Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion a...Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion after epicutaneous sensitization can trigger severe allergic responses.Therefore,this study focused on the initial stages of allergic symptoms before they become severe and investigated the mechanisms underlying food ingestion-induced mild itching following epicutaneous sensitization.Methods:Female mice were epicutaneously sensitized with ovalbumin(OVA).Scratching behavior was recorded,and serum and tissue samples were collected.Levels of OVA-specific immunoglobulin(Ig)E/IgG1,histamine,and mast cell protease-1(MCPT-1)were measured by ELISA.Histological analysis of skin tissues and immune cell infiltration was performed via staining.Results:OVA challenge following epicutaneous sensitization induced mild itching in the OVA group.Scratching behavior peaked between 1 and 2 h and persisted for 8 h before returning to baseline.This itching was accompanied by dynamic fluctuations in OVA-specific IgE and IgG1,histamine,and MCPT-1 levels.Histological analysis revealed increased epidermal thickness and granulocytic infiltration,particularly of mast cells and eosinophils,within 2 h of OVA challenge.Mast cell and eosinophil migration into the skin tissues was significant,with eosinophil migration into the dermis persisted despite normalization of histamine levels and mast cell degranulation.These results suggest that mast cells and eosinophils play significant roles even in mild itching.Conclusion:This study provides insights into the early immune responses involved in food allergies,contributing to a better understanding of how mild symptoms can progress to more severe reactions.展开更多
Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has becom...Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has become prevalent.Specifically,active sleep deprivation(ASD),resulting from extended use of smartphones and other recreational activities,has risen as a global health issue.Clinical research has underscored a strong correlation between chronic pain and inadequate sleep[2].The relationship between pain and sleep is reciprocal:pain disturbs sleep,while poor sleep quality,in turn,reduces pain tolerance and exacerbates spontaneous pain sensations[3].While these interplays are well-documented in cases of passive sleep deprivation(PSD)associated with external pressures or illnesses,understanding how and which regions of the brain collaborate to recalibrate the intricate neural circuitry governing pain perception during ASD remains a crucial yet unresolved frontier.展开更多
How to reduce peanut allergies has always been a main food safety concern.Plant polyphenol complex peanut sensitizing protein was proposed as a new desensitization strategy.Gallic acid(GA),as a natural plant polypheno...How to reduce peanut allergies has always been a main food safety concern.Plant polyphenol complex peanut sensitizing protein was proposed as a new desensitization strategy.Gallic acid(GA),as a natural plant polyphenol,has anti-inflammatory and immunomodulatory effects.Therefore,the aim of this study was to investigate the effect of GA on peanut protein(PP)sensitization under high moisture extrusion conditions.The contents of free sulfhydryl groups and disulfide bonds in the PP-GA complex were determined,and the structure of the complex was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Fourier transform infrared spectroscopy.The results showed that with increasing GA content,the number of free sulfhydryl groups increased while the number of disulfide bonds decreased.The secondary structure of PP-GA showed that the random coils andβ-turns were transformed toα-helices andβ-sheets.A BALB/c mouse model was also established,wherein Al(OH)3 was used as an adjuvant when the complex was administered via intraperitoneal injection,and the mice showed mild allergic symptoms and a decreased immune organ index.In addition,the serum levels of specific antibodies(immunoglobulin E(IgE),immunoglobulin G1(IgG1),and immunoglobulin G2a(IgG2a)),cytokines(interleukin-5(IL-5),interleukin 13(IL-13),and interferon gamma(IFN-γ))and histamine were reduced.In summary,this study proved that GA can relieve the sensitization of PP induced by high moisture extrusion.展开更多
Background:The channel-forming protein Pannexin1(Panx1)has been implicated in both human studies and animal models of chronic pain,but the underlying mechanisms remain incompletely understood.Methods:Wild-type(WT,n=24...Background:The channel-forming protein Pannexin1(Panx1)has been implicated in both human studies and animal models of chronic pain,but the underlying mechanisms remain incompletely understood.Methods:Wild-type(WT,n=24),global Panx1 KO(n=24),neuron-specific Panx1 KO(n=20),and glia-specific Panx1 KO(n=20)mice were used in this study at Albert Einstein College of Medicine.The von Frey test was used to quantify pain sensitivity in these mice following complete Freund’s adjuvant(CFA)injection(7,14,and 21 d).The qRT-PCR was employed to measure mRNA levels of Panx1,Panx2,Panx3,Cx43,Calhm1,andβ-catenin.Laser scanning confocal microscopy imaging,Sholl analysis,and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons(DRGNs)in which Panx1 expression or function was manipulated.Ethidium bromide(EtBr)dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate(ATP)sensitivity.β-galactosidase(β-gal)staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia(TG)and DRG of transgenic mice.Results:Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli(7,14,and 21 d;P<0.01 vs.WT group),indicating that Panx1 was positively correlated with pain sensitivity.In Neuro2a,global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group(P<0.05),revealing that Panx1 enhanced neurogenesis and excitability.Similarly,global Panx1 deletion significantly suppressed Wnt/β-catenin dependent DRG neurogenesis following 5 d of nerve growth factor(NGF)treatment(P<0.01 vs.WT group).Moreover,Panx1 channels enhanced DRG neuron response to ATP after CFA injection(P<0.01 vs.Panx1 KO group).Furthermore,ATP release increased Ca2+responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment(P<0.01 vs.Panx1 KO group),suggesting that Panx1 in glia also impacts exaggerated neuronal excitability.Interestingly,neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs,as evidenced by stunted neurite outgrowth(P<0.05 vs.Panx1 KO group;P<0.01 vs.WT group or GFAP-Cre group),blunted activation of Wnt/β-catenin signaling(P<0.01 vs.WT,Panx1 KO and GFAP-Cre groups),and diminished cell excitability(P<0.01 vs.GFAP-Cre group)and response to ATP stimulation(P<0.01 vs.WT group).Analysis ofβ-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher(2.5-fold increase)in the DRG than in the TG.Conclusions:The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability.This hyperexcitability dependence on neuronal Panx1 contrasts with inflammatory orofacial pain,where similar studies revealed a prominent role for glial Panx1.The apparent differences in Panx1 expression in neuronal and non-neuronal TG and DRG cells are likely responsible for the distinct impact of these cell types in the two pain models.展开更多
Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue b...Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue bioimaging and non-invasive biodetection,owing to their superior advantages including good photochemical stability,sharp emission peaks,large penetration depth,and high signal-to-noise ratio[1].Conventionally,Yb3t-and Nd3t-sensitized NCs have been utilized as NIR-II luminescent nanoprobes for in vivo bioimaging upon excitation with 980 and 808 nm diode laser,respectively[2].展开更多
