[Repeated stellate ganglion blockade for the treatment of ventricular tachycardia storm in patients with nonischemic cardiomyopathy: a new therapeutic option for patients with malignant arrhythmias].

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.

Leptin regulation of the p53-HIF1α/PKM2-aromatase axis in breast adipose stromal cells: a novel mechanism for the obesity-breast cancer link.

BACKGROUND/OBJECTIVES: Obesity (body mass index (BMI)⩾30 kg m-2) is associated with an increased risk of estrogen-dependent breast cancer after menopause. Levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis, are elevated in breast tissue of obese women. Recently, the regulation of aromatase by the p53-hypoxia-inducible factor-1α (HIF1α)/pyruvate kinase M2 (PKM2) axis was characterized in adipose stromal cells (ASCs) of women with Li-Fraumeni Syndrome, a hereditary cancer syndrome that predisposes to estrogen-dependent breast cancer. The current study aimed to determine whether stimulation of aromatase by obesity-associated adipokine leptin involves the regulation of the p53-HIF1α/PKM2 axis. SUBJECTS/METHODS: Human breast ASCs were used to characterize the p53-HIF1α/PKM2-aromatase axis in response to leptin. The effect of pharmacological or genetic modulation of protein kinase C (PKC), mitogen-activated protein kinase (MAPK), p53, Aha1, Hsp90, HIF1α and PKM2 on aromatase promoter activity, expression and enzyme activity was examined. Semiquantitative immunofluorescence and confocal imaging were used to assess ASC-specific protein expression in formalin-fixed paraffin-embedded tissue sections of breast of women and mammary tissue of mice following a low-fat (LF) or high-fat (HF) diet for 17 weeks. RESULTS: Leptin-mediated induction of aromatase was dependent on PKC/MAPK signaling and the suppression of p53. This, in turn, was associated with an increase in Aha1 protein expression, activation of Hsp90 and the stabilization of HIF1α and PKM2, known stimulators of aromatase expression. Consistent with these findings, ASC-specific immunoreactivity for p53 was inversely associated with BMI in breast tissue, while HIF1α, PKM2 and aromatase were positively correlated with BMI. In mice, HF feeding was associated with significantly lower p53 ASC-specific immunoreactivity compared with LF feeding, while immunoreactivity for HIF1α, PKM2 and aromatase were significantly higher. CONCLUSIONS: Overall, findings demonstrate a novel mechanism for the obesity-associated increase in aromatase in ASCs of the breast and support the study of lifestyle interventions, including weight management, which may reduce breast cancer risk via effects on this pathway.

Comparative genome-wide gene expression analysis of rheumatoid arthritis and osteoarthritis.

Both rheumatoid arthritis (RA) and osteoarthritis (OA) are complex diseases. Studies and treatment of RA and OA have mainly focused on individual factors. However, there is still no clear understanding of their causes and adequate treatment alternatives are still being sought. We applied gene set-enrichment analysis to microarray datasets of RA and OA to look for regulatory mechanisms. We found 32 highly significant pathways, including 18 downregulated and 14 upregulated pathways associated with RA. We also identified 18 highly significant pathways, including 7 downregulated and 11 up-regulated pathways associated with OA. Several such pathways were found in both RA and OA, including an upregulated PPAR signaling pathway and downregulated leukocyte transendothelial migration. Regulatory mechanisms in RA seem to be more complex than in OA. This information could be useful for diagnosis and treatment of these two diseases.

Periprostatic adipose inflammation is associated with high-grade prostate cancer.

BACKGROUND: Obesity, a cause of subclinical inflammation, is associated with increased risk of high-grade prostate cancer (PC) and poor outcomes. Whether inflammation occurs in periprostatic white adipose tissue (WAT), and contributes to the negative impact of obesity on PC aggressiveness, is unknown. METHODS: In a single-center, cross-sectional design, men with newly diagnosed PC undergoing radical prostatectomy were eligible for study participation. The primary objective was to examine the prevalence of periprostatic WAT inflammation defined by the presence of crown-like structures (CLS-P) as detected by CD68 immunohistochemistry. Secondary objectives were to explore the clinical and systemic correlates of periprostatic WAT inflammation. Tumor characteristics and host factors including BMI, adipocyte diameter, and circulating levels of lipids, adipokines, and other metabolic factors were measured. Wilcoxon rank-sum, Chi-square, or Fisher's exact tests, and generalized linear regression were used to examine the association between WAT inflammation and tumor and host characteristics. RESULTS: Periprostatic fat was collected from 169 men (median age 62 years; median BMI 28.3). Periprostatic WAT inflammation was identified in 49.7% of patients and associated with higher BMI (P=0.02), larger adipocyte size (P=0.004) and Gleason grade groups IV/V tumors (P=0.02). The relationship between WAT inflammation and high Gleason grade remained significant after adjusting for BMI (P=0.04). WAT inflammation correlated with higher circulating levels of insulin, triglycerides, and leptin/adiponectin ratio, and lower high density lipoprotein cholesterol, compared to those without WAT inflammation (P's <0.05). CONCLUSION: Periprostatic WAT inflammation is common in this cohort of men with PC and is associated with high-grade PC.

