Association between the triglyceride to high density lipoprotein cholesterol ratio and the incidence of metabolic dysfunction-associated fatty liver disease: a retrospective cohort study.

BACKGROUND: The triglyceride to high density lipoprotein cholesterol ratio (TG/HDL-C) is a confirmed predictive factor for insulin resistance and is suggested to be closely related to metabolic dysfunction-associated fatty liver disease (MAFLD), but previous research is inconclusive. The association between TG/HDL-C and MAFLD incidence was further explored in this large-sample, long-term retrospective cohort study. METHODS: Individuals who participated in the Kailuan Group health examination from July 2006 to December 2007 (n = 49,518) were included. Data from anthropometric and biochemical indices, epidemiological surveys, and liver ultrasound examinations were collected and analysed statistically, focusing on the association between TG/HDL-C and the incidence of MAFLD. RESULTS: During a mean follow-up period of 7.62 ± 3.99 years, 24,838 participants developed MAFLD. The cumulative MAFLD incidence rates associated with the first to fourth quartiles of TG/HDL-C were 59.16%, 65.04%, 71.27%, and 79.28%, respectively. The multivariate Cox proportional hazards regression model revealed that the hazard ratios (HRs) (95% CIs) for MAFLD in the second, third, and fourth quartiles were 1.20 (1.16-1.25), 1.50 (1.45-1.56), and 2.02 (1.95-2.10) (P for trend < 0.05), respectively, and the HR (95% CI) corresponding to an increase of one standard deviation in TG/HDL-C was 1.10 (1.09-1.11) (P < 0.05). Subsequent subgroup and sensitivity analyses yielded results similar to those of the main analyses. CONCLUSIONS: TG/HDL-C is independently associated with MAFLD risk, with higher TG/HDL-C indicating greater MAFLD risk.

Abdominal obesity, chronic inflammation and the risk of non-alcoholic fatty liver disease.

INTRODUCTION AND OBJECTIVES: The purpose of this study was to evaluate the effect of abdominal obesity and chronic inflammation on risk of non-alcoholic fatty liver disease (NAFLD) among Chinese population. MATERIALS AND METHODS: Overall, 50776 staff from the Kailuan Group who participated in and finished physical examinations between 2006 and 2007 were included in the cohort study. Their medical information was collected and they were followed after examination. The correlations of waist-to-height ratio (WHtR) or serum high-sensitivity C-reactive protein (hs-crp) with NAFLD were analyzed. Then, we categorized all participants into four groups: non-abdominal obesity and non-chronic inflammation group, abdominal obesity and non-chronic inflammation group, non-abdominal obesity and chronic inflammation group, abdominal obesity and chronic inflammation group, and non-abdominal obesity and non-chronic inflammation group was used as a control group. The combined effects of abdominal obesity and chronic inflammation with NAFLD were analyzed using the Cox proportional hazard regression model. RESULTS: After a mean follow-up of 5.59±1.79 years, a total of 15451 NAFLD cases occurred. We found the WHtR and hs-crp increase the risk for NAFLD, respectively. Compared with the non-abdominal obesity and non-chronic inflammation group, the risk of NAFLD was significantly increased in the abdominal obesity and non-chronic inflammation group (HR 1.21, 95%CI 1.11-1.32), non-abdominal obesity and chronic inflammation group (HR 1.32, 95%CI 1.27-1.38), abdominal obesity and chronic inflammation group (HR 1.60, 95% CI 1.52-1.70). And, a significant interaction effect was found of abdominal obesity and chronic inflammation on NAFLD. CONCLUSIONS: In this study, it was demonstrated in the Chinese population that both abdominal obesity and chronic inflammation increase the risk of NAFLD, and there is an interaction between the two factors in the incidence of NAFLD.

Hepatitis B virus infection and the risk of gastrointestinal cancers among Chinese population: A prospective cohort study.

