Curcumin suppresses colorectal cancer by induction of ferroptosis via regulation of p53 and solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 signaling axis.

Driven by iron-dependent lipid peroxidation, ferroptosis is regulated by p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on ferroptosis in CRC. The efficacies of CUR on the malignant phenotype of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, and clonogenic assays. The effects of CUR on ferroptosis of CRC cells were evaluated by transmission electron microscopy, lactate dehydrogenase release assay, Fe2+ staining, and analyses of reactive oxygen species, lipid peroxide, malondialdehyde, and glutathione levels. CUR's targets in ferroptosis were predicted by network pharmacological study and molecular docking. With SW620 xenograft tumors, the efficacy of CUR on CRC was investigated, and the effects of CUR on ferroptosis were assessed by detection of Fe2+, malondialdehyde, and glutathione levels. The effects of CUR on expressions of p53, SLC7A11, and GPX4 in CRC cells and tumors were analyzed by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. CUR suppressed the proliferation, migration, and clonogenesis of CRC cells and xenograft tumor growth by causing ferroptosis, with enhanced lactate dehydrogenase release and Fe2+, reactive oxygen species, lipid peroxide, and malondialdehyde levels, but attenuated glutathione level in CRC. In silico study indicated that CUR may bind p53, SLC7A11, and GPX4, consolidated by that CUR heightened p53 but attenuated SLC7A11 and GPX4 mRNA and protein levels in CRC. CUR may exert an inhibitory effect on CRC by inducing ferroptosis via regulation of p53 and SLC7A11/glutathione/GPX4 axis.

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target.

BACKGROUND: The Wnt signaling pathway is a complex network of protein interactions that functions most commonly in embryonic development and cancer, but is also involved in normal physiological processes in adults. The canonical Wnt signaling pathway regulates cell pluripotency and determines the differentiation fate of cells during development. The canonical Wnt signaling pathway (also known as the Wnt/ß-catenin signaling pathway) is a recognized driver of colon cancer and one of the most representative signaling pathways. As a functional effector molecule of Wnt signaling, the modification and degradation of ß-catenin are key events in the Wnt signaling pathway and the development and progression of colon cancer. Therefore, the Wnt signaling pathway plays an important role in the pathogenesis of diseases, especially the pathogenesis of colorectal cancer (CRC). OBJECTIVE: Inhibit the Wnt signaling pathway to explore the therapeutic targets of colorectal cancer. METHODS: Based on studying the Wnt pathway, master the biochemical processes related to the Wnt pathway, and analyze the relevant targets when drugs or inhibitors act on the Wnt pathway, to clarify the medication ideas of drugs or inhibitors for the treatment of diseases, especially colorectal cancer. RESULTS: Wnt signaling pathways include: Wnt/ß-catenin or canonical Wnt signaling pathway, planar cell polarity (Wnt-PCP) pathway and Wnt-Ca2+ signaling pathway. The Wnt signaling pathway is closely related to cancer cell proliferation, stemness, apoptosis, autophagy, metabolism, inflammation and immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis. Drugs/phytochemicals and molecular preparations for the Wnt pathway of CRC treatment have now been developed. Wnt inhibitors are also commonly used clinically for the treatment of CRC. CONCLUSION: The development of drugs/phytochemicals and molecular inhibitors targeting the Wnt pathway can effectively treat colorectal cancer clinically.

Ursolic acid inhibits the activation of smoothened-independent non-canonical hedgehog pathway in colorectal cancer by suppressing AKT signaling cascade.

