Highlights • Low level expression of let-7c is associated with metastasis of NSCLC. • Let-7c suppresses cell migration and invasion in vitro. • Let-7c targets ITGB3 and MAP4K3 and regulates their ...expression.
To determine the rate of abdominal lymph node metastasis after radical surgery for esophageal cancer and define the radiotherapy target area.
Of the 1593 patients who underwent R0 radical ...esophagectomy for thoracic esophageal squamous cell carcinoma (TE-SCC), 148 developed abdominal lymph node (LN) metastases within three years of surgery. During that time interval, patients were examined by various imaging methods (enhanced computer tomography, magnetic resonance imaging, and positron emission tomography-CT) at set time points. The emerging recurrence pattern, preferred sites for abdominal metastasis, and correlation with added clinical factors were carefully recorded, to permit for delineation of a target area for radiotherapy.
We found postoperative metastatic abdominal LNs in 9.3% of the patients treated for esophageal cancer. Lesions in the upper, middle, and lower esophageal segments metastasized to abdominal LNs at 2.3%, 7.8%, and 26.6% (P < 0.0001), respectively. Of all cases, 4.8% had fewer than two affected LNs, while 20.1% had more than three metastatic LNs (P< 0.0001). The metastasis rates of negative and positive celiac LNs were 4.6% and 22.7%, respectively. Abdominal LN metastasis rates for the following LNs: 16a2 and 16a1 of para-aortic, celiac artery, posterior surface of the pancreatic head and common hepatic artery were 64.9%, 41.2%, 37.8%, 32.4%, and 20.9%, respectively. The overall rate of metastasis to these groups of LNs was 91.9%.
This study determined that stations 16a1 and 16a2 of the para-aortic, truncus coeliacus, posterior surface of the pancreatic head, and arteria hepatica communis lymph nodes were the preferred sites for abdominal LN metastasis, thus defining target areas for postoperative radiotherapy.
Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture ...and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.
Abstract
Background
The relationship between air pollution and atrial fibrillation (AF) recorded by electrocardiograph (ECG) has not yet been illustrated which worsens AF precaution and treatment. ...This research evaluated the association between air pollution and daily hospital visits for AF with ECG records.
Methods
The study enrolled 4933 male and 5392 female patients whose ECG reports indicated AF from 2015 to 2018 in our hospital. Such data were then matched with meteorological data, including air pollutant concentrations, collected by local weather stations. A case-crossover study was performed to assess the relationship between air pollutants and daily hospital visits for AF recorded by ECG and to investigate its lag effect.
Results
Our analysis revealed statistically significant associations between AF occurrence and demographic data, including age and gender. This effect was stronger in female (
k
= 0.02635,
p
< 0.01) and in patients over 65 y (
k
= 0.04732,
p
< 0.01). We also observed a hysteretic effect that when exposed to higher nitrogen dioxide(NO
2
), counting AF cases recorded by ECG may elevate at lag 0 with a maximum odds ratio(OR) of 1.038 (95% CI 1.014–1.063), on the contrary, O
3
reduced the risk of daily visits for AF and its maximum OR was at lag 2, and the OR value was 0.9869 (95% CI 0.9791–0.9948). Other air pollutants such as PM
2.5
, PM
10
, and SO
2
showed no clear relationship with the recorded AF.
Conclusion
The associations between air pollution and AF recorded with ECG were preliminarily discovered. Short-term exposure to NO
2
was significantly associated with daily hospital visits for AF management.
The Meiyu season is a typical rainy season in East Asia that is controlled by summer monsoon. Despite extensive research on its impact, it is unclear how urbanization modifies precipitation during ...the Meiyu season in the background of the monsoon influence. To address this gap, this study investigated the effects of urbanization and monsoon on the modification of precipitation during the Meiyu season (PDM) in the megacity of Shanghai, China. Through homogenization analysis of the original observational data, we assessed the temporal and spatial variation in PDM in Shanghai during two stages of urbanization. Our findings revealed that both total precipitation and extreme daily precipitation during the Meiyu season in Shanghai have significantly increased since 1961. The spatial heterogeneity of PDM has also enhanced during the rapid urban process that has occurred since 1986. The long-term trend of increasing precipitation in Shanghai showed a synchronous variation with the East Asian subtropical summer monsoon (EASM) in 1961–2021. Over the interannual time scale, the significant positive correlation between PDM and EASM during the slow urbanization period (Stage 1: 1961–1985) changed to a non-significant correlation during the rapid urbanization period (Stage 2: 1986–2021), which was associated with the enhanced convective precipitation in Shanghai during the Meiyu season. Urbanization induced more convective precipitation and further weakened the association between PDM and EASM over the central city and nearby areas during Stage 2. The rapid urbanization process also resulted in increased differences in near-surface wind between urban and non-urban areas, which facilitated more PDM over the central city due to the urban friction effect and wind shear in Stage 2. Furthermore, our analysis suggests that the increase in precipitation may be associated with the enhanced coupling of cold air intrusion with the warmer climate background due to the urban heat effect occurring in Stage 2. These findings contribute to a better understanding of how urbanization and monsoons affect PDM in East Asian megacities and serve as a unique reference for climate prediction in this region.
