Volume 136 · Issue 11 · 2023

In the last decade, it has become increasingly recognized that a balanced gut microbiota plays an important role in maintaining the health of the host. Numerous clinical and preclinical studies have shown that changes in gut microbiota composition are associated with a variety of neurological diseases, e.g., Parkinson’s disease, Alzheimer’s disease, and myasthenia gravis. However, the underlying molecular mechanisms are complex and remain unclear. Behavioral phenotypes can be transmitted from humans to animals through gut microbiota transplantation, indicating that the gut microbiota may be an important regulator of neurological diseases. However, further research is required to determine whether animal-based findings can be extended to humans and to elucidate the relevant potential mechanisms by which the gut microbiota regulates neurological diseases. Such investigations may aid in the development of new microbiota-based strategies for diagnosis and treatment and improve the clinical management of neurological disorders. In this review, we describe the dysbiosis of gut microbiota and the corresponding mechanisms in common neurological diseases, and discuss the potential roles that the intestinal microbiome may play in the diagnosis and treatment of neurological disorders.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by progressive lung fibrogenesis and histological features of usual interstitial pneumonia. IPF has a poor prognosis and presents a spectrum of disease courses ranging from slow evolving disease to rapid deterioration; thus, a differential diagnosis remains challenging. Several biomarkers have been identified to achieve a differential diagnosis; however, comprehensive reviews are lacking. This review summarizes over 100 biomarkers which can be divided into six categories according to their functions: differentially expressed biomarkers in the IPF compared to healthy controls; biomarkers distinguishing IPF from other types of interstitial lung disease; biomarkers differentiating acute exacerbation of IPF from stable disease; biomarkers predicting disease progression; biomarkers related to disease severity; and biomarkers related to treatment. Specimen used for the diagnosis of IPF included serum, bronchoalveolar lavage fluid, lung tissue, and sputum. IPF-specific biomarkers are of great clinical value for the differential diagnosis of IPF. Currently, the physiological measurements used to evaluate the occurrence of acute exacerbation, disease progression, and disease severity have limitations. Combining physiological measurements with biomarkers may increase the accuracy and sensitivity of diagnosis and disease evaluation of IPF. Most biomarkers described in this review are not routinely used in clinical practice. Future large-scale multicenter studies are required to design and validate suitable biomarker panels that have diagnostic utility for IPF.

Triggering receptor expressed on myeloid cells 2 (TREM2) is a membrane receptor on myeloid cells and plays an important role in the body’s immune defense. Recently, TREM2 has received extensive attention from researchers, and its activity has been found in Alzheimer’s disease, neuroinflammation, and traumatic brain injury. The appearance of TREM2 is usually accompanied by changes in apolipoprotein E (ApoE), and there has been a lot of research into their structure, as well as the interaction mode and signal pathways involved in them. As two molecules with broad and important roles in the human body, understanding their correlation may provide therapeutic targets for certain diseases. In this article, we reviewed several diseases in which TREM2 and ApoE are synergistically involved in the development. We further discussed the positive or negative effects of the TREM2-ApoE pathway on nervous system immunity and inflammation.

Accumulating studies have demonstrated that non-coding RNAs (ncRNAs), functioning as important regulators of transcription and translation, are involved in the establishment and maintenance of pregnancy, especially the maternal immune adaptation process. The endometrial stromal cells (ESCs), trophoblast cells, and decidua immune cells that reside at the maternal-fetal interface are thought to play significant roles in normal pregnancy and pregnancy-associated diseases. Here, we reviewed the up-to-date evidence on how microRNA, long non-coding RNA, and circular RNA regulate ESCs, trophoblast cells, and immune cells and discussed the potential applications of these ncRNAs as diagnostic and therapeutic markers in pregnancy complications.

It remains unclear whether circulating malondialdehyde (MDA) levels change in people with diabetic retinopathy (DR). This systematic review compared circulating MDA levels in diabetic people with and without DR.

