A patient with spinal cavernous vascular malformation: case report and review of the literature.

BACKGROUND: Spinal cavernous vascular malformation (SCM) is a rare type of spinal vascular malformation that can be easily misdiagnosed and overlooked, accounting for 5%-12% of all spinal vascular malformations. To date, surgical resection has been the gold standard for treating SCM, particularly in symptomatic patients. The risk of secondary hemorrhage in SCM is as high as 66%. Therefore, early, timely, and accurate diagnosis is crucial for patients with SCM. CASE REPORT: In this report, we describe a 50-year-old female patient who was admitted to the hospital with recurrent bilateral lower extremity pain and numbness for 10 years, with recurring symptoms for 4 months. The patient's symptoms initially improved after conservative treatment but then worsened again. An MRI revealed a spinal cord hemorrhage, and after surgical treatment, the patient's symptoms improved significantly. A postoperative pathological examination confirmed the diagnosis of SCM. CONCLUSIONS: This case, along with a review of the literature, suggests that for SCM, early surgery using techniques such as microsurgery and intraoperative evoked potential monitoring may result in better outcomes for the patient.

First-line treatment and overall survival in EGFR mutation-positive advanced non-small cell lung cancer: a national cohort study.

OBJECTIVE: Non-squamous non-small cell lung cancer (NSCLC) is the first leading cause of cancer-related deaths in Taiwan. This study aimed at evaluating the effectiveness of first-line targeted therapy for advanced epidermal growth factor receptor (EGFR) mutation-positive non-squamous NSCLC in Taiwan. PATIENTS AND METHODS: This was a real-world, retrospective, observational study of patients diagnosed with advanced non-squamous NSCLC (N=63,248). Between 2011 and 2019, 19,458 patients received targeted therapy and 22,994 patients received chemotherapy alone; between 2002 and 2010, 20,796 patients received chemotherapy alone. Overall survival (OS) was determined. RESULTS: The median OS for patients treated with first-line targeted therapy (22.9 months) was longer than that of patients receiving chemotherapy alone (11.7 months). HR: 0.521, log-rank test, p<0.001. CONCLUSIONS: These data represent the potential survival outcomes of Taiwanese patients with advanced EGFR mutation-positive non-squamous NSCLC in clinical practice.

Efficacy and safety of intracoronary pro-urokinase injection during percutaneous coronary intervention in treating ST elevation myocardial infarction patients: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Intracoronary injection of pro-urokinase (Pro-UK) during percutaneous coronary intervention (PCI) seems to be a promising treatment in improving myocardial perfusion. In this systematic review and meta-analysis, we aimed at investigating the efficacy and safety of intracoronary Pro-UK injection during PCI in ST elevation myocardial infarction (STEMI) patients. MATERIALS AND METHODS: A comprehensive literature searched on PubMed, Embase, Cochrane, Ovid-MEDLINE, Ovid-Embase, Ovid-Cochrane Databases and ClinicalTrials.gov from inception until June 1, 2022, in English only. The primary outcome was myocardial perfusion, including thrombolysis in myocardial infarction (TIMI) grades, corrected TIMI frame count (CTFC), TIMI myocardial perfusion grades (TMPG). The secondary outcomes were ST-segment resolution (STR), major adverse cardiovascular events (MACE), myocardial marker, cardiac function and hemorrhagic complications. RESULTS: We identified 5 studies (all RCTs) involving 761 participants. Under PCI procedure, compared with placebo, intracoronary Pro-UK injection may improve myocardial perfusion, including increasing the TIMI grades [odd ratio (OR) 0.46; 95% confidence interval (CI) 0.28-0.75; p = 0.002; I2 = 0%] , CTFC (OR -3.47; 95% CI [-5.60, -1.33]; p = 0.001; I2 = 0%) and TMPG (OR 0.17; 95% CI [0.06-0.44]; p = 0.0003; I2 = 0%), increase the rate of STR (OR 2.25; 95% CI [1.56-3.26]; p < 0.0001; I2 = 0%), reduce the incidence of MACE (OR 0.51; 95% CI [0.33-0.81]; p = 0.004; I2 = 0%) and reduce myocardial infarct size (CK, standardized mean difference [SMD] -0.45; 95% [CI] [-0.62, -0.28]; p < 0.00001; I2 = 10%. CK-MB, [SMD] -0.43; 95% CI [-0.68, -0.18]; p = 0.0007; I2 = 60%. cTnI, [SMD] -0.31; 95% CI [-0.46, -0.17]; p < 0.0001; I2 = 0%). Moreover, the treatment may improve the cardiac functions (LVFE, pooled mean difference [MD] 1.23; 95% CI [0.66-1.79]; p < 0.0001; I2 = 24%. LVEDd, pooled MD -0.13; 95% CI [-0.17, -0.09]; p < 0.00001; I2 = 0%). But there is no statistically significant difference between the Pro-UK group and placebo in the occurrence of hemorrhagic complications (OR 1.19; 95% CI [0.75-1.87]; p = 0.46; I2 = 0%). CONCLUSIONS: Intracoronary Pro-UK injection during PCI in STEMI patients is an effective and safe treatment to perform. The treatment may improve myocardial perfusion and rate of STR, as well as decreasing the incidence of MACE and myocardial infarct size. Importantly, the treatment may improve the cardiac functions and life quality. In the future, more multi-centered and massive sample studies are required.

