Vibration-Dependent Dual-Phosphorescent Cu4 Nanocluster with Remarkable Piezochromic Behavior.

The dual emission (DE) characteristics of atomically precise copper nanoclusters (Cu NCs) are of significant theoretical and practical interest. Despite this, the underlying mechanism driving DE in Cu NCs remains elusive, primarily due to the complexities of excited state processes. Herein, a novel [Cu4(PPh3)4(C≡C-p-NH2C6H4)3]PF6 (Cu4) NC, shielded by alkynyl and exhibiting DE, was synthesized. Hydrostatic pressure was applied to Cu4, for the first time, to investigate the mechanism of DE. With increasing pressure, the higher-energy emission peak of Cu4 gradually disappeared, leaving the lower-energy emission peak as the dominant emission. Additionally, the Cu4 crystal exhibited notable piezochromism transitioning from cyan to orange. Angle-dispersive synchrotron X-ray diffraction results revealed that the reduced inter-cluster distances under pressure brought the peripheral ligands closer, leading to the formation of new C-H···N and N-H···N hydrogen bonds in Cu4. It is proposed that these strengthened hydrogen bond interactions limit the ligands´ vibration, resulting in the vanishing of the higher-energy peak. In situ high-pressure Raman and vibrationally resolved emission spectra demonstrated that the benzene ring C=C stretching vibration is the structural source of the DE in Cu4.

Diagnostic Value of Clear Cell Likelihood Score v1.0 and v2.0 for Common Subtypes of Small Renal Masses: A Multicenter Comparative Study.

BACKGROUND: Clear cell likelihood score (ccLS) is reliable for diagnosing small renal masses (SRMs). However, the diagnostic value of Clear cell likelihood score version 1.0 (ccLS v1.0) and v2.0 for common subtypes of SRMs might be a potential score extension. PURPOSE: To compare the diagnostic performance and interobserver agreement of ccLS v1.0 and v2.0 for characterizing five common subtypes of SRMs. STUDY TYPE: Retrospective. POPULATION: 797 patients (563 males, 234 females; mean age, 53 ± 12 years) with 867 histologically proven renal masses. FIELD STRENGTH/SEQUENCES: 3.0 and 1.5 T/T2 weighted imaging, T1 weighted imaging, diffusion-weighted imaging, a dual-echo chemical shift (in- and opposed-phase) T1 weighted imaging, multiphase dynamic contrast-enhanced imaging. ASSESSMENT: Six abdominal radiologists were trained in the ccLS algorithm and independently scored each SRM using ccLS v1.0 and v2.0, respectively. All SRMs had definite pathological results. The pooled area under curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the diagnostic performance of ccLS v1.0 and v2.0 for characterizing common subtypes of SRMs. The average κ values were calculated to evaluate the interobserver agreement of the two scoring versions. STATISTICAL TESTS: Random-effects logistic regression; Receiver operating characteristic analysis; DeLong test; Weighted Kappa test; Z test. The statistical significance level was P < 0.05. RESULTS: The pooled AUCs of clear cell likelihood score version 2.0 (ccLS v2.0) were statistically superior to those of ccLS v1.0 for diagnosing clear cell renal cell carcinoma (ccRCC) (0.907 vs. 0.851), papillary renal cell carcinoma (pRCC) (0.926 vs. 0.888), renal oncocytoma (RO) (0.745 vs. 0.679), and angiomyolipoma without visible fat (AMLwvf) (0.826 vs. 0.766). Interobserver agreement for SRMs between ccLS v1.0 and v2.0 is comparable and was not statistically significant (P = 0.993). CONCLUSION: The diagnostic performance of ccLS v2.0 surpasses that of ccLS v1.0 for characterizing ccRCC, pRCC, RO, and AMLwvf. Especially, the standardized algorithm has optimal performance for ccRCC and pRCC. ccLS has potential as a supportive clinical tool. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Role of radiomics in staging liver fibrosis: a meta-analysis.

