Lensless super-resolved quantitative phase imaging with cm-level lateral translations of two glass plates.

In this Letter, we propose a new, to the best of our knowledge, lensless on-chip holographic microscopy platform, which can acquire sub-pixel-shifting holograms through centimeter (cm)-level lateral translations. An LED light source is used to illuminate the sample, and two orthogonally tilted step-structure glass plates are inserted into the optical path. By merely displacing the glass plates under cm-level precision, a series of holograms with sub-pixel displacements can be obtained. Combined with our improved pixel super-resolution (PSR) algorithm, high-quality PSR phase imaging can be achieved. Tests on the high-resolution USAF1951 target demonstrate that the system can achieve a half-width resolution of 870 nm by a camera with a pixel size of 1.67 µm. Additionally, imaging experiments were conducted on phase-type sinusoidal gratings, yeasts, red blood cells, and lilium ovary sections, respectively. The results show that the system can achieve large field-of-view, high-resolution phase imaging under low-cost hardware conditions and holds promise for its applications in biology and medicine.

Effects of Hyperbaric Oxygen Therapy Combined with Music Therapy on Brain Function and Mental Health of Patients with Aneurismal Subarachnoid Hemorrhage: A Retrospective Study.

BACKGROUND: Hyperbaric oxygen therapy (HBOT), which is widely used in clinical practice, is aimed at improving nerve function impairment after brain injury. Meanwhile, the effects of music therapy on brain function are unclear. This retrospective study was conducted to explore the application effect of HBOT combined with music therapy on patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). METHODS: For this retrospective study, 130 patients with aSAH after HBOT were selected from our hospital from June 2021 to June 2022. The patients were divided into the observation (n = 70) and control (n = 60) groups based on whether they received music therapy. Comparisons were made on general demographic data, blood flow rate in median cerebral artery (MCA), cerebral vasospasm (CVS), National Institutes of Health Stroke Scale (NIHSS), activities of daily living (ADL) score, Self-Rating Depressive Scale (SDS), and Self-Rating Anxiety Scale (SAS) of patients. RESULTS: Baseline data between the two groups showed no statistically significant difference (P > 0.05). After management, patients in the observation group presented significantly lower SAS and SDS scores (P < 0.05), lower blood flow rate in MCA, CVS and NIHSS scores (P < 0.05), and higher ADL scores than the control group (P < 0.05). CONCLUSIONS: The combination of HBOT and music therapy can considerably improve cerebral neurological deficits, slow down cerebral arterial blood flow, promote the recovery of postoperative cerebral function in aSAH patients, and improve anxiety and depression and the patients' ADL.

N6-methyladenosine (m6A) writer METTL5 represses the ferroptosis and antitumor immunity of gastric cancer.

Emerging evidence has shown that ferroptosis and antitumor immunity response of T lymphocytes play critical roles in multiple malignancies, including gastric cancer (GC). Here, the present research aims to reveal the function of novel N6-methyladenosine (m6A) methyltransferase METTL5 on GC immune microenvironment. Clinically, elevated METTL5 was negatively correlated to the prognosis of GC patients. METTL5 high-expression repressed the Fe2+ accumulation and ferroptosis to promote the GC immune evasion escaping from activated PBMCs' killing effect. Mechanistically, upregulation of METTL5 promoted NRF2 mRNA stability, thereby inactivating the ferroptosis and repressing PBMCs' cells antitumor immunity. One valuable finding is that ferroptosis inhibitor (Ferrostatin-1, Fer-1) could reduce the antitumor immunity of cocultured PBMCs. In other words, the increase of ferroptosis might contribute to the anti-tumor efficacy of immunotherapy. Further study revealed that m6A reader IGF2BP1 mediated the stability of NRF2 mRNA via METTL5/m6A/NRF2 axis. Collectively, these results demonstrate that METTL5 functions as an oncogene in GC immune microenvironment, and highlights a critical role in T lymphocytes' antitumor immunity.

Pyroptosis inhibition alleviates acute lung injury via E-twenty-six variant gene 5-mediated downregulation of gasdermin D.