Burr hole craniostomy vs. minicraniotomy of chronic subdural hematoma: a systematic review and meta-analysis.

OBJECTIVE: Surgery is the mainstay of treatment for chronic subdural hematoma (CSDH). However, the best surgical method is still controversial. Three different methods including burr hole craniostomy (BHC), minicraniotomy (MC), and twist drill craniostomy (TDC) are commonly utilized. Besides, large craniotomy, trephine craniotomy [TC (single or double)], small craniotomy, and endoscopic removal are befittingly used in some situations, too. Hence, we performed a systematic review and meta-analysis to compare the effects between BHC and MC for surgical treatment in CSDH. MATERIALS AND METHODS: A literature research was conducted according to the PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that directly compared BHC and MC for CSDH. The following endpoints were compared between BHC and MC: recurrence rate, reoperation rate, duration of operation, days of hospital treatment, postoperative complications, mortality, and rate of good outcome. RESULTS: Thirteen papers [n = 3,559 (3,580 operation sites), BHC: 1,936 operation sites, MC: 1,644 operation sites] met the inclusion criteria. The recurrence rate (OR: 0.56, 95% CI: 0.34-0.91, p = 0.02; I2 = 66%) was lower and the reoperation rate was also significantly lower (OR: 0.45, 95% CI: 0.25-0.81, p = 0.008; I2 = 72%) in the BHC group compared with the MC group. The duration of operation (MD: -20.15 min, 95% CI: -28.99 to -11.31, p < 0.00001; I2 = 0%) was significantly shorter in the BHC group compared with the MC group. Nevertheless, there was no statistically significant difference between the two groups in mortality (OR: 1.22, 95% CI: 0.92-1.61, p = 0.16; I2 = 38%), postoperative complications (OR: 0.68, 95% CI: 0.033-1.37, p = 0.28; I2 = 82%), days of hospital treatment (MD: 1.59, 95% CI: -10.44 to 13.62, p = 0.14; I2 = 85%) and rate of good outcome (OR: 1.40, 95% CI: 0.94-2.08, p = 0.10; I2 = 0%). CONCLUSIONS: A systematic review and meta-analysis of the included literature showed that BHC reduces the recurrence rate, reoperation rate and duration of operation compared to MC. BHC is much more minimal invasive when compared to MC. More invasions may signify more post-operative complications, which may cause the increasing rate of recurrence and reoperation. No significant difference in mortality, post-operative complications, days of hospital treatment and rate of good outcome was observed between the two groups.

Association of the stress hyperglycemia ratio and clinical outcomes in patients with cardiovascular diseases: a systematic review and meta-analysis.

