Lan Zhu, Zichen Zhao, Attilio Di Spiezio Sardo, Maribel Acién, Joel Naftalin, Thierry Van den Bosch, Charleen Sze-yan Cheung, Dabao Xu, Xiaowu Huang, Grigoris Grimbizis
Muhammad Babar Khawar, Ali Afzal, Shuangshuang Dong, Yue Si, Haibo Sun
Chinese Medical JournalVol.138,No.132025
DOI: 10.1097/CM9.0000000000003346
Abstract
Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promises, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors. Nevertheless, the specific mechanisms underlying CAR NK cell trafficking and their interplay within the complex tumor microenvironment require further in-depth exploration. Herein, we provide insights into the design and engineering of CAR NK cells, antigen targets in CRC, and success in overcoming resistance mechanisms with an emphasis on the potential for clinical trials.
In recent years, growing evidence indicates that the nervous system plays an indispensable role in tumor development and metastasis. Elucidating crosstalk between the nervous system and tumor progression has thrived as a hot topic and a new direction for understanding cancer pathogenesis. Notably, many novel discoveries have suggested that neurotransmitter receptors (NRs) are not only widely expressed in cancer cells, but also play key roles in regulating cancer initiation and progression by diverse approaches. In this review, we summarized the latest advance in cancer neuroscience, especially emphasizing the important roles of different NRs in cancer development and prevention. The exemplary studies presented herein illustrate the emerging view that NRs are profoundly influential, manifested in tumor growth, apoptosis, angiogenesis, metastasis, resistance to drugs, and participate in the formation of neural–cancer interactions. In addition, NRs also regulate cellular metabolic processes and tumor microenvironment (TME) remodeling. More importantly, numerous basic and clinical studies have suggested that NRs may be potential targets for cancer treatments, and corresponding agonists or antagonists have been identified effectively in controlling tumor growth and metastasis. In conclusion, NRs are emerging as novel targets for anti-cancer drug exploration and clinical cancer treatments, while trying to uncover deeper mechanisms and connections between NRs and cancer is of high clinical significance and translational value.
Baiqiang Dong, Shuohan Zheng, Kelly Chen, Xuan Zhu, Sijuan Huang, Xiaobo Jiang, Wenchao Diao, Hua Li, Lecheng Jia, Feng Chi, et al.
Chinese Medical JournalVol.138,No.132025
DOI: 10.1097/CM9.0000000000003299
Abstract
Definitive treatment of lung cancer with radiotherapy is challenging, as respiratory motion and anatomical changes can increase the risk of severe off-target effects during radiotherapy. Online adaptive radiotherapy (ART) is an evolving approach that enables timely modification of a treatment plan during the interfraction of radiotherapy, in response to physiologic or anatomic variations, aiming to improve the dose distribution for precise targeting and delivery in lung cancer patients. The effectiveness of online ART depends on the seamless integration of multiple components: sufficient quality of linear accelerator-integrated imaging guidance, deformable image registration, automatic recontouring, and efficient quality assurance and workflow. This review summarizes the present status of online ART for lung cancer, including key technologies, as well as the challenges and areas of active research in this field.
Kuanyu Xia, Lang Min, Wenqing Xie, Guang Yang, Dong Keon Yon, Seung Won Lee, Ai Koyanagi, Louis Jacob, Lee Smith, Jae Il Shin, et al.
Chinese Medical JournalVol.138,No.132025
DOI: 10.1097/CM9.0000000000003193
Abstract
Background:
The choice of unicompartmental knee arthroplasty (UKA) vs. total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA.
Methods:
PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards.
Results:
Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01–1.45; P <0.001), greater knee function (MD: 1.78; 95% CI: 0.34–3.22; P = 0.020), less pain (MD: 0.75; 95% CI: 0.43–1.06; P <0.001), and better health status (MD: 3.75; 95% CI: 0.81–6.69; P = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45–0.78; P <0.001) and shorter hospital stays (MD: –0.89; 95% CI: –1.57 to –0.22; P = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction.