Our study aims to explore the relationship between chronic hepatitis B virus (HBV) infection and the risk of gastrointestinal (GI) cancers including liver, gastric, gallbladder or extrahepatic bile duct, pancreatic, small intestine, esophageal and colorectal cancer in the Kailuan Cohort study. We prospectively examined the relationship between HBV infection and new-onset GI cancers among 93 402 participants. Cox proportional hazards regression models, subgroup analyses and competing risk analyses were used to evaluate the association between HBV infection and the risk of new-onset GI cancers. During a median follow-up of 13.02 years, 1791 incident GI cancer cases were diagnosed. Compared to HBsAg seronegative participants, a significant positive association between HBV infection and GI cancers was observed in the multivariate-adjusted models (HR 5.59, 95% CI: 4.84-6.45). In the site-specific analyses, participants with HBsAg seropositive exhibited an increased risk of liver cancer (HR = 21.56, 95% CI: 17.32-26.85), gallbladder or extrahepatic bile duct cancer (HR = 14.89, 95% CI: 10.36-21.41), colorectal cancer (HR = 1.75, 95% CI: 1.15-2.96) and pancreatic cancer (HR = 1.86, 95% CI: 1.10-3.99). After taking death as the competing risk event, the associations of HBV infection with the risk of these cancers were attenuated but remained significant both in the cause-specific hazards models, the subdistribution proportional hazards models and sensitivity analyses. Our study suggests that HBV infection is associated with the elevated risk of liver cancer and extrahepatic cancer including gallbladder or extrahepatic bile duct, pancreatic and colorectal cancer among adults in Northern China.

C-reactive protein trajectories and the risk of all cancer types: A prospective cohort study.

A single CRP measurement is insufficient to examine the association of long-term patterns of CRP concentration with cancer risk. We prospectively examined the relationship between CRP trajectory patterns and new-onset cancers among 52 276 participants. Latent mixture modeling was used to identify CRP trajectories. Cox proportional hazards regression models were used to evaluate the association between CRP trajectory patterns and the risk of overall and specific-site cancer. Four CRP trajectories patterns were identified: low-stable pattern (n = 43 258), moderate-increasing pattern (n = 2591), increasing-decreasing pattern (n = 2068) and elevated-decreasing pattern (n = 4359). Relative to the low-stable pattern, the moderate-increasing trajectory pattern was associated with an elevated risk of overall, lung, breast, leukemia, bladder, stomach, colorectal, liver, gallbladder or extrahepatic bile duct cancer and leukemia. Participants in the increasing-decreasing trajectory pattern were associated with an elevated risk of overall, lung, breast, bladder, pancreatic and liver cancer. The increasing-decreasing trajectory pattern was also associated with decreased risk of colorectal cancer in the multivariate analyses. Elevated-decreasing trajectory pattern was associated with increased risk of leukemia and decreased risk of esophageal and colorectal cancer. CRP trajectories play an important role in the occurrence of cancers, especially in the lung, breast, bladder, stomach, colorectal, liver, gallbladder and extrahepatic bile duct cancer and leukemia.

Cumulative triglyceride-glucose index is a risk for CVD: a prospective cohort study.

BACKGROUND: Previous studies has shown a significant relationship between baseline triglyceride-glucose (TyG) index and cardiovascular disease (CVD). However, the long-term effect of TyG index and incident CVD remains uncertain. This study aimed to investigate the association between cumulative TyG index and the risk of CVD. METHOD: In this study, we recruited individuals participating in Kailuan Study from 2006 to 2013 without stroke, myocardial infarction, and cancer in the four consecutive examinations. Cumulative TyG index was calculated by multiplying the average TyG index and the time between the two consecutive examinations. Cumulative TyG index levels were categorized into four quartile groups: Q1 group, ≤ 50.65 (as reference group), Q2 group, 50.65-53.86, Q3 group, 53.86-57.44, Q4 group, > 57.44. The association between cumulative TyG index and the risk of CVD was estimated by multivariable Cox proportional hazard models. RESULT: A total of 44,064 individuals participated in the final analysis. After a mean follow-up of 6.52 ± 1.14 years, incident CVD, MI and stroke occurred in 2057, 395 and 1695, respectively. The risk of developing CVD increased with the quartile of cumulative in TyG index, after adjustment for multiple potential confounders, the HR for CVD events were 1.25 (1.08-1.44) in Q2, 1.22 (1.05-1.40) in Q3 and 1.39 (1.21-1.61) in Q4, compared to Q1 group. The longer duration of higher TyG index exposure was significantly associated with increased CVD risk. Similar results were obtained in the subgroup and sensitivity analysis. CONCLUSION: Cumulative TyG index was associated with increased risk of CVD. Maintaining an appropriate level of TG and FBG within the desirable range and better control of cumulative TyG index are important for prevention of CVD.

Association between the TyG index and TG/HDL-C ratio as insulin resistance markers and the risk of colorectal cancer.

