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Posterior capsule opacification (PCO) is the most common complication after cataract surgery and is likely to cause the second loss of vision. Pharmacological PCO prophylaxis has been proved to be effective, yet no clinical option is available due to the lack of a suitable mode of administration. In this work, we propose a unique concept of NIR dual-triggered drug release from black phosphorus (BP)-based implantable intraocular lens (IOL) for controlled drug release and chemo-photothermal combination therapy of PCO. Here, IOL is used as a “reservoir” of doxorubicin-loaded black phosphorus (BP-DOX), and BP is used as NIR activation agent for controlled drug release and photothermal therapy. This BP-DOX integrated IOL, namely BP-DOX@IOL, shows the characteristics of good transmittance, good mechanical property, NIR dual-triggered drug release behaviors, and excellent photothermal efficacy. In vivo studies reveal that there is no PCO occurrence in rabbits' model by using BP-DOX@IOL combined NIR irradiation, which exhibits distinct superiority on inhibiting PCO than the control group (100% PCO occurrence) 28 days post-surgery. This novel IOL drug delivery system would be a promising strategy for the future clinical application for PCO prophylaxis and treatment.

BACKGROUND: The main symptoms of chemotherapy-induced peripheral neuropathy (CIPN) include pain and numbness. Neuronal G protein–coupled receptor kinase 2 (GRK2) plays an important role in various pain models. Cisplatin treatment can induce the activation of proinflammatory microglia in spinal cord. The purpose of this study was to investigate the role of spinal neuronal GRK2 in cisplatin-induced CIPN and in the prevention of CIPN by electroacupuncture (EA). METHODS: The pain and sensory deficit behaviors of mice were examined by von Frey test and adhesive removal test. The expression of neuronal GRK2 in the spinal cord is regulated by intraspinal injection of adeno-associated virus (AAV) containing neuron-specific promoters. The protein levels of GRK2, triggering receptor expressed on myeloid cells 2 (TREM2), and DNAX-activating protein of 12 kDa (DAP12) in spinal dorsal horn were detected by Western blot, the density of intraepidermal nerve fibers (IENFs) was detected by immunofluorescence, and microglia activation were evaluated by real-time polymerase chain reaction (PCR). RESULTS: In this study, cisplatin treatment led to the decrease of GRK2 expression in the dorsal horn of spinal cord. Overexpression of neuronal GRK2 in spinal cord by intraspinal injection of an AAV vector expressing GRK2 with human synapsin (hSyn) promotor significantly inhibited the loss of IENFs and alleviated the mechanical pain and sensory deficits induced by cisplatin. Real-time PCR analysis showed that the overexpression of neuronal GRK2 significantly inhibited the messenger RNA (mRNA) upregulation of proinflammatory cytokine interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), and M1 microglia marker cluster of differentiation (CD)16 induced by cisplatin. Furthermore, the TREM2 and DAP12, which has been demonstrated to play a role in microglia activation and in the development of CIPN, were also downregulated by overexpression of neuronal GRK2 in this study. Interestingly, preventive treatment with EA completely mimics the effect of overexpression of neuronal GRK2 in the spinal cord in this mouse model of cisplatin-induced CIPN. EA increased GRK2 level in spinal dorsal horn after cisplatin treatment. Intraspinal injection of AAV vector specifically downregulated neuronal GRK2, completely reversed the regulatory effect of EA on CIPN and microglia activation. All these indicated that the neuronal GRK2 mediated microglial activation contributed to the process of CIPN. CONCLUSIONS: Neuronal GRK2 in the spinal cord contributed to the preventive effect of EA on CIPN. The neuronal GRK2 may be a potential target for CIPN intervention.

Small tourism firms (STFs) established and operated by local families can be an engine of sustainable rural tourism. This paper stresses the intimate intertwining of family and business in rural STFs and conceptualizes their entrepreneurial success as a combination of business performance and family well-being. Integrating the resource-based view and network embeddedness theory, relationships among the STF owners’ dual social networks (family and industry networks), entrepreneurial resource acquisition, and entrepreneurial success are proposed and tested with a sample of 276 STFs in rural China. The empirical analyses reveal that (1) compared with tangible and knowledge-based resources, the owners’ acquisition of psychic resources has the strongest effect on entrepreneurial success; and (2) although industry networks provide more diverse access to entrepreneurial resources, family networks are superior in facilitating psychic resource acquisition, thus are especially important to the entrepreneurial success of rural STFs. Theoretical and practical implications are discussed.

Unlike adult cardiomyocytes, neonatal cardiomyocytes can readily proliferate that contributes to a transient regenerative potential after myocardial injury in mice. We have recently reported that CD4+ regulatory T-cells promote this process; however, the role of other CD4+ T-cell subsets as well as CD8+ T-cells in postnatal heart regeneration has been less studied. Methods: by comparing the regenerating postnatal day (P) 3 and the non-regenerating P8 heart after injury, we revealed the heterogeneity of CD4+ and CD8+ T-cells in the myocardium through single cell analysis. We also specifically ablated CD4+ and CD8+ T-cells using the lytic anti-CD4 and -CD8 monoclonal antibodies, respectively, in juvenile mice at P8 after myocardial injury. Results: we observe significantly more CD4+FOXP3- conventional T-cells in the P8 heart when compared to that of the P3 heart within a week after injury. Surprisingly, such a difference is not seen in CD8+ T-cells that appear to have no function as their depletion does not reactivate heart regeneration. On the other hand, specific ablation of CD4+ T-cells contributes to mitigated cardiac fibrosis and increased cardiomyocyte proliferation after injury in juvenile mice. Single-cell transcriptomic profiling reveals a pro-fibrotic CD4+ T-cell subset in the P8 but not P3 heart. Moreover, there are likely more Th1 and Th17 cells in the P8 than P3 heart. We further demonstrate that cytokines of Th1 and Th17 cells can directly reduce the proliferation and increase the apoptosis of neonatal cardiomyocytes. Moreover, ablation of CD4+ T-cells can directly or indirectly facilitate the polarization of macrophages away from the pro-fibrotic M2-like signature in the juvenile heart. Nevertheless, ablation of CD4+ T-cells alone does not offer the same protection in the adult heart after myocardial infarction, suggesting a developmental change of immune cells including CD4+ T-cells in the regulation of age-related mammalian heart repair. Conclusions: our results demonstrate that ablation of CD4+ but not CD8+ T-cells promotes heart regeneration in juvenile mice; and CD4+ T-cells play a distinct role in the regulation of heart regeneration and repair during development.

