Deciphering the in situ phonon evolution of potassium sodium niobate under varying temperature and electric fields.

The application of in situ Raman spectroscopy under multiple fields is widely recognized as an effective approach for investigating the physical mechanism of phase transitions in ferroelectrics, because it can directly provide the detailed information about the vibration evolution of various phonon modes within lattices, such as bond stretching and rotation. Based on this technique, our work aims to thoroughly probe the dynamics of phase transitions in traditional ferroelectric potassium sodium niobate [(K,Na)NbO3, KNN] under external fields, by analyzing the in situ dependence of wavenumber and intensity of phonon modes under the varying temperature and electric fields. The results indicate that different vibration modes respectively relating to the A-site ions and NbO6 octahedra in KNN exhibit distinct and abrupt distortion behavior during the orthorhombic-tetragonal and tetragonal-cubic transitions. Moreover, a certain degree of distortion can still be observed in the cubic phase above the Curie temperature. With an applied electric field, KNN presents quite different electrostriction in orthorhombic and tetragonal phases. Particularly, more than one kind of phonon mode undergoes non-linear variations under the varying electric fields, accompanied by the mutations at some fixed fields. These findings will be conducive to further understanding the phase transition mechanism in KNN from the perspective of phonon evolution. Simultaneously, it will also give crucial guidance for the design and development of KNN-based ferroelectrics as well as functional devices.

[Analysis of the efficacy and safety of pulsed radiofrequency for the treatment of thoracic postherpetic neuralgia in elderly patients with different pain phenotypes].

Objective: To analyze the efficacy and safety of pulsed radiofrequency (PRF) for the treatment of thoracic postherpetic neuralgia (PHN) in elderly patients with different pain phenotypes. Methods: A total of 201 elderly thoracic PHN patients, including 110 males and 91 females aged (72.2±6.9) years who received high-voltage, long-duration PRF at the dorsal root ganglion at Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine from January 2020 to December 2022, were retrospectively included. The neuropathic pain symptom inventory (NPSI) was used to evaluate the five different pain phenotypes, which included superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia, and to analyze the distribution of the five pain phenotypes. The numerical rating scale (NRS) and NPSI scores of all patients were compared before treatment and three months after treatment to evaluate the efficacy and safety of PRF for different pain phenotypes and pain phenotype combinations. Results: All patients had two or more pain phenotypes, and 50.2% (101/201) of the patients had five pain phenotypes at the same time. Compared with those before treatment, three months after treatment, the NPSI scores for superficial spontaneous pain, deep spontaneous pain, paroxysmal pain, evoked pain and paresthesia/dysesthesia decreased (all P<0.05), and the scores decreased byï¼»M（Q1，Q3）］3.0 (2.0, 4.0), 1.5 (0.5, 2.5), 3.0 (2.5, 4.0), 2.3 (1.0, 4.0), and 1.0 (0.5, 2.0) points, respectively, the differences were statistically significant (P<0.001). The decrease in the NPSI score in patients with paroxysmal pain was greater than that in patients with the other 4 pain phenotypes (all P<0.05). After treatment, the NRS score decreased by 4.0 (3.0, 5.0), 4.0 (3.0, 5.0), 4.0 (3.0, 5.0) and 5.0 (4.0, 6.0) points in patients with 2, 3, 4 and 5 pain phenotypes, respectively, and the difference was statistically significant (P<0.001). The decrease in the NRS score was greater in patients with a combination of 5 pain phenotypes than that in patients with a combination of 3 and 4 pain phenotypes (all P<0.05). No complications, such as pneumothorax, haematoma or infection, occurred in any of the patients during treatment. Conclusion: PRF has different therapeutic effects on PHN patients with different pain phenotypes, it has the best effect on paroxysmal pain, and the treatment is safe.

[Acidophil stem cell pituitary neuroendocrine tumors/adenoma: a clinicopathological analysis of five cases].

