Racial and ethnic differences in epithelial ovarian cancer risk: an analysis from the Ovarian Cancer Association Consortium.

BACKGROUND: Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander (NHPI) women. METHODS: Participants included 1734 Asian (785 cases, 949 controls), 266 NHPI (99 cases, 167 controls), 1149 Hispanic (505 cases, 644 controls), and 24,189 White (9,981 cases, 14,208 controls) women from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations by race and ethnicity. RESULTS: Heterogeneity in EOC risk associations by race and ethnicity (p ≤ 0.02) was observed for oral contraceptive (OC) use, parity, tubal ligation and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in NHPI and Asian women. The inverse association for tubal ligation with risk was most pronounced for NHPI participants (OR=0.25, 95% CI 0.13-0.48), versus Asian and White participants, respectively (OR=0.68, 95% CI 0.51-0.90; OR=0.78, 95% CI 0.73-0.85). CONCLUSIONS: Differences in EOC risk factor associations were observed across racial and ethnic groups, which could in part be due to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies.

CD163+ macrophages in the triple-negative breast tumor microenvironment are associated with improved survival in the Women's Circle of Health Study and the Women's Circle of Health Follow-Up Study.

BACKGROUND: Tumor-associated macrophages (TAMs) are a prominent immune subpopulation in the tumor microenvironment that could potentially serve as therapeutic targets for breast cancer. Thus, it is important to characterize this cell population across different tumor subtypes including patterns of association with demographic and prognostic factors, and breast cancer outcomes. METHODS: We investigated CD163+ macrophages in relation to clinicopathologic variables and breast cancer outcomes in the Women's Circle of Health Study and Women's Circle of Health Follow-up Study populations of predominantly Black women with breast cancer. We evaluated 611 invasive breast tumor samples (507 from Black women, 104 from White women) with immunohistochemical staining of tissue microarray slides followed by digital image analysis. Multivariable Cox proportional hazards models were used to estimate hazard ratios for overall survival (OS) and breast cancer-specific survival (BCSS) for 546 cases with available survival data (median follow-up time 9.68 years (IQR: 7.43-12.33). RESULTS: Women with triple-negative breast cancer showed significantly improved OS in relation to increased levels of tumor-infiltrating CD163+ macrophages in age-adjusted (Q3 vs. Q1: HR = 0.36; 95% CI 0.16-0.83) and fully adjusted models (Q3 vs. Q1: HR = 0.30; 95% CI 0.12-0.73). A similar, but non-statistically significant, association was observed for BCSS. Macrophage infiltration in luminal and HER2+ tumors was not associated with OS or BCSS. In a multivariate regression model that adjusted for age, subtype, grade, and tumor size, there was no significant difference in CD163+ macrophage density between Black and White women (RR = 0.88; 95% CI 0.71-1.10). CONCLUSIONS: In contrast to previous studies, we observed that higher densities of CD163+ macrophages are independently associated with improved OS and BCSS in women with invasive triple-negative breast cancer. Trial registration Not applicable.

Dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer.

Objectives: In this study, we compared the dynamic changes in body composition during XELOX/SOX chemotherapy in patients with gastric cancer. Furthermore, we investigated the potential impact of these changes on the occurrence of toxic side effects. Methods: Patients with gastric cancer who received adjuvant or first-line XELOX/SOX chemotherapy between January 2020 and June 2023 were enrolled. The Brief Conghua Scale was used to assess energy intake, and nutritional management was carried out with reference to the Chinese Guidelines for Nutritional Therapy of Cancer 2020. The NRS 2002 Nutritional Risk Screening Scale, PG-SGA scale, bioelectrical impedance analysis, and dynamic changes in lumbar 3 vertebral skeletal muscle index were compared between baseline and post-chemotherapy in the study. The neutropenia was evaluated using the Common Terminology Criteria for Adverse Events V.5.0, developed by the National Institutes of Health. Results: Dynamic follow-up was completed in 39 cases, with a mean follow-up time of 117.62 ± 43.38 days. The incidence of sarcopenia increased significantly after chemotherapy, escalating from 46.2% to 51.3%. After chemotherapy, the mean L3SMI decreased from 36.00 cm2/m2 to 34.99 cm2/m2. Furthermore, when compared to pre-chemotherapy values, the body composition indexes body mass index (BMI), SL3, fat mass free index (FFMI), lean body mass (LBM), and body surface area (BSA) were significantly reduced after chemotherapy. Regardless of baseline or post-chemotherapy status, the incidence of grade ≥ 3 neutropenia was significantly higher in the sarcopenia group than in the non-sarcopenia group. Furthermore, when the skeletal muscle index decreased during chemotherapy, the incidence of grade ≥ 3 neutropenia was significantly higher in both the sarcopenia and non-sarcopenia groups compared to baseline. When the incidence of grade ≥ 3 neutropenia in the post-chemotherapy sarcopenia group was compared to baseline status, the increase was significantly higher in the sarcopenia group than in the maintenance/increase group. Conclusions: Skeletal muscle mass decreased progressively during XELOX/SOX chemotherapy in gastric cancer patients, followed by a higher incidence of grade ≥ 3 neutropenia.