Tourists’ pro-environmental behaviour (PEB) in travel destinations features the social attributes of altruism and collective action. In addition to recognising the power of individual attitudes (e....

Morphine and other opiates are highly effective for treating moderate to severe pain. However, morphine-induced hyperalgesia and analgesic tolerance prevent durable efficacy in patients. Here, we investigated the underlying molecular mechanisms of this phenomenon. We found that repeated subcutaneous injections of morphine in mice increased the abundance of the cytokine interleukin-33 (IL-33) primarily in oligodendrocytes and astrocytes and that of its receptor ST2 mainly in astrocytes. Pharmacological inhibition or knockdown of IL-33 or ST2 in the spinal cord attenuated morphine-induced hyperalgesia and analgesic tolerance in mice, as did global knockout of either

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) are T cells-mediated life-threatening immune reactions, most commonly induced by drug. The last decade has seen significant progress in SCARs research. Recent studies have unveiled the pathogenesis of SCARs involved in susceptible genes, including human leukocyte antigens (HLA) and drugs-T cell receptor (TCR) interaction that may trigger T cell activation with downstream immune signaling of cytokines/chemokines and specific cytotoxic proteins releases. Advances in identification of multiple genetic alleles associated with specific drugs related SCARS in different populations is an important breakthrough in recent years for prevention of SCARs. This article summarized the findings on genetic factors related to SJS/TEN, especially for HLA.

In the international education market, much attention has been paid to China, as it is the world’s largest source country in sending students abroad. The other side of the story, that is, China, as...

Many indigenous communities are greatly influenced by tourism development and their support for tourism matters to both developers and tourists’ experiences. Therefore, it is important to u...

The chronic neuropathic pain-associated psychiatric disorders have seriously disturbed the quality of patients' life, such as depression and anxiety. Neuroinflammation in the hippocampus plays an important role in the neuropathic pain-associated depressive and anxiety disorders, but the underlying mechanism has not been thoroughly elucidated to date. The Nod-like receptor protein (NLRP)-1 inflammasome, which controls the production of pro-inflammatory cytokines, was broadly involved in the neuroinflammation-related diseases. In the present study, we show that the NLRP1 inflammasome is significantly activated in the hippocampus of rats subjected to the chronic constriction injury (CCI)-induced neuropathic pain. Inhibiting the product of NLRP1 inflammasome not only attenuated the depression-like behaviors but also suppressed the production of mature IL-1β in the hippocampus of CCI rats. The double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) has been recently shown to be a pivotal regulator for the activation of inflammasome. In the rats subjected to CCI neuropathic pain, the PKR was simultaneously activated in hippocampus. Functional inhibition of PKR suppressed the NLRP1 inflammasome activation and effectively attenuated the CCI-induced depression-like behaviors. These results indicate that the hippocampal PKR/NLRP1 inflammasome pathway play an important role in the development of the depressive behaviors after chronic neuropathic pain. Thus, interrupting this pathway might provide a novel therapeutic strategy for neuropathic pain-associated depressive disorders.

This study explores the current status of research on inbound tourism to China, which ranks third globally among tourist receiving countries. The importance of inbound tourism as an indicator of na...

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a progressive, enduring, and often irreversible adverse effect of many antineoplastic agents, among which sensory abnormities are common and the most suffering issues. The pathogenesis of CIPN has not been completely understood, and strategies for CIPN prevention and treatment are still open problems for medicine. Objectives: The objective of this paper is to review the mechanism-based therapies against sensory abnormities in CIPN. Methods: This is a literature review to describe the uncovered mechanisms underlying CIPN and to provide a summary of mechanism-based therapies for CIPN based on the evidence from both animal and clinical studies. Results: An abundance of compounds has been developed to prevent or treat CIPN by blocking ion channels, targeting inflammatory cytokines and combating oxidative stress. Agents such as glutathione, mangafodipir and duloxetine are expected to be effective for CIPN intervention, while Ca/Mg infusion and venlafaxine, tricyclic antidepressants, and gabapentin display limited efficacy for preventing and alleviating CIPN. And the utilization of erythropoietin, menthol and amifostine needs to be cautious regarding to their side effects. Conclusions: Multiple drugs have been used and studied for decades, their effect against CIPN are still controversial according to different antineoplastic agents due to the diverse manifestations among different antineoplastic agents and complex drug-drug interactions. In addition, novel therapies or drugs that have proven to be effective in animals require further investigation, and it will take time to confirm their efficacy and safety.

The role of children in family tourism has been recognized increasingly. However, their travel experiences are under-researched. This is the first study that focuses on children's views of family tourism in the world's most populous country, China. It explores Chinese children's views of family tourism experiences. More than one hundred (139) children aged 8–11 from three schools in a coastal Chinese city participated in the research by drawing pictures and sharing stories with the researchers. The results suggest that Chinese children, at least in these schools, have extensive travel experiences and a clear idea of what constitutes a memorable family tourism experience. Such experiences usually occur with their nuclear family, and are centered upon family togetherness and physical activities. Animal encounters, tasting local food, and appreciation of natural and built environments also matter. As future tourists, their views offer implications for destinations interested in attracting more Chinese tourists.

Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. Mefloquine reversed the pT-ION-induced upregulation of Cx36, glutamate receptor ionotropic kainate 2 (GluK2), transient receptor potential ankyrin 1 (TRPA1), and phosphorylated extracellular signal regulated kinase (p-ERK) in the trigeminal ganglion. Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-020-00594-4) contains supplementary material, which is available to authorized users.

Background Patients with traumatic injuries are often accompanied by emotional disorders, which seriously impede functional gains. The objective of this study was to identify the prevalence and risk factors associated with underlying anxiety and depression in orthopaedic trauma patients. Methods From July 2015 to December 2017, all orthopaedic trauma patients were included in the retrospective study. Patients with conditions that might affect cognitive impairment were excluded from the study. Basic demographic data were collected. All patients were screened for emotional disorders on admission using a simple questionnaire called “Huaxi Emotional-Distress Index” (HEI). Bivariate analyses and logistic regression were used to identify the factors associated with a HEI score of > 8. Results One hundred and sixty-two patients (8.1%) had a HEI score of > 8. About 1.0% of enrolled patients had severe emotional disorders (HEI score ≥ 17). The reasons caused by emotional disorders in patients with orthopaedic trauma were a higher Injury Severity Score (ISS), a higher visual analogue score (VAS) and type of surgery. On logistic regression, marital status was a protective factor for emotional disorders, while VAS and ISS were the risk factors for emotional disorders. Conclusions Although a significantly low percentage of orthopaedic trauma patients in our setting have emotional disorders, traumatic orthopaedic surgeons still need to pay attention to the risk of emotional disorders and integrate effective screening tools into clinical practice to screen for these factors and stratify emotional disorders. Appropriate targeted psychological intervention and treatment should be adopted according to the stratification of emotional disorders.

In order to improve the real-time performance and accuracy of localization for mobile robot in indoor environment, a neural network data fusion approach is proposed to eliminate the affection caused by errors from environment or measurements. In the approach, the odometry data are firstly obtained by calculating the collected encoder data through the Dead Reckoning (DR), then we fuse the odometry data and the lidar data by inputting them into a three-layer neural network. Experimental results show that the trained network improved the robot localization performance and its position accurate is within 6cm with good real time response.

Trigeminal neuralgia (TN) is debilitating and is usually accompanied by mood disorders. The lateral habenula (LHb) is considered to be involved in the modulation of pain and mood disorders, and the present study aimed to determine if and how the LHb participates in the development of pain and anxiety in TN. To address this issue, a mouse model of partial transection of the infraorbital nerve (pT-ION) was established. pT-ION induced stable and long-lasting primary and secondary orofacial allodynia and anxiety-like behaviors that correlated with the increased excitability of LHb neurons. Adeno-associated virus (AAV)-mediated expression of hM4D(Gi) in glutamatergic neurons of the unilateral LHb followed by clozapine-N-oxide application relieved pT-ION-induced anxiety-like behaviors but not allodynia. Immunofluorescence validated the successful infection of AAV in the LHb, and microarray analysis showed changes in gene expression in the LHb of mice showing allodynia and anxiety-like behaviors after pT-ION. Among these differentially expressed genes was Tacr3, the downregulation of which was validated by RT-qPCR. Rescuing the downregulation of Tacr3 by AAV-mediated Tacr3 overexpression in the unilateral LHb significantly reversed pT-ION-induced anxiety-like behaviors but not allodynia. Whole-cell patch clamp recording showed that Tacr3 overexpression suppressed nerve injury-induced hyperexcitation of LHb neurons, and western blotting showed that the pT-ION-induced upregulation of p-CaMKII was reversed by AAV-mediated Tacr3 overexpression or chemicogenetic inhibition of glutamatergic neurons in the LHb. Moreover, not only anxiety-like behaviors, but also allodynia after pT-ION were significantly alleviated by chemicogenetic inhibition of bilateral LHb neurons or by bilateral Tacr3 overexpression in the LHb. In conclusion, Tacr3 in the LHb plays a protective role in treating trigeminal nerve injury-induced allodynia and anxiety-like behaviors by suppressing the hyperexcitability of LHb neurons. These findings provide a rationale for suppressing unilateral or bilateral LHb activity by targeting Tacr3 in treating the anxiety and pain associated with TN.

Tourists’ green behavior has recently attracted much academic interest. The majority of the existing studies use quantitative research methods and explore how tourists’ cognitive and emotional factors influence their environmental actions. This study assesses tourists' green behavior from a unique perspective, that is, how hosts at rural Chinese B&Bs interact with tourists and shape their sustainable actions. The research team analyzed why the rural hosts are motivated to promote tourists’ green behavior, and identified the strategies they pursue to convince the tourists to be more sustainable. Guzhu Village, well known for its rural tourism and popular with senior tourists in the Yangtze River Delta, was the site for the study. Auto-ethnography was used as the key research method. It was found that both tangible and intangible environmental benefits motivate the hosts to guide tourists’ sustainable behavior. Hosts specifically structure some leisure activities and use compelling signage to both promote positive environmental actions and simultaneously enhance tourists’ satisfaction. This is the first study to emphasize the active roles of the hosts in shaping tourists’ green behavior through dynamic social interaction. The findings highlight the processes, such as humor and social approval, which have broad international applicability. Further, it was noted that the hosts employ ‘face’, a distinctive Chinese concept, to limit tourists’ less-desirable behaviors. Practical implications are also offered for sustainable destination management.

This study seeks to assess the factors influencing the satisfaction of Chinese tourists when they undertake self-drive international vacations. There are few existing studies about this independent travel market. Semi-structured interviews were undertaken to gather initial views about the attributes contributing to self-drive satisfaction. A questionnaire-based survey was then employed in Shanghai. Multiple linear regression analysis was used to test the factors which significantly affected tourists’ satisfaction. Analysis of the data reflected some of the findings from limited previous studies of other international groups: the scenery, road facilities, and available activities all have a significant positive impact on satisfaction. However, for the Chinese drive tourists, the responses of the local community to their trip, as well as key environmental issues, notably air quality, are distinctively important concerns. Implications are identified for international destination management organizations which are interested in promoting to and developing this self-drive Chinese market.

