喉罩通气下不同剂量羟考酮诱导对腹腔镜胆囊切除术的影响

目的探讨不同剂量的羟考酮诱导喉罩置入腹腔镜胆囊切除术(LC)中的临床效果。方法选取2017年1月—2017年6月大连大学附属中山医院行LC手术患者80例,采用随机数字表法分为4组,每组20例。不同剂量的羟考酮组(O_1、O_2及O_3)分别静脉注射羟考酮0.10、0.15和0.25 mg/kg,依托咪酯0.3 mg/kg和罗库溴铵0.6 mg/kg诱导喉罩置入后行机械通气,对照组(C)将羟考酮换成舒芬太尼0.25μg/kg,其他相同。术中静脉泵注丙泊酚50～150μg/(kg·min)和瑞芬太尼0.1～0.3μg/(kg·min)维持麻醉,调控泵速维持脑电双频指数(BIS)值40～60。记录4组患者手术时间、苏醒时间、拔喉罩时间,以及丙泊酚和瑞芬太尼用量。比较4组患者入室(T0)、插喉罩前(T_1)、插喉罩后1 min(T_2)、气腹时(T_3)及切胆时(T_4)平均血压(MBP)和心率(HR)的变化。评估4组患者拔喉罩后5 min(T_5),1 h(T_6),4 h(T_7),8 h(T_8)及12 h(T_9)的疼痛视觉模拟量表评分(VAS),以及对镇痛药的需求情况。记录呛咳、恶心呕吐、头晕、嗜睡及高血压的发生情况。结果 4组患者T1时血压、心率低于T0(P <0.05),T2时O_1组血压高于C、O_2和O_3组(P<0.05),T_3时O_1组和C组血压高于O_2和O_3组(P <0.05);O1组在T_5、T_6,O_2组和O_3组在T_5、T_8时VAS评分低于C组(P <0.05);O_2组和O_3组在T_5、T_8时VAS评分低于O_1组(P <0.05);O_3组在T_5、T_6时VAS评分低于O_2组(P <0.05);O_1组、O_2组和O_3组诱导期呛咳反应、术后曲马多使用低于C组,O_3组术后曲马多使用低于O_1组和O_2组(P <0.05);O_2组和O_3组术中高血压低于O_1组和C组(P <0.05)。结论 0.25 mg/kg羟考酮可以安全有效地应用于喉罩LC手术的全身麻醉诱导,既有利于术中血流动力学稳定和术后镇痛,又不影响术后苏醒。

Role of serum β2-microglobulin, glycosylated hemoglobin, and vascular endothelial growth factor levels in diabetic nephropathy

BACKGROUND Diabetic nephropathy(DN)is a common complication of type 1 and type 2 diabetes that can lead to kidney damage and high blood pressure.Increasing evidence support the important roles of microproteins and cytokines,such asβ2-microglobulin(β2-MG),glycosylated hemoglobin(HbA1c),and vascular endothelial growth factor(VEGF),in the pathogenesis of this disease.In this study,we identified novel therapeutic options for this disease.AIM To analyze the guiding significance ofβ2-MG,HbA1c,and VEGF levels in patients with DN.METHODS A total of 107 patients with type 2 diabetes mellitus complicated with nephropathy and treated in our hospital from May 2018 to February 2021 were included in the study.Additionally,107 healthy individuals and 107 patients with simple diabetes mellitus were selected as the control groups.Changes inβ2-MG,HbA1c,and VEGF levels in the three groups as well as the different proteinuria exhibited by the three groups were examined.RESULTS Changes inβ2-MG,HbA1c,and VEGF levels in the disease,healthy,and simple diabetes groups were significantly different(P<0.05).The expression of these factors from high to low were evaluated in different groups by pairwise comparison.In the disease group,high to low changes inβ2-MG,HbA1c,and VEGF levels were noted in the massive proteinuria,microproteinuria,and normal urinary protein groups,respectively.Changes in these factors were positively correlated with disease progression.CONCLUSION The expression of serumβ2-MG,HbA1c,and VEGF was closely correlated with DN progression,and disease progression could be evaluated by these factors.

