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This study was to investigate the protective effect of hyperbaric oxygen (HBO) on HT22 and PC12 cell damage caused by oxygen-glucose deprivation/reperfusion-induced ferroptosis. A 2-h oxygen-glucose deprivation and 24-h reperfusion model on HT22 and PC12 cells was used to simulate cerebral ischemia-reperfusion injury. Cell viabilities were detected by Cell Counting Kit-8 (CCK-8) method. The levels of reactive oxygen species (ROS) and lipid reactive oxygen species (Lipid ROS) were detected by fluorescent probes Dihydroethidium (DHE) and C11 BODIPY 581/591. Iron Colorimetric Assay Kit, malondialdehyde (MDA) and glutathione (GSH) activity assay kits were used to detect intracellular iron ion, MDA and GSHcontent. Cell ferroptosis-related ultrastructures were visualized using transmission electron microscopy (TEM). Furthermore, PCR and Western blot analyses were used to detect the expressions of ferroptosis-related genes and proteins. After receiving oxygen-glucose deprivation/reperfusion, the viabilities of HT22 and PC12 cells were significantly decreased; ROS, Lipid ROS, iron ions and MDA accumulation occurred in the cells; GSH contents decreased; TEM showed that cells were ruptured and blebbed, mitochondria atrophied and became smaller, mitochondrial ridges were reduced or even disappeared, and apoptotic bodies appeared. And the expressions of Nrf2, SLC7A11 and GPX4 genes were reduced; the expressions of p-Nrf2/Nrf2, xCT and GPX4 proteins were reduced. Notably, these parameters were significantly reversed by HBO, indicating that HBO can protect HT22 cells and PC12 cells from damage caused by oxygen-glucosedeprivation/reperfusion via the inhibition of Nrf2/System Xc-/GPX4 axis-mediated ferroptosis.

Objective To examine the effectiveness and safety of non-pharmacological interventions to reduce bone loss among post-stroke adult patients. Data sources Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database for Systematic Reviews, MEDLINE, CINAHL, ScienceDirect, Scopus, PubMed and PeDRO databases were searched from inception up to 31st August 2021. Methods A systematic review of randomized controlled trials, experimental studies without randomization and prospective cohort studies with concurrent control of non-pharmacological interventions for adult stroke patients compared with placebo or other stroke care. The review outcomes were bone loss, fall and fracture. The Cochrane Risk of Bias Tools were used to assess methodological quality, and Grading of Recommendations, Assessment, Development and Evaluations Framework to assess outcome quality. Synthesis Without Meta-Analysis (SWiM) was used for result synthesis. Results Seven studies (n = 453) were included. The methodological and outcome qualities varied from low to moderate. There were statistically significant changes between the intervention and parallel/placebo group in bone mineral density, bone mineral content, cortical thickness and bone turnover markers with specific physical and vibration therapies (pConclusion There was low to moderate evidence that physical and vibration therapies significantly reduced bone loss in post-stroke patients at the expense of a higher falls rate. The sample size was small, and the interventions were highly heterogeneous with different duration, intensities and frequencies. Despite osteoporosis occurring with ageing and accelerated by stroke, there were no studies on vitamin D or protein supplementation to curb the ongoing loss. Effective, high-quality non-pharmacological intervention to improve post-stroke bone health is required.

ObjectiveTo examine the effectiveness and safety of non-pharmacological interventions to reduce bone loss among post-stroke adult patients.Data sourcesCochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database for Systematic Reviews, MEDLINE, CINAHL, ScienceDirect, Scopus, PubMed and PeDRO databases were searched from inception up to 31st August 2021.MethodsA systematic review of randomized controlled trials, experimental studies without randomization and prospective cohort studies with concurrent control of non-pharmacological interventions for adult stroke patients compared with placebo or other stroke care. The review outcomes were bone loss, fall and fracture. The Cochrane Risk of Bias Tools were used to assess methodological quality, and Grading of Recommendations, Assessment, Development and Evaluations Framework to assess outcome quality. Synthesis Without Meta-Analysis (SWiM) was used for result synthesis.ResultsSeven studies (n = 453) were included. The methodological and outcome qualities varied from low to moderate. There were statistically significant changes between the intervention and parallel/placebo group in bone mineral density, bone mineral content, cortical thickness and bone turnover markers with specific physical and vibration therapies (pConclusionThere was low to moderate evidence that physical and vibration therapies significantly reduced bone loss in post-stroke patients at the expense of a higher falls rate. The sample size was small, and the interventions were highly heterogeneous with different duration, intensities and frequencies. Despite osteoporosis occurring with ageing and accelerated by stroke, there were no studies on vitamin D or protein supplementation to curb the ongoing loss. Effective, high-quality non-pharmacological intervention to improve post-stroke bone health is required.

