Predicting surgical benefit of primary tumor resection in patients with stage IV colorectal cancer.

BACKGROUND: There exists continuous controversy regarding the benefit of primary tumor resection (PTR) for stage IV colorectal cancer (CRC) patients. Little is known about how to predict the patients' benefit from PTR. This study aimed to develop a tool for surgical benefit prediction. METHODS: Stage IV CRC patients diagnosed between 2010 and 2015 from the Surveillance, Epidemiology and End Results database were included. Patients receiving PTR who survived longer than the median cancer-specific survival (CSS) time of those who did not undergo PTR were considered to benefit from surgery. Logistic regression analysis identified prognostic factors influencing surgical benefit, based on which a nomogram was constructed. The data of patients who underwent PTR from our institution was used for external validation. A user-friendly webserver was then built for convenient clinical use. RESULTS: The median CSS of the PTR group was 23 months, significantly longer than that of the non-PTR group (7 months, P < 0.001). In the PTR group, 23.3% of patients did not benefit from surgery. Logistic regression analysis identified age, marital status, tumor location, CEA level, chemotherapy, metastasectomy, tumor size, tumor deposits, number of examined lymph nodes, N stage, histological grade and number of distant metastases as independently associated with surgical benefit. The established prognostic nomogram demonstrated satisfactory performance in both the internal and external validation. CONCLUSION: PTR was associated with prolonged CSS in stage IV CRC. The proposed nomogram could be used as an evidenced-based platform for risk-to-benefit assessment to select appropriate patients for undergoing PTR.

Circular RNA circTATDN3 promotes the Warburg effect and proliferation in colorectal cancer.

As one of the key metabolic enzymes in the glycolytic pathway, lactate dehydrogenase A (LDHA) might be linked to tumor proliferation by driving the Warburg effect. Circular RNAs (circRNAs) are widely implicated in tumor progression. Here, we report that circTATDN3, a circular RNA that interacts with LDHA, plays a critical role in proliferation and energy metabolism in CRC. We found that circTATDN3 expression was increased in CRC cells and tumor tissues and that high circTATDN3 expression was positively associated with poor postoperative prognosis in CRC patients. Additionally, circTATDN3 promoted the proliferation of CRC cells in vivo and vitro. Mechanistically, circTATDN3 was shown to function as an adaptor molecule that enhances the binding of LDHA to FGFR1, leading to increased LDHA phosphorylation and consequently promoting the Warburg effect. Moreover, circTATDN3 increased the expression of LDHA by sponging miR-511-5p, which synergistically promoted CRC progression and the Warburg effect. In conclusion, circTATDN3 may be a target for the treatment of CRC.

How are APOE4, changes in body weight, and longevity related? Insights from a causal mediation analysis.

The ε4 allele of the APOE gene (APOE4) is known for its negative association with human longevity; however, the mechanism is unclear. APOE4 is also linked to changes in body weight, and the latter changes were associated with survival in some studies. Here, we explore the role of aging changes in weight in the connection between APOE4 and longevity using the causal mediation analysis (CMA) approach to uncover the mechanisms of genetic associations. Using the Health and Retirement Study (HRS) data, we tested a hypothesis of whether the association of APOE4 with reduced survival to age 85+ is mediated by key characteristics of age trajectories of weight, such as the age at reaching peak values and the slope of the decline in weight afterward. Mediation effects were evaluated by the total effect (TE), natural indirect effect, and percentage mediated. The controlled direct effect and natural direct effect are also reported. The CMA results suggest that APOE4 carriers have 19%-22% (TE p = 0.020-0.039) lower chances of surviving to age 85 and beyond, in part, because they reach peak values of weight at younger ages, and their weight declines faster afterward compared to non-carriers. This finding is in line with the idea that the detrimental effect of APOE4 on longevity is, in part, related to the accelerated physical aging of ε4 carriers.

Comparative single-cell analysis reveals heterogeneous immune landscapes in adenocarcinoma of the esophagogastric junction and gastric adenocarcinoma.

