Diagnostic performance of contrast-enhanced mammography for suspicious findings in dense breasts: A systematic review and meta-analysis.

PURPOSE: Contrast-enhanced spectral imaging (CEM) is a new mammography technique, but its diagnostic value in dense breasts is still inconclusive. We did a systematic review and meta-analysis of studies evaluating the diagnostic performance of CEM for suspicious findings in dense breasts. MATERIALS AND METHODS: The PubMed, Embase, and Cochrane Library databases were searched systematically until August 6, 2023. Prospective and retrospective studies were included to evaluate the diagnostic performance of CEM for suspicious findings in dense breasts. The QUADAS-2 tool was used to evaluate the quality and risk of bias of the included studies. STATA V.16.0 and Review Manager V.5.3 were used to meta-analyze the included studies. RESULTS: A total of 10 studies (827 patients, 958 lesions) were included. These 10 studies reported the diagnostic performance of CEM for the workup of suspicious lesions in patients with dense breasts. The summary sensitivity and summary specificity were 0.95 (95% CI, 0.92-0.97) and 0.81 (95% CI, 0.70-0.89), respectively. Enhanced lesions, circumscribed margins, and malignancy were statistically correlated. The relative malignancy OR value of the enhanced lesions was 28.11 (95% CI, 6.84-115.48). The relative malignancy OR value of circumscribed margins was 0.17 (95% CI, 0.07-0.45). CONCLUSION: CEM has high diagnostic performance in the workup of suspicious findings in dense breasts, and when lesions are enhanced and have irregular margins, they are often malignant.

Clinical observation of acupuncture at Huiyin (CV 1) for chronic severe functional constipation / 中国针灸

OBJECTIVE@#To compare the effect of acupuncture at Huiyin (CV 1) and oral administration of western medication in treatment of chronic severe functional constipation (CSFC).@*METHODS@#A total of 64 patients with CSFC were randomly divided into an acupuncture group (32 cases, 5 cases dropped off) and a western medication group (32 cases, 4 cases dropped off). Both groups were given routine basic treatment. The acupuncture group was treated by directly puncture of 20-30 mm at Huiyin (CV 1), once a day for the first 4 weeks, 5 times a week, once every other day for the next 4 weeks, 3 times a week, totally for 8 weeks. The western medication group was treated with 2 mg prucalopride succinate tablets orally before breakfast every day for 8 weeks. The average number of weekly spontaneous bowel movement (SBM) of the two groups were observed before treatment and 1-8 weeks into treatment. The constipation symptom score before and after treatment, and in follow-up of 1 month after treatment, as well as quality of life [patient assessment of constipation quality of life questionnaire (PAC-QOL) score and the proportion of patients of PAC-QOL score difference before and after treatment≥1] before and after treatment were compared in the two groups. The clinical effects of the two groups were evaluated after treatment and in follow-up.@*RESULTS@#Compared before treatment, the average number of weekly SBM in the two groups was increased 1-8 weeks into treatment (P<0.05). The average number of weekly SBM in the acupuncture group was less than that in the western medication group 1 week into treatment (P<0.05), and the average number of weekly SBM in the observation group was more than that in the western medication group 4-8 weeks into treatment (P<0.05). The scores of constipation symptom after treatment and in follow-up and scores of PAC-QOL after-treatment in the two groups were lower than those before treatment (P<0.05), and those in the acupuncture group were lower than the western medication group (P<0.05). The proportion of patients of PAC-QOL score difference before and after treatment≥1 in the acupuncture group was higher than that in the west medication group (P<0.05). The total effective rates after treatment and in follow-up in the acupuncture group were 81.5% (22/27) and 78.3% (18/23), respectively, which were better than 42.9% (12/28) and 43.5% (10/23) in the western medication group (P<0.05).@*CONCLUSION@#Acupuncture at Huiyin (CV 1) can effectively increase the number of spontaneous defecation in patients with CSFC, reduce constipation symptoms, improve the quality of life, and the effect after treatment and in follow-up is better than oral western medication.