BACKGROUND: Fibrosis has important pathoetiological and prognostic roles in chronic liver disease. This study evaluates the role of radiomics in staging liver fibrosis. METHOD: After literature search in electronic databases (Embase, Ovid, Science Direct, Springer, and Web of Science), studies were selected by following precise eligibility criteria. The quality of included studies was assessed, and meta-analyses were performed to achieve pooled estimates of area under receiver-operator curve (AUROC), accuracy, sensitivity, and specificity of radiomics in staging liver fibrosis compared to histopathology. RESULTS: Fifteen studies (3718 patients; age 47 years [95% confidence interval (CI): 42, 53]; 69% [95% CI: 65, 73] males) were included. AUROC values of radiomics for detecting significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4) were 0.91 [95%CI: 0.89, 0.94], 0.92 [95%CI: 0.90, 0.95], and 0.94 [95%CI: 0.93, 0.96] in training cohorts and 0.89 [95%CI: 0.83, 0.91], 0.89 [95%CI: 0.83, 0.94], and 0.93 [95%CI: 0.91, 0.95] in validation cohorts, respectively. For diagnosing significant fibrosis, advanced fibrosis, and cirrhosis the sensitivity of radiomics was 84.0% [95%CI: 76.1, 91.9], 86.9% [95%CI: 76.8, 97.0], and 92.7% [95%CI: 89.7, 95.7] in training cohorts, and 75.6% [95%CI: 67.7, 83.5], 80.0% [95%CI: 70.7, 89.3], and 92.0% [95%CI: 87.8, 96.1] in validation cohorts, respectively. Respective specificity was 88.6% [95% CI: 83.0, 94.2], 88.4% [95% CI: 81.9, 94.8], and 91.1% [95% CI: 86.8, 95.5] in training cohorts, and 86.8% [95% CI: 83.3, 90.3], 94.0% [95% CI: 89.5, 98.4], and 88.3% [95% CI: 84.4, 92.2] in validation cohorts. Limitations included use of several methods for feature selection and classification, less availability of studies evaluating a particular radiological modality, lack of a direct comparison between radiology and radiomics, and lack of external validation. CONCLUSION: Although radiomics offers good diagnostic accuracy in detecting liver fibrosis, its role in clinical practice is not as clear at present due to comparability and validation constraints.

Onset of acute severe autoimmune hepatitis after severe acute respiratory syndrome coronavirus 2 infection: a case report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can trigger autoimmune inflammation in the liver, leading to acute autoimmune hepatitis (AIH). We herein report a case involving a 39-year-old woman with a 23-day history of yellow skin and urine. Using the revised original scoring system of the International AIH Group, we definitively diagnosed the patient with acute severe AIH (AS-AIH). She began treatment with 80 mg/day intravenous methylprednisolone, which was gradually reduced and followed by eventual transition to oral methylprednisolone. The patient finally achieved a biochemical response after 30 days of therapy, and liver transplantation was avoided. Clinicians should be aware that the onset of AS-AIH after SARS-CoV-2 infection differs from the onset of conventional AIH with respect to its clinical and pathological features. Early diagnosis and timely glucocorticoid treatment are crucial in improving outcomes.

Multispecies transcriptomics identifies SIKE as a MAPK repressor that prevents NASH progression.

Nonalcoholic fatty liver (NAFL) remains relatively benign, but high-risk to end-stage liver diseases become highly prevalent when it progresses into nonalcoholic steatohepatitis (NASH). Our current understanding of the development of NAFL to NASH remains insufficient. In this study, we revealed MAP kinase (MAPK) activation as the most notable molecular signature associated with NASH progression across multiple species. Furthermore, we identified suppressor of IKKε (SIKE) as a conserved and potent negative controller of MAPK activation. Hepatocyte-specific overexpression of Sike prevented NASH progression in diet- and toxin-induced mouse NASH models. Mechanistically, SIKE directly interacted with TGF-ß-activated kinase 1 (TAK1) and TAK1-binding protein 2 (TAB2) to interrupt their binding and subsequent TAK1-MAPK signaling activation. We found that indobufen markedly up-regulated SIKE expression and effectively improved NASH features in mice and macaques. These findings identify SIKE as a MAPK suppressor that prevents NASH progression and provide proof-of-concept evidence for targeting the SIKE-TAK1 axis as a potential NASH therapy.