The 595-nm pulsed dye laser (PDL) has been used to treat vascular anomalies for about 30 years; however, there are insufficient data in Chinese patients concerning therapeutic efficacy, optimized parameters, and procedure techniques.To study the efficacy and relevant factors in PDL therapy for vascular anomalies in Chinese patients.We enrolled 431 patients with 8 different vascular anomalies and no previous treatment in this retrospective study. A detailed classification of vascular anomalies and various parameters and techniques of PDL were studied. The clinical outcomes were analysed using the Investigator Global Assessment.Improvements were significantly correlated with infantile haemangioma (IH) subtypes (p 0.05). A significant correlation between efficacy and lesion colour, anatomical sites, and hypertrophic-type port-wine stain (PWS) was found (p 0.05). There was no significant correlation between efficacy and age or sex (p 0.05).PDL is an effective and safe therapeutic modality for managing vascular anomalies in Chinese patients. We determined that differentiating and identifying IH subtypes prior to treatment could be a useful parameter for predicting therapeutic results. Lesion colour, sites, and hypertrophic changes in PWS are relevant therapeutic factors. PDL parameters and techniques differ according to the various vascular anomalies to achieve optimal results.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Cancer pain is a pervasive clinical symptom impairing life quality. Vascular endothelial growth factor A has been well studied in tumor angiogenesis and is recognized as a therapeutic target for anti-cancer treatment. This study tested the hypothesis that vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 contribute to bone cancer pain regulation associated with spinal central sensitization. Methods This study was performed on female rats using a metastatic breast cancer bone pain model. Nociceptive behaviors were evaluated by mechanical allodynia, thermal hyperalgesia, spontaneous pain, and CatWalk gait analysis. Expression levels were measured by real-time quantitative polymerase chain reaction, western blot, and immunofluorescence analysis. Excitatory synaptic transmission was detected by whole-cell patch-clamp recordings. The primary outcome was the effect of pharmacologic intervention of spinal vascular endothelial growth factor A/vascular endothelial growth factor receptor 2–signaling on bone cancer pain behaviors. Results The mRNA and protein expression of vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 were upregulated in tumor-bearing rats. Spinal blocking vascular endothelial growth factor A or vascular endothelial growth factor receptor 2 significantly attenuated tumor-induced mechanical allodynia (mean ± SD: vascular endothelial growth factor A, 7.6 ± 2.6 g vs. 5.3 ± 3.3 g; vascular endothelial growth factor receptor 2, 7.8 ± 3.0 g vs. 5.2 ± 3.4 g; n = 6; P < 0.0001) and thermal hyperalgesia (mean ± SD: vascular endothelial growth factor A, 9.0 ± 2.4 s vs. 7.4 ± 2.7 s; vascular endothelial growth factor receptor 2, 9.3 ± 2.5 s vs. 7.5 ± 3.1 s; n = 6; P < 0.0001), as well as spontaneous pain and abnormal gaits. Exogenous vascular endothelial growth factor A enhanced excitatory synaptic transmission in a vascular endothelial growth factor receptor 2–dependent manner, and spinal injection of exogenous vascular endothelial growth factor A was sufficient to cause pain hypersensitivity via vascular endothelial growth factor receptor 2–mediated activation of protein kinase C and Src family kinase in naïve rats. Moreover, spinal blocking vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 pathways suppressed protein kinase C-mediated N-methyl-d-aspartate receptor activation and Src family kinase-mediated proinflammatory cytokine production. Conclusions Vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 contributes to central sensitization and bone cancer pain via activation of neuronal protein kinase C and microglial Src family kinase pathways in the spinal cord.

Objective: This study aims to systematically evaluate the efficacy and safety of catgut implantation at acupoints (CIA) treating asthma, extracting data from the published clinical trials. Methods: The Cochrane Library, PubMed, Chinese Biomedical Database (CBM), CNKI, WANFANG and VIP databases were searched up to February 2017. Randomized controlled trials (RCTs) involving CIA or CIA plus conventional medicine treatment (CMT) were selected with CMT as control. We assessed the methodological quality of RCTs using the Cochrane Handbook for Systematic Review of Interventions. The outcome data of trials were analyzed using RevMan5.3. Results: A total of 12 studies ([Formula: see text]) were included. Most of the included studies were assessed to have high risk of bias with low quality of methodology. CIA application significantly improved the overall therapeutic efficacy ([Formula: see text]) and pulmonary function (forced expiratory volume in 1[Formula: see text]s (FEV1) and FEV1%, [Formula: see text] and [Formula: see text]) and reduced the overall scores of TCM symptoms ([Formula: see text]). Further, it significantly relieved several TCM symptoms including shortness of breath, chest distress and cough ([Formula: see text]). However, CIA only exerted a protective tendency for expectoration and wheezing without significant difference and had no effects on recurrence rate (all [Formula: see text]). Conclusions: CIA treatment could improve the overall efficacy and pulmonary function and relief several symptoms. However, the evidence remains weak. Rigorous and larger trials will be the basis of the effectiveness and long-term effects of CIA therapies.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse side effect of many antineoplastic agents. Patients treated with chemotherapy often report pain and paresthesias in a “glove-and-stocking” distribution. Diverse mechanisms contribute to the development and maintenance of CIPN. However, the role of spinal microglia in CIPN is not completely understood. In this study, cisplatin-treated mice displayed persistent mechanical allodynia, sensory deficits and decreased density of intraepidermal nerve fibers (IENFs). In the spinal cord, activation of microglia, but not astrocyte, was persistently observed until week five after the first cisplatin injection. Additionally, mRNA levels of inflammation related molecules including IL-1β, IL-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and CD16, were increased after cisplatin treatment. Intraperitoneal (i.p.) or intrathecal (i.t.) injection with minocycline both alleviated cisplatin-induced mechanical allodynia and sensory deficits, and prevented IENFs loss. Furthermore, cisplatin enhanced triggering receptor expressed on myeloid cells 2 (TREM2) /DNAX-activating protein of 12 kDa (DAP12) signaling in the spinal cord microglia. The blockage of TREM2 by i.t. injecting anti-TREM2 neutralizing antibody significantly attenuated cisplatin-induced mechanical allodynia, sensory deficits and IENFs loss. Meanwhile, anti-TREM2 neutralizing antibody prominently suppressed the spinal IL-6, TNF-α, iNOS and CD16 mRNA level, but it dramatically up-regulated the anti-inflammatory cytokines IL-4 and IL-10. The data demonstrated that cisplatin triggered persistent activation of spinal cord microglia through strengthening TREM2/DAP12 signaling, which further resulted in CIPN. Functional blockage of TREM2 or inhibition of microglia both benefited for cisplatin-induced peripheral neuropathy. Microglial TREM2/DAP12 may serve as a potential target for CIPN intervention.