Mechanism of Ginseng-Rhodiola rosea in treatment of myocardial ischemia-reperfusion injury based on network pharmacology and molecular docking / 中国药理学通报

Aim To investigate the sites and mechanisms of action of Ginseng-Rhodiola rosea in the treat ment of myocardial ischemia-reperfusion injury ( MI-RI) via using network pharmacology approach, molecu¬lar docking techniques and experimental studies. Methods The active ingredients and targets of Gin¬seng-Rhodiola rosea were screened through the TCMSP database and literature supplementation, and the GEN-EC ARDS ,DISGENET and DRUGBANK databases were searched to obtain the targets of MIRI. Functional pro¬tein interaction networks (PPIs) and the STRING database were used to screen out core targets. The DAVID database was also selected for gene ontology functional analysis ( GO) and KEGG signaling pathway enrich¬ment analysis. Lastly, the preliminary validation was performed with the help of molecular docking techniques and experimental studies. Results Forty-three active ingredients and 348 potential targets of Ginseng-Rhodiola were obtained, and targets such as IL-6 , TNF-α and VEGFA were found to be closely related to MIRI, mainly involving TNF, PDK-Akt, HIF-1 and other signaling pathways.The molecular docking results showed that soysterol, ginsenoside rh2 and rhodioloside had good binding effects and high matching with IL-6, TNF-α,Caspase-3,VEGFA,MAPK1 and other targets, among which the best binding was between Caspase-3 and ginsenoside rh2. The results of the experimental study further showed that Ginseng-Rhodiola rosea could improve myocardial tissue necrosis after myocardial ischemia-reperfusion , reduce myocardial cell edema and vascular congestion, and decrease the expression levels of TNF-α and IL-6 in MIRI rats. Conclusions Ginseng-Rhodiola may modulate multiple targets such as IL-6,TNF-α, Caspase-3, VEGFA and MAPK1 through dousterol, ginsenoside rh2 and rhodiol glycosides to inhibit inflammatory response and oxidative stress, reduce cardiomyocyte damage and exert therapeutic effects on MIRI.

The influence of pre-existing hypertension on coronavirus disease 2019 patients.

Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21% vs. 10%, P = 0.007). Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.

Transcriptome Analyses Reveal Systematic Molecular Pathology After Optic Nerve Crush.

The function of glial cells in axonal regeneration after injury has been the subject of controversy in recent years. Thus, deeper insight into glial cells is urgently needed. Many studies on glial cells have elucidated the mechanisms of a certain gene or cell type in axon regeneration. However, studies that manipulate a single variable may overlook other changes. Here, we performed a series of comprehensive transcriptome analyses of the optic nerve head over a period of 90 days after optic nerve crush (ONC), showing systematic molecular changes in the optic nerve head (ONH). Furthermore, using weighted gene coexpression network analysis (WGCNA), we established gene module programs corresponding to various pathological events at different times post-ONC and found hub genes that may be potential therapeutic targets. In addition, we analyzed the changes in different glial cells based on their subtype markers. We revealed that the transition trend of different glial cells depended on the time course, which provides clues for modulating glial function in further research.

Pre-existing Health Conditions and Epicardial Adipose Tissue Volume: Potential Risk Factors for Myocardial Injury in COVID-19 Patients.

Background: Myocardial injury is a life-threatening complication of coronavirus disease 2019 (COVID-19). Pre-existing health conditions and early morphological alterations may precipitate cardiac injury and dysfunction after contracting the virus. The current study aimed at assessing potential risk factors for COVID-19 cardiac complications in patients with pre-existing conditions and imaging predictors. Methods and Results: The multi-center, retrospective cohort study consecutively enrolled 400 patients with lab-confirmed COVID-19 in six Chinese hospitals remote to the Wuhan epicenter. Patients were diagnosed with or without the complication of myocardial injury by history and cardiac biomarker Troponin I/T (TnI/T) elevation above the 99th percentile upper reference limit. The majority of COVID-19 patients with myocardial injury exhibited pre-existing health conditions, such as hypertension, diabetes, hypercholesterolemia, and coronary disease. They had increased levels of the inflammatory cytokine interleukin-6 and more in-hospital adverse events (admission to an intensive care unit, invasive mechanical ventilation, or death). Chest CT scan on admission demonstrated that COVID-19 patients with myocardial injury had higher epicardial adipose tissue volume ([EATV] 139.1 (83.8-195.9) vs. 92.6 (76.2-134.4) cm2; P = 0.036). The optimal EATV cut-off value (137.1 cm2) served as a useful factor for assessing myocardial injury, which yielded sensitivity and specificity of 55.0% (95%CI, 32.0-76.2%) and 77.4% (95%CI, 71.6-82.3%) in adverse cardiac events, respectively. Multivariate logistic regression analysis showed that EATV over 137.1 cm2 was a strong independent predictor for myocardial injury in patients with COVID-19 [OR 3.058, (95%CI, 1.032-9.063); P = 0.044]. Conclusions: Augmented EATV on admission chest CT scan, together with the pre-existing health conditions (hypertension, diabetes, and hyperlipidemia) and inflammatory cytokine production, is associated with increased myocardial injury and mortality in COVID-19 patients. Assessment of pre-existing conditions and chest CT scan EATV on admission may provide a threshold point potentially useful for predicting cardiovascular complications of COVID-19.