BACKGROUND: No previous prospective research has explored the association of the TyG (fasting triglyceride-glucose) index and TG/HDL-C ratio as insulin resistance markers with the risk of colorectal cancer (CRC) incidence in the Northern Chinese population. METHODS: In this prospective cohort study, we included 93,659 cancer-free participants with the measurements of TyG index and TG/HDL-C ratio. Participants were divided by the quartiles of the TyG index or TG/HDL-C ratio. The associations of TyG index, TG/HDL-C ratio, and their components with CRC risk were assessed using Cox proportional hazards regression models. RESULTS: During a median follow-up of 13.02 years, 593 incident CRC cases were identified. Compared with the lowest quartile of the TyG index (Q1), the risk of CRC was higher in persons in the third (Q3) and highest quartiles (Q4) of the TyG index, with corresponding multivariable-adjusted HRs (95% CI) of 1.36 (1.06, 1.76) and 1.50 (1.19, 1.91), respectively. The elevated risks of CRC incidence were observed in people in the second, third, and highest quartiles of the TG/HDL-C ratio groups, with corresponding multivariable-adjusted HRs (95% CI) of 1.33 (1.05, 1.70), 1.36 (1.07, 1.73) and 1.37 (1.07, 1.75), respectively. CONCLUSIONS: Elevated TyG index and TG/HDL-C ratio were associated with a higher risk of developing CRC among adults in Northern China.

Association between metabolic syndrome, C-reactive protein, and the risk of primary liver cancer: a large prospective study.

BACKGROUND AND AIMS: High-sensitivity C-reactive protein (hs-CRP) levels and metabolic syndrome (MetS) are known to be associated with an increased incidence of different cancers. We aimed to evaluate the effect of MetS combined with high hs-CRP levels on the risk of primary liver cancer (PLC). METHODS: Participants were recruited from the Kailuan cohort study and were classified into four groups according to the presence or absence of MetS and inflammation (hs-CRP ≥ 3 or < 3 mg/L). The associations of MetS and inflammation with the risk of PLC were assessed using Cox proportional hazards models. RESULTS: This study included 92,770 participants. The mean age was 51.4 years old. Over a median follow-up of 13.02 years, 395 participants were diagnosed as PLC. Compared to the control participants without inflammation (hs-CRP < 3 mg/L) and MetS (n = 69,413), participants with high hs-CRP levels combined with MetS (n = 2,269) had a higher risk of PLC [hazard ratios (HR) 2.91; 95% confidence interval (CI), 1.77-4.81], and participants with high hs-CRP levels and without MetS (n = 14,576) had the same trend (HR, 1.36; 95%CI, 1.05-1.75). However, participants with low hs-CRP levels and MetS (n = 6,512) had no significant association with an elevated risk of PLC (HR, 1.18; 95%CI, 0.76-1.82). After excluding participants who had cancer during the first year of follow-up, sensitivity analysis showed the same trend. In addition, co-occurrence of MetS and high hs-CRP levels had significant interactive effects on the risk of PLC between the sexes (P < 0.001) and the patients with HBV infection (P = 0.012). CONCLUSIONS: Participants with co-occurrence of MetS and high hs-CRP levels have an elevated risk of PLC. TRIAL REGISTRATION: Kailuan study, ChiCTR-TNRC-11001489. Registered 24 August, 2011-Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=8050.

The combination of metabolic syndrome and inflammation increased the risk of colorectal cancer.

BACKGROUND: Inflammation and metabolic syndrome (MetS) may act synergistically and possibly accelerate the initiation and progression of colorectal cancer (CRC). We prospectively examined the joint effect of MetS and inflammation on the risk of CRC. METHODS: We studied 92,770 individuals from the Kailuan study. MetS was defined based on the presence of three or more of the following components. (1) high glucose: FPG > 5.6 mmol/L; (2) high blood pressure: SBP ≥ 130 mmHg or DBP ≥ 85 mmHg; (3) high triglycerides: triglycerides > 1.69 mmol/L; (4) low HDL-C: HDL-C < 1.04 mmol/L in men or 1.29 mmol/L in women; and (5) visceral adiposity: waist circumference ≥ 85 cm in men or 80 cm in women. Inflammation was defined as hs-CRP ≥ 3 mg/L. We divided participants into four groups for the primary exposure according to the presence/absence of inflammation and presence/absence of MetS. Cox proportional hazards regression models were used to evaluate the association of MetS and/or inflammation with the risk of CRC. RESULTS: Compared with metabolically healthy noninflammatory individuals, inflammatory participants without MetS and inflammatory participants with MetS were associated with a 1.3-fold and 4.18-fold increased risk of CRC with corresponding HRs (95% CI) of 1.34 (1.09, 1.64) and 4.18 (3.11, 5.62), respectively. The combination of MetS and inflammation was associated with the highest risk of CRC in all subgroups, especially among participants who were female, in younger age, and obese. Sensitivity analyses further validated our primary findings. CONCLUSIONS: We found the combination of MetS and inflammation could significantly increase the risk of CRC. Including CRP in the diagnosis of MetS may help to identify additional high-risk participants who should be targeted for early diagnosis and prevention of CRC. Trial registration Kailuan study, ChiCTR-TNRC-11001489. Registered 24 August, 2011-Retrospectively registered, http:// www.chictr.org.cn/showprojen.aspx?proj=8050.