BACKGROUND AND OBJECTIVE:The sinoatrial nodal artery (SANa) is a highly variable vessel which supplies blood to the sinoatrial node (SAN). Due to its variability and susceptibility to iatrogenic injury, our study aimed to assess the anatomy of the SANa and determine the prevalence of its anatomical variations. STUDY DESIGN:An extensive search of major electronic databases was performed to identify all articles reporting anatomical data on the SANa. No lower date limit or language restrictions were applied. Anatomical data regarding the artery were extracted and pooled into a meta-analysis. RESULTS:Sixty-six studies (n = 21455 hearts) were included in the meta-analysis. The SANa usually arose as a single vessel with a pooled prevalence of 95.5% (95%CI:93.6-96.9). Duplication and triplication of the artery were also observed with pooled prevalence of 4.3% (95%CI:2.8-6.0) and 0.3% (95%CI:0-0.7), respectively. The most common origin of the SANa was from the right coronary artery (RCA), found in 68.0% (95%CI:55.6-68.9) of cases, followed by origin from the left circumflex artery, and origin from the left coronary artery with pooled prevalence of 22.1% (95%CI:15.0-26.2) and 2.7 (95%CI:0.7-5.2), respectively. A retrocaval course of the SANa was the most common course of the artery with a pooled prevalence of 47.1% (95%CI:36.0-55.5). The pooled prevalence of an S-shaped SANa was 7.6% (95%CI:2.9-14.1). CONCLUSIONS:The SANa is most commonly reported as a single vessel, originating from the RCA, and taking a retrocaval course to reach the SAN. Knowledge of high risk anatomical variants of the SANa, such as an S-shaped artery, must be taken into account by surgeons to prevent iatrogenic injuries. Specifically, interventional or cardiosurgical procedures, such as the Cox maze procedure for atrial fibrillation, open heart surgeries through the right atrium or intraoperative cross-clamping or dissection procedures during mitral valve surgery using the septal approach can all potentiate the risk for injury in the setting of high-risk morphological variants of the SANa.

A review of 6 years of hospitalization charts from Zhongshan Ophthalmic Center (ZOC) revealed that congenital cataracts (CC) accounted for 2.39% of all cataract in-patient cases and that the age at surgery was decreasing before the establishment of the Childhood Cataract Program of the Chinese Ministry of Health (CCPMOH) in December 2010. We aimed to investigate data from the 4 years (January 2011 to December 2014) following the establishment of the CCPMOH, compared, and combined with data from the previous study period (January 2005 to December 2010) to generate a 10-year overview of the hospital-based prevalence and treatment of CC. In the 4-year period after CCPMOH establishment, the prevalence of CC was 2.01% in all hospitalizations, and was 2.78% in all cataract in-patients. Most of the eligible CC in-patients (71%) lived in south China. The ratio of boys to girls was 1.42:1. Nearly 2/3 of the patients underwent cataract extraction with primary intraocular lens (IOL) implantation at a mean age of 78.40±51.45 months, and cataract extraction surgeries without IOL implantation were performed in the remaining 1/3 of patients at a mean age of 10.03±15.92 months. After CCPMOH establishment, an increased incidence of CC was revealed, and the CC in-patients were younger than the patients in the previous period. The 10-year overview (2421 CC in-patients from 206630 hospitalizations) revealed upward trends in both the number and the prevalence of CC and a further reduction in age at surgery. In conclusion, the data from 4-year period after CCPMOH establishment and the 10-year overview showed upward trends in the hospital-based prevalence of CC cases and a further reduction in age at surgery, likely reflecting the effects of the CCPMOH establishment and providing useful information for further CC studies and a valuable foundation for the prevention and treatment of this cause of childhood blindness.

Apurinic/apyrimidinic endonuclease 1 (APE1) is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5' to abasic sites. APE1 also has 3'-5' DNA exonuclease and 3' DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76-85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3' of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60-80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.

Congenital cataract (CC) is the primary cause of treatable childhood blindness. Population-based assessments of prevalence and surgery age of CC, which are critical for improving management strategies, have been unavailable in China until now. We conducted a hospital-based, cross-sectional study of the hospital charts of CC patients younger than 18 years old from January 2005 to December 2010 at Zhongshan Ophthalmic Center (ZOC) in Guangzhou, China. Residence, gender, age at surgery, hospitalization time, and the presence of other ocular abnormalities were extracted and statistically analyzed in different subgroups. The search identified 1314 patients diagnosed with CC from a total of 136154 hospitalizations, which accounted for 2.39% of all the cataract in-patients and 1.06% of the total in-patients over the six-year study period. Of the identified CC patients, 9.2% had ≥ 2 hospitalizations due to the necessity of additional surgeries, with a total ratio of boys to girls of 1.75 ∶ 1. Based on a subgroup analysis according to age, patients 2-6 years old constituted the highest proportion (29.22%) of all hospitalized CC patients, and those 13-18 years old constituted the lowest proportion (13.47%) of the total number. The average age at surgery was 27.62 ± 23.36 months, but CC patients ≤ 6 years old (especially ≤ 6 months old) became increasingly prevalent throughout the 6-year study period. A total of 276 cases (20.93%) of CC were associated with one or more other ocular abnormalities, the highest incidence rates were observed for exotropia (6.24%), nystagmus (6.16%), and refractive error (3.65%). In conclusion, CC patients accounted for 2.39% of all cataract in-patients in a review of 6 years of hospitalization charts from ZOC. The age at the time of surgery decreased over the 6-year study period, which probably reflects the continuing improvement of public awareness of children's eye care in China.

