Decoding the influence of low temperature on biofilm development: The hidden roles of c-di-GMP.

Biofilms are widely used and play important roles in biological processes. Low temperature of wastewater inhibits the development of biofilms derived from wastewater activated sludge. However, the specific mechanism of temperature on biofilm development is still unclear. This study explored the mechanism of temperature on biofilm development and found a feasible method to enhance biofilm development at low temperature. The amount of biofilm development decreased by approximately 66 % and 55 % at 4 °C and 15 °C, respectively, as compared to 28 °C. The cyclic dimeric guanosine monophosphate (c-di-GMP) concentration also decreased at low temperature and was positively correlated with extracellular polymeric substance (EPS) content, formation, and adhesion strength. Microbial community results showed that low temperature inhibited the normal survival of most microorganisms, but promoted the growth of some psychrophile bacteria like Sporosarcina, Caldilineaceae, Gemmataceae, Anaerolineaceae and Acidobacteriota. Further analysis of functional genes demonstrated that the abundance of functional genes related to the synthesis of c-di-GMP (K18968, K18967 and K13590) decreased at low temperature. Subsequently, the addition of exogenous spermidine increased the level of intracellular c-di-GMP and alleviated the inhibition effect of low temperature on biofilm development. Therefore, the possible mechanism of low temperature on biofilm development could be the inhibition of the microorganism activity and reduction of the communication level between cells, which is the closely related to the EPS content, formation, and adhesion strength. The enhancement of c-di-GMP level through the exogenous addition of spermidine provides an alternative strategy to enhance biofilm development at low temperatures. The results of this study enhance the understanding of the influence of temperature on biofilm development and provide possible strategies for enhancing biofilm development at low temperatures.

Stochastic processes shape microbial community assembly in biofilters: Hidden role of rare taxa.

Stochastic and deterministic processes are the major themes governing microbial community assembly; however, their roles in bioreactors are poorly understood. Herein, the mechanisms underlying microbial assembly and the effect of rare taxa were studied in biofilters. Phylogenetic tree analysis revealed differences in microbial communities at various stages. Null model analysis showed that stochastic processes shaped the community assembly, and deterministic processes emerged only in the inoculated activated sludge after domestication. This finding indicates the dominant role of stochastic factors (biofilm formation, accumulation, and aging). The Sloan neutral model corroborated the advantages of stochastic processes and mainly attributed these advantages to rare taxa. Cooccurrence networks revealed the importance of rare taxa, which accounted for more than 85% of the keystones. Overall, these results provide good foundations for understanding community assembly, especially the role of rare taxa, and offer theoretical support for future community design and reactor regulation.

A method establishment and application for biofilm quorum quenching activity assay.

The existence of quorum sensing (QS) and quorum quenching (QQ) plays important roles in biofilm formation. However, direct detection of QS ability is difficult due to the low concentrations of signal molecules inside the biofilm. Therefore, QQ activity is typically used to indicate the attribution of QS/QQ to the biofilm. Nevertheless, current detection methods of QQ activity based on biosensors present undesirable operability and accuracy. In this study, the 96-well plate assay based on a specific biosensor, Agrobacterium tumefaciens A136, and a colorimetric substance, X-gal was established. The reliable fitting results were obtained by standardizing the composition of the A136 X-gal assay solution and optimizing the operating conditions. This method improved the accuracy of QQ activity detection and reduced time and cost consumption. Finally, the 96-well plate assay was successfully applied to detect the QQ activities of biofilm samples and explore possible environmental influencing factors. In general, this study provided a new strategy for understanding the QQ effect in biofilm systems.

Microbial community evolution and functional trade-offs of biofilm in odor treatment biofilters.

