STAT3-EphA7 axis contributes to the progression of esophageal squamous cell carcinoma.

BACKGROUND: Our previous study has revealed that EphA7 was upregulated in patient-derived esophageal squamous cell carcinoma (ESCC) xenografts with hyper-activated STAT3, but its mechanism was still unclear. MATERIALS AND METHODS: To assess the association between EphA7 and STAT3, western blotting, immunofluorescence, ChIP assay, and qRT-PCR were conducted. Truncated mutation and luciferase assay were performed to examine the promoter activity of EphA7. CCK-8 assay and colony formation were performed to assess the proliferation of ESCC. Cell-derived xenograft models were established to evaluate the effects of EphA7 on ESCC tumor growth. RNA-seq analyses were used to assess the effects of EphA7 on related signals. RESULTS: In this study, EphA7 was found upregulated in ESCC cell lines with high STAT3 activation, and immunofluorescence also showed that EphA7 was co-localized with phospho-STAT3 in ESCC cells. Interestingly, suppressing STAT3 activation by the STAT3 inhibitor Stattic markedly inhibited the protein expression of EphA7 in ESCC cells, in contrast, activation of STAT3 by IL-6 obviously upregulated the protein expression of EphA7. Moreover, the transcription of EphA7 was also mediated by the activation of STAT3 in ESCC cells, and the -2000∼-1500 region was identified as the key promoter of EphA7. Our results also indicated that EphA7 enhanced the cell proliferation of ESCC, and silence of EphA7 significantly suppressed ESCC tumor growth. Moreover, EphA7 silence markedly abolished STAT3 activation-derived cell proliferation of ESCC. Additionally, RNA-seq analyses indicated that several tumor-related signaling pathways were significantly changed after EphA7 downregulation in ESCC cells. CONCLUSION: Our results showed that the transcriptional expression of EphA7 was increased by activated STAT3, and the STAT3 signaling may act through EphA7 to promote the development of ESCC.

Dietary ginger polysaccharides (Gps) improve symptoms in hyperlipidemia rats via alterations in gut microbiota.

The aim of this research is to investigate lipid-lowering influence of dietary ginger (Zingier officinales Rocs) polysaccharides (GPS) on hyperlipidemia rats. Rat models with hyperlipidemia was established by high-fat food diet (HFD). Comparing to GP-negative model group, GPS attenuated several effects of HFD feeding, including the levels of blood lipid biochemistry, serum inflammatory markers (tumor necrosis factor TNF-a, interleukin IL-6), antioxidant capacity (superoxide dismutase SOD, glutathione peroxidase GSH-Px, total antioxidant capacity T-AOC, propylene dialdehyde MDA), uric acid and immune index. 16 S rDNA gene sequencing of fecal samples showed that GPS increased the growth of Akkermansia muciniphila and decreased the proportion of Firmicutes to Bacteroidetes; This changes in microbial community structure can help prevent diet-induced metabolic disease. These results suggest that GPs may act on the gut, changing the structure of the gut microbial community, thereby reducing intestinal and systemic inflammation, thus improved metabolic outcomes.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

[Composition changes reveal relationship between color and enzymatic reaction of Magnoliae Officinalis Cortex during "sweating" process].

In this study, we employed Q Exactive to determine the main differential metabolites of Magnoliae Officinalis Cortex du-ring the "sweating" process. Further, we quantified the color parameters and determined the activities of polyphenol oxidase(PPO), peroxidase(POD), and tyrosinase of Magnoliae Officinalis Cortex during the "sweating" process. Gray correlation analysis was performed for the color, chemical composition, and enzyme activity to reveal the effect of enzymatic reaction on the color of Magnoliae Officinalis Cortex during the "sweating" process. Magnoliae Officinalis Cortex sweating in different manners showed similar metabolite changes. The primary metabolites that changed significantly included amino acids, nucleotides, and sugars, and the secondary metabolites with significant changes were phenols and phenylpropanoids. Despite the different sweating methods, eleven compounds were commonly up-regulated, including L-glutamic acid, acetylarginine, hypoxanthine, and xanthine; six compounds were commonly down-re-gulated, including L-arginine, L-aspartic acid, and phenylalanine. The brightness value(L~*), red-green value(a~*), and yellow-blue value(b~*) of Magnoliae Officinalis Cortex kept decreasing during the "sweating" process. The changes in the activities of PPO and POD during sweating were consistent with those in the color parameter values. The gray correlation analysis demonstrated that the main differential metabolites such as amino acids and phenols were closely related to the color parameters L~*, a~* and b~*; POD was correlated with amino acids and phenols; PPO had strong correlation with phenols. The results indicated that the color change of Magnoliae Officinalis Cortex during "sweating" was closely related to the reactions of enzymes dominated by PPO and POD. The study analyzed the correlations among the main differential metabolites, color parameters, and enzyme activities of Magnoliae Officinalis Cortex in the "sweating" process. It reveals the common law of material changes and ascertains the relationship between color changes and enzymatic reactions of Magnoliae Officinalis Cortex during "sweating". Therefore, this study provides a reference for studying the "sweating" mechanism of Magnoliae Officinalis Cortex and is of great significance to guarantee the quality of Magnoliae Officinalis Cortex.