Skin sensitization is a common adverse effect of a wide range of small reactive chemicals,leading to allergic contact dermatitis(ACD),the most frequent manifestation of immunotoxicity in humans.The prevalence of ACD i...Skin sensitization is a common adverse effect of a wide range of small reactive chemicals,leading to allergic contact dermatitis(ACD),the most frequent manifestation of immunotoxicity in humans.The prevalence of ACD is increasing,affecting up to 20%of the Western European population.This trend was particularly pronounced in high-risk occupational sectors,including healthcare,food services,metal and construction workers,and hairdressers[1].The skin sensitization adverse outcome pathway(AOP)comprises 11 elements,with four designated key events(KEs):formation of proteinhapten complexes(KE-1),inflammatory keratinocyte response(KE-2),dendritic cell(DC)activation(KE-3),and T-cell proliferation(KE-4)[2].As there is no cure for ACD,preventive strategies are of great relevance.In addition to avoiding exposure,preventive measures,such as the use of latex gloves,barrier creams,emollients,and moisturizers,often have limited effectiveness[3].展开更多
In the era of digital intelligence,data is a key element in promoting social and economic development.Educational data,as a vital component of data,not only supports teaching and learning but also contains much sensit...In the era of digital intelligence,data is a key element in promoting social and economic development.Educational data,as a vital component of data,not only supports teaching and learning but also contains much sensitive information.How to effectively categorize and protect sensitive data has become an urgent issue in educational data security.This paper systematically researches and constructs a multi-dimensional classification framework for sensitive educational data,and discusses its security protection strategy from the aspects of identification and desensitization,aiming to provide new ideas for the security management of sensitive educational data and to help the construction of an educational data security ecosystem in the era of digital intelligence.展开更多
Introduction: Food allergies are on the constant increase worldwide. Among them is peanut allergy, which also affects children. The aim of this study was to determine the profile of peanut sensitization in children at...Introduction: Food allergies are on the constant increase worldwide. Among them is peanut allergy, which also affects children. The aim of this study was to determine the profile of peanut sensitization in children attending a pneumo-allergology consultation. Methods: This was a cross-sectional study, which ran from January 1, 2018, to December 31, 2022, on children sensitized to peanuts seen in pneumo-allergology consultations at the Teaching Hospital Campus of Lomé. Results: The sample included 137 children aged 3 months to 18 years. The frequency of peanut sensitization was 25.3%. The mean age of patients was 6.3 ± 4.3 years (minimum 6 months and maximum 18 years). The 6 months to 5 years age group was the most represented (43.1%). The sex ratio was 1.3. The main reasons for consultation were rhinorrhea (67.9%), sneezing (36.5%) and cough (35.8%). Allergic rhinitis was identified as a personal history in 75.2% of patients. Peanut allergy was manifested as rhinorrhea (62.5%), asthma (26.8%) and eczema (8.9%). The risk of onset of symptoms within 15 - 30 minutes was 1.87 times (p = 0.001, CI = [1.2 - 2.1]) for peanuts consumed in roasted form with shell. Severe clinical signs such as Quincke’s Edema and anaphylactic shock were found in 1.4% of cases. Conclusion: Peanut allergy was common in children. Severe clinical signs were rare.展开更多
Gold nanomaterials exhibit unique advantages in tumor radiotherapy sensitization due to their enhanced X-ray deposition capability, excellent biocompatibility, and superior chemical, electronic, and optical properties...Gold nanomaterials exhibit unique advantages in tumor radiotherapy sensitization due to their enhanced X-ray deposition capability, excellent biocompatibility, and superior chemical, electronic, and optical properties. To date, studies on gold nanomaterial-mediated radiosensitization have been reported, with related mechanisms including catalyzing reactive oxygen species (ROS) production, depleting intracellular glutathione (GSH), overcoming tumor hypoxia, and regulating cell cycles. This article will elaborate on the research progress of gold nanomaterial-mediated tumor radiotherapy sensitization and discuss its mechanisms and future research directions. In addition, the limitations of gold nanomaterials in clinical applications will be further discussed.展开更多
To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated （i.p.） with saline or morphine 10 mg/kg twice daily for 3 d and then drug...To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated （i.p.） with saline or morphine 10 mg/kg twice daily for 3 d and then drug manipulation was suspended for 5 d. On day 9, a challenge dose of morphine （10 mg/kg） was given and the locomotor activity was measured for 60 rain to confkrm the establishment of behavioral sensitization in mice. Moreover, 5-hydroxytryptophan （5-HTP）, a precursor of serotonin, at the doses of 20-80 mg/kg was given i.p. in combination with daily morphine treatment （induction）, during the morphine treatment suspension （transfer） or prior to the challenge dose of morphine （expression） and locomotor activity was measured on day 9 after the challenge dose of morphine. Twice daily of morphine injection induced robust behavioral sensitization in mice as evidenced by significantly higher locomotion on day 9 for multiple treatment with morphine than saline in mice. 5-HTP treatment selec- tively and dose-dependently blocked the induction, but not the transfer nor the expression of morphine induced behavioral sensitization. This study provides clear evidence that up-regulation of central serotonergic system may suppress the induction of morphine sensitization in mice.展开更多
Objective:Weed pollens are common sources of allergens worldwide.The prevalence of weed pollen sensitization is not yet fully known in China.The purpose of this study was to investigate the prevalence of sensitization...Objective:Weed pollens are common sources of allergens worldwide.The prevalence of weed pollen sensitization is not yet fully known in China.The purpose of this study was to investigate the prevalence of sensitization to weed allergens from Artemisia,Ambrosia,and Humulus in northern China.Methods:A total of 1144 subjects(aged from 5 to 68 years) visiting our clinic from June to October 2011 underwent intradermal testing using a panel of 25 allergen sources.Subjects with positive skin responses to any pollen were further tested for their serum concentrations of IgE antibodies against Artemisia vulgaris,Ambrosia artemisiifolia,and Humulus scandens,and against the purified allergens,Art v 1 and Amb a 1.Results:Of 1144 subjects,170 had positive intradermal reactions to pollen and 144 donated serum for IgE testing.The prevalence of positive intradermal responses to pollens of Artemisia sieversiana,Artemisia annua,A.artemisiifolia,and H.scandens was 11.0%,10.2%,3.7%,and 6.6%,respectively.Among the intradermal positive subjects,the prevalence of specific IgE antigens to A.vulgaris was 58.3%,to A.artemisiifolia 14.7%,and to H.scandens 41.0%.The prevalence of specific IgE antigens to the allergen Art v 1 was 46.9%,and to Amb a 1 was 11.2%.The correlation between the presence of IgE antibodies specific to A.vulgaris and to the Art v 1 antigen was very high.Subjects with A.artemisiifolia specific IgE also had A.vulgaris specific IgE,but with relatively high levels of A.vulgaris IgE antibodies.There were no correlations between the presence of IgE antibodies to H.scandens and A.vulgaris or to H.scandens and A.artemisiifolia.Conclusions:The intradermal prevalence of weed pollen sensitization among allergic subjects in northern China is about 13.5%.Correlations of specific IgE antibodies suggest that pollen allergens from Artemisia and Humulus are independent sources for primary sensitization.展开更多