The family, as a leisure unit, is an important museum consumer group. The literature on family leisure in museums concentrates on the cognitive and the learning aspects in science museums and art g...

The hospitality industry has been suffering from a pervasive climate of suspicion among guests who are concerned about potential hygiene or safety issues. From the perspective of protection motivation theory, this study presents a conceptual model elucidating the underlying mechanism through which generalized distrust shapes hotel guests' defensive coping behavior. Exploratory semi-structured interviews and online posts were combined to identify hotel guests' on-site coping strategies and underlying mechanisms. Then, an online questionnaire was distributed to 532 respondents, and structural equation modeling was used to test the proposed research model. Results provide empirical support for the “cognition–emotion–coping behavior” pattern in cognitive appraisal theory. This study offers valuable insight into the management of hotel guests’ generalized distrust.

Family travel is conducive to family function and tourists' personal development. Despite its long-established emphasis of family and learning through travel, limited effort has been invested in understanding Chinese adolescents' learning outcomes in the family tourism literature. This study adopted a mixed-method approach to establish a measure for such learning outcomes and validated the measurement scale via three rounds of surveys. The results suggested an eighteen-item and four-factor learning outcome structure with acceptable levels of reliability and validity. The four factors were family awareness, personal capability, destination knowledge and self-reflection. Family awareness was found to be the strongest predictor for Chinese adolescents’ well-being in family travel.

Seasonal migration is an emerging trend among seniors in China. In comparison with the lifestyle-oriented migrations of seniors in much of the western world, Chinese seniors often travel with a focus on improving their health and longevity. Adapting the concept of a therapeutic landscape, the changes experienced by seniors with health problems who visit Bama County, a remote area in southwest China well-known for the longevity of its residents, are explored through personal observation and in-depth interviews. All seniors reported improvements, to different degrees, in their physical, mental and social health. These positive transformations were attributed to the therapeutic physical, social and symbolic landscapes of Bama, as well as to the seniors’ proactive actions and their positive mindset. Implications are offered to the service industry, especially the broad tourism and hospitality industry, that is interested in attracting and catering to the aging Chinese population.

Narrative communities consist of closely interacting participants who frequently discuss their views of the world. The aims of this study were to establish the credibility of using a narrative community approach to the recreational vehicle (RV) market and, if appropriate, both identify common themes in the public discourse and direct attention to sensitive issues which those seeking to influence this market need to consider. Primary data were collected in Australia through focus groups at a typical regional RV rally site. This material was supplemented by close study of the main membership magazine produced for the target group. The researchers were able to confirm the applicability of the narrative community approach through noting the frequent repetition of symbolic stories, recurring phrases and highly favoured topics. The extended focus group conversations and the supplementary materials revealed six highly consistent themes binding the perspectives of the RV tourists. The celebrated common concerns were enjoying a new family, safety, freedom, health and living economically while contributing to the communities visited. This commonality was seen as constituting enthusiastic advocacy for RV travel and opens lines of communication for those seeking to influence RV users.

Purpose This study aims to assess international customers’ experiences in the leading hotels of the iconic city of Shanghai. Design/methodology/approach Leximancer, a qualitative analysis software program, was used to examine over 2,000 reviews appraising Shanghai’s superior hotels. The reviews were posted on Agoda.com. Findings Overall, the international tourists were actually quite satisfied with the superior Shanghai hotels. This study highlighted the continuing importance of the attentive and professional “staff”, physical attributes of the “hotel”, comfort of the “room”, “location”, proximity to a “shopping” area and co-creation possibilities to deliver some “beautiful” experiences. Segments of the market based on tourists’ origins, travel style and hotel management styles emphasized different expressive and instrumental features. Some strong commonalities were identified. The most satisfied customers, no matter what their backgrounds, were those who were more impressed with the expressive and intangible elements in the hotel, especially their interaction with and the service qualities of the hotels’ professional and attentive staff. Practical implications The work offers a potential range of insights and emphases for individual properties in Shanghai and other locations to help market and co-create experiences in their properties in distinctive ways. Originality/value The work is framed within the wider theoretical concerns of extending the meaning of co-creation in the experience economy. The work argues that co-creation is not limited to the on-site experience but rather that post-visit appraisals through user-generated contents constitute an extended form of interaction which may assist in understanding the full trajectory of the hotel experience.

With increases in disposable income in China as well as the traditional focus on family life, family tourism is one of the fastest growing segments in contemporary Chinese tourism. This study presents a systematic review of 66 research articles from Chinese academic journals published between 1995 and 2015. The general trend, themes and methods are analyzed. Listening to children’s voices, paying attention to diverse family types, the influence of social media on family travel, collaboration among researchers with different backgrounds, and thinking through the role of Chinese culture are posited as topics requiring increased attention to enhance future family tourism research in China.