Isoenzymes of phenol oxidase in adult female Schistosoma japonicum.

Isoelectric focusing was used to study the phenol oxidase isozymes in adult female worms of Schistosoma japonicum. More than one form of phenol oxidase has been demonstrated in extracts of female worms when incubated with 3,4-dihydroxyphenylalanine (DOPA), catechol or cresol as substrates. DOPA is the best substrate among all of them. The 5-6 bands of phenol oxidase exhibit pI values in the range of 6.0-7.5, the major band is at pI 6.0.

Genes relevant with osteoarthritis by comparison gene expression profiles of synovial membrane of osteoarthritis patients at different stages.

BACKGROUND: This study aimed to identify biological markers about osteoarthritis (OA) which is a polygenic disease by investigating the gene expression profiles of the synovium samples from early-stage and end-stage OA patients for the diagnosis and treatment of OA. METHODS: The gene expression profile of GSE32317 was downloaded from Gene Expression Omnibus (GEO) database, including 10 samples from early-stage OA patients and 9 samples from end-stage OA patients. The differentially expressed genes (DEGs) were identified by Significance Analysis of Microarrays. The co-expression network of DEGs was constructed by Pearson correlation test. Then, modules in the constructed co-expression network were selected by MCODE Plugin. What's more, EASE (Expression Analysis Systematic Explorer) was used to define the significant functions and pathways in the identified modules. RESULTS: Total 419 DEGs were identified, among which 112 were up-regulated and 307 down-regulated. We selected 7 statistically significant modules with gene number above 10 and phenotypic correlation test of modules showed that all the modules had significant correlation with OA (p < 0.05). The genes of module 1, module 2 and module 7 were significantly related to immune system functions, protein glycosylation functions, bone, chondrocytes and cartilage functions, respectively. The most significant pathway in module 3 and module 5 was Wnt signal pathway, and in module 4 was Toll-like receptor signal pathway. CONCLUSIONS: DEGs related to immune response, cartilage development, protein glycosylation, muscle development, and DEGs participated in the Wnt signaling pathway and Toll-like receptor (TLR) signaling pathway might be the potential target genes for the OA treatment.

[Intercepted orthopedic treatment of skeletal maxillary protrusion deformity].

Maxillary protrusion deformity may be divided into three types: functional, skeletal and their combination. The diagnosis of which should be differentiated carefully. The treatment of skeletal maxillary protrusion is very difficult. It must be diagnosed in the growing stage of children and treated with intercepted orthopedic appliance in time. In order to bring the mandible into harmony with maxilla, the growth of maxilla should be inhibited while the mandible is stimulated. In this article an efficient orthopedic appliance using orthopedic force to inhibit the growth of maxilla was introduced. The factors which influenced the orthopedic effect were introduced by cases report. The use of the roentgenography cephalometric in diagnosing the maxillary protrusion deformity was discussed.

[A study on mechanism of skin penetration by cercaria of S. japonicum and screening of preventive drugs].

Mice pretreated with PG cyclo-oxygenase inhibitor aspirin, at 300 mg/kg/d x 5, and ibuprofen, at 100 mg/kg/d x 5 orally and 20 mg/kg/d x 3 intraperitoneally revealed moderate chemoprophylactic effects and the reduction of the penetration of worms by 23% when compared to controls. Daily oral administration of aspirin, at 300 mg/kg for 15 days the worms reduction increased to 41.7%. In estimation of PGE1 in cercariae of S. japonicum by radioimmunoassay, the PGE1 was 49 pg/100 cercariae. In normal mouse skin PGE1 has been measured to amount to 3105 +/- 691.7 pg/10 mg on average. In cercarial penetrated mouse skin, 1.5 hours after exposure the PGE1 assessed in 100 and 250 cercariae in the infected skin were 5506 +/- 1127.1 and 12085 +/- 2622.9 pg/10 mg respectively, which were significantly higher than that of the non-penetrated skin. These studies in conjunction with our previous work indicate that: 1.PGs, similar to S. mansoni, were probably necessary for cercarial penetration. 2.PG inhibitors could reduce cercarial penetration. Receptors antagonist etc. e.g. diphenhydramine, chlorpheniramine, atropine, practolol could not reduce cercarial penetration, but praziquantel in the pretreated mice could reduce cercarial penetration significantly. e.g. 400 mg/kg orally 2 hours prior to affection of cercariae about 100% reduction of the penetration, but if pretreated with praziquantel, 4, 8, 24, 36 hours prior to the affection the reduction penetration decreased to 51.7, 46.1, 9.4, 8.9% respectively.