Egg-adaptive mutations in H3N2v vaccine virus enhance egg-based production without loss of antigenicity or immunogenicity

The recently detected zoonotic H3N2 variant influenza A (H3N2v) viruses have caused 343 documented cases of human infection linked to contact with swine. An effective vaccine is needed for these viruses, which may acquire transmissibility among humans. However, viruses isolated from human cases do not replicate well in embryonated chicken eggs, posing an obstacle to egg-based vaccine production. To address this issue, we sought to identify egg-adaptive mutations in surface proteins that increase the yield of candidate vaccine viruses (CVVs) in eggs while preserving their immunizing effectiveness. After serial passage of a representative H3N2v isolate (A/Indiana/08/2011), we identified several egg-adaptive combinations of HA mutations and assessed the egg-based replication, antigenicity, and immunogenicity of A/Puerto Rico/8/34 (H1N1, PR8)-based 6 + 2 reverse genetics CVVs carrying these mutations. Here we demonstrate that the respective combined HA substitutions G186₁V + N246₁K, N165₁K + G186₁V, T128₁N + N165₁K + R76₂G, and T128₁N + N165₁K + I10₂M, all identified after egg passage, enhanced the replication of the CVVs in eggs without substantially affecting their antigenicity or immunogenicity. The mutations were stable, and the mutant viruses acquired no additional substitutions during six subsequent egg passages. We found two crucial mutations, G186V, which was previously defined, and N246K, which in combination improved virus yield in eggs without significantly impacting antigenicity or immunogenicity. This combination of egg-adaptive mutations appears to most effectively generate high egg-based yields of influenza A/Indiana/08/2011-like CVVs.     

原发性开角型青光眼患者单侧小梁切除术后对侧眼眼压变化

目的　观察原发性开角型青光眼患者单眼行外路小梁切除术后对侧眼眼压变化趋势。方法　回顾性分析2016年12月至2021年1月于我院行单眼外路小梁切除术的37例原发性开角型青光眼患者资料,随访并记录患者术后1 d、2 d、3 d、1周、2周、1个月和3个月对侧未手术眼眼压,与术前基线眼压比较。结果　术后1 d、2 d、3 d及1周、2周、1个月和3个月患者对侧眼眼压分别由术前(16.38±4.25)mmHg（1 kPa=7.5 mmHg）升至（18.11±4.03）mmHg、(18.35±5.29)mmHg、（18.03±5.35）mmHg、（17.21±3.33）mmHg、(17.96±3.82)mmHg、（18.57±4.45）mmHg、(17.27±3.73)mmHg,差异均有统计学意义(均为P<0.05）。术后1 d患者对侧眼眼压开始升高,增幅最大出现在术后1个月［(3.36±4.56)mmHg(升高21%)］。术后3个月患者对侧眼眼压开始回归基线水平。相关性分析结果显示,术后不同时间点患者对侧眼眼压改变与年龄、性别均无相关性(均为P>0.05),与术前基线眼压均呈正相关（均为P<0.05）,术后随访期内有11例患者对侧眼眼压控制不佳（继续同术前用药,眼压≥21 mmHg）需要手术或加用降眼压药物。术后对侧眼眼压改变与术前降眼压药物使用时间相关。除术后1 d(P=0.31)外,术前持续用药患者与新用药患者术后其他时间点对侧眼眼压改变差异均有统计学意义(均为P<0.05)。结论　原发性开角型青光眼患者行单侧外路小梁切除术后,患者早期可能会出现对侧眼眼压升高,3个月后逐渐降低,恢复至术前基线水平。单侧小梁切除术后应加强未手术眼的眼压监测。     

天麻钩藤颗粒联合硝苯地平控释片治疗颈源性高血压的疗效

目的 观察天麻钩藤颗粒联合硝苯地平控释片在颈源性高血压患者中的应用效果。方法 选取120例颈源性高血压患者,随机分为3组,试验组同时口服天麻钩藤颗粒和硝苯地平控释片,对照1组口服硝苯地平控释片,对照2组口服天麻钩藤颗粒,治疗周期为4周,观察周期为8周。在第4、8周分别对比三组患者治疗前后的血压变化、颈部NDI评分、颈部NRS疼痛评分。结果 三组患者治疗后4周三组颈部NRS疼痛评分和NDI评分均降低,且差异无统计学意义,治疗后8周试验组和对照2组NRS疼痛评分低于对照1组,P＜0.05。在治疗后4周三组收缩压、舒张压均降低,治疗后第8周试验组和对照1组降压效果优于对照2组,P＜0.05。结论 天麻钩藤颗粒联合硝苯地平控释片可以改善颈源性高血压患者的颈肩部疼痛的临床症状,降压效果显著,患者满意度高,值得临床推广。     