Biofilters inoculated with activated sludge are widely used for odor control in WWTP. In this process, biofilm community evolution plays an important role in the function of reactor and is closely related to reactor performance. However, the trade-offs in biofilm community and bioreactor function during the operation are still unclear. Herein, an artificially constructed biofilter for odorous gas treatment was operated for 105 days to study the trade-offs in the biofilm community and function. Biofilm colonization was found to drive community evolution during the start-up phase (phase 1, days 0-25). Although the removal efficiency of the biofilter was unsatisfactory at this phase, the microbial genera related to quorum sensing and extracellular polymeric substance secretion led to the rapid accumulation of the biofilm (2.3 kg biomass/m3 filter bed /day). During the stable operation phase (phase 2, days 26-80), genera related to target-pollutant degradation showed increases in relative abundance, which accompanied a high removal efficiency and a stable accumulation of biofilm (1.1 kg biomass/m3 filter bed/day). At the clogging phase (phase 3, days 81-105), a sharp decline in the biofilm accumulation rate (0.5 kg biomass/m3 filter bed /day) and fluctuating removal efficiency were observed. The quorum quenching-related genera and quenching genes of signal molecules increased, and competition for resources among species drove the evolution of the community in this phase. The results of this study highlight the trade-offs in biofilm community and functions during the operation of bioreactors, which could help improve bioreactor performance from a biofilm community perspective.

Engineering a Pseudomonas putida as living quorum quencher for biofilm formation inhibition, benzenes degradation, and environmental risk evaluation.

Bacterial communication interruption based on quorum quenching (QQ) has been proven its potential in biofilm formation inhibition and biofouling control. However, it would be more satisfying if QQ could be combined with the efficient degradation of contaminants in environmental engineering. In this study, we engineered a biofilm of Pseudomonas putida through introducing a QQ synthetic gene, which achieved both biofilm formation inhibition and efficient degradation of benzene series in wastewater. The aiiO gene introduced into the P. putida by heat shock method was highly expressed to produce QQ enzyme to degrade AHL-based signal molecules. The addition of this engineered P. putida reduced the AHLs concentration, quorum sensing gene expression, and connections of the microbial community network in activated sludge and therefore inhibited the biofilm formation. Meanwhile, the sodium benzoate degradation assay indicated an enhanced benzene series removal ability of the engineering bacteria on activated sludge. Besides, we also demonstrated a controllable environmental risk of this engineered bacteria through monitoring its abundance and horizontal gene transfer test. Overall, the results of this study suggest an alternative strategy to solve multiple environmental problems through genetic engineering means and provide support for the application of engineered bacteria in environmental biotechnology.

Microbial community regulation and performance enhancement in gas biofilters by interrupting bacterial communication.

BACKGROUND: Controlling excess biomass accumulation and clogging is important for maintaining the performance of gas biofilters and reducing energy consumption. Interruption of bacterial communication (quorum quenching) can modulate gene expression and alter biofilm properties. However, whether the problem of excess biomass accumulation in gas biofilters can be addressed by interrupting bacterial communication remains unknown. RESULTS: In this study, parallel laboratory-scale gas biofilters were operated with Rhodococcus sp. BH4 (QQBF) and without Rhodococcus sp. BH4 (BF) to explore the effects of quorum quenching (QQ) bacteria on biomass accumulation and clogging. QQBF showed lower biomass accumulation (109 kg/m3) and superior operational stability (85-96%) than BF (170 kg/m3; 63-92%) at the end of the operation. Compared to BF, the QQBF biofilm had lower adhesion strength and decreased extracellular polymeric substance production, leading to easier detachment of biomass from filler surface into the leachate. Meanwhile, the relative abundance of quorum sensing (QS)-related species was found to decrease from 67 (BF) to 56% (QQBF). The QS function genes were also found a lower relative abundance in QQBF, compared with BF. Moreover, although both biofilters presented aromatic compounds removal performance, the keystone species in QQBF played an important role in maintaining biofilm stability, while the keystone species in BF exhibited great potential for biofilm formation. Finally, the possible influencing mechanism of Rhodococcus sp. BH4 on biofilm adhesion was demonstrated. Overall, the results of this study achieved excess biomass control while maintaining stable biofiltration performance (without interrupting operation) and greatly promoted the use of QQ technology in bioreactors. Video Abstract.

The role of PTEN in primary sensory neurons in processing itch and thermal information in mice.