It is being brought to light that smoothened (SMO)-independent non-canonical Hedgehog signaling is associated with the pathogenesis of various cancers. Ursolic acid (UA), a pentacyclic triterpenoid present in many medicinal herbs, manifests potent effectiveness against multiple malignancies including colorectal cancer (CRC). In our previous study, UA was found to protect against CRC in vitro by suppression of canonical Hedgehog signaling cascade. Here, the influence of UA on SMO-independent non-canonical Hedgehog signaling in CRC was investigated in the present study, which demonstrated that UA hampered the proliferation and migration, induced the apoptosis of HCT-116hSMO- cells with SMO gene knockdown, accompanied by the augmented expression of the suppressor of fused (SUFU), and lessened levels of MYC (c-Myc), glioma-associated oncogene (GLI1) and Sonic Hedgehog (SHH), and lowered phosphorylation of protein kinase B (PKB, AKT), suggesting that UA diminished non-canonical Hedgehog signal transduction in CRC. In HCT-116hSMO- xenograft tumor, UA ameliorated the symptoms, impeded the growth and caused the apoptosis of CRC, with heightened SUFU expression, and abated levels of MYC, GLI1, and SHH, and mitigated phosphorylation of AKT, indicating that UA down-regulated non-canonical Hedgehog signaling cascade in CRC. Taken together, UA may alleviate CRC by suppressing AKT signaling-dependent activation of SMO-independent non-canonical Hedgehog pathway.

Anti-silencing function 1B histone chaperone promotes cell proliferation and migration via activation of the AKT pathway in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies. Anti-silencing function 1B histone chaperone (ASF1B) has been reported to be involved in various diseases. However, its role in ccRCC is largely unknown. In the present study, using genetic data and clinical information obtained from the TCGA data portal and GEO database, we found that ASF1B was highly expressed in ccRCC cancer tissue compared with normal tissue, and ASF1B expression was positively correlated with tumor stage, tumor grade and patient survival. The function of ASF1B in cell proliferation and migration was assessed by pathological and molecular analyses. The results showed that ASF1B overexpression significantly enhanced the proliferation and migration of 786-O cells and Caki-1 cells, while silencing ASF1B expression significantly inhibited the proliferation and migration. In addition, ASF1B overexpression enhanced cell proliferation by upregulating PCNA and downregulating P27 expression and promoted cell migration by upregulating MMP2 and MMP9. Furthermore, the phosphorylation levels of protein kinase B (AKT) and P-P70 S6K1 were significantly upregulated in the ASF1B overexpression group. More importantly, AKT inhibitor blocked the promotional effect of ASF1B on proliferation and migration. In summary, the present study demonstrated that ASF1B overexpression promoted tumor cell proliferation and migration, which was dependent on the AKT/P70 S6K1 pathway.

Armeniacae semen amarum: a review on its botany, phytochemistry, pharmacology, clinical application, toxicology and pharmacokinetics.

Armeniacae semen amarum-seeds of Prunus armeniaca L. (Rosaceae) (ASA), also known as Kuxingren in Chinese, is a traditional Chinese herbal drug commonly used for lung disease and intestinal disorders. It has long been used to treat coughs and asthma, as well as to lubricate the colon and reduce constipation. ASA refers to the dried ripe seed of diverse species of Rosaceae and contains a variety of phytochemical components, including glycosides, organic acids, amino acids, flavonoids, terpenes, phytosterols, phenylpropanoids, and other components. Extensive data shows that ASA exhibits various pharmacological activities, such as anticancer activity, anti-oxidation, antimicrobial activity, anti-inflammation, protection of cardiovascular, neural, respiratory and digestive systems, antidiabetic effects, and protection of the liver and kidney, and other activities. In clinical practice, ASA can be used as a single drug or in combination with other traditional Chinese medicines, forming ASA-containing formulas, to treat various afflictions. However, it is important to consider the potential adverse reactions and pharmacokinetic properties of ASA during its clinical use. Overall, with various bioactive components, diversified pharmacological actions and potent efficacies, ASA is a promising drug that merits in-depth study on its functional mechanisms to facilitate its clinical application.

Enhanced image quality and lesion detection in FLAIR MRI of white matter hyperintensity through deep learning-based reconstruction.