De-ubiquitination of p300 by USP12 Critically Enhances METTL3 Expression and Ang II-induced cardiac hypertrophy.

Stresses, such as neurohumoral activation, induced pathological cardiac hypertrophy is the main risk factor for heart failure. The ubiquitin-proteasome system (UPS) plays a key role in maintaining protein homeostasis and cardiac function. However, research on the role and mechanism of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is limited. Here, we observe that the deubiquitinating enzyme ubiquitin-specific protease 12(USP12) is upregulated in Ang II-induced hypertrophic hearts and primary neonatal rat cardiomyocytes (NRCMs). Inhibition of USP12 ameliorate Ang II-induced myocardial hypertrophy, while overexpression of USP12 have the opposite effect. USP12 deficiency also significantly attenuate the phenotype of Ang II-induced cardiac hypertrophy in vivo. Moreover, we demonstrate that USP12 aggravate Ang II-induced cardiac hypertrophy by enhancing METTL3, a methyltransferase which catalyze N6-methyladenosine (m6A) modification on messenger RNA and acts as a harmful factor in pathological cardiac hypertrophy. Upregulation of METTL3 reverse the reduction of myocardial hypertrophy induced by USP12 silencing in NRCMs. In contrast, knockdown of METTL3 attenuate the aggravation of myocardial hypertrophy in USP12-overexpressing NRCMs. Furthermore, we discover that USP12 promote the expression of METTL3 via upregulating p300. Mechanistically, USP12 binds and stabilizes p300, thereby activating the transcription of its downstream gene METTL3. Finally, our data show that USP12 is partially dependent on the stabilization of p300 to activate METTL3 expression and promote myocardial hypertrophy. Taken together, our results demonstrate that USP12 acts as a pro-hypertrophic deubiquitinating enzyme via enhancing p300/METTL3 axis, indicating that targeting USP12 could be a potential treatment strategy for pathological cardiac hypertrophy.

[Distal radius T-plate for 18 patients with vertical shear medial malleolus fractures].

OBJECTIVE: To explore clinical effects of distal radius T-plates in treating vertical shear medial malleolus fractures. METHODS: From March 2014 and March 2016, clinical data of 18 patients with vertical shear medial malleolus fractures were retrospectively analyzed, including 12 males and 6 females aged from 22 to 63 years old with an average of (41.3±5.2) years old; 6 patients were on the left side and 12 patients were on the right side; 5 patients combined with external malleolus fractures and 13 patients combined with external malleolus and posterior malleolus fractures. All patients were treated with distal radius T-plate fixation. Fracture healing time, loss of reduction, stability of internal fixation, occurrence of osteoarthritis were observed, postoperative AOFAS score at 12 months was used to evaluate clinical effects. RESULTS: All patients were followed up from 18 to 36 months with an average of (22.5±4.3) months. All incisions healed well at stageⅠ. Review of X-ray showed that ankle joints were got anatomically reset. All fractures healed well ranged from 12 to 18 weeks with an average of (13.4±2.4) weeks. After surgery, patients resumed normal walking from 12 to 17 weeks with an average of (14.5±1.3) weeks. No complications such as loss of reduction, loosening or rupture of internal fixation, nonunion of fracture, radiographic appearance of osteoarthritis occurred during following up. AOFAS scores was 92.4 ±6.7 at 12 months after operation, and 15 patients got excellent result, 3 moderate. CONCLUSION: Distal radius T-plates for treatment of vertical shear medial malleolus fractures have advantages of firm fixation, conforming to biomechanical requirements, better matching with plate anatomy, and less soft tissue stimulation. It could achieve early function exercise, obtain good recovery of function, and it is an ideal choice for the treatment of vertical shear medial malleolus fractures.