Association Between Polymorphisms of DNA Repair Gene XRCC1 and DNA Damage in Asbestos-Exposed Workers

Objective To compare the asbestos-induced DNA damage and repair capacities of DNA damage between 104 asbestosexposed workers and 101 control workers in Qingdao City of China and to investigate the possible association between polymorphisms in codon 399 of XRCC1 and susceptibility to asbestosis. Methods DNA damage levels in peripheral blood lymphocytes were determined by comet assay, and XRCC1 genetic polymorphisms of DNA samples from 51 asbestosis cases and 53 non-asbestosis workers with a similar asbestos exposure history were analyzed by PCR/RFLP. Results The basal comet scores （3.95±2.95） were significantly higher in asbestos-exposed workers than in control workers （0.10±0.28）. After 1 h H2O2 stimulation, DNA damage of lymphocytes exhibited different increases. After a 4 h repair period, the comet scores were 50.98±19.53 in asbestos-exposed workers and 18.32±12.04 in controls. The residual DNA damage （RD） was significantly greater （P〈0.01） in asbestos-exposed workers （35.62%） than in controls （27.75%）. XRCC1 genetic polymorphism in 104 asbestos-exposed workers was not associated with increased risk of asbestosis. But compared with polymorphisms in the DNA repair gene XRCC1 （polymorphisms in codon 399） and the DNA damage induced by asbestos, the comet scores in asbestosis cases with Gin/Gin, Gln/Arg, and Arg/Arg were 40.26±18.94, 38.03±28.22, and 32.01±11.65, respectively, which were higher than those in non-asbestosis workers with the same genotypes （25.58±11.08, 37.08±14.74, and 29.38±10.15）. There were significant differences in the comet scores between asbestosis cases and non-asbestosis workers with Gin/Gin by Student＇s t-test （P〈0.05 or 0.01）. The comet scores were higher in asbestosis workers with Gin/Gin than in those with Arg/Arg and in non-asbestosis workers exposed to asbestos, but without statistically significant difference. Conclusions Exposure to asbestos may be related to DNA damage or the capacity of cells to repair H2O2-induced DNA damage. DNA repair gene XRCC 1 codon 399 may be responsible for the inter-individual susceptibility in DNA damage and repair capacities.

Advances in the design and development of SARS-CoV-2 vaccines

Since the end of 2019,coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread worldwide.The RNA genome of SARS-CoV-2,which is highly infectious and prone to rapid mutation,encodes both structural and non-structural proteins.Vaccination is currently the only effective method to prevent COVID-19,and structural proteins are critical targets for vaccine development.Currently,many vaccines are in clinical trials or are already on the market.This review highlights ongoing advances in the design of prophylactic or therapeutic vaccines against COVID-19,including viral vector vaccines,DNA vaccines,RNA vaccines,live-attenuated vaccines,inactivated virus vaccines,recombinant protein vaccines and bionic nanoparticle vaccines.In addition to traditional inactivated virus vaccines,some novel vaccines based on viral vectors,nanoscience and synthetic biology also play important roles in combating COVID-19.However,many challenges persist in ongoing clinical trials.

PM_(2.5) obtained from urban areas in Beijing induces apoptosis by activating nuclear factor-kappa B

Background: Particulate matter(PM), which has adverse effects on citizen health, is a major air pollutant in Beijing city. PM_(2.5) is an indicator of PM in urban areas and can cause serious damage to human health. Many epidemiological studies have shown that nuclear factor-kappa B(NF-κB) is involved in PM_(2.5)-induced cell injury, but the exact mechanisms are not well understood.Methods: The cytotoxic effects of PM_(2.5) at 25–1600μg/ml for 24 h were determined by MTT assay in Chinese hamster ovary cells(CHO) cells. Flow cytometry was used to determine the apoptosis rate induced by PM_(2.5). The destabilized enhanced green fluorescent protein(d2 EGFP) green fluorescent protein reporter system was used to determine the NF-κB activity induced by PM_(2.5). The expression of pro-apoptotic Bcl-2-associated death promoter(BAD) proteins induced by PM_(2.5) was determined by Western blotting to explore the relationship between PM_(2.5) and the NF-κB signaling pathway and to determine the toxicological mechanisms of PM_(2.5).Results: PM_(2.5) collected in Beijing urban districts induces cytotoxic effects in CHO cells according to MTT assay with 72.28% cell viability rates even at 200μg/ml PM_(2.5) and flow cytometry assays with 26.97% apoptosis rates at 200μg/ml PM_(2.5). PM_(2.5) increases the activation levels of NF-κB, which have maintained for 24 h. 200μg/ml PM_(2.5) cause activation of NF-κB after exposure for 4 h, the activation peak appears after 13.5 h with a peak value of 25.41%. The average percentage of NF-κB activation in whole 24 h is up to 12.90% by 200μg/ml PM_(2.5). In addition, PM_(2.5) decreases the expression level of the pro-apoptotic protein BAD in a concentration-dependent manner.Conclusion: PM_(2.5) induces NF-κB activation, which persists for 24 h. The expression of pro-apoptotic protein BAD decreased with increased concentrations of PM_(2.5). These findings suggest that PM_(2.5) plays a major role in apoptosis by activating the NF-κB signaling pathway and reducing BAD protein expression.

