Volume 136 · Issue 13 · 2023

Asthma is characterized by chronic airway inflammation and airway hyper-responsiveness. However, the differences in pathophysiology and phenotypic symptomology make a diagnosis of "asthma" too broad hindering individualized treatment. Four asthmatic inflammatory phenotypes have been identified based on inflammatory cell profiles in sputum: eosinophilic, neutrophilic, paucigranulocytic, and mixed-granulocytic. Paucigranulocytic asthma may be one of the most common phenotypes in stable asthmatic patients, yet it remains much less studied than the other inflammatory phenotypes. Understanding of paucigranulocytic asthma in terms of phenotypic discrimination, distribution, stability, surrogate biomarkers, underlying pathophysiology, clinical characteristics, and current therapies is fragmented, which impedes clinical management of patients. This review brings together existing knowledge and ongoing research about asthma phenotypes, with a focus on paucigranulocytic asthma, in order to present a comprehensive picture that may clarify specific inflammatory phenotypes and thus improve clinical diagnoses and disease management.

Lung cancer has the highest risk of brain metastasis (BM) among all solid carcinomas. The emergence of BM has a significant impact on the selection of oncologic treatment for patients. Immune checkpoint inhibitors (ICIs) are the most promising treatment option for patients without druggable mutations and have been shown to improve survival in patients with non-small cell lung cancer (NSCLC) BM in clinical trials with good safety. Moreover, ICI has shown certain effects in NSCLC BM, and the overall intracranial efficacy is comparable to extracranial efficacy. However, a proportion of patients showed discordant responses in primary and metastatic lesions, suggesting that multiple mechanisms may exist underlying ICI activity in BM. According to studies pertaining to tumor immune microenvironments, ICIs may be capable of provoking immunity in situ. Meanwhile, systematic immune cells activated by ICIs can migrate into the central nervous system and exert antitumor effects. This review summarizes the present evidence for ICI treatment efficacy in NSCLC BM and proposes the possible mechanisms of ICI treatment for NSCLC BMs based on existing evidence.

Previous studies have revealed that the number of cancer survivors developing a second primary malignancy is increasing, especially among thyroid cancer patients, and lung cancer is still the main cause of cancer death. Therefore, we aimed to investigate the risk of second primary lung cancer (SPLC) in patients with thyroid cancer.

We searched the PubMed, Web of Science, Embase, and Scopus databases up to November 24, 2021, for relevant research and merged the standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) to evaluate the risk of developing SPLC in patients with thyroid cancer.

Fourteen studies involving 1,480,816 cases were included in our meta-analysis. The pooled result demonstrated that thyroid cancer patients may have a higher risk of SPLC than the general population (SIR = 1.21, 95% CI: 1.07-1.36, P < 0.01, I² = 81%, P < 0.01). Subgroup analysis stratified by sex indicated that female patients may have a markedly higher risk of SPLC than male patients (SIR = 1.65, 95% CI: 1.40-1.94, P < 0.01, I² = 75%, P < 0.01).

Thyroid cancer patients are more likely to develop SPLC than the general population, especially women. However, other risk factors must be investigated, and more prospective studies are needed to confirm our results.

International Prospective Register of Systematic Reviews: No. CRD42021285399.

Patellofemoral joint (PFJ) degeneration has traditionally been regarded as a contraindication to unicompartmental knee arthroplasty (UKA). More recently, some researchers have proposed that PFJ degeneration can be ignored in medial UKA, and others have proposed that this change should be reviewed in PFJ degenerative facets and severity. This study aimed to systematically evaluate the effect of PFJ degeneration on patient-reported outcome measures (PROMs) and revision rates after medial UKA.

Electronic databases (PubMed, Embase, Web of Science, etc.) were searched for studies assessing the influence of PFJ degeneration on medial UKA. A random-effects meta-analysis was conducted for the Oxford knee score (OKS), Knee society score (KSS), and revision rates and stratified by PFJ degenerative facets (medial/lateral/trochlear/unspecified), severe PFJ degeneration (bone exposed), and bearing type (mobile/fixed). Heterogeneity was assessed by the Cochran Q test statistic and chi-squared tests with the I-squared statistic.