[Study on regulation of NLRP3/SOCS3-TLR4-NF-κB inflammatory pathway by wogonoside to improve hepatic insulin resistance].

This study was to investigate the hypoglycemic effect of wogonoside to improve hepatic insulin resistance( IR) and its relative anti-inflammatory mechanism. The stable IR-Hep G2 cell model was established by the combination of 1×10-9 mol·L-1 insulin and 3. 75×10-6 mol·L-1 dexamethasone for 48 hours. The changes of glucose consumption in IR-Hep G2 cells with different concentrations of wogonoside( 1,5,10,20,50 µmol·L-1) at different time points( 30,36,48,54 h) were detected by glucose oxidase assay to determine the optimal onset time. Glycogen content and cell viability were respectively detected by ketone method and CCK-8 method. Cryptothermal protein 3( NLRP3),suppressor of cytokine signaling 3( SOCS3),Toll-like receptor 4( TLR4),nuclear factor( NF-κB),interleukin( IL-1ß),IL-6,tumor necrosis factor( TNF-α) involving in the inflammatory signaling pathway,as well as leptin,Ob-R,p-IRS2/IRS2,p-PI3 K/PI3 K( p85),p-Akt/Akt and glucose transporter( GLUT1/2/4) involving in the insulin signaling pathway were detected in IR-HepG2 cells by Western blot. RESULTS: showed that 20 and 50 µmol·L-1 wogonoside significantly up-regulated the glucose consumption of IR-HepG2 cells( P<0. 001) as compared with IR model group,and the optimal onset time was 48 h.Wogonoside had no obvious effect on the cell viability of Hep G2 cells. Further studies showed that 20,50 µmol·L-1 wogonoside respectively increased the glycogen content of IR-HepG2 cells after 48 h treatment,especially in 50 µmol·L-1 group( P<0. 001). Compared with IR model group,wogonoside not only inhibited the protein expression of inflammatory nuclear transcriptional factors NLRP3,SOCS3,TLR4,NF-κB,but also decreased the expression of downstream inflammatory effect factors IL-1ß,IL-6 and TNF-α． In addition,wogonoside elevated Ob-R,p-IRS2/IRS2,p-PI3 K/PI3 K( p85),p-Akt/Akt and GLUT1/2/4 protein expression,whereas it suppressed leptin expression that was regulated by SOCS3. Wogonoside could promote glucose uptake and increase glycogen content to enhance insulin sensitivity in IR-Hep G2 cells. The hypoglycemic effect may be related to the intervention of NLRP3/SOCS3-TLR4-NF-κB inflammatory pathway and decrease of inflammatory factor expression.

Treatment of chronic heart failure in the 21st century: A new era of biomedical engineering has come.

Chronic heart failure (CHF) is a challenging burden on public health. Therapeutic strategies for CHF have developed rapidly in the past decades from conventional medical therapy, which mainly includes administration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists, to biomedical engineering methods, which include interventional engineering, such as percutaneous balloon mitral valvotomy, percutaneous coronary intervention, catheter ablation, biventricular pacing or cardiac resynchronization therapy (CRT) and CRT-defibrillator use, and implantable cardioverter defibrillator use; mechanical engineering, such as left ventricular assistant device use, internal artery balloon counterpulsation, cardiac support device use, and total artificial heart implantation; surgical engineering, such as coronary artery bypass graft, valve replacement or repair of rheumatic or congenital heart diseases, and heart transplantation (HT); regenerate engineering, which includes gene therapy, stem cell transplantation, and tissue engineering; and rehabilitating engineering, which includes exercise training, low-salt diet, nursing, psychological interventions, health education, and external counterpulsation/enhanced external counterpulsation in the outpatient department. These biomedical engineering therapies have greatly improved the symptoms of CHF and life expectancy. To date, pharmacotherapy, which is based on evidence-based medicine, large-scale, multi-center, randomized controlled clinical trials, is still a major treatment option for CHF; the current interventional and mechanical device engineering treatment for advanced CHF is not enough owing to its individual status. In place of HT or the use of a total artificial heart, stem cell technology and gene therapy in regenerate engineering for CHF are very promising. However, each therapy has its advantages and disadvantages, and it is currently possible to select better therapeutic strategies for patients with CHF according to cost-efficacy analyses of these therapies. Taken together, we think that a new era of biomedical engineering for CHF has begun.

