Hypertensive retinopathy can predict stroke: A systematic review and meta-analysis based on observational studies: Running title: HTR and Stroke: Meta-analysis.

OBJECTIVE: The aim of this study was to determine whether hypertensive retinopathy is specifically associated with stroke. METHODS: The relevant studies published until December 18, 2023 were identified as well as selected from PubMed, Embase, Web of science, WanFang, CNKI, VIP, and CBM databases. Hazard ratios (HRs), risk ratios (RRs), and 95% confidence intervals (CIs) were combined. RESULTS: Six cohort studies were included in this analysis. Patients with hypertensive retinopathy exhibited a significantly higher overall risk of stroke than those without hypertensive retinopathy (RR=1.46, 95%CI: 1.29-1.65). When subgroups were analyzed by region, patients with hypertensive retinopathy in Asia had the highest risk of stroke (RR=1.53, 95%CI: 1.33-1.77). In addition, among the different severity grades of hypertensive retinopathy, the risk of stroke in patients with grade 3/4 hypertensive retinopathy (RR=1.82, 95%CI: 1.41-2.34) was observed to be higher than that in patients with grade 1/2 hypertensive retinopathy (RR=1.43, 95%CI: 1.27-1.61). CONCLUSIONS: Hypertensive retinopathy was found to be associated with an increased risk of stroke. Thus, it is necessary to include retinopathy in the routine screening of patients with hypertension.

Digirseophene A promotes recovery in injured developing cerebellum via AMPK/AKT/GSK3ß pathway-mediated neural stem cell proliferation.

Neural stem cells (NSCs) exhibit a remarkable capacity for self-renewal and have the potential to differentiate into various neural lineage cells, which makes them pivotal in the management of neurological disorders. Harnessing the inherent potential of endogenous NSCs for enhancing nerve repair and regeneration represents an optimal approach to addressing diseases of the nervous system. In this study, we explored the potential of a novel benzophenone derivative named Digirseophene A (DGA), which was isolated from the endophytic fungus Corydalis tomentella. Previous experiments have extensively identified and characterized DGA, revealing its unique properties. Our findings demonstrate the remarkable capability of DGA to stimulate neural stem cell proliferation, both in vitro and in vivo. Furthermore, we established a model of radiation-induced cerebellar injury to assess the effects of DGA on the distribution of different cell subpopulations within the damaged cerebellum, thereby suggesting its beneficial role in cerebellar repair. In addition, our observations on a primary NSCs model revealed that DGA significantly increased cellular oxygen consumption, indicating increased energy and metabolic demands. By utilizing various pathway inhibitors in combination with DGA, we successfully demonstrated its ability to counteract the suppressive impacts of AMPK and GSK3ß inhibitors on NSC proliferation. Collectively, our research results strongly suggest that DGA, as an innovative compound, exerts its role in activating NSCs and promoting injury repair through the regulation of the AMPK/AKT/GSK3ß pathway.

IFN-γ promotes radioresistant Nestin-expressing progenitor regeneration in the developing cerebellum by augmenting Shh ligand production.

BACKGROUND: Patients with brain tumors, especially pediatric brain tumors such as cerebellar medulloblastoma, always suffer from the severe side effects of radiotherapy. Regeneration of neural cells in irradiation-induced cerebellar injury has been reported, but the underlying mechanism remains elusive. METHODS: We established an irradiation-induced developing cerebellum injury model in neonatal mice. Microarray, KEGG analysis and semi in vivo slice culture were performed for mechanistic study. RESULTS: Nestin-expressing progenitors (NEPs) but not granule neuron precursors (GNPs) were resistant to irradiation and able to regenerate after irradiation. NEPs underwent less apoptosis but similar DNA damage following irradiation compared with GNPs. Subsequently, they started to proliferate and contributed to granule neurons regeneration dependent on the sonic hedgehog (Shh) pathway. In addition, irradiation increased Shh ligand provided by Purkinje cells. And microglia accumulated in the irradiated cerebellum producing more IFN-γ, which augmented Shh ligand production to promote NEP proliferation. CONCLUSIONS: NEP was radioresistant and regenerative. IFN-γ was increased post irradiation to upregulate Shh ligand, contributing to NEP regeneration. Our study provides insight into the mechanisms of neural cell regeneration in irradiation injury of the developing cerebellum and will help to develop new therapeutic targets for minimizing the side effects of radiotherapy for brain tumors.

