Armored bicistronic CAR T cells with dominant-negative TGF-ß receptor II to overcome resistance in glioblastoma.

Chimeric antigen receptor (CAR) T cells have shown significant efficacy in hematological diseases. However, CAR T therapy has demonstrated limited efficacy in solid tumors, including glioblastoma (GBM). One of the most important reasons is the immunosuppressive tumor microenvironment (TME), which promotes tumor growth and suppresses immune cells used to eliminate tumor cells. The human transforming growth factor ß (TGF-ß) plays a crucial role in forming the suppressive GBM TME and driving the suppression of the anti-GBM response. To mitigate TGF-ß-mediated suppressive activity, we combined a dominant-negative TGF-ß receptor II (dnTGFßRII) with our previous bicistronic CART-EGFR-IL13Rα2 construct, currently being evaluated in a clinical trial, to generate CART-EGFR-IL13Rα2-dnTGFßRII, a tri-modular construct we are developing for clinical application. We hypothesized that this approach would more effectively subvert resistance mechanisms observed with GBM. Our data suggest that CART-EGFR-IL13Rα2-dnTGFßRII significantly augments T cell proliferation, enhances functional responses, and improves the fitness of bystander cells, particularly by decreasing the TGF-ß concentration in a TGF-ß-rich TME. In addition, in vivo studies validate the safety and efficacy of the dnTGFßRII cooperating with CARs in targeting and eradicating GBM in an NSG mouse model.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.

OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.

Assessment of Laparoscopic Indocyanine Green Tracer-guided Lymphadenectomy After Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness of indocyanine green (ICG)-guided lymph node (LN) dissection during laparoscopic radical gastrectomy after neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC). BACKGROUND: Studies on ICG imaging use in patients with LAGC on NAC are rare. METHODS: Patients with gastric adenocarcinoma (clinical T2-4NanyM0) who received NAC were randomly assigned to receive ICG-guided laparoscopic radical gastrectomy or laparoscopic radical gastrectomy alone. Here, we reported the secondary endpoints including the quality of lymphadenectomy (total retrieved LNs and LN noncompliance) and surgical outcomes. RESULTS: Overall, 240 patients were randomized. Of whom, 236 patients were included in the primary analysis (118 in the ICG group and 118 in the non-ICG group). In the ICG group, the mean number of LNs retrieved was significantly higher than in the non-ICG group within the D2 dissection (48.2 vs 38.3, P < 0.001). The ICG fluorescence guidance significantly decreased the LN noncompliance rates (33.9% vs 55.1%, P = 0.001). In 165 patients without baseline measurable LNs, ICG significantly increased the number of retrieved LNs and decreased the LN noncompliance rate ( P < 0.05). For 71 patients with baseline measurable LNs, the quality of lymphadenectomy significantly improved in those who had a complete response ( P < 0.05) but not in those who did not ( P > 0.05). Surgical outcomes were comparable between the groups ( P > 0.05). CONCLUSIONS: ICG can effectively improve the quality of lymphadenectomy in patients with LAGC who underwent laparoscopic radical gastrectomy after NAC.

All-optical Einstein-Podolsky-Rosen steering swapping.

Einstein-Podolsky-Rosen (EPR) steering, an important resource in quantum information, describes the ability of one party to influence the state of another party through local measurements. It differs from Bell nonlocality and entanglement due to its asymmetric property. EPR steering swapping allows two spatially independent parties to present EPR steering without direct interaction. Here, we theoretically propose an all-optical EPR steering swapping (AOSS) scheme based on low-noise high-broadband optical parametric amplifiers (OPAs). A low-noise high-broadband OPA is utilized to implement the function of Bell-state measurement without detection, avoiding the optic-electro and electro-optic conversions. After AOSS, one-way and two-way EPR steering between two independent optical modes can be obtained. Our scheme provides a guidance for the construction of a measurement-free, all-optical broadband quantum network utilizing EPR steering swapping.

CircUBA2 promotes the cancer stem cell-like properties of gastric cancer through upregulating STC1 via sponging miR-144-5p.

