Long-term outcomes of 1-2 cm rectal neuroendocrine tumors after local excision or radical resection: A population-based multicenter study.

Objectives: Studies on rectal neuroendocrine tumors (R-NETs) that are 1-2 cm in size are limited, and the optimal treatment for these tumors is not well established. Methods: Data from patients with primary localized R-NETs 1-2 cm in size were retrospectively collected from 17 large-scale referral medical centers in China. Long-term prognosis, quality of life (QOL), and fecal incontinence were evaluated, and the effects of local excision (LE) or radical resection (RR) were elucidated using propensity score matching (PSM). Results: A total of 272 patients were included in this study; 233 underwent LE, and the remaining 39 underwent RR. Patients in the LE group showed lower tumor location, fewer postoperative Clavien-Dindo III-V complications, more G1 tumors, and lower tumor stage. There were no significant differences in the relapse-free survival or overall survival (OS) between the LE and RR groups after PSM. Patients in the LE group reported superior physical, role, emotional, social, and cognitive functions, global QOL, and Wexner fecal incontinence scores compared with those in the RR group (all P < 0.050). Eighteen (6.6%) patients had lymph node metastases. Multivariable analysis revealed that tumor location (odds ratio [OR] = 3.19, 95% confidence interval [CI] 1.04-10.07, P = 0.010), neutrophil-to-lymphocyte ratio (NLR) > 1.80 (OR = 4.50, 1.46-15.89, P = 0.012), and T3-T4 (OR = 36.31, 95% CI 7.85-208.62, P < 0.001) were independent risk factor for lymph node metastasis. Conclusions: R-NETs measuring 1-2 cm generally have a favorable prognosis, and there is no difference in postoperative survival between LE and RR. For patients without lymph node metastasis, LE should be the preferred choice; however, for patients with a higher tumor location, preoperative NLR >1.8 or T3/T4 tumors, RR should be considered.

Inverse association between age and risk of lymph node metastasis in patients with early gastric cancer: a surveillance, epidemiology, and end results analysis.

Background: Recent studies have shown that young patients with gastric cancer are at a more advanced stage and have poor survival, but the cause is still unclear. The prognosis of gastric cancer is closely related to LNM, but the relationship between age and LNM in early gastric cancer (EGC) is currently unclear. Therefore, we aimed to study the relationship between age and the risk of LNM in EGC. Materials and Methods: We screened out patients with EGC who underwent surgery from the SEER research database from 1975 to 2016, and retrospectively analyzed the proportion of LNM in different age groups. We grouped age into 18-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years old, and used univariate analysis and multivariate logistic regression to analyze the correlation between age and LNM. Results: We included 9231 patients with EGC, with LNM rates of 20.3%, 23.3%, 21.0%, 19.8%, 18.1%, and 13.2% in the age groups of 18-39 years old (2.3%), 40-49 (6.1%), 50-59 years old (15.7%), 60-69 years old (24.8%), 70-79 years old (27.2%) and ≥80 years old (23.9%), respectively. We found that when older than 39 years old, the risk of LNM and postoperative survival time of EGC patients decrease (p<0.001). Multivariate analysis results showed that age, tumor size, the number of retrieved lymph nodes (rN), tumor grade, and tumor location were related to LNM. Conclusions: This study found that age in patients with EGC was inversely related to the risk of LNM, and positively correlated with postoperative survival. For older patients with EGC, endoscopic treatment is more appropriate. For young patients with EGC, LNM should be considered when choosing endoscopic treatment.

Hybrid Membrane-Coated Nanoparticles for Precise Targeting and Synergistic Therapy in Alzheimer's Disease.

The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane-coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C-C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single-mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug-loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane-coated nanomaterials offer new opportunities for precise drug delivery and disease-specific targeting, which represent a versatile platform for targeted therapy in AD.

Nonlocal metasurface for dark-field edge emission.

Nonlocal effects originating from interactions between neighboring meta-atoms introduce additional degrees of freedom for peculiar characteristics of metadevices, such as enhancement, selectivity, and spatial modulation. However, they are generally difficult to manipulate because of the collective responses of multiple meta-atoms. Here, we experimentally demonstrate the nonlocal metasurface to realize the spatial modulation of dark-field emission. Plasmonic asymmetric split rings (ASRs) are designed to simultaneously excite local dipole resonance and nonlocal quasi-bound states in the continuum and spatially extended modes. With one type of unit, nonlocal effects are tailored by varying array periods. ASRs at the metasurface's edge lack sufficient interactions, resulting in stronger dark-field scattering and thus edge emission properties of the metasurface. Pixel-level spatial control is demonstrated by simply erasing some units, providing more flexibility than conventional local metasurfaces. This work paves the way for manipulating nonlocal effects and facilitates applications in optical trapping and sorting at the nanoscale.