Inhibition of the IGF signaling pathway reverses cisplatin resistance in ovarian cancer cells.

BACKGROUND: This study was aimed at investigating whether metformin can reverse the resistance of ovarian cancer cells to cisplatin and exploring the underlying mechanism. METHODS: Ovarian cancer cell proliferation in vitro was evaluated using a CCK-8 assay. The resistance index of platinum-resistant ovarian cancer cells was determined and cell cycle and apoptosis rate determined by annexin V/propidium iodide double-staining in CP70 cells. Western blotting was used to determine IGF1, IGF1R, AKT, p-IGF1, p-IGF1R, p-AKT, and MRP2 levels in cells treated with different concentrations of metformin and LY29400, an inhibitor of the insulin-like growth factor pathway. Changes in gene expression levels of MRP2, IGF1, IGF1R, and AKT were determined by fluorescence real-time quantitative PCR assay of CP70 cells treated with metformin. Tumors of human ovarian cancer cell lines CP70 and A2780 were established by subcutaneous transplantation of cells in nude mice and the effect of metformin on MRP2 expression and tumor inhibition assessed. RESULTS: The IC50 value of cisplatin in CP70 cells decreased significantly as metformin concentration increased (P < 0.05). The cell cycle distribution in CP70 cells changed with metformin treatment; the percentage of cells in the G0/G1 phase, as well as the natural apoptosis rate was significantly increased with metformin treatment (P < 0.05). IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002. Moreover, changes in the expression of MRP2, IGF1, IGF1R, and AKT was metformin-concentration dependent, and was significantly different from that in the untreated control group (P < 0.05). In nude mice, the tumor volumes of the cisplatin-treated groups were significantly less than in the control group, and was further suppressed by co-treatment with cisplatin and metformin (P < 0.05), indicating that these 2 drugs had a synergistic effect on tumor inhibition. CONCLUSION: Metformin can improve the sensitivity of ovarian cancer CP70 cells to cisplatin in a concentration-dependent manner by activating the AKT signaling pathway, inhibiting the IGF1R signaling pathway, and reducing MRP2 expression.

Novel strategies halt cardiovascular, diabetes, and cancer strips.

In this article, we introduce briefly several strategies for preventing atherosclerotic cardiovascular disease and promoting healthcare for non-communicable diseases (NCDs). These novel strategies include four core elements of health - sleep, emotion, exercise, and diet - and consist of SEED intervention (SEEDi) and E(e)SEEDi due to supplementation of the environment as a core element, and Hu's healthy lifestyles intervention (HHLi) which originates from E(e)SEED-BasED healthy lifestyles. They are suitable for the early evaluation of risk factors, and play a key role in the prevention and management of human NCDs when combined with the RT-ABCDEF strategy and the Grade 210 prevention, which include obesity-OSA-hypertension syndrome and C-type hypertension, especially in halting cardiovascular, diabetes and cancer (CDC) strips we first discovered. After successful clinical practice, we may expect our novel strategies for controlling these chronic diseases according to the conception of mass prevention and treatment.

Effect of propofol, sevoflurane, and isoflurane on postoperative cognitive dysfunction following laparoscopic cholecystectomy in elderly patients: A randomized controlled trial.

STUDY OBJECTIVE: To compare the incidence of postoperative cognitive dysfunction (POCD) in elderly surgical patients (>60years) receiving different anesthetics (propofol, sevoflurane, or isoflurane) and to identify potential biomarkers of POCD in this patient population. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: University-affiliated teaching hospital. PATIENTS: One hundred and fifty elderly patients scheduled for laparoscopic cholecystectomy. INTERVENTIONS: Elderly patients undergoing laparoscopic cholecystectomy were randomly assigned to receive propofol, sevoflurane, or isoflurane anesthesia. MEASUREMENTS: Cognitive function was assessed using neuropsychological tests at baseline (1day before surgery [D0]), and on postoperative day 1 (D1) and day 3 (D3). Plasma S-100ß and Aß1-40 protein, IL-1ß, IL-6 and TNF-α concentrations were assessed before induction of anesthesia (T0), after extubation (T1), and 1h (T2) and 24h (T3) postoperatively. MAIN RESULTS: The incidence of POCD was significantly lower in the propofol group compared to the isoflurane group and the sevoflurane group at D1 and D3 (propofol vs. isoflurane: D1 and D3, P<0.001; propofol vs. sevoflurane: D1, P=0.012; D3, P=0.013). The incidence of POCD was significantly lower in the sevoflurane group compared to the isoflurane group at D1 (P=0.041), but not at D3. Postoperatively, plasma S-100ß and Aß1-40 protein, IL-1ß, IL-6, and TNF-α concentrations were significantly decreased in the propofol group compared to the isoflurane group. CONCLUSIONS: Propofol anesthesia may be an option for elderly surgical patients.