Transition Dipole, Charge Transfer, and Electron-hole Coherence in Two-photon Absorption： Visualizations with Two Dimensional Site and Three Dimensional Cube Representations

The developed visualization methods of two dimensional （2D） site and three dimensional （3D） cube representations have been performed to show the orientation of transition dipole, charge transfer, and electron-hole coherence in two-photon absorption （TPA）. The 3D cube representations of transition density can reveal visually the orientation and strength of transition dipole moment, and charge different density show the orientation of charge transfer in TPA. The 2D site representation can reveal visually the electron-hole coherence in TPA. The combination of 2D site and 3D cube representations provide clearly inspect into the charge transfer process and the contribution of excited molecular segments for TPA.

The afterglow emission from a stratified jet in GRB 170817A

The afterglow of GRB 170817 A has been detected for more than three years,but the origin of the multi-band afterglow light curves remains under debate.A classical top-hat jet model is faced with difficulties in producing a shallow rise of the afterglow light curves as observed(E_(v) ∝ T^(0.8)).Here we reconsider the model of stratified ejecta with an energy profile of E(> Γβ)=E_0(Γβ)^(-k) as the origin of the afterglow light curves of the burst,where Γ and β are the Lorentz factor and speed of the ejecta,respectively.k is the power-law slope of the energy profile.We consider that the ejecta are collimated into jets.Two kinds of jet evolutions are investigated,including a lateral-spreading jet and a non-lateral-spreading jet.We fit the multi-band afterglow light curves,including the X-ray data at one thousand days post-burst,and find that both the models of the spreading and non-spreading jets can fit the light curves well,but the observed angular size of the source and the apparent velocity of the flux centroid for the spreading jet model are beyond the observation limits,while the non-spreading jet model meets the observation limits.Some of the best-fit parameters for the non-spreading jet model,such as the number density of the circumburst medium~10^(-2) cm^(-3) and the total jet kinetic energy E ~ 4.8 × 10^(51) erg,also appear plausible.The best-fit slope of the jet energy profile is k ~7.1.Our results suggest that the afterglow of GRB 170817 A may arise from the stratified jet and that the lateral spreading of the jet is not significant.

Different Features of Jets and Isotropic Fireballs in Gamma-ray Burst Phase

We investigated physical quantities including the spectrum, emission lines and pulse profiles expected from a uniform jet, a spherical fireball and the 1/Г region （the portion of the spherical fireball with opening angle 1/Г） in the prompt emission phase, after taking into consideration of the Doppler effect under the fireball framework. Our study shows that： a） for these physical quantities the spherical fireball and the uniform jets do not present obvious differences, so we cannot use these to distinguish a spherical fireball from a uniform jet; b） for the spherical fireball and a uniform jet, the observed quantities mainly come from the 1/Г region, so we can simply use the 1/Г region in approximate calculations; c） broadening of emission lines is a general phenomena, which mainly comes from the curvature effect; d） the 1/Г region plays different roles in different frequency ranges, and the radiation from the 1/Г region is greater in the higher than in the lower frequencies.

GRB Energies and E_γ-E_(peak) Correlation with the Jet Expanding Laterally at the Sound Speed

A Gamma-ray burst （GRB） is generally believed to be a jet with a small opening angle, this opening angle is usually derived with the afterglow light curve break time using an analytical method. Here we show that the method is not accurate. Using the set of equations of hydrodynamic evolution with the sideways expansion at the local sound speed derived by previous authors and the observed light curve break times, we numerically derive the initial opening angles. Then the collimation-corrected energies （Eγ） for a sample of GRBs are calculated. They are found to show a wide spread, suggesting that the previously declared clustering by some authors may not exist. Also, the Epeak - Eγ relation, claimed by some other authors （Epeak is the spectral peak energy）, is found still to hold, with a slightly stronger correlation.