Multi-step validation of a Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis prediction system integrating multi-modal data: A multi-center study.

BACKGROUND AND STUDY AIMS: The impact of various categories of information on the prediction of Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis (PEP) remains uncertain. We aimed to comprehensively investigate the risk factors associated with PEP by constructing and validating a model incorporating multi-modal data through multiple steps. PATIENTS AND METHODS: A total of 1,916 cases underwent ERCP were retrospectively collected from multiple centers for model construction. Through literature research, 49 electronic health record (EHR) features and one image feature related to PEP were identified. The EHR features were categorized into baseline, diagnosis, technique, and prevent strategies, covering pre-ERCP, intra-ERCP, and peri-ERCP phases. We first incrementally constructed models 1-4 incorporating these four feature categories, then added the image feature into models 1-4 and developed models 5-8. All models underwent testing and comparison using both internal and external test sets. Once the optimal model was selected, we conducted comparison among multiple machine learning algorithms. RESULTS: Compared with model 2 incorporating baseline and diagnosis features, adding technique and prevent strategies (model 4) greatly improved the sensitivity (63.89% vs 83.33%, p<0.05) and specificity (75.00% vs 85.92%, p<0.001). Similar tendency was observed in internal and external tests. In model 4, the top three features ranked by weight were previous pancreatitis, NSAIDS, and difficult cannulation. The image-based feature has the highest weight in model 5-8. Lastly, model 8 employed Random Forest algorithm showed the best performance. CONCLUSIONS: We firstly developed a multi-modal prediction model for identifying PEP with clinical-acceptable performance. The image and technique features are crucial for PEP prediction.

Methylomonas defluvii sp. nov., a type I methane-oxidizing bacterium from a secondary sedimentation tank of a wastewater treatment plant.

An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20 °C to 37 °C (optimum 30 °C). The major cellular fatty acids were C14 : 0, C16 : 1ω7c/C16 : 1ω6c and C16 : 1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64 % 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5 %, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.

Isolation, Identification and Chemical Modification of Bufadienolides from Bufo melanostictus Schneider and Their Cytotoxic Activities against Prostate Cancer Cells.

The traditional Chinese medicine toad venom (Venenum bufonis) has been extensively used to treat various diseases, including cancers, in China and other Southeast Asian countries. The major constituents of toad venom, e.g., bufadienolides and alkaloids, exhibit broad-spectrum pharmacological effects in cancers. Herein, two new bufadienolides (1 and 2), along with eleven known compounds (3-13) were successfully isolated from Bufo melanostictus Schneider. Their structures were elucidated by extensive spectroscopic data and X-ray diffraction analysis. Furthermore, four lactam derivatives were synthesized through the transformation of bufadienolides lactones. The inhibitory effects of these compounds against human prostate cancer cell lines PC-3 and DU145 were evaluated. The outcomes indicated a notable trend, with a substantial subset displaying nanomolar range IC50 values against PC-3 and DU145 cells, underscoring their pronounced cytotoxicity. Moreover, a noteworthy distinction surfaces, wherein lactones consistently outperformed their lactam counterparts, further validating their heightened potency for the treatment of prostate cancer. This study contributes significant preclinical evidence substantiating the therapeutic viability of bufadienolides and toad venom as intervention strategies for prostate cancer.

Clinical manifestation, lifestyle, and treatment patterns of chronic erosive gastritis: A multicenter real-world study in China.

