Maternal vitamin D status during pregnancy and infant's gut microbiota: a prospective cohort study.

Objectives: To prospectively explore the association of maternal serum 25(OH)D levels with the infant's gut microbiota in Chinese populations, and to evaluate its potential influence on the dynamic change patterns of offspring's gut microbiota from 1 to 6 months old. Methods: Eighty-seven mother-infant dyads (vitamin D insufficient group vs. normal group = 59 vs. 28) were included in this longitudinal study. Two fecal samples were collected for the included infant at home by the parents at 1 month of age ("M1 phase") and 6 months of age ("M6 phase"). Gut microbiota were profiled by 16S rRNA gene sequencing. We performed mixed effects models on alpha diversity metrics, PERMANOVA tests on beta diversity distances, and linear discriminant analysis (LDA) to identify differently abundant taxa. Results: We observed significantly lower Pielou's evenness and Shannon diversity in the vitamin D insufficient group in the M6 phase (p = 0.049 and 0.015, respectively), but not in the M1 phase (p > 0.05), and the dynamic changes in alpha diversity from 1 to 6 months old were significantly different according to maternal vitamin D status (p < 0.05). There were also significant differences in gut microbiota composition between the vitamin D insufficient group and normal group, both in the M1 and M6 phases (LDA score > 2.0, p < 0.05). Moreover, among the predicted metagenome functions, pathways related to amino acid biosynthesis, starch degradation, and purine nucleotides biosynthesis were enriched in the vitamin D insufficient group. Conclusion: Our findings highlight that maternal vitamin D status plays a pivotal role in shaping the early-life gut microbiota of the next generation.

The role of sex hormone binding globulin levels in the association of surgical and natural premature menopause with incident type 2 diabetes.

OBJECTIVE: To examine associations of surgical and natural menopause before the age of 40 years with the risk of type 2 diabetes (T2D) in women. METHODS: A total of 273,331 women from the United Kingdom were recruited between 2006 and 2010 in the UK Biobank (UKB) study, and 146,343 women aged 40 to 69 years who were postmenopausal at baseline were included in the analysis. Surgical menopause and natural premature menopause were defined as bilateral oophorectomy before the age of 40 and menopause before the age of 40 without oophorectomy, respectively. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between premature menopause and the incidence of T2D. RESULTS: During a median follow-up of 10.4 years, 47 women with surgical premature menopause, 244 women with natural premature menopause, and 4724 women without premature menopause developed T2D. Compared with women without premature menopause, both surgical premature menopause (adjusted HR = 1.46, 95 % CI: 1.09-1.95; P = 0.01) and natural premature menopause (adjusted HR = 1.20, 95 % CI: 1.06-1.37; P < 0.01) were associated with higher risks of incident T2D in the multivariable-adjusted models. Additionally, we observed a significant interaction between levels of sex hormone binding globulin (SHBG) (Pinteraction < 0.01) and the effects of premature menopause on incident T2D. The association between premature menopause and T2D risk appeared to be stronger in women with higher SHBG levels. Furthermore, a joint association was detected between premature menopause and the genetic risk score (GRS) of T2D, with a higher score indicating a higher risk of developingT2D. The highest risk of T2D was observed with higher T2D GRS and surgical premature menopause (adjusted HR = 2.61, 95 % CI: 1.65-4.12; P < 0.01). CONCLUSIONS: Surgical menopause and natural menopause before the age of 40 years were associated with an increased risk of T2D among postmenopausal women. The findings also suggest potential interactions of premature menopause with SHBG levels, with the association appearing to be stronger in higher SHBG levels, as well as a joint association between menopause status and genetic risk factors on T2D incidence.

Identification of protein signatures for lung cancer subtypes based on BPSO method.

The objective of this study was to identify protein biomarkers that can distinguish between LUAD and LUSC, critical for personalized treatment plans. The proteomic profiling data of LUAD and LUSC samples from TCPA database, along with phenotype and survival information from TCGA database were downloaded and preprocessed for analysis. We used BPSO feature selection method and identified 10 candidate protein biomarkers that have better classifying performance, as analyzed by t-SNE and PCA algorithms. To explore the causalities among these proteins and their associations with tumor subtypes, we conducted the PCStable algorithm to construct a regulatory network. Results indicated that 4 proteins, MIG6, CD26, NF2, and INPP4B, were directly linked to the lung cancer subtypes and may be useful in guiding therapeutic decision-making. Besides, spearman correlation, Cox proportional hazard model and Kaplan-Meier curve was employed to validate the biological significance of the candidate proteins. In summary, our study highlights the importance of protein biomarkers in the classification of lung cancer subtypes and the potential of computational methods for identifying key biomarkers and understanding their underlying biological mechanisms.

