2024年 · 第137卷第20期

Parkinson’s disease (PD) is a neurodegenerative disease characterized by various motor and non-motor symptoms. The complexity of its symptoms suggests that PD is a heterogeneous neurological disorder. Its pathological changes are not limited to the substantia nigra-striatal system, but gradually extending to other regions including the cerebellum. The cerebellum is connected to a wide range of central nervous system regions that form essential neural circuits affected by PD. In addition, altered dopaminergic activity and α-synuclein pathology are found in the cerebellum, further suggesting its role in the PD progression. Furthermore, an increasing evidence obtained from imaging studies has demonstrated that cerebellar structure, functional connectivity, and neural metabolism are altered in PD when compared to healthy controls, as well as among different PD subtypes. This review provides a comprehensive summary of the cerebellar pathophysiology and results from neuroimaging studies related to both motor and non-motor symptoms of PD, highlighting the potential significance of cerebellar assessment in PD diagnosis, differential diagnosis, and disease monitoring.

Tuberculosis (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

酒精相关性肝病（ALD）是由长期大量饮酒引起的。在美国和一些欧洲国家，该疾病仍然是肝病发病率负担的重要因素。在过去二十年中，在亚洲也观察到ALD发病率增加的趋势。^[1]

Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.

We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9.

Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment.

Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented.

In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs).

In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years.

These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression.

Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC.

NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models.

Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

Very low birth weight (VLBW) infants are the key populations in neonatology, wherein morbidity and mortality remain major challenges. The study aimed to analyze the clinical characteristics of VLBW infants.

A retrospective cohort study was conducted in West China Second Hospital between January 2016 and December 2021. Neonates with a birth weight of <1500 g were included. Mortality, care practices, and major morbidities were analyzed, and compared with those of previous 7 years (2009-2015).

Of the total 1750 VLBW, 1386 were infants born with birth weight between 1000-1499 g and 364 infants were born with weight below 1000 g; 42.9% (751/1750) required delivery room resuscitation; 53.9% (943/1750) received non-invasive ventilation only; 38.2% (669/1750) received invasive ventilation; 1517 VLBW infants received complete treatment. Among them, 60.1% (912/1517) of neonates had neonatal respiratory distress syndrome (NRDS), 28.7% (436/1517) had bronchopulmonary dysplasia (BPD), 22.0% (334/1517) had apnea, 11.1% (169/1517) had culture-confirmed sepsis, 8.4% (128/1517) had pulmonary hemorrhage, 7.6% (116/1517) had severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL), 5.7% (87/1517) had necrotizing enterocolitis (NEC), and 2.0% (31/1517) had severe retinopathy of prematurity. The total and in-hospital mortality rates were 9.7% (169/1750) and 3.0% (45/1517), respectively. The top three diagnoses of death among those who had received complete treatment were sepsis, NRDS, and NEC. In 2009-2015, 1146 VLBW were enrolled and 895 infants received complete treatment. The proportions of apnea, IVH, and IVH stage ≥3/PVL, were higher in 2009-2015 compared with those in 2016-2021, while the proportions of NRDS and BPD were characterized by significant increases in 2016-2021. The total and in-hospital mortality rates were 16.7% (191/1146) and 5.6% (50/895) respectively in 2009-2015.

Among VLBW infants born in 2016-2021, the total and in-hospital mortality rates were lower than those of neonates born in 2009-2015. Incidences of NRDS and BPD increased in 2016-2021, which affected the survival rates and long-term prognosis of VLBW.

Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.

This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes (n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group (n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls (n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed.

The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.

The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.

Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.

ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure (P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively).

Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.

Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

慢性自发性荨麻疹(CSU)被定义为由于已知或未知原因而自发出现风团、血管性水肿或两者超过六周。与在欧洲（0.5%）和北美（0.1%）进行的研究相比，亚洲研究中CSU的患病率（1.4%）更高。指南建议标准剂量的第二代H1抗组胺药（sgAHs）作为CSU的一线治疗。^[1]然而，对CSU患者的研究表明，某些个体对常规剂量的H1抗组胺药（AHs）的反应可能有限。^[2]

喉功能的丧失深刻地影响了喉结构扭曲或全喉切除术的特定患者的生活质量，尤其是在社会背景下。因此，同种异体移植已成为恢复喉功能的潜在解决方案。该领域的一个重要里程碑是Strome成功进行的全喉移植等人^[1]1998年，在令人印象深刻的13年术后期间证明了移植物的生存能力。在这一进展的基础上，法威尔等人^[2]和Grajek等人^[3]分别于2012年和2015年进行了第二次和第三次手术。

致编辑：双重抗血小板治疗(DAPT)，包括阿司匹林加P2Y₁₂受体抑制剂是减少患有冠状动脉疾病的个体的心脏和全身缺血事件的标准方法。^[1]虽然DAPT减少了缺血发作，但也增加了出血的风险。在急性冠状动脉综合征（ACS）患者中，住院期间的出血事件不仅大大增加了住院死亡的风险，还增加了长期死亡率和主要不良心血管事件的风险。^[2]因此，DAPT的管理必须同时考虑出血和缺血风险。

致编辑：吞咽相关咳嗽是口咽吞咽困难的常见表现，并证实了误吸和窒息的风险。^[1,2]窒息相关死亡是老年人意外死亡的常见原因。由于急救困难，80%的窒息者在急救小组到达之前死亡，这强调了监测和预防吞咽相关咳嗽的重要性。^[3]此外，吞咽障碍与各种衰老相关疾病交织在一起，如虚弱、肌肉减少症和痴呆，是衰老相关健康下降的交叉表现。^[2]目前，吞咽相关咳嗽主要被认为是吞咽困难的筛查标准之一和吸入性肺炎的危险指标，而临床实践中的实际筛查率极低。^[1,2]吸入性肺炎和吞咽困难的临床指南（涉及吞咽相关咳嗽）建议加强口腔护理，测试吞咽困难，并尽早启动吞咽康复。但是这些行动高度依赖于正式的护理人员和专家。考虑到缺乏正式护理人员的情况，找到一个容易注意到的风险因素会更务实。综合老年评估（CGA）是老年人多学科医疗保健的共识解决方案。然而，在缺乏正式护理人员的情况下启动CGA仍未解决。从健康监测员的角度来看，吞咽相关咳嗽的优势是容易注意到的。研究吞咽相关咳嗽对老年人健康下降的临床意义并确定其是否是一个值得使用的指标是有价值的。此外，探讨吞咽相关咳嗽的相关因素也是至关重要的，这可以指导吞咽相关咳嗽的预防和管理，最大限度地减少高危人群对重症监护的需求。因此，本研究调查了吞咽相关咳嗽的患病率和相关因素，并评估了其与老年人健康下降的关系。

致编辑：中风是世界范围内死亡和残疾的首要原因。^[1]中风事件可导致严重的运动后遗症，包括运动协调障碍、轻偏瘫和偏瘫。虽然康复训练是脑卒中后治疗的必要组成部分，但单纯康复训练可能无法显著改善慢性脑卒中患者的运动功能。近期，大量临床前研究和动物实验初步验证了神经电刺激技术用于脑卒中后慢性运动康复的安全性和有效性，等待大规模临床应用。运动皮层刺激（MCS）、迷走神经刺激（VNS）、深部脑刺激（DBS）和脊髓刺激（SCS）是针对慢性中风患者的侵入性神经电刺激技术【补充图1，http：//links.lww.com/CM9/C135】。我们综述了这些技术的机制、疗效、靶点和回路的研究进展。

致编辑：涎腺腺样囊性癌（SACC）的特征是肿瘤进展过程中高频率的神经周围侵犯（PNI）行为。然而，SACC细胞和周围非恶性细胞之间的细胞间通讯对PNI的影响仍不清楚。雪旺细胞作为周围神经系统的主要组成细胞，已有报道与PNI过程密切相关。癌细胞来源的外来体通常作为癌细胞和局部微环境之间的重要信号介质。因此，本研究旨在阐明癌症PNI期间癌细胞和雪旺细胞之间通过外来体的相互作用，并确定PNI的潜在治疗靶点。