Factors associated with secondary coronary artery disease in rheumatoid arthritis patients: A systematic review and meta-analysis based on observational studies.

OBJECTIVE: The main objective of this systematic review was to investigate the factors influencing the development of coronary artery disease (CAD) in patients with rheumatoid arthritis (RA). METHODS: PubMed, Embase, Web of Science, Wan Fang Date, CBM, CNKI, and VIP databases were systematically searched to select the relevant literature. The quality of the incorporated studies was assessed with reference to the Newcastle-Ottawa Scale. Stata16 was adopted to summarise the odds ratios, risk ratios, hazard ratios, and 95% confidence intervals for meta-analysis. RESULTS: A total of 29 studies were included in this analysis, wherein the average age of RA patients was 50.5-81 years and the proportion of women was 44.4%-92%. The present meta-analysis suggested that increased CAD risk in RA patients was associated with age, male gender, smoking, glucocorticoids, Health Assessment Questionnaire scores, hyperlipidaemia, hypertension, diabetes, and C-reactive protein concentration. CONCLUSION: The present systematic review revealed the influencing factors of secondary CAD in RA patients, some of which could reduce the risk of secondary CAD through effective interventions, such as smoking cessation, exercise, and medications. However, the effects of age, RA severity, and different medication subgroups on CAD risk stratification warrant further investigation.

Hypertension Treatment in Frail Older Adults: A Systematic Review and Appraisal of Guidelines.

BACKGROUND: Managing hypertension in frail older patients is challenging. Several institutions and organizations have published up-to-date hypertension guidelines suggesting frailty screening among older hypertensive patients, with new recommendations for blood pressure-lowering treatment among the frail population. However, the quality of current hypertension guidelines and the consistency of antihypertension treatment recommendations for frail older patients and their supporting evidence remain unknown. OBJECTIVE: In this review, we aimed to systematically collect guidelines with antihypertension treatment recommendations for frail older patients, examine and compare these recommendations, and critically assess reporting and methodology quality of these guidelines. METHODS: A literature search was conducted on two databases and three major websites of guideline development organizations. The AGREE instrument and RIGHT checklist were used to evaluate the methodology and reporting quality of the guidelines, respectively. The consistency of recommendations within the guidelines were compared using descriptive analysis. RESULTS: We identified 13 hypertension guidelines. The overall methodology quality scores (range 23.35-79.07%) and reporting rates (range 10/35-29/35) varied among these guidelines. Four guidelines provided an explicit definition of frailty. Considering treatment tolerability or increased likelihood of adverse effects while using pharmacotherapy in frail older patients was mentioned in all guidelines. Ten guidelines recommended adjusting blood pressure targets or specific pharmacotherapy programs. Four guidelines recommended using clinical judgment when prescribing. However, the specific recommendations lacked clarity and unity without sufficient evidence. CONCLUSIONS: There were considerable variations in methodology and reporting quality across the 13 included hypertension guidelines. Furthermore, the depth and breadth of antihypertension treatment recommendations for frail older patients were varied and inconsistent. Further trials exploring optimal treatment are urgently required to promote the development of specific guidelines for managing frail older hypertensive patients.

[Cluster needling of scalp points improves cognitive dysfunction by regulating NF-κB activity in rats with Alzheimer's disease].

