Medical services for sports injuries and illnesses in the Beijing 2022 Olympic Winter Games.

BACKGROUND: Beijing 2022 Olympic Winter Games was the second Games held amid the COVID-19 pandemic. To a certain extent, it has altered the way sporting activities operate. There is a lack of knowledge on injury risk and illness occurrence in elite winter sport athletes amid the COVID-19 pandemic. This study aimed to describe the incidence of injuries and illnesses sustained during the XXIV Olympic Winter Games in Beijing from February 4 to 20, 2022. METHODS: We recorded the daily number of injuries and illnesses among athletes reported by Beijing 2022 medical staff in the polyclinic, medical venues, and ambulance. We calculated injury and illness incidence as the number of injuries or illnesses occurring during competition or training, respectively, with incidence presented as injuries/illnesses per 100 athlete-days. RESULTS: In total, 2,897 athletes from 91 nations experienced injury or illness. Beijing 2022 medical staff reported 326 injuries and 80 illnesses, equaling 11.3 injuries and 2.8 illnesses per 100 athletes over the 17-day period. Altogether, 11% of the athletes incurred at least one injury and nearly 3% incurred at least one illness. The number of injured athletes was highest in the skating sports (n=104), followed by alpine skiing (n=53), ice track (n=37), freestyle skiing (n=36), and ice hockey (n=35), and was the lowest in the Nordic skiing disciplines (n=20). Of the 326 injuries, 14 (4.3%) led to an estimated absence from training or competition of more than 1 week. A total of 52 injured athletes were transferred to hospitals for further care. The number of athletes with illness (n=80) was the highest for skating (n=33) and Nordic skiing (n=22). A total of 50 illnesses (62.5%) were admitted to the department of dentistry/ophthalmology/otolaryngology, and the most common cause of illness was other causes, including preexisting illness and medicine (n=52, 65%). CONCLUSION: Overall, 11% of athletes incurred at least one injury during the Games, which is similar to the findings during the Olympic Winter Games in 2014 and 2018. Regarding illness, 2% of athletes were affected, which is approximately one-third of the number affected in the 2018 Olympic Winter Games.

Difference of pain vulnerability in adult and juvenile rodents: the role of SIRT1-mediated ClC-3 trafficking in sensory neurons.

ABSTRACT: Adults are more likely to suffer from chronic pain than minors, and its underlying mechanism remains unclear. SIRT1 an important age-related protein with function of lifespan extension; whether SIRT1 plays a role in the different pain vulnerability of adult and juvenile remains unclear. Here, we found that the expression level of SIRT1 in dorsal root ganglia (DRG) was related to the pain vulnerability. After nerve injury, the expression of SIRT1 in DRG was decreased in adult rodents whereas increased in juvenile rodents. Differential manipulation of SIRT1 abolished the different pain vulnerability between adult and juvenile rodents. Furthermore, SIRT1 interacted with ClC-3 channel and mediated ClC-3 membrane trafficking and Cl- current in DRG neurons. Differential manipulation of ClC-3 also abolished the difference in pain vulnerability between adult and juvenile rodents. The different anti-inflammatory ability determined the different change trends of SIRT1 and ClC-3 trafficking contributed to the different pain vulnerability in adult and juvenile rodents. In addition, the serum SIRT1 level was negatively correlated with the pain score in patients with chronic pain. These findings revealed the mechanism of the difference in pain vulnerability between adult and juvenile rodents and provided evidence for age-specific treatment of chronic pain.

Vortex formation of spherical self-propelled particles around a circular obstacle.

A vortex is a common ratchet phenomenon in active systems. The spatial symmetry is usually broken by introducing asymmetric shapes or spontaneously by collective motion in the presence of hydrodynamic interactions or other alignment effects. Unexpectedly, we observe, by simulations, the formation of a vortex in the simplest model of a circular obstacle immersed in a bath of spherical self-propelled particles. No symmetry-breaking factors mentioned above are included in this model. The vortex forms only when the particle activity is high, i.e. large persistence. The obstacle size is also a key factor and the vortex only forms in a limited range of obstacle sizes. The sustainment of the vortex originates from the bias of the rotating particle cluster around the obstacle in accepting the incoming particles based on their propelling directions. Our results provide new understanding of and insights into the spontaneous symmetry-breaking and ratchet phenomena in active matter.