PTEN is known as a tumor suppressor and plays essential roles in brain development. Here, we report that PTEN in primary sensory neurons is involved in processing itch and thermal information in adult mice. Deletion of PTEN in the dorsal root ganglia (DRG) is achieved in adult Drg11-CreER: PTENflox/flox (PTEN CKO) mice with oral administration of tamoxifen, and CKO mice develop pathological itch and elevated itch responses on exposure to various pruritogens. PTEN deletion leads to ectopic expression of TRPV1 and MrgprA3 in IB4+ non-peptidergic DRG neurons, and the TRPV1 is responsive to capsaicin. Importantly, the elevated itch responses are no longer present in Drg11-CreER: PTENflox/flox: TRPV1flox/flox (PTEN: TRPV1 dCKO) mice. In addition, thermal stimulation is enhanced in PTEN CKO mice but blunted in dCKO mice. PTEN-involved regulation of itch-related gene expression in DRG neurons provides insights for understanding molecular mechanism of itch and thermal sensation at the spinal level.

Risk factors for urban road traffic injuries in Hangzhou, China.

OBJECTIVE: To investigate factors that most influence urban road traffic injuries (RTI) mortality and morbidity. METHODS: The study used linked police and hospital records of RTI patients in the city of Hangzhou during the 3-year period 2004-2006. Three RTI outcome groups were included: (1) fatally injured; (2) severely injured; and (3) mildly injured persons. RESULTS: High risks for fatal road traffic accidents (RTA) were found on urban links, over weekend, during night hours, in male drivers who drove old vehicles without using seat belts, and at exceeding speeds, or with night time accidents and bad weather condition. In case of higher risk for all urban road users on urban junctions, the numbers on mildly injury cases were increasing. The highest combined risk for dying or being severely injured was found in male drivers driving at excessive speed, on urban links, and with night time accidents. CONCLUSIONS: Intensifying safety education of motor vehicle drivers, enhancing traffic management and keeping balance of "person-vehicle-road" system will greatly reduce the urban traffic accidents and casualties.

[Analysis of clinical risk factors in progression from acute lung injury to acute respiratory distress syndrome in severe trauma patients].

OBJECTIVES: To investigate the potential risk factors of affecting progression from acute lung injury (ALI) to acute respiratory distress syndrome in severe trauma population. METHODS: Twenty potential risk factors of affecting progression of acute lung injury were examined by univariate and multivariate logistic analyses among the severe trauma patients in a retrospective study. RESULTS: All of 375 specially severe trauma patients with ALI were included for analysis. The six risk factors that affected the progression from acute lung injury to acute respiratory distress syndrome were sepsis, duration of trauma, APACHE II score, DIC, aspiration of gastric contents, and advanced age. Specific risk factors also affected different patient subpopulations at different degrees. CONCLUSION: Impact of sepsis, DIC and duration of trauma that predict progression of ALI exists throughout the entire treatment period while aspiration of gastric contents and APACHE II score might affect aggravation of ALI only during the early period; due to deterioration of pulmonary function and severely traumatic injury, advanced age is still an independent risk factor; patients with these risk factors need aggressive supportive cares as early as possible in order to prevent further aggravations.

Risk factors of mortality in road traffic injury patients with acute respiratory distress syndrome.