Comparing patient-reported outcomes and lifestyle factors before and after the COVID-19 pandemic among Black and Hispanic breast cancer survivors in New Jersey.

PURPOSE: The impact of the COVID-19 pandemic restrictions in the US since March 2020 on cancer survivorship among Black and Hispanic breast cancer (BC) survivors remains largely unknown. We aimed to evaluate associations of the pandemic with participant characteristics, patient-reported outcomes (PROs), and lifestyle factors among Black and Hispanic BC survivors in the Women's Circle of Health Follow-Up Study and the New Jersey BC Survivors Study. METHODS: We included 447 Black (npre = 364 and npost = 83) and 182 Hispanic (npre = 102 and npost = 80) BC survivors who completed a home interview approximately 24 months post-diagnosis between 2017 and 2023. The onset of the pandemic was defined as March 2020. The association of the pandemic with binary outcomes was estimated using robust Poisson regression models. RESULTS: Hispanic and Black BC survivors recruited after the onset of the pandemic reported higher socioeconomic status and fewer comorbidities. Black women in the post-pandemic group reported a higher prevalence of clinically significant sleep disturbance (prevalence ratio (PR) 1.43, 95% CI 1.23, 1.68), lower sleep efficiency, and lower functional well-being, compared to the pre-pandemic group. Hispanic women were less likely to report low health-related quality of life (vs. high; PR 0.62, 95% CI 0.45, 0.85) after the onset of the pandemic. CONCLUSIONS: Ongoing research is crucial to untangle the impact of the pandemic on racial and ethnic minorities participating in cancer survivorship research, as well as PROs and lifestyle factors. IMPLICATIONS FOR CANCER SURVIVORS: This study highlights the importance of considering the impact of the pandemic in all aspects of research, including the interpretation of findings.

Albiflorin ameliorates thioacetamide-induced hepatic fibrosis: The involvement of NURR1-mediated inflammatory signaling cascades in hepatic stellate cells activation.

Thioacetamide (TAA) within the liver generates hepatotoxic metabolites that can be induce hepatic fibrosis, similar to the clinical pathological features of chronic human liver disease. The potential protective effect of Albiflorin (ALB), a monoterpenoid glycoside found in Paeonia lactiflora Pall, against hepatic fibrosis was investigated. The mouse hepatic fibrosis model was induced with an intraperitoneal injection of TAA. Hepatic stellate cells (HSCs) were subjected to treatment with transforming growth factor-beta (TGF-ß), while lipopolysaccharide/adenosine triphosphate (LPS/ATP) was added to stimulate mouse peritoneal macrophages (MPMs), leading to the acquisition of conditioned medium. For TAA-treated mice, ALB reduced ALT, AST, HYP levels in serum or liver. The administration of ALB reduced histopathological abnormalities, and significantly regulated the expressions of nuclear receptor-related 1 protein (NURR1) and the P2X purinoceptor 7 receptor (P2×7r) in liver. ALB could suppress HSCs epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, and pro-inflammatory factor level. ALB also remarkably up-regulated NURR1, inhibited P2×7r signaling pathway, and worked as working as C-DIM12, a NURR1 agonist. Moreover, deficiency of NURR1 in activated HSCs and Kupffer cells weakened the regulatory effect of ALB on P2×7r inhibition. NURR1-mediated inhibition of inflammatory contributed to the regulation of ALB ameliorates TAA-induced hepatic fibrosis, especially based on involving in the crosstalk of HSCs-macrophage. Therefore, ALB plays a significant part in the mitigation of TAA-induced hepatotoxicity this highlights the potential of ALB as a protective intervention for hepatic fibrosis.