OBJECTIVE: To delve deeper into the study of degenerative diseases, it becomes imperative to investigate whether deep-learning reconstruction (DLR) can improve the evaluation of white matter hyperintensity (WMH) on 3.0T scanners, and compare its lesion detection capabilities with conventional reconstruction (CR). METHODS: A total of 131 participants (mean age, 46 years ±17; 46 men) were included in the study. The images of these participants were evaluated by readers blinded to clinical data. Two readers independently assessed subjective image indicators on a 4-point scale. The severity of WMH was assessed by four raters using the Fazekas scale. To evaluate the relative detection capabilities of each method, we employed the Wilcoxon signed rank test to compare scores between the DLR and the CR group. Additionally, we assessed interrater reliability using weighted k statistics and intraclass correlation coefficient to test consistency among the raters. RESULTS: In terms of subjective image scoring, the DLR group exhibited significantly better scores compared to the CR group (P < 0.001). Regarding the severity of WMH, the DL group demonstrated superior performance in detecting lesions. Majority readers agreed that the DL group provided clearer visualization of the lesions compared to the conventional group. CONCLUSION: DLR exhibits notable advantages over CR, including subjective image quality, lesion detection sensitivity, and inter reader reliability.

Prevalence and associations of cataract in a rural Chinese adult population: the Handan Eye Study.

BACKGROUND: Cataract remains the leading cause of blindness and visual impairment in the world and in China. However, data on the prevalence of cataract based on standardized lens grading protocols from mainland China are limited. This paper estimated the age- and gender-specific prevalence and risk factor for cataract METHODS: In a population-based Chinese sample, participants underwent a comprehensive ophthalmic examination, including assessment of cortical, nuclear, posterior subcapsular (PSC) and mixed lens opacities from slit-lamp grading using the Lens Opacities Classification System III. RESULTS: Of the 7,557 eligible subjects, 6,830 took part in the study (90.4% response rate), and 6,544 participants (95.8%, mean age 52.0 ± 11.8 years) had lens data for analyses. The prevalence of any cataract surgery in at least one eye was 0.8% (95% confidence interval [CI], 0.62, 1.06), with similar rates between men and women. The overall prevalence of any cataract or cataract surgery was 20.8% (95% CI, 19.8, 21.8), higher in women than in men after adjusting for age (23.6% vs 17.6%; OR: 1.78; 95% CI: 1.54-2.07). When distinct lens opacity was categorized in each eye as cortical, nuclear, PSC or mixed, based on one randomly selected eye, cortical cataract was the most common distinct subtype (12.3%), followed by mixed (3.2%), nuclear (1.7%), and PSC (0.2%) cataract. The prevalence of all lens opacities increased with age (P < 0.001). After excluding other causes for visual impairment, the proportion of people with best corrected visual acuity <20/60 was 21% among those with PSC, and 12% among those with mixed opacities in the better-seeing eye. In multivariable logistic regression models, myopia was associated with all cataract types, while higher fasting plasma glucose and diabetes were only associated with PSC cataract. CONCLUSIONS: Cataract affects 20% of the population aged 30 years and older living in rural China, with cortical cataract the most common subtype. Risk factors for cataract include myopia and diabetes.

[Association analysis of serum γ-glutamyltransferase with risk of metabolic syndrome in Beijing healthy population].

OBJECTIVE: To study the association of γ-glutamyltransferase (GGT) with the development of the metabolic syndrome (MS). METHODS: Subjects without MS at baseline in Beijing health-checkup database during 2003 and 2010, from MJ Health Management Centers, with complete key variables and at least two records were selected to derive a cohort, after comparison of the median trend, and analysis with Cox regression models and spline regression models, and to study the association of GGT with the development of MS and the dose-response relationship trend. RESULTS: Out of 10 076 (46.20/1 000 person-years) in the cohort, 1 181 subjects developed MS after follow-up of 2.54 years on average. With adjustment for age, gender, cigarette smoking, alcohol intake, physical activity, body mass index, family history of cardiovascular disease, systolic blood pressure, white blood cell count, high-density lipoprotein cholesterol, fasting blood glucose, triglycerides and C-reacted protein in Cox regression model, the hazard ratio for MS in quartiles 4 level of GGT was 1.60(95% confidence interval: 1.18-2.17). After adjustment with the use of spline regression model, the dose-response relationship showed an increasing curve with a degressive slope. The elevated GGT level was associated with an increased risk of MS, but the contribution of GGT augmented less when the GGT level was high. CONCLUSION: The elevated GGT level, an important risk factor and predictor, may be associated with an increased risk of MS.

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/ß-Catenin Signaling Pathway Activity.

