Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.     

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.     

花宝金教授基于调气解毒法论治癌性疼痛

癌性疼痛是癌症患者的常见症状之一,其严重地摧残着患者的身心健康，影响着生命质量。中医药能够减轻疼痛，减少止痛药物的用量及减少不良反应，能够明显改善生命质量。花宝金教授指出正气不足为癌痛发作的内因，正气不足，脏腑功能失调，气血阴阳虚损，病邪乘虚而入，经脉不荣可发为疼痛。此外各种因素导致的气滞为癌痛发生的诱发因素，可导致形成血瘀、痰湿、热毒等积滞搏结发为癌肿，闭阻脉络，瘀塞不通，而致疼痛。病程日久所形成的癌毒为夙根，是癌痛反复发作的根本原因。“调气解毒法”是花宝金教授治疗癌性疼痛的主要方法之一，通过辨癌毒，从病机、治法、方药等方面论述调气解毒法在癌性疼痛中的应用。     

Cannabis and orofacial pain: a systematic review

The naturally occurring cannabis plant has played an established role in pain management throughout recorded history. However, in recent years, both natural and synthetic cannabis-based products for medicinal use (CBPM) have gained increasing worldwide attention due to growing evidence supporting their use in alleviating chronic inflammatory and neuropathic pain associated with an array of conditions. In view of these products’ growing popularity in both the medical and commercial fields, we carried out a systematic review to ascertain the effects of cannabis and its synthetically derived products on orofacial pain and inflammation. The application of topical dermal cannabidiol formulation has shown positive findings such as reducing pain and improving muscle function in patients suffering from myofascial pain. Conversely, two orally-administered synthetic cannabinoid receptor agonists (AZD1940 and GW842166) failed to demonstrate significant analgesic effects following surgical third molar removal. There is a paucity of literature pertaining to the effects of cannabis-based products in the orofacial region; however, there is a wealth of high-quality evidence supporting their use for treating chronic nociceptive and neuropathic pain conditions in other areas. Further research is warranted to explore and substantiate the therapeutic role of CBPMs in the context of orofacial pain and inflammation. As evidence supporting their use expands, healthcare professionals should pay close attention to outcomes and changes to legislation that may impact and potentially benefit their patients.     

Impact of abdominal imaging on the diagnosis of acute pancreatitis in patients with painless lipase elevation

Abdominal pain is considered a cardinal feature of acute pancreatitis (AP), and abdominal imaging is only required to diagnose AP when the pain is atypical, or serum enzyme elevation does not match the clinical picture. While painless lipase elevation is being increasingly associated with worse outcomes in various diseases, the diagnostic approach to such elevation is so-far unclear. We thus aimed to learn the impact of pain on the diagnosis of AP.MethodsAll patients presenting to the Mayo Clinic Arizona Hospital emergency department with a serum lipase ≥3x upper limit of normal between April 2016 and January 2020 were prospectively followed. Their charts were reviewed for the nature of pain, serum lipase levels on presentation, abdominal imaging, and whether a diagnosis of AP was made. Chronic pancreatitis was excluded.ResultsAmong 320 patients, 85 (26.5%) had painless lipase elevation. These patients had abdominal imaging less often (56/85, 66%) than in those with abdominal pain (201/235, 83%; p = 0.001). The diagnosis of AP increased overall from 31/63 (49%) without imaging to 198/257 (77%) with imaging (P < 0.001). Imaging increased the diagnosis of AP in patients with painless lipase elevation from 2/29 (7%) without imaging to 16/56 (29%; p = 0.025) among those who were imaged.ConclusionsPainless lipase elevation >3-fold the upper limit of normal is common in emergency department patients. 1/3 to 1/4 of these may have AP. Abdominal imaging increases the diagnosis of AP in patients with painless lipase elevation. Therefore, abdominal imaging in such patients may help detect AP that otherwise eludes diagnosis.     

不同时期COPD患者血清DcR3、Survivin表达水平及临床意义

目的 探讨不同时期慢性阻塞性肺疾病(COPD)患者血清诱饵受体3(DcR3)、凋亡抑制蛋白(Survivin)表达水平及临床意义。方法 选取2018年9月—2019年12月本院收治的92名COPD患者为研究对象,其中稳定型COPD 50例,急性加重期COPD 42例;同期本院健康体检者88例为对照组。测定各组研究对象血清DcR3、Survivin水平及肺功能指标。 与对照组[DcR3(106.54±48.35)pg/mL,Survivin(98.85±26.59)pg/mL]比较,稳定期组和急性加重期组血清DcR3[(395.23±123.85)pg/mL,(1 248.81±213.59)pg/mL]、Survivin [(267.54±84.69)pg/mL,(1 233.95±307.26)pg/mL]水平升高;与稳定期组比较,急性加重期组血清DcR3、Survivin水平升高。与对照组比较,稳定期组和急性加重期组FEV1%、FEV1 /FVC、DLCO%水平降低(P<0.001);与稳定期组比较,急性加重期组FEV1%、FEV1 /FVC、DLCO%水平降低(P<0.001)。随着低氧血症严重程度的增加,COPD患者血清DcR3、Survivin水平逐渐增加(P<0.001)。多因素logistics回归分析显示,高水平DcR3、Survivin、IL-12、hs-CRP为COPD病情的危险因素(P<0.001)。DcR3、Survivin与FEV、FEV1 /FVC呈负相关,与IL-12、TNF-α、hs-CRP呈正相关(P<0.001)。 COPD稳定期、急性加重期患者血清DcR3、Survivin表达水平升高,且DcR3、Survivin与COPD病情严重程度呈正相关。     

The effect of heel-to-toe drop of running shoes on patellofemoral joint stress during running

BackgroundTraditional running shoes with heel-to-toe drops is thought to be a contributor to increased patellofemoral joint stress, which is proposed as a mechanism of patellofemoral pain.Research questionIs there an increase in patellofemoral joint stress when running in shoes with drops compared to running in shoes without a drop?MethodsLower limbs kinematics and ground reaction force were collected from eighteen healthy runners during over-ground running in shoes with 15 mm, 10 mm, 5 mm drops, and without a drop. Patellofemoral joint force and stress were calculated from the kinematic and kinetic data using a biomechanical model of the patellofemoral joint.ResultsThe peak patellofemoral joint stress was increased by more than 15% when running in shoes with 15 mm and 10 mm drops compared to running in shoes without a drop (p = 0.003, p = 0.001). The knee flexion angle was significantly increased when running in shoes with 15 mm, 10 mm and 5 mm drops (p = 0.014, p = 0.003, p = 0.002), the knee extension moment (p = 0.009, p = 0.002) and patellofemoral joint force (p = 0.003, p = 0.001) were increased when running in shoes with 15 mm and 10 mm drops, compared to running in shoes without a drop.SignificanceCompared to running in shoes without a drop, running in shoes with drops > 5 mm increase the peak patellofemoral joint stress significantly, which is mainly due to the increased knee extension moment.