BACKGROUND: Although chronic erosive gastritis (CEG) is common, its clinical characteristics have not been fully elucidated. The lack of consensus regarding its treatment has resulted in varied treatment regimens. AIM: To explore the clinical characteristics, treatment patterns, and short-term outcomes in CEG patients in China. METHODS: We recruited patients with chronic non-atrophic or mild-to-moderate atrophic gastritis with erosion based on endoscopy and pathology. Patients and treating physicians completed a questionnaire regarding history, endoscopic findings, and treatment plans as well as a follow-up questionnaire to investigate changes in symptoms after 4 wk of treatment. RESULTS: Three thousand five hundred sixty-three patients from 42 centers across 24 cities in China were included. Epigastric pain (68.0%), abdominal distension (62.6%), and postprandial fullness (47.5%) were the most common presenting symptoms. Gastritis was classified as chronic non-atrophic in 69.9% of patients. Among those with erosive lesions, 72.1% of patients had lesions in the antrum, 51.0% had multiple lesions, and 67.3% had superficial flat lesions. In patients with epigastric pain, the combination of a mucosal protective agent (MPA) and proton pump inhibitor was more effective. For those with postprandial fullness, acid regurgitation, early satiety, or nausea, a MPA appeared more promising. CONCLUSION: CEG is a multifactorial disease which is common in Asian patients and has non-specific symptoms. Gastroscopy may play a major role in its detection and diagnosis. Treatment should be individualized based on symptom profile.

Absence of long-term balancing selection on variation in EuMYB3, an R2R3-MYB gene responsible for the anther-color polymorphism in Erythronium umbilicatum.

Balancing selection has been shown to be common in plants for several different types of traits, such as self-incompatibility and heterostyly. Generally, for these traits balancing selection is generated by interactions among individuals or between individuals and other species (e.g., pathogens or pollinators). However, there are phenotypic polymorphisms in plants that do not obviously involve types of interactions that generate balancing selection. Little is known about the extent to which balancing selection also acts to preserve these polymorphisms. Here we ask whether balancing selection preserves an anther-color polymorphism in Erythronium umbilicatum (Liliaceae). We identified a major gene underlying this polymorphism. We then attempted to detect signatures of balancing selection on that gene by developing a new coalescence test for balancing selection. We found that variation in anther color is in large part caused by variation in a paralog of EuMYB3, an anthocyanin-regulating R2R3-MYB transcription factor. However, we found little evidence for balancing selection having acted historically on EuMYB3. Our results thus suggest that plant polymorphisms, especially those not involved in interactions that are likely to generate negative frequency-dependent selection, may reflect a transient state in which one morph will eventually be fixed by either genetic drift or directional selection. Our results also suggest that regulation of the anthocyanin pathway is more evolutionarily labile than is generally believed.

Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis.

Stroke is a debilitating condition that often leads to disability and death. The increasing prevalence of stroke has drawn worldwide attention. Extensive evidence indicates a crucial role of genetic determinants in the occurrence and perpetuation of stroke. An Icelandic study identified a significant correlation of the phosphodiesterase 4D (PDE4D) single-nucleotide polymorphism (SNP) rs2910829 with stroke susceptibility. However, subsequent studies reported in Chinese populations were contradictory. We implemented a meta-analysis to inspect whether SNP rs2910829 is related to stroke susceptibility in Chinese populations and subsequently performed an in silico analysis to predict its potential functions. Finally, we analysed data from 24 studies comprising 7,484 Chinese stroke patients and 7,962 control individuals. Compared with the CC genotype, the TT genotype was associated with increased susceptibility to stroke (pooled odds ratio [OR] 1.28, 95% confidence interval [CI] 1.13-1.46, P < 0.001), whereas the CT genotype was not. Correspondingly, a significant association was detected under the recessive model (TT vs CT + CC: OR 1.30, 95% CI 1.15-1.47, P < 0.001). Similar results were obtained in large artery atherosclerosis (LAA) stroke but not in small vessel stroke. Bioinformatics analysis also revealed that SNP rs2910829 and its linked SNPs might be implicated in transcriptional regulation. This meta-analysis reveals significant relationships between the PDE4D SNP rs2910829 and susceptibility to stroke and subtype-LAA stroke in Chinese individuals, and further investigations are warranted to evaluate this effect.

Nuclear transport of phosphorylated LanCL2 promotes invadopodia formation and tumor progression of glioblastoma by activating STAT3/Cortactin signaling.