BACKGROUND: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. METHODS: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. RESULTS: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. CONCLUSIONS: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC.

Deterministic All-Optical Continuous-Variable Quantum Telecloning.

Quantum telecloning, a pivotal multiuser quantum communication protocol in the realm of quantum information science, facilitates the copy of a quantum state across M distinct locations through teleportation technique. In the continuous-variable regime, the implementation of quantum telecloning necessitates the distribution of multipartite entanglement among the sender and M receiver parties. Following this, the sender carries out optic-electro conversion and transmits information via classical channel to M spatially separated receivers simultaneously. To successfully reconstruct the input state, electro-optic conversion needs to be employed by each receiver. However, due to these conversions, the bandwidth of the optical mode in this process is largely constrained. In this Letter, we present an all-optical version of the 1→2 continuous-variable quantum telecloning scheme, wherein both optic-electro and electro-optic conversions are replaced by optical components. Our scheme allows the two receivers to achieve input state reconstruction solely by utilizing beam splitters, significantly simplifying its complexity. We experimentally demonstrate all-optical 1→2 quantum telecloning of coherent state and achieve the fidelities of 58.6%±1.0% and 58.6%±1.1% for two clones, exceeding the corresponding classical limits (51.9%±0.5% and 51.9%±0.6%). Our results establish a platform for constructing a flexible all-optical multiuser quantum network and promote the field of all-optical quantum information processing.

Orbital Angular Momentum Multiplexed Deterministic All-Optical Quantum Erasure-Correcting Code.

Quantum erasure-correcting code, which corrects the erasure in the transmission of quantum information, is an important protocol in quantum information. In the continuous variable regime, the feed-forward technique is needed for realizing quantum erasure-correcting code. This feed-forward technique involves optic-electro and electro-optic conversions, limiting the bandwidth of quantum erasure-correcting code. Moreover, in the previous continuous variable quantum erasure-correcting code, only two modes are protected against erasure, limiting the applications of quantum erasure-correcting code in high-capacity quantum information processing. In this Letter, by utilizing the orbital angular momentum (OAM) multiplexed entanglement in the encoding part and replacing the feed-forward technique with OAM mode-matched phase-sensitive amplifier in the decoding part, we experimentally demonstrate a scheme of OAM multiplexed deterministic all-optical quantum erasure-correcting code. We experimentally demonstrate that four orthogonal modes can be simultaneously protected against one arbitrary erasure. Our results provide an all-optical platform to implement quantum erasure-correcting code and may have potential applications in implementing all-optical fault-tolerant quantum information processing.

Deterministic All-Optical Quantum Teleportation of Four Degrees of Freedom.

Quantum teleportation, disembodied transfer of the unknown quantum state between two locations, has been experimentally demonstrated for both discrete and continuous variable states in one degree of freedom (DOF). Generally, multiple DOFs are needed to fully characterize a quantum state. Therefore, to implement intact quantum teleportation, multiple DOFs of quantum state should be teleported simultaneously. Recently, teleporting a single photon encoded in two DOFs has been experimentally demonstrated in discrete variable regime. However, the teleportation of more than two DOFs remains unexplored. Here, by utilizing continuous variable hyperentanglement in four DOFs (azimuthal and radial indexes of Laguerre-Gaussian mode, frequency, and polarization), we experimentally demonstrate deterministic all-optical quantum teleportation of four DOFs. Moreover, we experimentally construct 24 parallel teleportation channels. Our results pave the way for deterministically implementing multiple-DOF quantum communication protocols.

Cardiometabolic factors and population risks of cardiovascular disease in community-dwelling adults with varied blood pressure statuses.