Overwhelming evidence points to an abnormally active Wnt/ß-catenin signaling as a key player in colorectal cancer (CRC) pathogenesis. Ursolic acid (UA) is a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices, and medicinal plants. UA has been shown to have potent bioactivity against a variety of cancers, including CRC, with the action mechanism obscure. Our study tried to learn more about the efficacy of UA on CRC and its functional mechanism amid the Wnt/ß-catenin signaling cascade. We determined the efficacy of UA on CRC SW620 cells with respect to the proliferation, migration, clonality, apoptosis, cell cycle, and Wnt/ß-catenin signaling cascade, with assessment of the effect of UA on normal colonic NCM460 cells. Also, the effects of UA on the tumor development, apoptosis, cell cycle, and Wnt/ß-catenin signaling axis were evaluated after a subcutaneous SW620 xenograft tumor model was established in mice. In this work, we showed that UA drastically suppressed proliferation, migration, and clonality; induced apoptosis; and arrested the cell cycle at the G0/G1 phase of SW620 cells, without the influence on NCM460 cells, accompanied by weakened activity of the Wnt/ß-catenin signaling pathway. Besides, UA markedly deterred the growth of the xenograft tumor, ameliorated pathological features, triggered apoptosis, and arrested the cell cycle in xenograft CRC tissue, by lessening the Wnt/ß-catenin signaling cascade. Overall, UA may inhibit the malignant phenotype, induce apoptosis, and arrest the cell cycle of CRC, potentially by attenuating the Wnt/ß-catenin signaling axis, providing insights into the mechanism for the potency of UA on CRC.

Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF-κB signaling cascade and inhibiting NLRP3 inflammasome activation.

Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated with the pathogenesis of ALI. Since ALI poses a huge challenge to human health, it is urgent to tackle this affliction with therapeutic intervention. Qinhuo Shanggan oral solution (QHSG), a traditional Chinese herbal formula, is clinically used for effective medication of various lung diseases including ALI, with the action mechanism obscure. In the present study, with the rat model of lipopolysaccharide (LPS)-induced ALI, QHSG was unveiled to ameliorate ALI by alleviating the pathological features, reversing the alteration in white blood cell profile and impeding the production of inflammatory cytokines through down-regulation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. In LPS-stimulated RAW264.7 mouse macrophages, QHSG was discovered to hinder the generation of inflammatory cytokines by lessening TLR4/NF-κB signaling pathway activity and weakening NLRP3 inflammasome activation. Taken together, QHSG may resolve acute lung injury, attributed to its anti-inflammation and immunoregulation by attenuation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. Our findings provide a novel insight into the action mechanism of QHSG and lay a mechanistic foundation for therapeutic intervention in acute lung injury with QHSG in clinical practice.

Berberine is a suppressor of Hedgehog signaling cascade in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignant affliction that burdens people globally. Overactivated Hedgehog signal is highly implicated in CRC pathogenesis. Phytochemical berberine exerts strong potency on CRC, with molecular mechanism elusive. PURPOSE: We sought to study berberine's anti-CRC action and explore its underlying mechanism based on Hedgehog signaling cascade. METHODS: In CRC HCT116 cells and SW480 cells treated with berberine, the proliferation, migration, invasion, clonogenesis, apoptosis and cell cycle were measured, with determination of Hedgehog signaling pathway activity. Following establishment of mouse model of HCT116 xenograft tumor, the efficacies of berberine on carcinogenesis, pathological manifestation and malignant phenotypes of CRC were examined, with analysis of Hedgehog signaling axis in HCT116 xenograft tumor tissues. Additionally, toxicological study of berberine was conducted on zebrafish. RESULTS: Berberine was discovered to suppress the proliferation, migration, invasion and clonogenesis of HCT116 cells and SW480 cells. Furthermore, berberine caused cell apoptosis and blockaded cell cycle at phase G0/G1 in CRC cells, with dampened Hedgehog signaling cascade. In HCT116 xenograft tumor of nude mice, berberine inhibited tumor growth, alleviated pathological score, and promoted apoptosis and cell cycle arrest in tumor tissues, through constraining Hedgehog signaling. The toxicological study of berberine on zebrafish indicated that berberine incurred damage to the liver and heart of zebrafish at high dosage and prolonged administration. CONCLUSIONS: Taken together, berberine may inhibit the malignant phenotypes of CRC through diminishing Hedgehog signaling cascade. However, the potential adverse reactions should be taken into account upon abuse of berberine.