A total of 34 articles with 7007 knees (2267 with PFJ degeneration) were included (5762 mobile-bearing and 1145 fixed-bearing and 100 unspecified). Slight to moderate degenerative changes in the medial and trochlear facets did not decrease the OKS and KSS, and only lateral facets significantly decreased the OKS (mean difference [MD] = -2.18, P < 0.01) and KSS (MD = -2.61, P < 0.01). The severity degree of PFJ degeneration had no additional adverse effect on the OKS, KSS, or revision rates. For mobile-bearing UKA, only lateral PFJ degeneration significantly decreased the OKS (MD = -2.21, P < 0.01) and KSS (MD = -2.44, P < 0.01). For fixed-bearing UKA, no correlation was found between PROMs/revision rates and PFJ degeneration.

For medial mobile-bearing UKA, slight to moderate degenerative changes in the PFJ, except lateral facet, did not compromise PROMs or revision rates. For medial fixed-bearing UKA, although it might not be conclusive enough, PROMs or revision rates were not adversely affected by PFJ degeneration (regardless of the facet).

Postoperative pulmonary complications often lead to increased mortality and financial burden. Residual paralysis plays a critical role in postoperative pulmonary complications. This meta-analysis was performed to determine whether sugammadex overmatches neostigmine in reducing postoperative pulmonary complications.

PubMed, Embase, Web of Science, Medline through Ovid, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and Chinese BioMedical Literature Databases were searched from their inception to 24 June, 2021. Random effects models were used for all analyses. Cochrane risk of bias tool was used to assess the quality of RCTs, while Newcastle Ottawa Quality Assessment Scale was used to assess for the quality of cohort studies.

Seventeen studies were included in the meta-analysis. Pooled data from cohort studies showed reversing neuromuscular blocking with sugammadex had less risk of compound postoperative pulmonary complications (relative risk [RR]: 0.73; 95% confidence interval [CI]: 0.60-0.89; P = 0.002; I² = 81%), pneumonia (RR: 0.64; 95% CI: 0.48-0.86; I² = 42%) and respiratory failure (RR: 0.48; 95% CI: 0.41-0.56; I² = 0%). However, pooled data from RCTs did not show any difference between the two groups in pneumonia (RR: 0.58; 95% CI: 0.24-1.40; I² = 0%) and no respiratory failure was reported in the included RCTs. The difference was not found between sugammadex and neostigmine about atelectasis in pooled data from either RCTs (RR: 0.85; 95% CI: 0.69-1.05; I² = 0%) or cohort studies (RR: 1.01; 95% CI: 0.87-1.18; I² = 0%).

The evidence of superiority of sugammadex was limited by the confounding factors in cohort studies and small scale of RCTs. Whether sugammadex precedes neostigmine in preventing pulmonary complications after surgery is still unknown. Well-designed RCTs with large scale are needed.

PROSPERO (https://www.crd.york.ac.uk/PROSPERO/); CRD 42020191575

氨苯砜超敏综合征(DHS)最早由Lowe和Smith报道^[1]1949年在尼日利亚被Allday和Barnes称为“氨苯砜综合征”^[2]1951年。DHS是由氨苯砜4’4’-二氨基二苯基砜（DDS）引起的药物性超敏反应综合征（DIHS）。DHS的特征是发热、皮疹、淋巴结肿大和肝炎，通常在患者接受DDS治疗5至6周后出现。流行病学研究估计DHS患病率和死亡率分别为1.4%和9.9%。^[3]直到最近，“观望”方法被用于疑似DHS的患者。在此，我们回顾了DHS研究的最新进展，重点是其病因、发病机制、诊断和预防，通过在DDS给药前前瞻性排除易感患者，使DDS成为大多数人群更安全的药物。