Two Novel Mutations at the CD36 Gene Splicing Sites and Their Molecular Basis for the CD36 Deficiency / 中国实验血液学杂志

OBJECTIVE@#To study two novel CD36 gene mutations at the CD36 splicing sites found in Guangxi population, as well as the molecular basis and population incidence of them.@*METHODS@#DNA sequencing and cDNA clonal sequencing were used to detect CD36 exon sequence and the protein coding region sequence of CD36 mRNA for 2 CD36 deficient individuals (HHC and WGM) found in Guangxi population. Eukaryotic expression cell lines were established for the discovery of CD36 mRNA abnormal transcripts and Western blot assay was used to verify the effect of abnormal CD36 mRNA transcripts on CD36 expression. A DNA PCR-SSP genotyping method was established for the two CD36 novel mutations, and the population distribution was investigated among 110 CD36 deficient individuals in Guangxi region and 296 random individuals in Guangxi population.@*RESULTS@#Novel mutation of c.430 -1G>C was found at the CD36 splicing site in HHC and WGM individuals, and novel mutation of c.1006 +2T>G at the CD36 splicing site was also found in the WGM individual. CD36 cDNA clonal sequencing showed that CD36 c.430 -1G>C could lead to the production of the two CD36 mRNA transcript variants: c.429_430ins［430-17_430-2;C］(p.Ala144fsTer1) and c.430_609del(p.Ala144_Pro203del)(GenBank:HM 217023.1); and CD36 c.1006 +2T>G could lead to the production of CD36 mRNA transcript variant of c.819_1006 del (p.Ser274GlufsTer16) (GenBank: HM217025.1). It was verified that all the three transcript variants could lead to CD36 deficiency by establishment of eukaryotic expression cell lines and Western blot assay. A study of the population incidence of two novel CD36 splicing site mutations found showed that in 110 CD36 deficient individuals and in 296 random individuals in Guangxi region, the mutation rate of CD36 c.430 -1G>C was 10.91% (12/110) and 1.35% (4/296), respectively, while CD36 c.1006 +2T>G was 2.73% (3/110) and 0 (0/296), respectively.@*CONCLUSION@#This study identifies two novel CD36 mutations at CD36 splicing site, and preliminary clarified their molecular basis for the CD36 deficiency and the distribution characteristics in Guangxi population as well. It provides an experimental and theoretical basis for studying the molecular mechanism and characteristics of CD36 deficiency in Chinese population.

A phenotype-directed chemical screen identifies ponalrestat as an inhibitor of the plant flavin monooxygenase YUCCA in auxin biosynthesis.

Plant development is regulated by both synergistic and antagonistic interactions of different phytohormones, including a complex crosstalk between ethylene and auxin. For instance, auxin and ethylene synergistically control primary root elongation and root hair formation. However, a lack of chemical agents that specifically modulate ethylene or auxin production has precluded precise delineation of the contribution of each hormone to root development. Here, we performed a chemical genetic screen based on the recovery of root growth in ethylene-related Arabidopsis mutants with constitutive "short root" phenotypes (eto1-2 and ctr1-1). We found that ponalrestat exposure recovers root elongation in these mutants in an ethylene signal-independent manner. Genetic and pharmacological investigations revealed that ponalrestat inhibits the enzymatic activity of the flavin-containing monooxygenase YUCCA, which catalyzes the rate-limiting step of the indole-3-pyruvic acid branch of the auxin biosynthesis pathway. In summary, our findings have identified a YUCCA inhibitor that may be useful as a chemical tool to dissect the distinct steps in auxin biosynthesis and in the regulation of root development.