致编辑：基因组不稳定性是癌症的标志，遗传变化和DNA损伤增加。肿瘤基因组中累积的突变可以产生新抗原，从而触发抗肿瘤免疫反应。此外，作为基因组不稳定性的结果，核DNA的泄漏可以直接提醒免疫系统恶性细胞的存在。环磷酸鸟苷-磷酸腺苷合酶（cGAS）是触发先天免疫应答的主要DNA传感器。^[1]双链DNA片段在细胞质中的积累可以直接与cGAS结合，作为干扰素基因（STING）的激活剂或刺激剂发挥作用。STING作为信号平台募集坦克结合激酶1（TBK1）和干扰素调节因子3（IRF3）进行磷酸化。磷酸化的IRF3易位到细胞核，在细胞核中它作为转录因子发挥作用以促进I型干扰素（IFN）和免疫刺激细胞因子的表达。这导致各种免疫细胞的迁移和激活。

致编辑：中国现在拥有世界上最多的糖尿病（DM）患者，使糖尿病视网膜病变（DR）成为中国劳动年龄人口中致盲的主要原因。^[1]糖尿病患者的眼底筛查很重要，以便眼科医生及时治疗视网膜病变并延缓视力丧失的发展。然而，我们在眼底筛查的临床实践中发现了一些问题。微动脉瘤（MA）和小点视网膜内出血（HEM），尽管早期治疗糖尿病视网膜病变研究组（ETDRS）对此进行了精确描述，^[2]是散瞳检眼镜上的红色和圆形斑点，由于患者屈光度介质不完全透明，除非进行眼底荧光素血管造影（FFA），否则不容易区分。问题总是会出现：在对DR的严重程度进行分级时，我们必须区分这两种病变吗？

致编辑：雄激素性脱发（AGA）是一种常见的慢性脱发疾病，通常始于青春期，伴有毛囊小型化。^[1]临床表现包括毛发直径和体积减少，可能导致秃顶。AGA以进行性脱发为特征，可影响两性。毛囊周围的炎症、压力、情绪紧张以及不良的生活方式和饮食习惯会进一步加重AGA的症状。^[2]目前，米诺地尔和非那雄胺（FNS）是FDA唯一专门批准用于AGA的药物疗法。^[3]但这两种药物副作用明显，患者依从性差，迫切需要寻找一种安全有效的AGA临床治疗方法。

致编辑：肠易激综合征（IBS）是最常见的成人功能性胃肠疾病（FGIDs）之一，估计全球患病率为1.5-11.2%。焦虑和抑郁症状和障碍的患病率强调了对IBS患者的心理影响，强调了对针对特定人群的综合诊断工具的需求。^[1]IBS的主要诊断参考是罗马标准，它现在是全世界IBS诊断的标准实践。最近的迭代是罗马IV[补充表1，http://links.lww.com/CM9/C102]。尽管罗马标准被广泛接受，但验证研究表明，罗马标准在诊断IBS方面表现不佳，并且在临床实践中，罗马标准并不常用。在IBS的诊断中必须考虑IBS和FGIDs症状之间的重叠，并且在基于症状的诊断工具的开发中应考虑到这一点。

致编辑：腹部外科手术与术后肺部并发症（PPC）的高发生率有关，可通过麻醉期间给予肺保护性机械通气来缓解。^[1,2]迄今为止，还没有相关研究关注专门针对腹腔镜结肠直肠癌（CRC）的保护性肺通气策略。在此，我们提出了一种创新的易于使用的肺保护策略，具有较低的潮气量（VT）、气腹压（PnP）和深部神经肌肉阻滞（NMB），并评估其在减少PPC方面是否优于传统的肺保护策略。

致编辑：骨是不断经历动态生物重塑的复杂组织。然而，当骨缺损超过自修复阈值时，它们被视为临界大小的骨缺损（CBDs），^[1]并且需要人工干预来辅助修复过程。植入三维（3D）打印假体是重建肢体CBD的一种有前途的候选物。这些打印假体的几何形状、孔径和孔隙率可以通过基于患者特定模型数据的逐层制造过程来定制。^[2]已经进行了许多研究来引入用于修复CBD的3D打印假体，证实了它们的生物相容性、稳定性和成骨作用。然而，至今仍缺乏系统的系列病例临床报道。