Objectives:To investigate the clinical and therapeutic effects of acupuncture at the pain-sensitive points of patients with chronic nonspecific low back pain and optimize the acupuncture treatment for chronic nonspeci...Objectives:To investigate the clinical and therapeutic effects of acupuncture at the pain-sensitive points of patients with chronic nonspecific low back pain and optimize the acupuncture treatment for chronic nonspecific low back pain.Methods:Using the FDK 20 pressure algometer,the pain-sensitive points were probed in 30 patients with chronic nonspecific low back pain.The top 5 points that elicited the most painful reaction were selected and stimulated with an even-needling technique after deqi.The needles were retained for 30 min.TDP irradiation was concurrently administered.The treatment was administered once daily on weekdays(Monday to Friday) and discontinued for 2 days during the weekend(Saturday and Sunday).The treatment lasted for 2 consecutive weeks.The changes in the range of motion(ROM) of the lumbar vertebrae,visual analogous scale(VAS) score,and the Oswestry disability index(ODI) score of the lumbar vertebrae were assessed before treatment and after 5 and 10 treatment sessions.Results:Compared with the data before treatment,the spinal ROM increased after 5 and 10 treatment sessions in the patients with chronic nonspecific low back pain.The ROM after 10 treatment sessions was remarkably wider than that after 5 treatments,with statistical significance(all P<0.05).Compared with that before treatment,the immediate VAS score showed statistically significant reduction after 5 treatment sessions(P<0.05).Moreover,compared with the score after 5 treatment sessions,the immediate VAS score reduced after 10 treatment sessions,but without any statistical significance.After 5 and 10 treatment sessions,the ODI score was reduced in the patients and it was significantly different from that before treatment(both P<0.05).Conclusion:Acupuncture at the pain-sensitive points alleviates pain and improves lumbar vertebral function in patients with chronic nonspecific low back pain.Thus,further research is needed to confirm whether acupuncture can be a better intervention for chronic nonspecific low back pain.展开更多
OBJECTIVE:To explore the sensitization acupoints of women with primary dysmenorrhea(PD)by comparing infrared radiation temperatures between acupoints and non-acupoints.METHODS:We tested 10 acupoints of every woman wit...OBJECTIVE:To explore the sensitization acupoints of women with primary dysmenorrhea(PD)by comparing infrared radiation temperatures between acupoints and non-acupoints.METHODS:We tested 10 acupoints of every woman with PD and healthy subjects on premenstrual,menstrual,and postmenstrual days using an infrared imaging device.The primary outcome was the absolute value of body surface temperature difference(AVTD)between the left and right sides of the same testing point.RESULTS:A total of 58 PD patients and 57 healthy volunteers completed the test from May 2016 to May 2017.Compared with the healthy group,we observed a significant reduction and increase in the AVTD in Taichong(LR3)and Sanyinjiao(SP6),respectively,during menstrual days in the PD group(P=0.01;P=0.04);while during postmenstrual days,all AVTDs of Shuiquan(KI5),Diji(SP8),and Xuehai(SP10)were diminished in the PD group(P=0.01;P=0.03;P=0.01,respectively).No significant differences in AVTD were detected at any other points or testing times.CONCLUSIONS:Compared with the healthy group,the AVTDs of Taichong(LR3),Sanyinjiao(SP6),Shuiquan(KI5),Diji(SP8),and Xuehai(SP10)at menstruationrelevant points of PD patients were sensitized,providing a reference for the selection of acupoints in the treatment of PD.展开更多
AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus.The current study systematically investigated th...AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus.The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization.METHODS: Thirty healthy subjects were included.Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area,volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine.RESULTS: The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change.CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions.The new model can be used to study abnormal sensorymotor mechanisms in visceral organs.展开更多
A nonlinear ultrasonic technique has been developed to evaluate sensitization in Type 304 stainless steel. In order to achieve diferent degree of sensitization（DOS）, specimens have been subjected to heat treatment a...A nonlinear ultrasonic technique has been developed to evaluate sensitization in Type 304 stainless steel. In order to achieve diferent degree of sensitization（DOS）, specimens have been subjected to heat treatment at 675℃ at varying soaking time（0.5, 1.0, 2.0, 3.0 and 4.0 h）. Heat treated specimens were subjected to intergranular corrosion tests as per ASTM standards A262 and G108. Sensitization in longer soaked material has been confirmed through ditch microstructures, cracks on the bend tested specimens and higher degree of sensitization. Nonlinear ultrasonic studies showed variation in the nonlinearity parameter with soaking time which also confirms sensitization. A good correlation was observed between the degree of sensitization measured by the electrochemical potentiokinetic reactivation test and the ultrasonic nonlinearity parameter.This study clearly demonstrated that nonlinear ultrasonic technique can be used as a potential technique for non-destructive characterization of sensitization in austenitic stainless steel.展开更多
BACKGROUND： Central sensitization, a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation, is an important mechanism underlying hyper...BACKGROUND： Central sensitization, a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation, is an important mechanism underlying hyperalgesia and neuropathic pain. Participation of the glutamate-glutamine cycle in central sensitization of the spinal cord remains poorly understood. OBJECTIVE： To determine whether the astrocyte-neuronal glutamate-glutamine cycle is involved in formalin-induced central sensitization in the spinal cord. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Orthopedics, Second Hospital, Lanzhou University, China from September 2007 to August 2008. MATERIALS： Methionine sulfoximine （MSO, 0.1 mmol/L）, glutamine （0.25 mmol/L）, and formalin were used for this study. METHODS： A total of 43 male, Sprague Dawley rats, aged 4 months, were randomly assigned to a sham operation group （n = 6） and a model group （n = 37）. Rats in the model group received intrathecal infusion in the spinal cord. 7 days later, 37 model rats were randomly divided into PBS, MSO, glutamine, MSO ＋ glutamine and formalin subcutaneous injection alone groups. The PBS, MSO, glutamine, MSO ＋ glutamine groups were respectively intrathecally injected with PBS, MSO, glutamine, MSO ＋ glutamine （50 μL each）, and then infused with 10 μL of saline. Rats from the sham operation group were not subjected to intrathecal infusion in the spinal cord. At 15 minutes after intrathecal injection, a rat model of formalin-induced inflammatory pain was established by subcutaneous injection of 5% formalin （50 μL） in the left hindpaw. MAIN OUTCOME MEASURES： Changes in spontaneous nociceptive behavior （licking/biting or flinching） were observed following formalin injection into the rat hindpaw. RESULTS： Compared with the PBS group, duration of licking/biting was significantly shortened, and flinching frequency was significantly diminished in the MSO group （P 〈 0.05）. Compared with the MSO group, duration of licking/biting was significantly prolonged, and flinching frequency was significantly increased in the MSO ＋ glutamine group （P 〈 0.05）. There was no significant difference in inflammatory pain behaviors among the sham operation, PBS, glutamine, MSO ＋ glutamine, and formalin subcutaneous injection alone groups （P 〉 0.05）. CONCLUSION： The astrocyte-neuronal glutamate-glutamine cycle in the spinal cord was shown to be involved in central sensitization induced by formalin subcutaneous injection into the hindpaw.展开更多