Open and Endovascular Management of Severe Cerebral Ischemia in Takayasu's Arteritis.

BACKGROUND: Severe cerebral ischemia in patients with Takayasu's arteries was caused by occlusion of most supra-aortic arteries. Arterial revascularization is necessary to decrease the incidence of stroke and improve the quality of life but may be complicated with multiple occlusive lesions and inflammation condition of this disease. This study was to assess options and long-term outcomes of surgical and endovascular treatment. METHODS: Twenty-nine patients with severe cerebral ischemic symptoms underwent surgical or endovascular treatment from January 1991 to July 2015. Demographic characteristics, surgical and endovascular procedures, and follow-up outcomes were reviewed. Risk factors associated with primary patency of surgical treatment and assisted primary patency of endovascular treatment was identified by Cox regression analyses. RESULTS: There were 29 patients with a median age of 24 (range 9-37 years), 9 in active and 20 in inactive phase. Seventeen patients underwent a variety of bypass procedures. Fourteen endovascular procedures were performed in 12 patients. No death occurred within 30 days after both procedures. Complications within 30 days after bypass included stroke in 1 patient, infection in 2 patients, and heart failure in 1 patient. Nine patients developed brain hyperperfusion after bypass. Transient hemiplegic paralysis occurred in 1 patient during dilation of the carotid artery. During a median follow-up time of 41 months, primary and secondary patency rate of bypass at 1 and 3 years was 93.75% and 100% and 87.5% and 100%, respectively. Assisted primary and secondary patency rate of endovascular treatment at 1 and 3 years was 85.71% and 92.86% and 68.18% and 75.66%, respectively. There was no independent risk factor associated with either primary patency of surgical treatment or assisted primary patency of endovascular treatment. Disease activity was independent risk factor associated with combined rate of primary patency of surgical treatment and assisted primary patency of endovascular treatment (HR: 0.17, 95% CI: 0.03-0.93, P = 0.04). CONCLUSIONS: Bypass is the preferred treatment in majority of patients with good long-term patency, even has a higher propensity for postoperative complications. Endovascular treatment should be preserved for short lesions in inappropriate or high-risk surgical patients but needs more reintervention and close monitoring of lesion for better outcomes. Long-term patency of surgical and endovascular treatment is related with disease activity. Combination of surgical or endovascular treatment and medical therapy may improve the efficacy of interventions.

[RITA combined with temozolomide inhibits the proliferation of human glioblastoma U87 cells].

OBJECTIVE: To observe the effect of RITA, a small molecule that targets p53, combined with temozolomide (TMZ) on proliferation, colony formation and apoptosis of human glioblastoma U87 cells and explore the underlying mechanism. METHODS: Cultured U87 cells were treated with RITA (1, 5, 10, 20 µmol/L), TMZ, or RITA+TMZ (half dose) for 24, 48 or 72 h. MTS assay were used to detect the cell proliferation, and the cell proliferation rate and inhibitory rate were calculated. The effect of combined treatments was evaluated by the q value. The expressions of p53, p21 and other apoptosis-associated genes were detected by qRT-PCR and Western blotting; cell apoptosis was assayed using flow cytometry with Annexin V/PI double staining; colony formation of the cells was detected with crystal violet staining. RESULTS: MTS assay showed that RITA at the 4 doses more potently inhibited U87 cell viability than TMZ at 72 h (P=0.000) with inhibitory rates of 25.94%-41.38% and 3.84%-8.20%, respectively. RITA combined with TMZ caused a more significant inhibition of U87 cells (29.21%-52.11%) than RITA (P<0.01) and TMZ (P=0.000) alone. At the doses above 5 µmol/L, the combined treatments with RITA+TMZ for 48 h resulted in q values exceeding 1.2 and showed an obvious synergistic effect of the drugs. Both RITA and TMZ, especially the latter, significantly increased the expressions of p53, p21, puma, and other apoptosis-associated genes to accelerate apoptosis and inhibit the growth and colony formation of U87 cells, and the effect was more obvious with a combined treatment. CONCLUSION: RITA inhibits the growth of human glioblastoma cells and enhance their sensitivity to TMZ by up-regulating p53 expression, and when combined, RITA and TMZ show a synergistic effect to cause a stronger cell inhibition.