Prognostic value of 11-factor modified frailty index in postoperative adverse outcomes of elderly gastric cancer patients in China.

BACKGROUND: Preoperative evaluation of frailty is limited to a few surgical procedures. However, the evaluation in Chinese elderly gastric cancer (GC) patients remains blank. AIM: To validate and estimate the prognostic value of the 11-index modified frailty index (mFI-11) for predicting postoperative anastomotic fistula, intensive care unit (ICU) admission, and long-term survival in elderly patients (over 65 years of age) undergoing radical GC. METHODS: This study was a retrospective cohort study which included patients who underwent elective gastrectomy with D2 Lymph node dissection between April 1, 2017 and April 1, 2019. The primary outcome was 1-year all-cause mortality. The secondary outcomes were admission to ICU, anastomotic fistula, and 6-mo mortality. Patients were divided into two groups according to the optimal grouping cutoff of 0.27 points from previous studies: High risk of frailty marked as mFI-11High and low risk of frailty marked as mFI-11Low. Survival curves between the two groups were compared, and univariate and multivariate regression analyses were performed to explore the relationship between preoperative frailty and postoperative complications in elderly patients undergoing radical GC. The discrimination ability of the mFI-11, prognostic nutritional index, and tumor-node-metastasis pathological stage to identify adverse postoperative outcomes was assessed by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: A total of 1003 patients were included, of which 13.86% (139/1003) were defined as having mFI-11High and 86.14% (864/1003) as having mFI-11Low. By comparing the incidence of postoperative complications in the two groups of patients, it was found that mFI-11High patients had higher rates of 1-year postoperative mortality, admission to ICU, anastomotic fistula, and 6-mo mortality than the mFI-11Low group (18.0% vs 8.9%, P = 0.001; 31.7% vs 14.7%, P < 0.001; 7.9% vs 2.8%, P < 0.001; and 12.2% vs 3.6%, P < 0.001). Multivariate analysis revealed mFI-11 as an independent predictive indicator for postoperative outcome [1-year postoperative mortality: Adjusted odds ratio (aOR) = 4.432, 95% confidence interval (95%CI): 2.599-6.343, P = 0.003; admission to ICU: aOR = 2.058, 95%CI: 1.188-3.563, P = 0.010; anastomotic fistula: aOR = 2.852, 95%CI: 1.357-5.994, P = 0.006; 6-mo mortality: aOR = 2.438, 95%CI: 1.075-5.484, P = 0.033]. mFI-11 showed better prognostic efficacy in predicting 1-year postoperative mortality [area under the ROC curve (AUROC): 0.731], admission to ICU (AUROC: 0.776), anastomotic fistula (AUROC: 0.877), and 6-mo mortality (AUROC: 0.759). CONCLUSION: Frailty as measured by mFI-11 could provide prognostic information for 1-year postoperative mortality, admission to ICU, anastomotic fistula, and 6-mo mortality in patients over 65 years old undergoing radical GC.

Early assessment of circulating exosomal lncRNA-GC1 for monitoring neoadjuvant chemotherapy response in gastric cancer.

BACKGROUND: The timing of surgery for patients with gastric cancer (GC) who undergo neoadjuvant chemotherapy (neoCT) was mainly guided by serial radiologic imaging. However, an earlier assessment was indispensable to avoid delayed treatment for nonresponders and excessive toxicity for responders. Our previous study has identified circulating extracellular vesicles-derived lncRNA-GC1 as a biomarker for early detection and monitoring progression of GC. However, the potential role of neoCT remains poorly understood. METHODS: In this explorative biomarker analysis, we conducted a multi-cohort study to examine longitudinal levels of circulating extracellular vesicles-derived lncRNA-GC1 in 798 patients enrolled in the RESONANCE study (NCT01583361). Both circulating extracellular vesicles-derived lncRNA-GC1 and traditional gastrointestinal biomarkers were assessed at defined time nodes. Computed tomography (CT) scans were performed before treatment and 8-10 weeks and assessed based on the RECIST criteria. RESULTS: Circulating extracellular vesicles-derived lncRNA-GC1 could be detected in 96.3% of patients at baseline, and significant reductions were observed before cycle 2 (P<0.0001). Levels of circulating extracellular vesicles-derived lncRNA-GC1 showed a stronger correlation with tumor burden and exhibited earlier dynamic changes than the traditional gastrointestinal biomarkers during the first cycle of neoCT. Strong agreement was observed between circulating extracellular vesicles-derived lncRNA-GC1 response (reduction >50%) and radiographic response (Cohen's κ, 0.704). Importantly, circulating extracellular vesicles-derived lncRNA-GC1 maintained predictive value in two external cohorts. Patients with circulating extracellular vesicles-derived lncRNA-GC1 response showed superior disease-free survival [hazard ratio (HR), 0.6238; 95% CI, 0.4095-0.9501; P=0.0118] and overall survival (HR, 0.6131; 95% CI, 0.4016-0.9358; P=0.0090). CONCLUSION: Circulating extracellular vesicles-derived lncRNA-GC1 is an early marker of neoCT efficacy and predicts superior survival in GC patients treated with neoCT.