Adenocarcinoma of the esophagogastric junction (AEG) is a type of tumor that arises at the anatomical junction of the esophagus and stomach. Although AEG is commonly classified as a subtype of gastric adenocarcinoma (GAC), the tumor microenvironment (TME) of AEG remains poorly understood. To address this issue, we conducted single-cell RNA sequencing (scRNA-seq) on tumor and adjacent normal tissues from four AEG patients and performed integrated analysis with publicly available GAC single-cell datasets. Our study for the first time comprehensively deciphered the TME landscape of AEG, where heterogeneous AEG malignant cells were identified with diverse biological functions and intrinsic malignant nature. We also depicted transcriptional signatures and T cell receptor (TCR) repertoires for T cell subclusters, revealing enhanced exhaustion and reduced clone expansion along the developmental trajectory of tumor-infiltrating T cells within AEG. Notably, we observed prominent enrichment of tumorigenic cancer-associated fibroblasts (CAFs) in the AEG TME compared to GAC. These CAFs played a critical regulatory role in the intercellular communication network with other cell types in the AEG TME. Furthermore, we identified that the accumulation of CAFs in AEG might be induced by malignant cells through FGF-FGFR axes. Our findings provide a comprehensive depiction of the AEG TME, which underlies potential therapeutic targets for AEG patient treatment.

Pathological-Features-Modified TNM Staging System Improves Prognostic Accuracy for Rectal Cancer.

BACKGROUND: Variations in survival outcomes are observed in the eighth edition of the American Joint Committee on Cancer TNM staging system. OBJECTIVE: Machine learning ensemble methods were used to develop and evaluate the effectiveness of a pathological-features-modified TNM staging system in predicting survival for patients with rectal cancer by use of commonly reported pathological features, such as histological grade, tumor deposits, and perineural invasion, to improve the prognostic accuracy. DESIGN: This was a retrospective population-based study. SETTINGS: Data were assessed from the database of the Surveillance, Epidemiology, and End Results Program. PATIENTS: The study cohort comprised 14,468 patients with rectal cancer diagnosed between 2010 and 2015. The development cohort included those who underwent surgery as the primary treatment, whereas patients who received neoadjuvant therapy were assigned to the validation cohort. MAIN OUTCOME MEASURES: The primary outcome measures included cumulative rectal cancer survival, adjusted HRs, and both calibration and discrimination statistics to evaluate model performance and internal validation. RESULTS: Multivariable Cox regression analysis identified all 3 pathological features as prognostic factors, after which patients were categorized into 4 pathological groups based on the number of pathological features (ie, 0, 1, 2, and 3). Distinct survival differences were observed among the groups, especially with patients with stage III rectal cancer. The proposed pathological-features-modified TNM staging outperformed the TNM staging in both the development and validation cohorts. LIMITATIONS: Retrospective in design and lack of external validation. CONCLUSIONS: The proposed pathological-features-modified TNM staging could complement the current TNM staging by improving the accuracy of survival estimation of patients with rectal cancer. See Video Abstract . EL SISTEMA DE ESTADIFICACIN TNM CON CARACTERSTICAS PATOLGICAS MODIFICADO MEJORA LA PRECISIN DEL PRONSTICO DEL CNCER DE RECTO: ANTECEDENTES:Se observan variaciones en los resultados de supervivencia en el sistema de estadificación TNM del Comité Conjunto Americano del Cáncer 8º ediciónOBJETIVO:Se utilizaron métodos conjuntos de aprendizaje automático para desarrollar y evaluar la eficacia de un sistema de estadificación con características patológicas modificadas de tumores, ganglios y metástasis para predecir la supervivencia de pacientes con cáncer de recto, utilizando algunas características patológicas comúnmente informadas, como el grado histológico, depósitos tumorales e invasión perineural, para mejorar la precisión del pronóstico.DISEÑO:Este fue un estudio retrospectivo de base poblacional.ENTERNO CLINICO:Se recuperaron y evaluaron datos de la base de datos de Vigilancia, Epidemiología y Resultados Finales.PACIENTES:La cohorte del estudio estuvo compuesta por 14,468 pacientes con cáncer de recto diagnosticados entre 2010 y 2015. La cohorte de desarrollo incluyó a aquellos que se sometieron a cirugía como tratamiento primario, mientras que los pacientes que recibieron terapia neoadyuvante fueron asignados a la cohorte de validación.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas de resultado primarias incluyeron supervivencia acumulada del cáncer de recto, índices de riesgo ajustados y estadísticas de calibración y discriminación para evaluar el rendimiento del modelo y la validación interna.RESULTADOS:El análisis de regresión multivariable de Cox identificó las tres características patológicas como factores pronósticos, después de lo cual los pacientes se clasificaron en cuatro grupos patológicos según el número de características patológicas (es decir, 0, 1, 2 y 3). Se observaron distintas diferencias en la supervivencia entre los grupos, especialmente en los pacientes en estadio III. La estadificación propuesta con características patológicas modificadas de tumores-ganglios-metástasis superó a la estadificación TNM tanto en las cohortes de desarrollo como en las de validación.LIMITACIONES:Diseño retrospectivo y falta de validación externa.CONCLUSIONES:La estadificación propuesta con características patológicas modificadas de tumores-ganglios-metástasis podría complementar la estadificación TNM actual al mejorar la precisión de la estimación de supervivencia de los pacientes con cáncer de recto. (Traducción- Dr. Francisco M. Abarca-Rendon ).