Curcumin: An epigenetic regulator and its application in cancer.

Nowadays, one of the leading causes of death in humans is cancer, which is still on the rise globally and is in great need of intense study on the pathogenic mechanism and effective therapy. Epigenetics is a discipline that studies heritable changes in gene expression without alteration of DNA sequence. Epigenetic changes mainly involve DNA methylation, histone modifications and non-coding RNA (ncRNA) expression, which are interconnected to play a crucial role in the initiation and progression of various malignancies. Curcumin is a type of plant-derived polyphenolic compound with strong bioactivity against various disorders, particularly cancer. Retrieving commonly used databases such as PubMed, Google Scholar and CNKI, we summarized recent advances in the efficacy of curcumin on cancer and its epigenetic regulation in terms of DNA methylation, histone modifications and ncRNA expression. Furthermore, we also focused on improving the bioavailability of curcumin by development of novel curcumin analogs with high bioavailability, nanoparticles-loaded drug delivery system for curcumin, and combination therapy of curcumin with other agents. This review provides comprehensive insights into the molecular mechanisms, on the basis of epigenetic regulation, underlying the clinical application of curcumin in cancer.

Peppermint essential oil: its phytochemistry, biological activity, pharmacological effect and application.

Mentha (also known as peppermint), a genus of plants in the taxonomic family Lamiaceae (mint family), is widely distributed throughout temperate regions of the world. Mentha contains various constituents that are classified as peppermint essential oil (PEO) and non-essential components. PEO, consisting mainly of menthol, menthone, neomenthol and iso-menthone, is a mixture of volatile metabolites with anti-inflammatory, antibacterial, antiviral, scolicidal, immunomodulatory, antitumor, neuroprotective, antifatigue and antioxidant activities. Mounting evidence indicates that PEO may pharmacologically protect gastrointestinal, liver, kidney, skin, respiratory, brain and nervous systems, and exert hypoglycemic and hypolipidemic effects. Clinically, PEO is used for gastrointestinal and dermatological diseases, postoperative adjuvant therapy and other fields. This review aims to address the advances in the extraction and isolation of PEO, its biological activities, pharmacological effects, toxicity and applications, with an emphasis on the efficacy of PEO on burn wounds and psoriasis, providing a comprehensive foundation for research, development and application of PEO in future.

Suppression of colitis-associated colorectal cancer by scutellarin through inhibiting Hedgehog signaling pathway activity.

BACKGROUND: Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer (CRC) and mainly develops from long-term intestinal inflammation. Mounting evidence reveals that activated Hedgehog signaling pathway plays a vital role in the pathogenesis of CRC. Scutellarin is a type of phytochemical flavonoid with a powerful efficacy on various malignancies, including CRC. AIM: Here, we studied the therapeutic effect of scutellarin on CRC and its direct regulating targets. METHODS: The CAC model in mice was established by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by detection of the efficacies of scutellarin on the carcinogenesis, apoptosis, inflammation, Hedgehog signaling cascade and complicated inflammatory networks in CAC tissues of mice. In CRC SW480 cells, the effects of scutellarin on malignant phenotype, apoptosis and Hedgehog signaling were examined. In TNF-α-stimulated IEC-6 intestinal epithelial cells, the actions of scutellarin on inflammatory response and Hedgehog signals were assessed as well. RESULTS: Scutellarin significantly ameliorated AOM/DSS-caused CAC in mice and induced apoptosis in CAC tissues of mice, by inhibiting NF-κB (nuclear factor kappa B) -mediated inflammation and Hedgehog signaling axis. RNA-seq and transcriptome analysis indicated that scutellarin regulated complicated inflammatory networks in mouse CAC. Also, scutellarin suppressed the proliferation, migration, colony formation, and induced apoptosis of SW480 cells by down-regulation of Hedgehog signaling pathway activity. Additionally, scutellarin lessened NF-κB-mediated inflammatory response in TNF-α-stimulated IEC-6 cells, by attenuating Hedgehog signaling cascade. CONCLUSION: Scutellarin potently ameliorates CAC by suppressing Hedgehog signaling pathway activity, underpinning the promising application of scutellarin to CRC in clinical settings.