BACKGROUND Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral hypersensitivity.Since pelvic organs share common sensory pathways,it is likely that those syndromes i...BACKGROUND Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral hypersensitivity.Since pelvic organs share common sensory pathways,it is likely that those syndromes involve a cross-sensitization of the bladder and the colon.The precise pathophysiology remains poorly understood.AIM To develop a model of chronic bladder-colon cross-sensitization and to investigate the mechanisms involved.METHODS Chronic cross-organ visceral sensitization was obtained in C57BL/6 mice using ultrasound-guided intravesical injections of acetic acid under brief isoflurane anesthesia.Colorectal sensitivity was assessed in conscious mice by measuring intracolonic pressure during isobaric colorectal distensions.Myeloperoxidase,used as a marker of colorectal inflammation,was measured in the colon,and colorectal permeability was measured using chambers.c-Fos protein expression,used as a marker of neuronal activation,was assessed in the spinal cord(L6-S1 level)using immunohistochemistry.Green fluorescent protein on the fractalkine receptor-positive mice were used to identify and count microglia cells in the L6-S1 dorsal horn of the spinal cord.The expression of NK1 receptors and MAPK-p38 were quantified in the spinal cord using western blot.RESULTS Visceral hypersensitivity to colorectal distension was observed after the intravesical injection of acetic acid vs saline(P<0.0001).This effect started 1 h post-injection and lasted up to 7 d postinjection.No increased permeability or inflammation was shown in the bladder or colon 7 d postinjection.Visceral hypersensitivity was associated with the increased expression of c-Fos protein in the spinal cord(P<0.0001).In green fluorescent protein on the fractalkine receptor-positive mice,intravesical acetic acid injection resulted in an increased number of microglia cells in the L6-S1 dorsal horn of the spinal cord(P<0.0001).NK1 receptor and MAPK-p38 levels were increased in the spinal cord up to 7 d after injection(P=0.007 and 0.023 respectively).Colorectal sensitization was prevented by intrathecal or intracerebroventricular injections of minocycline,a microglia inhibitor,by intracerebroventricular injection of CP-99994 dihydrochloride,a NK1 antagonist,and by intracerebroventricular injection of SB203580,a MAPK-p38 inhibitor.CONCLUSION We describe a new model of cross-organ visceral sensitization between the bladder and the colon in mice.Intravesical injections of acetic acid induced a long-lasting colorectal hypersensitivity to distension,mediated by neuroglial interactions,MAPK-p38 phosphorylation and the NK1 receptor.展开更多
Increasing incidences showed that food allergies have attracted more and more attention from researchers.BALB/c mice were sensitized with wheat gluten combined with aluminum hydroxide adjuvant via intraperitoneal inje...Increasing incidences showed that food allergies have attracted more and more attention from researchers.BALB/c mice were sensitized with wheat gluten combined with aluminum hydroxide adjuvant via intraperitoneal injection,transdermal sensitization,and oral gavage sensitization route.Results showed that all the three sensitization methods could induce allergic symptoms;increase the serum antibody(total immunoglobulin E(IgE),specific IgE,IgG,IgA)and histamine content;promote the secretion of Th2 cytokines(interleukin(IL)-4,IL-5,IL-13)and inflammatory factors(IL-6,IL-17 A,IL-10);and inhibit the production of Th1 cytokines(IFN-γ,IL-2).However,the allergic symptoms of mice sensitized by intraperitoneal injection were the most obvious among the three models.The level of serum antibodies in intraperitoneal injection group was significantly higher than control.Subsequently,16 S rRNA sequencing technology was used to analyze the intestinal flora of mice.The results showed that the abundance of Firmicutes in the wheat protein sensitized group was lower than that in the normal group,while the abundance of Bacteroidetes was higher,and Lactobacillus was the difference marker in normal group.Bacterial species diversity analysis showed that the species richness and diversity of intestinal flora in mice were decreased,the difference between mice induced by intraperitoneal injection and normal control group mice was the most significant.Taken together,these results show that among three sensitization methods used to build a mouse model with aluminum hydroxide as adjuvant,intraperitoneal injection is the comparably best way to build a mouse sensitization mode.展开更多
Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by2 months in combination with gemcitabine.However,prognosis and survival improvement remain unsatisfactory,and effective the...Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by2 months in combination with gemcitabine.However,prognosis and survival improvement remain unsatisfactory,and effective therapies are urgently needed.Piperlongumine has been demonstrated to have therapeutic potentials against various cancers.In this study,we synthesized a series of piperlongumine derivatives and provided evidence that piperlongumine derivatives could be used as effective radiosensitizers in pancreatic cancer.Two compounds enhanced the radiosensitivity of Panc-1 and SW1990 cells.In a pancreatic bi-flank xenograft tumor model,they significantly inhibited tumor growth.Piperlongumine derivatives could induce reactive oxygen species(ROS)expression and regulate the Keapl-Nrf2 protective pathway with enhancement of radiation-induced DNA damage,G2/M-phase cell cycle arrest,and apoptosis.Collectively,our data offer a proof of concept for the use of piperlongumine derivatives as a novel class of radiosensitizers for the treatment of pancreatic cancer.展开更多
In order to develop the heroin abstainers＇ cue-sensitization questionnaire （HACSQ）, and evaluate its reliability and validity, during March and April in 2006, the cross-sectional sample survey and cluster sampling ...In order to develop the heroin abstainers＇ cue-sensitization questionnaire （HACSQ）, and evaluate its reliability and validity, during March and April in 2006, the cross-sectional sample survey and cluster sampling were adopted among 939 volunteer participants who were heroin abstainers from 5 compulsive detoxification centers in China. The data were collected by the self-report questionnaires. The reliability analysis included Cronbach＇s a coefficient, split reliability and test-retest reliability, while construction validity was analyzed in the light of exploratory and confirmatory factor analysis. Based upon the exploratory factor analysis, 4 factors were extracted, which were social emotion cue （SEC）, direct implement cue （DIC）, personnel cue （PC） and indirect implement cue （IIC） and they together explained 64.52% variance. According to the data, test-retest reliability coefficient ranged from 0.57 to 0.63, and Cronbach＇s α coefficient ranged from 0.86 to 0.95 across the 4 factors and HACSQ. The adjusted goodness of fit index was 0.75. It was suggested that the HACSQ demonstrated good validities and reliabilities, and may be used as a reliable assessment tool for the cue-sensitization among the heroin abstainers.展开更多
基金supported by JSPS KAKENHI Grant Number(22K11779).