Semi-Bone Tunnel Technique Using Double-Row Suture Bridge Combined With Platelet-Rich Plasma Hydrogel for Rotator Cuff Repair in a Rabbit Model.

BACKGROUND: The approach to managing the footprint area and reconstructing the tendon-bone interface (TBI) is critical for optimal healing. PURPOSE: To evaluate the outcomes of the semi-bone tunnel (SBT) technique using a double-row suture bridge combined with platelet-rich plasma (PRP) hydrogel for rotator cuff repair in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 48 New Zealand White rabbits were divided into 4 groups. The supraspinatus tendons were severed at the footprint to create a rotator cuff tear model in the surgical groups. Rabbits were treated with the traditional onto-surface repair (control group), SBT technique (SBT group), and SBT technique combined with PRP hydrogel implantation (SBT+PRP group). The rabbits without surgery were the normal group. At 8 weeks after surgery, macroscopic observation, magnetic resonance imaging (MRI) and micro-computed tomography (µCT) examinations, histological evaluations, and biomechanical tests were performed to assess the curative effects of the given treatments. RESULTS: The MRI results showed that the repaired supraspinatus tendon presented a uniform signal, minimal inflammatory response, and the lowest signal-to-noise quotient value in the SBT+PRP group. The µCT results suggested that the SBT technique did not reduce the local bone mineral density in the TBI area compared with the onto-surface repair technique. The histological staining results showed that the regenerated TBI in the SBT+PRP group had a 4-layer structure similar to the natural tissue. The highest values for biomechanical properties were observed in the SBT+PRP group, and there was no significant difference between the SBT+PRP group and normal group. CONCLUSION: The SBT technique presented a better tendon-bone healing effect for rotator cuff tear in the rabbit model compared with the traditional onto-surface repair technique. The specimens in the SBT+PRP group had a similar TBI structure and biomechanical properties to the natural tissue. CLINICAL RELEVANCE: The SBT technique can be an alternative surgical approach for rotator cuff repair, especially for moderate to large tears and cases requiring scaffold implantation.

Risk of HBV reactivation in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors in the antiviral era.

BACKGROUND: Although routine antiviral therapy has been implemented in HCC patients, the risk of HBV reactivation (HBVr) remains with the use of programmed cell death-1(PD-1) blockade-based combination immunotherapy and the relevant risk factors are also unclear. Therefore, we aimed to identify the incidence and risk factors of HBVr in HCC patients undergoing combination therapy of PD-1 inhibitors and angiogenesis inhibitors and concurrent first-line antivirals. METHODS: We included a total of 218 HBV-related HCC patients with first-line antivirals who received PD-1 inhibitors alone or together with angiogenesis inhibitors. According to the anti-tumor therapy modalities, patients were divided into PD-1 inhibitors monotherapy group (anti-PD-1 group) and combination therapy group (anti-PD-1 plus angiogenesis inhibitors group). The primary study endpoint was the incidence of HBVr. RESULTS: HBVr occurred in 16 (7.3%) of the 218 patients, 2 cases were found in the anti-PD-1 group and the remaining 14 cases were in the combination group. The Cox proportional hazard model identified 2 independent risk factors for HBVr: combination therapy (hazard ratio [HR], 4.608, 95%CI 1.010-21.016, P = 0.048) and hepatitis B e antigen (HBeAg) positive (HR, 3.695, 95%CI 1.246-10.957, P = 0.018). Based on the above results, we developed a simple risk-scoring system and found that the high-risk group (score = 2) developed HBVr more frequently than the low-risk group (score = 0) (Odds ratio [OR], 17.000, 95%CI 1.946-148.526, P = 0.01). The area under the ROC curve (AUC-ROC) was 7.06 (95%CI 0.581-0.831, P = 0.006). CONCLUSION: HBeAg-positive patients receiving combination therapy have a 17-fold higher risk of HBVr than HBeAg-negative patients with PD-1 inhibitors monotherapy.