Trends and characteristics in pre-hospital emergency care in Beijing from 2008 to 2017.

BACKGROUND: We aimed to describe and analyze the pre-hospital emergency medical service (EMS) in Beijing and provide information for the government and medical institutions to optimize EMS. METHODS: We collected all pre-hospital emergency data in Beijing from 2008 to 2017. The chief complaint in each case was classified according to the Medical Priority Dispatch System (MPDS). The sites' administrative districts were determined through geo-encoding of addresses and then classified into four functional regions. We analyzed the demand for EMS, emergency response times (ERT), and disease spectrum for Beijing as a whole, and for each functional region. RESULTS: A total of 4,192,870 pre-hospital EMS cases met the inclusion criteria, with a significant increase (P < 0.001) of 51.60% from 2008 to 2017. EMS demand was positively associated with population (r = 0.946, P < 0.001). The pre-hospital EMS demand rate was 1907.05 in 2008 and 2172.23 in 2017 per 100,000, with no significant change (P = 0.57). ERT increased significantly (P = 0.001), from 19.18 min in 2008 to 24.51 min in 2016. According to MPDS classifications, the demand for pre-hospital care increased for 14 diseases, remained stable for 19, and decreased for only 1 disease. Cases of injury-related disease increased significantly from approximately 90,000 in 2017, accounting for 20% of all pre-hospital EMS cases, and the demand rate decreased in the core region but increased in the sub-urban regions. Cases of heart problems and stroke/transient ischemic attack also increased significantly in the four functional regions, with the highest demand rate in the Core Functional Region. CONCLUSIONS: More resources and effort should be devoted to pre-hospital EMS according to the increased pre-hospital EMS demand and prolonged ERT in Beijing over our 10-year study period. Changes in disease spectrum and differences between functional regions should also be considered.

Establishment of trauma treatment teams within a regional severe trauma treatment system in China: study protocol for a national cluster-randomised trial.

INTRODUCTION: The implementation of first aid processes for patients with trauma in China faces significant challenges. These challenges include long response times of prehospital first aid services, lack of information exchange between prehospital first aid services and in-hospital emergency services, lack of a professional rescue team in the majority of hospitals, and lack of standardised training for prehospital and in-hospital emergency personnel. The purpose of the trial is to guide the establishment of an urban trauma treatment system in China, highlight the construction of a trauma treatment system tailored to the Chinese context and improve levels of medical treatment by selecting approximately 100 counties across China as pilots to establish a regional trauma treatment system. METHODS AND ANALYSIS: A cluster-randomised controlled trial will be performed in 98 county-level research institutes. Included research institutes will be randomised into an experimental group and a control group. Patients in both experimental and control groups will receive basic treatments. A trauma treatment team will be established in the experimental group. The primary outcome measure is in-hospital mortality rate of patients. The secondary outcome measures include mortality rate of patients within 30 days after trauma attack and within 30 days after discharge, the time between arrival in the institution and receiving consultation, and the time from admission to the start of surgery. The effects of establishment of trauma treatment teams on the treatment of severe trauma will be evaluated in all counties. ETHICS AND DISSEMINATION: The procedures have been approved by The Medical Ethics Committee of Peking University People's Hospital (No.2017PHB098-01) and conform to the Declaration of Helsinki. Data will be collected and analysed in accordance with participant privacy laws and regulations. Results will be disseminated through policy briefs, workshops, peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT03363880; Pre-results.

Feasibility study of a human papillomavirus E6 and E7 oncoprotein test for the diagnosis of cervical precancer and cancer.