PubMed, Medline (Ovid), Embase (Ovid), and Web of Science were searched for case-control studies conducted before May 2022 in English that compared circulating MDA levels in people with and without DR. The following MeSH search terms were used: ( "malondialdehyde" or "thiobarbituric acid reactive substances [TBARS]" or "lipid peroxidation" or "oxidative stress" ) and "diabetic retinopathy." Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Random-effects pairwise meta-analysis pooled the effect size with standardized mean difference (SMD) and 95% confidence intervals (CIs).

This meta-analysis included 29 case-control studies with 1680 people with DR and 1799 people with diabetes but not DR. Compared to people without DR, the circulating MDA levels were higher in those with DR (SMD, 0.897; 95% CI, 0.631 to 1.162; P < 0.001). The study did not identify credible subgroup effects or publication bias and the sensitivity analysis confirmed the robustness of the study.

Circulating MDA levels are higher in people with DR compared to those without. Future comparative studies that use more specific methods are required to draw firm conclusions.

PROSPERO; https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022352640.

Current guidelines recommend hepatocellular carcinoma (HCC) screening in high-risk populations. However, the ideal HCC screening interval and screening modality have not been determined. This study aimed to compare the screening efficacy among different modalities with various intervals.

PubMed and other nine databases were searched through June 30, 2021. Binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs). Survival rates were also pooled using RR with 95% CIs because most eligible studies only provided the number of survival patients instead of hazard ratio.

In all, 13 studies were included. Two random controlled trials (RCTs) and six cohort studies compared screening intervals for ultrasonography (US) screening and found no significant differences between shorter (3- or 4-month) and longer (6- or 12-month) screening intervals in terms of early HCC proportion, HCC significant mortality, 1-year survival rate; screening at 6-month interval significantly increased the proportion of early HCC (RR = 1.17, 95% confidence interval [CI]: 1.08-1.26) and prolonged the 5-year survival rate (RR = 1.39, 95% CI: 1.07-1.82) relative to the 12-month interval results. Three other RCTs and two cohort studies compared different screening modalities in cirrhosis or chronic hepatitis B, which indicated no statistical differences in the proportion of early HCC (RR = 0.89, 95% CI: 0.40-1.96) and HCC mortality (RR = 0.69, 95% CI: 0.23-2.09) between the biannual US and annual computed tomography (CT screening). Biannual US screening showed a lower proportion of early HCC than biannual magnetic resonance imaging (MRI) (RR = 0.60, 95% CI: 0.37-0.97) and biannual US combined with annual CT (RR = 1.31, 95% CI: 1.13-1.51) screening. The proportion of early HCC in the contrast-enhanced US group was slightly higher than that in the B-mode US (RR= 1.08, 95% CI: 1.00-1.23) group.

The evidence suggests that 6 months may be the best HCC screening interval for US screening. The effectiveness of CT and MRI is better than US during same screening intervals. However, MRI and CT are more expensive than US, and CT also can increase the risk of radiation exposure. The selection of CT or MRI instead of US should be carefully considered.

No. CRD42020148258 at PROSPERO website (https://www.crd.york.ac.uk/PROSPERO/).

Amygdala plays an important role in the neurobiological basis of panic disorder (PD), and the amygdala contains different subregions, which may play different roles in PD. The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the amygdala subregions in PD using resting-state functional magnetic resonance imaging and to explore the relationship between the abnormal spontaneous functional connectivity patterns of the regions of interest (ROIs) and the clinical symptoms of PD patients.

Fifty-three drug-naïve, non-comorbid PD patients and 70 healthy controls (HCs) were recruited. Seed-based resting-state functional connectivity (rsFC) analyses were conducted using the bilateral amygdalae and its subregions as the ROI seed. Two samples t test was performed for the seed-based Fisher's z-transformed correlation maps. The relationship between the abnormal spontaneous functional connectivity patterns of the ROIs and the clinical symptoms of PD patients was investigated by Pearson correlation analysis.