From theory to therapy: a bibliometric and visual study of stem cell advancements in age-related macular degeneration.

BACKGROUND AIMS: Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, offer groundbreaking therapeutic potential for degenerative diseases and cellular repair. Despite their significance, a comprehensive bibliometric analysis in this field, particularly in relation to age-related macular degeneration (AMD), is yet to be conducted. This study aims to map the foundational and emerging areas in stem cell and AMD research through bibliometric analysis. METHODS: This study analyzed articles and reviews on stem cells and AMD from 2000 to 2022, sourced from the Web of Science Core Collection. We used VOSviewer and CiteSpace for analysis and visualization of data pertaining to countries, institutions, authors, journals, references and key words. Statistical analyses were conducted using R language and Microsoft Excel 365. RESULTS: In total, 539 publications were included, indicating an increase in global literature on stem cells and AMD from 2000 to 2022. The USA was the leading contributor, with 239 papers and the highest H-index, also the USA had the highest average citation rate per article (59.82). Notably, 50% of the top 10 institutions were from the USA, with the University of California system being the most productive. Key authors included Masayo Takahashi, Michiko Mandai, Dennis Clegg, Pete J. Coffey, Boris Stanzel, and Budd A. Tucker. Investigative Ophthalmology & Visual Science published the majority of relevant papers (n = 27). Key words like "clinical trial," "stem cell therapy," "retinal organoid," and "retinal progenitor cells" were predominant. CONCLUSIONS: Research on stem cells and AMD has grown significantly, highlighting the need for increased global cooperation. Current research prioritizes the relationship between "ipsc," "induced pluripotent stem cell," "cell culture," and "human embryonic stem cell." As stem cell culture and safety have advanced, focus has shifted to prognosis and complications post-transplantation, signifying the movement of stem cell research from labs to clinical settings.

Identification and effective regulation of scarb1 gene involved in pigmentation change in autotetraploid Carassius auratus.

The autotetraploid Carassius auratus (4nRR, 4 n=200, RRRR) is derived from whole-genome duplication of Carassius auratus red var. (RCC, 2 n=100, RR). In the current study, we demonstrated that chromatophores and pigment changes directly caused the coloration and variation of 4nRR skin (red in RCC, brownish-yellow in 4nRR). To further explore the molecular mechanisms underlying coloration formation and variation in 4nRR, we performed transcriptome profiling and molecular functional verification in RCC and 4nRR. Results revealed that scarb1, associated with carotenoid metabolism, underwent significant down-regulation in 4nRR. Efficient editing of this candidate pigment gene provided clear evidence of its significant role in RCC coloration. Subsequently, we identified four divergent scarb1 homeologs in 4nRR: two original scarb1 homeologs from RCC and two duplicated ones. Notably, three of these homeologs possessed two highly conserved alleles, exhibiting biased and allele-specific expression in the skin. Remarkably, after precise editing of both the original and duplicated scarb1 homeologs and/or alleles, 4nRR individuals, whether singly or multiply mutated, displayed a transition from brownish-yellow skin to a cyan-gray phenotype. Concurrently, the proportional areas of the cyan-gray regions displayed a gene-dose correlation. These findings illustrate the subfunctionalization of duplicated scarb1, with all scarb1 genes synergistically and equally contributing to the pigmentation of 4nRR. This is the first report concerning the functional differentiation of duplicated homeologs in an autopolyploid fish, substantially enriching our understanding of coloration formation and change within this group of organisms.