黄褐斑（chloasma）是一种高度流行和美容毁容的色素性皮肤病，主要表现为面部暴露于阳光的区域的双侧不规则棕色斑块。^[1]尽管黄褐斑不会引起身体不适，但由于令人苦恼的美容问题，它给患者带来了重大的心理负担。持续的表皮过度黑化是黄褐斑的显著病理特征，其通常被认为是由过度活跃的黑色素细胞过度产生黑色素引起的。^[2]然而，现有的抑制黑素细胞和酪氨酸酶（黑色素合成途径中的限速酶）的治疗干预未能达到令人满意的结果，特别是对于病变倾向于反弹的顽固性黄褐斑患者。^[2]

After major liver resection, the volume status of patients is still undetermined. However, few concerns have been raised about postoperative fluid management. We aimed to compare gut function recovery and short-term prognosis of the patients after laparoscopic liver resection (LLR) with or without inferior vena cava (IVC) respiratory variability-directed fluid therapy in the anesthesia intensive care unit (AICU).

This randomized controlled clinical trial enrolled 70 patients undergoing LLR. The IVC respiratory variability was used to optimize fluid management of the intervention group in AICU, while the standard practice of fluid management was used for the control group. The primary outcome was the time to flatus after surgery. The secondary outcomes included other indicators of gut function recovery after surgery, postoperative length of hospital stay (LOS), liver and kidney function, the severity of oxidative stress, and the incidence of severe complications associated with hepatectomy.

Compared with patients receiving standard fluid management, patients in the intervention group had a shorter time to anal exhaust after surgery (1.5 ± 0.6 days vs. 2.0 ± 0.8 days) and lower C-reactive protein activity (21.4 [95% confidence interval (CI): 11.9-36.7] mg/L vs. 44.8 [95%CI: 26.9-63.1] mg/L) 24 h after surgery. There were no significant differences in the time to defecation, serum concentrations of D-lactic acid, malondialdehyde, renal function, and frequency of severe postoperative complications as well as the LOS between the groups.

Postoperative IVC respiratory variability-directed fluid therapy in AICU was facilitated in bowel movement but elicited a negligible beneficial effect on the short-term prognosis of patients undergoing LLR.

ChiCTR-INR-17013093.

Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States.

This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes.

After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: -0.07 to -0.02; P = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses.

Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.

Lung cancer has been the leading cause of cancer-related deaths worldwide for many years. This study aimed to investigate the global patterns and trends of lung cancer.

Lung cancer incidence and mortality were derived from the GLOBOCAN 2020 database. Continuous data from Cancer Incidence in Five Continents Time Trends were used to analyze the temporal trends from 2000 to 2012 using Joinpoint regression, and average annual percent changes were calculated. The association between the Human Development Index and lung cancer incidence and mortality was assessed by linear regression.

An estimated 2.2 million new lung cancer cases and 1.8 million lung cancer-related deaths occurred in 2020. The age-standardized incidence rate (ASIR) ranged from 36.8 per 100,000 in Demark to 5.9 per 100,000 in Mexico. The age-standardized mortality rate (ASMR) varied from 32.8 per 100,000 in Poland to 4.9 per 100,000 in Mexico. Both ASIR and ASMR were approximately twice higher in men than in women. The ASIR of lung cancer showed a downward trend in the United States of America (USA) between 2000 and 2012, and was more prominent in men. The age-specific incidence rates of lung cancer for ages of 50 to 59 years showed an upward trend in China for both men and women.

The burden of lung cancer is still unsatisfactory, especially in developing countries like China. Considering the effectiveness of tobacco control and screening in developed countries, such as the USA, there is a need to strengthen health education, accelerate the establishment of tobacco control policies and regulations, and improve early cancer screening awareness to reduce the future burden of lung cancer.

There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension.

The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD.

During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association.

NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.

Stroke is the leading cause of death in China, and predicting the stroke burden could provide essential information guiding the setting of medium- and long-term health policies and priorities. The study aimed to project trends associated with stroke burden in China through 2050, not only in terms of incidence and mortality but also for prevalence and disability-adjusted life years (DALYs).