A Liquid Biopsy Signature for the Early Detection of Gastric Cancer in Patients.

BACKGROUND & AIMS: Diagnosing gastric cancer (GC) while the disease remains eligible for surgical resection is challenging. In view of this clinical challenge, novel and robust biomarkers for early detection thus improving prognosis of GC are necessary. The present study is to develop a blood-based long noncoding RNA (LR) signature for the early-detection of GC. METHODS: The present 3-step study incorporated data from 2141 patients, including 888 with GC, 158 with chronic atrophic gastritis, 193 with intestinal metaplasia, 501 healthy donors, and 401 with other gastrointestinal cancers. The LR profile of stage I GC tissue samples were analyzed using transcriptomic profiling in discovery phase. The extracellular vesicle (EV)-derived LR signature was identified with a training cohort (n = 554) and validated with 2 external cohorts (n = 429 and n = 504) and a supplemental cohort (n = 69). RESULTS: In discovery phase, one LR (GClnc1) was found to be up-regulated in both tissue and circulating EV samples with an area under the curve (AUC) of 0.9369 (95% confidence interval [CI], 0.9073-0.9664) for early-stage GC (stage I/II). The diagnostic performance of this biomarker was further confirmed in 2 external validation cohorts (Xi'an cohort, AUC: 0.8839; 95% CI: 0.8336-0.9342; Beijing cohort, AUC: 0.9018; 95% CI: 0.8597-0.9439). Moreover, EV-derived GClnc1 robustly distinguished early-stage GC from precancerous lesions (chronic atrophic gastritis and intestinal metaplasia) and GC with negative traditional gastrointestinal biomarkers (CEA, CA72-4, and CA19-9). The low levels of this biomarker in postsurgery and other gastrointestinal tumor plasma samples indicated its GC specificity. CONCLUSIONS: EV-derived GClnc1 serves as a circulating biomarker for the early detection of GC, thus providing opportunities for curative surgery and improved survival outcomes.

Association of Gestational Diabetes With the Dynamic Changes of Gut Microbiota in Offspring From 1 to 6 Months of Age.

AIMS: The present study aimed to prospectively evaluate the influence of gestational diabetes mellitus (GDM) on the gut microbiota in 1- and 6-month-old offspring, as well as the dynamic changes from 1 to 6 months of age. METHODS: Seventy-three mother-infant dyads (34 GDM vs 39 non-GDM) were included in this longitudinal study. Two fecal samples were collected for each included infant at home by the parents at 1 month of age ("M1 phase") and again at 6 months of age ("M6 phase"). Gut microbiota were profiled by 16S rRNA gene sequencing. RESULTS: Although no significant differences were observed in diversity and composition between GDM and non-GDM groups in the M1 phase, we observed differential structures and composition in the M6 phase between the 2 groups (P < .05), with lower levels of diversity, 6 depleted and 10 enriched gut microbes among infants born to GDM mothers. The dynamic changes in alpha diversity from the M1 to M6 phase were also significantly different according to GDM status (P < .05). Moreover, we found that the altered gut bacteria in the GDM group were correlated with infants' growth. CONCLUSION: Maternal GDM was associated not only with the community structure and composition in the gut microbiota of offspring at a specific time point, but also with the differential changes from birth to infancy. Altered colonization of the GDM infants' gut microbiota might affect their growth. Our findings underscore the critical impact of GDM on the formation of early-life gut microbiota and on the growth and development of infants.

Identification of key biomarkers for STAD using filter feature selection approaches.

Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Discovery of diagnostic biomarkers prompts the early detection of GC. In this study, we used limma method combined with joint mutual information (JMI), a machine learning algorithm, to identify a signature of 11 genes that performed well in distinguishing tumor and normal samples in a stomach adenocarcinoma cohort. Other two GC datasets were used to validate the classifying performances. Several of the candidate genes were correlated with GC tumor progression and survival. Overall, we highlight the application of feature selection approaches in the analysis of high-dimensional biological data, which will improve study accuracies and reduce workloads for the researchers when identifying potential tumor biomarkers.

3D laparoscopic-assisted vs open gastrectomy for carcinoma in the remnant stomach: A retrospective cohort study.

BACKGROUND: Three-dimensional (3D) laparoscopic technique has gradually been applied to the treatment of carcinoma in the remnant stomach (CRS), but its clinical efficacy remains controversial. AIM: To compare the short-term and long-term results of 3D laparoscopic-assisted gastrectomy (3DLAG) with open gastrectomy (OG) for CRS. METHODS: The clinical data of patients diagnosed with CRS and admitted to the First Medical Center of Chinese PLA General Hospital from January 2016 to January 2021 were retrospectively collected. A total of 84 patients who met the inclusion and exclusion criteria were enrolled. All their clinical data were collected and a database was established. All patients were treated with 3DLAG or OG by experienced surgeons and were divided into two groups based on the different surgical methods mentioned above. By using outpatient and telephone follow-up, we were able to determine postoperative survival and tumor status. The postoperative short-term efficacy and 1-year and 3-year overall survival (OS) rates were compared between the two groups. RESULTS: Among 84 patients with CRS, 48 were treated with OG and 36 with 3DLAG. All patients successfully completed surgery. There was no significant difference between the two groups in terms of age, gender, body mass index, ASA score, initial disease state (benign or malignant), primary surgical anastomosis method, interval time of carcinogenesis, and tumorigenesis site. Patients in the 3DLAG group experienced less intraoperative blood loss (188.33 ± 191.35 mL vs 305.83 ± 303.66 mL; P = 0.045) and smaller incision (10.86 ± 3.18 cm vs 20.06 ± 5.17 cm; P < 0.001) than those in the OG group. 3DLAGC was a more minimally invasive method. 3DLAGC retrieved significantly more lymph nodes than OG (14.0 ± 7.17 vs 10.73 ± 6.82; P = 0.036), whereas the number of positive lymph nodes did not differ between the two groups (1.56 ± 2.84 vs 2.35 ± 5.28; P = 0.413). The complication rate (8.3% vs 20.8%; P = 0.207) and intensive care unit admission rate (5.6% vs 14.5%; P = 0.372) were equivalent between the two groups. In terms of postoperative recovery, the 3DLAGC group had a lower visual analog score, shorter indwelling time of gastric and drainage tubes, shorter time of early off-bed motivation, shorter time of postoperative initial flatus and initial soft diet intake, shorter postoperative hospital stay and total hospital stay, and there were significant differences, showing better short-term efficacy. The 1-year and 3-year OS rates of OG group were 83.2% [95% confidence interval (CI): 72.4%-95.6%] and 73.3% (95%CI: 60.0%-89.5%) respectively. The 1-year and 3-year OS rates of the 3DLAG group were 87.3% (95%CI: 76.4%-99.8%) and 75.6% (95%CI: 59.0%-97.0%), respectively. However, the 1-year and 3-year OS rates were similar between the two groups, which suggested that long-term survival results were comparable between the two groups (P = 0.68). CONCLUSION: Compared with OG, 3DLAG for CRS achieved better short-term efficacy and equivalent oncological results without increasing clinical complications. 3DLAG for CRS can be promoted safely and effectively in selected patients.

Does the addition of Braun anastomosis to Billroth II reconstruction on laparoscopic-assisted distal gastrectomy benefit patients?