Regulation of the Nur77-P2X7r Signaling Pathway by Nodakenin: A Potential Protective Function against Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is the main factor that induces liver-related death worldwide and represents a common chronic hepatopathy resulting from binge or chronic alcohol consumption. This work focused on revealing the role and molecular mechanism of nodakenin (NK) in ALD associated with hepatic inflammation and lipid metabolism through the regulation of Nur77-P2X7r signaling. In this study, an ALD model was constructed through chronic feeding of Lieber-DeCarli control solution with or without NK treatment. Ethanol (EtOH) or NK was administered to AML-12 cells, after which Nur77 was silenced. HepG2 cells were exposed to ethanol (EtOH) and subsequently treated with recombinant Nur77 (rNur77). Mouse peritoneal macrophages (MPMs) were treated with lipopolysaccharide/adenosine triphosphate (LPS/ATP) and NK, resulting in the generation of conditioned media. In vivo, histopathological alterations were markedly alleviated by NK, accompanied by reductions in serum triglyceride (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and the modulation of Lipin-1, SREBP1, and Nur77 levels in comparison to the EtOH-exposed group (p < 0.001). Additionally, NK reduced the production of P2X7r and NLRP3. NK markedly upregulated Nur77, inhibited P2X7r and Lipin-1, and promoted the function of Cytosporone B, a Nur77 agonist (p < 0.001). Moreover, Nur77 deficiency weakened the regulatory effect of NK on P2X7r and Lipin-1 inhibition (p < 0.001). In NK-exposed MPMs, cleaved caspase-1 and mature IL-1ß expression decreased following LPS/ATP treatment (p < 0.001). NK also decreased inflammatory-factor production in primary hepatocytes stimulated with MPM supernatant. NK ameliorated ETOH-induced ALD through a reduction in inflammation and lipogenesis factors, which was likely related to Nur77 activation. Hence, NK is a potential therapeutic approach to ALD.

Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema.

AIM: To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide (TA) in treating diabetic macular edema (DME) and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection. METHODS: Totally 67 DME patients (67 eyes) and 30 cataract patients (32 eyes) were enrolled as the DME group and the control group, respectively. The DME group was divided into the aflibercept group (34 cases) and the aflibercept combined with TA group (combined group, 33 cases). The aqueous humor of both groups was collected during the study period. The aqueous levels of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß) were detected using a microsphere suspension array technology (Luminex 200TM). Aqueous cytokines, best-corrected visual acuity (BCVA), central macular thickness (CMT), and complications before and after treatment were compared between the aflibercept group and combined group. RESULTS: The concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group (all P<0.01). After 1mo of surgery, the concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group (all P<0.01). The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment (P<0.01). However, the difference was not statistically significant after 3mo of treatment (P>0.05). CONCLUSION: The cytokines VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor of DME patients are significantly increased. Aflibercept and aflibercept combined with TA have good efficacy in DME patients, can effectively reduce CMT, improve the patient's vision, and have high safety. Aflibercept combined with TA can quickly down-regulate the aqueous humor cytokines and help to relieve macular edema rapidly. However, the long-term efficacy is comparable to that of aflibercept alone.

Addressing Social Risks to Accelerate Health Equity in Cancer Prevention and Control.

Addressing social risks in cancer prevention and control presents a new opportunity for accelerating cancer health equity. As members of the American Society of Preventive Oncology (ASPO) Cancer Health Disparities Special Interest Group, we describe the current state of science on social risks in oncology research and practice. To reduce and eliminate the unjust burden of cancer, we also provide recommendations for multilevel research examining social risks as contributors to inequities and the development of social risks-focused interventions. Suggestions for research and practice are provided within levels of the socio-ecological model, including the interpersonal, organizational, community, and policy levels.

Characterization of the Microbial Community Structures, Soil Chemical Properties, and Enzyme Activity of Stellera chamaejasme (Thymelaeaceae) and Its Associated Forages in Alpine Grassland of Northwestern China.

