Derivation and validation of a nomogram incorporating modifiable lifestyle factors to predict development of colorectal adenomas after negative index colonoscopy.

This retrospective cohort study aimed to identify baseline patient characteristics involving modifiable lifestyle factors that are associated with the development of colorectal adenomas, and establish and validate a nomogram for risk predictions among high-risk populations with negative index colonoscopy. A total of 83,076 participants who underwent an index colonoscopy at the Tianjin Union Medical Center between 2004 and 2019 were collected. According to meticulous inclusion and exclusion criteria, 249 subjects were enrolled and categorized into the primary and validation cohorts. Based on the primary cohort, we utilized the LASSO-Cox regression and the univariate/multivariate Cox proportional hazards (Cox-PH) regression parallelly to select variables, and incorporated selected variables into two nomogram models established using the multivariate Cox-PH regression. Comparison of the Akaike information criterion and the area under the receiver operating characteristic curve of the two models demonstrated that the nomogram model constituted by four covariates retained by the LASSO-Cox regression, including baseline age, body mass index, physical activity and family history of colorectal cancer (CRC) in first-degree relatives, performed better at predicting adenoma-free survival probabilities. Further validation including the concordance index, calibration plots, decision curve analysis and Kaplan-Meier survival curves also revealed good predictive accuracy, discriminating ability, clinical utility and risk stratification capacity of the nomogram model. Our nomogram will assist high-risk individuals with negative index colonoscopy to prevent colorectal adenoma occurrence and CRC morbidity with improved cost-effectiveness.

Hemodynamic analysis of thoracic endovascular aortic repair with left subclavian artery reconstructed by chimney stent.

OBJECTIVES: The purpose of this study was to investigate the hemodynamic consequences of thoracic endovascular aortic repair which reconstructed left subclavian artery by chimney stent (ch-TEVAR). METHODS: Two patients who underwent thoracic endovascular aortic repair (TEVAR) and left subclavian artery (LSA) reconstruction using chimney stents were selected. Preoperative and postoperative CTA images were collected to reconstruct hemodynamic models for comparing and analyzing blood pressure, blood flow velocity, and wall shear stress in the aortic arch and its major branches. Concurrently, morphological alterations and position of chimney stent were also assessed. RESULTS: After the reconstruction of LSA in ch-TEVAR, no endoleak was seen, but the stent in LSA was compressed. The blood flow velocity of the LSA increased and disordered, the pressure was reduced, and the WSS was increased. Even more, there were a large amount of turbulence found in the LSA of one case, and its LSA was blocked. CONCLUSION: Chimney stent reduces the occurrence of endoleak due to its excellent deformation ability, but the compressed stent has a greater impact on the hemodynamics of LSA and eventually leads to LSA occlusion; in order to keep the LSA unobstructed, it is necessary to pay attention to the position of the chimney stent and keep it straight and do not fold or twist. Chimney stent has little influence on the aortic arch and the rest of the aortic arch branches.

Sulfonamide-induced DNA hypomethylation disturbed sugar metabolism in rice (Oryza sativa L.).

DNA methylation is well-accepted as a bridge to unravel the complex interplay between genome and environmental exposures, and its alteration regulated the cellular metabolic responses towards pollutants. However, the mechanism underlying site-specific aberrant DNA methylation and metabolic disorders under pollutant stresses remained elusive. Herein, the multilevel omics interferences of sulfonamides (i.e., sulfadiazine and sulfamerazine), a group of antibiotics pervasive in farmland soils, towards rice in 14 days of 1 mg/L hydroponic exposure were systematically evaluated. Metabolome and transcriptome analyses showed that 57.1-71.4 % of mono- and disaccharides were accumulated, and the differentially expressed genes were involved in the promotion of sugar hydrolysis, as well as the detoxification of sulfonamides. Most differentially methylated regions (DMRs) were hypomethylated ones (accounting for 87-95 %), and 92 % of which were located in the CHH context (H = A, C, or T base). KEGG enrichment analysis revealed that CHH-DMRs in the promoter regions were enriched in sugar metabolism. To reveal the significant hypomethylation of CHH, multi-spectroscopic and thermodynamic approaches, combined with molecular simulation were conducted to investigate the molecular interaction between sulfonamides and DNA in different sequence contexts, and the result demonstrated that sulfonamides would insert into the minor grooves of DNA, and exhibited a stronger affinity with the CHH contexts of DNA compared to CG or CHG contexts. Computational modeling of DNA 3D structures further confirmed that the binding led to a pitch increase of 0.1 Å and a 3.8° decrease in the twist angle of DNA in the CHH context. This specific interaction and the downregulation of methyltransferase CMT2 (log2FC = -4.04) inhibited the DNA methylation. These results indicated that DNA methylation-based assessment was useful for metabolic toxicity prediction and health risk assessment.