Patterns of Aging Changes in Bodyweight May Predict Alzheimer's Disease.

Relationships between patterns of aging-changes in bodyweight and AD are not fully understood. We compared mean age-trajectories of weight between those who did and did not develop late-onset-AD, and evaluated impact of age at maximum weight (AgeMax), and slope of decline in weight, on AD risk. Women with late-onset-AD had lower weight three or more decades before AD onset, and ∼10 years younger AgeMax, compared to AD-free women. APOE4 carriers had younger AgeMax and steeper slope. Older AgeMax and flatter slope predicted lower AD risk. Premature decline in weight could be a sign of accelerated physical aging contributing to AD.

NF-κB downstream miR-1262 disturbs colon cancer cell malignant behaviors by targeting FGFR1.

Despite substantial advancements in screening, surgery, and chemotherapy, colorectal cancer remains the second most lethal form of the disease. Nuclear factor kappa B (NF-κB) signaling is a critical driver facilitating the malignant transformation of chronic inflammatory bowel diseases. In this study, deregulated miRNAs that could play a role in colon cancer are analyzed and investigated for specific functions in vitro using cancer cells and in vivo using a subcutaneous xenograft model. miRNA downstream targets are analyzed, and predicted binding and regulation are verified. miR-1262, an antitumor miRNA, is downregulated in colon cancer tissue samples and cell lines. miR-1262 overexpression suppresses colon cancer malignant behaviors in vitro and tumor development and metastasis in a subcutaneous xenograft model and a lung metastasis mouse model in vivo. miR-1262 directly targets fibroblast growth factor receptor 1 (FGFR1) and inhibits FGFR1 expression. FGFR1 overexpression shows oncogenic functions through the regulation of cancer cell proliferation, invasion, and migration; when cotransfected, lv-FGFR1 partially attenuates the antitumor effects of agomir-1262. NF-κB binds to the miR-1262 promoter region and inhibits transcription activity. The NF-κB inhibitor CAPE exerts antitumor effects; miR-1262 inhibition partially reverses CAPE effects on colon cancer cells. Conclusively, miR-1262 serves as an antitumor miRNA in colon cancer by targeting FGFR1. The NF-κB/miR-1262/FGFR1 axis modulates colon cancer cell phenotypes, including proliferation, invasion, and migration.

Interactions between genes involved in physiological dysregulation and axon guidance: role in Alzheimer's disease.

