Comparative split-face study of durational changes in hyaluronic acid fillers for mid-face volume augmentation.

Subsequent changes after injection should be considered when determining the precise volume of injected dermal filler. Several studies have used scoring systems to evaluate facial volumes; however, these scoring systems are not particularly objective. This present study aimed to evaluate the volumetric changes over time on three-dimensional (3D) images and the maintenance potential of various hyaluronic acid (HA) fillers used for mid-face volume augmentation. This split-face clinical study included nine Korean subjects who each received a mid-facial injection of the test filler (B) on one side and a random control filler (J, R, or Y) on the contralateral side. Global, photographic, and 3D scanning assessments were conducted at baseline and after 30 min, 3 days, and 2, 4, 12, and 24 weeks. In all nine cases, the 3D images revealed the largest differences in height where the test filler (B) was injected. The results of subjective scoring systems correlated with the results of 3D imaging. The volumes of monophasic fillers (B and J) were maintained for longer periods of time than those of biphasic fillers (R and Y). The B filler yielded excellent volumizing and spreading effects and good injectability. This filler would be suitable for injection into high-pressure areas, such as the lateral cheek, chin, and nasolabial fold. Moreover, the 3D imaging analysis provided objective and digitized data. The present authors hope that their data will allow physicians to better understand the durational changes in HA fillers and, thus, provide accurate predictions to their patients.

Aldehyde dehydrogenase 2 (ALDH2) polymorphism gene and coronary artery disease risk: a meta-analysis.

We studied the association between aldehyde dehydrogenase 2 (ALDH2) polymorphism and coronary artery disease (CAD) and clarified the mechanisms underlying this association. We searched the ISI, Medline (Ovid), PubMed, CNKI, Wanfang, and Weipu Databases. Statistical analysis was performed using Revman 5.0 and Stata12.0 softwares. A total of 3305 cases and 5016 controls in 12 case-control studies were included in this meta-analysis. Variant A allele carriers showed a 48% increased risk of CAD compared with homozygote A allele [odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.18-1.87 for AA + AG vs GG]. In subgroup analysis by gender, significantly elevated risks were found in the mixed group (OR = 1.78, 95%CI = 1.42-2.22) but not in males (OR = 1.12, 95%CI = 0.79-1.57). In subgroup analysis by disease type, significant elevated risks were associated with A allele carriers in myocardial infarction [OR = 1.69, 95%CI = (1.05-2.71)], in coronary heart disease (OR = 1.36, 95%CI = 1.00-1.86), but not in coronary heart disease plus diabetes mellitus subjects (OR = 1.57, 95%CI = 0.58-4.29). Moreover, those with the GG genotype consumed significantly more alcohol than those with the AA/AG genotypes (standard mean deviation: 6.32 g, 95%CI = 2.09-10.55, P = 0.000). ALDH2 polymorphisms may be risk factors for CAD. Moreover, CAD patients with ALDH2 genotypes AG and AA consumed significantly less alcohol than those with GG. To further evaluate gene-gene and gene-environment interactions between ALDH2 polymorphisms and the risk of CAD, more studies with larger groups of patients are required.

[Construction and application of a risk index of Echinococcus infection based on the classification of echinococcosis lesions].