The Treatment of Alar Base Depression in Rhinoplasty with Diced Autologous Cartilage or Mass Cartilage: A Systematic Review.

BACKGROUND: Alar base is the basal part where the two sides of the nose and the upper lip are connected. Alar base depression affects the overall facial contour by making the nasolabial folds deepen, the nasolabial angle smaller, the center of the face flat, etc. Despite the rapid development of rhinoplasty, controversy still exists regarding the treatment of alar base depression. This systematic review aims to evaluate the efficacy and safety of two prevalent techniques-diced autologous cartilage and mass cartilage-for addressing alar base depression. METHODS: A systematic review was conducted by searching the literature published in PubMed, Embase and Web of Science, Cochrane from January 2000 to April 2023 with the key words 'alar base depression or depressed alar base' and 'alar base augmentation,' and 2 investigators independently screened the retrieved literature according to inclusion and exclusion criteria. RESULTS: A total of 269 articles were obtained through database search. After removing duplicates, reading titles and abstracts, and finally reviewing the full text, 6 articles were included in the final study, including 165 patients. CONCLUSIONS: The results demonstrate that both diced autologous cartilage and mass cartilage techniques exhibit favorable outcomes in correcting alar base depression. Diced autologous cartilage offers better malleability, lighter border contours, and a more natural appearance. On the other hand, diced autologous cartilage seems to offer superior long-term effects, while mass cartilage presents certain surgical procedural advantages. Also, compared to diced cartilage, mass cartilage may have a lower rate of long-term resorption and a lower risk of displacement. This review emphasizes the need for personalized treatment selection based on individual patient characteristics. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .

Differential whole-genome doubling based signatures for improvement on clinical outcomes and drug response in patients with breast cancer.

Whole genome doublings (WGD), a hallmark of human cancer, is pervasive in breast cancer patients. However, the molecular mechanism of the complete impact of WGD on survival and treatment response in breast cancer remains unclear. To address this, we performed a comprehensive and systematic analysis of WGD, aiming to identify distinct genetic alterations linked to WGD and highlight its improvement on clinical outcomes and treatment response for breast cancer. A linear regression model along with weighted gene co-expression network analysis (WGCNA) was applied on The Cancer Genome Atlas (TCGA) dataset to identify critical genes related to WGD. Further Cox regression models with random selection were used to optimize the most useful prognostic markers in the TCGA dataset. The clinical implication of the risk model was further assessed through prognostic impact evaluation, tumor stratification, functional analysis, genomic feature difference analysis, drug response analysis, and multiple independent datasets for validation. Our findings revealed a high aneuploidy burden, chromosomal instability (CIN), copy number variation (CNV), and mutation burden in breast tumors exhibiting WGD events. Moreover, 247 key genes associated with WGD were identified from the distinct genomic patterns in the TCGA dataset. A risk model consisting of 22 genes was optimized from the key genes. High-risk breast cancer patients were more prone to WGD and exhibited greater genomic diversity compared to low-risk patients. Some oncogenic signaling pathways were enriched in the high-risk group, while primary immune deficiency pathways were enriched in the low-risk group. We also identified a risk gene, ANLN (anillin), which displayed a strong positive correlation with two crucial WGD genes, KIF18A and CCNE2. Tumors with high expression of ANLN were more prone to WGD events and displayed worse clinical survival outcomes. Furthermore, the expression levels of these risk genes were significantly associated with the sensitivities of BRCA cell lines to multiple drugs, providing valuable insights for targeted therapies. These findings will be helpful for further improvement on clinical outcomes and contribution to drug development in breast cancer.

Association of metabolomics with PD-1 inhibitor plus chemotherapy outcomes in patients with advanced non-small-cell lung cancer.