BACKGROUND: Among the deaths due to trauma, about one half of the patients suffer from road traffic injury (RTI). Most of RTI patients complicate acute respiratory distress syndrome (ARDS) and severe multiple injuries. ARDS is a major contributor to morbidity and mortality in trauma patients. Although many injuries and conditions are believed to be associated with ARDS independent risk factors in trauma patients, their relative importance in development of the syndrome are undefined. We hypothesize that not all of the traditional risk factors impacting mortality are independently associated with patients strictly identified by traffic injury. This study aimed to sieve distinctive risk factors in our RTI population, meanwhile, we also hypothesize that there may exist significantly different risk factors in these patients. METHODS: This was a retrospective cohort study regarding RTI as a single cause for emergency intensive care unit (EICU) admission. Patients identified as severe RTI with post-traumatic ARDS were enrolled in a prospectively maintained database between May 2002 and April 2007 and observed. Twenty-three items of potential risk impacting mortality were calculated by univariate and multivariate Logistic analyses in order to find distinctive items in these severe RTI patients. RESULTS: There were 247 RTI patients with post-traumatic ARDS admitted to EICU during the study period. The unadjusted odds ratio (OR) and 95% confidence intervals (CI) of mortality were associated with six risk factors out of 23: APACHE II score, duration of trauma factor, pulmonary contusion, aspiration of gastric contents, sepsis and duration of mechanical ventilation. The adjusted ORs with 95% CI were denoted with respect to surviving beyond 96 hours EICU admission (APACHE II score, duration of trauma factor, aspiration of gastric contents), APACHE II score beyond 20 EICU admission (duration of trauma factor, sepsis, duration of mechanical ventilation) and mechanical ventilation beyond 7 days EICU admission (duration of trauma factor and sepsis). CONCLUSIONS: We have retrospectively demonstrated an adverse effect of six different risk factors out of 23 items in mortality of post-traumatic ARDS within severe RTI patients and, moreover, gained distinct outcomes in stratified patients under real emergency trauma circumstance. An impact of APACHE II score and pulmonary contusion contributing to prediction of mortality may exist in prophase after traffic injury. Sepsis is still a vital risk factor referring to systemic inflammatory response syndrome, infection, and secondary multiple organs dysfunction. Eliminating trauma factors as early as possible becomes the critical therapeutic measure. Aspiration of gastric contents could lead to incremental mortality due to severe ventilation associated pneumonia. Long-standing mechanical ventilation should be constrained on account of severe refractory complications.

Comparison of the new injury severity score and the injury severity score in multiple trauma patients.

OBJECTIVE: To assess whether these characteristics of less misclassification and greater area under receiver operator characteristic (ROC) curve of the new injury severity score (NISS) are better than the injury severity score (ISS) as applying it to our multiple trauma patients registered into the emergency intensive care unit (EICU). METHODS: This was a retrospective review of registry data from 2 286 multiple trauma patients consecutively registered into the EICU from January 1,1997 to December 31, 2006 in the Second Affiliated Hospital, Medical School of Zhejiang University in China. Comparisons between ISS and NISS were made using misclassification rates, ROC curve analysis, and the H-L statistics by univariate and multivariate logistic progression model. RESULTS: Among the 2 286 patients, 176 (7.7%) were excluded because of deaths on arrival or patients less than 16 years of age. The study population therefore comprised 2 110 patients. Mean EICU length of stay (LOS) was 7.8 days ?2.4 days. Compared with the blunt injury group, the penetrating injury group had a higher percentage of male, lower mean EICU LOS and age. The most frequently injured body regions were extremities and head/neck, followed by thorax, face and abdomen in the blunt injury group; whereas, thorax and abdomen were more frequently seen in the penetrating injury group. The minimum misclassification rate for NISS was slightly less than ISS in all groups (4.01% versus 4.49%). However, NISS had more tendency to misclassify in the penetrating injury group. This, we noted, was attributed mainly to a higher false-positive rate (21.04% versus 15.55% for ISS, t equal to 3.310, P less than 0.001), resulting in an overall misclassification rate of 23.57% for NISS versus 18.79% for ISS (t equal to 3.290, P less than 0.001). In the whole sample, NISS presented equivalent discrimination (area under ROC curve: NISS equal to 0.938 versus ISS equal to 0.943). The H-L statistics showed poorer calibration (48.64 versus 32.11, t equal to 3.305, P less than 0.001) in the penetrating injury group. CONCLUSIONS: NISS should not replace ISS because they share similar accuracy and calibration in predicting multiple blunt trauma patients. NISS may be more sensitive but less specific than ISS in predicting mortality in certain penetrating injury patients.

Research progress in mechanism of traumatic brain injury affecting speed of fracture healing.