Data on stroke rates in incidence, prevalence, deaths, and DALYs in China between 1990 and 2019 were obtained from a recent Global Burden of Disease study. Demographic-specific trends in rates over time were estimated using three models: the loglinear model, the Lee-Carter model, and a functional time series model. The mean absolute percentage error and the root mean squared error were used for model selection. Projections up to 2050 were estimated using the best fitting model. United Nations population data were used to project the absolute numbers through 2050.

From 2019 to 2050, the crude rates for all measures of the stroke burden are projected to increase continuously among both men and women. We project that compared with those in 2019, the incidence, prevalence, deaths, and DALYs because of stroke in China in 2050 will increase by 55.58%, 119.16%, 72.15%, and 20.04%, respectively; the corresponding increases in number were 2.19, 34.27, 1.58, and 9.21 million. The age-standardized rate is projected to substantially decline for incidence (8.94%), death (40.37%), and DALYs (43.47%), but the age-standardized prevalence rate is predicted to increase by 10.82%. By 2050, the burden of stroke among the population aged ≥65 years will increase significantly: by 104.70% for incidence, by 218.48% for prevalence, by 100.00% for death, and by 58.93% for DALYs.

With the aging population in China increasing over the next three decades, the burden of stroke will be markedly increased. Continuous efforts are needed to improve stroke health care and secondary prevention, especially for older adults.

致编辑：哮喘是一种异常的慢性炎性疾病，其特征在于涉及复杂的细胞网络。屏障上皮细胞（ECs）代表第一道防线，并表达模式识别受体以识别2型细胞介导的免疫损伤。夸大的异常屏障功能或不充分的免疫应答可能有助于哮喘的病理生理学。^[1,2]

致编辑：心脏手术患者的总生存率显著提高，降低死亡率和术后并发症仍然至关重要。营养不良是住院患者的常见病。有几种方法可以评估营养状况；然而，营养不良的一些因素很难衡量。控制营养状况（CONUT）评分是一种客观的营养指标，也是一种易于实施的实用筛查工具，使用血清白蛋白、外周淋巴细胞计数和总胆固醇。具体来说，这三种成分的组合可以评估蛋白质储备、免疫防御和卡路里消耗。^[1]最近，CONUT评分的预测价值已在患有外周动脉疾病、恶性肿瘤和心脏病的手术患者中得到验证。^[2]几项研究发现，在接受经导管主动脉瓣植入（TAVI）、经皮冠状动脉介入治疗或冠状动脉旁路移植术的患者中，高CONUT评分与高死亡率相关。^[2,3]然而，CONUT评分对接受心脏手术的中国患者的预后影响尚未得到充分研究。因此，本研究旨在确定营养不良对接受心脏手术的患者预后的影响，通过CONUT评分评估。

致编辑：慢性阻塞性肺疾病(COPD)是一种包括一系列慢性、进行性和衰弱性呼吸系统疾病的临床综合征，越来越被认为是一种多系统异质性疾病。^[1]由于东亚COPD患者的特征不同于西方人，因此研究东亚和西方人群之间是否存在COPD遗传表现的变异将是实用的。^[2]

致编辑：经胸针吸（TTNA）和支气管镜检查一直是疑似肺癌肺结节取样的首选方法。然而，尽管具有更高的诊断准确性，TTNA与高气胸率相关。此外，气胸发生率低的常规支气管镜检查对周围肺结节，特别是结节的诊断率低<2厘米大小或没有支气管直接通向它们的人。因此，赫思等人^[1]在阿基米德虚拟支气管镜导航（VBN）系统的指导下，开发了一种称为支气管镜透肺结节入路（BTPNA）的新型支气管镜技术，旨在使用透肺入路进入肺结节，而不依赖气道接近病变。在这里，我们系统地回顾了有关BTPNA的证据，为这种新方法的安全实施和发展提供了一般指导。

