Should we perform sigmoidoscopy for colorectal cancer screening in people under 45 years?

BACKGROUND: The strategy for preventing colorectal cancer is screening by colonoscopy, which offers a direct way for detection and removal of adenomatous polyps (APs). American College of Gastroenterology guidelines recommend that people aged ≥ 45 years should undergo colonoscopy; however, how to deal with people aged ≤ 45 years is still unknown. AIM: To compare the prevalence of APs and high-grade neoplasia between the left and right colon in patients ≤ 45 years. METHODS: A retrospective observational study was conducted at a single tertiary III hospital in China. This study included patients aged 18-45 years with undergoing initial colonoscopy dissection and pathological diagnosis AP or high-grade neoplasia between February 2014 and January 2021. The number of APs in the entire colon while screening and post-polypectomy surveillance in following 1-3 years were evaluated. RESULTS: A total of 3053 cases were included. The prevalence of APs in the left and right colon was 55.0% and 41.6%, respectively (OR 1.7, 95%CI 1.6-2.4; P < 0.05). For APs with high-grade neoplasia, the prevalence was 2.7% and 0.9%, respectively (OR 3.0, 95%CI 2.0-4.6; P < 0.05). Therefore, the prevalence of APs and high-grade neoplasia in the left colon was significantly higher than in the right colon in patients aged ≤ 45 years. There were 327 patients who voluntarily participated in post-polypectomy surveillance in following 1-3 years, and APs were found in 216 cases (66.1%); 170 cases had 1-3 polyps (52.0%) and 46 cases had > 3 polyps (14.1%; OR 0.3, 95%CI 0.1-0.6; P < 0.05). CONCLUSION: This study suggests that flexible sigmoidoscopy would be an optimal approach for initial screening in people aged ≤ 45 years and would be a more cost-effective and safe strategy.

Seizure as the clinical presentation of massive pulmonary embolism: Case report and literature review.

Massive pulmonary embolism (MPE) is a high-risk medical emergency. Seizure as the clinical presentation of MPE is extremely rare, and to our knowledge, there have been no reports on successful percutaneous, catheter-based treatment of MPE presenting with new-onset seizures and cardiac arrest. In this report, we discuss the case of a 64-year-old woman who presented with an episode of seizure that lasted 5 h. Seizure occurred four times within 12 h after arrival at the hospital, and in the end, she sustained a cardiac arrest. The patient had no past history of seizure or cardiopulmonary disease. Bilateral MPE was detected by a computed tomography pulmonary angiogram, and she was successfully treated with percutaneous, catheter-directed anticoagulant therapy. Pulmonary embolism-related seizures are more difficult to diagnose and have higher mortality rates than seizures. MPE should be suspected in patients presenting with new-onset seizures and hemodynamic instability.

A gastro-colic fistula secondary to high-grade B-cell gastric lymphoma in a patient with AIDS: a case report.

To the best of our knowledge, there are no previous reports of a gastro-colic fistula (GCF) secondary to primary high-grade B-cell gastric lymphoma associated with acquired immunodeficiency syndrome (AIDS). Here, we report a 37-year-old man who presented with paroxysmal abdominal pain for 4 months, diarrhea for 15 days and weight loss of 4 kg. He had a history of human immunodeficiency virus (HIV) infection and was diagnosed with AIDS in 2013. The patient was diagnosed with a GCF secondary to primary high-grade B-cell gastric lymphoma by gastroscopy and histopathological examination. Two weeks after diagnosis, he died in another hospital. This is an uncommon case in which the GCF occurred secondary to malignant gastric lymphoma in a patient with AIDS. Supported by the literature, patients with HIV infection who complain of abdominal pain or a mass, severe diarrhea, and weight loss should be assessed for a GCF secondary to lymphoma because of its worse prognosis.

PP2A subunit PPP2R2C is downregulated in the brains of Alzheimer's transgenic mice.