In patients who have sustained traumatic brain injury with associated extremity fracture, there is often a clinical perception that the rate of new bone formation around the fracture site increases.(1) An overgrowth of callus is observed and ectopic ossification even occurs in the muscle,(2) but the mechanism remains unclear. Whether this rapidly-formed new bone is fracture callus or a variant of heterotopic ossification, a common complication of traumatic brain injury, is the subject of some debates.(3) It is generally believed that the process of fracture healing is a recapitulation of normal embryonic osteogenesis,(4) i.e. ,a series of changes in the intracellular and extracellular matrix, which start from the injury of cells, blood vessels and bone matrix to a complete reconstruction of the bone.(5) It is a complex process influenced by multi-level and multi-route regulations of the general and local environments in the body, and many growth factors participate in this process, which is the base of bone healing;(6) whatever methods are used to promote bone healing, they are based on accelerating the changes of growth factors.(7) So it is worth making a thorough study on the mechanism, by which traumatic brain injury influences the expression levels of growth factors and consequently affects the speed of bone healing.

Rapid detection of pneumothorax by ultrasonography in patients with multiple trauma.

INTRODUCTION: Early detection of pneumothorax in multiple trauma patients is critically important. It can be argued that the efficacy of ultrasonography (US) for detection of pneumothorax is enhanced if it is performed and interpreted directly by the clinician in charge of the patients. The aim of this study was to assess the ability of emergency department clinicians to perform bedside US to detect and assess the size of the pneumothorax in patients with multiple trauma. METHODS: Over a 14 month period, patients with multiple trauma treated in the emergency department were enrolled in this prospective study. Bedside US was performed by emergency department clinicians in charge of the patients. Portable supine chest radiography (CXR) and computed tomography (CT) were obtained within an interval of three hours. Using CT and chest drain as the gold standard, the diagnostic efficacy of US and CXR for the detection of pneumothorax, defined as rapidity and accuracy (sensitivity, specificity, positive predictive value, negative predictive value), were compared. The size of the pneumothorax (small, medium and large) determined by US was also compared to that determined by CT. RESULTS: Of 135 patients (injury severity score = 29.1 +/- 12.4) included in the study, 83 received mechanical ventilation. The time needed for diagnosis of pneumothorax was significantly shorter with US compared to CXR (2.3 +/- 2.9 versus 19.9 +/- 10.3 minutes, p < 0.001). CT and chest drain confirmed 29 cases of pneumothorax (21.5%). The diagnostic sensitivity, specificity, positive and negative predictive values and accuracy for US and radiography were 86.2% versus 27.6% (p < 0.001), 97.2% versus 100% (not significant), 89.3% versus 100% (not significant), 96.3% versus 83.5% (p = 0.002), and 94.8% versus 84.4% (p = 0.005), respectively. US was highly consistent with CT in determining the size of pneumothorax (Kappa = 0.669, p < 0.001). CONCLUSION: Bedside clinician-performed US provides a reliable tool and has the advantages of being simple and rapid and having higher sensitivity and accuracy compared to chest radiography for the detection of pneumothorax in patients with multiple trauma.

Development of the trauma emergency care system based on the three links theory.

The three links theory applied in trauma emergency care system refers to an integrated system with the three important components of trauma emergency care system, viz. prehospital trauma services, hospital trauma services and critical care services. The development of the trauma emergency care system should be guided by the three links theory so as to set up a practical and highly efficient system: a prompt operating and monitoring transportation system, a smooth and real-time information system, a rational and sustainable system of regulations and contingency plans, and a system for cultivating all-round trauma physicians.

Basic fibroblast growth factor alleviates brain injury following global ischemia reperfusion in rabbits.

