stripped skin and intact skin of hairless mice were (385.81±12.88), (0.88±0.20) μg·cm<sup>-2</sup>·h<sup>-1</sup>, respectively. The permeation rate in stripped skin was 438 times higher than that in intact skin. The results of percutaneous permeation kinetics analysis showed that the solubility and diffusion coefficient of SNH in stratum corneum were relatively low, which were (70.82±9.63)×10<sup>3</sup> g·m<sup>-3</sup> and (3.07±1.52)×10<sup>-14</sup> cm<sup>2</sup>·s<sup>-1</sup>, respectively. Under the optimized electroporation conditions (voltage of 72 V, time of 60 min), the 24 h cumulative permeation amount of SNH through skin of mice was (10 008.39±1 961.57) μg·cm<sup>-2</sup>, and the steady-state permeation rate was (456.01±51.26) μg·cm<sup>-2</sup>·h<sup>-1</sup>, which were 5.4 times and 5.1 times higher than those of blank group, respectively. <italic>In vivo</italic> studies in mice showed that the contents of SNH in skin and muscle of electroporation group were 2.0 times and 1.5 times higher than those of blank group. Conclusion:The low solubility and low diffusion coefficient of SNH in the stratum corneum are the main factors hindering the percutaneous permeation of SNH. Electroporation can significantly increase the percutaneous permeation of SNH and its retention in skin and muscle of mice.
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BACKGROUND@#The open reduction and internal fixation (ORIF) was a standard treatment approach for fracture at distal humerus intercondylar, whereas the optimal way before ORIF remains inconclusive. We, therefore, performed a systematic review and meta-analysis to assess the efficacy and safety of olecranon osteotomy vs. triceps-sparing approach for patients with distal humerus intercondylar fracture.@*METHODS@#The electronic searches were systematically performed in PubMed, EmBase, Cochrane library, and Chinese National Knowledge Infrastructure from initial inception till December 2019. The primary endpoint was the incidence of excellent/good elbow function, and the secondary endpoints included Mayo elbow performance score, duration of operation, blood loss, and complications.@*RESULTS@#Nine studies involving a total of 637 patients were selected for meta-analysis. There were no significant differences between olecranon osteotomy and triceps-sparing approach for the incidence of excellent/good elbow function (odds ratio [OR]: 1.37; 95% confidence interval [CI]: 0.69-2.75; P = 0.371), Mayo elbow performance score (weight mean difference [WMD]: 0.17; 95% CI: -2.56 to 2.89; P = 0.904), duration of operation (WMD: 4.04; 95% CI: -28.60 to 36.69; P = 0.808), blood loss (WMD: 33.61; 95% CI: -18.35 to 85.58; P = 0.205), and complications (OR: 1.93; 95% CI: 0.49-7.60; P = 0.349). Sensitivity analyses found olecranon osteotomy might be associated with higher incidence of excellent/good elbow function, longer duration of operation, greater blood loss, and higher incidence of complications as compared with triceps-sparing approach.@*CONCLUSIONS@#This study found olecranon osteotomy did not yield additional benefit on the incidence of excellent/good elbow function, while the duration of operation, blood loss, and complications in patients treated with olecranon osteotomy might be inferior than triceps-sparing approach.
Subject(s)
Humans , Elbow Joint/surgery , Fracture Fixation, Internal , Humeral Fractures/surgery , Humerus , Olecranon Process/surgery , Osteotomy , Range of Motion, Articular , Treatment OutcomeABSTRACT
In this study, we investigated the inhibitory effect of SYT-1, a new compound of tetrahydroisoquino-line, on tumor cell proliferation and underlying mechanisms. Cell counting kit-8 (CCK-8) method was used to detect cell proliferation; clone formation experiment was used to detect cell clone formation ability; JC-1 probe was used to detect cell mitochondrial membrane potential; 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) probe was used to detect intracellular reactive oxygen species; Annexin V-FITC/PI (fluorescein isothiocyanate/propidium) counterstaining method was used to detect apoptosis; Western blot assay was used to detect the expression level of related proteins. The experimental results show that SYT-1 has a significant inhibitory effect on the proliferation of six human-derived cancer cells. Among them, the inhibitory effect on breast cancer MCF-7 cells is the strongest, the half maximal inhibitory concentration (IC50) of SYT-1 of 48 h administration on MCF-7 cells is 5.87 μmol·L-1, which is better than that of cisplatin (8.92 μmol·L-1). Further studies have shown that SYT-1 can dose-dependently inhibit the monoclonal formation ability of MCF-7 cells, and can cause the mitochondrial membrane potential of the cells to decrease and the level of reactive oxygen species to increase. In addition, SYT-1 can significantly inhibit the activation of PI3K-Akt (phosphatidylinositol 3-kinase/protein kinase B) signaling pathway and induce apoptosis of MCF-7 cells. The above research results show that, as a new type of tetrahydroisoquinoline compound, SYT-1 has the potential to inhibit tumor cell proliferation.