BACKGROUND: Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy. METHOD: 200 patients with advanced NSCLC receiving either first-line or second-line PD-1 inhibitor plus chemotherapy, and 50 patients undergoing first-line chemotherapy were enrolled in this study. The 200 patients receiving combination therapy were divided into a Discovery set (n=50) and a Validation set (n=150). These sets were further categorized into respond and non-respond groups based on progression-free survival PFS criteria (PFS≥12 and PFS<12 months). Serum samples were collected from all patients before treatment initiation for untargeted metabolomics analysis, with the goal of identifying and validating biomarkers that can predict the efficacy of immunotherapy plus chemotherapy. Additionally, the validated metabolites were grouped into high and low categories based on their medians, and their relationship with PFS was analyzed using Cox regression models in patients receiving combination therapy. RESULTS: After the impact of chemotherapy was accounted for, two significant differential metabolites were identified in both the Discovery and Validation sets: N-(3-Indolylacetyl)-L-alanine and methomyl (VIP>1 and p<0.05). Notably, upregulation of both metabolites was observed in the group with a poorer prognosis. In the univariate analysis of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were associated with longer PFS (HR=0.59, 95% CI, 0.41 to 0.84, p=0.003), and a prolonged PFS was also indicated by lower levels of methomyl (HR=0.67, 95% CI, 0.47 to 0.96, p=0.029). In multivariate analyses of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were significantly associated with a longer PFS (HR=0.60, 95% CI, 0.37 to 0.98, p=0.041). CONCLUSION: Improved outcomes were associated with lower levels of N-(3-Indolylacetyl)-L-alanine in patients with stage IIIB-IV NSCLC lacking driver gene mutations, who underwent first-line or second-line therapy with PD-1 inhibitors combined with chemotherapy. Further exploration of the potential predictive value of pretreatment detection of N-(3-Indolylacetyl)-L-alanine in peripheral blood for the efficacy of combination therapy is warranted. STATEMENT: The combination of ICIs and chemotherapy has established itself as the new standard of care for first-line or second-line treatment in patients with advanced NSCLC lacking oncogenic driver alterations. Therefore, identifying biomarkers that can predict the efficacy and prognosis of immunotherapy plus chemotherapy is of paramount importance. Currently, the only validated predictive biomarker is programmed cell death ligand-1 (PD-L1), but its predictive value is not absolute. Our study suggests that the detection of N-(3-Indolylacetyl)-L-alanine in patient serum with untargeted metabolomics prior to combined therapy may predict the efficacy of treatment. Compared with detecting PD-L1 expression, the advantage of our biomarker is that it is more convenient, more dynamic, and seems to work synergistically with PD-L1 expression.

Temporal trend analysis of acute hepatitis B virus infection in China, 1990-2019.

China faces challenges in meeting the World Health Organization (WHO)'s target of reducing hepatitis B virus (HBV) infections by 95% using 2015 as the baseline. Using Global Burden of Disease (GBD) 2019 data, joinpoint regression models were used to analyse the temporal trends in the crude incidence rates (CIRs) and age-standardized incidence rates (ASIRs) of acute HBV (AHBV) infections in China from 1990 to 2019. The age-period-cohort model was used to estimate the effects of age, period, and birth cohort on AHBV infection risk, while the Bayesian age-period-cohort (BAPC) model was applied to predict the annual number and ASIRs of AHBV infections in China through 2030. The joinpoint regression model revealed that CIRs and ASIRs decreased from 1990 to 2019, with a faster decline occurring among males and females younger than 20 years. According to the age-period-cohort model, age effects showed a steep increase followed by a gradual decline, whereas period effects showed a linear decline, and cohort effects showed a gradual rise followed by a rapid decline. The number of cases of AHBV infections in China was predicted to decline until 2030, but it is unlikely to meet the WHO's target. These findings provide scientific support and guidance for hepatitis B prevention and control.

Predicting thermal desorption efficiency of PAHs in contaminated sites based on an optimized machine learning approach.