OBJECTIVE: Cardiovascular disease (CVD) and cerebrovascular disease are the leading cause of death around the world all the time. A novel marker described as the stress hyperglycemia ratio (SHR) can reflect the acute hyperglycemic status and is associated with poor outcomes in patients with acute illness, such as stroke and myocardial infarction (MI). Our previous study has shown that SHR was strongly related to the clinical outcomes of stroke patients. Nevertheless, the association between SHR and clinical outcomes in patients with CVD is still unclear and controversial. Consequently, in the current study, we analyzed the association of SHR and clinical outcomes in CVD patients by systematic review and meta-analysis. MATERIALS AND METHODS: We searched the electronic databases to identify SHR studies of patients who met the eligibility criteria for CVD. We performed our study complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We utilized a ten terms tool to assess the potential bias of included studies. Major adverse cardiovascular and cerebrovascular events (MACCEs), all-cause death, left ventricular ejection fraction (LVEF), and other exciting outcome data were extracted for statistical analysis. Moreover, we used the DerSimonian and Laird random-effects model to perform the meta-analysis and conducted subgroup analyses to identify factors associated with substantial heterogeneity. RESULTS: The study cohort included nine studies comprising 32,292 patients with CVD. Our meta-analysis found that MACCEs in the high SHR group were 1.68 folds compared with that in the low SHR group [odds ratio (OR) 1.68, 95% confidence interval (CI) 1.41-2.00, p < 0.00001]. Besides, all-cause death in the high SHR group was 1.52 folds compared with that in the low SHR group (OR 1.52, 95% CI 1.15-2.01, p < 0.00001). Higher SHR meant the lower LVEF (mean difference [MD] -2.03, 95% CI [-3.28-0.79], p = 0.001). The risk of cardiogenic shock and stroke were 2.47 and 1.53 folds in the high SHR group, respectively, compared with the low SHR group. Yet, no statistically significant difference was observed for revascularization (OR 0.88, 95% CI 0.77-1.01, p = 0.08), recurrent MI (OR 1.27, 95% CI 0.69-2.33, p = 0.44), and left ventricular end-diastolic diameter (LVEDD) (MD 0.61, 95% CI [-1.65, 2.87], p = 0.60) between the two groups. Subgroup analyses identified that different study design was associated with heterogeneity about MACCEs and LVEF. Besides, studies from different countries were associated with heterogeneity about all-cause death. CONCLUSIONS: Higher SHR significantly increases the occurrence of MACCEs and all-cause death and decreases LVEF. Moreover, Higher SHR means a higher risk of cardiogenic shock and stroke. Nevertheless, SHR had no relationship with revascularization, recurrent MI, and LVEDD. As a novel and non-invasive marker, SHR should be paid more attention to in clinical practice. Future investigation should focus on the diagnostic value of SHR in CVD and the early control of stress hyperglycemia. Although no randomized, double-blind studies have been conducted, the available massive sample studies reflect the actual situation in the clinic and assist clinical decision-making.

Real-world results of immune checkpoint inhibitors from the Taiwan National Health Insurance Registration System.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) are a major advance in cancer treatment, but their payment benefits are unclear, resulting in financial risk. In Taiwan, the National Health Insurance Administration (NHIA) has adapted risk-sharing mechanisms to cover ICIs by collecting and assessing real-world evidence, such as case registration data, to adjust benefit packages for each medication, increase payment benefits of ICIs, and enable national health insurance sustainability. PATIENTS AND METHODS: This nationwide, multicenter, retrospective cohort study assessed the real-world use, effectiveness, and safety of ICIs reimbursed by the NHIA for treating multiple advanced cancers in Taiwan. We obtained data mainly from the NHIA Immune Checkpoint Inhibitor Registry Database. RESULTS: Between April 1, 2019, and March 31, 2020, 1644 patients received at least one dose of ICIs. The overall response rate (RR) was 29.1%. The metastatic urothelial carcinoma of patients ineligible for chemotherapy showed the highest RR. The estimated median progression-free survival (PFS) was 2.8 months (95% confidence interval [CI]=2.7-3 months), and renal cell carcinoma showed the longest PFS. The median PFS was reached in patients with most cancers except classic Hodgkin's lymphoma, which had a small sample size. The estimated survival probability was 50%. CONCLUSIONS: Under the national registration tracking system, Taiwan's high-cost drug policy has enabled access to new medicines and maximized patient benefits.