Histone demethylase KDM1A promotes hepatic steatosis and inflammation by increasing chromatin accessibility in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease without specific Food and Drug Administration-approved drugs. Recent advances suggest that chromatin remodeling and epigenetic alteration contribute to the development of NAFLD. The functions of the corresponding molecular modulator in NAFLD, however, are still elusive. KDM1A, commonly known as lysine-specific histone demethylase 1, has been reported to increase glucose uptake in hepatocellular carcinoma. In addition, a recent study suggests that inhibition of KDM1A reduces lipid accumulation in primary brown adipocytes. We here investigated the role of KDM1A, one of the most important histone demethylases, in NAFLD. In this study, we observed a significant upregulation of KDM1A in NAFLD mice, monkeys, and humans compared to the control group. Based on these results, we further found that the KDM1A can exacerbate lipid accumulation and inflammation in hepatocytes and mice. Mechanistically, KDM1A exerted its effects by elevating chromatin accessibility, subsequently promoting the development of NAFLD. Furthermore, the mutation of KDM1A blunted its capability to promote the development of NAFLD. In summary, our study discovered that KDM1A exacerbates hepatic steatosis and inflammation in NAFLD via increasing chromatin accessibility, further indicating the importance of harnessing chromatin remodeling and epigenetic alteration in combating NAFLD. KDM1A might be considered as a potential therapeutic target in this regard.

TRIM56 protects against nonalcoholic fatty liver disease by promoting the degradation of fatty acid synthase.

Nonalcoholic fatty liver disease (NAFLD) encompasses a disease continuum from simple steatosis to nonalcoholic steatohepatitis (NASH). However, there are currently no approved pharmacotherapies for NAFLD, although several drugs are in advanced stages of clinical development. Because of the complex pathophysiology and heterogeneity of NAFLD, the identification of potential therapeutic targets is clinically important. Here, we demonstrated that tripartite motif 56 (TRIM56) protein abundance was markedly downregulated in the livers of individuals with NAFLD and of mice fed a high-fat diet. Hepatocyte-specific ablation of TRIM56 exacerbated the progression of NAFLD, while hepatic TRIM56 overexpression suppressed it. Integrative analyses of interactome and transcriptome profiling revealed a pivotal role of TRIM56 in lipid metabolism and identified the lipogenesis factor fatty acid synthase (FASN) as a direct binding partner of TRIM56. TRIM56 directly interacted with FASN and triggered its K48-linked ubiquitination-dependent degradation. Finally, using artificial intelligence-based virtual screening, we discovered an orally bioavailable small-molecule inhibitor of FASN (named FASstatin) that potentiates TRIM56-mediated FASN ubiquitination. Therapeutic administration of FASstatin improved NAFLD and NASH pathologies in mice with an optimal safety, tolerability, and pharmacokinetics profile. Our findings provide proof of concept that targeting the TRIM56/FASN axis in hepatocytes may offer potential therapeutic avenues to treat NAFLD.

Neutrophil-to-lymphocyte ratio associated with symptomatic saccular unruptured intracranial aneurysm.