Thermal desorption (TD) remediation of polycyclic aromatic hydrocarbon (PAH)-contaminated sites is known for its high energy consumption and cost implications. The key to solving this issue lies in analyzing the PAHs desorption process, defining remediation endpoints, and developing prediction models to prevent excessive remediation. Establishing an accurate prediction model for remediation efficiency, which involves a systematic consideration of soil properties, TD parameters, and PAH characteristics, poses a significant challenge. This study employed a machine learning approach for predicting the remediation efficiency based on batch experiment results. The results revealed that the extreme gradient boosting (XGB) model yielded the most accurate predictions (R2 = 0.9832). The importance of features in the prediction process was quantified. A model optimization scheme was proposed, which involved integrating features based on their relevance, importance, and partial dependence. This integration not only reduced the number of input features but also enhanced prediction accuracy (R2 = 0.9867) without eliminating any features. The optimized XGB model was validated using soils from sites, demonstrating a prediction error of less than 30%. The optimized XGB model aids in identifying the most optimal conditions for thermal desorption to maximize the remediation efficiency of PAH-contaminated sites under relative cost and energy-saving conditions.

A magnetic resonance conditional robot for lumbar spinal injection: Development and preliminary validation.

PURPOSE: This work presents the design and preliminary validation of a Magnetic Resonance (MR) conditional robot for lumbar injection for the treatment of lower back pain. METHODS: This is a 4-degree-of-freedom (DOF) robot that is 200 × 230 × 130 mm3 in volume and has a mass of 0.8 kg. Its lightweight and compact features allow it to be directly affixed to patient's back, establishing a rigid connection, thus reducing positional errors caused by patient movements during treatment. RESULTS: To validate the positioning accuracy of the needle by the robot, an electromagnetic (EM) tracking system and a needle with an EM sensor embedded in the tip were used for the free space evaluation with position accuracy of 0.88 ± 0.46 mm and phantom mock insertions using the Loop-X CBCT scanner with target position accuracy of 3.62 ± 0.92 mm. CONCLUSION: Preliminary experiments demonstrated that the proposed robot showed improvements and benefits in its rotation range, flexible needle adjustment, and sensor protection compared with previous and existing systems, offering broader clinical applications.

Well-Defined Oligo(azobenzene-graft-mannose): Photostimuli Supramolecular Self-Assembly and Immune Effect Regulation.

The immune system can recognize and respond to pathogens of various shapes. Synthetic materials that can change their shape have the potential to be used in vaccines and immune regulation. The ability of supramolecular assemblies to undergo reversible transformations in response to environmental stimuli allows for dynamic changes in their shapes and functionalities. A meticulously designed oligo(azobenzene-graft-mannose) was synthesized using a stepwise iterative method and "click" chemistry. This involved integrating hydrophobic and photoresponsive azobenzene units with hydrophilic and bioactive mannose units. The resulting oligomer, with its precise structure, displayed versatile assembly morphologies and chiralities that were responsive to light. These varying assembly morphologies demonstrated distinct capabilities in terms of inhibiting the proliferation of cancer cells and stimulating the maturation of dendritic cells. These discoveries contribute to the theoretical comprehension and advancement of photoswitchable bioactive materials.

Epon Post Embedding Correlative Light and Electron Microscopy.

Correlative light and electron microscopy (CLEM) is a comprehensive microscopy that combines the localization information provided by fluorescence microscopy (FM) and the context of cellular ultrastructure acquired by electron microscopy (EM). CLEM is a trade-off between fluorescence and ultrastructure, and usually, ultrastructure compromises fluorescence. Compared with other hydrophilic embedding resins, such as glycidyl methacrylate, HM20, or K4M, Epon is superior in ultrastructure preservation and sectioning properties. Previously, we had demonstrated that mEosEM can survive osmium tetroxide fixation and Epon embedding. Using mEosEM, we achieved, for the first time, Epon post embedding CLEM, which maintains the fluorescence and the ultrastructure simultaneously. Here, we provide step-by-step details about the EM sample preparation, the FM imaging, the EM imaging, and the image alignment. We also improve the procedures for identifying the same cell imaged by FM imaging during the EM imaging and detail the registration between the FM and EM images. We believe one can easily achieve Epon post embedding correlative light and electron microscopy following this new protocol in traditional EM facilities.

Left atrial strain, embolic stroke of undetermined source, and atrial fibrillation detection.