Objective To evaluate the clinical value of human papillomavirus (HPV) E6 and E7 oncoprotein (HPV E6/E7) detection in the early screening of cervical cancer. Methods This prospective study evaluated all patients with suspected cervical intraepithelial neoplasia (CIN) as identified by the presence of at least one positive indicator from a ThinPrep cytologic test (TCT) and/or a Hybrid Capture 2 (HC2) HPV DNA test. The levels of E6/E7 oncoproteins were determined using Western blot analysis. The diagnostic value of the HPV E6/E7 protein assay was compared with the clinical diagnosis from TCT, HC2 and the gold standard of cervical biopsy histology. Results A total of 450 patients were enrolled in the study and based on histological findings, 102 patients were diagnosed with CIN1 (22.7%), 241 with CIN2 (53.6%), 96 with CIN3 (21.3%) and 11 with squamous cell carcinoma (2.4%). For a diagnosis of CIN2+, although the sensitivity of the HPV E6/E7 assay was lower than HC2 (65.5% versus 96.6%, respectively), the specificity was higher (38.2% versus 5.9%, respectively). The sensitivity of the HPV E6/E7 assay was higher than TCT (65.5% versus 36.2%, respectively). Conclusion Measuring HPV E6/E7 oncoprotein levels is a potential new biomarker for HPV type 16.

Medical Response to the Tianjin Explosions: Lessons Learned.

BACKGROUND: On August 12, 2015, a hazardous chemical explosion occurred in the Tianjin Port of China. The explosions resulted in 165 deaths, 8 missing people, injuries to thousands of people. We present the responses of emergency medical services and hospitals to the explosions and summarize the lessons that can be learned. METHODS: This study was a retrospective analysis of the responses of emergency medical services and hospitals to the Tianjin explosions. Data on injuries, outcomes, and patient flow were obtained from the government and the hospitals. RESULTS: A total of 46 ambulances and 143 prehospital care professionals were dispatched to the scene, and 198 wounded were transferred to hospitals by ambulance. More than 4000 wounded casualties surged into hospitals, and 798 wounded were admitted. Both emergency medical services and hospitals were quick and successful in the early stage of the explosions. The strategy of 4 centralizations (4Cs) for medical services management in a mass casualty event was successfully applied. CONCLUSIONS: The risk of accidental events has increased in recent years. We should take advantage of the lessons learned from the explosions and apply these in future disasters. (Disaster Med Public Health Preparedness. 2018; 12: 411-414).

Disturbed Matrix Metalloproteinase Pathway in Both Age-Related Macular Degeneration and Alzheimer's Disease.

Purpose. Abnormal protein deposits including ß-amyloid, found in ageing Bruch's membrane and brain, are susceptible to degradation by matrix metalloproteinases (MMPs). In ageing Bruch's membrane, these MMPs become less effective due to polymerisation and aggregation reactions (constituting the MMP Pathway), a situation much advanced in age-related macular degeneration (AMD). The likely presence of this MMP Pathway in brain with the potential to compromise the degradation of ß-amyloid associated with Alzheimer's disease (AD) has been investigated. Methods. Presence of high molecular weight MMP species (HMW1 and HMW2) together with the much larger aggregate termed LMMC was determined by standard zymographic techniques. Centrigugation and gel filtration techniques were used to separate and quantify the distribution between bound and free MMP species. Results. The MMP Pathway, initially identified in Bruch's membrane, was also present in brain tissue. The various MMP species displayed bound-free equilibrium and in AD samples, the amount of bound HMW1 and pro-MMP9 species was significantly reduced (p < 0.05). The abnormal operation of the MMP Pathway in AD served to reduce the degradation potential of the MMP system. Conclusion. The presence and abnormalities of the MMP Pathway in both brain and ocular tissues may therefore contribute to the anomalous deposits associated with AD and AMD.

Phase transition of a symmetric diblock copolymer induced by nanorods with different surface chemistry.

We investigate the phase transition of a symmetric diblock copolymer induced by nanorods with different surface chemistry. The results demonstrate that the system occurs the phase transition from a disordered structure to ordered parallel lamellae and then to the tilted layered structure as the number of rods increases. The dynamic evolution of the domain size and the order parameter of the microstructure are also examined. Furthermore, the influence of rod property, rod-phase interaction, rod-rod interaction, rod length, and polymerization degree on the behavior of the polymer system is also investigated systematically. Moreover, longer amphiphilic nanorods tend to make the polymer system form the hexagonal structure. It transforms into a perpendicular lamellar structure as the polymerization degree increases. Our simulations provide an efficient method for determining how to obtain the ordered structure on the nanometer scales and design the functional materials with optical, electronic, and magnetic properties.

Association between IL-6 Gene (-174 & -572 G/C) Polymorphisms and Endometrial Adenocarcinoma Risk.