热释光探测器在头部CT检查中监测晶状体器官的辐射剂量

目的探讨应用热释光探测器(TLD)监测头部CT检查患者晶状体所接受的辐射剂量的价值。方法将TLD分别放置于仿真人模体右眼晶状体和左眼眼睑表面,应用常规扫描条件和高质量扫描条件进行头部CT扫描,比较不同位置和不同扫描条件下TLD所测辐射剂量的差异。收集10例接受头部CT检查的患者,于左眼眼睑表面放置TLD,分析TLD对图像质量的影响。结果常规扫描条件下模体晶状体和眼睑表面TLD所测辐射剂量分别为(7.91±0.13)mGy和(8.02±0.09)mGy,差异无统计学意义(P0.05),高质量扫描条件下模体晶状体和眼睑表面TLD所测辐射剂量分别为(12.68±0.25)mGy和(12.89±0.39)mGy,差异亦无统计学意义(P0.05)。高质量扫描时晶状体和眼睑处TLD所测辐射剂量均高于常规扫描(P均0.05)。10例接受头部扫描患者眼睑表面处TLD所测辐射剂量为(8.73±0.27)mGy;TLD所在层面图像左右眼玻璃体SNR分别为4.83±0.25和4.68±0.22(P0.05)。结论头部CT检查中,在眼睑处放置TLD,对监测晶状体所接受辐射剂量具有一定价值。     

The relationships between type 2 diabetic retinopathy and VEGF-634G/C and VEGF-460C/T polymorphisms in Han Chinese subjects

ObjectiveTo investigate how VEGF-634G/C and VEGF-460C/T SNPs are related to diabetic retinopathy (DR) in Han Chinese subjects from the Shijiazhuang region of China.MethodsTotally 376 DM cases were divided into non-proliferative diabetic retinopathy (NPDR) group (n = 124), proliferative diabetic retinopathy (PDR) group (n = 108), and diabetes without retinopathy (DWR) group (n = 144). PCR/LDRwas utilised to detect and assess the genotypes and allele distribution frequencies at the VEGF-634G/C and VEGF-460C/T loci in each group.ResultsThe differences between NPDR, PDR and DWR groups were not significant in genotypes and allele distribution frequencies at VEGF-634G/C locus (P > 0.05). But there were significant differences between NPDR and DWR groups in genotypes (P = 0.013) and allele distribution frequencies (P = 0.002) at VEGF-460C/T locus, at which CT + CC genotypes were associated with a reduced risk of developing NPDR. There were no significant differences in genotypes (P = 0.759) or allele distribution frequencies (P = 0.433) at VEGF-460C/T locus between PDR and DWR groups.ConclusionsAmong Chinese Han individuals with type-2 DM, polymorphism − 634G/C of the VEGF gene was not correlated with NPDR or PDR; however, polymorphism-460C/T of the VEGF gene was correlated with NPDR, and C allele was associated with lower NPDR risk than T allele.     

急性非接触性前交叉韧带撕裂后关节伴随损伤的性别差异

 目的 对比分析急性非接触性前交叉韧带(ACL)撕裂后关节伴随损伤男女性别组间的不同点。方法 回顾性分析193例经临床证实为急性非接触性ACL撕裂患者的MRI资料,其中男性112例,女性81例,对男女性别组的膝关节伴随损伤情况分类统计并进行统计学分析。结果 在112例男性病例中,发现骨挫伤107例(95.5%),其中联合间室骨挫伤32例,外侧间室骨挫伤70例,内侧间室骨挫伤5例;81例女性病例中,发现骨挫伤72例(88.9%),其中联合间室骨挫伤16例,外侧间室骨挫伤49例,内侧间室骨挫伤7例;两组比较,联合间室骨挫伤发生率差异有统计学意义(χ²=4.315,P=0.038)。男女组伴发内外侧半月板(MM、LM)损伤发生率分别为(33.9%、46.4%)和(25.9%、32.1%),两组比较,LM损伤发生率差异有统计学意义(χ²=4.008,P=0.045)。男女组伴发内、外侧副韧带损伤发生率分别为(20.5%、7.1%)和(18.5%、3.7%),两组比较,差异均无统计学意义。男女组伴发关节软骨损伤发生率为17.9%和7.4%,两组比较,差异有统计学意义(χ²=4.403,P=0.036)。结论 男性患者较女性患者在急性非接触性ACL撕裂后更易伴发联合间室骨挫伤、LM损伤和关节软骨损伤。     

Prevention of pulmonary fibrosis with salvianolic acid A by inducing fibroblast cell cycle arrest and promoting apoptosis