BACKGROUND: Operation is the primary therapeutic option for patients with distal gastrectomy. Braun anastomosis is usually performed after Billroth II reconstruction, which is wildly applied on distal gastrectomy because it is believed to benefit patients. However, studies are needed to confirm that. AIM: To identify whether the addition of Braun anastomosis to Billroth II reconstruction on laparoscopy-assisted distal gastrectomy benefits patients. METHODS: A total of 143 patients with gastric cancer underwent laparoscopy-assisted distal gastrectomy at Centre 1 of PLA general hospital between January 2015 and December 2019. Clinical data of the patients were collected, and 93 of the 143 patients were followed up. These 93 patients were divided into two groups: Group 1 (Billroth II reconstruction, 33 patients); and Group 2 (Billroth II reconstruction combined with Braun anastomosis, 60 patients). Postoperative complication follow-up data and relevant clinical data were compared between the two groups. RESULTS: There were no significant differences between Group 1 and Group 2 in postoperative complications (6.1% vs 6.7%, P = 0.679), anal exhaust time or blood loss. The follow-up prevalence of reflux gastritis indicated no significant difference between Group 1 and Group 2 (68.2% vs 51.7%, P = 0.109). The follow-up European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 scores revealed no evident difference between Group 1 and Group 2 as well. Group 1 had a shorter operating time than Group 2 on average (234.6 min vs 262.0 min, P = 0.017). CONCLUSION: Combined with Billroth II reconstruction, Braun anastomosis has been applied due to its ability to reduce the prevalence of reflux gastritis. Whereas in this study, the prevalence of reflux gastritis showed no significant difference, leading to a conclusion that under the circumstance of Braun anastomosis costing more time and more money, simple Billroth II reconstruction should be widely applied.

Laparoscopic-assisted vs open transhiatal gastrectomy for Siewert type II adenocarcinoma of the esophagogastric junction: A retrospective cohort study.

BACKGROUND: The studies of laparoscopic-assisted transhiatal gastrectomy (LTG) in patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG) are scarce. AIM: To compare the surgical efficiency of LTG with the open transhiatal gastrectomy (OTG) for patients with Siewert type II AEG. METHODS: We retrospectively evaluated a total of 578 patients with Siewert type II AEG who have undergone LTG or OTG at the First Medical Center of the Chinese People's Liberation Army General Hospital from January 2014 to December 2019. The short-term and long-term outcomes were compared between the LTG (n = 382) and OTG (n = 196) groups. RESULTS: Compared with the OTG group, the LTG group had a longer operative time but less blood loss, shorter length of abdominal incision and an increased number of harvested lymph nodes (P < 0.05). Patients in the LTG group were able to eat liquid food, ambulate, expel flatus and discharge sooner than the OTG group (P < 0.05). No significant differences were found in postoperative complications and R0 resection. The 3-year overall survival and disease-free survival performed better in the LTG group compared with that in the OTG group (88.2% vs 79.2%, P = 0.011; 79.7% vs 73.0%, P = 0.002, respectively). In the stratified analysis, both overall survival and disease-free survival were better in the LTG group than those in the OTG group for stage II/III patients (P < 0.05) but not for stage I patients. CONCLUSION: For patients with Siewert type II AEG, LTG is associated with better short-term outcomes and similar oncology safety. In addition, patients with advanced stage AEG may benefit more from LTG in the long-term outcomes.

Influences of gestational diabetes mellitus on the oral microbiota in offspring from birth to 1 month old.

BACKGROUND: Maternal gestational diabetes mellitus (GDM) had long-term influences on the health of their children. However, the influences of GDM on the oral microbiota, which was closely related to oral and systemic health in offspring, were less documented. The present study aimed to explore the oral microbiota of neonates born to mothers with GDM is differentially colonized compared with those born to mothers without GDM, and whether any such differences persist to 1 month of age. METHODS: Oral samples were collected from children of mothers with (n = 20) and without GDM (n = 34) at birth and again at an average age of 1 month. The oral microbiota was characterized by 16S rRNA sequencing (V3-V4). Differences in diversity and composition according to maternal GDM status were assessed, and different metabolic functional pathways and microbial ecological networks were also analyzed. RESULTS: Although no significant differences were observed in diversity metrics between GDM and non-GDM groups (P > 0.05), we found significant differences in the taxonomic composition of oral microbiota from phylum to genus level between the two groups, with the GDM group exhibiting less abundance of Veillonella in both "Day 1" (P < 0.001) and "Day 30" (P < 0.05) phases. Metabolic pathways analysis showed that 5-aminoimidazole ribonucleotide biosynthesis and inosine-5'-phosphate biosynthesis were enriched in GDM subjects in the "Day 30" phase. Moreover, ecological network analysis revealed apparent differences between GDM and control groups, with the non-GDM group containing more high-degree nodes and microbial interactions compared with the GDM group. CONCLUSION: Maternal GDM was associated with an altered oral microbial composition in neonates, although the distinct difference between GDM and non-GDM groups diminished in infancy. The oral microbiota functions and ecological networks differed dramatically between the two groups, highlighting the importance of maternal GDM status on initial oral microbiota in offspring.