We aimed to evaluate the association of IL-6 gene polymorphisms at positions of -174 and -572 and predisposition of endometrial adenocarcinoma (EAC) in a Chinese population. EAC patients have remarkably higher frequency of IL-6 -174 CC genotype [odds ratio (OR) =1.56, 95 % confidence interval (CI) =1.07-2.23; P = 0.03], IL-6 -572 CC genotype (OR =1.93, 95%CI =1.17-3.15; P = 0.01) and IL-6 -174 C allele (OR =1.22, 95 % CI =1.03-1.46; P = 0.04) compared with healthy controls. When stratified with FIGO stage, patients with III-IV EAC have a significantly higher frequency of IL-6 -174 CC genotype (OR =1.66, 95% CI =1.06-2.58; P = 0.02) than healthy controls. The CC genotype of IL-6 gene polymorphisms at positions of -174 and -572 may denote potential high risk of EAC.

IL-13 receptor α2 is a negative prognostic factor in human lung cancer and stimulates lung cancer growth in mice.

IL-13 receptor subunit alpha-2 (IL13Rα2) is associated with poor prognosis in some cancers. However, the role of IL13Rα2 in lung cancer remains unknown. We showed that IL13Rα2 overexpression was associated with late stages of disease progression and shorter disease-free survival (DFS) as well as overall survival (OS) in resected lung cancer patients. IL13Rα2 promoted the migration, invasion and anoikis resistance of lung cancer cells in vitro. Silencing of IL13Rα2 in lung cancer cells decreased invasion in vitro and lung metastasis in vivo. IL13Rα2 activated phosphatidylinositol 3 kinase (PI3K), Akt, and transcriptional coactivator with PDZ-binding motif (TAZ). Inhibition of PI3K attenuated activation of TAZ and its downstream target genes by IL13Rα2. We suggest that inhibition of IL13Rα2 is a potential therapeutic approach in lung cancer.

Relationship between haze and acute cardiovascular, cerebrovascular, and respiratory diseases in Beijing.

Haze is an atmospheric phenomenon in which dry particulate pollutants obscure the sky. Haze has been associated with chronic diseases, but its relationship with acute diseases is less clear. We aimed to determine the association between haze and acute cardiovascular, cerebrovascular, and respiratory diseases, in order to determine the influence of haze on human health. We compared the number of cases of acute cardiovascular, cerebrovascular, and respiratory diseases in Beijing Emergency Center between 2006 and 2013, with haze data from Beijing Observatory. The relationship between the number of hazy days and the number of cases of the above types of diseases was analyzed using univariate analyses. Both the number of cases and the number of hazy days showed a rising trend. The average number of cases per day for all three diseases was higher on hazy days than on non-hazy days. There was a positive correlation between the number of hazy days and the number of cases, and this correlation showed a hysteretic quality. Haze has an influence on acute cardiovascular (CVDs), cerebrovascular (CBDs), and respiratory system (RSDs) diseases. Haze seems to have an additive effect, since the associations between haze and number of cases were stronger in the following month than in the preceding month. The increasing trend in the number of hazy days might worsen the problem of haze-related diseases.

[Traffic injuries of pre-hospital treatment in the urban area of Beijing].

OBJECTIVE: To evaluate the current condition of urban road traffic injuries (RTIs) according to Beijing Emergency Medical Center (BEMC) from Jan. 1, 2004 to Dec. 31, 2010, analyze the social characteristics and explore the possible methods for prevention and improvement. METHODS: Using data from the Beijing Emergency Medical Center, we collected 19 550 victims who were involved in RTIs in Beijing from Jan. 1, 2004 to Dec. 31, 2010. The personal information, time of the injury event, road user type and striking vehicle type, as well as the site and severity of injury, were analyzed using Excel 2007 and SPSS 17.0 software with ANOVA of variance and Chi-squared tests. RESULTS: The annual rate of RTIs was 120.0 per 100 000 people in Beijing, and the mortality rate was about 4.97 per 100 000 people. Male victims were more than female victims (11 737 persons vs. 7 618 persons).The mean age was (72.92 ± 5.67) years. Overall, RTIs in all the age groups happened in October commonly, and were inclined to daytime, especially at noon. But different age groups had their special hour distribution features of RTIs. Traffic collisions occurred most frequently in pedestrians and cyclists (7 588,38.81%;3 790,19.39%). Majorities of victims presented with head injuries and lower-limb injuries(8 343,42.68%; 6 828,34.93%). These collisions included car striking accidents (11 490, 58.77%). And most of the older adults were classified as medium in severity (11 718, 59.94%). CONCLUSION: The prevention and treatment of RTIs, should focus on targeted prevention solutions and standardized pre-hospital rescue, according to specific population, time interval and vehicle usage.