OBJECTIVE: To observe the effect of cluster needling of scalp points on nuclear transcription factor kappa B p65 (NF-κB p65)，NF-κB inhibitory protein α (IKBα)ï¼Œß secretase 1 (BACE1)，beta-amyloid protein (Aß) and hippocampal morphology in Alzheimer's disease (AD) rats，so as to reveal its mechanism underlying improvement of AD. METHODS: Male Wistar rats were randomly divided into sham operation，model，clustering acupuncture and medication groups，with 12 trats in each group. AD model was induced by Aß1-42 injection into bilateral hippocampus. In the clustering acupuncture group，"Baihui" (DU20) and 1 mm on left and right sides of DU20 were needled for 30 min，once daily for 14 d. Rats of the medication group were given donepezil hydrochloride (0.5 mg·kg-1·d-1) intragastric perfusion once a day for 14 d. Morris water maze test was used to evaluate the cognitive function of rats. HE staining was used to observe the structure changes of hippocampal tissue. The expressions of NF-κB p65，IKBα and BACE1 in hippocampus were detected by Western blot. ELISA was used to detect the levels of Aß in hippocampus and serum of rats. RESULTS: Compared with sham operation group，the escape latency of Morris water maze test in the model group was prolonged，the number of crossing the original platform was decreased(P<0.01)，the protein expressions of NF-κB p65 and BACE1 in hippocampus，and the levels of Aß in hippocampus and serum of AD rats were increased (P<0.01，P<0.05)，while the expression of IKBα protein was decreased (P<0.01). Compared with the model group，the escape latency of Morris water maze test was shortened and the number of crossing the original platform was increased in the clustering acupuncture and medication groups (P<0.01，P<0.05)，and the protein expressions of NF-κB p65 and BACE1 in hippocampus，the levels of Aß in hippocampus and serum were decreased (P<0.01，P<0.05)，while the expression of IKBα protein was increased (P<0.01). In comparison of the medication group，the protein expressions of NF-κB p65 and IKBα was lower in the clustering acupuncture group (P<0.05). HE staining showed that cells in the hippocampus were arranged loosely and disordered，some cytoplasm was hyperchromatic，nucleus was pyknotic，inflammatory cells were infiltrated in the model group，which were relatively milder in the clustering acupuncture and medication groups. CONCLUSION: Cluster needling at scalp points may improve the cognitive impairment in AD rats by reducing inflammatory infiltration in hippocampus，regulating the expressions of NF-κB p65，IKBα and BACE1，and inhibiting the aggregation of Aß.

Effects of programmed flexor-extensor alternating electrical acupoint stimulation on upper limb motor functional reconstruction after stroke: study protocol for a double-blind, randomized controlled trial.

BACKGROUND: Stroke's prevalence and morbidity are increasing (Guano, et al. Neuro 89:53-61, 2017), and limb motor dysfunction is left in most patients (Gittler, et al. JAMA 319:820-821, 2018). Particularly, the rehabilitation of upper limbs is more difficult and time-consuming (Borges, et al. The Cochrane database of systematic reviews 10:CD011887, 2018). METHODS: A double-blind randomized controlled trial (RCT) will be conducted to investigate whether a new functional electrical stimulation (FES) combined with acupoint therapy is more effective in the rehabilitation of upper limb motor dysfunction after stroke. Patients who meet the inclusion criteria will be randomly divided into two groups: programmed flexor-extensor alternating electrical acupoint stimulation group (PES group) and conventional flexor-extensor alternating electrical acupoint stimulation group (CES group), which will be treated for 3 weeks. The primary outcome measures are electroencephalogram (EEG) and surface electromyogram (sEMG). The secondary outcome variables include MBI (modified Barthel index), China Stroke Scale (CSS), FMA-U (Fugl-Meyer assessment upper limb), MMT (manual muscle testing), and Brunnstrom. DISCUSSION: The results of this study are expected to verify the efficacy of PES therapy in the rehabilitation of upper limb motor function after stroke. This may promote the widespread use of the therapy in hospitals, communities, and homes for early and continuous treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05333497. Registered on April 11, 2022.

Quality of reporting and adherence to the ARRIVE guidelines 2.0 for preclinical degradable metal research in animal models of bone defect and fracture: a systematic review.

In vivo testing is crucial for the evaluation of orthopedic implant efficacy and safety. However, the translation and reproducibility of preclinical animal experiments are not always satisfactory, and reporting quality is among the essential factors that ensure appropriate delivery of information. In this study, we assessed the reporting quality of in vivo investigations that examined the use of degradable metal materials in fracture or bone defect repair. We employed scientific databases, such as PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, WanFang, VIP and Sinomed to screen for in vivo investigations on fracture or bone defect repair using degradable metal materials, and extracted both epidemiological and main characteristics of eligible studies, and assessed their reporting quality using the ARRIVE guidelines 2.0. Overall, 263 publications were selected, including 275 animal experiments. The overall coincidence rate of Essential 10 (22 sub-items) and Recommended Set (16 sub-items) were 42.0% and 41.5%, respectively. Based on our analysis, the reporting quality of the published in vivo investigations examining fracture/bone defect repair with degradable metal materials was low, and there was a lack of transparent, accurate and comprehensive reporting on key elements of the experimental design and other elements that are meant to avoid bias.