Local OAM manipulation of a terahertz wave from the air filament by chirping the few-cycle vortex pump laser.

We propose a scheme to manipulate the local orbital angular momentum (OAM) of the ultra-broadband (0.1-30 THz) terahertz (THz) waves from the laser-induced short air filament via chirping the few-cycle vortex laser pump. The simulation results show that either the THz vortex pulses with linear azimuth-dependent phases or the THz angular accelerating vortex beams (AAVBs) with nonlinear azimuth-dependent phases can be produced by tuning the chirp parameter of the pump. Thus, the dominant physical mechanism for THz generation can be determined. The THz temporal and transverse spatial distributions can be also controlled by the chirp parameter. Furthermore, their local OAM density distributions present very complex structures because most of the modulated azimuthal intensity and the corresponding local angular helicity distributions are not able to cancel out completely. Via analyzing the simulated THz results at the different pump intensities, we classify the initial pump intensity into three cases. For the low intensity case, the Kerr effect comes into prominence, so the generated THz radiation shall be vortex pulses. While for the high intensity case, the leading plasma effect dominates. In contrast, when the pump intensity is at the medium level, the Kerr nonlinearity and the plasma effect may be comparable and competitive. Basically, THz AAVBs are generated for both high and medium intensity cases. Our study will provide the possibility for studying the optically induced rotation technology more intuitively from the perspective of angular momentum transfer.

The abdominal-transhiatal surgical approach versus the thoracoabdominal surgical approach in Siewert type II adenocarcinoma of the esophagogastric junction: protocol for a multicenter prospective, open, parallel, and randomized controlled trial.

BACKGROUND: To date, Siewert type II adenocarcinoma of the esophagogastric junction (ST-II AEG) can be removed radically utilizing either the abdominal-transhiatal (TH) or the right thoracoabdominal (RTA) approaches. Because of a paucity of high-quality direct evidence, the appropriate surgical approach for ST-II AEG remains debatable. In the present, only several retrospective studies are available, representing ambiguous results. Thus, prospective randomized clinical trials are demanded to compare the survival, oncological outcomes, safety and efficiency and life quality between the TH and RTA approach in patients with resectable AEG of Siewert type II. METHODS: A prospective, multicenter, open, randomized, and parallel controlled study named S2AEG will be conducted. Three hundred and twelve patients who match the inclusion criteria but not the exclusion criteria will be participating in the trial and randomly divided into the TH (156) and RTA (156) cohorts. The primary efficacy endpoint is the 3-year disease-free survival (DFS) following the operation. The rate of R0-resection, the number and site of lymph nodes infiltrated and dissected, postoperative complications, hospital days and life quality are the second endpoints. DISCUSSION: This study is the first prospectively randomized controlled trial aiming to compare the surgical outcomes between TH and RTA approaches in patients with resectable ST-II AEG. It is hypothesized that patients in the TH cohort would harvest equivalent oncological results and survival while maintaining acceptable life quality when compared to patients in the RTA cohort. Our findings will provide high-level clinical evidence for clinical decision-making on the appropriate surgical approach for patients with ST-II AEG. Embarked in November 2019, this research will be completed 3 years after the final participant's enrolment date. TRIAL REGISTRATION: Clinical Trial.gov ID: NCT04910789 May 29, 2021. Name: S2AEG.

Circulating exosomal gastric cancer-associated long noncoding RNA1 as a noninvasive biomarker for predicting chemotherapy response and prognosis of advanced gastric cancer: A multi-cohort, multi-phase study.

BACKGROUND: A previous validated study has identified the diagnostic value of circulating exosomal lncRNA-GC1 for detecting and monitoring gastric cancer. We aimed to further determine the predictive role of circulating exosomal lncRNA-GC1 for prognosis and chemotherapy response. METHODS: We retrospectively conducted a multi-phase analysis with four independent cohorts of 981 patients. A training cohort was used to generate the predictive model. One internal and two external cohorts were recruited as validation cohorts. Patients with stage II or III gastric cancer in the combined cohort were used to evaluate the predictive value of circulating exosomal lncRNA-GC1 for chemotherapy response. FINDINGS: In the training cohort, circulating exosomal lncRNA-GC1 was identified as an independent prognostic predictor for disease-free and overall survival. A prognostic risk stratification model based on circulating exosomal lncRNA-GC1 and AJCC stage revealed better predictive accuracy for disease-free and overall survival than the traditional AJCC stage system alone (C-index: DFS 0.701 vs 0.614; OS 0.720 vs 0.611, both P<0.05). And it has been further verified in the validation cohorts. In interaction analysis, for stage II and III GC, patients with low-level of circulating exosomal lncRNA-GC1 derived more survival benefit from adjuvant chemotherapy (P < 0.05); while those with high-level did not. INTERPRETATION: Measurement of circulating exosomal lncRNA-GC1 provides clinically important prognostic information and could complement the AJCC stage to optimize decision-making for selecting patients who could benefit more from fluorouracil-based chemotherapy after surgery. FUNDING: The funders are listed in the Acknowledgement.