BACKGROUND: Acute lung injury (ALI) is a life-threatening condition characterized by excessive pulmonary inflammation, yet its precise pathophysiology remains elusive. Pyroptosis, a programmed cell death mechanism controlled by gasdermin D (GSDMD), has been linked to the etiology of ALI. This study investigated the regulatory functions of the transcription factor E-twenty-six variant gene 5 (ETV5) and GSDMD in ALI. METHODS: Lipopolysaccharide (LPS) was used to treat BEAS-2B cells (50 mmol/mL) and establish an LPS-induced mouse model of ALI (by intratracheal administration, 3 mg/kg). Protein-protein docking, immunofluorescence analysis, western blotting, real-time quantitative polymerase chain reaction, and dual-luciferase reporter gene assay were used to examine ETV5-mediated negative feedback regulation of GSDMD and its effects on pyroptosis and ALI. RESULTS: Our results showed that the physiological function of ETV5 was reduced by its downregulated expression, which impeded its nuclear translocation in ALI mice. Increased pyroptosis and enhanced production of inflammatory cytokines were associated with LPS-induced ALI. ETV5 overexpression in LPS-treated BEAS-2B cells decreased the expression of total and membrane-bound GSDMD, negatively regulated GSDMD, and prevented pyroptosis. The expression of inflammatory cytokines was subsequently reduced due to this inhibition, which, in turn, reduced ALI. Molecular docking analysis and dual-luciferase reporter gene assay results indicated a direct interaction between ETV5 and GSDMD, which inhibited GSDMD production. CONCLUSION: Our results indicate that ETV5 inhibits pyroptosis, decreases the expression of inflammatory cytokines, and negatively regulates GSDMD expression to ameliorate ALI symptoms.

Genome-Wide Characterization of ABC Transporter Genes and Expression Profiles in Red Macroalga Pyropia yezoensis Expose to Low-Temperature.

Pyropia yezoensis is an important economic macroalga widely cultivated in the East Asia countries of China, Korea, and Japan. The ATP-binding cassette (ABC) transporter gene family is one of the largest transporter families in all forms of life involved in various biological processes. The characteristics of ABC transporter genes in P. yezoensis (PyABC) and their functions in stress resistance, however, remain largely unknown. In this study, PyABCs were identified and characterized their expression patterns under low-temperature stress. A total of 48 PyABCs transporters were identified and divided into eight subfamilies, which are mostly predicted as membrane-binding proteins. The cis-elements of phytohormone and low-temperature response were distinguished in promoter sequences of PyABCs. Transcriptome analysis showed that PyABCs are involved in response to low-temperature stress. Among them, 12 PyABCs were significantly up-regulated after 24 h of exposure to low temperature (2 °C). Further quantitative RT-PCR analysis corroborated the highest expression happened at 24 for detected genes of PyABCC8, PyABCF3, and PyABCI1, extraordinarily for PyABCF3, and followed by decreased expression at 48 h. The expression of PyABCI1 was generally low in all tested strains. Whereas, in a strain of P. yezoensis with lower tolerance to low temperature, the expression was observed higher in PyABCC1, PyABCC8, and remarkably high in PyABCF3. This study provided valuable information on ABC gene families in P. yezoensis and their functional characteristics, especially on low-temperature resistance, and would help to understand the adaptive mechanisms of P. yezoensis to adverse environments.

The mediating role of depression in the association between socioeconomic status and cardiovascular disease: A nationwide cross-sectional study from NHANES 2005-2018.

Disparities in socioeconomic status (SES) are associated with an increased risk of cardiovascular disease (CVD). Depression is a highly prevalent cardiovascular risk factor among individuals with low SES. The present study aimed to gain a better understanding of the association between SES and CVD by examining the mediating effects of depression. 30,127 participants, 50.77 % female, with a mean age of 47.37 years from the National Health and Nutrition Examination Survey (NHANES) 2005-2018, were included. Weighted multivariable logistic regression analyses estimated the association between SES and CVD. Mediation analyses tested the mediating effects of depression. The multivariable-adjusted odds ratio (OR) of high SES for CVD was 0.42 (95 % confidence interval (CI): 0.36, 0.50; P < 0.001). In parallel, depression was negatively associated with SES, in which the multivariable-adjusted ß was -1.42 (95 % CI: -1.62, -1.22; P < 0.001) in high SES compared to low SES. For the association between depression and CVD, the multivariable-adjusted OR per 1-point increase of PHQ-9 score for CVD was 1.08 (95 % CI: 1.07, 1.09; P < 0.001). The mediation models indicated that depression mediated 10.92 % of the total association between SES and CVD when fully adjusted. Identifying individuals with depression for appropriate treatment is promising for reducing the CVD burden among populations with low SES.