Effect of α7nAChR on learning and memory dysfunction in a rat model of diffuse axonal injury.

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and significantly contributes to cognitive deficits. The mechanisms that underlie these cognitive deficits are often associated with complex molecular alterations. α7nAChR, one of the abundant and widespread nicotinic acetylcholine receptors (nAChRs) in the brain, plays important physiological functions in the central nervous system. However, the relationship between temporospatial alterations in the α7nAChR and DAI-related learning and memory dysfunction are not completely understood. Our study detected temporospatial alterations of α7nAChR in vulnerable areas (hippocampus, internal capsule, corpus callosum and brain stem) of DAI rats and evaluated the development and progression of learning and memory dysfunction via the Morris water maze (MWM). We determined that α7nAChR expression in vulnerable areas was mainly reduced at the recovery of DAI in rats. Moreover, the escape latency of the injured group increased significantly and the percentages of the distance travelled and time spent in the target quadrant were significantly decreased after DAI. Furthermore, α7nAChR expression in the vulnerable area was significantly positively correlated with MWM performance after DAI according to regression analysis. In addition, we determined that a selective α7nAChR agonist significantly improved learning and memory dysfunction. Rats in the α7nAChR agonist group showed better learning and memory performance than those in the antagonist group. These results demonstrate that microstructural injury-induced alterations of α7nAChR in the vulnerable area are significantly correlated with learning and memory dysfunctions after DAI and that augmentation of the α7nAChR level by its agonist contributes to the improvement of learning and memory function.

Inhibition of miRNA-21 promotes retinal ganglion cell survival and visual function by modulating Müller cell gliosis after optic nerve crush.

BACKGROUND: Müller cell gliosis not only plays an important physiological role by maintaining retinal neuronal homeostasis but is also associated with multiple pathological events in the retina, including optic nerve crush (ONC) injury. Modulating Müller cell gliosis contributes to the creation of a permissive environment for neuronal survival. However, the underlying mechanism of Müller cell gliosis has remained elusive. OBJECTIVE: To investigate the underlying mechanism of Müller cell gliosis after ONC. METHODS: Rats with ONC injury were transfected with miRNA-21 (miR-21) agomir (overexpressing miR-21) or antagomir (inhibiting miR-21) via intravitreous injection. Immunofluorescence and western blotting were performed to confirm the effects of miR-21 on Müller cell gliosis. The retinal nerve fiber layer (RNFL) thickness was measured using optical coherence tomography and the positive scotopic threshold response (pSTR) was recorded using electroretinogram. RESULTS: In the acute phase (14 days) after ONC, compared with the crushed group, inhibiting miR-21 promoted Müller cell gliosis, exhibiting thicker processes and increased GFAP expression. In the chronic phase (35 days), inhibiting miR-21 ameliorated Müller cell gliosis, which exhibited thicker and denser processes and increased GFAP expression. Retinal ganglion cell (RGC) counts in retinas showed that the number of surviving RGCs increased significantly in the antagomir group. The thickness of the RNFL increased significantly, and pSTR showed significant preservation of the amplitudes in the antagomir group. CONCLUSIONS: Inhibition of miR-21 promotes RGC survival, RNFL thickness and the recovery of RGC function by modulating Müller cell gliosis after ONC.

Neuronal GAP-Porf-2 transduces EphB1 signaling to brake axon growth.

Axonal outgrowth and guidance require numerous extracellular cues and intracellular mediators that transduce signals in the growth cone to regulate cytoskeletal dynamics. However, the way in which cytoskeletal effectors respond to these signals remains elusive. Here, we demonstrate that Porf-2, a neuron-expressed RhoGTPase-activating protein, plays an essential role in the inhibition of initial axon growth by restricting the expansion of the growth cone in a cell-autonomous manner. Furthermore, the EphB1 receptor is identified as an upstream controller that binds and regulates Porf-2 specifically upon extracellular ephrin-B stimulation. The activated EphB forward signal deactivates Rac1 through the GAP domain of Porf-2, which inhibits growth cone formation and brakes axon growth. Our results therefore provide a novel GAP that regulates axon growth and braking sequentially through Eph receptor-independent and Eph receptor-dependent pathways.