PURPOSE: Inflammatory cataracts secondary to Behcet's disease (BD) or Vogt-Koyanagi-Harada disease (VKH) are thought to result from a pathological dysregulation of cytokines that is different from that of age-related (AR) cataracts. However, little is known about the function of cytokines in the development of inflammatory cataracts. The purpose of this study was to identify possible differences in cytokine expression in inflammation- and age-related cataract patients. METHODS: Analysis techniques involving the concomitant use of a cocktail of antibody-coated non-magnetic beads were used to determine the cytokine expression profiles of BD, VKH and AR cataract patients. Furthermore, anterior chamber aqueous flares and inflammatory cells were quantitatively measured with a laser flare cell meter (LFCM). RESULTS: The expressions of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17A, and interferon-γ (IFN-γ) were analyzed in aqueous humor (AqH), phytohemagglutinin (PHA)-stimulated and non-PHA-stimulated cultures of peripheral blood mononuclear cells (PBMCs) from the three types of cataract patients. IL-6 and IFN-γ were identified above the detection limits, but, among the BD and VKH cataract patients, only the levels of IL-6 were significantly higher in both the AqH and PBMC non-PHA cultures compared with the levels observed in the AR cataract patients. In contrast, IFN-γ was significantly elevated in the AqH of the BD cataract patients compared with the VKH and AR cataract patients. In the PHA-stimulated PBMC cultures, IL-2, IFN-γ, IL-6, and IL-17A were significantly increased, and the IL-6 level was significantly higher in the VKH patients than in the BD and AR cataract patients. The correlation analyses of the cytokines and inflammation indexes of the AqH obtained with the LFCM revealed that only IL-6 was significantly correlated with the inflammation index. CONCLUSION: Distinct expression profiles of cytokines and the correlations of these profiles with in vivo inflammatory indexes for inflammatory and AR cataract patients were identified.

Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here we utilized a proteomic approach to identify novel serum biomarkers for distinguishing HCC patients from non-cancer controls. We profiled the serum proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using the RayBio® L-Series 507 Antibody Array and found 113 serum markers that were significantly modulated between HCC and control groups. Selected potential biomarkers from this list were quantified using a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126 resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)), confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in HCC patients. This finding of serum MCP-1 elevation in HCC patients was validated in a separate cohort of serum samples from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP, while MCP-1 also correlated with disease stage. Subsequent receiver operating characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and comparing their area under the ROC curve (AUC) indicated that neither prolactin nor MCP-1 on their own performed better than AFP. However, the combination of AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP alone (AUC, 0.942; p

BackgroundAccumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90(+) liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90(+) cells sorted from tumor (CD90(+)CSCs) with parallel non-tumorous liver tissues (CD90(+)NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis.Methodology/principal findingsCD90(+) cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90(+) cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90(+)CSCs and CD90(+)NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90(+)CSCs and CD90(+)NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90(+)CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90(+)CSCs compared to CD90(+)NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90(+)CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90(+)CSCs in liver tumor tissues.Conclusions/significanceThe identified genes, such as GPC3 that are distinctly expressed in liver CD90(+)CSCs, may be promising gene candidates for HCC therapy without inducing damages to normal liver stem cells.

BACKGROUND: Research on the effects of dietary nutrients on respiratory health in human populations have not investigated curcumin, a potent anti-oxidant and anti-inflammatory compound present principally in turmeric used in large amounts in Asian curry meals. OBJECTIVES: To examine the association of curry intake with pulmonary function among smokers and non-smokers. DESIGN: The frequency of curry intake, respiratory risk factors and spirometry were measured in a population-based study of 2,478 Chinese older adults aged 55 and above in the Singapore Longitudinal Ageing Studies. RESULTS: Curry intake (at least once monthly) was significantly associated with better FEV(1) (b = 0.045±0.018, p = 0.011) and FEV(1)/FVC (b = 1.14±0.52, p = 0.029) in multivariate analyses that controlled simultaneously for gender, age, height, height-squared, smoking, occupational exposure and asthma/COPD history and other dietary or supplementary intakes. Increasing levels of curry intake ('never or rarely', 'occasional', 'often', 'very often') were associated with higher mean adjusted FEV(1) (p for linear trend = 0.001) and FEV(1)/FVC% (p for linear trend = 0.048). Significant effect modifications were observed for FEV(1) (curry* smoking interaction, p = 0.028) and FEV(1)/FVC% (curry*smoking interaction, p = 0.05). There were significantly larger differences in FEV(1) and FEV(1)/FVC% between curry intake and non-curry intake especially among current and past smokers. The mean adjusted FEV(1) associated with curry intake was 9.2% higher among current smokers, 10.3% higher among past smokers, and 1.5% higher among non-smokers. CONCLUSION: The possible role of curcumins in protecting the pulmonary function of smokers should be investigated in further clinical studies.