Targeting of PP2A suggests a close link to tau-related cognitive and functional declines. However, little is known about how the expression of PP2A subunits and PP2A activity are dysregulated in the course of AD, precluding any specific targeting strategy for restoring PP2A in AD patients. Although the PP2A heterotrimer containing the regulatory subunit PR55/Bα (encoded by the PPP2R2A gene) is the major tau phosphatase, the involvement of other brain-specific PP2A regulatory subunits in tau dephosphorylation remains unknown. PR55/Bγ (encoded by the PPP2R2C gene) is a pivotal phosphatase in the brain, and single-nucleotide polymorphisms (SNPs) of PPP2R2C are involved in several mental disorders. By measuring the differential spatiotemporal expression patterns of PPP2R2C in Wt and transgenic AD mice, we revealed that PPP2R2C expression is downregulated in the aged AD mouse brain as compared to the Wt mouse brain. In cultured cells, PPP2R2C expression regulates PP2A activity and tau dephosphorylation. These results suggest that dysregulation of PPP2R2C expression may be involved in the onset of AD and that specifically targeting PPP2R2C expression or activity is a promising strategy against brain dementia disorders, including AD and other tauopathies.

Mitochondrial function in skeletal myofibers is controlled by a TRF2-SIRT3 axis over lifetime.

Telomere shortening follows a developmentally regulated process that leads to replicative senescence of dividing cells. However, whether telomere changes are involved in postmitotic cell function and aging remains elusive. In this study, we discovered that the level of the TRF2 protein, a key telomere-capping protein, declines in human skeletal muscle over lifetime. In cultured human myotubes, TRF2 downregulation did not trigger telomere dysfunction, but suppressed expression of the mitochondrial Sirtuin 3 gene (SIRT3) leading to mitochondrial respiration dysfunction and increased levels of reactive oxygen species. Importantly, restoring the Sirt3 level in TRF2-compromised myotubes fully rescued mitochondrial functions. Finally, targeted ablation of the Terf2 gene in mouse skeletal muscle leads to mitochondrial dysfunction and sirt3 downregulation similarly to those of TRF2-compromised human myotubes. Altogether, these results reveal a TRF2-SIRT3 axis controlling muscle mitochondrial function. We propose that this axis connects developmentally regulated telomere changes to muscle redox metabolism.

The differential spatiotemporal expression pattern of shelterin genes throughout lifespan.

Shelterin forms the core complex of telomere proteins and plays critical roles in protecting telomeres against unwanted activation of the DNA damage response and in Emaintaining telomere length homeostasis. Although shelterin expression is believed to be ubiquitous for stabilization of chromosomal ends. Evidences suggest that some shelterin subunits have tissue-specific functions. However, very little is known regarding how shelterin subunit gene expression is regulated during development and aging. Using two different animal models, the mouse and zebrafish, we reveal herein that shelterin subunits exhibit distinct spatial and temporal expression patterns that do not correlate with the proliferative status of the organ systems examined. Together, this work shows that the shelterin subunits exhibit distinct spatiotemporal expression patterns, suggesting important tissue-specific functions during development and aging.

Test anxiety and telomere length: Academic stress in adolescents may not cause rapid telomere erosion.

Academic stress (AS) is one of the most important health problems experienced by students, but no biomarker of the potential psychological or physical problems associated with AS has yet been identified. As several cross-sectional studies have shown that psychiatric conditions accelerate aging and shorten telomere length (TL), we explored whether AS affected TL.Between June 2014 and July 2014, we recruited 200 junior high school students with imminent final examinations for participation in this study. The students were divided into three subgroups (mild, moderate, and severe anxiety) using the Sarason Test Anxiety Scale (TAS). Saliva samples were collected for TL measurement via quantitative polymerase chain reaction (qPCR).Students from both a specialized and a general school suffered from anxiety (p > 0.05). A total 35% had severe anxiety (score: 26.09±3.87), 33% had moderate anxiety (16.98±2.64), and 32% had mild anxiety (7.89±1.92). The TAS values differed significantly (p < 0.05) among the three subgroups, but the TLs of saliva cells differed only slightly (p > 0.05): 1.14±0.46 for those with severe anxiety, 1.02±0.40 for those with moderate anxiety, and 1.12±0.45 for those with mild anxiety.Previous reports have found that AS is very common in Asian adolescents. We found no immediate telomere shortening in adolescents with AS. Longitudinal observations are required to determine if TL is affected by AS.