PD patients showed increased rsFC of the bilateral amygdalae and almost all the amygdala subregions with the precuneus/posterior cingulate gyrus compared with the HC group (left amygdala [lAMY]: t = 4.84, P <0.001; right amygdala [rAMY]: t= 4.55, P <0.001; left centromedial amygdala [lCMA]: t= 3.87, P <0.001; right centromedial amygdala [rCMA]: t= 3.82, P= 0.002; left laterobasal amygdala [lBLA]: t= 4.33, P <0.001; right laterobasal amygdala [rBLA]: t= 4.97, P <0.001; left superficial amygdala [lSFA]: t= 3.26, P = 0.006). The rsFC of the lBLA with the left angular gyrus/inferior parietal lobule remarkably increased in the PD group (t = 3.70, P = 0.003). And most of the altered rsFCs were located in the default mode network (DMN). A significant positive correlation was observed between the severity of anxiety and the rsFC between the lSFA and the left precuneus in PD patients (r = 0.285, P = 0.039).

Our research suggested that the increased rsFC of amygdala subregions with DMN plays an important role in the pathogenesis of PD. Future studies may further explore whether the rsFC of amygdala subregions, especially with the regions in DMN, can be used as a biological marker of PD.

Tri-ponderal mass index (TMI) has been reported to be a more accurate estimate of body fat than body mass index (BMI). This study aims to compare the effectiveness of TMI and BMI in identifying hypertension, dyslipidemia, impaired fasting glucose (IFG), abdominal obesity, and clustered cardio-metabolic risk factors (CMRFs) in 3- to 17-year-old children.

A total of 1587 children aged 3 to 17 years were included. Logistic regression was used to evaluate correlations between BMI and TMI. Area under the curves (AUCs) were used to compare discriminative capability among indicators. BMI was converted to BMI-z scores, and accuracy was compared by false-positive rate, false-negative rate, and total misclassification rate.

Among children aged 3 to 17 years, the mean TMI was 13.57 ± 2.50 kg/m³ for boys and 13.3 ± 2.33 kg/m³ for girls. Odds ratios (ORs) of TMI for hypertension, dyslipidemia, abdominal obesity, and clustered CMRFs ranged from 1.13 to 3.15, higher than BMI, whose ORs ranged from 1.08 to 2.98. AUCs showed similar ability of TMI (AUC: 0.83) and BMI (AUC: 0.85) in identifying clustered CMRFs. For abdominal obesity and hypertension, the AUC of TMI was 0.92 and 0.64, respectively, which was significantly better than that of BMI, 0.85 and 0.61. AUCs of TMI for dyslipidemia and IFG were 0.58 and 0.49. When 85th and 95th of TMI were set as thresholds, total misclassification rates of TMI for clustered CMRFs ranged from 6.5% to 16.4%, which was not significantly different from that of BMI-z scores standardized according to World Health Organization criteria.

TMI was found to have equal or even better effectiveness in comparison with BMI in identifying hypertension, abdominal obesity, and clustered CMRFs TMI was more stable than BMI in 3- to 17-year-old children, while it failed to identify dyslipidemia and IFG. It is worth considering the use of TMI for screening CMRFs in children and adolescents.

Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.

Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements.

Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.

PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.

低密度脂蛋白胆固醇（LDL-C）是动脉粥样硬化性心血管疾病（ASCVD）的独立危险因素。即使在使用他汀类药物或他汀类药物-依折麦布进行降脂治疗（LLT）后，仍有很大比例的极高风险患者仍未达到LDL-C目标（<1.4 mmol/L且降低≥50%）。^[1,2]前蛋白转化酶枯草杆菌蛋白酶/kexin 9型抑制剂（PCSK9i）推荐用于他汀类药物治疗不足以降低LDL-C的高或极高心血管风险患者或他汀类药物不耐受患者。PCSK9i在中国的使用数据有限。Evolocumab是一种PCSK9i，于2019年在中国获批成为首个同类PCSK9i。然而，在中国，evolocumab用于治疗高危患者、探索其疗效和耐受性的真实世界证据仍然很少。本研究旨在报告极高危患者服用evolocumab的结果（n=63），但在单中心实践的真实环境中，他汀类药物未能充分降低LDL-C。