The invasion of toxic weeds was detrimental to the growth of original vegetation and speed up the degraded grasslands. The purpose of this study was to explore the difference in microbial community, soil physicochemical properties, and enzyme activity in the rhizosphere of Stellera chamaejasme and its associated forages (Stipa purpurea and Polygonum viviparum). The rhizosphere soil microbial communities of S. chamaejasme and its associated forages were determined by high-throughput sequencing technology, the physicochemical properties, and enzyme activities were also measured using soil chemical methods. We performed biological statistical analyses to explore the correlation of rhizosphere micro-ecological environment between the invading poisonous herb S. chamaejasme and its associated forages. The Ascomycota community in the rhizosphere soil of S. chamaejasme was significantly decreased when compared with its associated forages. S. chamaejasme and S. purpurea had a similar bacterial composition, while the rhizosphere of P. viviparum was associated with more Acidobacteria and Bacteroidetes. The RDA analysis showed S. chamaejasme had highly correlated with acid proteinase, invertase, polyphenol oxidase, cellulose, and neutral protease and S. purpurea had highly associated with N-acetyl-beta-D-glucosaminidase, ß-D-Glucosidase, and the P. viviparum had highly associated with total phosphorus, total nitrogen, ammonium nitrogen, soil organic matter, pH, acid phosphatase, and catalase. Along with the invasion of S. chamaejasme, the microbial composition, soil physicochemical properties, and enzyme activity of the growing area changed considerably compared with the associated forages. Taken together, our results suggested that the composition and diversity of microbial communities associated with S. chamaejasme and its associated forages exhibited different patterns, and the rhizosphere soil microbial communities in different plants were regulated by different environmental factors in this alpine grassland ecosystem.

Bibliometric analysis of global research trends in adeno-associated virus vector for gene therapy (1991-2022).

Background: Gene therapy involves introducing and editing foreign genes in the body to treat and prevent genetic diseases. Adeno-associated virus (AAV) vector has become a widely used tool in gene therapy due to its high safety and transfection efficiency. Methods: This study employs bibliometric analysis to explore the foundation and current state of AAV vector application in gene therapy research. A total of 6,069 publications from 1991 to 2022 were analyzed, retrieved from the Science Citation Index Expanded (SCI-E) within the Web of Science Core Collection (WoSCC) of Clarivate Analytics. Institutions, authors, journals, references, and keywords were analyzed and visualized by using VOSviewer and CiteSpace. The R language and Microsoft Excel 365 were used for statistical analyses. Results: The global literature on AAV vector and gene therapy exhibited consistent growth, with the United States leading in productivity, contributing 3,868 papers and obtaining the highest H-index. Noteworthy authors like Wilson JM, Samulski RJ, Hauswirth WW, and Mingozzi F were among the top 10 most productive and co-cited authors. The journal "Human Gene Therapy" published the most papers (n = 485) on AAV vector and gene therapy. Current research focuses on "gene editing," "gene structure," "CRISPR," and "AAV gene therapy for specific hereditary diseases." Conclusion: The application of AAV vector in gene therapy has shown continuous growth, fostering international cooperation among countries and institutions. The intersection of gene editing, gene structure, CRISPR, and AAV gene therapy for specific hereditary diseases and AAV vector represents a prominent and prioritized focus in contemporary gene therapy research. This study provides valuable insights into the trends and characteristics of AAV gene therapy research, facilitating further advancements in the field.

Symmetrical femtosecond laser arc incision in correcting corneal astigmatism in cataract patients.

AIM: To evaluate the effect of symmetrical arc incision correcting corneal astigmatism in femtosecond laser-assisted phacoemulsification (FLACS). METHODS: This study enrolled patients with cataract combined with regular corneal astigmatism of >0.75 D, who underwent FLACS. Symmetrical arc incision was set at 8 mm diameter and 85% depth. The follow-up time was 3-24mo (4.92±3.49mo). Pentacam recorded the corneal astigmatism and higher-order aberration at pre-operation and post-operation. The changes in corneal astigmatism were analyzed by Alpins method. The correlation of astigmatism type, age, corneal horizontal diameter, corneal thickness, arc incision length, and correction index (CI) was analyzed, and the residual corneal astigmatism was compared with the residual whole eye astigmatism. RESULTS: Totally 79 patients (102 eyes) were enrolled, 10 patients had corneal epithelial injury, 1 patient occurred corneal epithelial hyperplasia. The corneal astigmatism was 1.23±0.38 D pre-operation, and decreased to 0.76±0.39 D post-operation (t=10.146, P=0.000). Corneal high-order aberration was 0.17±0.08 µm pre-operation and 0.24±0.11 µm post-operation (t=-5.186, P=0.000). The residual corneal astigmatism and residual whole eye astigmatism were no significant difference (t=-0.347, P=0.729). Using Alpin's method, the following were determined: target-induced astigmatism (TIA) =1.23±0.38 D, surgery-induced astigmatism (SIA) =0.77±0.45 D, difference vector (DV)=0.77±0.39 D, and CI=0.54±0.28. Age, astigmatism size, corneal horizontal diameter, corneal thickness, and arc incision length were not correlated with CI. The CI for against the rule astigmatism (ATR) was better than that for with the rule astigmatism (WTR; P=0.001). CONCLUSION: Femtosecond laser-assisted astigmatic keratotomy has better CI of ATR, but increase higher-order corneal aberration. CI is not ideal, it's not a perfect choice if we pursue ideal correction effect.