文摘Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion after epicutaneous sensitization can trigger severe allergic responses.Therefore,this study focused on the initial stages of allergic symptoms before they become severe and investigated the mechanisms underlying food ingestion-induced mild itching following epicutaneous sensitization.Methods:Female mice were epicutaneously sensitized with ovalbumin(OVA).Scratching behavior was recorded,and serum and tissue samples were collected.Levels of OVA-specific immunoglobulin(Ig)E/IgG1,histamine,and mast cell protease-1(MCPT-1)were measured by ELISA.Histological analysis of skin tissues and immune cell infiltration was performed via staining.Results:OVA challenge following epicutaneous sensitization induced mild itching in the OVA group.Scratching behavior peaked between 1 and 2 h and persisted for 8 h before returning to baseline.This itching was accompanied by dynamic fluctuations in OVA-specific IgE and IgG1,histamine,and MCPT-1 levels.Histological analysis revealed increased epidermal thickness and granulocytic infiltration,particularly of mast cells and eosinophils,within 2 h of OVA challenge.Mast cell and eosinophil migration into the skin tissues was significant,with eosinophil migration into the dermis persisted despite normalization of histamine levels and mast cell degranulation.These results suggest that mast cells and eosinophils play significant roles even in mild itching.Conclusion:This study provides insights into the early immune responses involved in food allergies,contributing to a better understanding of how mild symptoms can progress to more severe reactions.
基金supported by the National Natural Science Foundation of China(U21A20418).
文摘Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has become prevalent.Specifically,active sleep deprivation(ASD),resulting from extended use of smartphones and other recreational activities,has risen as a global health issue.Clinical research has underscored a strong correlation between chronic pain and inadequate sleep[2].The relationship between pain and sleep is reciprocal:pain disturbs sleep,while poor sleep quality,in turn,reduces pain tolerance and exacerbates spontaneous pain sensations[3].While these interplays are well-documented in cases of passive sleep deprivation(PSD)associated with external pressures or illnesses,understanding how and which regions of the brain collaborate to recalibrate the intricate neural circuitry governing pain perception during ASD remains a crucial yet unresolved frontier.
基金supported by the Natural Science Foundation of China(32072139)Liaoning Province Natural Science Foundation Project(2022-MS-307).
文摘How to reduce peanut allergies has always been a main food safety concern.Plant polyphenol complex peanut sensitizing protein was proposed as a new desensitization strategy.Gallic acid(GA),as a natural plant polyphenol,has anti-inflammatory and immunomodulatory effects.Therefore,the aim of this study was to investigate the effect of GA on peanut protein(PP)sensitization under high moisture extrusion conditions.The contents of free sulfhydryl groups and disulfide bonds in the PP-GA complex were determined,and the structure of the complex was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Fourier transform infrared spectroscopy.The results showed that with increasing GA content,the number of free sulfhydryl groups increased while the number of disulfide bonds decreased.The secondary structure of PP-GA showed that the random coils andβ-turns were transformed toα-helices andβ-sheets.A BALB/c mouse model was also established,wherein Al(OH)3 was used as an adjuvant when the complex was administered via intraperitoneal injection,and the mice showed mild allergic symptoms and a decreased immune organ index.In addition,the serum levels of specific antibodies(immunoglobulin E(IgE),immunoglobulin G1(IgG1),and immunoglobulin G2a(IgG2a)),cytokines(interleukin-5(IL-5),interleukin 13(IL-13),and interferon gamma(IFN-γ))and histamine were reduced.In summary,this study proved that GA can relieve the sensitization of PP induced by high moisture extrusion.
基金This work was NIH(R01NS092466),NSFC(U2004201)Central Plains Thousand People Plan of Henan Province(204200510013)+1 种基金Henan Overseas Expertise Introduction Center for Discipline Innovation(CXJD2021002)Key Special Project of Zhengzhou University Disciplinary Construction(XKZDJC202001)。
文摘Background:The channel-forming protein Pannexin1(Panx1)has been implicated in both human studies and animal models of chronic pain,but the underlying mechanisms remain incompletely understood.Methods:Wild-type(WT,n=24),global Panx1 KO(n=24),neuron-specific Panx1 KO(n=20),and glia-specific Panx1 KO(n=20)mice were used in this study at Albert Einstein College of Medicine.The von Frey test was used to quantify pain sensitivity in these mice following complete Freund’s adjuvant(CFA)injection(7,14,and 21 d).The qRT-PCR was employed to measure mRNA levels of Panx1,Panx2,Panx3,Cx43,Calhm1,andβ-catenin.Laser scanning confocal microscopy imaging,Sholl analysis,and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons(DRGNs)in which Panx1 expression or function was manipulated.Ethidium bromide(EtBr)dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate(ATP)sensitivity.β-galactosidase(β-gal)staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia(TG)and DRG of transgenic mice.Results:Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli(7,14,and 21 d;P<0.01 vs.WT group),indicating that Panx1 was positively correlated with pain sensitivity.In Neuro2a,global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group(P<0.05),revealing that Panx1 enhanced neurogenesis and excitability.Similarly,global Panx1 deletion significantly suppressed Wnt/β-catenin dependent DRG neurogenesis following 5 d of nerve growth factor(NGF)treatment(P<0.01 vs.WT group).Moreover,Panx1 channels enhanced DRG neuron response to ATP after CFA injection(P<0.01 vs.Panx1 KO group).Furthermore,ATP release increased Ca2+responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment(P<0.01 vs.Panx1 KO group),suggesting that Panx1 in glia also impacts exaggerated neuronal excitability.Interestingly,neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs,as evidenced by stunted neurite outgrowth(P<0.05 vs.Panx1 KO group;P<0.01 vs.WT group or GFAP-Cre group),blunted activation of Wnt/β-catenin signaling(P<0.01 vs.WT,Panx1 KO and GFAP-Cre groups),and diminished cell excitability(P<0.01 vs.GFAP-Cre group)and response to ATP stimulation(P<0.01 vs.WT group).Analysis ofβ-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher(2.5-fold increase)in the DRG than in the TG.Conclusions:The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability.This hyperexcitability dependence on neuronal Panx1 contrasts with inflammatory orofacial pain,where similar studies revealed a prominent role for glial Panx1.The apparent differences in Panx1 expression in neuronal and non-neuronal TG and DRG cells are likely responsible for the distinct impact of these cell types in the two pain models.
基金supported by the National Natural Science Foundation of China(Nos.12474418,U22A20398,and 22135008).
文摘Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue bioimaging and non-invasive biodetection,owing to their superior advantages including good photochemical stability,sharp emission peaks,large penetration depth,and high signal-to-noise ratio[1].Conventionally,Yb3t-and Nd3t-sensitized NCs have been utilized as NIR-II luminescent nanoprobes for in vivo bioimaging upon excitation with 980 and 808 nm diode laser,respectively[2].