BACKGROUND: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. METHODS: The study population included patients with ESUS and noncardioembolic (NCE) stroke presenting to the Rhode Island Hospital Stroke Center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the three phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow-up detection of AF in ESUS patients. RESULTS: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266-2.986, p = .002), contractile (aOR 1.568, 95% CI 1.035-2.374, p = .034), and conduit strain (aOR 2.288, 95% CI 1.448-3.613, p = .001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029-6.236, p = .043), contractile strain (OR 2.828, 95% CI 1.158-6.903, p = .022), and conduit strain (OR 2.614, 95% CI 1.003-6.815, p = .049) were significantly associated with subsequent detection of AF. CONCLUSION: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies.

Overexpression of lncRNA LINC00665 inhibits the proliferation and chondroblast differentiation of bone marrow mesenchymal stem cells by targeting miR-214-3p.

BACKGROUND: Osteoarthritis is a chronic disease mainly involving the damage of articular cartilage and the whole articular tissue, which is the main cause of disability in the elderly. To explore more effective treatment measures, this study analyzed the regulatory role and molecular mechanism of lncRNA LINC00665 (LINC00665) in the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), providing a valuable theoretical basis for the pathogenesis and patient treatment of osteoarthritis. METHODS: Osteoarthritis tissues and healthy tissues were obtained from 52 patients with osteoarthritis and 34 amputated patients without osteoarthritis, and the levels of LINC00665 and miR-214-3p were assessed by RT-qPCR. BMSCs were cultured and induced chondrogenic differentiation. The proliferation ability of BMSCs was detected by CCK-8 method, and the apoptosis level of BMSCs was evaluated by flow cytometry. The content of proteoglycan-glycosaminoglycan (GAG) in cartilage matrix was determined by Alcian blue staining. In addition, the binding relationship between LINC00665 and miR-214-3p was verified by luciferase reporter assay, and the molecular mechanism was further analyzed. RESULTS: In osteoarthritis tissues, LINC00665 was elevated and miR-214-3p was down-regulated. With the chondrogenic differentiation of BMSCs, the level of GAG increased, and LINC00665 expression gradually decreased, while miR-214-3p level was on the contrary. After transfection of pcDNA3.1-LINC00665 in BMSCs, cell proliferation capacity was decreased, apoptosis rate was increased, and GAG content was reduced. Moreover, LINC00665 sponged miR-214-3p and negatively regulate its expression. Transfection of pcDNA3.1-LINC00665-miR-214-3p mimic changed the regulation of pcDNA3.1-LINC00665 on the viability and chondrogenic differentiation of BMSCs. CONCLUSIONS: Overexpression of lncRNA LINC00665 inhibited the proliferation and chondrogenic differentiation of BMSCs by targeting miR-214-3p. The LINC00665/miR-214-3p axis may improve joint damage and alleviate the progression of osteoarthritis.

Geodetector analysis of individual and joint impacts of natural and human factors on maternal and child health at the provincial scale.

This ecological study examined the individual and joint impacts of natural-human factors on the spatial patterns of maternal and child health status in China at the provincial scale in 2020. We considered natural factors (forest coverage, average temperature, and total sulfur dioxide and particulate matter emissions) and human factors (economic development, urbanization, healthcare access, and education level). We combined maternal, infant, and under-five mortality rates into a composite maternal and child health index using the entropy method. The spatial autocorrelation analysis of this index highlighted distinct health patterns across provinces, whereas the geodetector method assessed the effects of natural-human factors on the patterns. A notable east-central-west stepwise decline in health status was observed. Global Moran's I showed positive spatial clustering, with high-high clustering areas in the Yangtze River Delta and low-low clustering areas in western regions. Factor detection identified eight significant natural-human factors impacting maternal and child health, with total sulfur dioxide emission density having the greatest impact. The interaction between average schooling years and total sulfur dioxide emission notably affected maternal and child health patterns. The study concludes that natural-human factors critically affect the spatial distribution of maternal and child health.

Total versus proximal gastrectomy for proximal gastric cancer after neoadjuvant chemotherapy: a multicenter retrospective propensity score-matched cohort study.