Slow light nanocoatings for ultrashort pulse compression.

Transparent materials do not absorb light but have profound influence on the phase evolution of transmitted radiation. One consequence is chromatic dispersion, i.e., light of different frequencies travels at different velocities, causing ultrashort laser pulses to elongate in time while propagating. Here we experimentally demonstrate ultrathin nanostructured coatings that resolve this challenge: we tailor the dispersion of silicon nanopillar arrays such that they temporally reshape pulses upon transmission using slow light effects and act as ultrashort laser pulse compressors. The coatings induce anomalous group delay dispersion in the visible to near-infrared spectral region around 800 nm wavelength over an 80 nm bandwidth. We characterize the arrays' performance in the spectral domain via white light interferometry and directly demonstrate the temporal compression of femtosecond laser pulses. Applying these coatings to conventional optics renders them ultrashort pulse compatible and suitable for a wide range of applications.

The extremely low energy cost of biosynthesis in holometabolous insect larvae.

The metabolic cost of growth, which quantifies the amount of energy required to synthesize a unit of biomass, is an important component of an animal's ontogenetic energy budget. Here we investigated this quantity as well as other energy budget variables of the larvae of a holometabolous insect species, Vanessa cardui (painted lady). We found that the high growth rate of this caterpillar cannot be explained by its metabolic rate and the percentage of the metabolic energy allocated to growth; the key to understanding its fast growth is the extremely low cost of growth, 336 Joules/gram of dry mass. The metabolic cost of growth in caterpillars is 15-65 times lower than that of the endothermic and ectothermic species investigated in previous studies. Our results suggest that the low cost cannot be attributed to its body composition, diet composition, or body size. To explain the "cheap price" of growth in caterpillars, we assumed that a high metabolic cost for biosynthesis resulted in a high "quality" of cells, which have fewer errors during biosynthesis and higher resistance to stressors. Considering the life history of the caterpillars, i.e., tissue disintegration during metamorphosis and a short developmental period and lifespan, we hypothesized that an energy budget that allocates a large amount of energy to biosynthesizing high quality cells would be selected against in this species. As a preliminary test of this hypothesis, we estimated the metabolic cost of growth in larvae of Manduca sexta (tobacco hornworm) and nymphs of Blatta lateralis (Turkestan cockroach). The preliminary data supported our hypothesis.

Expression of miR-195 in laryngeal squamous cell carcinoma and its effect on proliferation and apoptosis of Hep-2.

OBJECTIVE: To investigate the expression of miR-195 and its relationship with clinicopathological characteristics in laryngeal squamous cell carcinoma (LSCC), and to explore its effect and possible mechanism on proliferation and apoptosis of Hep-2. PATIENTS AND METHODS: Real-time fluorescence quantitative PCR was used to detect the expression of miR-195 in laryngeal carcinoma tissues and adjacent normal tissues from 98 cases. Dual-luciferase reporter plasmid with Bcl-2 wild type and mutant type 3' untranslated region was created to verify the target of miR-195 by luciferase assay. After Hep-2 cells were transfected with miR-195/Bcl-2, miR-195, Bcl-2 siRNA and negative control by lipofectamine, the protein expression of Bcl-2 was detected by Western blot analysis. The proliferation and apoptosis of Hep-2 were detected by MTS method and flow cytometry, respectively. RESULTS: Compared with adjacent normal tissues, the expression of miR-195 was lower in laryngeal carcinoma tissues (p < 0.01). The low expression of miR-195 was positively correlated with distant metastasis and clinical stage (p < 0.05). The average survival time of patients with low expression was shorter than those with high expression by Kaplan-Meier method (p < 0.01). Multivariate Cox analysis showed that miR-195 expression and lymph node metastases were independent prognostic factors (p < 0.05). CONCLUSIONS: The expression of miR-195 was significantly decreased in laryngeal carcinoma tissues, which was closely related to the clinicopathological characteristics of LSCC. miR-195 may inhibit the proliferation and promote the apoptosis of Hep-2 by regulating Bcl-2 expression, which as an anti-oncogene could have the potential to be a therapeutic strategy in the treatment of LSCC.