HSP70 and APX1 play important roles in cotton male fertility by mediating ROS homeostasis.

Male sterility is used in the production of hybrid seeds and can improve the breeding efficiency of cotton hybrids. Reactive oxygen species is closely associated with the tapetum and pollen development, but their relationship in cotton male fertility remains unclear. In this study, we comprehensively compared the cytology and proteome of the anthers from an Upland cotton (Gossypium hirsutum) material, Shida 98 (WT), and its nearly-isogenic male sterile line Shida 98A (MS). Cytology indicated delayed PCD in the tapetum and defects in microspores in MS anthers. And further studies revealed disruption of ROS homeostasis. Proteomic analysis identified proteins with differential abundance mainly being related to redox homeostasis, protein folding, and apoptotic signaling pathways. GhAPX1 interacted with GhHSP70 and played a crucial role in the development of cotton anthers. Exogenous application of HSP70 inhibitor increased H2O2 content and decreased the activity of APX1 and pollen viability. The GhAPX1 mutants generated by CRISPR/Cas9-mediated gene editing exhibited premature degradation of the tapetum, significant decrease in pollen viability, and significant increase in H2O2 content. Altogether, our results imply HSP70 and APX1 being the key players jointly regulating male fertility by mediating ROS homeostasis. These results provide insights into the proteins associated with male fertility.

Altitude and prognosis after PCI: A propensity score-matched analysis.

Background: The impact of altitude on the prognosis of patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI) deserves further discussion and research. Methods: We conducted a post hoc analysis of a prospective observational study involving 5453 patients post-PCI, divided into medium-altitude and low-altitude groups. To control for confounding factors, propensity score matching was employed to pair patients with similar baseline characteristics between the two groups. The impact of altitude factors on patients' prognosis post-PCI was examined through endpoint events over a 2-year follow-up period. Results: During the 2-year follow-up, patients at medium altitude exhibited a lower risk of MACE (including cardiovascular mortality, myocardial infarction, revascularization, and stroke) compared to those at low altitude (1196 versus 1196 patients [medium-altitude versus low-altitude, respectively]; hazard ratio [HR], 0.781 [95 % CI, 0.629-0.969]; P = 0.025) during 2-year follow-up. Even after excluding stroke, a significant difference in heart-related adverse events (HRAE) persisted between the two groups (HR, 0.794; 95 % CI, 0.636-0.991; P = 0.042). The incidences of individual MACE components were not significantly different between the two groups. Conclusions: Patients post-PCI residing at medium altitude exhibited a lower risk of 2-year MACE compared to those at low altitude. Further research is necessary to provide more robust evidence.

GGPPS Negatively Regulates the Formation of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Acute Lung Injury.

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are life-threatening diseases. Neutrophil extracellular traps (NETs) play a key role in lung damage. Geranylgeranyl diphosphate synthase (GGPPS) is associated with the development of inflammatory diseases. We aimed to explore the role of GGPPS in NETs formation in ARDS/ALI. First, lung pathological changes in lipopolysaccharide (LPS)-induced ALI mice after myeloid-specific GGPPS deletion were evaluated. The level of NETs formation was analyzed by immunofluorescence, PicoGreen assay and Western blotting. Next, we determined the role of GGPPS in NETs formation and underlying mechanisms using immunofluorescence, flow cytometry, DCFH-DA, and SYTOX GREEN staining in vitro. Finally, the correlation between GGPPS expression incirculating neutrophils and dsDNA levels in plasma was evaluated. Myeloid-specific GGPPS deletion mice showed increased NETs deposition in lung tissue and aggravated histopathological damage of lung tissue. In vitro, GGPPS deficiency in neutrophils resulted in increased NETs formation by Phorbol-12-myristate-13-acetate (PMA), which was reversed by Geranylgeranyl diphosphate (GGPP). In addition, inhibitors blocking protein kinase C (PKC) and NADPH-oxidase (NOX) decreased NETs formation induced by GGPPS deletion. Importantly, GGPPS expression in circulating neutrophils was decreased in ARDS patients compared with the healthy control, and the level of dsDNA in plasma of ARDS patients was negatively correlated with the GGPPS expression. Taken together, GGPPS deficiency in neutrophils aggravates LPS-induced lung injury by promoting NETs formation via PKC/NOX signaling. Thus, neutrophil GGPPS could be a key therapeutic target for ARDS.