Characterization of the gelatinase system of the laminar human optic nerve, and surrounding annulus of Bruch's membrane, choroid, and sclera.

PURPOSE: We determined the presence and levels of gelatinase matrix metalloproteinases (MMPs) in the optic nerve and surrounding rim region of the human fundus. METHODS: Samples of optic nerve, rim region, and Bruch's membrane-choroid from macular and peripheral regions were isolated from 9 pairs of human donor eyes. The MMPs were extracted and separated by gelatin zymography. Individual gelatinase species were identified by their respective molecular weights and levels quantified by standard densitometric techniques. Ratios of active/latent MMPs were calculated as representative indicators of the degree of proteolytic activity at each of the locations examined. RESULTS: All of the gelatinase species normally found in Bruch's membrane also were present in the optic nerve region. The presence of the high molecular weight MMP species (HMW1 and HMW2) was indicative of the age-related accumulation of polymerized MMPs 2 and 9. Level of activated MMPs was considerably raised in comparison with their latent forms at the optic nerve and surrounding region indicative of greater ongoing turnover of the matrix (P < 0.005). CONCLUSIONS: The components of the gelatinase pathway mediating matrix turnover in Bruch's membrane also were present in the optic nerve region. The presence of high levels of active MMPs 2 and 9 in comparison with the latent forms in the optic nerve and rim area is indicative of a high rate of matrix remodeling in these regions. Enhanced matrix turnover within the optic nerve region may represent an important mechanism for maintaining the plasticity of the lamina cribrosa.

Transformation of heavy metal speciation during sludge drying: mechanistic insights.

Speciation can fundamentally affect on the stability and toxicity of heavy metals in sludge from wastewater treatment plants. This research investigated the speciation of heavy metals in sludge from both municipal and industrial sources, and metal speciation change as a result of drying process to reduce sludge volume. The changes in sludge properties including sludge moisture content, temperature, density, and electrical conductivity were also monitored to provide insights into the mechanisms causing the change in heavy metal speciation. The results show that the drying process generally stabilized Cr, Cu, Cd, and Pb in sludge by transforming acid-soluble, reducible, and oxidizable species into structurally stable forms. Such transformation and stabilization occurred regardless of the sludge source and type, and were primarily caused by the changes in sludge properties associated with decomposition of organic matter and sulfide. The results enhanced our understanding of the geochemical behavior of heavy metals in municipal sludge, and are useful for designing a treatment system for environment-friendly disposal of sludge.

Prehospital road traffic injuries among the elderly in Beijing, China: data from the Beijing Emergency Medical Center, 2004-2010.

BACKGROUND: Road traffic injuries (RTIs) are a worldwide issue associated with increasing development and motorization. However, statistical studies do not include any analyses of Beijing's geriatric population. Using data from the Beijing Emergency Medical Center, we present the main characteristics of traffic injuries involving the elderly in Beijing. We also provide objective information for those concerned with the safety of traffic systems and the prevention of traffic injuries. METHODS: In a longitudinal, retrospective study, data were collected on 1706 victims aged 65 years and older who sustained traffic injuries in Beijing between 2004 and 2010. Personal information, time of injury event, emergency care response time, road user type, striking vehicle type, injury site, and severity of injury were analyzed using χ(2) tests and Logistic regression analysis. RESULTS: The annual rate of traffic injuries was 21.80 per 100 000 elderly people in Beijing, and the morbidity rate decreased from 2004 to 2010 (P < 0.001). The mean age was (72.92 ± 5.67) years, and 911 (53.40%) of the victims were male. The majority of victims sustained head and lower limb injuries and were classified as being of medium severity. Traffic collisions occurred most frequently in the daytime excluding rush hours; these collisions included being hit by a car (85.64%) and pedestrian victim injuries (79.19%). Our statistical analysis found three factors for injury severity: abdominal injuries (P < 0.001), number of injury sites (P = 0.027), and head injuries (P = 0.034). The decline in traffic injuries is due to a decrease in victims aged 65-74 years and pedestrians; the severity of RTIs also decreased. CONCLUSIONS: This study highlights the declining trend in traffic injuries among older adults in Beijing. However, traffic injuries remain a serious public health problem for the elderly and effective measures are required to reduce their incidence.