Effect of sodium citrate on asphaltene film at the oil-water interface.

HYPOTHESIS: Sodium citrate (Na3Cit) has been proven to improve the oil sands extraction recovery, but its mechanism is still unclear. Here we hypothesize that the presence of Na3Cit affects the asphaltene behaviour at the oil-water interface, which enhances oil-water separation and, thereby, heavy oil recovery. EXPERIMENTS: Na3Cit-asphaltene interaction was first investigated on their interfacial shear rheology at one heptol-water interface. Na3Cit-asphaltene interaction was further revealed by measuring the interaction forces between two heptol-water interfaces using the atomic force microscopy droplet technique combined with the Stokes-Reynolds-Young-Laplace (SRYL) model. Interfacial properties were further illustrated through interfacial tension, zeta potential, Langmuir trough, and FE-SEM. FINDINGS: Na3Cit was found to weaken the strength of the asphaltene film at the heptol-water interface. Moreover, Na3Cit could diminish the adhesion forces observed between two asphaltene-in-heptol droplets in high salinity solutions. Besides, Na3Cit also made the asphaltene-in-heptol droplet more negatively charged. These results collectively suggest that Na3Cit-asphaltene interaction results in a looser and more elastic asphaltene interfacial network with the slow formation and reduces the adhesion between two interfaces, all of which are most likely the consequence of increased electrostatic repulsion between asphaltene interfacial nanoaggregates. Our study provided new understandings of Na3Cit-asphaltene interactions at the interface.

Diabetic retinopathy and cognitive dysfunction: a systematic review and meta-analysis.

BACKGROUND: This study aims to determine the relationship between diabetic retinopathy (DR) and cognitive dysfunction as well as explores the effects of DR on different cognitive domains. METHODS: A systematic search of PubMed, Embase, Web of Science, Wanfang data, CBM, CNKI, and VIP databases from their inception to October 2021. The pooled odds ratio (ORs), hazard ratio (HRs), and 95% confidence interval (CIs) were calculated. RESULTS: Twenty-two studies met the inclusion criteria and meta-analysis included 15 studies. The presence of DR reflects a higher risk of cognitive dysfunction (OR = 2.45; 95% CI: 1.76-3.41; HR = 1.34 95% CI: 1.10-1.62). Cohort study combined risk was 2.62 (95% CI: 1.93-3.56), in cross-sectional study was 2.07 (95% CI: 1.11-3.88). The pooled OR was 2.38 (95% CI: 1.83-3.10) and 3.11 (95% CI: 1.15-8.40) in Asia and Oceania. No such association was found in North America (OR = 2.22; 95% CI: 0.77-6.38). The pooled risk was 2.47 (95% CI: 1.76-3.48) in patients with T2DM, while did not identify an association between these two conditions in T1DM. The combined unadjusted and adjusted ORs were 2.72 (95% CI: 1.99-3.73) and 2.06 (95% CI: 1.49-2.85). DR severity and the risk of cognitive impairment showed a positive correlation and mainly impaired the speeds of psychomotor and information processing. CONCLUSIONS: DR can help to identify people at high risk of cognitive dysfunction. Further studies are indispensable for exploring the relationship between DR and cognitive impairment in the patients for different age, gender and race, as well as to assess the risk of cognitive impairment in different populations.

Prevalence and Risk Factors of Sarcopenia in Patients With Diabetes: A Meta-analysis.