Dysregulation of physiological processes may contribute to Alzheimer's disease (AD) development. We previously found that an increase in the level of physiological dysregulation (PD) in the aging body is associated with declining resilience and robustness to major diseases. Also, our genome-wide association study found that genes associated with the age-related increase in PD frequently represented pathways implicated in axon guidance and synaptic function, which in turn were linked to AD and related traits (e.g., amyloid, tau, neurodegeneration) in the literature. Here, we tested the hypothesis that genes involved in PD and axon guidance/synapse function may jointly influence onset of AD. We assessed the impact of interactions between SNPs in such genes on AD onset in the Long Life Family Study and sought to replicate the findings in the Health and Retirement Study. We found significant interactions between SNPs in the UNC5C and CNTN6, and PLXNA4 and EPHB2 genes that influenced AD onset in both datasets. Associations with individual SNPs were not statistically significant. Our findings, thus, support a major role of genetic interactions in the heterogeneity of AD and suggest the joint contribution of genes involved in PD and axon guidance/synapse function (essential for the maintenance of complex neural networks) to AD development.

Which treatment strategy is optimal for acute left-sided malignant colonic obstruction? A Bayesian meta-analysis.

PURPOSE: This study aimed to determine the best treatment for acute left-sided malignant colonic obstruction (ALMCO) among emergency surgery (ES), self-expanding metallic stent (SEMS), transanal drainage tube (TD), and decompressive stoma (DS). METHOD: Articles that compared two or more treatments of ALMCO were searched from PubMed, Cochrane Library, and Embase. Network meta-analyses were performed to calculate the outcomes of primary anastomosis, stoma creation, morbidity, mortality, and 5-year survival. RESULTS: Fifty-one articles met inclusion criteria. TD was the optimal treatment in performing primary anastomosis [probability of ranking first (Pro-1) 0.96], while ES was the worst [probability of ranking fourth (Pro-4) 0.99]. More permanent stoma was formed in ES and TD groups than in SEMS and DS groups [OR (95%CI): TD vs SEMS: 4.12 (1.89, 9.45); TD vs DS: 3.39 (1.46, 8.75); ES vs DS: 2.55 (1.73, 4.17); SEMS vs ES: 0.33 (0.24, 0.42)]. More morbidity occurred in ES group than in SEMS group [OR (95%CI): ES vs SEMS: 1.44 (1.14, 1.82)]. Besides, SEMS was ranked first in avoiding infection (Pro-4 0.95). For in-hospital mortality, ES was ranked first (Pro-1 0.93). TD was ranked first in recurrence (Pro-1 0.97) and metastasis (Pro-1 0.98). There was no discrepancy in 5-year overall and disease-free survival among all strategies. CONCLUSION: SEMS as a bridge to surgery reduces stoma formation, and morbidity especially the infection rate with relatively great oncological outcomes. Therefore, SEMS should be recommended first for ALMCO in the medical center with experience and conditions.

Prediction of acute lung injury in severe acute pancreatitis by routine clinical data.

AIM: Acute lung injury (ALI) is a common complication of severe acute pancreatitis (SAP) with a high mortality. Early prediction of patients at risk in initial stage can improve the long-term survival. METHODS: A total of 91 patients with SAP out of 1647 acute pancreatitis patients from January 2015 to December 2020 were considered. A predictive model for SAP-associated ALI was constructed based on the valuable risk factors identified from routine clinical characteristics and plasma biomarkers. The value of the model was evaluated and compared with Lung Injury Prediction Score (LIPS). A nomogram was built to visualize the model. RESULTS: Diabetes, oxygen supplementation, neutrophil count and D-dimer were found to be associated with ALI in SAP. The predictive model based on these factors had an area under the receiver operating characteristic curve [AUC: 0.88, 95% confidence interval (CI): 0.81-0.95], which was superior to LIPS (AUC: 0.71, 95% CI: 0.60-0.83), also with the higher sensitivity (65%) and specificity (96%) than LIPS (62%, 74%, respectively). Decision curve analysis of the model showed a higher net benefit than LIPS. Visualization by a nomogram facilitated the application of the model. CONCLUSION: Diabetes, oxygen supplementation, neutrophil count and D-dimer were risk factors for SAP-associated ALI. The combination of these routine clinical data and the model visualization by a nomogram provided a simple and effective way in predicting ALI in the early phase of SAP.