[Short-course kidney-invigorating therapy improves near-term semen quality in asthenozoospermic men with kidney deficiency].

OBJECTIVE: To evaluate the effect of short-course kidney-invigorating therapy on near-term semen quality in asthenozoospermic men with kidney deficiency. METHODS: Based on the differential types in traditional Chinese medicine, 121 asthenozoospermia patients received at our clinic of andrology were divided into groups A (kidney-yin deficiency), B (kidney-yang deficiency) and C (spleen and kidney deficiency), and treated with Yougui Decoction plus Wuziyanzong Pills, Jinkuishenqi Pills plus Wuziyanzong Pills, and Shizi Decoction plus Liujunzi Decoction, respectively, all given once daily for 4 weeks. Sperm parameters of the patients were analyzed with the computer-assisted sperm analysis system before and after treatment and compared among the three groups. RESULTS: The baseline sperm concentrations in groups A, B and C ([70.4 +/- 38.6], [73.5 +/- 40.2] and [56.0 +/-34.4] x 10(6)/ml) showed no significant differences from those after medication ([74.4 +/- 32.6], [67.0 +/- 30.8] and [58.6 +/- 24.6] x 10(6)/ml) (P > 0.05). The percentages of grade a sperm in the three groups were (12.9 +/- 5.3)%, (13.7 +/- 7.7)% and (12.9 +/- 6.4)% respectively after treatment, significantly higher than (9.9 +/- 6.7)%, (9.3 +/- 5.4)% and (9.0 +/- 6.8)% before treatment (P < 0.05), and so were the percentages of grade a + b sperm ([37.4 +/- 10.2 ]%, [35.7 +/- 13.7]% and [35.9 +/- 12.3]% after treatment versus [29.6 +/- 13.2]%, [27.5 +/- 10.4]% and [28.3 +/- 12.1]% before treatment, P < 0.05). All the three groups showed significantly increased sperm motility after treatment ([53.8 +/- 10.5]%, [52.6 +/- 15.2]% and [51.1 +/- 13.1]%) as compared with the baseline levels ([44.3 +/- 14.0]%, [43.5 +/- 15.0]% and [42.4 +/- 14.9]%) (P < 0.05). The cure rate and total effectiveness rate were significantly higher in group B than in A (P < 0.05), but had no significant differences between either A and C or B and C (P > 0.05). CONCLUSION: Short-course kidney-invigorating therapy can significantly improve near-term semen quality in asthenozoospermic men with kidney asthenia, especially in those with kidney-yang deficiency, and it has no obvious adverse effects.

Modification of rat model of sciatica induced by lumber disc herniation and the anti-inflammatory effect of osthole given by epidural catheterization.

One of the most treatable causes of lower back pain and associated sciatica is lumbar disc herniation (LDH), which is characterized by rupture of the hard outer wall (annulus fibrosis) in a lumbar intervertebral disc. In the current study, we aimed to: (1) develop and characterize a rat model of sciatica induced by LDH, while introducing a novel method of epidural catheterization; (2) use this model to evaluate the effect of osthole on pain due to LDH, and (3) gain insight into the mechanisms through which osthole affects sciatica induced by LDH. The results indicate that our newly developed rat model maintained mechanical allodynia for 28 days without reduction. Moreover, cyclooxygenase-2 (COX-2) and nitric oxide synthase (NOS) were overexpressed in the associated inflammatory response, which is consistent with clinical manifestations of the disease. We then used this model to study the effect and mechanisms through which osthole affected pain due to LDH. Our study suggests that osthole is capable of reversing hyperalgesia due to LDH, potentially through modulation of activity of COX-2 and NOS, two important proteins for the exacerbation of pain due to LDH. Finally, a molecular modeling simulation showed that osthole has unique binding capabilities to both NOS and COX-2. As the model-induced mechanical hyperalgesia response was consistent, and the position of the catheter tip and the extension/spreading of the drug in the epidural space were reliable, this study developed an improved model to study remedies for sciatic pain. Moreover, our studies demonstrate that osthole may be a feasible treatment for the reduction of pain due to hyperalgesia.