Inhibition of miR-21 ameliorates excessive astrocyte activation and promotes axon regeneration following optic nerve crush.

Optic nerve injury is a leading cause of irreversible visual impairment worldwide and can even cause blindness. Excessive activation of astrocytes has negative effects on the repair and recovery of retinal ganglion cells following optic nerve injury. However, the molecular and cellular mechanisms underlying astrocyte activation after optic nerve injury remain largely unknown. In the present study, we explored the effects of microRNA-21 (miR-21) on axon regeneration and flash visual evoked potential (F-VEP) and the underlying mechanisms of these effects based on astrocyte activation in the rat model of optic nerve crush (ONC). To the best of our knowledge, this article is the first to report that inhibition of miR-21 enhances axonal regeneration and promotes functional recovery in F-VEP in the rat model of ONC. Furthermore, inhibition of miR-21 attenuates excessive astrocyte activation and glial scar formation, thereby promoting axonal regeneration by regulating the epidermal growth factor receptor (EGFR) pathway. In addition, we observed that the expression of tissue inhibitor of metalloproteinase-3, a target gene of miR-21, was inhibited during this process. Taken together, these findings demonstrate that inhibition of miR-21 regulates the EGFR pathway, ameliorating excessive astrocyte activation and glial scar progression and promoting axonal regeneration and alleviating impairment in F-VEP function in a model of ONC. This study's results suggest that miR-21 may represent a therapeutic target for optic nerve injury.

[Expression of ASPH Gene in Invasive Breast Cancer and Its Clinical Significance in Promoter Methylation].

OBJECTIVE: To investigate the expression of mRNA of aspartyl/asparaginyl beta-hydroxylase (ASPH) gene in invasive breast cancer (IBC) and the relationship between methylation of gene promoter and clinicopathological parameters. METHODS: In 91 cases of breast cancer tissues and matched normal tissues (MNT),mRNA expression of the ASPH gene was detected by reverse transcription of real-time fluorescence quantification PCR and the methylation status of CpG island in the ASPH gene promoter region was detected by methylation specific PCR (MSP).And the relationship between the expression and the clinicopathological features of breast cancer was analyzed. RESULTS: The expression of ASPH gene mRNA in IBC was significantly higher than that in MNT ( P<0.001).The fold change of ASPH mRNA expression was related to whether E-cadherin was positive (r=0.195, P=0.041).The positive rate of methylation of ASPH gene promoter in breast cancer and MNT was 47.3% (43/91) and 89.0% (81/91). The methylation rate of gene promoter was correlated with E-cadherin and tumor size ( P<0.05). CONCLUSION: The mRNA expression and promoter methylation rate of ASPH gene may play a role in the development and progression of breast cancer.

Human umbilical cord-derived mesenchymal stem cells in the treatment of myocardial infarction: existing problems, effects and prospects / 中国组织工程研究

BACKGROUND: Human umbilical cord-derived mesenchymal stem cells, because of convenient acquisition, will not bring pain and adverse effects to the fetus and their parturient. The success rate of culture is high. It has good application prospects in the treatment of myocardial infarction. OBJECTIVE: To review the new progress of human umbilical cord-derived mesenchymal stem cells transplantation in the treatment of myocardial infarction. METHODS: A computer-based online search of PubMed and Wanfang databases was performed to retrieve the related articles published from 1991 to 2017. We reviewed the initial data and the quotations from each document. Finally, we included randomized controlled animal experiments or clinical studies concerning human umbilical cord-derived mesenchymal stem cells for treatment of myocardial infarction. RESULTS AND CONCLUSION: Human umbilical cord-derived mesenchymal stem cells will become a new alternative source of cells in the treatment of myocardial infarction, with extremely broad prospects. However, there is no mature conclusion about the convenient route, optimal number of transplanted cells, optimal timing, differentiation, homing and evaluation after transplantation, which limits the clinical application of these cells.

Rac1 Guides Porf-2 to Wnt Pathway to Mediate Neural Stem Cell Proliferation.