OBJECTIVE: To investigate the feasibility of constructing the risk index of Echinococcus infection based on the classification of echinococcosis lesions, so as to provide insights into the management of echinococcosis. METHODS: The imaging data of echinococcosis cases were collected from epidemiological surveys of echinococcosis in China from 2012 to 2016, and the detection of incident echinococcosis cases was captured from the annual echinococcosis prevention and control reports across provinces (autonomous regions) and Xinjiang Production and Construction Corps in China from 2017 to 2022. After echinococcosis lesions were classified, a risk index of Echinococcus infection was constructed based on the principle of discrete distribution marginal probability and multi-group classification data tests. The correlation between the risk index of Echinococcus infection and the detection of incident echinococcosis cases was evaluated in the provinces (autonomous regions and corps) from 2017 to 2022, and the correlations between the short and medium-term risk indices and between the medium and long-term risk indices of Echinococcus infection were examined using a univariate linear regression model. RESULTS: A total of 4 014 echinococcosis cases in China from 2012 to 2016 were included in this study. The short-, medium- and long-term risk indices of E. granulosus infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ2 = 4.12 to 708.65, all P values < 0.05), with high short- (0.058), medium- (0.137) and long-term risk indices (0.104) in Tibet Autonomous Region, and the short-, medium- and long-term risk indices of E. multilocularis infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ2 = 6.74 to 122.60, all P values < 0.05), with a high short-term risk index in Sichuan Province (0.016) and high medium- (0.009) and long-term risk indices in Qinghai Province (0.018). There were no significant correlations between the risk index of E. granulosus infection and the detection of incident cystic echinococcosis cases during the study period (t = -0.518 to 2.265, all P values > 0.05), and strong correlations were found between the risk indices of E. multilocularis infection and the detection of incident alveolar echinococcosis cases (including mixed type) in 2018, 2020, 2021, 2022, during the period from 2017 through 2020, from 2017 through 2021, from 2017 through 2022 (all r values > 0.7, t = 2.521 to 3.692, all P values < 0.05). Linear regression models were established between the risk index of E. multilocular infection and the detection of alveolar echinococcosis cases (including mixed type), and the models were all statistically significant (b = 0.214 to 2.168, t = 2.458 to 3.692, F = 6.044 to 13.629, all P values < 0.05). The regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. granulosus infection were 2.339 and 0.765, and the regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. multilocular infection were 0.280 and 1.842, with statistical significance seen in both the regression coefficients and regression models (t = 16.479 to 197.304, F = 271.570 to 38 928.860, all P values < 0.05). CONCLUSIONS: The risk index of Echinococcus infection has been successfully established based on the classification of echinococcosis lesions, which may provide insights into the prevention and control, prediction, diagnosis and treatment, and classified management of echinococcosis.

Facial skin barrier function recovery after microneedle transdermal delivery treatment.

BACKGROUND: Microneedle treatment is currently used in the cosmetic industry for several skin conditions. Despite their extensive use, there is lack of sufficient data on the safety of microneedles. OBJECTIVE: To investigate the degree of acute skin damage and the time required for facial skin barrier function to recover using different microneedle lengths and numbers of applications. MATERIALS AND METHODS: Each side of a volunteer's face was randomly treated with one of the following treatments: five applications of 0.15-mm microneedles, five applications of 0.25-mm microneedles, 10 applications of 0.15-mm microneedles, or 10 applications of 0.25-mm microneedles. Transepidermal water loss, stratum corneum hydration, and skin erythema were measured at baseline, immediately after treatment, 4 hours after treatment, and 8 hours after treatment and at 24-hour intervals for 3 days. RESULTS: Prompt recovery of barrier function (within 72 hours) was observed after microneedle treatment. CONCLUSION: Microneedle treatment is simple and inexpensive, and the skin barrier disruption it causes resolves quickly. Therefore, it can serve as an effective physical method of enhancing transdermal delivery of medications for the treatment of many cosmetic and dermatological conditions.

[Effectiveness of a new health education pathway for echinococcosis control among primary school students in hyper-endemic regions].

