中西医结合治疗新型冠状病毒肺炎验案1例＊

在新型冠状病毒肺炎治疗救护工作中，中医药以其延缓轻症患者病情发展、提升疑似患者免疫机能等方面的诸多优势和效果得以参与其中。本文结合武汉一线的临床实践，探讨武汉一线新型冠状病毒肺炎验案1例，提出了治疗过程中的重要治则，以期对临床有所裨益。     

Formation and Function of Liquid-Like Viral Factories in Negative-Sense Single-Stranded RNA Virus Infections

Liquid–liquid phase separation (LLPS) represents a major physiochemical principle to organize intracellular membrane-less structures. Studies with non-segmented negative-sense (NNS) RNA viruses have uncovered a key role of LLPS in the formation of viral inclusion bodies (IBs), sites of viral protein concentration in the cytoplasm of infected cells. These studies further reveal the structural and functional complexity of viral IB factories and provide a foundation for their future research. Herein, we review the literature leading to the discovery of LLPS-driven formation of IBs in NNS RNA virus-infected cells and the identification of viral scaffold components involved, and then outline important questions and challenges for IB assembly and disassembly. We discuss the functional implications of LLPS in the life cycle of NNS RNA viruses and host responses to infection. Finally, we speculate on the potential mechanisms underlying IB maturation, a phenomenon relevant to many human diseases.     

罗仁治疗儿童肾病综合征蛋白尿经验介绍＊

本文介绍了罗仁教授治疗儿童肾病综合征蛋白尿的学术思想及理法方药。肾病综合征蛋白尿属中医学的“水肿”“尿浊”“虚劳”“腰痛”范畴，发病主要与肺、脾、肾三脏功能失调有关。蛋白尿是肾病综合征的必要诊断条件，不仅可直接导致低蛋白血症，引发水肿，还会促进肾功能的恶化。罗仁教授认为尿蛋白源于血浆，是水谷精微，为至阴之精，应固藏于肾，并且有赖于肺之宣发、脾之升清、肝之疏泄的共同作用，创立了肾病1号方从肺、脾、肝、肾四方面减少尿蛋白，使患者更早进入缓解期，延缓疾病进展，调节免疫，防止复发，尤其对激素抵抗、激素依赖患者具有更重要的意义，并随证或随症加减，对于病情复杂的复合病或复合证患者可用单双日疗法调整阴阳，单日用肾病1号方减少蛋白尿，双日用小生六汤调和脏腑，还从心理、运动、饮食三方面指导患者积极面对疾病。     

Inversion Recovery Ultrashort TE MR Imaging of Myelin is Significantly Correlated with Disability in Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE:MR imaging has been widely used for the noninvasive evaluation of MS. Although clinical MR imaging sequences are highly effective in showing focal macroscopic tissue abnormalities in the brains of patients with MS, they are not specific to myelin and correlate poorly with disability. We investigated direct imaging of myelin using a 2D adiabatic inversion recovery ultrashort TE sequence to determine its value in assessing disability in MS.MATERIALS AND METHODS:The 2D inversion recovery ultrashort TE sequence was evaluated in 14 healthy volunteers and 31 patients with MS. MPRAGE and T2-FLAIR images were acquired for comparison. Advanced Normalization Tools were used to correlate inversion recovery ultrashort TE, MPRAGE, and T2-FLAIR images with disability assessed by the Expanded Disability Status Scale.RESULTS:Weak correlations were observed between normal-appearing white matter volume (R = –0.03, P = .88), lesion load (R = 0.22, P = .24), and age (R = 0.14, P = .44), and disability. The MPRAGE signal in normal-appearing white matter showed a weak correlation with age (R = –0.10, P = .49) and disability (R = –0.19, P = .31). The T2-FLAIR signal in normal-appearing white matter showed a weak correlation with age (R = 0.01, P = .93) and disability (R = 0.13, P = .49). The inversion recovery ultrashort TE signal was significantly negatively correlated with age (R = –0.38, P = .009) and disability (R = –0.44; P = .01).CONCLUSIONS:Direct imaging of myelin correlates with disability in patients with MS better than indirect imaging of long-T2 water in WM using conventional clinical sequences.