The molecular and cellular mechanisms underlying the anti-proliferative effects of preoptic regulator factor 2 (Porf-2) on neural stem cells (NSCs) remain largely unknown. Here, we found that Porf-2 inhibits the activity of ras-related C3 botulinum toxin substrate 1 (Rac1) protein in hippocampus-derived rat NSCs. Reduced Rac1 activity impaired the nuclear translocation of ß-catenin, ultimately causing a repression of NSCs proliferation. Porf-2 knockdown enhanced NSCs proliferation but not in the presence of small molecule inhibitors of Rac1 or Wnt. At the same time, the repression of NSCs proliferation caused by Porf-2 overexpression was counteracted by small molecule activators of Rac1 or Wnt. By using a rat optic nerve crush model, we observed that Porf-2 knockdown enhanced the recovery of visual function. In particular, optic nerve injury in rats led to increased Wnt family member 3a (Wnt3a) protein expression, which we found responsible for enhancing Porf-2 knockdown-induced NSCs proliferation. These findings suggest that Porf-2 exerts its inhibitory effect on NSCs proliferation via Rac1-Wnt/ß-catenin pathway. Porf-2 may therefore represent and interesting target for optic nerve injury recovery and therapy.

Rho GTPase-activating proteins: Regulators of Rho GTPase activity in neuronal development and CNS diseases.

The Rho family of small GTPases was considered as molecular switches in regulating multiple cellular events, including cytoskeleton reorganization. The Rho GTPase-activating proteins (RhoGAPs) are one of the major families of Rho GTPase regulators. RhoGAPs were initially considered negative mediators of Rho signaling pathways via their GAP domain. Recent studies have demonstrated that RhoGAPs also regulate numerous aspects of neuronal development and are related to various neurodegenerative diseases in GAP-dependent and GAP-independent manners. Moreover, RhoGAPs are regulated through various mechanisms, such as phosphorylation. To date, approximately 70 RhoGAPs have been identified; however, only a small portion has been thoroughly investigated. Thus, the characterization of important RhoGAPs in the central nervous system is crucial to understand their spatiotemporal role during different stages of neuronal development. In this review, we summarize the current knowledge of RhoGAPs in the brain with an emphasis on their molecular function, regulation mechanism and disease implications in the central nervous system.

Exploring Optic Nerve Axon Regeneration.

BACKGROUND: Traumatic optic nerve injury is a leading cause of irreversible blindness across the world and causes progressive visual impairment attributed to the dysfunction and death of retinal ganglion cells (RGCs). To date, neither pharmacological nor surgical interventions are sufficient to halt or reverse the progress of visual loss. Axon regeneration is critical for functional recovery of vision following optic nerve injury. After optic nerve injury, RGC axons usually fail to regrow and die, leading to the death of the RGCs and subsequently inducing the functional loss of vision. However, the detailed molecular mechanisms underlying axon regeneration after optic nerve injury remain poorly understood. METHODS: Research content related to the detailed molecular mechanisms underlying axon regeneration after optic nerve injury have been reviewed. RESULTS: The present review provides an overview of regarding potential strategies for axonal regeneration of RGCs and optic nerve repair, focusing on the role of cytokines and their downstream signaling pathways involved in intrinsic growth program and the inhibitory environment together with axon guidance cues for correct axon guidance. A more complete understanding of the factors limiting axonal regeneration will provide a rational basis, which contributes to develop improved treatments for optic nerve regeneration. These findings are encouraging and open the possibility that clinically meaningful regeneration may become achievable in the future. CONCLUSION: Combination of treatments towards overcoming growth-inhibitory molecules and enhancing intrinsic growth capacity combined with correct guidance using axon guidance cues is crucial for developing promising therapies to promote axon regeneration and functional recovery after ON injury.

Rapid increase in cystic volume of an anaplastic astrocytoma misdiagnosed as neurocysticercosis: A case report.

Reports describing a rapid increase in the cystic volume of anaplastic astrocytoma (AA) in a short time frame are rare. The present study reports the case of a 68-year-old male who was admitted to the No. 9 People's Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), with a small cystic brain lesion and positive immunological testing for cysticercosis. Head magnetic resonance imaging (MRI) showed a cystic lesion, 6 mm in diameter, in the left frontal lobe. Neurocysticercosis was suspected and the patient was treated with a clinical trial of albendazole and steroids. A period of 25 days later, the patient's condition had deteriorated, and MRI revealed a cystic lesion in the left frontal lobe; thereafter, the cystic lesion was removed and a diagnosis of AA was established. The tumor was soft, ivory white and gelatinous due to myxoid degeneration. In this case, tumor-related angiogenesis and microvascular extravasation (blood-brain barrier disruption) may have been the main cause of the rapid increase in the cystic volume in such a short time frame. The similarity of the glioma and cysticercus antigens may have been the cause of the positive reactions in the cystic fluid. The present study reports the rare occurrence of a rapid increase of cystic volume and potential diagnostic difficulties.