Objective: To investigate the clinicopathological characteristics of acidophil stem cell pituitary neuroendocrine tumors (PitNET)/adenoma. Methods: Five cases of acidophil stem cell PitNET/adenoma were diagnosed between May 2022 and July 2023 at the Second Hospital of Hebei Medical University, Shijiazhuang, China. The clinicopathological features of the tumor were analyzed by using histology, immunohistochemistry, and electron microscopy. The relevant literature was reviewed. Results: There were 1 male and 4 females, aged from 23 to 69 years. Patient 3 was 55 years old at the time of diagnosis and first surgery, and relapsed 5 years later. The patients' median age was 32 years. Patients 1 and 5 showed elevated blood prolactin, with various degrees of hormonal symptoms except Patient 3, who showed only tumor compression symptoms. Imaging studies showed that all cases involved the sellar floor. The tumors of Patients 1, 2 and 5 were closely related to the cavernous sinus segment of the internal carotid artery. The tumors exhibited a diffuse growth pattern with chromophobic to slightly acidophilic cytoplasm. A few of tumor cells showed chromophobic cytoplasm. The nucleoli were conspicuous. Intranuclear inclusion bodies and variably-sized clear vacuoles were observed occasionally. Under electron microscope, marked mitochondrial abnormalities were observed, including increased mitochondria number, expanded hypertrophy, and absence of mitochondrial ridge fracture. Some mitochondrial matrices were dense, while some were vacuolated. Conclusions: Acidophil stem cell PitNET/adenoma is a rare type of pituitary adenomas/PitNETs. It often has a more clinically aggressive manner with immature cells, diffuse expression of PIT1, prolactin, and varying degrees of growth hormone expression. Because of the obvious diversity of their clinical hormone status and hormone immune expression, the diagnosis of this type tumor is still a challenge.

Del Nido cardioplegia or potassium induces Nrf2 and protects cardiomyocytes against oxidative stress.

Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We addressed here whether cardioplegia essential for cardiopulmonary bypass surgery activates Nrf2, a transcription factor regulating the expression of antioxidant and detoxification genes. With commonly used cardioplegic solutions, high K+, low K+, Del Nido (DN), histidine-tryptophan-ketoglutarate (HTK), and Celsior (CS), we found that DN caused a significant increase of Nrf2 protein in AC16 human cardiomyocytes. Tracing the ingredients in DN led to the discovery of KCl at the concentration of 20-60 mM capable of significant Nrf2 protein induction. The antioxidant response element (ARE) luciferase reporter assays confirmed Nrf2 activation by DN or KCl. Transcriptomic profiling using RNA-seq revealed that oxidation-reduction as a main gene ontology group affected by KCl. KCl indeed elevated the expression of classical Nrf2 downstream targets, including TXNRD1, AKR1C, AKR1B1, SRXN1, and G6PD. DN or KCl-induced Nrf2 elevation is Ca2+ concentration dependent. We found that KCl decreased Nrf2 protein ubiquitination and extended the half-life of Nrf2 from 17.8 to 25.1 mins. Knocking out Keap1 blocked Nrf2 induction by K+. Nrf2 induction by DN or KCl correlates with the protection against reactive oxygen species generation or loss of viability by H2O2 treatment. Our data support that high K+ concentration in DN cardioplegic solution can induce Nrf2 protein and protect cardiomyocytes against oxidative damage.NEW & NOTEWORTHY Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We report here that Del Nido cardioplegic solution or potassium is an effective inducer of Nrf2 transcription factor, which controls the antioxidant and detoxification response. This indicates that Del Nido solution is not only essential for open heart surgery but also exhibits cardiac protective activity.

Nrf2 signaling in heart failure: expression of Nrf2, Keap1, antioxidant, and detoxification genes in dilated or ischemic cardiomyopathy.

Increased levels of oxidative stress have been found with heart failure. Whether failing hearts express antioxidant and detoxification enzymes have not been addressed systematically. Nrf2 gene encodes a transcription factor that regulates the expression of antioxidant and detoxification genes. Using RNA-Seq data set from explanted hearts of 37 patients with dilated cardiomyopathy (DCM), 13 patients with ischemic cardiomyopathy (ICM), and 14 nonfailure (NF) donors as a control, we addressed whether failing hearts change the expression of Nrf2, its negative regulator Keap1, and antioxidant or detoxification genes. Significant increases in the ratio of Nrf2 to Keap1 were found to associate with DCM or ICM. Antioxidant genes showed decreased expression in both types of heart failure, including NQO1, SOD1, GPX3, GPX4, GSR, PRDX1, and TXNRD1. Detoxification enzymes, GCLM and EPHX1, also showed decreased expression, whereas the CYP1B1 transcript was elevated in both DCM and ICM. The genes encoding metal-binding protein ferritin were decreased, whereas five out of 12 metallothionein genes showed elevated expression. Our finding on Nrf2 gene expression has been validated by meta-analysis of seven independent data sets of microarray or RNA-Seq for differential gene expression in DCM and ICM from NF controls. In conclusion, minor elevation of Nrf2 gene expression is not coupled to increases in antioxidant and detoxification genes, supporting an impairment of Nrf2 signaling in patients with heart failure. Decreases in multiple antioxidant and detoxification genes are consistent with the observed increases of oxidative stress in failing hearts.