Berberine suppresses colorectal cancer by regulation of Hedgehog signaling pathway activity and gut microbiota.

BACKGROUND: A growing body of evidence reveals that dysregulation of Hedgehog signaling pathway and dysbiosis of gut microbiota are associated with the pathogenesis of colorectal cancer (CRC). Berberine, a botanical benzylisoquinoline alkaloid, possesses powerful activities against various malignancies including CRC, with the underlying mechanisms to be illuminated. PURPOSE: The present study investigated the potencies of berberine on CRC and deciphered the action mechanisms in the context of Hedgehog signaling cascade and gut microbiota. METHODS: The effects of berberine on the malignant phenotype, apoptosis, cell cycle and Hedgehog signaling of CRC cells were examined in vitro. In azoxymethane/dextran sulfate sodium-caused mouse CRC, the efficacies of berberine on the carcinogenesis, pathological profile, apoptosis, cell cycle and Hedgehog signaling were determined in vivo. Also, the influences of berberine on gut microbiota in CRC mice were assessed by high-throughput DNA sequencing analysis of 16S ribosomal RNA of fecal microbiome in CRC mice. RESULTS: In the present study, berberine was found to dampen the proliferation, migration, invasion and colony formation of CRC cells, without toxicity to normal colonic cells. Additionally, berberine induced apoptosis and arrested cell cycle at G0/G1 phase in CRC cells, accompanied by reduced Hedgehog signaling pathway activity in vitro. In mouse CRC, berberine suppressed tumor growth, ameliorated pathological manifestations, and potentially induced the apoptosis and cell cycle arrest of CRC, with lowered Hedgehog signaling cascade in vivo. Additionally, berberine decreased ß-diversity of gut microbiota in CRC mice, without influence on α-diversity. Berberine also enriched probiotic microbes and depleted pathogenic microbes, and modulated the functionality of gut microbiota in CRC mice. CONCLUSIONS: Overall, berberine may suppress colorectal cancer, orchestrated by down-regulation of Hedgehog signaling pathway activity and modulation of gut microbiota.

Normal macular thickness measurements using optical coherence tomography in healthy eyes of adult Chinese persons: the Handan Eye Study.

PURPOSE: To describe macular thickness measured by optical coherence tomography (OCT) in healthy eyes of adult Chinese persons. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Chinese adults aged 30+ years who were residents of Handan, North China. METHODS: The Handan Eye Study is a population-based study of eye disease in Chinese persons. Eligible residents underwent a comprehensive ophthalmic examination including OCT (Stratus OCT, Carl Zeiss Meditec Inc., Jena, Germany). Fast macular thickness scans were performed over maculae within 6 mm in diameter, divided into 3 regions (central, inner, and outer, with a diameter of 1, 3, and 6 mm, respectively) and 9 quadrants (1 in the central region and 4 each in the inner and outer regions). Retinal thickness (means and standard deviations) was calculated by OCT mapping software, presented for foveal minimum, central macula (within 1 mm diameter), and inner and outer regions divided by 8 quadrants. MAIN OUTCOME MEASURES: Macular thickness measured by OCT. RESULTS: Of the 6830 participants (90.4% response rate) examined, 2230 eyes of healthy subjects with high-quality OCT scans were selected (32.7% of participants; mean age, 46.4+/-9.9 years, 58.4% were women). The mean foveal minimum, central, inner, and outer macular thicknesses were 150.3 (18.1) microm, 176.4 (17.5) microm, 255.3 (14.9) microm, and 237.7 (12.4) microm, respectively (overall differences, P<0.001). The mean foveal volume was 0.139 (0.014) mm(3), and the mean total macular volume was 6.761 (0.516) mm(3). In the inner region, the nasal quadrant was thinner than the superior and inferior quadrants, and in the outer region, the nasal quadrant was the thickest (P<0.001). Age was positively correlated with foveal (beta coefficient = 3.582) and central macular (beta coefficient = 2.422) thicknesses. The foveal minimum, central, inner, and outer macular thicknesses were significantly greater in men than in women. Fasting plasma glucose was negatively correlated with central macular thickness (2.416 mm reduction per millimole/liter increase in glucose), and axial length was positively correlated with central macular thickness (2.138 mm increase per millimeter increase in axial length). CONCLUSIONS: Normal macular thickness measurements using OCT in a large population-based sample of adult Chinese persons aged 30 to 85 years were generally thinner in the foveal and central macular areas than measurements reported in other populations. Age and axial length were positively correlated with macular thickness.