INTRODUCTION: Our previous study showed that the abscisic acid receptor lanthionine synthetase C-like 2 (LanCL2) is a significant prognostic factor for overall survival in young glioblastoma patients. However, the role of LanCL2 in glioblastoma remains unclear yet. OBJECTIVES: This study aims to investigate the role of LanCL2 in regulating in-vitro cell invasion and in-vivo tumor progression of glioblastoma and its underlying mechanism. METHODS: Tyrosine 198 or 295 residue of LanCL2 was mutated using site-directed mutagenesis to block its phosphorylation. The role of LanCL2 in glioblastoma was investigated using transwell or 3D invasion assay, matrix degradation assay and intracranial xenograft model. RESULTS: This study showed that nuclear transport of LanCL2 was enhanced by overexpression of LanCL2 or its ligand abscisic acid in glioblastoma cells. Knockdown of LanCL2 suppressed migration, invasion and invadopodia formation of glioblastoma cells, whereas overexpression of wild-type LanCL2 enhanced them. Blocking of Tyr295 residue phosphorylation of LanCL2 impeded its nuclear transport, retarded glioblastoma cell motility and invadopodia formation, and deceased the phosphorylation of Cortactin and STAT3. c-Met was identified as the upstream tyrosine kinase of Tyr295 residue of LanCL2, and inhibition of c-Met markedly suppressed the nuclear transport of LanCL2. Moreover, overexpression of wild-type LanCL2 significantly promoted orthotopic tumor growth of glioblastoma in vivo and led to poor survival of mice with median survival time of 33.5 days, whereas Tyr295 mutation rescued it with median survival time of 49 days. CONCLUSION: Our findings suggested that Tyr295 phosphorylation is crucial to the activation and nuclear transport of LanCL2, as well as invadopodia formation and tumor progression of glioblastoma, providing the evidence of a novel signaling axis c-Met/LanCL2/STAT3/Cortactin and the first observation of the importance of Tyr295 phosphorylation to LanCL2.

Physical therapy for acute and sub-acute low back pain: A systematic review and expert consensus.

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.

Validation and psychometric testing of the Chinese version of the prenatal body image questionnaire.

BACKGROUND: The body image during pregnancy potentially affects both short- and long-term maternal and child health outcomes, including pregnancy mood, postpartum weight recovery, and the quality of mother-child interactions. However, research on the impact of body changes during pregnancy in the Chinese population is scarce. A comprehensive, practical, and reliable tool for assessing pregnant women is needed to detect, intervene in, and implement the reduction of physical dissatisfaction risk. This study translated the Prenatal Body Image Questionnaire (PBIQ) into the Chinese version (PBIQ-C) to assess the body image of pregnant women and evaluated its reliability and validity. METHODS: An improved Brislin translation model was used for the translation. A panel of experts determined the content validity. A convenience sample of 429 pregnant women was chosen from three third-class hospitals in different regions of Fujian Province, China. Factor analysis, Pearson's correlation, retest reliability, and Cronbach's alpha were employed to evaluate structural validity and reliability. RESULTS: The final PBIQ-C had five dimensions with 21 items. Exploratory factor analysis obtained a five-factor solution, which accounted for a total of 60.34%. Confirmatory factor analysis showed that the model fit of the five-factor model also reached a satisfactory model fit after modifying: The Comparative Fit Index was 0.93, and the Tucker-Lewis Index was 0.92; the Root Mean Square Error of Approximation was 0.079. The content validity index of the scale ranged from 0.63 ~ 1.00. The Cronbach's alpha coefficient was 0.95 for the total scale, and the test-retest reliability was 0.80. CONCLUSIONS: The findings indicated that the PBIQ-C is a valid and reliable instrument for assessing women's body image during pregnancy, which helps in the early identification of body dissatisfaction during pregnancy and enables the early prevention of postpartum depression.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

The impact of age and number of mutations on the size of clonal hematopoiesis.

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.

TRAF2 decrease promotes the TGF-ß-mTORC1 signal in MAFLD-HCC through enhancing AXIN1-mediated Smad7 degradation.