Osthole, a herbal compound, alleviates nucleus pulposus-evoked nociceptive responses through the suppression of overexpression of acid-sensing ion channel 3 (ASIC3) in rat dorsal root ganglion.

BACKGROUND: Osthole (Ost), a natural coumarin derivative, has been shown to inhibit many pro-inflammatory mediators and block voltage-gated Na+ channels. During inflammation, acidosis is an important pain inducer which activates nociceptors by gating depolarizing cationic channels, such as acid-sensing ion channel 3 (ASIC3). The aim of this study was to examine the effects of Ost on nucleus pulposus-evoked nociceptive responses and ASIC3 over-expression in the rat dorsal root ganglion, and to investigate the possible mechanism. MATERIAL/METHODS: Radicular pain was generated with application of nucleus pulposus (NP) to nerve root. Mechanical allodynia was evaluated using von Frey filaments with logarithmically incremental rigidity to calculate the 50% probability thresholds for mechanical paw withdrawal. ASIC3 protein expression in dorsal root ganglions (DRGs) was assessed with Western blot and immunohistochemistry. Membrane potential (MP) shift of DRG neurons induced by ASIC3-sensitive acid (pH6.5) was determined by DiBAC(4) (3) fluorescence intensity (F.I.). RESULTS: The NP-evoked mechanical hyperalgesia model showed allodynia for 3 weeks, and ASIC3 expression was up-regulated in DRG neurons, reaching peak on Day 7. Epidural administration of Ost induced a remarkable and prolonged antinociceptive effect, accompanied by an inhibition of over-expressed ASIC3 protein and of abnormal shift of MP. Amiloride (Ami), an antagonist of ASIC3, strengthened the antinociceptive effect of Ost. CONCLUSIONS: Up-regulation of ASIC3 expression may be associated with NP-evoked mechanical hyperalgesia. A single epidural injection of Ost decreased ASIC3 expression in DGR neurons and the pain in the NP-evoked mechanical hyperalgesia model. Osthole may be of great benefit for preventing chronic pain status often seen in lumbar disc herniation (LDH).

Laser-mediated activation of human retinal pigment epithelial cells and concomitant release of matrix metalloproteinases.

PURPOSE: To investigate cellular dynamics and associated matrix metalloproteinase (MMP) release patterns of human retinal pigment epithelium (RPE) cells subsequent to irradiation by nanosecond pulsed laser at energy levels below visual threshold. METHODS: Following a stabilization period, human RPE-Bruch's-choroid explants were irradiated with a nanosecond laser system (Q-switched, frequency doubled YAG laser, 532 nm), using a 400 µm spot size with a discontinuous energy distribution and total irradiance of 240 mJ/cm², and returned to the incubator for a further 14 days. RPE cellular dynamics were assessed using confocal laser scanning, conventional microscopy, cell viability, and proliferation assays. MMPs were quantified by gelatine zymography and densitometry. RESULTS: Within 4 hours of laser intervention, 47% ± 8% (mean ± SEM, n = 6) of the RPE cells within the treatment zone showed clear signs of injury. By posttreatment days 10 to 14, most of the injured beds were repopulated by migrating RPE cells from regions surrounding the lesion. Release of inactive MMP-2 was little altered over the 2-week experimental period, whereas levels of inactive MMP-9 increased 1.3-fold by day 1 to reach a 2.8-fold threshold by day 7 (n = 4; P < 0.05). However, changes in activated MMP-2 and MMP-9 were much more profound with levels increasing 6.7 ± 2.6-fold (mean ± SEM, n = 6; P < 0.001) and 4.4 ± 1.1-fold (mean ± SEM, n = 5; P < 0.01), respectively, above controls at day 7 post laser. CONCLUSIONS: The nanosecond laser pulse modality provides an avenue for transiently increasing the RPE-mediated release of active MMP enzymes. The likely impact of this enzymatic release on the structural and functional aspects of aging Bruch's membrane requires further evaluation.