AIMS: To examine the differential associations between cardiometabolic risk factors and cardiovascular disease (CVD), and to evaluate the population-attributable fractions (PAFs) for CVD among community-dwelling adults with varied blood pressure (BP) statuses. METHODS: This prospective cohort study included participants without prevalent CVD from a subcohort of the China Patient-Centred Evaluative Assessment of Cardiac Events Million Persons Project. Participants were divided into four BP groups according to the American College of Cardiology/American Heart Association guidelines. The study exposure comprised the selected cardiometabolic risk factors, including waist circumference (WC), body mass index, (BMI) heart rate, fasting blood glucose (FBG), low-density lipoprotein cholesterol, and remnant cholesterol. The outcome was hospitalizations for CVD. Cox proportional hazard models were conducted, and the PAFs were calculated in the analysis. RESULTS: Among the 94 183 participants (39.0% were men, mean age: 54.2 years), 26.6% had Stage 1 hypertension and 30.8% had Stage 2 hypertension. A total of 6065 hospitalizations for CVD were captured after a median follow-up of 3.5 years. BP (per 1-standard deviation [SD]: hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.29, 1.40), FBG (per 1-SD: HR 1.16, 95% CI 1.14, 1.19) and WC (per 1-SD: HR 1.41, 95% CI 1.36, 1.47) were three major contributors to CVD events. BP status significantly modified the associations of abdominal obesity, suboptimal BMI, suboptimal heart rate and abnormal FBG with CVD, with stronger associations with CVD observed in optimal BP groups compared to hypertensive groups (p for risk factor-by-BP group interaction <0.05). Participants with all cardiometabolic risk factors were at the highest risk for CVD, accounting for 35.6% (95% CI 30.0, 40.8) of the PAF for CVD. Among the risk factors, BP control explained the highest PAF for CVD (15.1%, 95% CI 8.2, 21.4) The overall PAFs of cardiometabolic risk factors for CVD were higher among the normotensive participants compared to the hypertensive participants. CONCLUSIONS: The awareness and control rates of hypertension were extremely low among Southern Chinese adults. BP status significantly modified the associations between cardiometabolic risk factors and CVD, and the overall PAFs for CVD were higher among people with normal BP. Dedicated efforts are needed to improve the management of cardiometabolic factors.

Life's Essential 8 and risk of incident heart failure in community population without cardiovascular disease: Results of the sub-cohort of China PEACE Million Persons Project.

OBJECTIVE: The American Heart Association has introduced the Life's Essential 8 metrics to evaluate and promote cardiovascular health (CVH) and we aimed to evaluate the association of CVH and incident heart failure (HF). METHODS: The China PEACE Million Persons Project is a population-based cardiovascular disease (CVD) screening study. This was a sub-cohort of the project that included individuals free of CVD at baseline. Components and classifications of CVH, including diet, physical activity, smoking status, sleep status, body mass index (BMI), non-high density lipoprotein (non-HDL), blood glucose and blood pressure, were determined based on the Life's Essential 8. CVH status was categorized as poor, intermediate and ideal status. HF cases were identified by linking hospital records. RESULTS: Among the cohort (n = 38,571, median age 54 years and women 60.5%), proportion of individuals with poor, intermediate and ideal CVH was 30.7%, 56.9% and 12.4%. After a median follow-up of 3.56 years, the incidence of HF in individuals with poor, intermediate and ideal CVH was 2.5%, 1.1% and 0.5% respectively. Compared to poor CVH, intermediate (adjusted HR: 0.52 [95% CI: 0.43-0.61]) and ideal CVH (adjusted HR: 0.38 [95% CI: 0.26-0.57]) were associated with a lower HF risk. A gradient of association between CVH and HF risk was observed (P-trend<0.001). Ideal physical activity, ideal smoking status, and intermediate and ideal status of BMI, blood glucose and blood pressure were associated with a lower HF risk. CONCLUSION: Poor CVH was associated with an increased risk of HF, and promotion of CVH may help prevent HF development.

Long-term oncological outcomes of 3D versus 2D laparoscopic gastrectomy for gastric cancer: a randomized clinical trial.