基金support was provided by the European Regional Development Fund(ERDF),through the Centro 2020 Regional Operational Programme,Portugal(Project No.:CENTRO-01-0145-FEDER-000012(HealthyAging2020))through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation and Portuguese National Funds via Fundaçao para a Ciencia e a Tecnologia,Portugal(Project Nos.:POCI-01-0145-FEDER-029369 UIDB/04539/2020,iBiMED UIDB/04501/2020,DOI identifier https://doi.org/10.54499/UIDB/04501/2020 and project reference UIDP/04501/2020,DOI identifier https://doi.org/10.54499/UIDP/04501/2020,and LA/P/0058/2020)supported by Fundaçao para a Ciencia e a Tecnologia through the individual PhD fellowships,Portugal(Grant Nos.:PD/BDE/142926/2018 and SFRH/BD/110717/2015)。
文摘Skin sensitization is a common adverse effect of a wide range of small reactive chemicals,leading to allergic contact dermatitis(ACD),the most frequent manifestation of immunotoxicity in humans.The prevalence of ACD is increasing,affecting up to 20%of the Western European population.This trend was particularly pronounced in high-risk occupational sectors,including healthcare,food services,metal and construction workers,and hairdressers[1].The skin sensitization adverse outcome pathway(AOP)comprises 11 elements,with four designated key events(KEs):formation of proteinhapten complexes(KE-1),inflammatory keratinocyte response(KE-2),dendritic cell(DC)activation(KE-3),and T-cell proliferation(KE-4)[2].As there is no cure for ACD,preventive strategies are of great relevance.In addition to avoiding exposure,preventive measures,such as the use of latex gloves,barrier creams,emollients,and moisturizers,often have limited effectiveness[3].
基金Education Science planning project of Jiangsu Province in 2024(Grant No:B-b/2024/01/152)2025 Jiangsu Normal University Graduate Research and Innovation Program school-level project“Research on the Construction and Desensitization Strategies of Education Sensitive Data Classification from the Perspective of Educational Ecology”。
文摘In the era of digital intelligence,data is a key element in promoting social and economic development.Educational data,as a vital component of data,not only supports teaching and learning but also contains much sensitive information.How to effectively categorize and protect sensitive data has become an urgent issue in educational data security.This paper systematically researches and constructs a multi-dimensional classification framework for sensitive educational data,and discusses its security protection strategy from the aspects of identification and desensitization,aiming to provide new ideas for the security management of sensitive educational data and to help the construction of an educational data security ecosystem in the era of digital intelligence.
文摘Introduction: Food allergies are on the constant increase worldwide. Among them is peanut allergy, which also affects children. The aim of this study was to determine the profile of peanut sensitization in children attending a pneumo-allergology consultation. Methods: This was a cross-sectional study, which ran from January 1, 2018, to December 31, 2022, on children sensitized to peanuts seen in pneumo-allergology consultations at the Teaching Hospital Campus of Lomé. Results: The sample included 137 children aged 3 months to 18 years. The frequency of peanut sensitization was 25.3%. The mean age of patients was 6.3 ± 4.3 years (minimum 6 months and maximum 18 years). The 6 months to 5 years age group was the most represented (43.1%). The sex ratio was 1.3. The main reasons for consultation were rhinorrhea (67.9%), sneezing (36.5%) and cough (35.8%). Allergic rhinitis was identified as a personal history in 75.2% of patients. Peanut allergy was manifested as rhinorrhea (62.5%), asthma (26.8%) and eczema (8.9%). The risk of onset of symptoms within 15 - 30 minutes was 1.87 times (p = 0.001, CI = [1.2 - 2.1]) for peanuts consumed in roasted form with shell. Severe clinical signs such as Quincke’s Edema and anaphylactic shock were found in 1.4% of cases. Conclusion: Peanut allergy was common in children. Severe clinical signs were rare.
文摘Gold nanomaterials exhibit unique advantages in tumor radiotherapy sensitization due to their enhanced X-ray deposition capability, excellent biocompatibility, and superior chemical, electronic, and optical properties. To date, studies on gold nanomaterial-mediated radiosensitization have been reported, with related mechanisms including catalyzing reactive oxygen species (ROS) production, depleting intracellular glutathione (GSH), overcoming tumor hypoxia, and regulating cell cycles. This article will elaborate on the research progress of gold nanomaterial-mediated tumor radiotherapy sensitization and discuss its mechanisms and future research directions. In addition, the limitations of gold nanomaterials in clinical applications will be further discussed.
基金National Natural Science Foundation of China (Grant No. 30570653)National Basic Research Program of China (Grant No. 2003CB515400)985 Program of China Ministry of Education
文摘To investigate the involvement of central serotonergic system in behavioral sensitization to morphine in mice. Male Kunming mice were treated （i.p.） with saline or morphine 10 mg/kg twice daily for 3 d and then drug manipulation was suspended for 5 d. On day 9, a challenge dose of morphine （10 mg/kg） was given and the locomotor activity was measured for 60 rain to confkrm the establishment of behavioral sensitization in mice. Moreover, 5-hydroxytryptophan （5-HTP）, a precursor of serotonin, at the doses of 20-80 mg/kg was given i.p. in combination with daily morphine treatment （induction）, during the morphine treatment suspension （transfer） or prior to the challenge dose of morphine （expression） and locomotor activity was measured on day 9 after the challenge dose of morphine. Twice daily of morphine injection induced robust behavioral sensitization in mice as evidenced by significantly higher locomotion on day 9 for multiple treatment with morphine than saline in mice. 5-HTP treatment selec- tively and dose-dependently blocked the induction, but not the transfer nor the expression of morphine induced behavioral sensitization. This study provides clear evidence that up-regulation of central serotonergic system may suppress the induction of morphine sensitization in mice.
文摘Objective:Weed pollens are common sources of allergens worldwide.The prevalence of weed pollen sensitization is not yet fully known in China.The purpose of this study was to investigate the prevalence of sensitization to weed allergens from Artemisia,Ambrosia,and Humulus in northern China.Methods:A total of 1144 subjects(aged from 5 to 68 years) visiting our clinic from June to October 2011 underwent intradermal testing using a panel of 25 allergen sources.Subjects with positive skin responses to any pollen were further tested for their serum concentrations of IgE antibodies against Artemisia vulgaris,Ambrosia artemisiifolia,and Humulus scandens,and against the purified allergens,Art v 1 and Amb a 1.Results:Of 1144 subjects,170 had positive intradermal reactions to pollen and 144 donated serum for IgE testing.The prevalence of positive intradermal responses to pollens of Artemisia sieversiana,Artemisia annua,A.artemisiifolia,and H.scandens was 11.0%,10.2%,3.7%,and 6.6%,respectively.Among the intradermal positive subjects,the prevalence of specific IgE antigens to A.vulgaris was 58.3%,to A.artemisiifolia 14.7%,and to H.scandens 41.0%.The prevalence of specific IgE antigens to the allergen Art v 1 was 46.9%,and to Amb a 1 was 11.2%.The correlation between the presence of IgE antibodies specific to A.vulgaris and to the Art v 1 antigen was very high.Subjects with A.artemisiifolia specific IgE also had A.vulgaris specific IgE,but with relatively high levels of A.vulgaris IgE antibodies.There were no correlations between the presence of IgE antibodies to H.scandens and A.vulgaris or to H.scandens and A.artemisiifolia.Conclusions:The intradermal prevalence of weed pollen sensitization among allergic subjects in northern China is about 13.5%.Correlations of specific IgE antibodies suggest that pollen allergens from Artemisia and Humulus are independent sources for primary sensitization.