An artificial intelligence difficulty scoring system for stone removal during ERCP: a prospective validation.

BACKGROUND: A computer-assisted (CAD) system was developed to assess, score, and classify the technical difficulty of common bile duct (CBD) stone removal during endoscopic retrograde cholangiopancreatography (ERCP). The efficacy of the CAD system was subsequently assessed through a multicenter, prospective, observational study. METHOD: All patients who met the inclusion criteria were included. Based on cholangiogram images, the CAD system analyzed the level of difficulty of stone removal and classified it into "difficult" and "easy" groups. Subsequently, differences in clinical endpoints, including attempts at stone extraction, stone extraction time, total operation time, and stone clearance rates were compared between the two groups. RESULTS: 173 patients with CBD stones from three hospitals were included in the study. The group classified as difficult by CAD had more extraction attempts (7.20 vs. 4.20, P < 0.001), more frequent machine lithotripsy (30.4 % vs. 7.1 %, P < 0.001), longer stone extraction time (16.59 vs. 7.69 minutes, P < 0.001), lower single-session stone clearance rate (73.9 % vs. 94.5 %, P < 0.001), and lower total stone clearance rate (89.1 % vs. 97.6 %, P = 0.019) compared with the group classified as easy by CAD. CONCLUSION: The CAD system effectively assessed and classified the degree of technical difficulty in endoscopic stone extraction during ERCP. In addition, it automatically provided a quantitative evaluation of CBD and stones, which in turn could help endoscopists to apply suitable procedures and interventional methods to minimize the possible risks associated with endoscopic stone removal.

Studies on endoscopic submucosal dissection in the past 15 years: A bibliometric analysis.

Background and aims: Endoscopic submucosal dissection (ESD) is an advanced minimally invasive technique for en bloc resection of superficial gastrointestinal lesions, which is drawn an increasing attention from its emergence. This bibliometric analysis is to evaluate the origin, current hotspots, and research trends on ESD. Methods: A total of 2,131 publications on ESD from 2006 to 2020 were obtained from the Web of Science Core Collection (WoSCC) database. Bibliometric visualization analyses of countries/regions, institutes, authors, journals, references and keywords were performed by CiteSpace V.5.8.R3. Results: The quantity of publications on ESD increased significantly during the past 15 years. Japan occupied the leading position in terms of research power. Professor Yutaka Saito, together with the institute he belongs, the Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan, were the most productive author and institute, respectively. Colorectal ESD led the main thematic concentrations in ESD research. The most prolific journal was Gastrointestinal Endoscopy. European ESD Guideline was the most frequently co-cited reference. Guideline, meta-analysis, endoscopic resection, poly-glycolic acid sheet, Barrett's esophagus, fibrin glue, risk and colorectal neoplasm will be the active research hotspots in the future. Conclusions: These findings provide the trends and frontiers in the field of ESD, as well as valuable information for clinicians and scientists to discover the future perspectives with potential collaborators.

A Novel Protein Encoded by Exosomal CircATG4B Induces Oxaliplatin Resistance in Colorectal Cancer by Promoting Autophagy.

Oxaliplatin is commonly used in chemotherapeutic regimens for colorectal cancer (CRC) after surgical resection. However, acquired chemoresistance seriously affects the curative effect in CRC patients, and the mechanism is still unclear. Here, a circular RNA, circATG4B is identified, which plays an important role in oxaliplatin resistance in CRC. circATG4B expression is found to be increased in exosomes secreted by oxaliplatin-resistant CRC cells. In addition, the results suggest that circATG4B induces oxaliplatin resistance by promoting autophagy. Further in vivo and in vitro studies indicate that the effect of circATG4B is attributed to its potential to encode a novel protein, circATG4B-222aa. Next, circATG4B-222aa is found to function as a decoy to competitively interact with TMED10 and prevent TMED10 from binding to ATG4B, which leads to increased autophagy followed by induction of chemoresistance. Therefore, this study reveals that exosomal circATG4B participates in the decreased chemosensitivity of CRC cells, providing a new rationale for a potential therapeutic target for oxaliplatin resistance in CRC.