BACKGROUND: Laparoscopy-assisted gastrectomy (LG) is rapidly gaining popularity owing to its minimal invasiveness. Previous studies have found that compared with two-dimensional (2D)-LG, three-dimensional (3D)-LG showed better short-term outcomes. However, the long-term oncological outcomes in patients with locally resectable gastric cancer (GC) remain controversial. METHODS: In this noninferiority, open-label, randomized clinical trial, a total of 438 eligible GC participants were randomly assigned in a 1:1 ratio to either 3D-LG or 2D-LG from January 2015 to April 2016. The primary endpoint was operating time, while the secondary endpoints included 5-year overall survival (OS), disease-free survival (DFS), and recurrence pattern. RESULTS: Data from 401 participants were included in the per-protocol analysis, with 204 patients in the 3D group and 197 patients in the 2D group. The 5-year OS and DFS rates were comparable between the 3D and 2D groups (5-year OS: 70.6% vs. 71.1%, Log-rank P = 0.743; 5-year DFS: 68.1% vs. 69.0%, log-rank P = 0.712). No significant differences were observed between the 3D and 2D groups in the 5-year recurrence rate (28.9% vs. 28.9%, P = 0.958) or recurrence time (mean time, 22.6 vs. 20.5 months, P = 0.412). Further stratified analysis based on the type of gastrectomy, postoperative pathological staging, and preoperative BMI showed that the 5-year OS, DFS, and recurrence rates of the 3D group in each subgroup were similar to those of the 2D group (all P > 0.05). CONCLUSIONS: For patients with locally resectable GC, 3D-LG performed by experienced surgeons in high-volume professional institutions can achieve long-term oncological outcomes comparable to those of 2D-LG. REGISTRATION NUMBER: NCT02327481 ( http://clinicaltrials.gov ).

Effect of sarcopenia on short-term and long-term outcomes of older patients with locally advanced gastric cancer: a multicenter study.

OBJECTIVE: To assess the effect of preoperative sarcopenia on the short-term and long-term outcomes in older patients with locally advanced gastric cancer (LAGC). METHODS: Clinicopathological data of older patients with LAGC who underwent radical surgery were retrospectively analyzed. Sarcopenia was defined as a skeletal muscle index of less than 36.4 cm2/m2 for men and less than 28.4 cm2/m2 for women. Comparing the postoperative complications and survival between sarcopenia and non-sarcopenia groups using multicenter data. RESULTS: A total of 406 older patients with LAGC were included in the analysis, including 145 (35.7%) with sarcopenia and 261 (64.3%) with non-sarcopenia. Multivariate logistic regression analysis showed that sarcopenia was an independent risk factor for postoperative complications with CD grade ≥ II (OR 1.616; P < 0.05). Kaplan-Meier survival curve analysis showed that the 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) in the sarcopenia group were lower than those in the non-sarcopenia group (P both < 0.05). Multivariate Cox regression analyses showed that sarcopenia was an independent prognostic factor for 5-year OS and RFS (P both < 0.05). The 5-year recurrence rate in the sarcopenia group was 57.2%, which was significantly higher than that in the non-sarcopenia group (46.4%; P = 0.036). Recurrence pattern analysis showed that the incidence of distant metastases in patients with sarcopenia (42.8%) was significantly higher than non-sarcopenia (31.4%; P = 0.022). CONCLUSION: Sarcopenia serves as a valuable predictor of both short-term and long-term outcomes in older patients with LAGC. Therefore, the significance of assessing preoperative nutritional status and implementing thorough postoperative follow-up for older LAGC patients with sarcopenia should be emphasized.

Developing a modified textbook outcome for elderly patients with gastric cancer: a multi-center study.