Advancing Social and Environmental Research in Cancer Registries Using Geomasking for Address-Level Data.

Understanding the social and environmental causes of cancer in the United States, particularly in marginalized communities, is a major research priority. Population-based cancer registries are essential for advancing this research, given their nearly complete capture of incident cases within their catchment areas. Most registries limit the release of address-level geocodes linked to cancer outcomes to comply with state health departmental regulations. These policies ensure patient privacy, uphold data confidentiality, and enhance trust in research. However, these restrictions also limit the conduct of high-quality epidemiologic studies on social and environmental factors that may contribute to cancer burden. Geomasking refers to computational algorithms that distort locational data to attain a balance between effectively "masking" the original address location while faithfully maintaining the spatial structure in the data. We propose that the systematic deployment of scalable geomasking algorithms could accelerate research on social and environmental contributions across the cancer continuum by reducing measurement error bias while also protecting privacy. We encourage multidisciplinary teams of registry officials, geospatial analysts, cancer researchers, and others engaged in this form of research to evaluate and apply geomasking procedures based on feasibility of implementation, accuracy, and privacy protection to accelerate population-based research on social and environmental causes of cancer.

Aldolase A promotes cervical cancer cell radioresistance by regulating the glycolysis and DNA damage after irradiation.

Radioresistance is the major obstacle that affects the efficacy of radiotherapy which is an important treatment for cervical cancer. By analyzing the databases, we found that aldolase A (ALDOA), which is a key enzyme in metabolic reprogramming, has a higher expression in cervical cancer patients and is associated with poor prognosis. We detected the expression of ALDOA in the constructed cervical cancer radioresistance (RR) cells by repetitive irradiation and found that it was upregulated compared to the control cells. Functional assays were conducted and the results showed that the knockdown of ALDOA in cervical cancer RR cells inhibited the proliferation, migration, and clonogenic abilities by regulating the cell glycolysis. In addition, downregulation of ALDOA enhanced radiation-induced apoptosis and DNA damage by causing G2/M phase arrest and further promoted radiosensitivity of cervical cancer cells. The functions of ALDOA in regulating tumor radiosensitivity were also verified by the mouse tumor transplantation model in vivo. Therefore, our study provides new insights into the functions of ALDOA in regulating the efficacy of radiotherapy and indicates that ALDOA might be a promising target for enhancing radiosensitivity in treating cervical cancer patients.

Development and Validation of a Novel Prognosis Model Based on a Panel of Three Immunogenic Cell Death-Related Genes for Non-Cirrhotic Hepatocellular Carcinoma.

Purpose: The accurate prediction of non-cirrhotic hepatocellular carcinoma (NCHCC) risk facilitates improved surveillance strategy and decreases cancer-related mortality. This study aimed to explore the correlation between immunogenic cell death (ICD) and NCHCC prognosis using The Cancer Genome Atlas (TCGA) datasets, and the potential prognostic value of ICD-related genes in NCHCC. Methods: Clinical and transcriptomic data of patients with NCHCC patients were retrieved from TCGA database. Weighted gene co-expression network analysis was performed to obtain the NCHCC phenotype-related module genes. Consensus clustering analysis was performed to classify the patients into two clusters based on intersection genes among differentially expressed genes (DEGs) between cancer and adjacent tissues, NCHCC phenotype-related genes, and ICD-related genes. NCHCC-derived tissue microarray was used to evaluate the correlation of the expression levels of key genes with NCHCC prognosis using immunohistochemical staining. Results: Cox regression analyses were performed to construct a prognostic risk score model comprising three genes (TMC7, GRAMD1C, and GNPDA1) based on DEGs between two clusters. The model stratified patients with NCHCC into two risk groups. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. Univariable and multivariable Cox regression analyses revealed that these signature genes are independent predictors of OS. Functional analysis revealed differential immune status between the two risk groups. Next, a nomogram was constructed, which demonstrated the potent distinguishing ability of the developed model based on receiver operating characteristic curves. In vitro functional validation revealed that the migration and invasion abilities of HepG2 and Huh7 cells were upregulated upon GRAMD1C knockdown but downregulated upon TMC7 knockdown. Conclusion: This study developed a prognostic model comprising three genes, which can aid in predicting the survival of patients with NCHCC and guide the selection of drugs and molecular markers for NCHCC.