Conclusions:
In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Background:
Severe stroke has high rates of mortality and morbidity. This study aimed to investigate the clinical course, causes of worsening, and outcomes of severe ischemic stroke.
Methods:
This prospective, multicenter cohort study enrolled adult patients admitted ≤30 days after ischemic stroke from nine hospitals in China between September 2017 and December 2019. Severe stroke was defined as a score of ≥15 on the National Institutes of Health Stroke Scale (NIHSS). Clinical worsening was defined as an increase of 4 in the NIHSS score from baseline. Unfavorable functional outcome was defined as a modified Rankin scale score ≥3 at 3 months and 1 year after stroke onset, respectively. We performed Logistic regression to explore baseline features and reperfusion therapies associated with clinical worsening and functional outcomes.
Results:
Among 4201 patients enrolled, 854 patients (20.33%) had severe stroke on admission. Of 3347 patients without severe stroke on admission, 142 (4.24%) patients developed severe stroke in hospital. Of 854 patients with severe stroke on admission, 33.95% (290/854) experienced clinical worsening (median time from stroke onset: 43 h, Q1–Q3: 20–88 h), with brain edema (54.83% [159/290]) as the leading cause; 24.59% (210/854) of these patients died by 30 days, and 81.47% (677/831) and 78.44% (633/807) had unfavorable functional outcomes at 3 months and 1 year respectively. Reperfusion reduced the risk of worsening (adjusted odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.12–0.49, P <0.01), 30-day death (adjusted OR: 0.22, 95% CI: 0.11–0.41, P <0.01), and unfavorable functional outcomes at 3 months (adjusted OR: 0.24, 95% CI: 0.08–0.68, P <0.01) and 1 year (adjusted OR: 0.17, 95% CI: 0.06–0.50, P <0.01).
Conclusions:
Approximately one-fifth of patients with ischemic stroke had severe neurological deficits on admission. Clinical worsening mainly occurred in the first 3 to 4 days after stroke onset, with brain edema as the leading cause of worsening. Reperfusion reduced the risk of clinical worsening and improved functional outcomes.
Ke Han, Xiangyao Wang, Yan Wang, Xiaotong Niu, Jingyuan Xiang, Nan Ru, Chunxu Jia, Hongyi Sun, Zhengting He, Yujie Feng, et al.
Chinese Medical JournalVol.138,No.132025
DOI: 10.1097/CM9.0000000000003190
Abstract
Background:
Epidemiological data on chronic diarrhea in the Chinese population are lacking, and the association between obesity and chronic diarrhea in East Asian populations remains inconclusive. This study aimed to investigate the prevalence of chronic diarrhea and its association with obesity in a representative community-dwelling Chinese population.
Methods:
This cross-sectional study was based on a multistage, randomized cluster sampling involving 3503 residents aged 20–69 years from representative urban and rural communities in Beijing. Chronic diarrhea was assessed using the Bristol Stool Form Scale (BSFS), and obesity was determined based on body mass index (BMI). Logistic regression analysis and restricted cubic splines were used to evaluate the relationship between obesity and chronic diarrhea.
Results:
The standardized prevalence of chronic diarrhea in the study population was 12.88%. The average BMI was 24.67 kg/m2. Of all the participants, 35.17% (1232/3503) of participants were classified as overweight and 16.13% (565/3503) as obese. After adjustment for potential confounders, individuals with obesity had an increased risk of chronic diarrhea as compared to normal weight individuals (odds ratio = 1.58, 95% confidence interval: 1.20–2.06). A nonlinear association between BMI and the risk of chronic diarrhea was observed in community residents of males and the overall participant group (P = 0.026 and 0.017, respectively).
Conclusions:
This study presents initial findings on the prevalence of chronic diarrhea among residents of Chinese communities while offering substantiated evidence regarding the significant association between obesity and chronic diarrhea. These findings offer a novel perspective on gastrointestinal health management.
