Early axonal loss predicts long-term disability in chronic inflammatory demyelinating polyneuropathy

ObjectiveTo investigate early pre-treatment nerve fiber loss as a predictor of long-term clinical outcome in chronic inflammatory demyelinating polyneuropathy (CIDP).MethodsIn 14 patients, motor and sensory conduction studies of the median, fibular, and sural nerves were performed at pre-treatment and follow-up 11–28 years later. Z-scores of amplitudes were combined as biomarkers of axonal loss and Z-scores of conduction properties as demyelination scores. The axonal loss was further examined by electromyography (EMG) and motor unit number estimation. Axonal and demyelination scores were compared to clinical outcomes in the Inflammatory Rasch-built Overall Disability Scale, the Neuropathy Impairment Score, and dynamometry.ResultsAt follow-up 12 patients walked independently, one needed support and one could not walk. The initial and follow-up axonal and demyelination scores were markedly abnormal. The initial axonal loss but not demyelination was strongly associated with both the follow-up axonal loss and the clinical measures. Moreover, delay of treatment initiation negatively influenced the axonal scores and clinical outcomes.ConclusionIn this hypothesis generating limited study, we found that axonal loss at early CIDP was highly predictive for long-term nerve fiber loss and disability.SignificanceThe study indicates that prompt initiation of treatment to prevent nerve fiber loss is necessary for outcome in CIDP.     

Non-alcoholic fatty liver disease in patients with intestinal,pulmonary or skin diseases: Inflammatory cross-talk that needs a multidisciplinary approach

Non-alcoholic fatty liver disease (NAFLD) is currently considered the most common cause of liver disease. Its prevalence is increasing in parallel with the obesity and type 2 diabetes mellitus (DM2) epidemics in developed countries. Several recent studies have suggested that NAFLD may be the hepatic manifestation of a systemic inflammatory metabolic disease that also affects other organs, such as intestine, lungs, skin and vascular endothelium. It appears that local and systemic proinflammatory/anti-inflammatory cytokine imbalance, together with insulin resistance and changes in the intestinal microbiota, are pathogenic mechanisms shared by NAFLD and other comorbidities. NAFLD is more common in patients with extrahepatic diseases such as inflammatory bowel disease (IBD), obstructive syndrome apnea (OSA) and psoriasis than in the general population. Furthermore, there is evidence that this association has a negative impact on the severity of liver lesions. Specific risk characteristics for NAFLD have been identified in populations with IBD (i.e. age, obesity, DM2, previous bowel surgery, IBD evolution time, methotrexate treatment), OSA (i.e. obesity, DM2, OSA severity, increased transaminases) and psoriasis (i.e. age, metabolic factors, severe psoriasis, arthropathy, elevated transaminases, methotrexate treatment). These specific phenotypes might be used by gastroenterologists, pneumologists and dermatologists to create screening algorithms for NAFLD. Such algorithms should include non-invasive markers of fibrosis used in NAFLD to select subjects for referral to the hepatologist. Prospective, controlled studies in NAFLD patients with extrahepatic comorbidities are required to demonstrate a causal relationship and also that appropriate multidisciplinary management improves these patients’ prognosis and survival.     

Role of the Anterior Cingulate Cortex in Translational Pain Research

As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and stages.In pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well discussed.In this review,we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain,neuropathic pain,and cancer pain in the ACC,and discuss the cellular receptors and signaling molecules from animal studies.We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management.The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.     

Progress in elucidating the relationship between Helicobacter pylori infection and intestinal diseases

Helicobacter pylori (H. pylori) infection causes changes to the intestinal flora, such as small intestinal bacterial overgrowth, and increases gastric acid secretion-stimulating gastrointestinal hormones, mainly gastrin, due to a decrease in gastric acid caused by atrophic gastritis. In addition, the cellular components of H. pylori travel through the intestinal tract, so the bacterial infection affects the immune system. Therefore, the effects of H. pylori infection are observed not only in the stomach and the proximal duodenum but also in the small and large intestines. In particular, meta-analyses reported that H. pylori-infected individuals had an increased risk of colorectal adenoma and colorectal cancer. Moreover, a recent study reported that the risk of developing colorectal cancer was increased in subjects carrying H. pylori vacuolating cytotoxin A antibody. In addition, it has been reported that H. pylori infection exacerbates the symptoms of Fabry’s disease and familial Mediterranean fever attack and is involved in irritable bowel syndrome and small intestinal ulcers. On the other hand, some studies have reported that the frequency of ulcerative colitis, Crohn’s disease, and celiac disease is low in H. pylori-infected individuals. Thus, H. pylori infection is considered to have various effects on the small and large intestines. However, few studies have reported on these issues, and the details of their effects have not been well elucidated. Therefore, additional studies are needed.     