Inversion of Soil Organic Matter Content Based on Improved Convolutional Neural Network.

Soil organic matter (SOM) is an important source of nutrients required during crop growth and is an important component of cultivated soil. In this paper, we studied the possibility of using deep learning methods to establish a multi-feature model to predict SOM content. Moreover, using Nong'an County of Changchun City as the study area, Sentinel-2A remote sensing images were taken as the data source to construct the dataset by using field sampling and image processing. The LeNet-5 convolutional neural network model was chosen as the deep learning model, which was improved based on the basic model. The evaluation metrics were selected as the root mean square error (RMSE) and the coefficient of determination R2. Through comparison, the R2 of the improved model was found to be higher than that of the linear regression method, Support Vector Machines (SVM) (RMSE = 2.471, R2 = 0.4035), and Random Forest (RF) (RMSE = 2.577, R2 = 0.4913). The result shows that: (1) It is feasible to use the multispectral data extracted from remote sensing images for soil organic matter content inversion based on the deep learning model with a minimum RMSE of 2.979 and with the R2 reaching 0.89. (2) The choice of features has an impact on the prediction of the model to a certain extent. After ranking the importance of features, selecting the appropriate number of features for inversion provides better results than full feature inversion, and the computational speed is improved.

Astrocytic YAP Promotes the Formation of Glia Scars and Neural Regeneration after Spinal Cord Injury.

Yes-associated protein (YAP) transcriptional coactivator is negatively regulated by the Hippo pathway and functions in controlling the size of multiple organs, such as liver during development. However, it is not clear whether YAP signaling participates in the process of the formation of glia scars after spinal cord injury (SCI). In this study, we found that YAP was upregulated and activated in astrocytes of C57BL/6 male mice after SCI in a Hippo pathway-dependent manner. Conditional knockout (KO) of yap in astrocytes significantly inhibited astrocytic proliferation, impaired the formation of glial scars, inhibited the axonal regeneration, and impaired the behavioral recovery of C57BL/6 male mice after SCI. Mechanistically, the bFGF was upregulated after SCI and induced the activation of YAP through RhoA pathways, thereby promoting the formation of glial scars. Additionally, YAP promoted bFGF-induced proliferation by negatively controlling nuclear distribution of p27Kip1 mediated by CRM1. Finally, bFGF or XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate YAP) injection indeed activated YAP signaling and promoted the formation of glial scars and the functional recovery of mice after SCI. These findings suggest that YAP promotes the formation of glial scars and neural regeneration of mice after SCI, and that the bFGF-RhoA-YAP-p27Kip1 pathway positively regulates astrocytic proliferation after SCI.SIGNIFICANCE STATEMENT Glial scars play critical roles in neuronal regeneration of CNS injury diseases, such as spinal cord injury (SCI). Here, we provide evidence for the function of Yes-associated protein (YAP) in the formation of glial scars after SCI through regulation of astrocyte proliferation. As a downstream of bFGF (which is upregulated after SCI), YAP promotes the proliferation of astrocytes through negatively controlling nuclear distribution of p27Kip1 mediated by CRM1. Activation of YAP by bFGF or XMU-MP-1 injection promotes the formation of glial scar and the functional recovery of mice after SCI. These results suggest that the bFGF-RhoA-YAP-p27Kip1 axis for the formation of glial scars may be a potential therapeutic strategy for SCI patients.

Associations Between Nonalcoholic Fatty Liver Disease and Cancers in a Large Cohort in China.