BACKGROUND: This study aimed to analyze and compare the short-term and long-term outcomes of proximal gastrectomy (PG) and total gastrectomy (TG) in patients with locally advanced proximal gastric cancer (GC) following neoadjuvant chemotherapy (NACT). METHOD: A multicenter retrospective cohort study and propensity score matching (PSM) were employed. The authors examined 367 patients with proximal GC who received NACT followed by PG ( n =164) or TG ( n =203) at two Chinese medical institutions between December 2009 and December 2022. Clinical and pathological parameters, postoperative complications, and 5-year overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. The dissection status and metastasis rate of each lymph node station were assessed. RESULTS: After PSM, 80 patients were enrolled in both TG and PG group, and baseline characteristics were comparable between the groups (all P >0.05). The TG group had a higher total number of lymph nodes retrieved ( P <0.001) and longer operative time ( P =0.007) compared to the PG group. The incidence of Clavien-Dindo grade II or higher postoperative complications was similar between the TG group (21.3%, 17/80) and the PG group (17.5%, 14/80) ( P =0.689). The 5-year OS rates were 68.4 for the PG group and 66.0% for the TG group ( P =0.881), while the 5-year RFS rates were 64.8 and 61.9%, respectively ( P =0.571), with no statistically significant differences. Metastasis rates at lymph node stations #4d, #5, #6, and #12a were notably low in the TG group, with values of 2.74, 0.67, 1.33, and 1.74%, respectively. CONCLUSION: For proximal GC patients following NACT, PG maintains comparable curative potential and oncological efficacy to TG, making it a safe option.

Disclosing the effect of exogenous betaine on growth of Suaeda salsa (L.) Pall in the Liaohe coastal wetland, North China.

Liaohe coastal wetland has experienced severe degradation of Suaeda salsa (L.) Pall (S. salsa) in recent years. However, the impact of exogenous betaine (GB) on S. salsa growth remains unclear. Therefore, we conducted a natural simulated cultivation in soils of coastal wetland to investigate the effects of GB on S. salsa growth. The results showed that GB increased the height and weight of S. salsa, and meanwhile stimulated the synthesis of endogenous betaine and amino acids, increased soluble sugars and elevated the activity of Na+, K+-ATPase (enhancing osmotic stability). In addition, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) increased, and malondialdehyde (MDA) and H2O2 decreased correspondingly, thereby improving the antioxidant capacity. Overall, GB application significantly alleviated salt stress and effectively promoted S. salsa growth. This study first indicated the important role of GB in influencing S. salsa growth, offering potential strategies for remediation in coastal wetlands.

Age- and sex-stratified detection rates and associated factors of colorectal neoplasia in the Tianjin colorectal cancer screening program from 2012 to 2020.

PURPOSE: Colorectal cancer (CRC) screening has been implemented in Tianjin, China since 2012. The objective was to estimate the neoplasia detection rate in a high-risk population by age and sex and to investigate the potential factors associated with colorectal neoplasia. PATIENTS AND METHODS: This study is based on data of the Tianjin CRC screening program from 2012 to 2020. Residents with a positive high-risk factors questionnaire (HRFQ) or a positive faecal immunochemical test (FIT) were identified as high-risk participants and were subsequently recommended for a free colonoscopy. RESULTS: A total of 4,117,897 eligible participants aged 40-74 years completed both a HRFQ and FIT, and 217,164 (5.3%) of them were identified as high-risk participants. Positive rates of preliminary screening increased with age and were higher in females than in males. For 57,971 participants undertaking colonoscopy, the detection rates of nonadvanced adenoma, advanced adenoma and CRC were 37.8%, 5.7% and 1.6%, respectively. Detection rates of advanced neoplasia increased from the age of 50 and were higher in males. For nonadvanced neoplasia, a strong increase was observed in males from the age of 40 and in females from the age of 50. Male sex had a greater impact on individuals aged 40-49 than on older individuals. Several factors including current smoking, drinking, and higher body mass index (BMI) were significantly associated with the presence of neoplasia, whereas, these associations were mainly restricted to individuals aged above 50 but not those aged 40-49 years. CONCLUSIONS: These findings support that age-specific risk stratification and sex-specific initiating ages for CRC screening should be recommended to improve the accuracy and effectiveness of current screening strategy.

Survival outcomes in locally advanced dMMR rectal cancer: surgery plus adjunctive treatment vs. surgery alone.