Metabolomics of oxidative stress: Nrf2 independent depletion of NAD or increases of sugar alcohols.

Nrf2 encodes a transcription factor best known for regulating the expression of antioxidant and detoxification genes. Recent evidence suggested that Nrf2 mediates metabolic reprogramming in cancer cells. However, the role of Nrf2 in the biochemical metabolism of cardiac cells has not been studied. Using LC-MS/MS-based metabolomics, we addressed whether knocking out the Nrf2 gene in AC16 human cardiomyocytes affects metabolic reprogramming by oxidative stress. Profiling the basal level metabolites showed an elevated pentose phosphate pathway and increased levels of sugar alcohols, sorbitol, L-arabitol, xylitol and xylonic acid, in Nrf2 KO cells. With sublethal levels of oxidative stress, depletion of NAD, an increase of GDP and elevation of sugar alcohols, sorbitol and dulcitol, were detected in parent wild type (WT) cells. Knocking out Nrf2 did not affect these changes. Biochemical assays confirmed depletion of NAD in WT and Nrf2 KO cells due to H2O2 treatment. These data support that although Nrf2 deficiency caused baseline activation of the pentose phosphate pathway and sugar alcohol synthesis, a brief exposure to none-lethal doses of H2O2 caused NAD depletion in an Nrf2 independent manner. Loss of NAD may contribute to oxidative stress associated cell degeneration as observed with aging, diabetes and heart failure.

[Early loss of primary molar and permanent tooth germ caused by the use of devitalizer during primary molar root canal therapy: Two cases report].

Devitalization has been widely used in the root canal therapy of primary and permanent teeth in China more than ten years ago. With the development of local anesthetic drugs and injection technologies, this treatment method with high potential risks has been gradually abandoned. However, a questionnaire survey targeted all the participants at the 2018 China Pediatric Dentistry Conference showed that the devitalizer utilization proportion was still as high as 38.1% (383/1 005), even though the ratio was much lower than 75.5% (105/139) in 2003. These doctors had pay more attention to tissue burn caused by devitalizer marginal leakage or direct leakage, and know how to identify and handle with devitalizer burn. Devitalizers were usually made of arsenic trioxide, metal arsenic or paraformaldehyde, which have cytotoxicity, allergenicity, mutagenicity, carcinogenicity, and teratogenic effects on animals. Marginal leakage of devitalizers have high risks of causing soft and hard tissue necrosis. Most of the dentists have an understanding of the potential damages of arsenic containing devitalizers, so they will choose parafor maldehyde with relatively less toxicity. Paraformaldehyde has a certain self limitation, and there are few cases reported, so some dentists lack of vigilance. Paraformaldehyde can also causes tissue necrosis if leakage happens, and the treatment methods are similar to that of arsenic containing devitalizers. When handling with devitalizers burn, the necrosed soft and hard tissue, for example gingiva, alveolar bone or teeth that cannot keep, must be completely removed until fresh blood appears, then rinse with large amount of saline and seal with iodoform gauze. This paper described two cases of devitalizer burn during the root canal treatment of primary molars, both of the doctors failed to identify the devitalizer burn symptoms in the early stage, thus didn't do proper treatments immediately after burning. Resulting in the necrosis of large area of gingiva and alveolar bone, loss of primary molars and permanent tooth germs 1-2 months after devitalizer burn. This paper reported these two cases in detail in order to warn dentists the high risks of using any kind of devitalizers, help them learn how to identify and treat devitalizer burn, and remind them to stop using devitalizers as soon as possible.

[Association study between the KCNE family gene polymorphisms of potassium channel gene and the susceptibility of atrial fibrillation].