MS is the most common demyelinating disease of the brain.¹ Demyelination affects many aspects of neurologic function, including speech, balance, and cognitive awareness. Across time, this frequently leads to severe and irreversible clinical disability. MR imaging has been widely used for accurate diagnosis of MS, with current techniques focused on imaging the long-T2 water components in WM and GM.^2-4 MS lesions often appear hypointense with T1-weighted gradient recalled-echo sequences² and hyperintense with T2-weighted FSE and T2-weighted FLAIR sequences.³ Active lesions can be highlighted with gadolinium-enhanced imaging.⁴ The magnetization transfer ratio has been used as an indirect marker of myelin disorder in regions of normal-appearing WM (NAWM).⁵ There are also several other advanced imaging techniques for indirect myelin imaging via assessment of myelin water, such as multicomponent T2 or T2* analysis^6,7 and direct visualization of components with short transverse relaxation times.^8,9While conventional MR imaging sequences are highly effective in detecting focal macroscopic brain tissue abnormalities, they are not specific for pathologic substrates of MS lesions such as demyelination and remyelination, and they may not correlate well with patients'' neurologic deficits. Current MR imaging techniques correlate only modestly with disability assessed by the Expanded Disability Status Scale (EDSS).^10-15 The total lesion load showed statistically significant-but-weak correlations with the EDSS score in several large-scale studies (R = 0.1–0.3).^10-12 Composite scores including relaxation times of different tissues and/or volumetric measures generally correlate more strongly with the EDSS score, with a maximum observed correlation of R = 0.34 (P < .001).¹³ Lesions seen with gadolinium-enhanced imaging are only moderately correlated with disability in the first 6 months and are not predictive of changes in the EDSS score in the subsequent 1 or 2 years.¹⁴ A large-scale multicenter study reported very limited correlation between the EDSS score and normalized brain volume (R = –0.18), cross-sectional area (R = –0.26), magnetization transfer ratio of whole-brain tissue (R = –0.16), and GM (R = –0.17).¹⁵The poor performance of conventional MR imaging sequences in assessing disability highlights the need for novel MR imaging techniques that can directly image myelin lipid and enable direct assessment of both myelin damage and repair. However, myelin has an extremely short transverse relaxation time and is not directly detectable with conventional MR images, which typically have TEs of several milliseconds or longer. Ultrashort TE (UTE) sequences can directly detect signal from myelin with ultrashort T2 (ie, excluding water with longer T2s).^16-21 In this study, we describe imaging of WM using a 2D adiabatic inversion recovery prepared UTE (IR-UTE) sequence in healthy volunteers and patients with MS and evaluate its performance in assessing disability in patients with MS compared with 2 conventional clinical sequences.     

Correlation between the sulfamethoxazole-trimethoprim resistance of Shigella flexneri and the sul genes

The aim of this study was to discuss the correlation between the sulfamethoxazole-trimethoprim resistance of Shigella flexneri (S. flexneri) and the antibiotic resistance genes sul1, sul2, and sul3 and SXT element.From May 2013 to October 2018, 102 isolates of S. flexneri were collected from the clinical samples in Jinan. The Kirby–Bauer (K-B) test was employed to determine the antibiotic susceptibility of the S. flexneri isolates. The antibiotic resistance rate was analyzed with the WHONET5.4 software. The isolates were subject to the PCR amplification of the sul genes (sul1, sul2, and sul3) and the SXT element. On the basis of the sequencing results, the correlation between the sulfamethoxazole-trimethoprim resistance of the S. flexneri isolates and the sul genes was analyzed.The antibiotic resistance rates of the 102 S. flexneri isolates to ampicillin, streptomycin, chloramphenicol, tetracycline, and sulfamethoxazole-trimethoprim were 90.2%, 90.2%, 88.2%, 88.2%, and 62.7%, respectively. The antibiotic resistance rates of these isolates to cefotaxime, ceftazidime, and ciprofloxacin varied between 20% and 35%. However, these isolates were 100% susceptible to cefoxitin. Positive fragments were amplified from 59.8% (61/102) of the 102 S. flexneri isolates, the sizes of the sul1 and sul2 genes being 338 bp and 286 bp, respectively. The sequence alignment revealed the presence of the sul1 and sul2 genes encoding for dihydrofolate synthase. The carrying rate of the sul1 gene was 13.7% (14/102), and that of the sul2 gene was 48.0% (49/102). No target gene fragments were amplified from the 3 isolates resistant to sulfamethoxazole-trimethoprim. The sul3 gene and SXT element were not amplified from any of the isolates. The testing and statistical analysis showed that the resistance of the S. flexneri isolates to sulfamethoxazole-trimethoprim correlated to the sul1 and sul2 genes.The acquired antibiotic resistance genes sul1 and sul2 were closely associated with the resistance of the 102 S. flexneri isolates to sulfamethoxazole-trimethoprim.     