基金Supported by Special Funds of Fujian Provincial Finance Department and Education Department:x2018002Clinical Special Project of School Management of Fujian University of Traditional Chinese Medicine:xb2020150。
文摘Objectives:To investigate the clinical and therapeutic effects of acupuncture at the pain-sensitive points of patients with chronic nonspecific low back pain and optimize the acupuncture treatment for chronic nonspecific low back pain.Methods:Using the FDK 20 pressure algometer,the pain-sensitive points were probed in 30 patients with chronic nonspecific low back pain.The top 5 points that elicited the most painful reaction were selected and stimulated with an even-needling technique after deqi.The needles were retained for 30 min.TDP irradiation was concurrently administered.The treatment was administered once daily on weekdays(Monday to Friday) and discontinued for 2 days during the weekend(Saturday and Sunday).The treatment lasted for 2 consecutive weeks.The changes in the range of motion(ROM) of the lumbar vertebrae,visual analogous scale(VAS) score,and the Oswestry disability index(ODI) score of the lumbar vertebrae were assessed before treatment and after 5 and 10 treatment sessions.Results:Compared with the data before treatment,the spinal ROM increased after 5 and 10 treatment sessions in the patients with chronic nonspecific low back pain.The ROM after 10 treatment sessions was remarkably wider than that after 5 treatments,with statistical significance(all P<0.05).Compared with that before treatment,the immediate VAS score showed statistically significant reduction after 5 treatment sessions(P<0.05).Moreover,compared with the score after 5 treatment sessions,the immediate VAS score reduced after 10 treatment sessions,but without any statistical significance.After 5 and 10 treatment sessions,the ODI score was reduced in the patients and it was significantly different from that before treatment(both P<0.05).Conclusion:Acupuncture at the pain-sensitive points alleviates pain and improves lumbar vertebral function in patients with chronic nonspecific low back pain.Thus,further research is needed to confirm whether acupuncture can be a better intervention for chronic nonspecific low back pain.
基金Supported by National Natural Science Foundation of China:on Acupoints on the Same Spinal Segment Different Meridians Reflecting Primary Dysmenorrhea Based on the Theory of One Source and Three Branches(No.81973755)Research on Variations of Biophysical Properties of Acupoints on Different Meridians with the Same Spinal Segments Based on Primary Dysmenorrhea(No.81573884)+2 种基金Based on the Study of Biophysical Characteristics of the Cytoplasm under Different Physiological States(No.81603542)Ministry of Science and Technology of China:International Cooperation on the Dominant Diseases of Acupuncture and Moxibustion based on the Guiding Principle of Acupoint Compatibility Classification(2019YFC171203)Graduate Innovation Funding Project of Hebei Province:Study on the Mechanism of Acupoint Specific Reaction in Different Pathological States of Uterus(No.XCXZZBS2021013)。
文摘OBJECTIVE:To explore the sensitization acupoints of women with primary dysmenorrhea(PD)by comparing infrared radiation temperatures between acupoints and non-acupoints.METHODS:We tested 10 acupoints of every woman with PD and healthy subjects on premenstrual,menstrual,and postmenstrual days using an infrared imaging device.The primary outcome was the absolute value of body surface temperature difference(AVTD)between the left and right sides of the same testing point.RESULTS:A total of 58 PD patients and 57 healthy volunteers completed the test from May 2016 to May 2017.Compared with the healthy group,we observed a significant reduction and increase in the AVTD in Taichong(LR3)and Sanyinjiao(SP6),respectively,during menstrual days in the PD group(P=0.01;P=0.04);while during postmenstrual days,all AVTDs of Shuiquan(KI5),Diji(SP8),and Xuehai(SP10)were diminished in the PD group(P=0.01;P=0.03;P=0.01,respectively).No significant differences in AVTD were detected at any other points or testing times.CONCLUSIONS:Compared with the healthy group,the AVTDs of Taichong(LR3),Sanyinjiao(SP6),Shuiquan(KI5),Diji(SP8),and Xuehai(SP10)at menstruationrelevant points of PD patients were sensitized,providing a reference for the selection of acupoints in the treatment of PD.
基金Supported by the "Det Obelske Familifond", "Spar Nord Fonden"and the Danish Technical Research Council
文摘AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus.The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization.METHODS: Thirty healthy subjects were included.Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area,volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine.RESULTS: The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change.CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions.The new model can be used to study abnormal sensorymotor mechanisms in visceral organs.
文摘A nonlinear ultrasonic technique has been developed to evaluate sensitization in Type 304 stainless steel. In order to achieve diferent degree of sensitization（DOS）, specimens have been subjected to heat treatment at 675℃ at varying soaking time（0.5, 1.0, 2.0, 3.0 and 4.0 h）. Heat treated specimens were subjected to intergranular corrosion tests as per ASTM standards A262 and G108. Sensitization in longer soaked material has been confirmed through ditch microstructures, cracks on the bend tested specimens and higher degree of sensitization. Nonlinear ultrasonic studies showed variation in the nonlinearity parameter with soaking time which also confirms sensitization. A good correlation was observed between the degree of sensitization measured by the electrochemical potentiokinetic reactivation test and the ultrasonic nonlinearity parameter.This study clearly demonstrated that nonlinear ultrasonic technique can be used as a potential technique for non-destructive characterization of sensitization in austenitic stainless steel.
基金the National Science Foundation of China,No.30800333
文摘BACKGROUND： Central sensitization, a state of increased excitability of nociceptive neurons in the spinal dorsal horn following peripheral tissue injury and/or inflammation, is an important mechanism underlying hyperalgesia and neuropathic pain. Participation of the glutamate-glutamine cycle in central sensitization of the spinal cord remains poorly understood. OBJECTIVE： To determine whether the astrocyte-neuronal glutamate-glutamine cycle is involved in formalin-induced central sensitization in the spinal cord. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Institute of Orthopedics, Second Hospital, Lanzhou University, China from September 2007 to August 2008. MATERIALS： Methionine sulfoximine （MSO, 0.1 mmol/L）, glutamine （0.25 mmol/L）, and formalin were used for this study. METHODS： A total of 43 male, Sprague Dawley rats, aged 4 months, were randomly assigned to a sham operation group （n = 6） and a model group （n = 37）. Rats in the model group received intrathecal infusion in the spinal cord. 7 days later, 37 model rats were randomly divided into PBS, MSO, glutamine, MSO ＋ glutamine and formalin subcutaneous injection alone groups. The PBS, MSO, glutamine, MSO ＋ glutamine groups were respectively intrathecally injected with PBS, MSO, glutamine, MSO ＋ glutamine （50 μL each）, and then infused with 10 μL of saline. Rats from the sham operation group were not subjected to intrathecal infusion in the spinal cord. At 15 minutes after intrathecal injection, a rat model of formalin-induced inflammatory pain was established by subcutaneous injection of 5% formalin （50 μL） in the left hindpaw. MAIN OUTCOME MEASURES： Changes in spontaneous nociceptive behavior （licking/biting or flinching） were observed following formalin injection into the rat hindpaw. RESULTS： Compared with the PBS group, duration of licking/biting was significantly shortened, and flinching frequency was significantly diminished in the MSO group （P 〈 0.05）. Compared with the MSO group, duration of licking/biting was significantly prolonged, and flinching frequency was significantly increased in the MSO ＋ glutamine group （P 〈 0.05）. There was no significant difference in inflammatory pain behaviors among the sham operation, PBS, glutamine, MSO ＋ glutamine, and formalin subcutaneous injection alone groups （P 〉 0.05）. CONCLUSION： The astrocyte-neuronal glutamate-glutamine cycle in the spinal cord was shown to be involved in central sensitization induced by formalin subcutaneous injection into the hindpaw.