An Evaluation of Laboratory Efficiency in Shanghai Emergency by Turn Around Times Level.

OBJECTIVE: China launched a health care reform policy due to the aging population and rapid urbanization. However, emergency overcrowding is not improved. We assessed the laboratory efficiency of emergency department (ED) in Shanghai hospitals. METHODS: We recorded the turn around times for processing laboratory biomarkers to assess laboratory efficiency at 17 EDs in national/regional hospitals. We compared TAT between national and regional hospitals and between central and ED laboratories to analyze the relationship between the laboratory efficiency and the ED overcrowding. RESULTS: All the participating hospitals have an emergency laboratory. The median TAT for c-TNT was 61 min (46-76 min) at regional EDs compared with 64 min (46-87 min) at national EDs; therefore, the TAT at regional EDs were more efficient (P < 0.05). The TAT were longer (65 min (53-85 min)) at ED labs than (60 min (42-83 min)) at central labs (P < 0.05), independent of the hospital tier and working period. We discovered that only 9% of investigated samples at Tier II EDs and 5% at Tier III EDs were assayed by point-of-care (POC) instruments. CONCLUSION: Our TAT level is approaching the recommended international standard. However, the TAT evaluation from ED laboratories demonstrates that their existence does not decrease the waiting time for laboratory reports compared to central laboratory. Thus, they have not yet approached a level to share the burden of the ED overcrowding. Further arrangement should be assigned to separate the function of emergency laboratory and central laboratory. It is worth deploying the POC assay in the ED, which will save twice the TAT level. The idea of evaluating routine laboratory efficiency by TAT at ED is fast, convenient, although it does not represent the general level of laboratory efficiency.

The clinical situation of point-of-care testing and its future development at the emergency department in Shanghai.

We assessed the efficiency of point-of-care (POC) tests in the emergency department (ED) by comparing them with the international standard. We recorded the turnaround times (TATs) for processing laboratory biomarkers to assess laboratory efficiency from 17 EDs in national/regional hospitals. We also compared patient components between national and regional hospitals. Although the 17 enrolled hospitals expanded their EDs, they contained only five POC machines among them. The P50 (P25, P75) of the TATs for POC tests was 47 min (39, 55.5 min) for cardiac troponin T, which was much longer than the international standard (30 min). The TATs of other cardiac biomarkers were also longer than 30 min. The low efficiency of TATs for POC tests was a common feature in both regional and national hospitals (p > 0.05). Myocardial infarction was diagnosed in 61% of investigated ED patients who visited national hospitals, which is more frequently than those diagnosed at regional hospitals (46%, p < 0.05). Chronic heart failure was less frequent at national hospitals (28%) than at regional hospitals (41%, p < 0.05). The patient distribution in this study indicates that patients have the tendency to choose hospitals when they are affected with chest pain. However, the POC panel is rarely used in the ED, which delayed the TAT level and affected laboratory efficiency. This finding indicates a severe problem in the administrative management of EDs. This issue should be addressed in the next version of the medical reform policy.

Telomeric impact of conventional chemotherapy.

The increased level of chromosome instability in cancer cells, leading to aneuploidy and gross chromosomal rearrangements, is not only a driving force for oncogenesis but also can be the Achille's heel of the disease since many chemotherapies (CT) kill cells by inducing a non-tolerable rate of DNA damage. A wealth of published evidence showed that telomere stability can be more affected than the bulk of the genome by several conventional antineoplasic drugs. These results raise the interesting possibility that CT with genotoxic drugs preferentially target telomeres. In agreement with this view, accelerated shortening of telomere length has been described in blood lineage cells following high-dose CT (stem cell transplantation) or non-myeloablative CT. However, almost nothing is known on the consequences of this shortening in terms of telomere stability, senescence and on the development of second cancers or post-treatment aging-like syndromes in cancer survivors (cognitive defect, fertility impairment, etc.). In this article, we propose: (1) telomeres of cancer cells are preferential genomic targets of chemotherapies altering chromosome maintenance; (2) telomere functional parameters can be a surrogate marker of chemotherapy sensitivity and toxicity; (3) the use of anti-telomere molecule could greatly enhance the sensitivity to standards chemotherapies.