Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

Comparative study on the manually-controlled variable-rate versus fixed-rate infusion of norepinephrine for preventing hypotension during spinal anesthesia for cesarean delivery

Study objectivePrevious studies have shown that prophylactic norepinephrine infusion is superior to intermittent bolus administration in preventing post-spinal hypotension. Nevertheless, it is still controversial whether manually-controlled variable-rate infusion is more effective than fixed-rate infusion. The purpose of the present study was to compare the efficacy of variable-rate infusion and fixed-rate infusion of norepinephrine for prophylaxis against maternal hypotension and maintaining hemodynamic stability during spinal anesthesia for cesarean delivery to determine more effective mode for clinical practice.DesignA prospective randomized, controlled study.SettingOperating room, Women's Hospital, Zhejiang University School of Medicine.PatientsA total of 161 parturients scheduled for elective cesarean delivery with spinal anesthesia were randomized into Group F (fixed-rate infusion) and Group V (variable-rate infusion).InterventionsParturients received prophylactic norepinephrine infusion concurrent with the intrathecal injection at rate started at 0.05 μg/kg/min. In Group F, norepinephrine was administered continuously at a fixed (on-off) rate, and a bolus of norepinephrine 5 μg or 10 μg was given when systolic blood pressure (SBP) decreased by 20% or more of baseline. In Group V, manually adjusted norepinephrine infusion within the range 0–0.14 μg/kg/min, according to SBP at 1-min intervals until delivery, aim to maintain values close to the baseline.MeasurementsDuring the study period, the incidence of maternal hypotension, hemodynamic performance, the number of physician interventions, reactive hypertension, bradycardia, nausea, vomiting, norepinephrine cumulative dose (before delivery), and neonatal outcomes were recorded.Main resultsThe incidence of maternal hypotension was significantly lower in Group V than that in Group F (9% versus 30%) (P < 0.001). No significant difference was found in the serial changes in SBP and heart rate (HR) for the first 15 min. Group V showed higher frequency of physician interventions compared with the Group F (P < 0.001). The incidence of hypertension, severe hypotension, nausea, vomiting, bradycardia, norepinephrine cumulative dose, and neonatal outcome were comparable between the two groups.ConclusionWhen norepinephrine was infused at an initial dose of 0.05 μg/kg/min for preventing hypotension during spinal anesthesia for cesarean delivery, due to technical limitations of inadequate dose design in this study, neither a variable-rate infusion (need more physician intervention) nor a fixed-rate infusion regimen (experience more transient hypotension) was optimal. However, in terms of clinical importance, how to prevent the parturients from experiencing more incidence of hypotension might be a greater concern for anesthesiologists.     

细辛碎补汤联合米诺环素对慢性牙周炎患者牙周指标及 龈沟液炎症因子的影响

目的 探讨细辛碎补汤联合米诺环素对慢性牙周炎患者牙周指标及龈沟液炎症因子的影响。方法 选取 2019 年 1 月~2021 年 8 月杭州市萧山区中医院接诊的 96 例慢性牙周炎患者作为研究对象。以双色球法将患者 分为对照组和试验组，每组各 48 例。对照组患者在常规治疗基础上加用米诺环素，试验组患者在对照组治疗 基础上加用细辛碎补汤。比较两组患者的临床疗效、牙周指标、龈沟液炎症因子及不良反应发生情况。结果 试 验组患者总有效率显著高于对照组（P<0.05）。治疗后两组患者的探诊深度、菌斑指数、探诊出血指数、龈沟 液 C–反应蛋白、肿瘤坏死因子–α 及白介素–6 水平均显著低于本组治疗前（均 P<0.05），且试验组以上指标均 显著低于对照组（均 P<0.05）。两组患者不良反应发生率比较差异无统计学意义（χ2 =0.154，P=0.695）。结论 细 辛碎补汤联合米诺环素可有效提高慢性牙周炎患者疗效，改善牙周指标，其作用机制可能与降低龈沟液炎症 因子有关。     

四君子汤合四磨汤加减治疗出口梗阻型便秘吻合器经肛门直肠切除术后的临床疗效

目的:观察四君子汤合四磨汤加减治疗出口梗阻型便秘(OOC)吻合器经肛门直肠切除术后(STARR)的临床疗效。方法:124例患者随机按数字表法分为对照组和观察组各62例。对照组术后给予芪蓉润肠口服液,20 mL/次/,3次/d;观察组术后给予四君子汤合四磨汤加减内服,1剂/d。两组疗程均连续治疗4周,并进行8周随访。分别于手术前、治疗后2周,4周、随访8周进行便秘主要症状评分和Longo ODS评分;于手术前和治疗后4周,进行超氧化物歧化酶(SOD),丙二醛(MDA)和便秘患者生存质量自评量表(PAC-QOL)评价,并进行肛门直肠测压,记录肛管静息压(ARP),肛管最大收缩压(MSP),直肠排便压力(RSP),初始感觉阈值(FSV),排便感觉阈值(CRS)和最大耐受容量(MTV)等指标;随访记录并发症发生率、复发率和排便正常率;术后4周进行满意度评价和安全性评价。结果:治疗后4周,观察组患者临床疗效优于对照组(Z=2.096,P0.05);治疗后2周,4周和随访8周,观察组便秘主要症状积分和Longo ODS评分均低于对照组(P0.01);观察组患者ARP,FSV,FSV,CRS均低于对照组(P0.01),MSP和RSP均高于对照组(P0.01);观察组并发症发生率、复发率分别为20.97%(13/62)和4.84%(3/62),分别低于对照组的39.71%(24/62)和16.13%(10/62)(P0.05);观察组排便正常率为91.94%(57/62),高于对照组的80.65%(50/62),组间差异无统计学意义;观察组PAC-QOL总分和各因子评分均低于对照组(P0.01);观察组SOD水平高于对照组,MDA水平低于对照组(P0.01);未发现干预中药相关不良反应。结论:四君子汤合四磨汤加减用于出口梗阻型便秘STARR术后患者,可进一步减轻便秘症状和病情程度,提高生活质量,降低术后并发症发生率和复发率,并可改善肛门直肠动力学指标和氧化应激指标,提高临床疗效。     

Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.     