Objective: To investigate the relationship between KCNE family gene polymorphisms of potassium channel gene and the susceptibility of atrial fibrillation (AF). Methods: In the case-control study, a total of 648 subjects were studied, of which 338 patients with atrial fibrillation were selected from the Department of Cardiovascular Medicine, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2019 to December 2019, and 310 healthy people were selected from the physical examination population during the same period. DNA sequencing technology and polymerase chain reaction (PCR) were used to detect the genotype and allele frequency of rs1805127 of KCNE1, rs9984281 of KCNE2, rs9516, rs626930 of KCNE3 and rs12621643 of KCNE4. Results: The ages of subjects in atrial fibrillation group and control group were (69±13) and (73±8) years, respectively (P=0.077). Men subjects accounted for 57.70% (195 men) and 40.00% (124 men) in the two groups, respectively (P=0.092). The distribution frequencies of the allele C at rs1805127 of gene KCNE1, the allele A at rs9984281 of gene KCNE2 and the allele G at rs12621643 of gene KCNE4 were significantly different between groups (P<0.05). After adjustment for sex, smoking, hypertension, cardiac insufficiency and other factors, it was found that the increase in the frequency of the above three loci would increase the risk of atrial fibrillation (rs1805127 OR=7.064, 95%CI:1.559-31.997; rs9984281 OR=4.210, 95%CI:1.118-15.850; rs12621643 OR=2.679, 95%CI:1.025-6.998). Conclusion: The rs1805127 of KCNE1, the rs9984281 of KCNE2,the rs12621643 of KCNE4 were significantly associated with the susceptibility to atrial fibrillation.

Blood group alters platelet binding kinetics to von Willebrand factor and consequently platelet function.

Blood type O is associated with a lower risk of myocardial infarction. Platelets play a critical role in myocardial infarction. It is not known whether the expression of blood group antigens on platelet proteins alters platelet function; we hypothesized that platelet function would be different between donors with blood type O and those with non-O. To address this hypothesis, we perfused blood from healthy type O donors (n = 33) or non-O donors (n = 54) over pooled plasma derived von Willebrand factor (VWF) protein and purified blood type-specific VWF at arterial shear and measured platelet translocation dynamics. We demonstrate for the first time that type O platelets travel farther at greater speeds before forming stable bonds with VWF. To further characterize these findings, we used a novel analytical model of platelet interaction. Modeling revealed that the kinetics for GPIb/VWF binding rate are significantly lower for type O compared with non-O platelets. Our results demonstrate that platelets from type O donors interact less with VWF at arterial shear than non-O platelets. Our results suggest a potential mechanism for the reduced risk of myocardial infarction associated with blood type O.

A systematic review of olfactory related questionnaires and scales.

PURPOSE: Although neglected by science for a long time, the sense of olfaction has received increasing attention from research areas including psychology, neuroscience, clinical medicine and nutrition. With the rise of psychophysical and neuroimaging re- search into olfaction, psychometric tools (e.g. questionnaires and scales) are the basis for the quantitative exploration of inter-in- dividual variability regarding olfactory related responses. The current systematic review is to summarize existing olfaction related questionnaires and/or scales. METHODS: Peer-reviewed literature on scales and questionnaires related to perception of odors were searched from online databa- ses (PubMed, Web of Science and PsycINFO). Twenty-one articles that meet the following criteria were included in the review: "human species", "physical odor stimuli" and "describing the original development of the tool" and "specific focus on olfaction or odor related responses or behaviors". The psychometric properties, advantages and possible disadvantages were discussed. RESULTS: Existing psychometric measures focus on various aspects of olfactory related responses and behaviors, including af- fective experiences of odor perception, awareness and attitude towards olfaction, olfactory function and the quality of life change due to olfactory dysfunction, and the ability to create vivid mental odor images. While most of them have been tested to have good reliability and validity, some were relatively time-consuming due to the number of questionnaire items. Besides, although many measures have been used in clinical populations, few have provided information on the predictive validity regarding effecti- veness of clinical intervention on changes of certain responses or behaviors. SUMMARY: The current review provides an overview of olfactory related questionnaires and scales, highlighting the emotional and affective impact of olfaction and the impact on quality of life due to olfactory dysfunction. With growing interest in olfaction as an important sense, the development and use of psychometrically sound measurements in conjunction with objective assess- ments will advance our understanding of human olfaction and olfactory dysfunction. The review provides a guide for researchers and clinicians alike to select olfactory scales suitable for olfactory research with different experimental purposes and specific samples.

[Relationship between insulin resistance, serum VCAM-1, FGF19, IGF-1 and colorectal polyps].