BACKGROUND & AIMS: The relationship between nonalcoholic fatty liver disease (NAFLD) and cancer, especially extrahepatic cancers, has not been fully clarified. We analyzed data from a large prospective cohort study to determine the relationship between NAFLD and development of cancers in men. METHODS: We collected data from the Kailuan cohort, a community-based cohort of 54,187 adult men in China, from June 2006 through October 2007. NAFLD was diagnosed by ultrasonography after excluding other causes related to chronic liver disease. Fine and Gray competing risk regression model was used to evaluate associations between NAFLD (without cirrhosis) and cancers. RESULTS: The prevalence of NAFLD was 32.3%. NAFLD was associated with increased risk of all cancers (hazard ratio [HR], 1.22; 95% CI, 1.10-1.36; P = .0001), thyroid cancer (HR, 2.79; 95% CI, 1.25-6.21; P = .01), and lung cancer (HR, 1.23; 95% CI, 1.02-1.49; P = .03). The association between NAFLD and risk of thyroid cancer increased with level of alanine aminotransferase (ALT). In men with NAFLD, level of ALT 80 U/L or more was associated with hepatocellular carcinoma (HR, 8.08; 95% CI, 2.46-26.56; P = .0006). NAFLD increased risk of colorectal cancer (HR, 1.96; 95% CI, 1.17-3.27) and lung cancer (HR, 1.38; 95% CI, 1.03-1.84) only in smokers. An association between NAFLD and kidney cancer (HR, 1.57; 95% CI, 1.03-2.40) was only observed in men without diabetes. CONCLUSIONS: A cohort study from China found that men with NAFLD have a higher risk of extrahepatic cancers, including thyroid and lung cancer. In men with NAFLD, higher levels of ALT were associated with higher risk of thyroid and hepatocellular cancer. NAFLD increased risk of colorectal and lung cancer only in smokers, and increased risk of kidney cancer in men without diabetes.

[Molecular analysis of an individual with CisAB phenotype].

OBJECTIVE: To explore the molecular basis for an individual with ABO subtype. METHODS: The ABO phenotype of the proband was determined by convention serological testing. Exons 6 and 7 of the ABO gene were subjected to PCR amplification and bi-directional Sanger sequencing. Haplotypes for exons 6 and 7 of the proband was determined using an ABO haplotype-specific amplification and sequencing technique. RESULTS: Red blood cells of the proband showed a 4+ agglutination strength with anti-A or anti-H, no agglutination reaction with anti-A1, and a 3+ agglutination strength with anti-B. His serum had no reaction with standard A cells, O cells or self cells, but was weakly reactive with B cells at 4℃. The proband was assigned as an ABO subtype based on his serological features. Bi-directional sequencing of the ABO gene revealed heterozygosity of 261 G/del, 297AG, 526CG, 657CT, 703GA, 803GC and 930GA, and homozygosity of 796CC in the proband. Haplotype-specific amplification and sequencing showed that one of his alleles was ABO*O.01.01, and another contained a c.796A>C variation compared with the ABO*B.01 allele, which led to replacement of methionine by leucine at position 266. Searching the ABO allele database of International Society of Blood Transfusion suggested the variation to be a novel one. CONCLUSION: The c.796A>C variation in the ABO*B.01 allele probably underlies the CisAB subtype. Accurate identification of the ABO subtype requires combined use of serological method and genetic testing.

[Association between the level of high sensitivity C-reactive protein and risk of breast cancer among non-diabetic females: a prospective study in Kailuan group].

OBJECTIVE: To evaluate the association between high sensitivity C-reactive protein (hsCRP) and breast cancer incidence among the non-diabetic females in a large-scale cohort study in Kailuan group. METHODS: The Kailuan cohort was established on May 1, 2006. Baseline information on demography, lifestyle, medical history, and anthropometry, i.e., body height and weight, were collected during the baseline interview, and breast cancer incidence, mortality and other related outcome information were obtained by follow-up every two years and the related health condition database information were collected every year. Multivariable Cox proportional-hazards regression model was used to calculate the hazard ratios (HRs) and 95%CI (confidence interval) between the level of hsCRP at baseline interview and breast cancer incidence adjusted for age group, body mass index (BMI), marital status (married and single) and tobacco smoking (smokers and non-smokers) when appropriate. RESULTS: By Dec 31, 2011, a total of 17 402 females were enrolled in the cohort. There were 85 286 person-years of follow-up with a mean follow-up period of (58.81 ± 4.52) months. A total of 75 incident breast cancer cases were collected. Subjects with the highest level (>3 mg/L) of hsCRP at baseline interview were associated with a significantly increased risk of breast cancer (adjusted HR = 1.80, 95%CI = 1.03-3.15) compared with those with the lowest level (<1 mg/L). CONCLUSIONS: Elevated levels of hsCRP at baseline interview may be associated with an increased risk of breast cancer among non-diabetic females. Further follow-up and etiological exploration will help to evaluate the association between the hsCRP level and the risk of breast cancer more reliably.