病毒性肺炎最近被定义为侵袭性肺曲霉病（IPA）的危险因素。沃特斯等人^[1]报道称，因猪源性甲型H1N1流感病毒感染而入住重症监护室（ICU）的危重患者中有23%发生了侵袭性曲霉病。432例因流感入院的患者中有83例（19%）被诊断为IPA；对于免疫功能低下的流感患者，IPA的发病率高达32%（117例患者中的38例），而在非免疫功能低下的流感组中，发病率为14%（315例患者中的45例）。^[2]在使用IPA的流感队列中，90天死亡率为51%，在不使用IPA的流感队列中为28%。^[2]据报道，在患有冠状病毒疾病的危重患者中，IPA的患病率在4%至9%之间。^[3]马吉拉等人^[4]发现在白血病患者和接受造血干细胞移植的患者中，由副流感病毒和呼吸道合胞病毒引起的呼吸道病毒感染经常先于IPA。考虑到IPA并发病毒性肺炎的高发病率和高死亡率，应确定其危险因素。因此，我们进行了一项研究来探索病毒性肺炎并发IPA的危险因素。

冠心病（CHD）危险因素的增加可以解释年轻CHD患者负担逐渐增加的原因。可改变的危险因素与急性心肌梗死（AMI）之间的关联已得到很好的确立，控制心血管危险因素可以降低后续事件的风险。^[1]与老年患者相比，年轻CHD患者的短期预后可能是可接受的；然而，年轻CHD患者的长期预后比年龄匹配的人群差，并且这些患者的复发事件和死亡率很高。^[2]已经观察到年轻和老年冠心病患者之间心血管危险因素的患病率存在显著差异。^[2,3]年轻CHD患者对心血管危险因素的控制不足，^[4]对于中国年轻患者是否达到治疗目标知之甚少。因此，本研究旨在评估心血管危险因素和AMI的控制情况，以确定哪些危险因素与年轻CHD患者的不良结局相关。

卢格敦葡萄球菌(卢格敦链球菌）是凝固酶阴性葡萄球菌包括正常皮肤微生物群，主要定居在下腹部和四肢。^[1]卢格敦链球菌自从Zipperer发现lugdunin以来，近年来引起了极大的关注等人^[2]2016年。Lugdunin是一种由非核糖体肽合成酶(NRPS)合成的次级代谢物，可抑制多种革兰氏阳性菌的生长，包括耐甲氧西林的细菌金黄色葡萄球菌(MRSA)、^[2]表明其作为抗生素的潜力。迄今为止，28个完整基因组序列和11个部分组装基因组序列卢格敦链球菌已经发表并上传到GenBank数据库（https：//www.ncbi.nlm.nih.gov/genome/browse/#！/prokaryotes/2548/，2022年1月18日）。然而，关于基因组序列的数据有限卢格敦链球菌地理起源对中国遗传变异的影响卢格敦链球菌保持未知。

致编辑：化疗引起的恶心和呕吐（CINV）是接受化疗的患者报告的最常见和最害怕的副作用。尽管取得了重大进展，但CINV的发病率仍然很高。^[1]预防是控制CINV的关键。循证止吐指南建议，预防CINV的策略应同时考虑化疗药物的呕吐风险和患者个体危险因素。^[2]迄今为止，已经确定了几个预测CINV高风险的个人因素，包括CINV的预期、女性、年轻、晨吐史和焦虑。^[3]已经努力开发不同的CINV风险预测模型，纳入所有上述因素，以指导个体化止吐预防。在这些模型中，最常被推荐的模型是2017年发表的大规模调查在肿瘤学年鉴基于非亚洲人口。^[4]然而，该模型对中国患者的适用性尚未得到研究。因此，我们进行了一项前瞻性研究，以验证现有的CINV预测模型，并对其进行优化，以识别高危中国患者。