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Objective:To systematically evaluate the relationship between sedentary behavior (SB) and the risk of developing gestational diabetes mellitus (GDM).Methods:PubMed, Medline, EMBASE, CINAHL, the Cochrane Library, the Rehabilitation & Sports Medicine Source, the Sedentary Behavior Research Database (SBRD), Wanfang Database, the China Journal full-text database, and the China Biomedical Literature Database were searched for cohort studies, case-control studies, and cross-sectional studies concerning the risk of SB and GDM from the establishment of the database to January 2021. Two researchers screened the literature, extracted data, evaluated the quality of the data according to the inclusion and exclusion criteria, and, finally, produced a descriptive analysis of the results.Results:A total of 11 studies were included, including eight cohort studies, two cross-sectional studies, and one case-control study. The overall quality of the studies was moderate. The prevalence of GDM was 5.04%-26.81%, and the prevalence of SB before and during pregnancy was 39.47%-40.21% and 28.86%-93.50%, respectively. In terms of the prevalence of SB before pregnancy, four moderate-quality studies reported no association with GDM risk. In terms of SB during pregnancy, four moderate-quality studies reported no association with GDM risks, and four studies (one of high quality and three of moderate quality) reported an association with GDM risks, two of which focused on the second trimester. There was considerable heterogeneity between studies on the diagnosis of GDM and SB.Conclusion:SB before pregnancy is not associated with the risk of GDM, while the relationship between SB and the risk of GDM is unclear, but the level of SB in the second trimester of pregnancy may be positively associated with the risk of GDM.
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Glucagon-like peptide-1 receptor (GLP-1R) agonists are efficacious antidiabetic medications that work by enhancing glucose-dependent insulin secretion and improving energy balance. Currently approved GLP-1R agonists are peptide based, and it has proven difficult to obtain small-molecule activators possessing optimal pharmaceutical properties. We report the discovery and mechanism of action of LY3502970 (OWL833), a nonpeptide GLP-1R agonist. LY3502970 is a partial agonist, biased toward G protein activation over ß-arrestin recruitment at the GLP-1R. The molecule is highly potent and selective against other class B G protein-coupled receptors (GPCRs) with a pharmacokinetic profile favorable for oral administration. A high-resolution structure of LY3502970 in complex with active-state GLP-1R revealed a unique binding pocket in the upper helical bundle where the compound is bound by the extracellular domain (ECD), extracellular loop 2, and transmembrane helices 1, 2, 3, and 7. This mechanism creates a distinct receptor conformation that may explain the partial agonism and biased signaling of the compound. Further, interaction between LY3502970 and the primate-specific Trp33 of the ECD informs species selective activity for the molecule. In efficacy studies, oral administration of LY3502970 resulted in glucose lowering in humanized GLP-1R transgenic mice and insulinotropic and hypophagic effects in nonhuman primates, demonstrating an effect size in both models comparable to injectable exenatide. Together, this work determined the molecular basis for the activity of an oral agent being developed for the treatment of type 2 diabetes mellitus, offering insights into the activation of class B GPCRs by nonpeptide ligands.
Subject(s)
Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/pharmacology , Protein Domains/genetics , Administration, Oral , Aminopyridines/pharmacology , Animals , Anti-Obesity Agents/pharmacology , Benzamides/pharmacology , Cryoelectron Microscopy , Glucagon-Like Peptide-1 Receptor/genetics , Glucagon-Like Peptide-1 Receptor/metabolism , Glucagon-Like Peptide-1 Receptor/ultrastructure , HEK293 Cells , Humans , Incretins/pharmacology , Macaca fascicularis , Male , Mice , Mice, Transgenic , Models, Molecular , Mutagenesis, Site-Directed , Rats , Species Specificity , Swine , Tryptophan/geneticsABSTRACT
BackgroundCurrently, the 2019-nCoV has spread to most countries of the world. Understanding the environmental factors that affect the spread of the disease COVID-19 infection is critical to stop the spread of the disease. The purpose of this study is to investigate whether population density is associated with the infection rate of the COVID-19. MethodsWe collected data from official webpages of cities in China and in the US. The data were uploaded on Excel spreadsheets for statistical analyses. We calculated the morbidity and population density of cities and regions in these two countries. We then examined the relationship between the morbidity and other factors. ResultsOur analysis indicated that the population density in cities in Hubei province where the COVID-19 was severe was associated with a higher percentage of morbidity, with an r value of 0.62. Similarly, in the US, the density of 51 states and territories is also associated with morbidity from COVID-19 with an r value of 0.55. In contrast, as a control group, there is no association between the morbidity and population density in 33 other regions of China, where the COVID-19 epidemic is well under control. Interestingly, our study also indicated that these associations were not influenced by the first case of COVID-19. The rate of morbidity and the number of days from the first case in the US has no association, with an r value of -0.1288. ConclusionsPopulation density is positively associated with the percentage of patients with COVID-19 infection in the population. Our data support the importance of such as social distancing and travel restriction in the prevention of COVID-19 spread.