Efficacy of Different Pancreatic Interventional Treatments for Chronic Calcific Pancreatitis: A Two-Year Multicenter Retrospective Study.

Background: Extracorporeal shock wave lithotripsy (ESWL) and endoscopic retrograde cholangiopancreatography (ERCP) are the main treatments for chronic calcific pancreatitis (CCP). However, clinical outcomes remain unclear for patients underwent different interventional therapies based on these two techniques. Methods: A total of 125 patients with CCP who underwent ESWL, ERCP or a combined treatment at two medical centers from January 2019 to January 2020 were considered. Patients were divided into four groups according to intervention types (ESWL-alone, ERCP-alone, ESWL-ERCP and ERCP-ESWL). A retrospective survey with a follow-up for 2 years was conducted. The main outcome measures were postoperative complications, abdominal pain and re-intervention during the follow-up. Possible prognostic factors were evaluated by multivariate analysis. Results: Patients in ESWL-ERCP group had the highest complete pain relief rate (49.28%), the lowest pain frequency (1 time/year) and intensity (VAS-score, 1.84±1.93) during the follow-up, which were statistically significant compared with the other three groups. ESWL-ERCP group also had the lowest postoperative complication rate (6%), while the highest complication rate (16%) was observed in ESWL-alone group. Both ESWL-alone and ESWL-ERCP group had significant lower frequencies of re-interventions (0.44 ± 0.73, 0.57±0.98, respectively) after the initial treatments. An analysis of treatment-based prognostic factors found significant interactions between age, course of CCP, max pancreatic duct stone diameter, calcium, glycosylated hemoglobin (HbA1c) and triglyceride. Conclusion: ESWL-ERCP was considered as the most effective interventional therapy for CCP with a better safety in a two-year follow-up. Prognostic factors may help to determine the patients who benefit by this technique.

Anatomic patterns and clinical significance of gastrocolic trunk of Henlé in laparoscopic right colectomy for colon cancer: Results of the HeLaRC trial.

BACKGROUND: Recent interest in laparoscopic right colectomy with D3 lymphadenectomy for right colon cancer, has raised renewed attention to the anatomic variations of the gastrocolic trunk of Henlé (GTH). Understanding the vascular structure of the GTH region for individual patients should improve surgical outcomes. The goal of this nationwide multicenter study (Anatomical Classification of Henlé's Trunk in Laparoscopic Right Hemi-colectomy (HeLaRC) trial) was to study the anatomic patterns of the GTH region, to clarify the implications of GTH in laparoscopic right colectomy with D3 lymphadenectomy (D3-RC) and analyze their clinical significance. METHODS: We enrolled 583 patients from 26 centers across China who underwent D3-RC. The number of tributaries, length and types of GTH constitutions and their influence on intra-operative data were investigated. A nomogram score (based on the length of GTH, body mass index (BMI), tumor location, T stage and type of GTH (type I vs. non-type I) was established to assess the potential hazard of bleeding. RESULTS: The GTH was found in 567 patients (97.3%). The distribution of GTH types was 0 (14.1%, n = 80), I (53.3%, n = 302), II (27.0%, n = 153), III (5.6%, n = 32). Of note, the type I GTH, T1 stage and tumor location at ileocecal or ascending colon were correlated with shorter exposure time of the GTH region (P < 0.0001). Short length of GTH (P = 0.002) and tumor location (transverse colon vs. non transverse colon) (P = 0.003) were correlated with the amount of GTH bleeding during the surgery. Nomogram discrimination was good (C-index: 0.72 (95% CI: 0.64, 0.80)). The dissection plane was better in patients with type I GTH than with other types (P = 0.023). CONCLUSION: GTH pattern variations may affect surgical outcomes in patients undergoing D3-RC. Better recognition of GTH anatomy might lead to a safer operation with better oncologic quality.