Toxic potential of palytoxin.

This review briefly describes the origin, chemistry, molecular mechanism of action, pharmacology, toxicology, and ecotoxicology of palytoxin and its analogues. Palytoxin and its analogues are produced by marine dinoflagellates. Palytoxin is also produced by Zoanthids (i.e. Palythoa), and Cyanobacteria (Trichodesmium). Palytoxin is a very large, non-proteinaceous molecule with a complex chemical structure having both lipophilic and hydrophilic moieties. Palytoxin is one of the most potent marine toxins with an LD50 of 150 ng/kg body weight in mice exposed intravenously. Pharmacological and electrophysiological studies have demonstrated that palytoxin acts as a hemolysin and alters the function of excitable cells through multiple mechanisms of action. Palytoxin selectively binds to Na(+)/K(+)-ATPase with a Kd of 20 pM and transforms the pump into a channel permeable to monovalent cations with a single-channel conductance of 10 pS. This mechanism of action could have multiple effects on cells. Evaluation of palytoxin toxicity using various animal models revealed that palytoxin is an extremely potent neurotoxin following an intravenous, intraperitoneal, intramuscular, subcutaneous or intratracheal route of exposure. Palytoxin also causes non-lethal, yet serious toxic effects following dermal or ocular exposure. Most incidents of palytoxin poisoning have manifested after oral intake of contaminated seafood. Poisonings in humans have also been noted after inhalation, cutaneous/systemic exposures with direct contact of aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing Cnidarian zoanthids. Palytoxin has a strong potential for toxicity in humans and animals, and currently this toxin is of great concern worldwide.

Cardiovascular, diabetes, and cancer strips: evidences, mechanisms, and classifications.

OBJECTIVES: To report and name firstly that there are cardiovascular disease (CVD), diabetes mellitus (DM) and cancers (CDC) strips; and disclose their mechanisms, classifications, and clinical significances. STUDY DESIGN: Narrative and systematic review study and interpretive analysis. DATA SOURCES AND STUDY SELECTION: to collect and present related evidences on CDC strips from evidence-based, open-access, both Chinese- and English-language literatures in recent 10 years on clinical trials from PubMed according to keywords "CVD, DM and cancers" as well as authors' extensive clinical experience with the treatment of more than fifty thousands of patients with CVD, diabetes and cancers over the past decades, and analyze their related mechanisms and categories which based on authors' previous works. DATA EXTRACTION: data were mainly extracted from 48 articles which are listed in the reference section of this review. Qualitative, quantitative and mixed data were included, narratively and systematically reviewed. RESULTS: With several conceptual and technical breakthrough, authors present related evidences on CDC strips, these are, CVD and DM, DM and cancers, cancers and CVD linked, respectively; And "Bad SEED" +/- "bad soil" theory or doctrine may explain this phenomenon due to "internal environmental injure, abnormal or unbalance" in human body resulting from the role of risk factors (RFs) related multi-pathways and multi-targets, which including organ & tissue (e.g., vascular-specific), cell and gene-based mechanisms. Their classifications include main strips/type B, and Branches/type A as showed by tables and figures in this article. CONCLUSIONS: There are CDC strips and related mechanisms and classifications. CDC strips may help us to understand, prevent, and control related common non-communicable diseases (NCDs) as well as these high risk strips.

A simple and effective coumarin-based fluorescent probe for cysteine.

Acrylic acid 3-acetyl-2-oxo-2 H-chromen-7-yl ester (ACA) was rationally designed and synthesized as a simple and effective fluorescent probe for sensing cysteine with high selectivity and naked-eye detection. The probe can detect cysteine by fluorescence spectrometry with a detection limit of 0.657 µM and can be used with calf serum and in live cell imaging. The conjugate addition/cyclization sequence mechanism of the reaction between ACA and cysteine was confirmed by ESI-MS and fluorescence spectra.

Novel pyrazoline-based fluorescent probe for detecting glutathione and its application in cells.