硫氧还蛋白相互作用蛋白在多囊卵巢综合征中作用的研究进展

多囊卵巢综合征（polycystic ovary syndrome，PCOS）是一种常见于育龄妇女的内分泌代谢性疾病，以月经不规则、高雄激素血症和卵巢多囊样改变为特征，常表现为肥胖、不孕和胰岛素抵抗。硫氧还蛋白相互作用蛋白（thioredoxin-interacting protein，TXNIP）是一种多功能调节剂，不仅参与胰岛素分泌和葡萄糖代谢的调节，还与氧化应激、炎症因子和情绪障碍密切相关。PCOS患者体内的TXNIP水平较健康人群明显增加，表明TXNIP可能参与PCOS及其并发症的发生、发展。近年体内外研究尝试应用中药提取物和西医药物抑制TXNIP的表达，TXNIP特异性抑制剂的发现使TXNIP有望成为抑制PCOS进程的有效靶点。综述TXNIP在PCOS中的作用进展，以期为PCOS发病机制的深入研究及临床诊疗提供新的思路和方向。     

Evaluation of minocycline combined with favipiravir therapy in coronavirus disease 2019 patients: A case-series study

The aim of this study was to investigate the efficacy and safety of minocycline (MIN) and favipiravir combination therapy in patients with coronavirus disease 2019 (COVID-19) admitted to our hospital in Fukui Prefecture, Japan, in March and April of 2020. In this retrospective study, a favipiravir monotherapy group (Control group, n = 9) was compared with a combined favipiravir plus MIN therapy group (MIN group, n = 12). No severe cases were present. The primary comparative endpoints evaluated were duration of fever, duration of hospitalization, duration from treatment initiation to severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)-negative results, and changes in cytokine and chemokine production. Median duration from start of treatment to negative PCR test was significantly shorter in the MIN group than in the Control group. Mean rates of cytokine and chemokine reduction were significantly greater for interleukin-6 and interleukin-8 in the MIN group. No difference in adverse event rates were seen between groups, and only minor adverse events were encountered. MIN has been reported to have not only broad antibacterial activity, but also antiviral and anti-inflammatory activity. The present results support the efficacy and safety of MIN plus favipiravir therapy for the treatment of COVID-19.     

慢性阻塞性肺疾病患者步态分析的初步研究

目的探讨慢性阻塞性肺疾病（COPD）患者与健康人之间步态分析的差异，评估气流受限程度和系统性炎症对慢阻肺患者步态的影响，从而及早预测慢阻肺患者的跌倒风险并制定跌倒预防策略。 方法选取2020年10月至2021年5月来苏州大学附属无锡九院呼吸科门诊就诊的稳定期COPD患者60例及健康体检者（对照组）36例，均行步态分析、坐-站起立测试、肺功能及外周血检查。首先比较COPD组与对照组之间步态分析等的差异；然后将COPD患者依据慢性阻塞性肺疾病全球倡议（GOLD）肺功能分级分为轻中度组，重度组和极重度组，分析气流受限程度对步态特征的影响；最后分析不同肺功能的COPD患者的炎症指标与步态分析之间的关系。 结果COPD组的步速、步行距离、步频、步长、摆动相时间、双足支撑时间、踝关节角速度、站立时长、步行周期、支撑相时间、髋关节屈、膝关节角速度、踝关节屈、踝关节伸及坐位时长与健康对照组之间有统计学差异（P＜0.05）；不同肺功能分级的COPD患者中，优势侧步频与第一秒用力呼气容积（FEV₁）有相关性（P＜0.05）；不同肺功能分级的COPD患者中，中性粒细胞淋巴细胞比值（NLR）与FEV₁呈正向弱相关，并且NLR与支撑相时间、站立时长及坐位时长均呈正向弱相关，与踝关节伸（跖屈角度）及踝关节角速度呈负向弱相关，血小板淋巴细胞比值（PLR）与中性粒细胞淋巴细胞比值（NLR）有相似结果（除支撑时间）。 结论COPD患者的活动耐力及步态稳定性明显低于健康对照者，并且随着其肺功能的进展，步态稳定性越差；炎症指标中性粒细胞淋巴细胞比值（NLR）及血小板淋巴细胞比值（PLR）与肺功能及步态分析之间也有一定的相关性。因此定量步态分析可以早期发现COPD患者异常的步态参数，及早识别患者的跌倒风险，从而进行早期干预。