BACKGROUND: Recent studies have shown that deficient mismatch repair (dMMR) rectal cancer may be related to treatment resistance, resulting in a worse prognosis than proficient MMR (pMMR) rectal cancer. The purpose of this study was to explore whether surgery plus other treatments (radiotherapy and chemotherapy) can bring more benefits to these patients than surgery alone. METHODS: A retrospective study of 168 patients with rectal adenocarcinoma who underwent total mesorectal excision was conducted using immunohistochemical methods to determine MMR status and a propensity score matching model to minimize potential confounding factors between subgroups of patients with different treatment regimens. Kaplan-Meier analysis, log-rank tests, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups. RESULTS: Only 6.9% (n = 168) of patients in the total cohort had dMMR rectal adenocarcinoma, and the most common cause of dMMR was a PMS2 deletion (103, 61.3%). The median DFS of the surgery alone group was 45.7 months (IQR, 40.9 to 77.8), and the median DFS of the surgery plus other treatment group was 43.9 months (IQR, 14.2 to 80.1). The surgery alone group was superior to the surgery plus other treatment group (HR, 0.16; 95% CI, 0.07 to 0.38; p = 0.005). There was no significant difference in OS (45.8 (IQR, 41.0 to 79.8) vs. 45.9 (IQR, 38.5 to 80.3)) between the two groups (HR, 0.57; 95% CI, 0.23 to 1.40; p = 0.263). CONCLUSIONS: For patients with locally advanced dMMR rectal adenocarcinoma, compared with surgery alone, surgery plus other treatment options (radiotherapy and chemotherapy) do not grant long-term survival benefits but rather shorten DFS.

Trends in sexually transmitted and blood-borne infections in China from 2005 to 2021: a joinpoint regression model.

BACKGROUND: Sexually transmitted and blood-borne infections (STBBIs) is a major public health concern in China. This study assessed the overall trends in STBBIs to improve the comprehensive understanding of the burden of STBBIs and provide evidence for their prevention and control. METHODS: Data for the period from 2005 to 2021 were analyzed across China on infections with hepatitis B or C; syphilis; gonorrhea; and HIV infection. Trends, annual percent change (APC), and average annual percent change (AAPC) in diagnosis rate was analyzed using joinpoint regression models for the five STBBIs together or individually. RESULTS: From 2005 to 2021, the overall diagnosis rate of all five STBBIs increased, with an AAPC of 1.3% [95% confidence interval (CI) -0.5% to 3.1%]. Diagnosis rates of HIV, syphilis and hepatitis C increased individually, but it decreased for infections of hepatitis B and gonorrhea. Joinpoint analysis identified four phases in diagnosis rate of hepatitis C; three phases in diagnosis rate of hepatitis B, HIV infection, and syphilis; two in diagnosis rate of gonorrhea infection. CONCLUSION: Despite national efforts to prevent and control STBBIs, their overall diagnosis rate has continued to rise in China, and they remain an important public health challenge. Further efforts should be made to educate the general population about STBBIs, particularly HIV. Interventions targeting vulnerable groups should be adopted and their efficacy monitored through regular analysis of trends.

Genetic insights into thymic carcinomas and thymic neuroendocrine neoplasms denote prognosis signatures and pathways.

BACKGROUND: Thymic carcinomas (TCs) and thymic neuroendocrine neoplasms (TNENs) are two aggressive subtypes of thymic malignancy. Traditional therapy for advanced TCs and TNENs has limited outcome. New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches. METHODS: We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017. Patient samples were sequenced using a 324-gene platform with licensed technologies. In this study, we focused on clinically relevant genomic alterations (CRGAs), which are previously proven to be pathogenic alterations, to identify the pathology-specific mutational patterns, prognostic signatures of TCs and TNENs. RESULTS: The mutational profiles between TCs and TNENs were diverse. The genetic alterations that ranked highest in TCs were in CDKN2A, TP53, ASXL1, CDKN2B, PIK3C2G, PTCH1, and ROS1 , while those in TNENs were in MEN1, MLL2, APC, RB1 , and TSC2 . Prognostic analysis showed that mutations of ROS1, CDKN2A, CDKN2B, BRAF, and BAP1 were significantly associated with worse outcomes in TC patients, and that mutation of ERBB2 indicated shortened disease-free survival (DFS) and overall survival (OS) in TNEN patients. Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control, chromatin remodeling/DNA methylation, phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), and receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase (MAPK) signaling. CONCLUSION: We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.