BACKGROUND AND PURPOSE: Whether symptomatic unruptured intracranial aneurysms (UIAs) lead to change in circulating inflammation remains unclear. This study aims to evaluate the role of hematological inflammatory indicators in predicting symptomatic UIA. METHODS: Adult patients diagnosed with saccular intracranial aneurysm from March 2019 to September 2023 were recruited retrospectively. Clinical and laboratory data, including the white blood cells (WBC), neutral counts (NEUT), lymphocyte counts (LYM), and monocyte counts (MONO) of each patient, were collected. The neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were calculated as NLR = NEUT/LYM, LMR = LYM/MONO, SII = PLT*NEUT/LYM. The hematological inflammatory indicators were compared in symptomatic saccular and asymptomatic UIA patients. Multivariable logistic regression analyses were performed to explore the factors predicting symptomatic UIA. RESULTS: One hundred and fifty UIA patients with a mean age of 58.5 ± 12.4 were included, of which 68% were females. The NLR and LMR were significantly associated with symptomatic UIA, and the association remained in small UIAs (< 7 mm). The multiple logistic regression analysis showed that NLR was independently associated with symptomatic UIA. On ROC curve analysis, the optimal cutoff value of NLR to differentiate symptomatic from asymptomatic was 2.38. In addition, LMR was significantly associated with symptomatic UIA smaller than 7 mm. CONCLUSION: There was a significant correlation between NLR and symptomatic UIA. The NLR was independently associated with symptomatic UIA.

Effect of sulfide on the nitrogen removal performance and microbial community of low-substrate Anammox process.

Anammox is one of the most innovative nitrogen removal technologies, while its functional bacteria-anaerobic ammonia-oxidizing bacteria (AAOB) is sensitive to the impurities in the wastewater. In this study, the long-term effects of sulfide at different concentrations (0, 5, 10, 20, 30, 50, 25 mg L-1) on low substrate Anammox process were studied. The results showed that when the sulfide was 25-30 mg L-1, AAOB was well coupled with sulfide-denitrifying bacteria and the total nitrogen removal efficiency (TNRE) reached a maximum of 91.0%. The hydroxylamine oxidoreductase activity and Heme-c reached 1.678 EU g-1 SS and 0.0023 mmol g-1 SS, respectively, with the hzo and nosZ gene concentrations as 2.52 × 108 and 4.45 × 107 copies mL-1. 50 mg L-1 sulfide inhibited the nitrogen removal by AAOB, resulting in the TNRE decreasing to 81.7%. The experimental results provide a reference for the practical application of Anammox in treating sulfur-containing wastewater.

Assessment of the Added Value of Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging in Identifying Non-Diabetic Renal Disease in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear. PURPOSE: To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. STUDY TYPE: Prospective. POPULATION: Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). FIELD STRENGTH/SEQUENCE: 3 T/ T2 weighted imaging (T2WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: The parameters derived from IVIM-DWI (true diffusion coefficient [D], pseudo-diffusion coefficient [D*], and pseudo-diffusion fraction [f]) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy [DR], fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant. RESULTS: The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively). DATA CONCLUSION: The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Association between questionnaire-based and accelerometer-based physical activity and the incidence of chronic kidney disease using data from UK Biobank: a prospective cohort study.