The aim of this study was to explore the protective effect of basic fibroblast growth factor (bFGF) on brain injury following global ischemia reperfusion and its mechanisms. Brain injury following global ischemia was induced by four vessels occlusion and systemic hypotension. Twenty-four rabbits were randomized into three groups: group A, only dissection of vessels; group B, intravenous infusion of normal saline after reperfusion for 6 h; group C, 30 microg/kg bFGF injected intravenously at the onset of reperfusion, then infused with 10 microg/(kg.h) for 6 h. Serum neuron specific enolase (NSE), S-100B, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-8 (IL-8) were measured before ischemia, 30 min after ischemia, 0.5, 1, 3, 6 h after reperfusion. Brain water content was determined and cerebral histopathological damages were compared. NSE and S-100B were increased 1 h after reperfusion and reached their peaks 6 h after reperfusion, but were much higher in group B than those in group C 3, 6 h after reperfusion. In groups B and C, TNF-alpha was increased after ischemia and IL-1 and IL-8 were increased significantly 0.5 h after reperfusion, then reached their peaks 6 h, 3 h, 6 h after reperfusion respectively. TNF-alpha and IL-8 at the time points of 1 h and 3 h and IL-1 at 3 h and 6 h in group C were correspondingly lower than those in group B. These indices in group A were nearly unchanged. There were less severe cerebral histopathological damages in group C compared with group B, but no difference in brain water content. It could be concluded that bFGF alleviates brain injury following global ischemia and reperfusion by down-regulating expression of inflammatory factors and inhibiting their activities.

Neurochemical characterization of pERK-expressing spinal neurons in histamine-induced itch.

Acute itch is divided into histamine- and non-histamine-dependent subtypes, and our previous study has shown that activation of ERK signaling in the spinal dorsal horn (SDH) is required selectively for histamine-induced itch sensation. Morphological characteristics of pERK-expressing neurons are required for exploring the mechanism underlying spinal itch sensation. To investigate whether pERK-expressing neurons are supraspinally-projecting neurons, we injected Fluorogold (FG) into the ventrobasal thalamic complex (VB) and parabrachial region, the two major spinal ascending sites in rodents. A small number (1%) of pERK-positive neurons were labeled by FG, suggesting that histamine-induced activation of ERK is primarily located in local SDH neurons. We then examined the co-localization of pERK with Calbindin and Lmx1b, which are expressed by excitatory neurons, and found that more than half (58%) of pERK-positive neurons expressed Lmx1b, but no co-expression with Calbindin was observed. On the other hand, approximately 7% of pERK-positive neurons expressed GAD67, and 27% of them contained Pax2. These results support the idea that pERK-expressing neurons serve as a component of local neuronal circuits for processing itch sensation in the spinal cord.

Epidemiological characteristics of expressway traffic trauma in 2040 cases.

OBJECTIVE: To evaluate the epidemiologic characteristics of expressway traffic trauma in 2040 cases in Zhejiang Province. METHODS: The data of 2040 cases of expressway traffic trauma taken from Zhejiang Provincial Expressway Traffic Bureau were analyzed with computer techniques. RESULTS: A total of 2040 persons were injured in 7963 expressway traffic accidents in Zhejiang Province from January 1999 to December 2001. Among them, 435 persons died (mortality, 21.3%) and 1 605 were injured. The economic losses were over 170 million yuan RMB. The accidents caused by human factors accounted for 84.9% (vehicle drivers accounting for 79.2%), which mainly included improper measures (20.4%), steering failure (17.7%), insufficient longitudinal space (15.9%), over-speed drive (12.5%), fatigue drive (6.4%), loading violation (5.9%) and careless drive (6.3%). Mechanical troubles and other factors took up 15.1%. There existed obvious uneven distribution among various regions. Jiaxing and Shaoxing were the sections with high incidence of accidents. The accidents mostly happened at 12:00-18:00, but the causing-dead ones most concentrated at 0:00-6:00. The main victims were young and middle-aged people (accounting for 72.3%), but accident-stricken children and elderly persons (over 70 years old) took up higher mortalities (30.2% and 40.7%, respectively). CONCLUSIONS: The number of expressway traffic accidents and the economic losses are increasing year by year, with obvious uneven distribution at different places, different time and under different weather conditions. To reduce the accident frequency, it is important to strengthen the enforcement of traffic regulation, to balance the system of "person-vehicle-road", and to improve the safety consciousness of people.

Dynamically monitoring tissue factor and tissue factor pathway inhibitor following secondary brain injury.