OBJECTIVE: Textbook outcome (TO) is widely recognized as a comprehensive prognostic indication for patients with gastric cancer (GC). This study aims to develop a modified TO (mTO) for elderly patients with GC. METHODS: Data from the elderly patients (aged ≥ 65 years) in two Chinese tertiary referral hospitals were analyzed. 1389 patients from Fujian Medical University Union Hospital were assigned as the training cohort and 185 patients from Affiliated Hospital of Putian University as the validation cohort. Nomogram was developed by the independent prognostic factors of Overall Survival (OS) based on Cox regression. RESULTS: In the training cohort, laparoscopic surgery was significantly correlated with higher TO rate (P < 0.05). Cox regression analysis revealed that surgical approach was also an independent factor of OS (P < 0.001), distinct from the traditional TO. In light of these findings, TO parameters were enhanced by the inclusion of surgical approach, rendering a modified TO (mTO). Further analysis showed that mTO, tumor size, pTNM staging, and adjuvant chemotherapy were independent prognostic factors associated with OS (all P < 0.05). Additionally, the nomogram incorporating these four indicators accurately predicted 1-, 3-, and 5-year OS in the training cohort, with AUC values of 0.793, 0.814, and 0.807, respectively, and exhibited outstanding predictive performance within the validation cohort. CONCLUSION: mTO holds a robust association with the prognosis of elderly patients with GC, meriting intensified attention in efforts aimed at enhancing surgical quality. Furthermore, the predictive model incorporating mTO demonstrates excellent predictive performance for elderly patients with GC.

Robot-assisted versus laparoscopic-assisted gastrectomy among malnourished patients with gastric cancer based on textbook outcome.

BACKGROUND: Textbook outcome (TO) has been widely employed as a comprehensive indicator to assess the short-term prognosis of patients with cancer. Preoperative malnutrition is a potential risk factor for adverse surgical outcomes in patients with gastric cancer (GC). This study aimed to compare the TO between robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG) in malnourished patients with GC. METHODS: According to the diagnostic consensus of malnutrition proposed by Global Leadership Initiative on Malnutrition (GLIM) and Nutrition Risk Index (NRI), 895 malnourished patients with GC who underwent RAG (n = 115) or LAG (n = 780) at a tertiary referral hospital between January 2016 and May 2021 were included in the propensity score matching (PSM, 1:2) analysis. RESULTS: After PSM, no significant differences in clinicopathological characteristics were observed between the RAG (n = 97) and LAG (n = 194) groups. The RAG group had significantly higher operative time and lymph nodes harvested, as well as significantly lower blood loss and hospital stay time compared to the LAG group. More patients in the RAG achieved TO. Logistic regression analysis revealed that RAG was an independent protective factor for achieving TO. There were more adjuvant chemotherapy (AC) cycles in the RAG group than in the LAG group. After one year of surgery, a higher percentage of patients (36.7% vs. 22.8%; P < 0.05) in the RAG group recovered from malnutrition compared to the LAG group. CONCLUSIONS: For malnourished patients with GC, RAG performed by experienced surgeons can achieved a higher rate of TO than those of LAG, which directly contributed to better AC compliance and a faster restoration of nutritional status.

Association between metabolic phenotypes of overweight/obesity and cardiovascular diseases in postmenopausal women.

BACKGROUND AND AIM: Obesity and metabolic abnormalities were associated with an increased risk of cardiovascular disease. However, it is unclear how metabolic weight phenotypes relate to cardiovascular diseases in postmenopausal women. This study aimed to explore the relationships in postmenopausal women. METHODS AND RESULTS: We included 15,575 postmenopausal women aged 35-75 years (median age, 60.6) without cardiovascular disease at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project. Metabolically unhealthy phenotype was defined as having ≥2 risk factors of metabolic syndrome: blood pressure ≥130/85 mm Hg or current use of antihypertensive drugs, fasting glucose ≥5.6 mmol/L or current use of antidiabetic agents, triglycerides ≥1.7 mmol/L, and high-density lipoprotein cholesterol <1.3 mmol/L. Cox regression analysis was used to evaluate the risks of cardiovascular diseases. Over a median follow-up period of 3.55 (interquartile range, 2.59-4.44) years, a total of 1354 cardiovascular events occurred. Compared to metabolically healthy normal weight, the multivariate-adjusted hazard ratios and their 95% confidence intervals were 1.41 (1.16-1.72) for metabolically unhealthy normal weight, 1.42 (1.16-1.73) for metabolically healthy overweight/obesity, and 1.75 (1.48-2.08) for metabolically unhealthy overweight/obesity. Subdividing overweight/obesity into separate groups revealed higher total cardiovascular disease risk only in metabolically unhealthy individuals across body mass index categories. CONCLUSION: In postmenopausal women, both metabolically healthy overweight/obesity and metabolically unhealthy normal weight were associated with a higher risk of cardiovascular disease compared to metabolically healthy normal weight, and the greatest risk was observed in the metabolically unhealthy overweight/obesity category.