Objective: To explore the relationship between insulin resistance, glucose and lipid metabolism related molecules and colorectal polyps. Methods: A total of 262 healthy people who underwent colonoscopy in Shandong cancer hospital from June 2019 to September 2020 were selected. The levels of serum vascular cell adhesion molecule-1 (VCAM-1), fibroblast growth factor 19 (FGF19), insulin like growth factor (IGF-1), fasting blood glucose and fasting blood insulin were detected by enzyme-linked immunosorbent assay (ELISA). Insulin resistance index (HOMA-IR) was calculated, and the influencing factors of occurrence, pathological type, size and number of polyps were analyzed. Results: Among 262 cases, 116 cases were polyp free, 113 cases were adenomatous polyp and 33 cases were inflammatory polyp. HOMA-IR, VCAM-1 and FGF19 in polyp group were 2.904±1.754, (334.415±139.573) ng/ml and (135.865±98.470) pg/ml, respectively, which were higher than 2.369±1.306, (302.480±99.946) ng/ml and(110.694±76.044) ng/ml in non-polyp group, respectively (P<0.05). Multivariate Logistic regression analysis showed that the gender (OR=4.269, 95%CI: 1.963-9.405) and FGF19 (77.0-131.4 pg/ml: OR=2.385, 95%CI: 1.155-4.926) were independent factors of colorectal polyps. The gender (OR=3.799, 95%CI: 1.650-8.748) and FGF19 (77.0-131.4 pg/ml: OR=2.290, 95%CI: 1.072-4.891) were independent factors of colorectal adenomatous polyps. The gender(OR=6.725, 95%CI: 1.853-24.410) and fasting plasma glucose (≥6.5 mmol/L: OR=0.047, 95%CI: 0.009-0.245) were independent factors of colorectal inflammatory polyps. The gender (OR=3.539, 95% CI: 1.293-9.689) was an independent factor for the occurrence of single polyp. The gender (OR=5.063, 95% CI: 2.048-12.515), FGF19 (77.0-131.4 pg/ml: OR=2.502, 95%CI: 1.102-5.681), fasting plasma glucose (≥6.5 mmol/L: OR=0.282, 95%CI: 0.095-0.839) were independent factors of multiple polyps. The gender (OR=3.416, 95% CI: 1.134-10.289) and fasting insulin (≥9.4 µU/ml: OR=9.480, 95% CI: 1.485-60.521) were independent risk factors for colorectal polyps<0.5 cm. The gender (OR=3.151, 95%CI: 1.244-7.984) and fasting plasma glucose (≥6.5 mmol/L: OR=0.310, 95%CI: 0.102-0.941) were independent risk factors for colorectal polyps with the size of 0.5-0.9 cm. The gender (OR=22.649, 95%CI: 4.154-123.485), age (55 to 64 years old: OR=4.473, 95%CI: 1.070-18.704; ≥65 years old: OR=5.815, 95%CI: 1.300-26.009), BMI (≥28 kg/m(2): OR=5.310, 95%CI: 1.224-23.032) and FGF19 (77.0-131.4 pg/ml: OR=7.474, 95%CI: 1.903-29.351) were independent factors for colorectal polyps with size ≥ 1.0 cm. Gender stratification analysis showed that FGF19 was an independent factor for the occurrence of male polyps (77.0-131.4 pg/ml: OR=6.109, 95%CI: 1.688-22.104) and adenomas (77.0-131.4 pg/ml: OR=6.401, 95%CI: 1.717-23.864). The age (55 to 64 years old: OR=3.783, 95%CI: 1.052-13.611) and VCAM-1 (≥352.8 ng/ml: OR=4.341, 95%CI: 1.142-16.493) were independent risk factors of female polyps. The age (55 to 64 years old: OR=5.743, 95%CI: 1.205-27.362, ≥65 years old: OR=6.885, 95%CI: 1.143-41.467), VCAM-1 (≥352.8 ng/ml: OR=6.313, 95%CI: 1.415-28.159) and IGF-1 (≥7.6 ng/ml: OR=5.621, 95%CI: 1.069-29.543) were independent factors of female adenoma. Conclusions: The occurrences of colorectal polyps and adenomatous polyps are related to insulin resistance and glucose and lipid metabolism. Serum FGF19 is an independent influencing factor for the occurrence of colorectal polyps and adenomatous polyps, and is a potential serological diagnostic marker and therapeutic target for colorectal polyps and adenomatous polyps.

[A comparative study of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of primary hyperaldosteronism on left side].