Signaling metabolite succinylacetone activates HIF-1α and promotes angiogenesis in GSTZ1-deficient hepatocellular carcinoma.

Aberrant angiogenesis in hepatocellular carcinoma (HCC) is associated with tumor growth, progression, and local or distant metastasis. Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor that plays a major role in regulating angiogenesis during adaptation of tumor cells to nutrient-deprived microenvironments. Genetic defects in Krebs cycle enzymes, such as succinate dehydrogenase and fumarate hydratase, result in elevation of oncometabolites succinate and fumarate, thereby increasing HIF-1α stability and activating the HIF-1α signaling pathway. However, whether other metabolites regulate HIF-1α stability remains unclear. Here, we reported that deficiency of the enzyme in phenylalanine/tyrosine catabolism, glutathione S-transferase zeta 1 (GSTZ1), led to accumulation of succinylacetone, which was structurally similar to α-ketoglutarate. Succinylacetone competed with α-ketoglutarate for prolyl hydroxylase domain 2 (PHD2) binding and inhibited PHD2 activity, preventing hydroxylation of HIF-1α, thus resulting in its stabilization and consequent expression of vascular endothelial growth factor (VEGF). Our findings suggest that GSTZ1 may serve as an important tumor suppressor owing to its ability to inhibit the HIF-1α/VEGFA axis in HCC. Moreover, we explored the therapeutic potential of HIF-1α inhibitor combined with anti-programmed cell death ligand 1 therapy to effectively prevent HCC angiogenesis and tumorigenesis in Gstz1-knockout mice, suggesting a potentially actionable strategy for HCC treatment.

Toxic effects of combined exposure to cadmium and nitrate on intestinal morphology, immune response, and microbiota in juvenile Japanese flounder (Paralichthys olivaceus).

Cadmium (Cd2+) and nitrate (NO3-) are important environmental pollutants in the offshore marine ecological environment. However, limited research has explored their combined effects, particularly regarding their impact on the microbiota and intestinal health of marine fish. In this study, juvenile Japanese flounders (P. olivaceus) were immersed in seawater samples with different combinations of Cd2+ (0, 0.2, and 2 mg/L) and NO3- (0 and 80 mg/L NO3N) for 30 days to explore their toxic impacts on intestinal morphology, tight junction (TJ) barrier, immune response, and microbiota. Our results showed that Cd2+ or NO3- exposure alone led to histopathological damage of the gut, while their co-exposure aggravated intestinal damage. Moreover, co-exposure substantially decreased TJ-related gene expression, including occludin, claudin-10, and ZO-2, suggesting increased TJ permeability in the gut. Regarding the immune response, we observed upregulated expression of immune-related markers such as HSP40, IL-1ß, TNF-α, and MT, suggesting the onset of intestinal inflammation. Furthermore, Cd2+ and NO3- exposure led to changes in intestinal microflora, characterized by decreased the abundance of Sediminibacterium and NS3a_marine_group while increasing the prevalence of pathogens or opportunistic pathogens such as Ralstonia, Proteus, and Staphylococcus. This alteration in microbiota composition increased network complexity and α-diversity, ultimately causing dysbiosis in the fish gut. Additionally, combined exposure resulted in metabolic disorders that affected the predicted functions of the intestinal microbiota. Overall, our study demonstrates that Cd2+-NO3- co-exposure amplifies the deleterious effects compared to single exposure. These findings enhance our understanding of the ecological risks posed by Cd2+-NO3- co-exposure in marine ecosystems.