CONTEXT: The prevalence of sarcopenia in patients with diabetes is 3 times higher than that in patients without diabetes and is associated with a poor prognosis. OBJECTIVE: To investigate the global pooled prevalence and risk factors of sarcopenia in patients with diabetes. DATA SOURCES: Relevant studies published until November 30, 2020, were identified from the PubMed, Embase, Web of Science, WanFang, CNKI, VIP, and CBM databases. STUDY SELECTION: Participants with age ≥ 18 years with clinically diagnosed diabetes. Sex and diabetes type were not restricted. DATA EXTRACTION: The data were extracted by 2 reviewers independently using a standard data collection form. DATA SYNTHESIS: The pooled prevalence of sarcopenia in patients with diabetes was 18% (95% CI, 16-20); subgroup analysis showed that sarcopenia was more prevalent in males than in females, as well as being more prevalent in Asia than in South America and Oceania. Age (odds ratio [OR], 1.10), glycated hemoglobin (HbA1c) (OR = 1.16), visceral fat area (VFA) (OR = 1.03), diabetic nephropathy (OR = 2.54), duration of diabetes (OR = 1.06), and high-sensitivity C-reactive protein (hs-CRP) (OR = 1.33) were risk factors for sarcopenia in patients with diabetes. CONCLUSIONS: Sarcopenia was more prevalent in patients with diabetes. Age, HbA1c, VFA, diabetic nephropathy, duration of diabetes, and hs-CRP were the probable risk factors. In the future, medical staff should not only pay attention to the early screening of sarcopenia in high-risk groups, but also provide information on its prevention.

Abnormal methylation characteristics predict chemoresistance and poor prognosis in advanced high-grade serous ovarian cancer.

BACKGROUND: Primary or acquired chemoresistance is a key link in the high mortality rate of ovarian cancer. There is no reliable method to predict chemoresistance in ovarian cancer. We hypothesized that specific methylation characteristics could distinguish chemoresistant and chemosensitive ovarian cancer patients. METHODS: In this study, we used 450 K Infinium Methylation BeadChip to detect the different methylation CpGs between ovarian cancer patients. The differential methylation genes were analyzed by GO and KEGG Pathway bioinformatics analysis. The candidate CpGs were confirmed by pyrosequencing. The expression of abnormal methylation gene was identified by QRT-PCR and IHC. ROC analysis confirmed the ability to predict chemotherapy outcomes. Prognosis was evaluated using Kaplan-Meier. RESULTS: In advanced high-grade serous ovarian cancer, 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) remained hypermethylated in chemoresistant patients. The sensitivity, specificity and AUC of 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) methylation to predict chemotherapy sensitivity were 63.60-97.00%, 46.40-89.30% and 0.774-0.846. PFS of 6 candidate genes (ITGB6:cg21105318, cg07896068; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934) hypermethylation patients was significantly shorter. The expression of NCALD and LAMA3 in chemoresistant patients was lower than that of chemosensitive patients. Spearman analysis showed that NCALD and LAMA3 methylations were negatively correlated with their expression. CONCLUSIONS: As a new biomarker of chemotherapy sensitivity, hypermethylation of NCALD and LAMA3 is associated with poor PFS in advanced high-grade serous ovarian cancer. In the future, further research on NCALD and LAMA3 will be needed to provide guidance for clinical stratification of demethylation therapy.

The ovarian carcinoma risk with the polymorphisms of CYP1B1 come from the positive selection.

Ovarian carcinoma is one of the major causes of gynecological cancer. This study aimed to evaluate the association of CYP1 family polymorphism with the risk of ovarian carcinoma and chemotherapy resistance. Positive selection was detected among human CYP1A1, CYP1A2, and CYP1B1, and other species. Several positive sites were detected by site models and brach-site models. Meta-analysis was conducted for the sites rs1056836 (MAF 0.39) and rs1056827 (MAF 0.36) of CYP1B1 to clarify the association between gene polymorphisms and ovarian carcinoma risk. Subgroup analysis showed the association of rs1056836 polymorphism with ovarian cancer risk among Caucasians and Asians, while all the six genetic models showed no association among African-Americans. All the six genetic models showed no association of rs1056827 polymorphism with ovarian cancer risk. The polymorphisms of rs1056836 associated with ovarian cancer risk were detected in chemotherapy-sensitive and drug-resistant ovarian cancer patients. DNA was extracted from 62 chemotherapy resistance Ovarian carcinoma tissue samples and 137 chemotherapy-sensitive ovarian carcinoma tissue samples as controls. Gene polymorphisms were genotyped using the Sequenom MassARRAY SNP approach. There was no significant association between the CYP1B1 rs1056836 polymorphism and chemotherapy resistance of ovarian cancer in all genetic models. The results suggest that rs1056836 polymorphism of gene CYP1B1 under obvious selection pressure had a significantly increased risk for ovarian carcinoma. However, it had no significant correlation with chemotherapy resistance of ovarian cancer.