Objective: To compare the therapeutic effect of transperitoneal transmesenteric approach versus paracolic sulci approach laparoscopic adrenal tumorectomy for treatment of left-sided primary hyperaldosteronism. Methods: From January 2017 to July 2019, the clinical data of 70 patients with left-sided primary hyperaldosteronism (PHA) who underwent surgery in the First Hospital of Lanzhou University and five other hospitals in Gansu Province were retrospectively analyzed. There are 43 male and 27 female patients. Among them,28 patients were performed transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy and 42 patients were performed transperitoneal paracolic sulci approach laparoscopic adrenal tumorectomy. The general information and perioperative data of the two groups were compared. Results: All 70 cases of surgery were successfully completed. As compared with the paracolic sulci approach group, the operation time was significantly shorter in the transmesenteric approach group[(26.7±8.8)vs (38.9±7.1)min,P<0.001)], and the estimated blood loss was less in the transmesenteric approach group[45(30,50) vs 50(40,60)ml,P=0.042]. There was no statistically significant difference in the postoperative hospitalization days between the two groups[(4.4±1.0)vs(4.5±1.0)d, P=0.669)]. The electrolytes and aldosterone to renin ratio returned to a healthy level in the postoperative one month, and the blood pressure also returned to a healthy level in 53 (75.7%) patients. Conclusion: Transperitoneal transmesenteric approach laparoscopic adrenal tumorectomy is safe and feasible, with a short operation time and relatively less estimated blood loss.

Resveratrol for protection against statin toxicity in C2C12 and H9c2 cells.

Statins are among the most commonly prescribed drugs for the treatment of high blood cholesterol. Myotoxicity of statins in certain individuals is often a severe side effect leading to withdrawal. Using C2C12 and H9c2 cells, both exhibiting characteristics of skeletal muscle cells, we addressed whether resveratrol (RSV) can prevent statin toxicity. Statins decreased cell viability in a dose and time-dependent manner. Among the five statins tested, atorvastatin, simvastatin, lovastatin, pravastatin, and fluvastatin, simvastatin is the most toxic one. Simvastatin at 10 µM caused about 65% loss of metabolic activity as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays in C2C12 cells or H9c2 cells. Inhibition of metabolic activity correlates with an increase in caspase activity. RSV was found to protect H9c2 cells from simvastatin-induced activation of caspase-3/7. However, such protection was not found in C2C12 cells. This cell type-dependent effect of RSV adds to the complexity in muscle cell toxicity of statins.

Role of nasal saline irrigation in the treatment of allergic rhinitis in children and adults: A systematic analysis.

BACKGROUND: This meta-analysis aims to access the efficacy of nasal saline irrigation in the treatment of allergic rhinitis (AR) in adults and children. METHODS: Two authors independently searched databases up to December 2018. Differences in efficacy between saline irrigation and other treatments were compared. Subgroup analyses of discrepancy in effects between children and adults were performed. RESULTS: (1) Saline irrigation vs. no irrigation, in both children and adults groups, saline irrigation showed significant efficacy. (2) Saline+medication vs. medication, in children group, there was no statistical difference of efficacy between saline+medication and medication; in adults group, efficacy of saline+medicine was superior to that of medication. (3) Saline irrigation vs. medication, in children group, there was no statistical difference between efficacy of saline irrigation and medication; in adults group, efficacy of medication was superior to that of saline irrigation. (4) Hypertonic saline vs. isotonic saline, for children, efficacy of hypertonic saline was superior to that of isotonic saline. Additionally, no adults reported adverse events in all trials. Adverse effects were reported during the first nasal irrigation in 20 children, and one child withdrew due to adverse reactions. CONCLUSIONS: Saline irrigation can significantly improve symptoms of AR in children and adults. Saline irrigation can serve as a safe adjunctive treatment to medication of AR in adults. Saline irrigation can be an alternative therapy for children and pregnant women with AR. Efficacy of hypertonic saline may be better than that of isotonic saline in treating AR of children.

[Effects of three self-etch adhesives and mild salivary contamination on the bonding durability of deciduous teeth].

OBJECTIVE: To compare the bonding durability of three different self-etch adhesives to primary enamel and dentin, and to investigate the effect of mild salivary contamination followed by air drying on the bonding durability. METHODS: Two hundred and forty enamel specimens were divided randomly into 16 groups (n=15/group)according to the adhesive system [self-etch adhesives: Clearfil SE Bond(SE), AdperTM Easy One (EO), Scotchbond Universal (SBU); total-etch adhesive: AdperTM Single Bond Plus(SL)], contamination status (non-contaminated vs. salivary-contaminated) and storage condition (stored in distilled water for 24 h vs. aging mode 5 000 thermal cycles in 5 ℃ and 55 ℃). Two hundred and forty dentin specimens were assigned in the same way. Shear bond strength for 12 specimens in each group were measured. The adhesive interface for the residual specimens in each group was observed by scanning electron microscopy(SEM). Data were analyzed by three-way analysis of variance and Tukey test(P < 0.05). RESULTS: For primary enamel, total-etch adhesive showed higher initial shear bond strength values (28.92±1.83) MPa and shear bond strength values (27.27±3.03) MPa after thermal cycles compared with the other groups, and the difference between the groups was statistically significant (P < 0.01). Shear bond strength values of EO decreased significantly in salivary-treated groups, regardless of storage conditions, and the difference was statistically significant (P < 0.01). For primary dentin, shear bond strength values of EO decreased significantly in salivary-treated groups after 24 h (P < 0.01). After 5 000 thermal cycles, total-etch adhesive showed significantly lower shear bond strength values (14.31±1.97) MPa compared with the other groups, and the difference between the groups was statistically significant (P < 0.01), and shear bond strength values of EO were significantly lower than those in SE and SBU groups (P < 0.01), regardless of contamination status. CONCLUSION: Total-etch adhesive SL has better bonding durability to primary enamel. SE and SBU have better bonding durability to primary dentin and have a certain resistance to salivary contamination, while the bonding performance of EO is compromised greatly by mild salivary contamination followed by air drying.