A novel compound, 2-(1,5-diphenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl acrylate (probe L), was designed and synthesized as a highly sensitive and selective fluorescent probe for recognizing and detecting glutathione among cysteine, homocysteine and other amino acids. The structures of related compounds were characterized using IR, NMR and HRMS spectroscopy analysis. The probe is a non-fluorescent compound. On being mixed with glutathione in buffered EtOH:PBS=3:7 solution at pH 7.4, the probe exhibited the blue emission of the pyrazoline at 474 nm and a 83-fold enhancement in fluorescence intensity. This probe is very sensitive and displayed a linear fluorescence off-on response to glutathione with fluorometric detection limit of 8.2 × 10(-8)M. The emission of the probe is pH independent in the physiological pH range. Live-cell imaging of HeLa cells confirmed the cell permeability of the probe and its ability to selectively discriminate GSH from Cys and Hcy in cells. The toxicity of the probe was low in cultured HeLa cells.

A novel pyrazoline-based selective fluorescent probe for detecting reduced glutathione and its application in living cells and serum.

A new fluorescent probe, N-(4-(1,5-diphenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-2,4-dinitrobenzenesulfonamide (probe 3), was designed and synthesized as a highly sensitive and selective fluorescent probe for recognizing and detecting glutathione among biological thiols in aqueous media. Probe 3 is a nonfluorescent compound. On being mixed with biothiols under neutral aqueous conditions, the 2,4-dinitrobenzenesulfoyl moiety can be cleaved off by glutathione, and the blue emission of the pyrazoline at 464 nm is switched on, with a fluorescence enhancement of 488-fold for glutathione. Furthermore, probe 3 was highly selective for glutathione without interference from some biologically relevant analytes. The detection limit of glutathione was 4.11 × 10(-7) M. The emission of the probe is pH independent in the physiological pH range. Moreover, the probe can be used for fluorescent imaging of cellular glutathione and can be used for detecting glutathione in calf serum.

[Evaluation of the key indicators in the pituitary-target gland axes in the animal model with shenyang deficiency syndrome using factor analysis].

OBJECTIVE: To evaluate the key indicators in the pituitary-target gland axes in the animal model of Shen-yang deficiency syndrome (SYDS). METHODS: The 8 biological indicators [thyroid stimulating hormone (TSH), 3, 3', 5-triiodothyronine (T3), thyroxine (T4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), adrenocorticotropic hormone (ACTH), and cortisol (CORT)] in the pituitary-target gland axes were grouped using factor analysis. Then the sensitivity of every indicator was calculated according to the sensitivity function defined in this paper, so as to find all the most sensitive indicators in every group as key indicators of SYDS. RESULTS: The key indicators in the early period of SYDS were T, LH, T4, and CORT. The key indicators in the middle period were LH,T, CORT, and ACTH. The key indicators in the late period were LH, T, CORT, and FSH. CONCLUSIONS: T, LH, and CORT were the common key indicators of the three periods, and other different key indicator of SYDS in the early, middle and late period were T4, ACTH, and FSH respectively, which changed from the thyroid axis to the adrenal axis and then to the gonadal axis as the period changed. The key indicators in the late period were mainly in the gonadal axis, showing gonadal dysfunction in the late period.

[Mutation analysis and first-trimester prenatal diagnosis for a Chinese family with hidrotic ectodermal dysplasia].

OBJECTIVE: To analyze GJB6 gene mutations in a Chinese family with hidrotic ectodermal dysplasia and to provide first-trimester prenatal diagnosis for a fetus. METHODS: Mutation scanning was carried out with PCR and bilateral direct sequencing in 2 affected and 6 unaffected individuals from the family. After the mutation was confirmed, prenatal diagnosis was performed on chorionic villi samples obtained at 11th gestational week. RESULTS: A heterozygous missense mutation c.31G>A of the GJB6 gene was discovered in all of the patients, which has led to substitution of glycine by arginine at codon 11 (p.G11R) at the N-terminal of the GJB6 protein. Prenatal diagnosis indicated that the fetus had also carried the same p.G11R mutation. Following termination of the pregnancy, analysis of the aborted tissues was consistent with prenatal diagnosis. CONCLUSION: The missense mutation c.31G>A(p.G11R) of the GJB6 gene probably underlies the disease in this family. Prenatal diagnosis with DNA sequencing can facilitate genetic counseling of this family.