[Study of an adherence rating score system for tuberculosis patients in China].

OBJECTIVE: To develop an adherence rating score (ARS) system specific for tuberculosis (TB) patients. METHODS: A cross-sectional survey of 124 TB patients was conducted to figure out risk factors for adherence to treatment. The step-wise logistic regression models were used for selecting adherence-related variables. ARS was developed based on the weighting scores of the parameters of all the predicted variables in the logistic model. The reliability and responsibility of ARS was evaluated by using external data from an open label randomized controlled trial on 574 TB patients. The patients were grouped as adherence group (247 patients) and non-adherence group (327 patients) based on the predicted ARS. And the non-adherence group was randomized divided into a trail group (146 patients) and a control group (181 patients). The intervention for the trail group was custom health educational material aimed to reduce ARS, while the intervention for control groups was general TB education material, which was routinely used in the current local TB control settings. The cumulative non-adherence rates of the three groups were compared with each other after six-month follow-up period of treatment. RESULTS: The ARS system had 7 items which covered the following domains: disease status, psychology, patients' KAP (knowledge, attitude, and practice), regularly life-style and social supports. The score of ARS was 2.38+/-0.18 (mean+/-SD) for adherence patients, and 4.69 +/-0.20 (mean+/-SD) for non-adherence patients (t=8.52, P<0.01). In the randomized controlled trial, the six months cumulative non-adherence rates ware 24.7% for the trail group and it was 41.4% for the control group(P<0.01); while the six months cumulative non-adherence rates were not statistical significant difference between trail group and adherence group (P>0.05). CONCLUSION: The ARS system was reliability and validity for evaluating the adherence of TB treatment in the stop TB settings in China.

Ubiquitin-Specific Peptidase 10 Protects Against Hepatic Ischaemic/Reperfusion Injury via TAK1 Signalling.

Ubiquitin-specific peptidase 10 (USP10) protein is a deubiquitination enzyme involved in many important biological processes. However, the function of USP10 in hepatic ischaemic/reperfusion (I/R) injury remains unknown. The aim of this study was to explore the role of USP10 in hepatic I/R injury. USP10 Heterozygote mice and primary hepatocytes were used to construct hepatic I/R models. The effect of USP10 on hepatic I/R injury was examined via pathological and molecular analyses. Our results indicated that USP10 was significantly downregulated in the livers of mice after hepatic I/R injury and in hepatocytes subjected to hypoxia/reoxygenation stimulation. USP10 Heterozygote mice exhibited exacerbated hepatic I/R injury, as evidenced by enhanced liver inflammation via the NF-κB signalling pathway and increased hepatocyte apoptosis. Additionally, USP10 overexpression inhibited hepatocyte inflammation and apoptosis in hepatic I/R injury in vitro and in vivo. Mechanistically, our study demonstrated that USP10 knockdown exerted its detrimental effects on hepatic I/R injury by inducing activation of the transforming growth factor ß-activated kinase 1 (TAK1)-JNK/p38 signalling pathways. TAK1 was required for USP10 function in hepatic I/R injury as TAK1 inhibition abolished USP10 function in vitro. In conclusion, our study demonstrated that USP10 plays a protective role in hepatic I/R injury by inhibiting the activation of the TAK1-JNK/p38 signalling pathways. Modulation of USP10/TAK1 might be a promising strategy to prevent this pathological process.

Refractive errors in a rural Chinese adult population the Handan eye study.