In Vitro Measurement and Modeling of Platelet Adhesion on VWF-Coated Surfaces in Channel Flow.

The process of platelet adhesion is initiated by glycoprotein (GP)Ib and GPIIbIIIa receptors on the platelet surface binding with von Willebrand factor on the vascular walls. This initial adhesion and detachment of a single platelet is a complex process that involves multiple bonds forming and breaking and is strongly influenced by the surrounding blood-flow environment. In addition to bond-level kinetics, external factors such as shear rate, hematocrit, and GPIb and GPIIbIIIa receptor densities have also been identified as influencing the platelet-level rate constants in separate studies, but this still leaves a gap in understanding between these two length scales. In this study, we investigate the fundamental relationship of the dynamics of platelet adhesion, including these interrelating factors, using a coherent strategy. We build a, to our knowledge, novel and computationally efficient multiscale model accounting for multibond kinetics and hydrodynamic effects due to the flow of a cellular suspension. The model predictions of platelet-level kinetics are verified by our microfluidic experiments, which systematically investigate the role of each external factor on platelet adhesion in an in vitro setting. We derive quantitative formulas describing how the rates of platelet adhesion, translocation, and detachment are defined by the molecular-level kinetic constants, the local platelet concentration near the reactive surface determined by red-blood-cell migration, the platelet effective reactive area due to its tumbling motion, and the platelet surface receptor density. Furthermore, if any of these aspects involved have abnormalities, e.g., in a disease condition, our findings also have clinical relevance in predicting the resulting change in the adhesion dynamics, which is essential to hemostasis and thrombosis.

let-7i inhibits proliferation and migration of bladder cancer cells by targeting HMGA1.

BACKGROUND: Let-7 is one of the earliest discovered microRNAs(miRNAs) and has been reported to be down-regulated in multiple malignant tumors. The effects and molecular mechanisms of let-7i in bladder cancer are still unclear. This study was to investigate the effects and potential mechanisms of let-7i on bladder cancer cells. METHODS: Total RNA was extracted from bladder cancer cell lines. The expression levels of let-7i and HMGA1 were examined by quantitative real-time PCR. Cell viability was detected using the CCK-8 and colony formation assays, while transwell and wound healing assays were used to evaluate migration ability. Luciferase reporter assay and western blot were used to confirm the target gene of let-7i. RESULTS: Compared with the SV-40 immortalized human uroepithelial cell line (SV-HUC-1), bladder cancer cell lines T24 and 5637 had low levels of let-7i expression, but high levels of high mobility group protein A1 (HMGA1) expression. Transfection of cell lines T24 and 5637 with let-7i mimic suppressed cell proliferation and migration. Luciferase reporter assay confirmed HMGA1 may be one of the target genes of let-7i-5p. Protein and mRNA expression of HMGA1 was significantly downregulated in let-7i mimic transfected cell lines T24 and 5637. CONCLUSIONS: Up-regulation of let-7i suppressed proliferation and migration of the human bladder cancer cell lines T24 and 5637 by targeting HMGA1. These findings suggest that let-7i might be considered as a novel therapeutic target for bladder cancer.

[Nearinfrared light transillumination for detection of incipient proximal caries in primary molars].