文摘BACKGROUND Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral hypersensitivity.Since pelvic organs share common sensory pathways,it is likely that those syndromes involve a cross-sensitization of the bladder and the colon.The precise pathophysiology remains poorly understood.AIM To develop a model of chronic bladder-colon cross-sensitization and to investigate the mechanisms involved.METHODS Chronic cross-organ visceral sensitization was obtained in C57BL/6 mice using ultrasound-guided intravesical injections of acetic acid under brief isoflurane anesthesia.Colorectal sensitivity was assessed in conscious mice by measuring intracolonic pressure during isobaric colorectal distensions.Myeloperoxidase,used as a marker of colorectal inflammation,was measured in the colon,and colorectal permeability was measured using chambers.c-Fos protein expression,used as a marker of neuronal activation,was assessed in the spinal cord(L6-S1 level)using immunohistochemistry.Green fluorescent protein on the fractalkine receptor-positive mice were used to identify and count microglia cells in the L6-S1 dorsal horn of the spinal cord.The expression of NK1 receptors and MAPK-p38 were quantified in the spinal cord using western blot.RESULTS Visceral hypersensitivity to colorectal distension was observed after the intravesical injection of acetic acid vs saline(P<0.0001).This effect started 1 h post-injection and lasted up to 7 d postinjection.No increased permeability or inflammation was shown in the bladder or colon 7 d postinjection.Visceral hypersensitivity was associated with the increased expression of c-Fos protein in the spinal cord(P<0.0001).In green fluorescent protein on the fractalkine receptor-positive mice,intravesical acetic acid injection resulted in an increased number of microglia cells in the L6-S1 dorsal horn of the spinal cord(P<0.0001).NK1 receptor and MAPK-p38 levels were increased in the spinal cord up to 7 d after injection(P=0.007 and 0.023 respectively).Colorectal sensitization was prevented by intrathecal or intracerebroventricular injections of minocycline,a microglia inhibitor,by intracerebroventricular injection of CP-99994 dihydrochloride,a NK1 antagonist,and by intracerebroventricular injection of SB203580,a MAPK-p38 inhibitor.CONCLUSION We describe a new model of cross-organ visceral sensitization between the bladder and the colon in mice.Intravesical injections of acetic acid induced a long-lasting colorectal hypersensitivity to distension,mediated by neuroglial interactions,MAPK-p38 phosphorylation and the NK1 receptor.
基金supported by the National Key Research and Development Program of China(2019YFC1605000)the National Natural Science Foundation(1872904)。
文摘Increasing incidences showed that food allergies have attracted more and more attention from researchers.BALB/c mice were sensitized with wheat gluten combined with aluminum hydroxide adjuvant via intraperitoneal injection,transdermal sensitization,and oral gavage sensitization route.Results showed that all the three sensitization methods could induce allergic symptoms;increase the serum antibody(total immunoglobulin E(IgE),specific IgE,IgG,IgA)and histamine content;promote the secretion of Th2 cytokines(interleukin(IL)-4,IL-5,IL-13)and inflammatory factors(IL-6,IL-17 A,IL-10);and inhibit the production of Th1 cytokines(IFN-γ,IL-2).However,the allergic symptoms of mice sensitized by intraperitoneal injection were the most obvious among the three models.The level of serum antibodies in intraperitoneal injection group was significantly higher than control.Subsequently,16 S rRNA sequencing technology was used to analyze the intestinal flora of mice.The results showed that the abundance of Firmicutes in the wheat protein sensitized group was lower than that in the normal group,while the abundance of Bacteroidetes was higher,and Lactobacillus was the difference marker in normal group.Bacterial species diversity analysis showed that the species richness and diversity of intestinal flora in mice were decreased,the difference between mice induced by intraperitoneal injection and normal control group mice was the most significant.Taken together,these results show that among three sensitization methods used to build a mouse model with aluminum hydroxide as adjuvant,intraperitoneal injection is the comparably best way to build a mouse sensitization mode.
基金supported by grants from the Shanghai Municipal Commission of Health and Family Planning(No.2017YQ052)the Young Elite Scientists Sponsorship Program by the China Association for Science and Technology(No.2017QNRC061)+3 种基金the National Natural Science Foundation of China(Nos.81673352,81872453)the Bio-Pharmaceutical Project of Science and Technology of Shanghai(No.15431901700)the Natural Science Foundation of Shanghai(No.18ZR1438700)the Key Research and Development Program of Ningxia(Nos.2018BFH02001 and 2019BFG02017)。
文摘Radiotherapy is commonly used to treat advanced pancreatic cancers and can improve survival by2 months in combination with gemcitabine.However,prognosis and survival improvement remain unsatisfactory,and effective therapies are urgently needed.Piperlongumine has been demonstrated to have therapeutic potentials against various cancers.In this study,we synthesized a series of piperlongumine derivatives and provided evidence that piperlongumine derivatives could be used as effective radiosensitizers in pancreatic cancer.Two compounds enhanced the radiosensitivity of Panc-1 and SW1990 cells.In a pancreatic bi-flank xenograft tumor model,they significantly inhibited tumor growth.Piperlongumine derivatives could induce reactive oxygen species(ROS)expression and regulate the Keapl-Nrf2 protective pathway with enhancement of radiation-induced DNA damage,G2/M-phase cell cycle arrest,and apoptosis.Collectively,our data offer a proof of concept for the use of piperlongumine derivatives as a novel class of radiosensitizers for the treatment of pancreatic cancer.
基金supported by a grant from National Natu-ral Sciences Foundation of China (No. 30872175).
文摘In order to develop the heroin abstainers＇ cue-sensitization questionnaire （HACSQ）, and evaluate its reliability and validity, during March and April in 2006, the cross-sectional sample survey and cluster sampling were adopted among 939 volunteer participants who were heroin abstainers from 5 compulsive detoxification centers in China. The data were collected by the self-report questionnaires. The reliability analysis included Cronbach＇s a coefficient, split reliability and test-retest reliability, while construction validity was analyzed in the light of exploratory and confirmatory factor analysis. Based upon the exploratory factor analysis, 4 factors were extracted, which were social emotion cue （SEC）, direct implement cue （DIC）, personnel cue （PC） and indirect implement cue （IIC） and they together explained 64.52% variance. According to the data, test-retest reliability coefficient ranged from 0.57 to 0.63, and Cronbach＇s α coefficient ranged from 0.86 to 0.95 across the 4 factors and HACSQ. The adjusted goodness of fit index was 0.75. It was suggested that the HACSQ demonstrated good validities and reliabilities, and may be used as a reliable assessment tool for the cue-sensitization among the heroin abstainers.