Na Li, Jingwei Mao, Haiying Tang, Xiaoyan Tan, Jian Bi, Hao Wu, Xiuli Chen, Yingde Wang
Chinese Medical JournalVol.138,No.132025
DOI: 10.1097/CM9.0000000000003493
Abstract
Background:
Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process.
Methods:
DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4+CD25- T-cells or CD4+CD25+ T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice.
Results:
CD103+CD11b+ DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3+Treg percentages within a co-culture system of CD4+CD25- T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3+ Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4+ T-cells or CD4+CD25+ T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice.
Conclusion:
The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Yao Li, Tingting Li, Fei Xiao, Lijun Wang, Xuelian Liao, Wei Zhang, Yan Kang
Chinese Medical JournalVol.138,No.132025
DOI: 10.1097/CM9.0000000000003606
Abstract
Background:
Immunosuppression is closely related to the pathogenesis of sepsis, but the underlying mechanisms have not yet been fully elucidated. In this study, we aimed to examine the role of the Sterile Alpha Motif, Src Homology 3 domain and nuclear localization signal 1 (SAMSN1) in sepsis and elucidate its potential molecular mechanism in sepsis induced immunosuppression.
Methods:
RNA sequencing databases were used to validate SAMSN1 expression in sepsis. The impact of SAMSN1 on sepsis was verified using gene knockout mice. Flow cytometry was employed to delineate how SAMSN1 affects immunity in sepsis, focusing on immune cell types and T cell functions. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing in RAW264.7 macrophages enabled interrogation of SAMSN1’s regulatory effects on essential macrophage functions, including cell proliferation and phagocytic capacity. The mechanism of SAMSN1 in the interaction between macrophages and T cells was investigated using the RAW264.7 cell line and primary cell lines.
Results:
SAMSN1 expression was significantly increased in patients with sepsis and was positively correlated with sepsis mortality. Genetic deletion of Samsn1 in murine sepsis model improved T cell survival, elevated T cell cytolytic activity, and activated T cell signaling transduction. Concurrently, Samsn1 knockout augmented macrophage proliferation capacity and phagocytic efficiency. In macrophage, SAMSN1 binds to Kelch-like epichlorohydrin-associated protein 1 (KEAP1), causing nuclear factor erythroid 2-related factor 2 (NRF2) to dissociate from the KEAP1–NRF2 complex and translocate into the nucleus. This promotes the transcription of the coinhibitory molecules CD48/CD86/carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), which bind to their corresponding receptors natural killer cell receptor 2B4/CD152/T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) on the surface of T cells, inducing T-cell exhaustion.
Conclusions:
SAMSN1 deletion augmented adaptive T cell immunity and macrophage phagocytic-proliferative dual function. Furthermore, it mediates the KEAP1–NRF2 axis, which affects the expression of coinhibitory molecules on macrophages, leading to T-cell exhaustion. This novel immunosuppression mechanism potentially provides a candidate molecular target for sepsis immunotherapy.
Li Zhang, Jinhua Xu, Chaoying Gu, Min Zheng, Meng Pan, Linfeng Li, Michael Lane, Andrew Platt, Shereen Hammad, Qichen Fan, et al.
Chinese Medical JournalVol.138,No.132025
DOI: 10.1097/CM9.0000000000003595
Abstract
致编辑：Upadacitinib是一种口服janus激酶（JAK）抑制剂，与JAK2、JAK3或酪氨酸激酶2相比，对JAK1表现出更高的抑制效力，使其成为治疗特应性皮炎（AD）的有前途的候选药物。全球试验Measure Up 1、Measure Up 2和AD Up已经证明了中重度AD的疗效和安全性数据，无论是作为单一疗法还是与局部皮质类固醇（TC）联合使用。[1,2]更新的52周结果初步报告了52周内的持续临床获益，[3,4]但是关于中国患者长期结果的数据仍然有限。AD病理生理学的种族差异，包括免疫特征的差异，强调了对地区特异性证据的需求。[5]这个事后对Measure Up 1和AD Up试验的分析评估了upadacitinib在中国患者中的140周疗效和安全性。