Ethnopharmacological relevanceDanshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine (TCM), often in combination with other herbs, to treat a diversity of ailments. More recent studies have focused on its possible roles in the treatment of respiratory diseases (pneumonia and pulmonary fibrosis) and found that it has pharmacological activity that protects pulmonary morphology and function. However, the mechanism underlying this activity has not yet been clarified.Materials and methodsThe purpose of this study was to investigate the anti-pulmonary fibrosis effects exerted by salvianolic acid A (SAA), the ingredient responsible for the pharmacological activity of Danshen, and the underlying mechanisms. Bleomycin (BLM)-induced rat pulmonary fibrosis was used to evaluate the antifibrotic role of SAA, and fibroblast cells were used to study the mechanism involved.ResultsBLM-treated rats exhibited increased alveolar wall thickness and collagen deposition in lung tissues, but these pathologies were greatly attenuated by daily administration of SAA. We also found that SAA significantly inhibited the proliferation, adhesion and migration of fibroblasts in vitro. This was partly due to a strong induction of cell cycle arrest and apoptosis upon SAA treatment. Consistent with these phenotypes, we observed decreased expression of the cell cycle-related proteins cyclin D1, cyclin E1, and cyclin B1, and increased expression of p53 and p21 in SAA-treated cells. In addition, the anti-apoptotic Bcl-2 protein decreased in a dose-dependent manner, while cleaved caspase-3 protein increased upon SAA treatment.ConclusionsThese results suggest that the alleviation of rat pulmonary fibrosis by SAA is due to the inhibition of fibroblast proliferation and induction of apoptosis, which occurs mainly through p53-dependent growth arrest and apoptosis. We suggest that SAA should be considered as a potential novel therapeutic agent for the treatment of fibrotic lung diseases.     

The role of nerve fibers and their neurotransmitters in regulating intervertebral disc degeneration

Intervertebral disc degeneration (IVDD) has been the major contributor to chronic lower back pain (LBP). Abnormal apoptosis, senescence, and pyroptosis of IVD cells, extracellular matrix (ECM) degradation, and infiltration of immune cells are the major molecular alternations during IVDD. Changes at tissue level frequently occur at advanced IVD tissue. Ectopic ingrowth of nerves within inner annulus fibrosus (AF) and nucleus pulposus (NP) tissue has been considered as the primary cause for LBP. Innervation at IVD tissue mainly included sensory and sympathetic nerves, and many markers for these two types of nerves have been detected since 1940. In fact, in osteoarthritis (OA), beyond pain transmission, the direct regulation of neuropeptides on functions of chondrocytes have attracted researchers’ great attention recently. Many physical and pathological similarities between joint and IVD have shed us the light on the neurogenic mechanism involved in IVDD. Here, an overview of the advances in the nervous system within IVD tissue will be performed, with a discussion on in the role of nerve fibers and their neurotransmitters in regulating IVDD. We hope this review can attract more research interest to address neuromodulation and IVDD itself, which will enhance our understanding of the contribution of neuromodulation to the structural changes within IVD tissue and inflammatory responses and will help identify novel therapeutic targets and enable the effective treatment of IVDD disease.     

骨膜在骨折愈合及骨组织修复过程中的作用

背景:骨膜因含有成骨潜能的细胞而参与骨折愈合及骨组织修复的过程,其在修复骨缺损方面的作用是目前研究的热点。目的:对骨膜在骨折愈合及骨组织修复过程中所发挥的作用进行综述。方法:第一作者应用计算机检索1964年1月至2019年12月PubMed、中国知网数据库等中英文期刊全文数据库有关骨膜在骨折愈合及骨组织修复过程中作用的文章,英文检索词"periosteum,bone healing,periosteum cells";中文检索词"骨膜,骨折愈合,骨膜细胞"。最终选择48篇重要文献进行综述。结果与结论:①骨膜的完整性对于骨折愈合和骨组织的修复极其重要,因其较好的成骨性能、优质的材料学特性和屏障作用等特点被广泛应用于骨组织工程;②骨膜在牵拉成骨过程中的作用机制目前尚且存在争议,研究证实骨膜缺如并不会影响下颌骨缺损牵拉成骨的效果,但在四肢骨缺损牵拉成骨中的作用仍有待进一步研究。     

Do patients know their post-operative plan? A prospective cohort study of orthopaedic trauma patients at a level I trauma center

ObjectivePatient compliance with weight bearing and physical therapy recommendations is critical following an orthopedic injury. Proper compliance requires knowledge of the postinjury plan, but there is little published data regarding comprehension of postinjury recommendations among orthopedic trauma patients. We hypothesized that patient knowledge of weight bearing and physical therapy instructions following an orthopaedic injury would be poor.DesignProspective Observational CohortSettingLevel I Trauma CenterPatients194 prospectively enrolled patients completed a questionnaire testing their knowledge of their weight bearing status and physical therapy plan at their first clinic visit following an inpatient admission with an orthopedic injuryResultsDespite the fact that 73% of patients were participating in physical therapy following hospital discharge, only 66% (95% CI 60–73%) of patients correctly identified their postinjury weight bearing status. A multivariate analysis found no significant correlation between chance of knowing postoperative weightbearing status or physical therapy plan and any of the socioeconomic patient factors we collected.ConclusionsOrthopedic trauma patients had a relatively poor understanding of even basic postinjury physical therapy instructions. This did not appear to be affected by age, gender, or socioeconomic factors. Orthopedic trauma surgeons should be aware of the significant potential for knowledge deficits among their patients and should make specific efforts to identify and correct those deficits.