Volume 137 · Issue 01 · 2024

系统综述使用系统和明确的方法来搜索、识别、筛选、批判性评估、提取和分析相关研究的数据，综合解决结构化临床问题的证据。^[1]另一方面，荟萃分析是一种统计方法，它结合了解决同一问题的可用主要研究的定量结果，以生成汇总估计值和置信区间（CI）。^[2]荟萃分析可以增加统计能力，提高精确度，并回答单一试验无法解决的问题。尽管有不适合荟萃分析的系统综述，但当它们进行和报告良好时，系统综述结合荟萃分析为临床医生、研究人员和决策者提供了有价值的信息。

自体骨移植物长期以来被认为是骨再生过程中的“金标准”和最有效的材料。^[1]自体骨移植用于修复骨不连、感染、肿瘤切除、脊柱关节融合等引起的骨缺损。^[2]据报道，美国每年进行超过200,000例自体骨移植。^[3]虽然国内每年进行的植骨手术数量没有具体统计，但自体骨移植是骨科最常见的手术技术。髂嵴仍然是最常见的供体部位，还有腓骨、肋骨、胫骨干骺端、肱骨近端、桡骨远端和大转子。^[4,5]各种骨移植选择提供不同数量和质量的皮质骨、松质骨和皮质松质骨。^[6,7]自体骨移植是成骨的，组织相容的，提供结构支持，并且没有疾病传播的风险。自体骨移植的缺点是其供应有限，并且由于需要收获骨移植材料而增加了手术量，这增加了手术时间、失血和并发症的风险。目前还没有关于自体骨移植适应症、技术和并发症的临床指南或共识报告。^[8]中华骨科协会创伤骨科分会和国家骨科、运动医学与康复临床医学研究中心制定了自体骨移植的适应症、技术和并发症的临床实践指南（详细信息见补充文件，http://links.lww.com/CM9/B551）。

γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs, which is mediated by cancer cachexia factors. Cancer cachexia factors, being the general name of inflammatory factors, circulating proteins, metabolites, and microRNA secreted by tumor or host cells, play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia. Cancer cachexia factors are also a potential target for the diagnosis and treatment. The pathogenesis of cachexia is unclear and no clear effective treatment is available. Thus, the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed. From the point of signal communication between organs mediated by cancer cachexia factors, finding a deeper understanding of the pathogenesis, diagnosis, and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment. This review begins with cancer cachexia factors released during the interaction between tumor and host cells, and provides a comprehensive summary of the pathogenesis, diagnosis, and treatment for cancer cachexia, along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors. This summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological status. These intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis, metabolism, and immune response. The disruption of microbiota, known as dysbiosis, has been implicated in many intestinal diseases, including colorectal cancer (CRC). As the third most common cancer and the second leading cause of cancer-related death worldwide, CRC poses a significant health burden. There is an urgent need for novel interventions to reduce CRC incidence and improve clinical outcomes. Modulating the intestinal microbiota has emerged as a promising approach for CRC prevention and treatment. Current research efforts in CRC probiotics primarily focus on reducing the incidence of CRC, alleviating treatment-related side effects, and potentiating the efficacy of anticancer therapy, which is the key to successful translation to clinical practice. This paper aims to review the traditional probiotics and new interventions, such as next-generation probiotics and postbiotics, in the context of CRC. The underlying mechanisms of probiotic anti-cancer effects are also discussed, including the restoration of microbial composition, reinforcement of gut barrier integrity, induction of cancer cell apoptosis, inactivation of carcinogens, and modulation of host immune response. This paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and immunotherapy. Despite all the promising findings presented in studies, the evaluation of potential risks, optimization of delivery methods, and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.

Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38.

lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer.

Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

The 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guideline lowered the threshold defining hypertension to 130/80 mmHg. However, how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains unclear. This study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese population.

Participants with stage 1 hypertension (n = 69,509) or normal BP (n = 34,142) were followed in this study from 2006/2007 to 2020. Stage 1 hypertension was defined as a systolic blood pressure of 130–139 mmHg or a diastolic blood pressure of 80–89 mmHg. None were taking antihypertensive medication or had a history of myocardial infarction (MI), stroke, or cancer at baseline. The primary outcome was a composite of MI, stroke, and all-cause mortality. The secondary outcomes were individual components of the primary outcome. Cox proportional hazards models were used for the analysis.