According to recent research, metabolic-associated fatty liver disease (MAFLD) has emerged as an important underlying etiology of hepatocellular carcinoma (HCC). However, the molecular mechanism of MAFLD-HCC is still unclear. Tumor necrosis factor receptor-associated factor 2 (TRAF2) is the key molecule to mediate the signal of inflammatory NF-κB pathway. This study aims to investigate the potential dysregulation of TRAF2 and its biological function in MAFLD-HCC. Huh7 TRAF2-/- demonstrated increased tumor formation ability compared to huh7 TRAF2+/+ when stimulated with transforming growth factor-ß (TGF-ß). The decisive role of TGF-ß in the development of MAFLD-HCC was confirmed through the specific depletion of TGF-ß receptor II gene in the hepatocytes (Tgfbr2ΔHep) of mice. In TRAF2-/- cells treated with TGF-ß, both the glycolysis rate and lipid synthesis were enhanced. We proved the signal of the mechanistic target of rapamycin complex 1 (mTORC1) could be activated in the presence of TGF-ß, and was enhanced in TRAF2-/- cells. The coimmunoprecipitation (co-IP) experiments revealed that TRAF2 fortified the Smurf2-mediated ubiquitination degradation of AXIN1. Hence, TRAF2 depletion resulted in increased Smad7 degradation induced by AXIN1, thus promoting the TGF-ß signal. We also discovered that PLX-4720 could bind with AXIN1 and restrained the tumor proliferation of TRAF2-/- in mice fed with high-fat diet (HFD). Our findings indicate that TRAF2 plays a significant role in the pathogenesis of MAFLD-HCC. The reduction of TRAF2 expression leads to the enhancement of the TGF-ß-mTORC1 pathway by facilitating AXIN1-mediated Smad7 degradation.

Role and Mechanism of Epigenetic Regulation in the Aging of Germ Cells: Prospects for Targeted Interventions.

In modern times, a notable trend toward delayed childbearing has been observed in most developed countries. As a result, sperm aging and quality loss, as well as premature ovarian failure (POF), have emerged as major causes of infertility. The pathogenesis of sperm aging and POF is complex and has not been clearly elucidated. However, evidence from some studies has linked germ cell aging to epigenetic modifications. Epigenetics refers to the heritable changes in gene expression that occur in the absence of any alterations to the gene's nucleotide sequence. This paper systematically reviewed and analyzed the relevant literature to describe the relationship of DNA methylation, non-coding RNA regulation, histone modifications, chromatin remodeling, and RNA modifications with sperm aging and POF. In addition, we analyzed how sperm aging and POF can be mitigated via epigenetic interventions. This review could provide new therapeutic insights and guide strategies for improving sperm quality and ovarian function.

A nomogram incorporating treatment data for predicting overall survival in gastroenteropancreatic neuroendocrine tumors: a population-based cohort study.

BACKGROUND: Over the last few decades, the annual global incidence of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) has steadily increased. Because of the complex and inconsistent treatment of GEP-NETs, the prognosis of patients with GEP-NETs is still difficult to assess. The study aimed to construct and validate the nomograms included treatment data for prediction overall survival (OS) in GEP-NETs patients. METHODS: GEP-NETs patients determined from the Surveillance, Epidemiology, and End Results (SEER)-13 registry database (1992-2018) and with additional treatment data from the SEER-18 registry database (1975-2016). In order to select independent prognostic factors that contribute significantly to patient survival and can be included in the nomogram, multivariate Cox regression analysis was performed using the minimum value of Akaike information criterion (AIC) and we analyzed the relationship of variables with OS by calculating hazard ratios (HRs) and 95% CIs. In addition, we also comprehensively compared the nomogram using to predict OS with the current 7th American Joint Committee on Cancer (AJCC) staging system. RESULTS: From 2004 to 2015, a total of 42 662 patients at diagnosis years with GEP-NETs were determined from the SEER database. The results indicated that the increasing incidence of GEP-NETs per year and the highest incidence is in patients aged 50-54. After removing cases lacking adequate clinicopathologic characteristics, the remaining eligible patients ( n =7564) were randomly divided into training (3782 patients) and testing sets (3782 patients). In the univariate analysis, sex, age, race, tumour location, SEER historic stage, pathology type, TNM, stage, surgery, radiation, chemotherapy, and CS tumour size were found to be significantly related to OS. Ultimately, the key factors for predicting OS were determined, involving sex, age, race, tumour location, SEER historic stage, M, N, grade, surgery, radiation, and chemotherapy. For internal validation, the C-index of the nomogram used to estimate OS in the training set was 0.816 (0.804-0.828). For external validation, the concordance index (C-index) of the nomogram used to predict OS was 0.822 (0.812-0.832). In the training and testing sets, our nomogram produced minimum AIC values and C-index of OS compared with AJCC stage. Decision curve analysis (DCA) indicated that the nomogram was better than the AJCC staging system because more clinical net benefits were obtained within a wider threshold probability range. CONCLUSION: A nomogram combined treatment data may be better discrimination in predicting overall survival than AJCC staging system. The authors highly recommend to use their nomogram to evaluate individual risks based on different clinical features of GEP-NETs, which can improve the diagnosis and treatment outcomes of GEP-NETs patients and improve their quality of life.

The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.