Orofacial pain is characterized by its easy spread to adjacent areas, thus presenting with primary hyperalgesia (hypersensitivity at the site of injury) and secondary hyperalgesia (extraterritorial hypersensitivity outside the injured zone). However, the mechanisms behind the secondary hyperalgesia are poorly understood. In the present study, we used a mouse model of partial transection of the infraorbital nerve (pT-ION) to study whether calcium channel subunit α2δ1 (Cavα2δ1) and its downstream signaling contributes to the development of secondary hyperalgesia in the orofacial area. pT-ION caused primary (V2 skin) and secondary (V3 skin) hyperalgesia, which was reversed by the Cavα2δ1 antagonist gabapentin and by the expression of Cavα2δ1-targeting interfering RNA in trigeminal ganglion (TG)-V3 neurons. pT-ION induced increased expression of PKC and TRPA1, which was reversed by Cavα2δ1-targeting interfering RNA, and PKC inhibition reversed the upregulation of TRPA1 and gap junction (GJ) proteins induced by pT-ION. Cavα2δ1 overexpression in TG-V2 neurons induced the upregulation of PKC, TRPA1, and the GJ proteins in the TG and trigeminal subnucleus caudalis and induced hypersensitivity in the V3 skin area, which was reversed by TRPA1, GJ, or PKC blockade. Thus, we conclude that Cavα2δ1 contributes to the development of secondary hyperalgesia through its downstream PKC-TRPA1/GJ signaling pathways. PERSPECTIVE: This study demonstrates that the activation of Cavα2δ1 and the downstream PKC-TRPA1/GJ signaling pathway contributes greatly to trigeminal nerve injury-induced secondary mechanical and cold hyperalgesia. This suggests that inhibitors of Cavα2δ1, TRPA1, or GJs might be effective treatments for nerve injury-induced spreading of orofacial pain.

Integrating craft heritage with tourism activities is one way to perpetuate craft culture. The museums alongside Hangzhou's Grand Canal innovatively address craft heritage perpetuation by fostering interactions between visitors and craft-makers. Combining social practice theory with interaction ritual theory, this study explores the viability of this initiative through interviews with artisans who work in museums and interact with visitors. Craft-makers' work routines consist of three practices: cultural production, transmission, and operation. These practices demonstrate both collaborative and competitive relationships. The nature of relationships depends on whether or not ritual ingredients are congruent. The craft-makers develop different levels of agency to cope with tensions. This study enhances understanding of heritage perpetuation and visitor engagement.

Human amniotic membrane mesenchymal stem cells (hAMSCs) are considered ideal candidate stem cells for cell-based therapy. In this study, we assessed whether hAMSCs transplantation promotes neurological functional recovery in rats after traumatic spinal cord injury (SCI). In addition, the potential mechanisms underlying the possible benefits of this therapy were investigated. Female Sprague–Dawley rats were subjected to SCI using a weight drop device and then hAMSCs, or phosphate-buffered saline (PBS) were immediately injected into the contused dorsal spinal cord at 2 mm rostral and 2 mm caudal to the injury site. Our results indicated that transplanted hAMSCs migrated in the host spinal cord without differentiating into neuronal or glial cells. Compared with the control group, hAMSCs transplantation significantly decreased the numbers of ED1+ macrophages/microglia and caspase-3+ cells. In addition, hAMSCs transplantation significantly increased the levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the injured spinal cord, and promoted both angiogenesis and axonal regeneration. These effects were associated with significantly improved neurobehavioral recovery in the hAMSCs transplantation group. These results show that transplantation of hAMSCs provides neuroprotective effects in rats after SCI, and could be candidate stem cells for the treatment of SCI.

Background Emerging evidence indicates that nerve damage–initiated neuroinflammation and immune responses, which are evidenced by the up-regulation of proinflammatory cytokines, contribute to the development of neuropathic pain. This study investigated the role of spinal interleukin (IL)-33 and its receptor ST2 in spared nerve injury (SNI)-induced neuropathic pain. Methods The von Frey test and acetone test were performed to evaluate neuropathic pain behaviors (n = 8 to 12), and Western blot (n = 4 to 6), immunohistochemistry, real-time polymerase chain reaction (n = 5), and Bio-Plex (n = 5) assays were performed to understand the molecular mechanisms. Results Intrathecal administration of ST2-neutralizing antibody or ST2 gene knockout (ST2−/−) significantly attenuated the SNI-induced mechanical and cold allodynia. On the 7th day after SNI, the expression of spinal IL-33 and ST2 was increased by 255.8 ± 27.3% and 266.4 ± 83.5% (mean ± SD), respectively. Mechanistic studies showed that the increased expression of the spinal N-methyl-d-aspartate (NMDA) receptor subunit 1 after SNI was reduced by ST2 antibody administration or ST2−/−. The induction of nociceptive behaviors in naive mice due to recombinant IL-33 was reversed by the noncompetitive NMDA antagonist MK-801. ST2 antibody administration or ST2−/− markedly inhibited the increased activation of the astroglial janus kinase 2 (JAK2)–signal transducer and activator of transcription 3 (STAT3) cascade and the neuronal calcium–calmodulin-dependent kinase II (CaMKII)–cyclic adenosine monophosphate response element–binding protein (CREB) cascade after SNI. Moreover, intrathecal pretreatment with the CaMKII inhibitor KN-93 or the JAK2–STAT3 cascade inhibitor AG490 attenuated recombinant IL-33-induced nociceptive behaviors and NMDA subunit 1 up-regulation in naive mice. Conclusion Spinal IL-33/ST2 signaling contributes to neuropathic pain by activating the astroglial JAK2–STAT3 cascade and the neuronal CaMKII–CREB cascade.