Correlation between magnetic resonance imaging characteristics and BRAF alteration status in individuals with optic pathway/hypothalamic pilocytic astrocytomas

Background and purposeMost individuals with optic pathway/hypothalamic pilocytic astrocytoma (OPHPA) harbor either the BRAF V600E mutation or KIAA1549-BRAF fusion (K-B). This study aimed to investigate the imaging characteristics of OPHPA in relation to BRAF alteration status.Materials and methodsSeven cases of OPHPA harboring either the BRAF V600E mutation or K-B fusion were included in the study. Preoperative magnetic resonance imaging (MRI) was assessed for degree of T2 hyperintensity on T2-weighted images (T2WI) and the ratio of nonenhancing T2 or fluid-attenuated inversion recovery (FLAIR) hyperintense area to the contrast enhanced area (CE) on gadolinium-enhanced-T1 weighted images (T2/FLAIR-CE mismatch). The T2 signal intensity was normalized to cerebrospinal fluid (T2/CSF) for both the V600E and K-B group and compared. T2/FLAIR-CE mismatch was assessed by calculating the proportion of the tumor volume of nonenhancing high T2 signal intensity to the whole lesion (nonenhancing and enhancing components).ResultsFour and three cases of OPHPA harboring the BRAF V600E mutation and K-B, respectively, were analyzed. The T2/CSF value was higher in the K-B group than in the V600E group. Moreover, the V600E group had a larger T2/FLAIR-CE mismatch than the K-B group.ConclusionsThe BRAF alteration status in individuals with OPHPA was associated with preoperative MRI by focusing on T2 signal intensity and T2/FLAIR-CE mismatch. The BRAF V600E mutation was associated with a lower T2/CSF value and larger T2/FLAIR-CE mismatch, whereas K-B fusion was associated with a higher T2/CSF value and smaller T2/FLAIR-CE mismatch.     

Improving the Catalytic CO2 Reduction on Cs2AgBiBr6 by Halide Defect Engineering: A DFT Study

Pb-free double halide perovskites have drawn immense attention in the potential photocatalytic application, due to the regulatable bandgap energy and nontoxicity. Herein, we first present a study for CO₂ conversion on Pb-free halide perovskite Cs₂AgBiBr₆ under state-of-the-art first-principles calculation with dispersion correction. Compared with the previous CsPbBr₃, the cell parameter of Cs₂AgBiBr₆ underwent only a small decrease of 3.69%. By investigating the adsorption of CO, CO₂, NO, NO₂, and catalytic reduction of CO₂, we found Cs₂AgBiBr₆ exhibits modest adsorption ability and unsatisfied potential determining step energy of 2.68 eV in catalysis. We adopted defect engineering (Cl doping, I doping and Br-vacancy) to regulate the adsorption and CO₂ reduction behavior. It is found that CO₂ molecule can be chemically and preferably adsorbed on Br-vacancy doped Cs₂AgBiBr₆ with a negative adsorption energy of −1.16 eV. Studying the CO₂ reduction paths on pure and defect modified Cs₂AgBiBr₆, Br-vacancy is proved to play a critical role in decreasing the potential determining step energy to 1.25 eV. Finally, we probe into the electronic properties and demonstrate Br-vacancy will not obviously promote the process of catalysis deactivation, as there is no formation of deep-level electronic states acting as carrier recombination center. Our findings reveal the process of gas adsorption and CO₂ reduction on novel Pb-free Cs₂AgBiBr₆, and propose a potential strategy to improve the efficiency of catalytic CO₂ conversion towards practical implementation.     

Evaluation of Central Venous Access with Accelerated Seldinger Technique Versus Modified Seldinger Technique

Background

Central vein catheter (CVC) placement using the modified Seldinger technique is a common procedure in the emergency department, but can be time consuming due to the multiple pieces of equipment included in central line kits and the number of steps in the procedure. Preassembled devices combine a needle, guidewire, dilator, and sheath into one unit and potentially simplify the process and reduce time required for CVC placement using the accelerated Seldinger technique.

脑脊液降钙素原及乳酸测定在早期诊断颅脑术后颅内感染的意义

目的研究降钙素原(PCT)及乳酸水平在早期诊断颅脑术后颅内感染的意义。方法颅脑术后颅内感染患者(n=20)和非颅内感染患者(n=20)的脑脊液和血液样本,检测脑脊液和血清PCT,脑脊液和血液乳酸水平等指标并进行统计分析。结果感染组脑脊液和血清PCT、乳酸水平较非感染组显著升高,差异有统计学意义(P0.05)。脑脊液PCT和乳酸水平诊断敏感性及特异性均较血清PCT和乳酸水平高。结论脑脊液PCT、乳酸在颅脑手术术后颅内感染的诊断中均有意义,其中脑脊液PCT较乳酸敏感性更高,临床应用价值更大。