OBJECTIVE: To evaluate the practical value of nearinfrared light transillumination (NILT, DIAGNOcam) on detection of incipient proximal caries in primary molars. METHODS: In this study, 4-9-year-old children with suspicious proximal lesions in primary molars were recruited. The target teeth were examined with clinical examination, bitewing radiograph and DIAGNOcam. And the caries indexes were rated as 0 (no caries), 1 (caries reaching outer 1/2 enamel), 2 (caries reaching inner 1/2 enamel), and 3 (dentine caries). Those primary molars with at least one of the adjacent molars according with the criteria of invasive treatment, i.e. the teeth were diagnosed as caries reaching inner 1/2 enamel or dentine with at least two detection methods, were included. The target teeth with caries index ≥2 accepted the invasive treatment. And the caries status of the adjacent teeth was observed under direct vision and those teeth of caries index ≥2 would also accept the invasive treatment. The relationship of lesions to enamel-dentine junction (EDJ) were recorded and used as reference standard to compare the sensitivity, specificity and accuracy of those three methods in detecting the incipient proximal caries in primary molars. RESULTS: In this study, 36 children with 104 suspicious proximal lesions in primary molars were recruited, of which 5 were diagnosed as no caries, 20 were diagnosed as superficial enamel caries, and 79 accepted invasive treatment, of which 22 were diagnosed as EDJ caries, and 57 as dentine caries. The sensitivity of clinical examination, bitewing radiograph, and DIAGNOcam were 68.69%, 81.82%, 78.79%, respectively. The specificity were 100.00%, 100.00%, 80.00%, and the accuracy were 75.96%, 85.65%, 78.85%, respectively. As for superficial enamel caries, the sensitivity of clinical examination was lowest, only 10%, while DIAGNOcam was 60%, higher than 40% of bitewing radiograph. As for EDJ caries, the sensitivity of bitewing radiograph was highest as 86.36%, followed by DIAGNOcam 72.73% and clinical examination 68.18%. As for dentine caries, the sensitivity of the three detection methods were higher than 85%, of which bitewing radiograph was the highest as 94.74%. CONCLUSION: The accuracy of DIAGNOcam in detecting incipient proximal caries in primary molars was comparable to that of bitewing radiograph. It was safe, and convenient with no exposure to radiation, which was applicable to be used in pediatric dentistry.

Nrf2 at the heart of oxidative stress and cardiac protection.

The NFE2L2 gene encodes the transcription factor Nrf2 best known for regulating the expression of antioxidant and detoxification genes. Gene knockout approaches have demonstrated its universal cytoprotective features. While Nrf2 has been the topic of intensive research in cancer biology since its discovery in 1994, understanding the role of Nrf2 in cardiovascular disease has just begun. The literature concerning Nrf2 in experimental models of atherosclerosis, ischemia, reperfusion, cardiac hypertrophy, heart failure, and diabetes supports its cardiac protective character. In addition to antioxidant and detoxification genes, Nrf2 has been found to regulate genes participating in cell signaling, transcription, anabolic metabolism, autophagy, cell proliferation, extracellular matrix remodeling, and organ development, suggesting that Nrf2 governs damage resistance as well as wound repair and tissue remodeling. A long list of small molecules, most derived from natural products, have been characterized as Nrf2 inducers. These compounds disrupt Keap1-mediated Nrf2 ubquitination, thereby prohibiting proteasomal degradation and allowing Nrf2 protein to accumulate and translocate to the nucleus, where Nrf2 interacts with sMaf to bind to ARE in the promoter of genes. Recently alternative mechanisms driving Nrf2 protein increase have been revealed, including removal of Keap1 by autophagy due to p62/SQSTM1 binding, inhibition of ßTrCP or Synoviolin/Hrd1-mediated ubiquitination of Nrf2, and de novo Nrf2 protein translation. We review here a large volume of literature reporting historical and recent discoveries about the function and regulation of Nrf2 gene. Multiple lines of evidence presented here support the potential of dialing up the Nrf2 pathway for cardiac protection in the clinic.

A novel splicing mutation of ectodysplasin A gene responsible for hypohidrotic ectodermal dysplasia.

Hypohidrotic ectodermal dysplasia (HED) is characterized by hypohidrosis, hypodontia, sparse hair, and characteristic facial features. This condition is caused by an ectodysplasin A (EDA) gene mutation. In this study, we examined two HED pedigrees and investigated the molecular genetics of the defect. Direct sequencing analysis revealed a previously unidentified mutation in the EDA splice donor site (c.526 + 1G>A). The function of the mutant EDA gene was predicted through online investigations and subsequently confirmed by splicing analysis in vitro. The mutation resulted in the production of a truncated EDA-A1 protein caused by complete omission of exon 3. This novel functional skipping-splicing EDA mutation was considered to be the cause of HED in the two pedigrees reported here. Our findings, combined with those reported elsewhere, provide an improved understanding of the pathogenic mechanism of HED as well as important information for a genetic diagnosis.