Dairy consumption and liver cancer risk: A meta­analysis of observational studies.

The connection between the consumption of dairy products and the risk of developing primary liver cancer (PLC) remains unclear. The present study performed a comprehensive meta-analysis with the aim of providing evidence for any connection between the risk of developing PLC and the consumption of dairy products. For this purpose, eligible studies were screened from the PubMed, Cochrane Library and Embase databases before December 2022. A total of 10 cohort studies and 8 case-control studies were included, making a total of 18 studies with 6,562,714 participants and 7,970 PLC cases. The relative risks (RRs) for milk and yogurt were 1.38 [95% confidence interval (CI), 1.07-1.77] and 0.49 (95% CI, 0.27-0.91), which revealed a positive and negative association, respectively, with the risk of developing PLC. There was no association between total dairy (RR, 1.04; 95% CI, 0.84-1.30) or cheese and curd (RR, 1.05; 95% CI, 0.87-1.27) consumption and the risk of developing PLC. On the whole, the findings of the present study demonstrated that high milk consumption was associated with a higher risk of developing PLC, while by contrast, yogurt consumption was associated with a lower risk of developing PLC. Consequently, further studies are required to further examine this association.

In Vitro Simulated Ketogenic Diet Inhibits the Proliferation and Migration of Liver Cancer Cells by Reducing Insulin Production and Down-regulating FOXC2 Expression.

Ketogenic diet (KD) may benefit patients with liver cancer, but the underlying mechanism of its anti-cancer effect remains an open issue. This work aimed to explore the influence of simulated KD on the proliferation and migration of cultured hepatoma cells. The low-glucose medium supplemented with ß-hydroxybutyrate (BHB-Glow) was utilized to simulate clinical KD treatment. Western blot was utilized for detecting the expression of glycolysis-related proteins, Seahorse XF96 for oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), and ELISA for insulin content. Expression of FOXC2 in liver cancer cells was analyzed by bioinformatics and qPCR. Cell Count Kit-8 (CCK-8) testing kit was utilized for testing cell viability. KD treatment significantly reduced the expression of glycolysis-related proteins in Huh-7 cells, inhibited insulin production in ß islet cells, reduced ECAR, and increased OCR. FOXC2 was significantly up-regulated in Huh-7 cell line, and sh-FOXC2 hindered the proliferation and migration of Huh-7 cells. The exogenous addition of insulin promoted the malignant progression of Huh-7 cells. Together, the medium simulating KD environment strengthened the protection of liver cancer cells by reducing insulin production and down-regulating FOXC2 expression. This study confirmed through in vitro cell experiments that KD could inhibit the proliferation and migration of liver cancer cells by targeting down regulation of insulin and FOXC2 expression, providing new theoretical basis for the treatment of liver cancer patients.

Protein expression of nucleolar protein 12 in the retina and its implication in protection of retina from UV irradiation damage.

Nucleolar protein 12 (NOL12), one of the nucleolar proteins which are primarily expressed in the nucleolus and play key roles in RNA metabolism, cell proliferation, cell cycle, and cell survival, is widely expressed in various species and multiple organs. Although it has been reported that the mRNA of Drosophila NOL12 homolog viriato is expressed in the eyes of Drosophila, the protein expression of NOL12 in mammalian eyes remains to be elucidated. In this study, we showed through immunohistochemistry that NOL12 was present in the rat retina, with predominant distribution in the cytoplasm of the retinal neuronal cells. In the human retinoblastoma cell line WERI-Rb1, we found that altering NOL12 expression led to a change in WERI-Rb1 cell viability. Knocking down NOL12 expression decreased cell viability. In contrast, overexpressing NOL12 increased cell viability. Furthermore, increasing NOL12 expression inhibited ultraviolet (UV)-induced apoptosis. These findings demonstrated that NOL12 may play an important protective role in retinal cells. In the WERI-Rb1 cells exposed to UV irradiation, we detected that NOL12 was degraded, but this degradation could be attenuated by a pan-Caspase inhibitor. Notably, the inhibitory effect of NOL12 against UV-induced apoptosis could be restrained by increasing the expression of ATR serine/threonine kinase (ATR), a kinase that, when activated by severe DNA damage, can result in apoptosis. We also found that upregulating NOL12 inhibited the activation of ATR caused by UV irradiation. Additionally, inhibiting ATR activity reduced apoptosis resulting from both silencing NOL12 expression and UV exposure. Thus, NOL12 may protect against UV irradiation-induced retinal damage by inhibiting ATR activity.