PURPOSE: To describe the prevalence of and risk factors for myopia and other refractive errors in a rural, adult, Chinese population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A clustered, random sampling procedure was used to select 7557 Chinese people aged >or=30 years from Handan, China. METHODS: All eligible subjects were invited to undergo a comprehensive eye examination, including standardized refraction. Myopia, high myopia, and hyperopia were defined as a spherical equivalent (SE) in the right eye of more than -0.5 diopter (D), less than -5.0 D, and 0.5 D or more, respectively. Astigmatism was less than -0.5 D of cylinder. Anisometropia was defined as a difference in SE of >1.0 D between the 2 eyes. Only phakic eyes were analyzed. MAIN OUTCOME MEASURES: Myopia and other refractive errors. RESULTS: We included 6491 (85.9% participation rate) eligible subjects in this study. Adjusted to the 2000 China population census, the prevalence rate of myopia was 26.7% (95% confidence interval [CI], 25.6-27.8), hyperopia 15.9 % (95% CI, 15.0-16.8), astigmatism 24.5% (95% CI, 23.5-25.5), and anisometropia 7.7% (95% CI, 7.0-8.4). The prevalence of high myopia was 1.8% (95% CI, 1.5-2.1). Using a multivariate regression model, current smoking (odds ratio [OR], 0.7, 95% CI, 0.5-0.9), hours of reading (OR, 1.2; 95% CI, 1.1-1.4), diabetes (OR, 8.4; 95% CI, 2.2-32.5), and number of family members with myopia (OR, 1.3; 95% CI, 1.1-1.7, for each family member) were associated with myopia in younger persons (30-49 years). High school or higher education (OR, 1.8; 95% CI, 1.1-3.1), diabetes (OR, 1.6; 95% CI, 1.2-2.7), nuclear opacity (OR, 1.7; 95% CI, 1.2-2.3), and number of family members with myopia (OR, 1.5; 95% CI, 1.2-1.9) were risk factors in persons >or=50 years of age. CONCLUSIONS: Myopia affects more than one quarter of rural Chinese persons >or=30 years of age. Myopia is more common in younger people and is associated with different risk factors than in older people.

Prevalence of diabetic retinopathy in rural China: the Handan Eye Study.

PURPOSE: To describe the age- and gender-specific prevalence, characteristics, and severity of diabetic retinopathy (DR) in a rural population in northern China. DESIGN: A population-based cross-sectional study. PARTICIPANTS: A total of 6830 Han Chinese aged 30 years and older from 13 villages of Yongnian County, Handan City, Hebei Province, China. METHODS: All participants underwent a standardized interview, a comprehensive eye examination, and fasting blood glucose testing according to the American Diabetes Association diagnostic criteria (fasting plasma glucose >or=7.0 mmol/l). Retinal photographs obtained after pupil dilation were graded for the presence and severity of DR according to the modified Early Treatment Diabetic Retinopathy Study classification system. MAIN OUTCOME MEASURES: Any DR, retinopathy grades, macular edema, or vision-threatening retinopathy. RESULTS: Of the 6830 eligible individuals participating in the study, 5597 (81.9%) had fasting blood glucose results available. Of these, 387 participants (6.9%) were diagnosed with diabetes mellitus, including 247 subjects with new diabetes mellitus (NDM) and 140 subjects with known diabetes mellitus (KDM). For these, gradable photographs were available for 368 subjects (95.1%). The overall prevalence of DR was 43.1% (95% confidence interval, 38.1-48.4) and was higher in persons with KDM (65.2%) than NDM (33.5%). The prevalence of proliferative DR, macular edema, and vision-threatening retinopathy was 1.6%, 5.2%, and 6.3%, respectively, with 12.1% with KDM having untreated vision-threatening DR. No age- or gender-related differences were present. The prevalence of DR was strongly related to duration of disease. CONCLUSIONS: Our study reports a high prevalence of DR among adults 30 years and older with diabetes in rural China. On the basis of estimates obtained from our study, we projected that in rural China, 21.1 million persons aged 30+ years have diabetes and 9.2 million have DR, including 1.3 million with vision-threatening DR. There is a pressing need for appropriate screening and management of diabetes and its complications in rural China.