Background: Prior studies on the relationship between chronic kidney disease (CKD) and physical activity (PA) mainly relied on subjective PA data and rarely considered the genetic risk. This study aims to thoroughly investigate this relationship by utilizing both accelerometer-measured and questionnaire-measured PA data. Methods: This prospective cohort study encompasses two cohorts from the UK Biobank. The questionnaire-based cohort involves 448,444 CKD-free participants who completed an International Physical Activity Questionnaire between 2006 and 2010 and had genetic data. PA was categorized into distinct activities: leisure, housework, job-related, and transportation. The accelerometer-based cohort involves 89,296 CKD-free participants who provided a full week of accelerometer-based physical activity data between 2013 and 2015 and had genetic data. PA was classified as light-intensity, moderate-intensity, vigorous-intensity, moderate to vigorous-intensity PA (LPA, MPA, VPA, MVPA), and total PA. Incident CKD was ascertained from linked hospital inpatient and death records. Genetic risk was assessed using polygenic risk scores. Cox proportional hazard models with restricted cubic splines were used for the analysis. Findings: In the questionnaire-based cohort, 18,184 (4.05%) participants developed CKD during 13.6 years of follow-up. Engaging in strenuous sports, other exercises, walking for pleasure, stair climbing, and heavy DIY were associated with a reduced risk of CKD. In the accelerometer-based cohort, 2297 (2.57%) participants developed CKD during 7.9 years of follow-up. Higher levels [highest quartile vs lowest quartile] of MPA (HR 0.639, 95% CI 0.554-0.737), VPA (HR 0.639, 95% CI 0.549-0.745), MVPA (HR 0.630, 95% CI 0.545-0.729), and total PA (HR 0.649, 95% CI 0.563-0.750) were associated with a lower CKD risk. There were significant interactions between MPA and genetic risk on the risk of CKD incidence (P for interaction = 0.025). A linear dose-response relationship was observed between MPA, total PA, and the risk of CKD incidence with no minimal or maximal threshold. These associations are robust in different subgroups and a series of sensitivity analyses. Interpretation: Engaging in multiple types of PA and higher levels of total PA, MPA, VPA, and MVPA may be associated with a lower risk of developing CKD, regardless of genetic risk. This finding holds substantial implications for clinical approaches to CKD prevention and provides evidence to inform future PA guideline development. Funding: Medical Science Advancement Program of Wuhan University, and the National Science Foundation of China.

[The research progress of high altitude environment-associated chronic obstructive pulmonary disease and therapeutic drugs].

The plateau environment is characterized by low oxygen, low air pressure, low temperature, and strong ultraviolet rays, etc. Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic lung disease. High altitude environment increases COPD prevalence, clinical manifestation and mortality. The therapeutic window of theophylline drugs for COPD is narrow, and the high altitude environment has an influence on the pharmacokinetics of the drugs. This review summarizes the differences in the prevalence, mortality, clinical manifestation and clinical symptoms of COPD in the plateau and plain, providing a basis for identifying the risk factors of COPD in the plateau areas. The effects of plateau hypoxic environment on the pharmacokinetics of COPD drugs were also discussed. It can provide a rationale for more effective prevention and treatment of COPD at high altitude.

From basic to clinical: Anatomy of Denonvilliers' fascia and its application in laparoscopic radical resection of rectal cancer.

The total mesorectal excision (TME) approach has been established as the gold standard for the surgical treatment of middle and lower rectal cancer. This approach is widely accepted to minimize the risk of local recurrence and increase the long-term survival rate of patients undergoing surgery. However, standardized TME causes urogenital dysfunction in more than half of patients, thus lowering the quality of life of patients. Of note, pelvic autonomic nerve damage during TME is the most pivotal cause of postoperative urogenital dysfunction. The anatomy of the Denonvilliers' fascia (DVF) and its application in surgery have been investigated both nationally and internationally. Nevertheless, controversy exists regarding the basic to clinical anatomy of DVF and its application in surgery. Currently, it is a hotspot of concern and research to improve the postoperative quality of life of patients with rectal cancer through the protection of their urinary and reproductive functions after radical resection. Herein, this study systematically describes the anatomy of DVF and its application in surgery, thus providing a reference for the selection of surgical treatment modalities and the enhancement of postoperative quality of life in patients with middle and low rectal cancer.

[Risk Assessment of Heavy Metals in Dust Fall Around Reservoirs in Typical Ecologically Fragile Areas and Traceability Based on APCS-MLR Model].