During a median follow-up of 11.09 years, we observed 10,479 events (MI, n = 995; stroke, n = 3408; all-cause mortality, n = 7094). After multivariable adjustment, the hazard ratios for stage 1 hypertension vs. normal BP were 1.20 (95% confidence interval [CI], 1.13–1.25) for primary outcome, 1.24 (95% CI, 1.05–1.46) for MI, 1.45 (95% CI, 1.33–1.59) for stroke, and 1.11 (95% CI, 1.04–1.17) for all-cause mortality. The hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90 (95% CI, 0.85–0.96).

Using the new definition, Chinese adults with untreated stage 1 hypertension are at higher risk for MI, stroke, and all-cause mortality. This finding may help to validate the new BP classification system in China.

Dilated cardiomyopathy (DCM) has a high mortality rate and is the most common indication for heart transplantation. Our study sought to develop a multiparametric nomogram to assess individualized all-cause mortality or heart transplantation (ACM/HTx) risk in DCM patients.

The present study is a retrospective cohort study. The demographic, clinical, blood test, and cardiac magnetic resonance imaging (CMRI) data of DCM patients in the tertiary center (Fuwai Hospital) were collected. The primary endpoint was ACM/HTx. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied for variable selection. Multivariable Cox regression was used to develop a nomogram. The concordance index (C-index), area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram.

A total of 218 patients were included in the present study. They were randomly divided into a training cohort and a validation cohort. The nomogram was established based on eight variables, including mid-wall late gadolinium enhancement, systolic blood pressure, diastolic blood pressure, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-diastolic volume index, free triiodothyronine, and N-terminal pro-B type natriuretic peptide. The AUCs regarding 1-year, 3-year, and 5-year ACM/HTx events were 0.859, 0.831, and 0.840 in the training cohort and 0.770, 0.789, and 0.819 in the validation cohort, respectively. The calibration curve and DCA showed good accuracy and clinical utility of the nomogram.

We established and validated a circulating biomarker- and CMRI-based nomogram that could provide a personalized prediction of ACM/HTx for DCM patients, which might help risk stratification and decision-making in clinical practice.

Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis.

In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10^–8). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR–Egger, and weighted median regression) were used to ensure that our results more reliable.

All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30–1.58, P = 2.51 × 10^-13). The results of MR–Egger and weighted median regression exhibited similar trends (MR–Egger OR = 1.40 [95% CI, 1.08–1.81], P = 1.61 × 10^-2; weighted median OR = 1.39 [95% CI, 1.21–1.61], P = 1.62 × 10^-6). MR–Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF.

Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.

With an increasing proportion of multiparas, proper interpregnancy intervals (IPIs) are urgently needed. However, the association between IPIs and adverse perinatal outcomes has always been debated. This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages.

We used individual data from China’s National Maternal Near Miss Surveillance System between 2014 and 2019. Multivariable Poisson models with restricted cubic splines were used. Each adverse outcome was analyzed separately in the overall model and stratified models. The stratified models included different categories of fertility policy periods (2014–2015, 2016–2017, and 2018–2019) and infant gestational age in previous pregnancy (<28 weeks, 28–36 weeks, and ≥37 weeks).

There were 781,731 pregnancies enrolled in this study. A short IPI (≤6 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.63 [1.55, 1.71] for vaginal delivery [VD] and 1.10 [1.03, 1.19] for cesarean section [CS]), low Apgar scores and small for gestational age (SGA), and a decreased risk of diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. A long IPI (≥60 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.18 [1.11, 1.26] for VD and 1.39 [1.32, 1.47] for CS), placenta previa, postpartum hemorrhage, diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes. The estimated risk of preterm birth, low Apgar scores, SGA, diabetes mellitus in pregnancy, and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss.