OBJECTIVE: To investigate the effectiveness of a new health education pathway for echinococcosis control among primary school students in regions highly prevalent for echinococcosis in China. METHODS: Six primary schools were randomly selected from echinococcosis hyper-endemic regions, with 13 classes assigned to the intervention group and 9 to the control group, and all students in these 21 classes were recruited as the study subjects. Echinococcosis health education was performed through the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices in the intervention group, while routine health education was given in the control group. A questionnaire survey was performed to assess the score of echinococcosis control knowledge (including theoretical knowledge score and mean daily practical capability score) before and after the health education interventions to evaluate the effectiveness of this new health education pathway for echinococcosis control. RESULTS: The mean score of echinococcosis control knowledge was 68.86 ± 18.70 points at baseline, with the mean theoretical knowledge score of 40.97 ± 10.75 points, and the mean daily practical capability score of 27.89 ± 12.50 points. Clustering analysis showed three types of populations, including "unsatisfactory", "learn and apply creatively", and "rote learning", which accounted for 24.62% (240/975), 45.74% (446/975) and 29.64% (289/975), respectively. The mean score of echinococcosis control knowledge was 81.08 ± 18.15 points in the intervention group during the final assessment, with the mean theoretical knowledge score of 43.65 ± 9.40 points, and the mean daily practical capability score of 37.43 ± 12.22 points, and both were significantly higher relative to baseline (t = -4.201 and -15.202, both P values < 0.01). The mean score of echinococcosis control knowledge was comparable between at baseline (70.55 ± 19.46 points) and final assessment (71.74 ± 19.37 points) in the control group (t = -0.87, P > 0.05). CONCLUSIONS: The awareness of echinococcosis control knowledge is fair among primary school students in echinococcosis hyper-endemic regions; however, the capability of combining theoretical learning and practices requires to be improved. The health education mode based on the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices seems to remarkably improve the understanding of echinococcosis control knowledge among primary school students in echinococcosis hyper-endemic regions.

MicroRNA-345 suppresses cell invasion and migration in non-small cell lung cancer by directly targeting YAP1.

OBJECTIVE: To investigate the roles and the underlying mechanism of miR-345 in regulating non-small cell lung cancer (NSCLC) cell migration and invasion. PATIENTS AND METHODS: Fifty-two pairs of NSCLC tissues and matched normal lung tissue samples were collected from NSCLC patients who had undergone surgical resection between June 2015 and August 2017 in our hospital. Human NSCLC cell lines (NCI-H460, NCI-H1299, A549 and GLC-82) and normal human bronchial epithelium cell BEAS-2B were cultured. NSCLC cell migration and invasion capacities were determined by transwell assays. The relative protein and mRNA expression level of yes-associated protein 1 (YAP1) were detected by Western blot and Quantitative Real-time polymerase chain reaction (qRT-PCR) analysis, respectively. RESULTS: MiR-345 was prominently downregulated in NSCLC tissue specimens. Results of transwell assays showed that miR-345 overexpression could dramatically inhibit NSCLC cell migration and invasion. Additionally, data in current study also identified YAP1 as a direct functional target of miR-345 in NSCLC cells. YAP1 expressions were negatively correlated with the miR-345 expressions in NSCLC tissue samples. Moreover, YAP1 was found to be involved in the functions of miR-345 in inhibiting NSCLC cell invasion and migration. CONCLUSIONS: All the above results indicated that miR-345 inhibited NSCLC cell migration and invasion by targeting YAP1, suggesting that miR-345/YAP1 axis might be a promising biomarker for NSCLC treatments.

Blockade of spinal glutamate recycling produces paradoxical antinociception in rats with orofacial inflammatory pain.

In our current study, we investigated the role of spinal glutamate recycling in the development of orofacial inflammatory pain. DL-threo-ß-benzyloxyaspartate (TBOA) or methionine sulfoximine (MSO) was administered intracisternally to block spinal glutamate transporter and glutamine synthetase activity in astroglia. Intracisternal administration of high dose TBOA (10 µg) produced thermal hyperalgesia in naïve rats but significantly attenuated the thermal hyperalgesia in rats that had been pretreated with interleukin (IL)-1ß or Complete Freund's Adjuvant (CFA). In contrast, intracisternal injection of MSO produced anti-hyperalgesic effects against thermal stimuli in CFA-treated rats only. To confirm the paradoxical antinociceptive effects of TBOA and MSO, we examined changes in c-Fos expression in the medullary dorsal horn produced by thermal stimulation in naïve, IL-1ß-, or CFA-treated rats, after intracisternal injections of TBOA and MSO. Intracisternal administration of TBOA significantly increased c-Fos immunoreactivity in naïve rats. In contrast, intracisternal administration of TBOA significantly decreased the up-regulation of c-Fos immunoreactivity in the medullary dorsal horn of IL-1ß- and CFA-treated rats. However, intracisternal injection of MSO blocked the up-regulation of c-Fos immunoreactivity in CFA-treated rats only. We also investigated the effects of botulinum toxin type A (BoNT-A) on TBOA-induced paradoxical antinociception in CFA-treated rats, as BoNT-A inhibits the release of neurotransmitters, including glutamate. BoNT-A treatment reversed behavioral responses produced by intracisternal administration of TBOA in CFA-treated rats. These results suggest that the paradoxical responses produced by blocking glutamate transporters under inflammatory pain conditions are mediated by the modulation of glutamate release from presynaptic terminals. Moreover, blockade of glutamate reuptake could represent a new therapeutic target for the treatment of chronic inflammatory pain conditions.