Chronic venous disease of lower limbs in young men at high-altitude: A cross-sectional survey.

OBJECTIVES: The aim of this study was to understand the prevalence of chronic venous disease (CVD) of lower limbs in young men at high-altitude in Xizang, and to provide prevention measures. METHODS: The convenient sampling method was used to conduct a questionnaire survey among males aged 18 to 40 above an altitude of 3000 meters in Xizang in April 2023. The contents of the questionnaire included basic information, symptoms of CVD of lower limbs, protection status and training needs. Multivariate logistic regression model was calculated to evaluate the risk factors for CVD. RESULTS: A total of 350 survey questionnaires were received, and 326 valid samples were collected. The prevalence of CVD of lower limbs (C1-C6) was 37.42% (95%CI: 32.17%-42.68%), the ratio of C0 to C5 were 62.58%, 27.30%, 3.07%, 4.60%, 2.15% and 0.31%, respectively, no one reached C6. The top three symptoms of CVD were lower limb fatigue (18.10%), heaviness (15.34%) and pain (13.19%). 46.01% of respondents were unaware of CVD, and 12.88% of respondents did not have any protective measures of CVD. Multivariate logistic regression showed that age (OR = 1.076, 95%CI: 1.018-1.137, p = .009), preference for spicy food (OR = 1.747, 95%CI: 1.083-2.818, p = .022), unbalanced diet (OR = 1.877, 95%CI: 1.049-3.358, p = .034) and physical exercise (OR 0.610, 95%CI: 0.377-0.986, p = .044) were the independent risk factors for CVD. CONCLUSIONS: This study provided data on the prevalence of CVD in young men at high-altitude and the risk factors for CVD. The findings of this study may facilitate the development of individualized clinical assessments and targeted prevention programs.

Modifiable risk factors and metabolic health in risk of cardiovascular disease among US adults: A nationwide cross-sectional study.

Background: Metabolic syndrome (MetS) could increase the risk of cardiovascular disease (CVD) by 2-fold. Ideal control of modifiable risk factors in Life's Simple 7 (LS7) could reduce the CVD risk among the general population. This study aimed to investigate the effects of controlling modifiable risk factors using LS7 in MetS to prevent CVD. Methods: 44463 participants in NHANES 1999-2018 were included. The primary endpoint was a composite of CVD, including angina pectoris, coronary artery disease, myocardial infarction, congestive heart failure, and stroke. Multivariable weighted logistic regression analyses estimated the associations. The diagnosis of MetS complied with Harmonized International Diabetes Federation Criteria. Measurement of modifiable risk factors used the 2010 American Heart Association LS7 guideline and was indicated by cardiovascular health (CVH). Results: 14034 individuals were diagnosed with MetS. 4835 participants had CVD. The weighted mean CVH was 8.06 ± 0.03. Intermediate and poor CVH were associated with increased risk for CVD in participants with similar metabolic states compared to ideal CVH. By taking participants with metabolic health and ideal CVH as health control, participants with MetS and poor CVH were demonstrated to have a 3-fold (adjusted odds ratio, 4.00; 95 % confidence interval, 3.21-4.98) greater risk for CVD. Notably, under the condition of ideal CVH, the risk of having CVD was comparable between metabolic health and MetS after fully adjusted. Conclusion: Ideal control of Life's Simple 7 in metabolic syndrome contributes to a comparable risk of cardiovascular disease with healthy subjects. LS7 could be recognized as a guideline for secondary prevention in MetS.

Inhibition of GLUD1 mediated by LASP1 and SYVN1 contributes to hepatitis B virus X protein-induced hepatocarcinogenesis.

Glutamate dehydrogenase 1 (GLUD1) is implicated in oncogenesis. However, little is known about the relationship between GLUD1 and hepatocellular carcinoma (HCC). In the present study, we demonstrated that the expression levels of GLUD1 significantly decreased in tumors, which was relevant to the poor prognosis of HCC. Functionally, GLUD1 silencing enhanced the growth and migration of HCC cells. Mechanistically, the upregulation of interleukin-32 through AKT activation contributes to GLUD1 silencing-facilitated hepatocarcinogenesis. The interaction between GLUD1 and AKT, as well as α-ketoglutarate regulated by GLUD1, can suppress AKT activation. In addition, LIM and SH3 protein 1 (LASP1) interacts with GLUD1 and induces GLUD1 degradation via the ubiquitin-proteasome pathway, which relies on the E3 ubiquitin ligase synoviolin (SYVN1), whose interaction with GLUD1 is enhanced by LASP1. In hepatitis B virus (HBV)-related HCC, the HBV X protein (HBX) can suppress GLUD1 with the participation of LASP1 and SYVN1. Collectively, our data suggest that GLUD1 silencing is significantly associated with HCC development, and LASP1 and SYVN1 mediate the inhibition of GLUD1 in HCC, especially in HBV-related tumors.