Early Famine Exposure Results in Left Ventricular Remodeled, Diastolic Dysfunction and Systolic Function Preserved in Adults.

INTRODUCTION: Malnutrition during a critical window of development in a fetus or infant can result in abnormal cardiac remodeling and function. It is uncertain whether the contribution of these effects continues to impact the cardiac remodeling and function of adults over the course of several decades of growth. Our study examined the impact of early Chinese famine exposure on cardiac remodeling, left ventricular (LV) diastolic function, and LV systolic function in adults. METHODS: Participants at high risk of cardiovascular disease from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project (PEACE MPP) were enrolled. The famine in China lasted from 1959 to 1962. A total of three groups were formed based on the participants' birth dates: pre-famine group, famine exposure group, and post-famine group. Logistic regression and linear mixed models were used to explore the association between famine exposure and cardiac remodeling, LV diastolic function and LV systolic function in adults. RESULTS: The study included 2,758 participants, the mean age was 57.05 years, 62.8% were female, 26.4% had LV hypertrophy (LVH), 59.6% had LV diastolic dysfunction (LVDD), and 10.5% had reduced global longitudinal strain (GLS). Compared to post-famine exposure, participants had independently increased risk of LVH in the famine exposure group (OR: 2.02, 95% CI: 1.60-2.56) and pre-famine exposure (OR: 1.36, 95% CI: 1.06-1.76). Compared to post-famine exposure, the risk of LVDD remarkably increased in the famine exposure group (OR: 3.04, 95% CI: 2.49-3.71) and pre-famine exposure group (OR: 1.87, 95% CI: 1.52-2.31). Famine exposure had no significant impact on GLS but was associated with a significant increase in LV ejection fraction (LVEF) and LV end-diastolic diameter (LVEDD). Significant interactions were observed between the effects of famine exposure and other clinical/sociodemographic variables (gender, systolic blood pressure [SBP] ≥140 mm Hg or not, high school or above or not, and annual income <50,000 RMB or not) on these outcomes. CONCLUSION: Exposure to famine, particularly during fetal and infant stages, increases the risk of LVH and LVDD in adults. However, the LV systolic function remains preserved. These impacts are more pronounced in females, individuals with SBP ≥140 mm Hg, those with low income, or those with high educational status.

Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035.

OBJECTIVE: To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. METHODS: Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex. RESULTS: More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5-2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6-5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20-44, Thailand [AAPC, 3.4; (95%cl, 1.3-5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035. CONCLUSION: In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45 years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth.

Promoting mechanism of nitrogen removal by Fe3O4 magnetic particles during the start-up phase in sequencing batch reactor.

In this paper, a magnetic sequencing batch reactor (SBR) was constructed, and the influence rule of magnetic particle dosing performance of denitrification was investigated. The diversity, structure, and potential functions of the microbial community were comprehensively explored. The results showed that the particle size and the dosage of Fe3O4 magnetic particles were the main parameters affecting the sedimentation performance of activated sludge. The start-up phase of the SBR reactor with Fe3O4 magnetic particles was 5 days less than the control. Moreover, total nitrogen removal efficiency during the start-up phase was improved, with the maximum value reaching 91.93%, surpassing the control by 9.7% with the Fe3O4 dosage of 1.2 g L-1. In addition, the activated sludge concentration and dehydrogenase activity were improved, compared to the control. High-throughput sequencing showed that the denitrifying bacterium Saccharimonadales dominated the reactor and was enriched by magnetic particles. According to predicted functions, the abundance of genes for denitrification increased with the addition of magnetic particles, suggesting the capacity of nitrogen removal was enhanced in the microbial community. Overall, the Fe3O4 magnetic particles provide great potential for enhanced wastewater nitrogen removal.