For pregnant women with shorter or longer IPIs, more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

The Global Leadership Initiative on Malnutrition (GLIM) criteria were published to build a global consensus on nutritional diagnosis. Reduced muscle mass is a phenotypic criterion with strong evidence to support its inclusion in the GLIM consensus criteria. However, there is no consensus regarding how to accurately measure and define reduced muscle mass in clinical settings. This study aimed to investigate the optimal reference values of skeletal muscle mass index for diagnosing sarcopenia and GLIM-defined malnutrition, as well as the prevalence of GLIM-defined malnutrition in hospitalized cirrhotic patients.

This retrospective study was conducted on 1002 adult patients with liver cirrhosis between January 1, 2018, and February 28, 2022, at Beijing You-An Hospital, Capital Medical University. Adult patients with a clinical diagnosis of liver cirrhosis and who underwent an abdominal computed tomography (CT) examination during hospitalization were included in the study. These patients were randomly divided into a modeling group (cohort 1, 667 patients) and a validation group (cohort 2, 335 patients). In cohort 1, optimal cut-off values of skeletal muscle index at the third lumbar skeletal muscle index (L3-SMI) were determined using receiver operating characteristic analyses against in-hospital mortality in different gender groups. Next, patients in cohort 2 were screened for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. Additionally, the reference values of reduced muscle mass in GLIM criteria were derived from the L3-SMI values from cohort 1. Multivariate logistic regression analysis was used to analyze the association between GLIM-defined malnutrition and clinical outcomes.

The optimal cut-off values of L3-SMI were 39.50 cm²/m² for male patients and 33.06 cm²/m² for female patients. Based on the cut-off values, 31.63% (68/215) of the male patients and 23.3% (28/120) of the female patients had CT-determined sarcopenia in cohort 2. The prevalence of GLIM-defined malnutrition in cirrhotic patients was 34.3% (115/335) and GLIM-defined malnutrition was an independent risk factor for in-hospital mortality in patients with liver cirrhosis (Wald = 6.347, P = 0.012).

This study provided reference values for skeletal muscle mass index and the prevalence of GLIM-defined malnutrition in hospitalized patients with liver cirrhosis. These reference values will contribute to applying the GLIM criteria in cirrhotic patients.

致编辑原发性纤毛运动障碍（PCD）是一种罕见的常染色体隐性遗传性疾病，以活动纤毛功能障碍为特征。DNAH5PCD中最常见的突变基因编码纤毛外动力蛋白臂（ODAs）的重链。在此，我们报告了两个携带两个新的纯合子的血缘家族中的两名Kartagener综合征患者（鼻窦炎、支气管扩张和位置倒置）DNAH5变体[补充图1A和1B，http://links.lww.com/CM9/B598]。

致编辑：肌酸激酶（CK），又称肌酸磷酸激酶，主要位于细胞质和线粒体中。它可用于诊断心脏疾病，如心肌梗塞、病毒性心肌炎和心包炎，因为它是一种与细胞内能量运作、肌肉收缩和三磷酸腺苷（ATP）再生直接相关的重要激酶。近年来多项研究证实，血清生物标志物如CK升高与阿尔茨海默病（AD）及其相关病理蛋白相关。^[1]先前的研究表明，全身性疾病，特别是心脑血管疾病，是认知障碍的重要危险因素，外周器官功能障碍也可能导致认知能力下降和AD。^[2]然而，CK和AD之间的联系仍然未知。因此，为了研究CK和脑脊液（CSF）AD病理学生物标志物之间的关联，我们分析了来自全球多中心数据库阿尔茨海默病神经成像倡议（ADNI）的数据。

致编辑：益生菌是功能性便秘(FC)的一种有前途的治疗方式；然而，影响个体对益生菌反应的因素仍不清楚。越来越多的证据表明，肠道微生物群和便秘以及相关的肠脑轴之间有很强的关系。^[1]肠道微生物群可以通过肠道代谢物调节肠道功能或触发肠道激素如肽YY、胃抑制性多肽和5-羟色胺的释放。^[2]反过来，肠道激素通过位于上皮、肠和平滑肌细胞上的受体影响肠道分泌、运动和感觉。^[2]基于这些发现，外源性益生菌已用于便秘患者；然而，很少有人产生一致的结果。^[3]在这项研究中，我们调查了几种特定益生菌菌株对便秘的疗效和安全性，并检查了益生菌个体化作用的潜在原因，这可能有助于FC患者的干预决策。