Retroperitoneal versus transperitoneal approach for elective open abdominal aortic aneurysm repair.

BACKGROUND: There has been extensive debate in the surgical literature regarding the optimum surgical access approach to the infrarenal abdominal aorta during an operation to repair an abdominal aortic aneurysm. The published trials comparing retroperitoneal (RP) and transperitoneal (TP) aortic surgery show conflicting results. This is an update of the review first published in 2016. OBJECTIVES: To assess the effectiveness and safety of the retroperitoneal versus transperitoneal approach for elective open abdominal aortic aneurysm repair on mortality, complications, hospital stay and blood loss. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials registers to 30 November 2020. The review authors searched the Chinese Biomedical Literature Database and handsearched reference lists of relevant articles to identify additional trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that assessed the RP approach versus the TP approach for elective open abdominal aortic aneurysm (AAA) repair. There were no restrictions on language or publication status. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials. We resolved any disagreements through discussion with a third review author. Two review authors independently assessed the risk of bias in included trials with the Cochrane risk of bias tool. For dichotomous outcomes, we calculated the odds ratio (OR) with the corresponding 95% confidence interval (CI). For continuous data, we calculated a pooled estimate of treatment effect by calculating the mean difference (MD) and standard deviation (SD) with corresponding 95% CIs. We pooled data using a fixed-effect model, unless we identified heterogeneity, in which case we used a random-effects model. We used GRADE to assess the overall certainty of the evidence. We evaluated the outcomes of mortality, complications, intensive care unit (ICU) stay, hospital stay, blood loss, aortic cross-clamp time and operating time. MAIN RESULTS: We identified no new studies from the updated searches. After reassessment, we included one study which had previously been excluded. Five RCTs with a combined total of 152 participants are included. The overall certainty of the evidence ranged from low to very low because of the low methodological quality of the included trials (unclear random sequence generation method and allocation concealment, and no blinding of outcome assessors), small sample sizes, small number of events, high heterogeneity and inconsistency between the included trials, no power calculations and relatively short follow-up. There was no evidence of a difference between the RP approach and the TP approach regarding mortality (odds ratio (OR) 0.32, 95% CI 0.01 to 8.25; 3 studies, 110 participants; very low-certainty evidence). Similarly, there was no evidence of a difference in complications such as hematoma (OR 0.90, 95% CI 0.13 to 6.48; 2 studies, 75 participants; very low-certainty evidence), abdominal wall hernia (OR 10.76, 95% CI 0.55 to 211.78; 1 study, 48 participants; very low-certainty evidence), or chronic wound pain (OR 2.20, 95% CI 0.36 to 13.34; 1 study, 48 participants; very low-certainty evidence) between the RP and TP approaches in participants undergoing elective open AAA repair. The RP approach may reduce ICU stay (mean difference (MD) -19.02 hours, 95% CI -30.83 to -7.21; 3 studies, 106 participants; low-certainty evidence); hospital stay (MD -3.30 days, 95% CI -4.85 to-1.75; 5 studies, 152 participants; low-certainty evidence); and blood loss (MD -504.87 mL, 95% CI -779.19 to -230.56; 4 studies, 129 participants; very low-certainty evidence). There was no evidence of a difference between the RP approach and the TP approach regarding aortic cross-clamp time (MD 0.69 min, 95% CI -7.23 to 8.60; 4 studies, 129 participants; very low-certainty evidence) or operating time (MD -15.94 min, 95% CI -34.76 to 2.88; 4 studies, 129 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Very low-certainty evidence from five small RCTs showed no clear evidence of a difference between the RP approach and the TP approach for elective open AAA repair in terms of mortality, or for rates of complications including hematoma (very low-certainty evidence), abdominal wall hernia (very low-certainty evidence), or chronic wound pain (very low-certainty evidence). However, a shorter intensive care unit (ICU) stay and shorter hospital stay was probably indicated following the RP approach compared to the TP approach (both low-certainty evidence). A possible reduction in blood loss was also shown after the RP approach (very low-certainty evidence). There is no clear difference between the RP approach and TP approach in aortic cross-clamp time or operating time. Further well-designed, large-scale RCTs assessing the RP approach versus TP approach for elective open AAA repair are required.

LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer.

OBJECTIVE: LAMA3 is a widely studied methylated gene in multiple tumors, but the relationship between chemotherapy resistance in ovarian cancer is unclear. In this study, LAMA3 methylation was predicted by bioinformatics, and the ability of LAMA3 methylation to predict the chemotherapy resistance and prognosis of ovarian cancer was confirmed in experiments. METHODS: Multiple databases have performed the bioinformatics analysis of methylation and transcription factor binding site (TFBS) on the promoter region of LAMA3 gene. Pyrosequencing detected the methylation of LAMA3. QRT-PCR and immunohistochemistry detected the expression of LAMA3. Real Time Cell Analyzer (RTCA) detects changes in cell proliferation, migration and invasion ability. Flow cytometry was used to detect apoptosis. RESULTS: CPG islands of 176 bp, 134 bp, 125 bp and 531 bp were predicted in the promoter region of LAMA3 gene. The 4 prediction results are basically overlapped. 7 transcription factor binding sites were predicted, and the one with the highest score was on the predicted CpG island located in the proximal promoter region. LAMA3 hypermethylation and low expression are both associated with chemotherapy resistance and poor prognosis in ovarian cancer. LAMA3 methylation was negatively correlated with expression. After upregulation of LAMA3, the proliferation ability of chemoresistant ovarian cancer cell decreased, while the ability of apoptosis, invasion and migration increased. CONCLUSION: LAMA3 hypermethylation is associated with chemotherapy resistance and poor prognosis. As a typical CpG island gene, LAMA3(cg20937934) and LAMA3(cg13270625) hypermethylation is negatively correlated with low expression. LAMA3 promotes the invasion, migration and apoptosis of SKOV3DDP. In the future, the mechanism of LAMA3 methylation in ovarian cancer will need to be further studied.

Low expression of NCALD is associated with chemotherapy resistance and poor prognosis in epithelial ovarian cancer.

BACKGROUND: Low expression of NCALD(neurocalcin delta) in peripheral blood of ovarian cancer patients predicts poor prognosis. However, the molecular mechanism of NCALD in ovarian cancer and its relationship with chemotherapy outcomes is unclear. The aim of this study was to investigate the potential signaling pathways of NCALD and to evaluate its ability to predict chemotherapy outcomes and prognosis. METHODS: High-throughput RNA sequencing data were downloaded from TCGA. GSEA explored the potential signaling pathways of NCALD. The expression of NCALD in chemotherapy sensitive and chemotherapy resistant ovarian cancer patients was detected by TCGA data and clinical samples. ROC analysis confirmed the ability of NCALD to predict chemotherapy outcomes. The association between NCALD expression and prognosis in ovarian cancer patients was assessed using Kaplan-Meier plotter. RESULTS: In patients with NCALD overexpression, genes expression related to ERK1 / 2 signaling pathway, NF-kappaB signaling pathway, TGF-ß signaling pathway and immune response pathway was increased, especially ERK1 / 2 signaling pathway. The expression of NCALD in chemoresistant patients was significantly lower than chemosensitive patients. In TCGA data and immunohistochemical samples, the AUC of NCALD expression predicting chemotherapy outcome was 0.59 and 0.64, respectively. In clinical samples, low expression of NCALD was associated with poor OS and PFS. CONCLUSIONS: NCALD may activate the ERK1 / 2 signaling pathway in ovarian cancer. As a new biomarker of chemotherapy sensitivity, NCALD was significantly down-regulated in chemotherapy resistance ovarian cancer patients. Low expression of NCALD in ovarian cancer is associated with poor OS and PFS. In the future, further research will be needed on the potential mechanism and clinical application value of NCALD in ovarian cancer.

Preoperative serum levels of HE4 and CA125 predict primary optimal cytoreduction in advanced epithelial ovarian cancer: a preliminary model study.