Intraoperative Adverse Events, Technical Performance, and Surgical Outcomes in Laparoscopic Radical Surgery for Gastric Cancer: A Pooled Analysis From 2 Randomized Trials.

OBJECTIVE: To verify an intraoperative adverse event (iAE) classification (ClassIntra grade) to evaluate quality control and to predict the prognostic performance of laparoscopic radical surgery for gastric cancer. BACKGROUND: Surgical quality control is a key factor in the evaluation of surgical treatment for tumors. And, there is no recognized iAE classification for gastric cancer. METHODS: We performed a retrospective post hoc analysis of previously collected data from the FUGES-001 study (NCT02327481) and a subset of the CLASS-01 study (NCT01609309). Patients were classified into the iAE and non-iAE groups. And iAE was further classified into 5 subgrades according to the ClassIntra grade (with I-V severity categories). Technical performance was evaluated using the Objective Structured Assessment of Technical Skills tool and the Generic Error Rating Tool. RESULTS: Overall, 528 gastric cancer patients were included in this study, with 105 patients (19.9%) in the iAE group and 423 (80.1%) in the non-iAE group. The survival curve showed that the overall, disease-specific, and recurrence-free survival of the non-iAE group were significantly better than those of the iAE group ( P =0.001). The prognosis of patients with ClassIntra grade ≥II was significantly worse than that of patients with ClassIntra grade ≤I. A higher ClassIntra grade, lower Objective Structured Assessment of Technical Skills score, and total gastrectomy were independent risk factors for severe postoperative complications. There was a significant increase in bleeding (grade IV) and injury with splenic hilar lymph node dissection during total gastrectomy. CONCLUSIONS: The ClassIntra grade is an effective prognostic and surgical quality control index for laparoscopic radical surgery for gastric cancer; therefore, it could be included in routine hospital care and surgical quality control.

Patient-Reported Outcomes of Individuals with Gastric Cancer Undergoing Totally Laparoscopic Versus Laparoscopic-Assisted Total Gastrectomy: A Real-World, Propensity Score-Matching Analysis.

OBJECTIVE: Totally laparoscopic total gastrectomy (TLTG) and laparoscopic-assisted total gastrectomy (LATG) are two types of minimally invasive radical gastrectomy procedures to treat gastric cancer (GC). This study compared the long-term prognosis and postoperative health-related quality of life (HRQoL) between TLTG and LATG. METHODS: A total of 106 patients who underwent TLTG and 1,076 patients who underwent LATG at the Union Hospital of Fujian Medical University (Fuzhou, China) between January 2014 and April 2018 were included in the propensity score matching (PSM, 1:2). Patient-reported outcomes at 3, 6, and 12 months after gastrectomy were analyzed. The questionnaire referred to the European Organization for Research and Treatment of Cancer (EORTC) 30-item core QoL (QLQ-C30)and the GC module (QLQ-STO22) questionnaire. RESULTS: After PSM, there were no significant differences in clinicopathological characteristics between the TLTG (n = 104) and the LATG groups (n = 208). Operative time and volume of blood loss were significantly lower in the TLTG group than in the LATG group. Kaplan-Meier survival analysis revealed similar 3-year survival rates between the TLTG and LATG groups (83.7 vs. 80.3%, respectively; P = 0.462). Tolerance to nonliquid diet, decrease in body weight, and albumin levels were also significantly lower in the TLTG group than in the LATG group (all P < 0.05). The HRQoL scale demonstrated that the overall score in the TLTG group was better than that in the LATG group at 3, 6, and 12 months after gastrectomy (all P < 0.05). CONCLUSIONS: Patients with GC undergoing TLTG reported better HRQoL and experienced faster recovery of social function than those undergoing LATG, although the two groups demonstrated similar short-term outcomes and long-term prognosis.