Effects of Preoperative Radiotherapy on Long-Term Bowel Function in Patients With Rectal Cancer Treated With Anterior Resection: A Systematic Review and Meta-analysis.

Background: Anterior resection is a common surgical approach used in rectal cancer surgery; however, this procedure is known to cause bowel injury and dysfunction. Neoadjuvant therapy is widely used in patients with locally advanced rectal cancer. In this study, we determined the effect of preoperative radiotherapy on long-term bowel function in patients who underwent anterior resection for treatment of rectal cancer. Methods: We performed a comprehensive literature search of the PubMed, Embase, Web of Science, and the Cochrane Library databases. A random-effects model was used in the meta-analysis by the Review Manager software, version 5.3. Results: This systematic review and meta-analysis included 12 studies, which used low anterior resection syndrome score with a total of 2349 patients. Based on them, we concluded that low anterior resection syndrome was significantly more common in the preoperative radiotherapy group (odds ratio 3.59, 95% confidence interval 2.68-4.81, P < .00001) and that major low anterior resection syndrome also occurred significantly more frequently in the preoperative radiotherapy group (odds ratio 3.28, 95% confidence interval 2.05-5.26, P < .00001). Subgroup analyses of long-course radiation, total mesorectal excision, and non-metastatic tumors were performed, and the results met the conclusions of the primary outcomes. Conclusions: Preoperative radiotherapy negatively affects long-term bowel function in patients who undergo anterior resection for rectal cancer.

Improving DNA Data Capacity: Forensic Parameters and Genetic Structure Analysis of Jinjiang Han Population with the Microreader™ Y Prime Plus ID System.

OBJECTIVE: Population genetic analysis based on genetic markers harbors valuable forensic applications. In this regard, it is informative and imperative to explore Han groups as they are the largest population of China. In particular, there is a largely underrepresented amount of information from recent decades regarding the southeast costal Han Chinese. Therefore, the aim of this study is to investigate the available genetic characteristics of the Han population living in the Jinjiang, Fujian Province, Southeastern China. METHODS: We sampled 858 saliva samples and used the commercially available Microreader™ Y Prime Plus ID System to identify population data of Y-short tandem repeat (STR) loci of this region. RESULTS: A total of 822 different haplotypes were observed. The overall haplotype diversity, discriminatory power and haplotype match probability were 0.9999, 0.9999 and 0.0012, respectively. CONCLUSION: Our results showed that the Jinjiang Han population was closely genetically related to Han groups of China. Overall, we identified a set of 37 Y-STRs that are highly polymorphic, and that can provide meaningful information in forensic practice and human genetic research.

Subclinical hypothyroidism in pregnancy rats impaired offspring's spatial learning and memory and the cerebellar development.

Subclinical hypothyroidism (SCH) is a very common preclinical condition during pregnancy. The adverse effect of maternal clinical hypothyroidism (CH) on the nervous system development of offspring is beyond doubt, but it is still controversial in SCH. The aim of this study was to investigate whether spatial learning and memory ability of offspring is inhibited in SCH rat model and its possible mechanism. 45 Wistar female rats were randomly divided into SCH, CH and control (CON) groups, which were induced by semi-thyroid electrocauterization, total thyroidectomy and sham operation, respectively. Rat pups were sacrificed at embryonic day 14 (E14), E18, postnatal day 1 (P1), P3, and P10, and pups' cerebellar tissues were collected. The proliferation, differentiation and migration of cerebellar cells were observed, and RNA level of the thyroid hormone receptor α (TRα) and TRß in the cerebellum was detected by real-time PCR, respectively. Morris Water Maze (MWM) test was performed to detect the spatial learning and memory ability of pups at P40. Our data indicated that maternal SCH will significantly extend the offspring's escape latency time, and pups perform worse in the spatial probe test compared with the CON group. Except for E14, the proliferation of pups' cerebellar granule cells (GCs), and the migration of pups' Purkinje cells (PCs) in the SCH group was significantly inhibited compared with that in the CON group at other time points (P < 0.05 or P < 0.01), and the differentiation of cerebellar astrocytes (As) in SCH group was higher than that in CON group at P3 and P10. Except for E14, the expression of TRα mRNA in SCH group was significantly lower than that in CON group (P < 0.05 or P < 0.01). And the difference of the differentiation of As and the spatial learning and memory between SCH and CH groups was not statistically significant. Our findings suggested that SCH during pregnancy nuisances the offspring's spatial learning and memory. It may be related to the decrease of the expression of TRα in cerebellum, which may further inhibit the proliferation of GCs and the migration of PCs, and increase the differentiation of As.