3D bioactive cell-free-scaffolds for in-vitro/in-vivo capture and directed osteoinduction of stem cells for bone tissue regeneration

Hydrophilic bone morphogenetic protein 2(BMP2)is easily degraded and difficult to load onto hydrophobic carrier materials,which limits the application of polyester materials in bone tissue engineering.Based on soybean-lecithin as an adjuvant biosurfactant,we designed a novel cell-free-scaffold of polymer of poly(ε-caprolactone)and poly(lactide-co-glycolide)-co-polyetherimide with abundant entrapped and continuously released BMP2 for in vivo stem cell-capture and in situ osteogenic induction,avoiding the use of exogenous cells.The optimized bioactive osteo-polyester scaffold(BOPSC),i.e.SBMP-10SC,had a high BMP2 entrapment efficiency of 95.35%.Due to its higher porosity of 83.42%,higher water uptake ratio of 850%,and sustained BMP2 release with polymer degradation,BOPSCs were demonstrated to support excellent in vitro capture,proliferation,migration and osteogenic differentiation of mouse adipose derived mesenchymal stem cells(mADSCs),and performed much better than traditional BMP-10SCs with unmodified BMP2 and single polyester scaffolds(10SCs).Furthermore,in vivo capture and migration of stem cells and differentiation into osteoblasts was observed in mice implanted with BOPSCs without exogenous cells,which enabled allogeneic bone formation with a high bone mineral density and ratios of new bone volume to existing tissue volume after 6 months.The BOPSC is an advanced 3D cell-free platform with sustained BMP2 supply for in situ stem cell capture and osteoinduction in bone tissue engineering with potential for clinical translation.

Effect of intensive multifactorial treatment on the intima-media thickness of large arteries in patients with new-onset type 2 diabetes mellitus

Objective: To quantify the changes in blood glucose, blood lipids, blood pressure, and the intima-media thickness (IMT) of large arteries in patients with new-onset type 2 diabetes mellitus who received either intensive multifactorial treatment or conventional treatment. Methods: Two-hundred and ten patients with new-onset type 2 diabetes mellitus were randomly assigned to two groups: an intensive treatment group (n=110) and a conventional treatment group (n=100). Fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c), blood pressure, blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein C (LDL-C), and high-density lipoprotein C (HDL-C)], and IMTs of large arteries (carotid, iliac, and femoral arteries) were determined before and at one and two years after starting treatment. The patients in the conventional treatment group received routine diabetes management in our outpatient department. Targets were established for patients in the intensive treatment group. Their blood glucose, blood lipids, and blood pressure levels were regularly monitored and therapeutic regimens were adjusted for those whose measurements did not meet the target values until all the parameters met the established targets. Within-group and between-group differences were evaluated. Results: A significantly greater percentage of patients in the intensive treatment group had LDL-C levels that reached the target value one year after starting treatment than those in the conventional treatment group (52.04% vs. 33.33%, P<0.05). No significant differences were found be- tween groups for FBG, HbA1c, blood pressure, TG, TC, or HDL-C. The percentages of patients with TG (51.02% vs. 34.48%), TC (52.04% vs. 33.33%), and LDL-C (61.22% vs. 43.67%) who met the respective target values in the in- tensive treatment group were all significantly higher than the corresponding percentages in the conventional treatment group two years after starting treatment (P<0.05). There were no significant differences in the percentages of patients with FBG, HbA1c, and blood pressure values meeting the respective targets between the groups at the two-year follow- up. One year after starting treatment, the LDL-C level, diastolic blood pressure (DBP), and the IMTs of the femoral and iliac arteries of the intensive treatment group were significantly lower compared to those of the conventional treatment group (P<0.05), although there was no significant difference in other metabolic parameters. Two years after starting treatment, the TC, LDL-C, blood pressure [systolic blood pressure (SBP) and DBP], and the IMTs of the carotid and femoral arteries of the intensive treatment group were significantly lower than those of the conventional treatment group (P<0.05). No significant differences in other metabolic parameters existed between the two groups two years after starting treatment. Conclusions: Early comprehensive and intensive treatment of type 2 diabetes mellitus can delay or even reverse the increase in IMT of large arteries. Lowering blood pressure and blood lipid regulation in patients with type 2 diabetes mellitus have great significance in decreasing the risk of diabetes-related macrovascular lesions.