Ambient air pollution, healthy diet and vegetable intakes, and mortality: a prospective UK Biobank study.

BACKGROUND: Recent studies suggest potential interactions of air pollutants with dietary factors and genetic susceptibility on mortality risk; however, evidence from prospective studies is still lacking. We aimed to assess the association between air pollution and mortality, and investigate the modification effects of a healthy diet and genetic susceptibility. METHODS: A total of 386 937 participants were enrolled from 2006 to 2010 and followed up to 2018 in the UK Biobank study. The annual average air pollutant concentrations of particulate matter (PM) with diameters ≤2.5 (PM2.5), ≤10 (PM10) and between 2.5 and 10 µm (PM2.5-10) and nitrogen oxides (NO2 and NOx) were calculated and linked to participants' residential addresses. Healthy dietary patterns were evaluated by a healthy diet score (HDS) based on intakes of vegetables, fruit, fish, unprocessed red meat and processed meat. We also calculated genetic risk score (GRS) of the lifespan. We examined potential interactions by setting variable cross-product terms of air pollutants with diets or GRS in the models. RESULTS: We identified 11 881 deaths [2426 from cardiovascular diseases (CVD), 1211 from coronary heart disease (CHD) and 466 from stroke] during a median follow-up of 8.9 years. We found that PM2.5 [hazard ratio (HR), 1.27; 95% CI, 1.05-1.55], PM10 (HR, 1.18; 95% CI, 1.04-1.34), NO2 (HR, 1.05; 95% CI, 1.01-1.08), and NOx (HR, 1.02; 95% CI, 1.01-1.03) were associated with all-cause mortality. PM2.5 was also associated with increased risks of CVD mortality (HR, 1.68; 95% CI, 1.10-2.56) and CHD mortality (HR, 2.08; 95% CI, 1.16-3.75). In addition, we found that adherence to healthy dietary patterns modified associations of PM2.5, NO2 and NOx with all-cause mortality (P-interaction = 0.006, 0.006 and 0.02, respectively). Among the individual dietary components, vegetable intakes showed interactions with PM2.5, NO2 and NOx (P-interaction = 0.007, 0.004 and 0.02, respectively). The associations between air pollutants and increased risks of all-cause mortality were attenuated among participants with higher vegetable intakes. We did not observe interactions between air pollutants and HDS on CVD, CHD or stroke mortality (P-interaction > 0.05). Besides, we did not find interactions between air pollutants and genetic risk for lifespan on mortality risk. CONCLUSION: This study provides evidence linking long-term exposure to various air pollutants to the risk of all-cause, CVD and CHD mortality, and the potential attenuation of a healthy diet, especially high vegetable intakes, on such relations. Our findings highlight the importance of adherence to a healthy diet in lowering ambient air-pollution-related mortality risk.

Red meat consumption and all-cause and cardiovascular mortality: results from the UK Biobank study.

PURPOSE: To investigate the prospective associations between red meat consumption and all-cause and cardiovascular diseases (CVD) mortality, and to assess the modification effects of lifestyle and genetic risk factors. METHODS: 180,642 individuals free of CVD or cancer were enrolled from 2006 to 2010 and followed up to 2018 in the UK Biobank. Information on demographics, lifestyles, and medical history was collected through a baseline touchscreen questionnaire. The information on diet was collected through a single touchscreen food-frequency questionnaire. A total of ten single-nucleotide polymorphisms were used to calculate the genetic risk score (GRS) of trimethylamine N-oxide (TMAO), a gut microbiota metabolite from red meat. Adjusted Cox proportional hazard regression models were used to assess the association of red meat consumption with mortality. RESULTS: We documented 3596 deaths [655 CVD deaths, 285 coronary heart disease (CHD) deaths, and 149 stroke deaths] during median 8.6 years of follow-up. Compared with the lowest red meat intake (< 1.5 times/week), the highest red meat intake (≥ 3.0 times/week) was associated with a 20%, 53%, and 101% elevated risk for CVD, CHD, and stroke mortality (P for trend = 0.04, 0.007, and 0.02, respectively), but not all-cause mortality. We found that the associations between red meat intake and mortality were not modified by dietary and lifestyle factors, as well as TMAO GRS. In addition, substitution analyses showed that a decrease in red meat consumption and an increase in the consumption of poultry or cereal was significantly associated with 9%-16% lower CVD or CHD mortality risk. CONCLUSION: Our results indicated that red meat consumption was associated with higher risks of CVD, CHD, and stroke mortality, and the associations were not modified by lifestyle and genetic risk factors. Replacing red meat by poultry or cereal was related to lower risks of CVD and CHD mortality.