OBJECTIVE: The aim of this study is to establish a noninvasive preoperative model for predicting primary optimal cytoreduction in advanced epithelial ovarian cancer by HE4 and CA125 combined with clinicopathological parameters. METHODS: Clinical data including preoperative serum HE4 and CA125 level of 83 patients with advanced epithelial ovarian cancer were collected. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of each clinical parameter were calculated. The Predictive Index score model and the logistic model were constructed to predict the primary optimal cytoreduction. RESULTS: Optimal surgical cytoreduction was achieved in 62.65% (52/83) patients. Cutoff values of preoperative serum HE4 and CA125 were 777.10 pmol/L and 313.60 U/ml. (1) Patients with PIV ≥ 6 may not be able to achieve optimal surgical cytoreduction. The diagnostic accuracy, NPV, PPV and specificity for diagnosing suboptimal cytoreduction were 71, 100, 68, and 100%, respectively. (2) The logistic model was: logit p = 0.12 age - 2.38 preoperative serum CA125 level - 1.86 preoperative serum HE4 level-2.74 histological type-3.37. AUC of the logistic model in the validation group was 0.71(95%CI 0.54-0.88, P = 0.025). Sensitivity and specificity were 1.00 and 0.44, respectively. CONCLUSION: Age, preoperative serum CA125 level and preoperative serum HE4 level are important non-invasive predictors of primary optimal surgical cytoreduction in advanced epithelial ovarian cancer. Our PIV and logistic model can be used for assessment before expensive and complex predictive methods including laparoscopy and diagnostic imaging. Further future clinical validation is needed.

Unraveling Interaction Mechanisms between Molybdenite and a Dodecane Oil Droplet Using Atomic Force Microscopy.

Molybdenite (MoS2) is a mineral that has drawn great interest because of its potential application in various fields. To facilitate the flotation of molybdenite, the mineral pulp is commonly treated with nonpolar oil additives to promote hydrophobicity and to form an oil bridge between ultrafine molybdenite particles for agglomeration. In this study, dodecane was chosen as a model oil to investigate the flotation mechanisms of molybdenite with nonpolar oil. The interaction forces between a micrometer-sized dodecane droplet and the molybdenite basal plane in various electrolyte solutions were directly measured by the atomic force microscope droplet probe technique. The effects of added salts, ionic strength, and solution pH on interaction forces were evaluated by considering van der Waals, electrical double-layer (EDL), and hydrophobic forces. The experimentally measured force curves were found to agree well with the Reynolds lubrication model and the augmented Young-Laplace equation. The results show that the competition between repulsive EDL forces and attractive hydrophobic forces was directly responsible for oil-molybdenite attachment behavior. High pH and low salinity (<24 mM NaCl) led to strong repulsive EDL forces, which stabilized the interaction and prevented the attachment of oil to molybdenite. Both low pH and high salinity facilitated the attachment of oil to molybdenite through the depression of EDL force, allowing attractive hydrophobic force to dominate. The hydrophobic attraction was quantified with an exponential decay length of 1.0 ± 0.1 nm. Furthermore, calcium ions decreased the magnitude of the surface potentials of both oil and molybdenite more than that seen with the same ionic strength of sodium ions, suggesting the suppressed EDL repulsion. This study provides quantitative information about the surface forces between oil and the molybdenite basal plane and an improved understanding of the fundamental interaction mechanisms governing molybdenite recovery by mineral flotation.

Hypermethylation of tumor suppressor genes is a risk factor for poor prognosis in ovarian cancer: A meta-analysis.

OBJECTIVE: DNA methylation is the earliest and most studied epigenetic modification in cancer. The literature reported that the abnormal methylation level of multiple genes was associated with poor prognosis in ovarian cancer. However, due to a small sample size, the results reported in the literature vary widely. In this study, the correlation between aberrant methylation level of genes and poor prognosis of ovarian cancer was reviewed in order to clarify the role of DNA methylation in the prognosis of ovarian cancer. METHODS: A systematic research of PubMed, EMbase, Cochrane Library, China Biology Medicine disc (CBMdisc), China National Knowledge Infrastructure (CNKI), Wanfang databases, and EMBASE was performed, and calculated the hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) and its 95% confidence interval. RESULTS: HR of the OS obtained of target genes was 2.32 (95% CI: 1.54-3.48, P = .000); HR of the PFS obtained of target genes was 1.318 (95% CI: 0.848-2.050, P = .220). HR of OS achieved by tumor suppressor genes was 3.09 (95% CI 1.80 - 5.30, P = .000). CONCLUSION: Hypermethylation of tumor suppressor genes indicate poor prognosis of ovarian cancer.