Risk factors and outcome of levofloxacin-resistant Elizabethkingia meningoseptica bacteraemia in adult patients in Taiwan.

Elizabethkingia meningoseptica is an emerging nosocomial pathogen associated with high mortality and inherently resistant to many antimicrobial agents. Levofloxacin has been considered as a therapeutic agent based on in vitro susceptibility. We aim to investigate the risk factors and outcomes for levofloxacin-resistant E. meningoseptica bacteraemia. Adult patients with E. meningoseptica bacteraemia were identified retrospectively in a medical centre in Taiwan from January 2011 to July 2015. These strains were identified by the Vitek2 automated system or matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. We compared clinical features and outcomes of patients with levofloxacin-resistant (MIC >2 µg/mL) and levofloxacin-susceptible (MIC ≤2 µg/mL) E. meningoseptica bacteraemia. A total of 93 patients were identified, including 51 (54.8%) with levofloxacin-resistant E. meningoseptica bacteraemia. The APACHE II score (OR, 1.08; 95% CI, 1.02-1.14; p = 0.008) was the only independent risk factor for levofloxacin-resistant E. meningoseptica bacteraemia. The 14-day mortality for patients with levofloxacin-resistant E. meningoseptica bacteraemia (attributable mortality: 30.7%) was significantly higher than that for patients with the levofloxacin-susceptible strain (56.9% versus 26.2%, p = 0.003). In the multivariate analysis of risk factors for mortality, appropriate definite antibiotic use was the only factor associated with 14-day survival (OR, 0.11; 95% CI, 0.02-0.55, p = 0.007). The levofloxacin-resistant strain was borderline significantly associated with mortality (OR, 3.09; 95% CI, 0.88-10.91, p = 0.079). The early identification of levofloxacin resistance in E. meningoseptica isolates is important to tackle this multi-drug resistance pathogen.

Prevalence of the Novel Torque Teno Sus Virus Species k2b from Pigs in the United States and Lack of Association with Post-Weaning Multisystemic Wasting Syndrome or Mulberry Heart Disease.

The family Anelloviridae includes a number of viruses infecting humans (Torque teno viruses, TTV) and other animals including swine (Torque teno sus viruses, TTSuV). Two genetically distinct TTSuV species have been identified from swine thus far (TTSuV1 and TTSuVk2), although their definitive association with disease remains debatable. In 2012, a novel TTSuV species was identified from commercial swine serum and classified in the genus Kappatorquevirus as TTSuVk2b. The other Kappatorquevirus species, TTSuVk2a, has been associated with post-weaning multisystemic wasting syndrome (PMWS) when coinfected with porcine circovirus type 2 (PCV2). Therefore, in this study, we initially amplified a portion of TTSuVk2b ORF1 and, subsequently, assessed the molecular prevalence of the virus in pigs in the United States. A total of 127 serum and 115 tissue samples were obtained from pigs with PMWS or mulberry heart disease (MHD) in six states and tested by PCR for the presence of TTSuVk2b DNA. Approximately 27.6% of the serum and 21.7% of tissue samples tested positive for TTSuVk2b DNA, and the positive products were confirmed by sequencing. However, we did not detect a correlation between TTSuVk2b infection and PMWS or MHD. The near full-length genomic sequence of US TTSuVk2b was determined, and sequence analysis revealed that the US TTSuVk2b isolates were 95% identical to the TTSuVk2b isolate from Spain, with most of the variations clustering in ORF1. We conclude that the novel TTSuVk2b species is present in pigs in the United States and its potential association with a disease warrants further investigation.

Increased risk of hepatocellular carcinoma in chronic hepatitis C patients with new onset diabetes: a nation-wide cohort study.