The aim of this study was to determine the impact of lymph node (LN) metastasis conditions on the prognosis of patients with esophageal squamous carcinoma and the minimum number of LNs that should be ...removed to maximize overall postoperative survival among patients with this specific pathologic subtype. In this study, 312 patients with thoracic squamous esophageal carcinoma who received in-patient thoracic surgery by the same surgeon in our hospital from August 1, 2003 to December 31, 2009 were recruited. Subsequently, Kaplan-Meier methods were used to determine associations between LN metastasis conditions and mortality and between the numbers of LNs removed during esophagectomy and mortality. Cox regression models were used to adjust for potential confounding covariates. According to Kaplan-Meier analyses, the number of metastatic LNs was a good predictor for the prognosis of patients with esophageal squamous carcinoma and the dissection of ≥ 29 LNs during thoracic surgery significantly improved patient survival (P = 0.011).Lymph node metastasis rates may be a significant predictor for the prognosis of patients with esophageal squamous carcinoma. The number of LNs removed during esophagectomy is an independent predictor for the survival of patients with esophageal squamous carcinoma with maximal postoperative survival after the removal of ≥ 29 LNs.
Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence, survival, and risk factors. Although the genomic characteristics of ESCC have been extensively characterized, the ...genomic differences between different geographic regions remain unclear.
In this study, we sequenced 111 patients with ESCC from northern (NC) and southern (SC) China, combined their data with those of 1081 cases from previous reports, and performed a comparative analysis among different regions. In total, 644 ESCC cases were collected from six geographic regions (NC, SC, Xinjiang, China XJC, Japan JP, Vietnam VN, and Europe & America EA) as the discovery cohort. Validation cohort 1 included 437 patients with ESCC from the NC region. Validation cohort 2 included 54 and 57 patients from the NC and SC regions, respectively.
Patients with ESCC in different regions had different genomic characteristics, including DNA signatures, tumor mutation burdens, significantly mutated genes (SMGs), altered signaling pathways, and genes associated with clinical features. Based on both the DNA mutation signature and the mutation profile of the most common genes, the NC and SC groups were clustered close together, followed by the JP, XJC, EA, and VN groups. Compared to patients with ESCC from SC, SMGs, including
,
, and
were more frequently identified in patients with ESCC from NC. Furthermore, some genes (
and
) correlated with overall survival in completely opposite ways in patients with ESCC from different geographical regions.
Our study provides insights into genomic differences in ESCC among different regions. These differences may be related to differences in environmental carcinogens, incidence, and survival.
Objective
To investigate the feasibility of laparoscopic abdominal mobilization in patients with cancers of the esophagus or gastroesophageal junction who have a history of abdominal surgery.
Methods
...A total of 132 patients who underwent resection for cancers of the esophagus or gastroesophageal junction from August 2018 to March 2022 in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, were selected (66 patients with a history of abdominal surgery (observation group) and 66 patients without a history of abdominal surgery (control group)). All patients were treated with preoperative neoadjuvant therapy, based on the clinical stage. Thoracoscopic and laparoscopic resection was performed under general anesthesia. The intraoperative and postoperative conditions and surgical complications were compared between the two groups.
Results
No significant differences were found in baseline data between the observation group and the control group (
p
> 0.05). Laparoscopic abdominal mobilization was completed in both groups, and there were no significant differences between the two groups in the total operation time (272.50 ± 86.45) min vs. (257.55 ± 67.96) min, abdominal mobilization time (25.03 ± 9.82) min vs. (22.53 ± 3.88) min, blood loss (119.09 ± 72.17) ml vs. (104.39 ± 43.82) ml, and postoperative time to first flatus (3.44 ± 0.73) d vs. (3.29 ± 0.60) d (
p
> 0.05). The abdominal mobilization time was longer in observation group than that in control group (
p
= 0.057). After excluding the patients (31/66) with a history of simple appendectomy from the observation group, the abdominal mobilization time was significantly longer in observation group than that in control group (27.97 ± 12.16) min vs. (22.53 ± 3.88) min (
p
< 0.05). There were significantly fewer dissected abdominal lymph nodes in the observation group than in the control group (18.44 ± 10.87) vs. (23.09 ± 10.95),
p
< 0.05. After excluding the patients (15/66) with a history of abdominal tumor surgery from the observation group, there was no significant difference in the number of dissected abdominal lymph nodes between the two groups (20.62 ± 10.81) vs. (23.09 ± 10.95) (
p
> 0.05).In addition, no postoperative complications, such as intestinal obstruction, abdominal infection and bleeding, occurred in either group.
Conclusion
Patients with cancers of the esophagus or gastroesophageal junction who have a history of abdominal surgery are suitable for minimally invasive laparoscopic mobilization.
Objective. The objective of this article is to provide a high-profile review and discussion on the study design and statistical analysis of pivotal clinical trials conducted to demonstrate the safety ...and effectiveness of closed-loop investigational artificial pancreas device systems (APDSs) in premarket approval applications. Methods. The United States Food and Drug Administration (FDA) guidance on the content of investigational device exemption and premarket approval applications for APDSs is reviewed with special emphasis on study design and statistical analysis of the pivotal clinical trials. The two pivotal studies for the MiniMed 670G hybrid closed-loop system by Medtronic in their premarket approval application are summarized and discussed. Results. The United States FDA established detailed recommendations on the study design and statistical analysis of pivotal clinical trials for the industry that seek market investigational APDSs and for FDA scientific reviewers that regulate the device applications. The recommendations cover specifics regarding patient population, clinical endpoints, and strategies for data analysis. However, the two pivotal studies that demonstrated the effectiveness of the FDA-approved MiniMed 670G hybrid closed-loop system were not typical randomized controlled trials as per FDA recommendations. Conclusion. The development and regulation of investigational APDSs require careful and sophisticated clinical study designs and data analysis in premarket approval applications. The regulatory evaluation process of the APDSs is rather complicated since the devices consist of multiple components that collaboratively function to mimic human pancreases.
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