Angelicin impedes the progression of glioblastoma via inactivation of YAP signaling pathway.

Glioblastoma (GBM) is a human malignant tumor with low survival and high recurrence rate. Angelicin, an active furanocoumarin compound, has been reported to possess potential antitumor activity towards various malignancies. However, the effect of angelicin on GBM cells and its mechanism are still unclear. In this study, we found that angelicin inhibited the proliferation of GBM by inducing the cell cycle arrested in G1 phase and suppressed the migration of GBM cells in vitro. Mechanically, we found that angelicin downregulated the expression of YAP and decreased the nuclear localization of YAP, and suppressed the expression of ß-catenin. Furthermore, overexpression of YAP partially restored the inhibitory effect of angelicin on GBM cells in vitro. Finally, we found that angelicin could inhibit the growth of tumor and reduce the expression of YAP in the subcutaneous xenograft model of GBM in nude mice and the syngeneic intracranial orthotopic model of GBM in C57BL/6 mice. Taken together, our results suggest that the natural product angelicin exerts its anticancer effects on GBM via YAP signaling pathway, and is expected to be a promising compound for the treatment of GBM.

Efficacy and Safety of Sevelamer Carbonate in Chinese Nondialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized, Double-Blind, Parallel-Group Study.

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia. Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4-12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8. Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (-0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly (p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group (p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group. Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia.

The relationship between serum uric acid and colorectal cancer: a prospective cohort study.

Serum uric acid (SUA) may play an important role in the occurrence of colorectal cancer (CRC). This study aims to explore the association of SUA with the risk of CRC incidence by drawing data from the Kailuan Study. We prospectively examined the association between SUA and risk of CRC incidence among 93,356 Chinese. Eligible participants were divided into three groups based on their tertiles of SUA. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC. During a median follow-up of 13.02 years, 583 new-onset CRC cases were identified. After adjustments were made for confounders, participants in the highest tertiles of SUA exhibited a 1.55-fold increased risk of CRC compared with patients with the lowest SUA levels (HRT3 vs. T1 = 1.55, 95% CI: 1.09-2.30). The associations of SUA with the risk of CRC were slightly reduced but remained substantial in the competing risk analyses when treating CRC unrelated death as the competing risk event. This study found a positive association of SUA with CRC incidence. Specific prevention efforts could be focused on the population with higher levels of SUA.

Insulin resistance and inflammation mediate the association of abdominal obesity with colorectal cancer risk.

Background: The close association of abdominal obesity rather than general obesity with colorectal cancer (CRC) risk might be mediated by IR and inflammation, which has never been systematically explored in large-scale prospective studies. Methods: We prospectively examined the mediation effects of the fasting triglyceride-glucose (TyG) index and C-reactive protein (CRP) on the associations of obesity (general and abdominal) with CRC risk among 93,659 participants. We used the Cox proportional hazards regression models and subgroup analyses to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CRC. The CAUSALMED procedure was used to perform the mediation analyses. Results: During 13.02 years of follow-up, a total of 586 CRC cases were verified. Male participants with general obesity and abdominal obesity had a 1.29-fold and a 1.28-fold increased risk of CRC. However, a significant association was only observed among female individuals with abdominal obesity. Both TyG index and CRP were associated with an elevated risk of CRC, and A significant interaction between the TyG index and CRP was found for the risk of CRC (P for interaction<0.05). CRP and the TyG index significantly mediated the positive association between abdominal obesity and CRC risk. Conclusion: CRP and TyG index increased the risk of CRC independently and synergistically. Mediation effects of CRP and the TyG index were found for the association between abdominal obesity and CRC risk.