BACKGROUND: The impact of diabetes for hepatocellular carcinoma (HCC) development in chronic hepatitis C (CHC) patients remains controversial. AIM: To investigate the risk of HCC in CHC patients who develop new onset diabetes. METHODS: We conducted a nation-wide cohort study by using Taiwanese National Health Insurance Research Database, which comprised of data from >99% of entire population. Among randomly sampled one million enrollees, 6251 adult CHC patients were identified from 1997 to 2009. Diabetes was defined as new onset in the patient who was given the diagnosis in the years 1999-2009 but not in 1997-1998. The cohorts of CHC with new onset diabetes (n = 1100) and 1:1 ratio age-, gender-, and inception point (onset date of diabetes) matched nondiabetes (n = 1087) were followed up from the inception point until the development of HCC, withdrawal from insurance, or December 2009. RESULTS: After adjustment for competing mortality, patients with new onset diabetes had a significantly higher cumulative incidence of HCC (Relative Risk = 1.544, 95% CI = 1.000-2.387, modified log-rank test, P = 0.047) as compared to those without. After adjustment for age, gender, cirrhosis, hyperlipidaemia, CHC treatment, diabetes treatment, comorbidity index, obesity and statins therapy by Cox proportional hazard model, diabetes was still an independent predictor for HCC (hazard ratio (HR) = 1.906, 95% CI = 1.102-3.295, P = 0.021). The risk for HCC was increased in those who were 40-59 years old, independent of other variables (HR = 3.086, 95% CI = 1.045-9.112, P = 0.041), and after adjustment for competing mortality (modified log-rank test, P = 0.009). CONCLUSION: Chronic hepatitis C patients who develop diabetes are at an increased risk of hepatocellular carcinoma over time.

Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with new onset diabetes: a nationwide cohort study.

BACKGROUND: Diabetes increases the risk of hepatocellular carcinoma (HCC), however, the time-relationship between hepatitis B virus and diabetes for the development of HCC remains unclear. AIM: To explore the risk of HCC in chronic hepatitis B patients with newly diagnosed diabetes. METHODS: We conducted a nationwide cohort study by using Taiwanese National Health Insurance Research Database, which covers over 99% of entire population. Among randomly sampled one million enrollees, 14 523 chronic hepatitis B patients were diagnosed in years 1997-2009. We defined new onset diabetes as patients who were given the diagnosis in the years 1999-2009, but not in 1997-1998. The cohorts of chronic hepatitis B with new onset diabetes (n = 2099) and 1:1 ratio age-, gender- and inception point (onset date of diabetes)- matched nondiabetes (n = 2080) were followed up from the inception point until development of HCC, withdrawal from insurance or December 2009. RESULTS: After adjustment for competing mortality, patients with new onset diabetes had a significantly higher cumulative incidence of HCC [relative risk = 1.628, 95% confidence interval (CI) = 1.114-2.378, modified log-rank test, P = 0.012] as compared to nondiabetes patients. After adjustment for age, gender, hyperlipidaemia, chronic hepatitis B treatment, statins therapy, cirrhosis, comorbidity index and obesity, diabetes was still an independent predictor for HCC (hazard ratio = 1.798, 95% CI = 1.194-2.707, P = 0.005). CONCLUSION: Chronic hepatitis B patients with newly diagnosed diabetes have an increased risk of hepatocellular carcinoma over time.

Use of non-steroidal anti-inflammatory drugs and risk of chronic kidney disease in people with Type 2 diabetes mellitus, a nationwide longitudinal cohort study.