The glial-neuronal GRK2 pathway participates in the development of trigeminal neuropathic pain in rats.

UNLABELLED: This study examined the role of the glial-neuronal G protein-coupled receptor kinase 2 (GRK2) pathway in the development of trigeminal neuropathic pain. Male Sprague Dawley rats, weighing 220 to 240 g, were anesthetized with ketamine (0.2 g/kg) and xylazine (0.02 g/kg). Under anesthesia, the left lower second molar was extracted, followed by the placement of a mini-dental implant to intentionally injure the inferior alveolar nerve. This injury produced mechanical allodynia along with the downregulation of neuronal GRK2 expression in the medullary dorsal horn. On the other hand, early intracisternal treatment with MDL28170, a calpain inhibitor, produced prolonged antiallodynic effects and blocked this downregulation of neuronal GRK2 expression. The intracisternal infusion of minocycline, a microglia inhibitor, and l-α-aminoadipic acid, an astrocytic specific inhibitor, also blocked the induced mechanical allodynia and downregulated neuronal GRK2 expression, respectively. Double immunofluorescence showed that the interleukin (IL)-1ß and IL-1R signals colocalize with the astrocytes and neurons, respectively, in the medullary dorsal horn following an inferior alveolar nerve injury. In addition, the intracisternal infusion of an IL-1 receptor antagonist also produced antiallodynic effects and blocked the downregulation of neuronal GRK2 expression. These results suggest that the glial-neuronal GRK2 pathway is a potentially important new target for treating neuropathic pain. Moreover, the IL-1ß expressed in astrocytes plays a significant role in modulating this pathway. PERSPECTIVE: This study showed that the glial-neuronal GRK2 pathway participates in the development of trigeminal neuropathic pain in rats. These results suggest that the glial-neuronal GRK2 pathway is a potentially important new target for the treatment of neuropathic pain.

Differential regulation of peripheral IL-1ß-induced mechanical allodynia and thermal hyperalgesia in rats.

This study examined the differential mechanisms of mechanical allodynia and thermal hyperalgesia after injection of interleukin (IL) 1ß into the orofacial area of male Sprague-Dawley rats. The subcutaneous administration of IL-1ß produced both mechanical allodynia and thermal hyperalgesia. Although a pretreatment with iodoresiniferatoxin (IRTX), a transient receptor potential vanilloid 1 (TRPV1) antagonist, did not affect IL-1ß-induced mechanical allodynia, it significantly abolished IL-1ß-induced thermal hyperalgesia. On the other hand, a pretreatment with D-AP5, an N-methyl-d-aspartate (NMDA) receptor antagonist, and NBQX, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, blocked IL-1ß-induced mechanical allodynia. Pretreatment with H89, a protein kinase A (PKA) inhibitor, blocked IL-1ß-induced mechanical allodynia but not thermal hyperalgesia. In contrast, pretreatment with chelerythrine, a protein kinase C (PKC) inhibitor, inhibited IL-1ß-induced thermal hyperalgesia. Subcutaneous injections of 2% lidocaine, a local anesthetic agent, blocked IL-1ß-induced thermal hyperalgesia but not IL-1ß-induced mechanical allodynia. In the resiniferatoxin (RTX)-pretreated rats, a subcutaneous injection of IL-1ß did not produce thermal hyperalgesia due to the depletion of TRPV1 in the primary afferent fibers. Double immunofluorescence revealed the colocalization of PKA with neurofilament 200 (NF200) and of PKC with the calcitonin gene-related peptide (CGRP) in the trigeminal ganglion. Furthermore, NMDA receptor 1 (NR1) and TRPV1 predominantly colocalize with PKA and PKC, respectively, in the trigeminal ganglion. These results suggest that IL-1ß-induced mechanical allodynia is mediated by sensitized peripheral NMDA/AMPA receptors through PKA-mediated signaling in the large-diameter primary afferent nerve fibers, whereas IL-1ß-induced thermal hyperalgesia is mediated by sensitized peripheral TRPV1 receptors through PKC-mediated signaling in the small-diameter primary afferent nerve fibers.