致编辑：随着百日咳疫苗的广泛摄入，与百日咳相关的发病率和死亡率显著下降。无细胞疫苗（ACV）在中国的应用比发达国家晚；相应地，百日咳在中国的死灰复燃也开始较晚。最新的全球基因型动态预测模型无法解释百日咳杆菌中国基因型变化趋势。^[1]中国的B.百日咳菌株逐渐形成了自己独特的发育分支。^[2]在这里，流行的系统发育树B.百日咳来自中国三个不同地区的菌株通过EvolView（http：//www.evolgenius.info/evolview.html）可视化。共199例隔离B.百日咳菌株用于系统发育分析。TheB.为了-百日咳以天津分离的毒株为外群，以我国广泛用作ACV生产疫苗毒株的中国毒株（CS）为参考毒株。特别是，我们分析了多位点序列分型（MLST）和大环内酯类耐药基因突变。

致编辑：随着新型冠状病毒病2019（COVID-19）大流行在全球迅速蔓延，它导致了前所未有的经济损失、社会动荡和对公众心理健康的不利影响。特别是，疾病控制措施的实施，如全国范围的封锁、社交距离、学校关闭和家庭隔离，在世界各地引起了广泛的社交焦虑（SA），从非临床表现到临床社交焦虑障碍（SAD）。^[1]鉴于SA的潜在严重损害和有限的精神卫生保健资源，确定在大流行期间是否存在导致SA进展的脆弱性/风险神经心理因素至关重要。此外，强迫症状/障碍（OCS/OCD）是大流行期间的另一个重要精神健康问题，在概念上和经验上与SA相关，并与SA共享一些神经解剖学基础；^[2]然而，在新冠肺炎疫情的背景下，这种潜在的联系很少被研究。因此，目前的研究旨在探索正常年轻人SA差异变化的神经解剖结构的差异，以及新冠肺炎疫情期间大流行特异性OCS在脑结构与SA变化联系中的潜在介导作用。

致编辑：以白色脂肪组织过度积聚为特征的肥胖症会增加妊娠糖尿病(GDM)的患病率。暴露于宫内高血糖会增加成年后代的长期后遗症，包括心血管异常和代谢综合征。^[1]早在二十年前，David Barker博士就提供了营养暴露的证据子宫内对后代成年后的健康状况有持久的影响。^[2]这强调了早期宫内环境暴露的关键作用，并突出了成人代谢疾病的潜在起源。

致编辑：为了控制冠状病毒疾病2019（新冠肺炎）疫情并减少疾病传播导致的并发症和死亡，多种新冠肺炎疫苗，如mRNA疫苗、腺病毒载体疫苗、灭活病毒疫苗等，已获得紧急使用许可。这些疫苗大部分是在成功完成3期临床试验后在不同国家推出的。疫苗生产和疫苗接种的扩大为大量人群提供了显著的保护，尽管一些疫苗可能会引起副作用。此外，随着严重急性呼吸综合征冠状病毒2型（新型冠状病毒）随着时间的推移发生变异并进一步传播，出现了一些值得注意的新变种，但这些变种是否容易受到目前可用疫苗的攻击仍有待确定。

致编辑：肿瘤是世界范围内死亡的主要原因之一。上睑下垂是一种新发现的细胞死亡形式，引起细胞肿胀和快速溶解，从而释放促炎介质，增强炎症反应。^[1]炎症增加对肿瘤的免疫应答并抑制其进展。癌症治疗的最终目标是最大限度地破坏肿瘤细胞，同时最小化对正常组织的损伤。^[2]靶向肿瘤细胞上睑下垂可以克服细胞凋亡抵抗，引发抗肿瘤免疫，是治疗肿瘤的良好手段。

致编辑：中国是脑出血（ICH）患者人数最多的国家，^[1]挖掘、利用和共享相关数据的努力是有保证的。由于ICH的结构化诊断和治疗管道已被证明可以改善患者结果，因此迫切需要构建一个大型医学数据库来存储相关数据，并促进数据挖掘、分析和共享。然而，传统卒中数据库以文本数据为主，缺乏全面的影像学数据，很少有研究关注ICH方面的数据库建设。^[2,3]为了整合ICH的多模态数据，规范数据处理和反馈，中国颅内出血影像数据库（CICHID）由北京协和医院于2019年建立，并在不断完善中。与传统的基于文本的数据库不同，CICHID是一个大型多模态数据仓库，实现了全面的临床数据存储和多维影像数据分析。