致编辑：冠心病（CHD）并发冠状病毒疾病2019（新冠肺炎）的患者发生冠状动脉事件的风险增加。许多研究报告了心血管疾病和新冠肺炎之间的联系。众所周知，如果新冠肺炎患者患有心血管疾病，他们的预后更差，死亡风险更高。^[1]根据世界卫生组织的一份报告，估计新冠肺炎死亡率总体约为3.4%；然而，在患有心血管疾病的患者中，这一数字增加到10.5%，高于患有潜在糖尿病（7.3%）或慢性呼吸道疾病（6.3%）的患者的死亡率。^[2]

致编辑：全膝关节置换术（TKA）是终末期膝关节骨关节炎患者安全有效的治疗方法，采用传统的内侧髌旁（MP）入路进行TKA，可以获得良好的膝关节可视化，有助于实现正确的截骨、适当的韧带平衡和良好的假体位置，这些都是良好的长期结果的重要因素。^[1]为了改善功能恢复和康复，一些研究采用了相对较小的切口手术来改善手术。其中，两种最常用的手术被命名为微型内侧髌旁（MMP）和股四头肌保留（QS）入路。^[2]但其他研究表明，微创方法可能会损害正确截骨、适当韧带平衡和良好假体位置的优势，以实现潜在的快速康复，可能会牺牲假体的长期临床结果和存活率。^[3]目前，大多数研究比较了评估随访不超过5年的不同方法。因此，获得长期临床比较的数据至关重要。在前期研究纵向队列结果的基础上，进行了10余年的随访研究。

致编辑：听神经瘤是桥小脑角（CPA）区最常见的肿瘤。听神经瘤的手术入路包括迷路、中颅窝、乙状窦后入路和迷路后入路。然而，无论采用何种方法暴露内听道（IAC）中的肿瘤，都必须擦伤IAC周围的骨，这不可避免地暴露周围的气室受到损伤，并增加了术后脑脊液（CSF）泄漏的风险。脑脊液漏是从CPA区域切除肿瘤后最常见的术后并发症，据报道，听神经瘤手术后的发生率为2%至10%。^[1,2,3]脑脊液漏的临床治疗具有挑战性；并且有时需要持续的腰椎穿刺引流或再次手术，以避免脑膜炎。因此，当进行手术切除CPA区域的肿瘤时，预防术后脑脊液漏是需要考虑的关键问题。

致编辑：融合基因E2A：：HLF(TCF3：：HLF）由t（17；19）（q21-22；p13）形成，其存在于<1%的B细胞急性淋巴细胞白血病（B-ALL），主要发生于年龄较大的儿童和青少年。^[1]此类患者常伴有耐药性和早期复发，预后极差，即使强化化疗和造血干细胞移植（HSCT）也不能提高其生存率。^[2]少数研究表明，嵌合抗原受体T（CAR-T）细胞疗法或BCL-2抑制剂可能使此类患者受益，但有效性需要进一步验证，因为CAR-T细胞疗法的优越性仅限于个别病例报告，而BCL-2抑制剂的疗效仅在细胞系的体外试验中得到证实。^[1,3]在此，我们回顾性分析了6例患者的临床资料E2A：：HLFB-ALL阳性，以进一步验证CAR-T细胞疗法和BCL-2抑制剂的有效性，这可以被认为是这些低风险患者的挽救治疗。

致编辑：中毒性表皮坏死（TEN）是一种严重的皮肤粘膜反应，以皮疹、水泡和表皮全身松弛为特征。^[1]阻断程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡1配体1（PD-L1）途径可以激活和增殖自身反应性CD8+T细胞，这是TEN中的关键步骤。可以通过激活PD-1/PD-L1途径来抑制抗CD19嵌合抗原受体-T(CAR-T)细胞的功效。^[2]因此，PD-1阻断和CAR-T细胞疗法的组合将增加CAR-T细胞的功能。^[3]本病例报告描述了一例难治性弥漫性大B细胞淋巴瘤（DLBCL）患者，该患者在CAR-T细胞治疗和PD-1阻断后出现了严重的TEN。