[Expressions and Clinical Significance of Autophagy-related Genes ATG2B, ATG4D, ATG9B in Breast Carcinoma].

OBJECTIVE: To investigate the expressions and clinical significance of autophagy-related gene 2B (ATG2B), autophagy-related gene 4D (ATG4D), autophagy-related gene 9B (ATG9B) in breast cancer cell lines and breast cancer. METHODS: Cancer Browser screening was applied to study the differential expressions of ATG2B, ATG4D, ATG9B genes in breast cancer. Quantitative Real-time PCR was used to measure the expressions of these three genes in human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435S and ZR-75-30) as well as 83 cases of breast cancer samples with paired normal breast tissues. The relationships between the expressions of these genes and clinicopathological characteristics were further analyzed. RESULTS: Cancer Browser screening found abnormal expressions of ATG2B, ATG4D, ATG9B in breast cancer (P = 0.015, P = 0.028, P = 0.040). All four breast cancer cell lines expressed ATG2B, ATG4D, ATG9B, and the expression of ATG2B, ATG9B was significantly lower than positive control (P < 0.001), but ATG4D expression was higher than positive control (P < 0.001). The expressions of ATG2B, ATG4D, ATG9B in breast cancer were all lower than those in the adjacent normal tissues (P < 0.001, P = 0.031, P < 0.001). Furthermore, the expression of ATG2B was correlated with ER (r = 0.949, P = 0.015), and the expression of ATG4D was related to age (r = -0.449, P = 0.005), the expression of ATG9B was correlated to lymph node metastasis and cytokeratin 5/6 status (r = 0.339, P = 0.043; r = 0.533, P = 0.043). CONCLUSION: ATG2B, ATG4D, ATG9B genes shows low expressions in breast cancer, which may become new molecular markers for the prognosis of breast cancer.

Aberrant methylation of ATG2B, ATG4D, ATG9A and ATG9B CpG island promoter is associated with decreased mRNA expression in sporadic breast carcinoma.

Epigenetic modifications are critical determinants in tumor initiation and progression. This study aims to detect the promoter methylation status and the mRNA expression levels of ATG2B, ATG4D, ATG9A and ATG9B, and then to explore their relationship in invasive ductal carcinomas (IDCs) and matched normal tissues (MNTs) of the breast. Methylation was observed as follows: 61.0% in ATG2B, 46.8% in ATG4D, 56.4% in ATG9A, and 74.0% in ATG9B of IDCs. Meanwhile, their mRNA expression levels of the IDCs was lower than that of the MNTs (P<0.001, P=0.019, P<0.001 and P<0.001, respectively). Methylated IDCs of ATG2B, ATG9A, ATG9B and unmethylated ATG4D, ATG9B showed significantly lower expression values compared to the MNTs (P=0.003, P<0.001, P<0.001, P=0.014 and P=0.002, respectively). The methylations of ATG2B and ATG9B were related to their lower expression levels in IDCs (P=0.017 and P=0.023). Moreover, ATG2B methylation was positively associated with the grade (P=0.024) and TNM stage (P=0.015); Methylation of ATG4D and ATG9A was positively correlated to lymph node involvement (P=0.012 and P=0.018), while methylation of ATG9B appeared susceptible to CK5/6 positive status and deteriorated TNM stages (P=0.003 and P=0.012). Moreover, the decreased expression of ATG2B was related to the ER and PR status (P=0.004 and P=0.003). The ER, HER-2 and lymph node metastasis status are the determinants to reducing the expression of ATG4D, ATG9A and ATG9B (P=0.026, P=0.010 and P=0.011, respectively). This study highlights the transcriptional inactivation mechanisms of ATG2B, ATG4D, ATG9A and ATG9B promoter methylation status and the possible origin of autophagy signal pathway repression in IDCs.