To assess the health risk status and pollution sources of heavy metals in the atmosphere of ecologically vulnerable areas, the surrounding area of Dahekou Reservoir in Xilingol League was selected as the study area. From 2021 to 2022, 12 monitoring points for atmospheric dust fall were collected for a period of one year. A total of 144 samples were collected to determine the contents of eight types of heavy metals, namely Cr, Ni, Pb, Cu, Zn, Mn, As, and Cd. The potential ecological index (Eri) and health risk assessment model were used to assess the risk level of atmospheric heavy metals on ecological security and human health. The analysis of enrichment factors, principal components, and the model of absolute principal component multiple linear regression (APCS-MLR) receptor were used to analyze the sources of heavy metal pollution qualitatively in the atmosphere of the study area. The results showed that:① the mean value of the comprehensive potential ecological risk of heavy metals in the annual atmospheric dust fall in the study area was at a high ecological risk, and only the Cd value was at a very high risk level among the heavy metals, whereas the remaining were at a slight risk. ② The results of the health risk showed that intake by hand, mouth, and skin contact were the main exposure routes, which led to non-carcinogenic and carcinogenic risks. Children were under non-carcinogenic and acceptable carcinogenic risks in different months. During those months, the main source of the risks was As. ③ Through enrichment factor analysis, principal component analysis, and APCS-MLR receptor model calculation, the results revealed that the proportion of wind-blown sources was the largest, accounting for 37.82%, and the contribution rates of coal combustion and traffic sources to Cu, Cd, Pb, and Zn were 73.01%, 40.22%, 70.31%, and 32.82%, respectively. The contribution rate of mining activities to As was 42.59%, while that of industrial sources of Cd was 22.01%; the contributions of other human activity sources of Cd, As, Pb, and Zn were 21.12%, 34.40%, 23.04%, and 32.15%, respectively.

CCK1R2R-/- ameliorates myocardial damage caused by unpredictable stress via altering fatty acid metabolism.

The heart is the main organ of the circulatory system and requires fatty acids to maintain its activity. Stress is a contributor to aggravating cardiovascular diseases and even death, and exacerbates the abnormal lipid metabolism. The cardiac metabolism may be disturbed by stress. Cholecystokinin (CCK), which is a classical peptide hormone, and its receptor (CCKR) are expressed in myocardial cells and affect cardiovascular function. Nevertheless, under stress, the exact role of CCKR on cardiac function and cardiac metabolism is unknown and the mechanism is worth exploring. After unpredictable stress, a common stress-inducing model that induces the development of mood disorders such as anxiety and reduces motivated behavior, we found that the abnormal contraction and diastole of the heart, myocardial injury, oxidative stress and inflammation of mice were aggravated. Cholecystokinin A receptor and cholecystokinin B receptor knockout (CCK1R2R-/-) significantly reversed these changes. Mechanistically, fatty acid metabolism was found to be altered in CCK1R2R-/- mice. Differential metabolites, especially L-tryptophan, L-aspartic acid, cholesterol, taurocholic acid, ADP, oxoglutaric acid, arachidonic acid and 17-Hydroxyprogesterone, influenced cardiac function after CCK1R2R knockout and unpredictable stress. We conclude that CCK1R2R-/- ameliorated myocardial damage caused by unpredictable stress via altering fatty acid metabolism.

Semisynthesis and anti-cancer properties of novel honokiol derivatives in human nasopharyngeal carcinoma CNE-2Z cells.

In this study, 21 new honokiol derivatives were synthesised, and their anti-cancer properties were investigated. Among these, compound 1g exhibited the most potent cytotoxic activity against human nasopharyngeal carcinoma CNE-2Z cells, human gastric cancer SGC7901 cells, human breast cancer MCF-7 cells, and mouse leydig testicular cancer I-10 lines with IC50 values of 6.04, 7.17, 6.83, and 5.30 µM, respectively. Compared to the parental compound, 1g displayed up to 5.18-fold enhancement of the cytotoxic effect on CNE-2Z cells. We further demonstrated that 1g inhibited cell growth, suppressed migration and invasion, and induced apoptosis of CNE-2Z cells by down-regulating HIF-1α, MMP-2, MMP-9, Bcl-2, Akt and up-regulating Bax protein levels. Transfection of CNE-2Z cells with HIF-1α siRNA reduced cell migration and invasion. In addition, in vivo experiments confirmed that 1g inhibited tumour growth in CNE-2Z cell-xenografted nude mice with low toxicity. Thus, our data suggested that 1g was a potent and safe lead compound for nasopharyngeal carcinoma therapy.