Effects of different modalities of transcranial magnetic stimulation on post-stroke cognitive impairment: a network meta-analysis.

OBJECTIVE: The study aimed to evaluate, using a network meta-analysis, the effects of different transcranial magnetic stimulation (TMS) modalities on improving cognitive function after stroke. METHODS: Computer searches of the Cochrane Library, PubMed, Web of Science, Embass, Google Scholar, CNKI, and Wanfang databases were conducted to collect randomized controlled clinical studies on the use of TMS to improve cognitive function in stroke patients, published from the time of database construction to November 2023. RESULTS: A total of 29 studies and 2123 patients were included, comprising five interventions: high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS), intermittent theta rhythm stimulation (iTBS), sham stimulation (SS), and conventional rehabilitation therapy (CRT). A reticulated meta-analysis showed that the rankings of different TMS intervention modalities in terms of the Montreal Cognitive Assessment (MoCA) scores, Mini-Mental State Examination scores (MMSE), and Modified Barthel Index (MBI) scores were: HF-rTMS > LF-rTMS > iTBS > SS > CRT; the rankings of different TMS intervention modalities in terms of the event-related potential P300. amplitude scores were HF-rTMS > LF-rTMS > iTBS > CRT > SS; the rankings of different TMS intervention modalities in terms of the P300 latency scores were: iTBS > HF-rTMS > LF-rTMS > SS > CRT. Subgroup analyses of secondary outcome indicators showed that HF-rTMS significantly improved Rivermead Behavior Memory Test scores and Functional Independence Measurement-Cognitive scores. CONCLUSIONS: High-frequency TMS stimulation has a better overall effect on improving cognitive functions and activities of daily living, such as attention and memory in stroke patients.

Angiographic microvascular resistance in patients with obstructive hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction (CMD) is an important feature of obstructive hypertrophic cardiomyopathy (oHCM). Angiographic microvascular resistance (AMR) offers a potent means for assessing CMD. This study sought to evaluate the prognostic value of CMD burden calculated by AMR among oHCM patients. METHODS: We retrospectively screened all patients diagnosed with oHCM from Fuwai Hospital between January 2017 and November 2021. Off-line AMR assessments were performed for all 3 major coronary vessels by the independent imaging core laboratory. Patients were followed every 6 months post discharge via office visit or telephone contacts. The primary outcome was major adverse cardiovascular events (MACE), including all-cause death, and unplanned rehospitalization for heart failure. RESULTS: A total of 342 patients presented with oHCM diseases enrolled in the present analyses. Mean age was 49.7, 57.6 % were men, mean 3-vessel AMR was 6.9. At a median follow-up of 18 months, high capability of 3-vessel AMR in predicting MACE was identified (AUC: 0.70) with the best cut-off value of 7.04. The primary endpoint of MACE was significantly higher in high microvascular resistance group (3-vessel AMR ≥ 7.04) as compared with low microvascular resistance group (56.5 % vs. 16.5 %; HR: 5.13; 95 % CI: 2.46-10.7; p < 0.001), which was mainly driven by the significantly higher risk of heart failure events in high microvascular resistance group. Additionally, 3-vessel AMR (HR: 4.37; 95 % CI: 1.99-9.58; p < 0.001), and age (per 1 year increase, HR: 1.03; 95 % CI: 1.01-1.06; p = 0.02) were independently associated with MACE. CONCLUSION: The present retrospective study demonstrated that the novel angiography-based AMR was a useful tool for CMD evaluation among patients with oHCM. High microvascular resistance as identified by 3-vessel AMR (≥7.04) was associated with worse prognosis.

Predictive values of novel high­density lipoprotein­related inflammatory indices in in­stent restenosis among patients undergoing elective percutaneous coronary intervention.