AIMS: To investigate the temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes mellitus. METHODS: We conducted a retrospective cohort study and followed up a population with Type 2 diabetes who were chronic kidney disease-free (n = 48,715) using national health insurance claims data in Taiwan. Exposure status to non-steroidal anti-inflammatory drugs in 2007 was measured. A total of 6406 subjects with incident chronic kidney disease were identified from the period 2008 to 2011. Multivariable proportional hazards models were applied to determine the temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease. RESULTS: We observed a significant temporal relationship between non-steroidal anti-inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes. Compared with people not taking any non-steroidal anti-inflammatory drug in 2007, those who were taking such drugs for at least 90 days in 2007 had a higher risk of chronic kidney disease development (adjusted hazard ratio 1.37, 95% CI 1.26-1.49). In subgroup analyses, those people (irrespective of age, sex, various comorbidities and use of anti-hypertensive drugs, aspirin or acetaminophen) who were taking non-steroidal anti-inflammatory drugs for at least 90 days were more likely to develop chronic kidney disease than people who were not taking any non-steroidal anti-inflammatory drug. CONCLUSIONS: The results suggest that there is a positive temporal relationship between non-steroidal anti-inflammatory drug use and increased risk of chronic kidney disease in people with Type 2 diabetes. The use of non-steroidal anti-inflammatory drugs should be based on clinical evaluations of benefits and risks, and should be prescribed with caution for people with Type 2 diabetes.

Physical wounding and ethylene stimulated embryogenic stem cell proliferation and plantlet regeneration in protocorm-like bodies of Phalaenopsis orchids.

Phalaenopsis orchids have been regenerated by inducing protocorm-like bodies (PLBs) from etiolated leaf sections. However, the physiological and molecular mechanisms of secondary PLB development and subsequent proliferation have not been explored. Bisectionally cutting primary PLBs resulted in more secondary PLBs at 5 weeks, suggesting an embryogenic stem cell property imposed by wounding of primary PLB tissues. The ethylene precursors ethephon and 1-aminocyclopropanecarboxylic acid and the ethylene perception inhibitor silver nitrate increased PLB formation, while aminoethoxyvinylglycine decreased PLB formation. Ethylene content in wounded PLB explants increased over culture time in media containing ethylene precursors or inhibitors. mRNA levels of PhACS2, PhACS3, and PhACO were increased by ethephon and decreased by ethylene inhibitors. Expression of genes in the ethylene signaling pathway was enhanced following ethylene-precursor treatment and was mitigated by ethylene inhibitors during PLB proliferation. Transcription of PhETR and PhEIN3, as well as PhERS, PhCTR, and PhGTP, was significantly increased 12 h after ethylene treatment. Ethylene and physical wounding stimulated secondary PLB formation in Phalaenopsis, probably through ethylene biosynthesis and signal transduction.

CpG island shore methylation regulates caveolin-1 expression in breast cancer.

Caveolin-1 (Cav1) is an integral membrane, scaffolding protein found in plasma membrane invaginations (caveolae). Cav1 regulates multiple cancer-associated processes. In breast cancer, a tumor suppressive role for Cav1 has been suggested; however, Cav1 is frequently overexpressed in aggressive breast cancer subtypes, suggesting an oncogenic function in advanced-stage disease. To further delineate Cav1 function in breast cancer progression, we evaluated its expression levels among a panel of cell lines representing a spectrum of breast cancer phenotypes. In basal-like (the most aggressive BC subtype) breast cancer cells, Cav1 was consistently upregulated, and positively correlated with increased cell proliferation, anchorage-independent growth, and migration and invasion. To identify mechanisms of Cav1 gene regulation, we compared DNA methylation levels within promoter 'CpG islands' (CGIs) with 'CGI shores', recently described regions that flank CGIs with less CG-density. Integration of genome-wide DNA methylation profiles ('methylomes') with Cav1 expression in 30 breast cancer cell lines showed that differential methylation of CGI shores, but not CGIs, significantly regulated Cav1 expression. In breast cancer cell lines having low Cav1 expression (despite promoter CGI hypomethylation), we found that treatment with a DNA methyltransferase inhibitor induced Cav1 expression via CGI shore demethylation. In addition, further methylome assessments revealed that breast cancer aggressiveness associated with Cav1 CGI shore methylation levels, with shore hypermethylation in minimally aggressive, luminal breast cancer cells and shore hypomethylation in highly aggressive, basal-like cells. Cav1 CGI shore methylation was also observed in human breast tumors, and overall survival rates of breast cancer patients lacking estrogen receptor α (ERα) negatively correlated with Cav1 expression. Based on this first study of Cav1 (a potential oncogene) CGI shore methylation, we suggest this phenomenon may represent a new prognostic marker for ERα-negative, basal-like breast cancer.