The Lifestyle-Related Cardiovascular Risk Is Modified by Sleep Patterns.

OBJECTIVE: To prospectively assess whether sleep patterns modified lifestyle-associated cardiovascular disease (CVD) risk. PATIENTS AND METHODS: This study included 393,690 participants without CVD at baseline measurements between March 13, 2006, and October 1, 2010, from UK Biobank. A lifestyle score was calculated on the basis of the 4 lifestyle factors (smoking, alcohol consumption, physical activity, and diet), and sleep patterns were constructed based on sleep duration, chronotype, insomnia, snoring, and daytime dozing. RESULTS: During a median follow-up of 8.93 years, we observed 10,218 incident CVD events, including 6595 myocardial infarctions (MIs) and 3906 strokes. We found that sleep patterns significantly modified the relations of the lifestyle score with incident CVD (P for interaction =.007) and MI (P for interaction =.004). Among participants with a poor sleep pattern, unfavorable lifestyle (per score increase) was associated with 25% (95% CI, 13% to 39%) and 29% (95% CI, 13% to 47%) increased risks for CVD and MI, while among participants with a healthy sleep pattern, unfavorable lifestyle was associated with 18% (95% CI, 15% to 21%) and 17% (95% CI, 13% to 21%) increased risks for CVD and MI. CONCLUSION: Our results indicate that adherence to a healthy sleep pattern may attenuate the CVD risk associated with an unfavorable lifestyle.

Panoramic smoking burden and genetic susceptibility in relation to all-cause and cause-specific mortality: a prospective study in UK Biobank.

BACKGROUND AND AIMS: Various smoking behaviors, including smoking initiation, age of initiation, heaviness of smoking and smoking cessation, have been individually related to the risk of mortality; however, no study has assessed these smoking behaviors jointly in relation to mortality. Our study aimed to measure prospectively the association of panoramic smoking burden (PSB), generated from the four aforementioned smoking behaviors, with all-cause and cause-specific mortality, and measure whether such associations are modified by genetic variations. DESIGN: Prospective cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 360 937 participants aged between 37 and 73 years were enrolled in 2006-10 and -followed-up to 2018. MEASUREMENTS: The exposure was PSB, constructed based on four smoking behaviors including smoking initiation, age of initiation, heaviness of smoking and smoking cessation in a weighted method. A genetically determined PSB was also constructed with smoking-associated single nucleotide polymorphisms (SNPs) and categorized into tertiles. The primary outcomes were all-cause and cause-specific mortality. FINDINGS: We identified 15 968 deaths [9022 from cancer and 5092 from cardiovascular disease (CVD)] over a median of 11.36 years' follow-up. For all-cause mortality, compared with participants with the PSB of zero, the hazard ratios of participants who had a PSB of one, two, three and four were 1.23 [95% confidence intervals (CI) = 1.18-1.29), 1.66 (95% CI = 1.59-1.75), 3.33 (95% CI = 3.17-3.51) and 5.76 (95% CI = 4.66-7.13), respectively. Among participants within each genetic risk category, low and intermediate PSB were associated with 45-58% reduced risk of all-cause death compared with high PSB. Analysis of population-attributable risk percentage indicated that 21.9, 19.1 and 24.7% of all-cause-, cancer- and CVD-specific death could have been avoided if all ever smokers initiated smoking after age 18 years, smoked < 20 cigarettes/day and quit smoking. CONCLUSIONS: The panoramic smoking burden, based on smoking initiation, age of initiation, heaviness of smoking and smoking cessation, appears to be associated with all-cause and cause-specific mortality in a gradient manner with increasing panoramic smoking burden independent of other traditional and genetic risk factors.