Inflammation and disorders in lipid metabolism play pivotal roles in the development and progression of in-stent restenosis (ISR). The present study aimed to investigate the association between the high-density lipoprotein (HDL)-related inflammatory indices and the risk of developing ISR among patients undergoing elective percutaneous coronary intervention (PCI). A sum of 1,471 patients undergoing elective PCI were retrospectively included and classified by tertiles of HDL-related inflammatory indices. The study endpoint was ISR. The multivariable Cox proportional hazards regression analysis with restricted cubic splines (RCS) was used to assess the associations. During a median follow-up of 62.27 months, 251 (17.06%) patients experienced ISR. The incidence of ISR increased with the increasing white blood cell-to-HDL ratio (WHR) tertiles (log-rank test, overall P=0.0082). After full adjustment, the highest tertile of WHR was significantly associated with a 1.603-fold risk of ISR (hazard ratio, 1.603; 95% confidence interval, 1.152-2.231; P=0.005) in contrast to the lowest tertile of the WHR. Results of RCS further indicated that the association between WHR and ISR was in a non-linear and dose-dependent manner (non-linear P=0.034; P overall=0.019). The lymphocyte-to-HDL ratio (LHR) and neutrophil-to-HDL ratio (NHR) were also significantly and positively associated with the risk of ISR, of which the third tertiles were at increased risk of 41.2 and 44.7% after full adjustment, respectively. Overall, lipid metabolism disorders and inflammation were interconnected in the development of ISR; therefore, HDL-related inflammatory indices, including WHR, LHR and NHR, might be potential predictors in the prognosis of elective PCI.

Association of Cardiovascular Health with Cognitive Function in US Older Adults: A Population-Based Cross-Sectional Study.

INTRODUCTION: Promoting cardiovascular health (CVH) by Life's Simple 7 is associated with better cognitive function. In 2022, the American Heart Association (AHA) prompted Life's Essential 8 (LE8) to strengthen CVH assessment. This study investigated the association between the new CVH metrics assessed by LE8 and cognitive function, thus providing evidence for implementing LE8 in the primordial prevention of cognitive impairment. METHODS: 2,050 participants aged 60 and older from National Health and Nutrition Examination Survey 2011-2014 were included. Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). The overall and domain-specific cognitive function z-score was created. CVH score was calculated following AHA's advisory. The multivariable linear regression model estimated the associations. RESULTS: The CVH score assessed by LE8 was independently, positively, and linearly associated with the overall cognitive function. A per-10 point increase in CVH was associated with higher overall cognitive z-scores (ß, 0.06; 95% confidence interval [CI], 0.03, 0.09), and participants with moderate (ß, -0.14; 95% CI, -0.22, -0.05) and low CVH (ß, -0.27; 95% CI, -0.37, -0.16) had lower overall cognitive z-scores compared to participants with high CVH. Similar patterns of associations were observed between CVH of AFT and DSST. Components of CVH were further associated with different domain-specific cognitive functions. CONCLUSION: Maintaining an ideal CVH improves cognitive function in older adults. Ideal adherence to individual components of LE8 was associated with improved overall and domain-specific cognitive functions. Therefore, promoting CVH according to LE8 might benefit cognitive function in the elderly.

A systematic review and meta-analysis of artificial intelligence-diagnosed endoscopic remission in ulcerative colitis.

Endoscopic remission is an important therapeutic goal in ulcerative colitis (UC). The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Mayo Endoscopic Score (MES) are the commonly used endoscopic scoring criteria. This systematic review and meta-analysis aimed to evaluate the accuracy of artificial intelligence (AI) in diagnosing endoscopic remission in UC. We also performed a meta-analysis of each of the four endoscopic remission criteria (UCEIS = 0, MES = 0, UCEIS = <1, MES = <1). Eighteen studies involving 13,687 patients were included. The combined sensitivity and specificity of AI for diagnosing endoscopic remission in UC was 87% (95% confidence interval [CI]:81-92%) and 92% (95% CI: 89-94%), respectively. The area under the curve (AUC) was 0.96 (95% CI: 0.94-0.97). The results showed that the AI model performed well regardless of which criteria were used to define endoscopic remission of UC.

Hepatitis B virus core protein stabilizes RANGAP1 to upregulate KDM2A and facilitate hepatocarcinogenesis.