Holiday camping and time spent in outdoor environments are critical childhood experiences. This study aims to identify the outcomes and processes underlying children's experiences of holiday camping. The researchers use the contextual model of learning as the theoretical background underpinning the study. Chinese children who left their families and participated in structured camping trips formed as the research respondents. Several child-centred research methods, including participant observation, focus group discussions, and interviews based on elicited drawings, were employed to study the children's construction of their experiences. Children mainly reported positive camping outcomes, including enhanced interpersonal skills, improved self-awareness, general knowledge and skills, and positive emotions. Negative outcomes including feelings of anxiety and boredom were also occasionally observed. The ongoing interplay of personal, social, and physical contexts works together to generate these camping outcomes. Practical and theoretical implications are offered to enhance positive outcomes and reduce negative ones when children go camping.

Acupoint catgut embedding (ACE) is a widely used traditional Chinese medicine method to manage various diseases, including chronic inflammatory pain. We sought to assess the possible analgesic effects of ACE in comparison with electroacupuncture (EA) and to study the analgesic mechanisms of ACE in a rat model of inflammatory pain induced by injection of complete Freund's adjuvant (CFA) into the hind paw of rats. The von Frey, radiant heat, and gait analysis tests were performed to evaluate the analgesic effects of ACE and EA, and Western blot and immunohistochemistry assays were carried out to determine the molecular mechanisms of ACE. ACE treatments were administered every 4 days or every week with different acupoints (ipsilateral, contralateral, or bilateral ST36 and GB30 acupoints). The most effective ACE strategy for attenuating the nocifensive response induced by CFA injection was performing ACE once a week at ipsilateral ST36 in combination with GB30. EA treatment every other day at ipsilateral ST36 and GB30 showed comparable analgesic effects. ACE inhibited the increased activation of the GluN1 subunit of the N-methyl-d-aspartate receptor and the subsequent Ca2+-dependent signals (CaMKII, ERK, and CREB) that take place in response to CFA. The effects of ACE were similar to intrathecal injection of vilazodone (a serotonin 1A receptor [5-HT1AR] agonist) and were blocked by WAY-100635 (a 5-HT1AR antagonist). In summary, we show that ACE attenuates CFA-induced inflammatory pain in rats by activating spinal 5-HT1AR and by inhibiting the phosphorylation of GluN1, thus, inhibiting the activation of Ca2+-dependent signaling cascades. PERSPECTIVE: This article presents the novel evidence concerning the spinal 5-HT1AR activation-related molecular signaling of ACE analgesia in a rat model of CFA-induced inflammatory pain. This work may help clinicians to verify the effectiveness of ACE analgesia and to better understand the underlying mechanism.

This study contributes to an understanding of how young citizens in developing tourist areas view and welcome tourists and tourism. The work is embedded in and builds on the conceptual and theoretical traditions of the tourist gaze and intercultural contact literature. The work was conducted in Lhasa, Tibet, and explored the views and preferences of over 250 young hosts for the types of tourists who visit the area. Photo-elicitation interviews, focus groups, and a questionnaire-based survey were employed in sequence to generate data. The welcome given to the tourists varied according to the classifications employed and the locations which the tourists visited. Five factors, which have relevance for other contexts, were identified to interpret the prospective welcome likely to be given to future tourists. The key issues shaping the young hosts’ responses were the immediate public impression tourists created, the extent of cultural distance between hosts and tourists, the nature of the tourist sites, local cultural values, and the hosts’ social life. Ways to assess young citizens’ views for incorporating in planning sustainable destination are offered.

Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a high-fat diet, we found that: (1) the acute thermal pain sensory threshold did not change in obese mice; (2) the model obese mice had fewer nociceptive responses in formalin-induced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation; (3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice, indicating the dysmodulation of topical leptin–leptin receptor signaling in these mice; and (4) leptin–leptin receptor signaling-deficient mice (ob/ob and db/db) or leptin–leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wild-type mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin–leptin receptor pathway could be a peripheral target against acute inflammatory pain.

Building on the under-utilized power of case studies, this conceptual review considers information to enhance Asian tourism sites and attractions. Soft infrastructure, defined as the total effect of the hospitality, interpretive and person-to-person encounters, was considered at 16 strategically selected locations drawn from 7 Asian countries. An emic, tourist-oriented perspective was used to appraise the effects of the soft infrastructure. The researchers employed information from academic publications, attraction websites, tourists' reviews and personal visits to identify common cross-site issues. Seven key issues were identified: the importance of emotional labour/sincerity; the value of quality and professionalism; creating understanding and the role of language; the appeal of performance and spectacle; the usefulness of immersion and participation; the power of authentic local voices; and the management of crowding and close encounters. Site and tourist precinct attraction managers can evaluate these...

Acupuncture or electroacupuncture (EA) has been demonstrated to have a powerful antihypernociceptive effect on inflammatory pain. The attenuation of G protein-coupled receptor kinase 2 (GRK2) in spinal cord and peripheral nociceptor has been widely acknowledged to promote the transition from acute to chronic pain and to facilitate the nociceptive progress. This study was designed to investigate the possible role of spinal GRK2 in EA antiallodynic in a rat model with complete Freund’s adjuvant (CFA) induced inflammatory pain. EA was applied to ST36 (“Zusanli”) and BL60 (“Kunlun”) one day after CFA injection. Single EA treatment at day 1 after CFA injection remarkably alleviated CFA induced mechanical allodynia two hours after EA. Repeated EA displayed significant antiallodynic effect from 2nd EA treatment and a persistent effect was observed during the rest of treatments. However, downregulation of spinal GRK2 by intrathecal exposure of GRK2 antisense 30 mins after EA treatment completely eliminated both the transient and persistent antiallodynic effect by EA treatment. These pieces of data demonstrated that the spinal GRK2 played an important role in EA antiallodynia on inflammatory pain.