Identification Strategy of Biological Half Sibling Relationship.

OBJECTIVES: To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship. METHODS: (1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting. RESULTS: (1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99. CONCLUSIONS: When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.

NAFLD: An Emerging Causal Factor for Cardiovascular Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide that poses a significant threat to human health. Cardiovascular disease (CVD) is the leading cause of mortality in NAFLD patients. NAFLD and CVD share risk factors such as obesity, insulin resistance, and type 2 diabetes. However, whether NAFLD is a causal risk factor for CVD remains a matter of debate. This review summarizes the evidence from prospective clinical and Mendelian randomization studies that underscore the potential causal relationship between NAFLD and CVD. The mechanisms of NAFLD contributing to the development of CVD and the necessity of addressing CVD risk while managing NAFLD in clinical practice are also discussed.

Epidemiological and Clinical Characteristics of Measles in Jinan, Shandong Province, China, from 1991 to 2022.

Objective: This study aimed to analyze the epidemiological and clinical characteristics of measles in Jinan, Shandong, China, over a 32-year stage to facilitate measles prevention in the future. Methods: Data on measles cases from 1991 to 2022 were obtained from the public health department and medical records of patients at Shandong Public Health Clinical Center. Retrospective analysis was conducted on the distribution of measles cases in different years, months, and age groups, and observation of the differences in clinical manifestations and complications among different age groups. Results: From January 1991 to December 2022, 7531 measles cases were recorded at Shandong Public Health Clinical Center. During the 32-year period, there were two outbreaks of measles in 2008 and 2016, respectively. During the COVID-19 pandemic period from 2020 to 2022, the number of cases reached the lowest point in the past 30 years. The number and percentage of cases in the 0-1y groups was significantly higher than in other age groups, and 97.75% patients in this group did not receive measles vaccine. Complications such as pneumonia and myocarditis appeared more frequent in patients under 12 years of age, but liver function damage is more common in adult patients. Conclusion: Although the measles epidemic has been greatly controlled since the use of measles vaccine, intermittent outbreaks still exist, so there is still a long way to go to eliminate measles. The proportion of infants under the age of 1 without measles vaccine and adults over 24 years old accounts for nearly 80% of the total. This group of people should be of concern, and feasible measures should be designated to protect these susceptible populations.

Prevalence and trend of atrial fibrillation and its associated risk factors among the population from nationwide health check-up centers in China, 2012-2017.

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, which poses huge disease burdens in China. A study was conducted to systematically analyze the recent prevalence trend of AF and age-related disparities in AF risk among the nationwide healthy check-up population. Method: We conducted a nationwide cross-sectional study involving 3,049,178 individuals ≥35 years from health check-up centers to explore the prevalence and trend of AF by age, sex, and region from 2012 to 2017. Additionally, we analyzed risk factors associated with AF among the overall population and different age groups via the Boruta algorithm, the LASSO regression, and the Logistic regression. Result: The age-, sex-. and regional-standardized prevalence of AF kept stable between 0.4%-0.45% among national physical examination individuals from 2012 to 2017. However, the prevalence of AF showed an undesirable upward trend in the 35-44-year age group (annual percentage changes (APC): 15.16 [95%CI: 6.42,24.62]). With increasing age, the risk of AF associated with the overweight or obesity gradually exceeds that associated with diabetes and hypertension. In addition to traditional leading risk factors such as age≥65 and coronary heart disease, elevated uric acid and impaired renal function were tightly correlated with AF in the population. Conclusion: The significant rise in the prevalence of AF in the 35-44 age group reminds us that in addition to the elderly (the high-risk group), younger people seem to be in more urgent need of attention. Age-related disparities in AF risk also exist. This updated information may provide references for the national prevention and control of AF.