Participation of the central p38 and ERK1/2 pathways in IL-1ß-induced sensitization of nociception in rats.

This study examined the participation of central mitogen-activated protein kinases (MAPKs) in the central sensitization produced by a subcutaneous injection of interleukin-1ß (IL-1ß) in male Sprague-Dawley rats. Formalin-induced responses were evaluated 24h after an IL-1ß injection. A subcutaneous injection of 10ng of IL-1ß elevated the formalin-induced scratching response significantly in the second phase compared to the vehicle-treated group. Pretreatment with an IL-1 receptor antagonist reduced the IL-1ß-induced sensitization. Pretreatment with IL-1ß increased the p-ERK and p-p38 expression induced by the formalin injection. Double immunofluorescence data revealed increases in phospho-extracellular signal-regulated kinase (p-ERK) immunoreactive cells that co-localize with neuronal nuclei (NeuN), a neuronal marker, and in phospho-p38 (p-p38) immunoreactive cells that co-localize with NeuN and OX42, a microglia marker. The intracisternal administration of minocycline (50µg), a microglia inhibitor, attenuated the increased formalin-induced scratching responses in the IL-1ß-treated rats. The intracisternal administration of PD98059 (1, 10µg), a MEK inhibitor, and SB203580 (1, 5µg), a p38 inhibitor, also attenuated the number of formalin-induced scratches in the second phase in the IL-1ß-treated rats. These results suggest that the IL-1ß-induced central sensitization of nociception is mediated by the central MAPK pathways, which are activated differentially in the neurons and microglia under inflammatory pain conditions. Therefore, blockade of the MAPK pathways can be as a potential therapeutic target for the central sensitization of inflammatory pain.

A novel trigeminal neuropathic pain model: compression of the trigeminal nerve root produces prolonged nociception in rats.

We demonstrate the establishment of a novel animal model for trigeminal neuropathic pain following compression of the trigeminal nerve root, which produces prolonged nociceptive behavior and demyelination of the trigeminal nerve root. Under anesthesia, male Sprague-Dawley rats (200-230 g) were mounted onto a stereotaxic frame and injections of a 4% agar solution (10 µl) were given to achieve compression of the trigeminal nerve root. A sham operation was performed using identical procedures but without agar injections. Nociceptive behavior was examined 3 days before and then at 3, 7, 10, 14, 17, 21, 24, 30, 40, 55, and 70 days after the surgery. Compression of the trigeminal nerve root caused mechanical allodynia, hyperalgesia, and cold hypersensitivity. Mechanical allodynia was established within 3 days and recovered to preoperative levels on postoperative day (POD) 40. Mechanical hyperalgesia and cold hypersensitivity persisted until 55 days following compression. The compression produced focal demyelination in the trigeminal nerve root. In the medullary dorsal horn, phospho-p38 (p-p38) mitogen-activated protein kinase (MAPK) was found to be exclusively expressed in the microglia on POD 14. Furthermore, intraperitoneal administration of carbamazepine (50mg/kg) significantly blocked mechanical allodynia and reduced p38 MAPK activation induced by the compression of the trigeminal nerve root. Our findings suggest that prolonged nociceptive behavior following compression of the trigeminal nerve root may mimic trigeminal neuralgia in this animal model and that the activation of p38 MAPK in the microglia contributes to pain hypersensitivity in rats that have undergone compression of the trigeminal nerve root.