The purpose of this study was to investigate whether whole-body vibration (WBV) combined with extra-load training can enhance the strength and speed of trained athletes compared with isolated WBV training or loaded training (LT) only. Twenty-one elite male track and field athletes were randomly assigned to a loaded vibration (LV) training group (n = 7), an unloaded vibration (ULV) training group (n = 7), and a LT group (n = 7). During 4 weeks of training, the LV group received the vibration stimulus (30 Hz and 4 mm) accompanied by a load comprising 75% of the maximum voluntary contraction (MVC), the ULV group received the same vibration stimulus without any load, and the LT group received only a load of 75% MVC without any vibration stimulus. The knee extensor isometric strength, and the concentric and eccentric strength were measured using an isokinetic dynamometer at 300°·s at a 30-m sprint speed before and after the training period. A 2-way mixed analysis of variance (time × group) was used to analyze the differences. Significant time × group interactions were observed for all the dependent variables (p ≤ 0.05). Regarding the post hoc analysis results, the LV group exhibited significant improvements for all the dependent variables after training (p ≤ 0.05), whereas the ULV group exhibited significantly reduced sprint speeds (p ≤ 0.05). The LV group demonstrated significantly superior eccentric strength compared with the ULV and LT groups after training (p ≤ 0.05), and the LV group also produced significantly superior sprint speeds compared with the ULV group after training (p ≤ 0.05). Vibration combined with extra-load training for 4 weeks significantly increased the muscle strength and speed of the elite male track and field athletes.

To solve the problem that wheeled robot in the path tracking is prone to slip or roll over at a sharp curve, structure of the wheeled robot and its path tracking features are analyzed, and a new Fuzzy-Neural Network (FNN) based path tracking method of two-stage (route and speed) control is proposed. In the first stage, a FNN controller determines the robot’s turning radius by processing robot’s pose information. In the second stage, the secondary controller adjusts angular and linear velocities by taking advantage of the turning radius and condition of the path ahead. The experiments show that the controlled robot can track the planned path accurately and robustly when it runs at high speed; the process of path tracking is stable and no slipping and rolling occur.

Chinese outbound tourists are pivotal global players in current international tourism. Their anticipated role in taking up new activities in the future warrants attention. This study focused on one emerging activity—drive tourism—as a model of the ways to manage the growth of new specialist interests. In detail, it examined Chinese recreational vehicle (RV) tourists’ self-reported safety concerns during their Australian RV trips. The study identified the successful coping mechanisms that Chinese tourists employ across the preparation, initial familiarity, and driving stages of their travels. A holistic safety and coping framework outlining 18 coping techniques was identified. The study revealed the symbiosis between tourists, tourism businesses, and associated organizations that can lead to positive behaviors to enhance safe and enjoyable experiences as new markets adopt novel activities in unfamiliar countries.

This study examines international tourists' experiences in Beijing's Silk Market, one of the China's most well-known tourist markets. Tourists' spontaneous reviews on TripAdvisor were analyzed through Leximancer, a computer-assisted qualitative data analysis software. The study confirms that markets can be major tourism attractions and can provide important experiences for international tourists. Most international tourists were impressed with their Silk Market trip. The dominant narratives of their experiences were the “price” of the items they “bought”, the “fun” of “bargaining”, and the “fake” quality of the products. Further analyses show that different satisfaction groups used somewhat different narratives to represent their shopping experiences and that male international tourists enjoyed the Silk Market experiences more than their female counterparts.

Transplantation of human amniotic mesenchymal stem cells (hAM-MSCs) seems to be a promising strategy for the treatment of neurodegenerative disorders, including Alzheimer's disease (AD). However, the clinical therapeutic effects of hAM-MSCs and their mechanisms of action in AD remain to be determined. Here, we used amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice to evaluate the effects of hAM-MSC transplantation on AD-related neuropathology and cognitive dysfunction. We found that hAM-MSC transplantation into the hippocampus dramatically reduced amyloid-β peptide (Aβ) deposition and rescued spatial learning and memory deficits in APP/PS1 mice. Interestingly, these effects were associated with increasing in Aβ-degrading factors, elevations in activated microglia, and the modulation of neuroinflammation. Furthermore, enhanced hippocampal neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG) and enhanced synaptic plasticity following hAM-MSC treatment could be another important factor in reversing the cognitive decline in APP/PS1 mice. Instead, the mechanism underlying the improved cognition apparently involves a robust increase in hippocampal synaptic density and neurogenesis that is mediated by brain-derived neurotrophic factor (BDNF). In conclusion, our data suggest that hAM-MSCs may be a new and effective therapy for the treatment of AD.

Cancer pain, particularly bone cancer pain, affects the quality of life of cancer patients, and current treatments are limited. Interleukin (IL)-33, a new member of the IL-1 super family, has been reported to be involved in the modulation of inflammatory pain. However, studies focused on its role in the modulation of cancer pain have been rare. The present study was designed to investigate whether spinal IL-33/ST2 signaling was involved in bone cancer-induced pain in mice. Bone cancer was induced via intra-femoral inoculation of 4T1 mammary carcinoma cells. The mice inoculated with carcinoma cells showed mechanical allodynia, heat hyperalgesia and a reduction in limb use, whereas phosphate-buffered saline or heat-killed cells-injected mice showed no significant difference compared to non-treated mice. The pain hypersensitive behaviors worsened over time and with bone destruction. Both the mRNA and the protein levels of IL-33 and relative cytokines (IL-1β, IL-6, TNF-a) were significantly increased in the spinal cord after the inoculation of carcinoma cells. Intrathecal administration of ST2 antibody to block IL-33/ST2 signaling alleviated pain behaviors in a dose-dependent manner in bone cancer pain mice compared with vehicle-injected mice. Moreover, the ST2(-/-) mice showed a significant amelioration of limb use and heat hyperalgesia compared to wild-type mice. Meanwhile, concentrations of spinal IL-1β, IL-6 and TNF-a in the cancer-bearing ST2(-/-) mice had no significant changes. These data further suggested that IL-33/ST2 signaling played a vital role in cancer pain. Our results provided evidence that IL-33 and its receptor ST2 may be a potential therapeutic target for the treatment of pain in bone cancer patients.