PURPOSE: As a vital component of the hepatitis B virus (HBV) nucleocapsid, HBV core protein (HBC) contributes to hepatocarcinogenesis. Here, we aimed to assess the effects of RANGAP1 and KDM2A on tumorigenesis induced by HBC. METHODS: Co-immunoprecipitation (Co-IP) combined with mass spectrometry were utilized to identify the proteins with the capacity to interact with HBC. The gene and protein levels of RANGAP1 and KDM2A in hepatocellular carcinoma (HCC) and HBV-positive HCC tissues were evaluated using different cohorts. The roles of RANGAP1 and KDM2A in HCC cells mediated by HBC were investigated in vitro and in vivo. Co-IP and western blot were used to estimate the interaction of HBC with RANGAP1 and KDM2A and assess RANGAP1 stabilization regulated by HBC. RESULTS: We discovered that HBC could interact with RANGAP1 and KDM2A, the levels of which were markedly elevated in HCC tissues. Relying on RANGAP1 and KDM2A, HBC facilitated HCC cell growth and migration. The increased stabilization of RANGAP1 mediated by HBC was relevant to the disruption of the interaction between RANGAP1 and an E3 ligase SYVN1. RANGAP1 interacted with KDM2A, and it further promoted KDM2A stabilization by disturbing the interaction between KDM2A and SYVN1. HBC enhanced the interaction of KDM2A with RANGAP1 and upregulated the expression of KDM2A via RANGAP1 in HCC cells. CONCLUSIONS: These findings demonstrate a novel mechanism by which HBC facilitates hepatocarcinogenesis. RANGAP1 and KDM2A could act as potential molecular targets for treating HBV-associated malignancy.

Reply to Siyu Tan: Associations of cardiovascular health assessed by life's essential 8 with diabetic retinopathy and mortality in type 2 diabetes. The author's reply.

The present study is a reply of authors regarding the commentary from Siyu Tan. In this study, we paid specific attention to (1) highlight the inclusion criterion and diagnosis of Type 2 diabetes mellitus; (2) explain the assessments of cardiovascular health and diabetic retinopathy.

Associations of cardiovascular health assessed by life's essential 8 with diabetic retinopathy and mortality in type 2 diabetes.

BACKGROUND: Vascular complications are the leading causes of reduced life quality and mortality in type 2 diabetes mellitus (T2DM). Life's Essential 8 (LE8) is a newly modified measurement of cardiovascular health (CVH) by American Heart Association (AHA). Promoting CVH has been previously shown to improve the prognosis of T2DM. However, studies regarding the effects of CVH by LE8 on diabetic retinopathy (DR), a major microvascular complication, and death from the cardiovascular and overall causes in T2DM are currently lacking. This study aimed to investigate these associations thus providing preliminary evidence. METHODS: A total of 3192 participants from the National Health and Nutrition Examination Survey (NHANES) were included in the final analysis. Records of mortality during follow-up were obtained by linking to the National Death Index. The multivariable logistic regression and Cox proportional hazard regression with restricted cubic splines were used to estimate the associations. Subgroup analyses were performed to examine the effects of gender, age, and duration of T2DM. RESULTS: 648 individuals had DR at baseline. During a median follow-up of 76 months, 645 overall deaths (incidence per 1000 person-years, 26.53%; 95% confidence interval (CI), 26.50-26.56) were ascertained, including 216 from cardiovascular causes (incidence per 1000 person-years, 8.96%; 95% CI, 8.94-8.98). The multivariable-adjusted odds ratio (OR) per 100-point increase of LE8 was 0.80 (95% CI, 0.71-0.90) for DR, and participants with high levels of LE8 were associated with 47% risk reduction (OR, 0.53; 95% CI, 0.40-0.70). The multivariable-adjusted hazard ratio (HR) per 100-point increase of LE8 was 0.71 (95% CI, 0.62-0.81) and 0.68 (95% CI, 0.58-0.85) for all-cause mortality and cardiovascular mortality, respectively. Similar patterns of inverse associations were observed in participants with moderate and high levels of LE8 for all-cause and cardiovascular mortality. Notably, stronger associations between LE8 and mortality were discovered in participants below 60 years (P < 0.05 for interaction). Moreover, LE8 was correlated with all-cause mortality in a linear way (P for nonlinear=0.32). CONCLUSION: The AHA's newly prompted LE8 was strongly and inversely associated with the risk of DR, all-cause mortality, and cardiovascular-specific mortality in T2DM. LE8 may be a feasible and effective approach in the tertiary prevention of T2DM.