Studies on Children With Developmental Coordination Disorder in the Past 20 Years: A Bibliometric Analysis via CiteSpace.

Children with developmental coordination disorder (DCD) have been commonly observed and drawn an increasing amount of attention over the past decades. The aim of the present study is to evaluate the origin, current hotspots, and research trends on children with DCD using a bibliometric tool. After searching with "children" and "developmental coordination disorder" as the "topic" and "title" words, respectively, 635 original articles with 12,559 references were obtained from the electronic databases, Web of Science Core Collection (WoSCC). CiteSpace V.5.7.R2 was used to perform the analysis. The number of publications in this field was increasing over the past two decades. John Cairney from the Department of Family Medicine, McMaster University, Canada, was found to be the most productive researcher. Meanwhile, McMaster University and Canada were the most productive research institution and country, respectively. Reference and journal co-citation analyses revealed the top landmark articles and clusters in this field. Clumsiness was the most strength burst keyword. Moreover, task, meta-analysis, difficulty, adult, and impact will be the active research hotspots in future. These findings provide the trends and frontiers in the field of children with DCD, and valuable information for clinicians and scientists to identify new perspectives with potential collaborators and cooperative countries.

Roles of interacting stress-related genes in lifespan regulation: insights for translating experimental findings to humans.

AIM: Experimental studies provided numerous evidence that caloric/dietary restriction may improve health and increase the lifespan of laboratory animals, and that the interplay among molecules that sense cellular stress signals and those regulating cell survival can play a crucial role in cell response to nutritional stressors. However, it is unclear whether the interplay among corresponding genes also plays a role in human health and lifespan. METHODS: Literature about roles of cellular stressors have been reviewed, such as amino acid deprivation, and the integrated stress response (ISR) pathway in health and aging. Single nucleotide polymorphisms (SNPs) in two candidate genes (GCN2/EIF2AK4 and CHOP/DDIT3) that are closely involved in the cellular stress response to amino acid starvation, have been selected using information from experimental studies. Associations of these SNPs and their interactions with human survival in the Health and Retirement Study data have been estimated. The impact of collective associations of multiple interacting SNP pairs on survival has been evaluated, using a recently developed composite index: the SNP-specific Interaction Polygenic Risk Score (SIPRS). RESULTS: Significant interactions have been found between SNPs from GCN2/EIF2AK4 and CHOP/DDI3T genes that were associated with survival 85+ compared to survival between ages 75 and 85 in the total sample (males and females combined) and in females only. This may reflect sex differences in genetic regulation of the human lifespan. Highly statistically significant associations of SIPRS [constructed for the rs16970024 (GCN2/EIF2AK4) and rs697221 (CHOP/DDIT3)] with survival in both sexes also been found in this study. CONCLUSION: Identifying associations of the genetic interactions with human survival is an important step in translating the knowledge from experimental to human aging research. Significant associations of multiple SNPxSNP interactions in ISR genes with survival to the oldest old age that have been found in this study, can help uncover mechanisms of multifactorial regulation of human lifespan and its heterogeneity.