OBJECTIVE: To study the altering rule of coagulation function at molecular level in patients with secondary brain injury (SBI). METHODS: Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were studied in 32 patients 1, 2, 3 and 7 days after craniocerebral injury. Repeated cranial CT scans and platelet counts were made simultaneously. Same measurements were done in 30 normal adults except CT scan. RESULTS: No obvious difference was found in age, sex and platelet count between the injured and the normal groups. TFPI/TF decreased markedly in the first week after injury in patients with SBI, but only decreased on the 7th day in the patients without obvious SBI. For the patients who developed delayed intracranial hematoma (DIH) or hematoma enlargement, TF rose only 1 and 2 days after injury, but TFPI had a tendency to rise again after a fall on the 3rd day. For those patients who developed no DIH, TF rose all the time within the 1st week. CONCLUSIONS: Decrease of TFPI/TF for a long time, especially within 3 days after injury, may be one of the most important reasons for SBI. High expression of TF for a relative short time and increase of TFPI after a fall within 3 days may be one of the important reasons for DIH or hematoma enlargement.

Development of the science of mass casualty incident management: reflection on the medical response to the Wenchuan earthquake and Hangzhou bus fire.

OBJECTIVE: In this paper, we review the previous classic research paradigms of a mass casualty incident (MCI) systematically and reflect the medical response to the Wenchuan earthquake and Hangzhou bus fire, in order to outline and develop an improved research paradigm for MCI management. METHODS: We searched PubMed, EMBASE, China Wanfang, and China Biology Medicine (CBM) databases for relevant studies. The following key words and medical subject headings were used: 'mass casualty incident', 'MCI', 'research method', 'Wenchuan', 'earthquake', 'research paradigm', 'science of surge', 'surge', 'surge capacity', and 'vulnerability'. Searches were performed without year or language restriction. After searching the four literature databases using the above listed key words and medical subject headings, related articles containing research paradigms of MCI, 2008 Wenchuan earthquake, July 5 bus fire, and science of surge and vulnerability were independently included by two authors. RESULTS: The current progresses on MCI management include new golden hour, damage control philosophy, chain of survival, and three links theory. In addition, there are three evaluation methods (medical severity index (MSI), potential injury creating event (PICE) classification, and disaster severity scale (DSS)), which can dynamically assess the MCI situations and decisions for MCI responses and can be made based on the results of such evaluations. However, the three methods only offer a retrospective evaluation of MCI and thus fail to develop a real-time assessment of MCI responses. Therefore, they cannot be used as practical guidance for decision-making during MCI. Although the theory of surge science has made great improvements, we found that a very important factor has been ignored-vulnerability, based on reflecting on the MCI response to the 2008 Wenchuan earthquake and July 5 bus fire in Hangzhou. CONCLUSIONS: This new paradigm breaks through the limitation of traditional research paradigms and will contribute to the development of a methodology for disaster research.

Extracellular signal-regulated kinase (ERK) activation is required for itch sensation in the spinal cord.

BACKGROUND: Itch, chronic itch in particular, can have a significant negative impact on an individual's quality of life. However, the molecular mechanisms underlying itch processing in the central nervous system remain largely unknown. RESULTS: We report here that activation of ERK signaling in the spinal cord is required for itch sensation. ERK activation, as revealed by anti-phosphorylated ERK1/2 immunostaining, is observed in the spinal dorsal horn of mice treated with intradermal injections of histamine and compound 48/80 but not chloroquine or SLIGRL-NH2, indicating that ERK activation only occurs in histamine-dependent acute itch. In addition, ERK activation is also observed in 2, 4-dinitrofluorobenzene (DNFB)-induced itch. Consistently, intrathecal administration of the ERK phosphorylation inhibitor U0126 dramatically reduces the scratching behaviors induced by histamine and DNFB, but not by chloroquine. Furthermore, administration of the histamine receptor H1 antagonist chlorpheniramine decreases the scratching behaviors and ERK activation induced by histamine, but has no effect on DNFB-induced itch responses. Finally, the patch-clamp recording shows that in histamine-, chloroquine- and DNFB-treated mice the spontaneous excitatory postsynaptic current (sEPSC) of dorsal horn neurons is increased, and the decrease of action potential threshold is largely prevented by bathing of U0126 in histamine- and DNFB-treated mice but not those treated with chloroquine. CONCLUSION: Our results demonstrate a critical role for ERK activation in itch sensation at the spinal level.