超声心动图诊断左心室射血分数减低的左冠状动脉异常起源于肺动脉的效果分析

目的探讨左心室射血分数（LVEF）减低的左冠状动脉异常起源于肺动脉（ALCAPA）的超声心动图特点及手术效果。 方法选取2008年10月至2018年9月首都医科大学附属北京儿童医院ALCAPA患者28例，根据LVEF分为LVEF减低组（LVEF＜50%）19例和LVEF正常组（LVEF≥50%）9例，比较2组患者超声心动图表现，应用两独立样本t检验比较2组患者间超声参数的差异。手术患者（17例）分别于术后1 d、1个月、6个月、1年进行超声心动图随访，应用配对t检验与术前超声参数进行对比。 结果LVEF减低组患者LVEF为30%~48%，平均年龄5.4个月；LVEF正常组LVEF为60%~73%，平均年龄2.5岁。LVEF减低组与LVEF正常组相比，左心室舒张末期内径大［（131.95±24.24）mm/m² vs（85.67±20.26）mm/m²］，右冠状动脉内径小［（3.06±0.51）mm vs（4.01±0.62）mm］，差异具有统计学意义（t=-4.465、4.075，P均＜0.001），易形成室壁瘤。LVEF减低组中10例行手术治疗，7例超声心动图随访至术后1年；与术前相比，术后1 d开始左心室舒张末期内径逐渐回缩［（109.98±16.06）mm/m²、（99.49±12.02）mm/m²、（89.48±10.90）mm/m²、（80.03±8.09）mm/m² vs（123.26±12.40）mm/m²］，差异具有统计学意义（t=-2.668、-7.519、-5.413、-6.526，P=0.004、0.001、0.012、0.007），LVEF术后1个月开始恢复，术后6个月达正常水平［（45.50±9.57）%、（66.25±10.34）%、（67.25±4.50）% vs（38.83±7.05）%］，差异具有统计学意义（t=3.162、3.683、5.869，P=0.025、0.014、0.002）。 结论LVEF减低的ALCAPA患儿年龄小、心脏病变重，超声心动图可以准确作出诊断，但需要与心内膜弹力纤维增生症、扩张型心肌病相鉴别。ALCAPA手术治疗远期效果较好，超声心动图在术后随访中有重要作用。     

Deletion of Krüppel-like factor-4 promotes axonal regeneration in mammals

Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01).

Chinese Library Classification No.R456; R741; Q344+.14     

从肝论治肠腑病的理论探讨＊

中医肠腑病多为肠道传化失常而出现的一系列肠腑病证。随着社会发展，人们情感心理障碍问题日益凸显，使得情志因素成为现代肠腑病发生与复发的重要影响因素，情志失常则会引起肝气或郁结或亢逆，致肝木横克脾土水湿不运而发肠腑病。因此，本文结合现代肠腑病的发病特点，通过论述肝与大肠之间的生理病理联系，分析从肝论治肠腑病的理论与临床依据，从调情志、舒肝气的角度论治肠腑病，为扩展临床治疗肠腑病的处方用药与针灸选穴思路提供借鉴与参考。