Pain Patterns of the Temporomandibular Joint Dysfunction and Implications of Stress-Related Behaviors: A Pilot Study / Patrones de Dolor de la Disfunción de la Articulación Temporomandibular e Implicaciones de los Comportamientos Relacionados con el Estrés: Un Estudio Piloto

SUMMARY: Temporomandibular joint dysfunction interferes with the quality of life and activities of daily living among patients. The symptoms of temporomandibular dysfunction, including pain and clicking and popping sounds, are worsened during stressful events, and patients report increased pain around the temporomandibular joint. Stress-related behaviors, such as teeth clenching and teeth grinding, are commonly reported as increasing during stress. The prevalence of temporomandibular dysfunction and stress-related behaviors is reported differently in the literature. Stress in higher education is common. The purpose of this pilot study was to investigate the prevalence of temporomandibular joint dysfunction and stress-related behaviors among staff members at a local University. The study also sought to explore pain patterns described by people experiencing temporomandibular joint dysfunction and the relationship between stress-related behaviors and pain symptoms experienced. Further, the impact of stress on symptoms experienced by people with temporomandibular dysfunction was investigated in this pilot study.

La disfunción de la articulación temporomandibular interfiere con la calidad de vida y las actividades de la vida diaria entre los pacientes. Los síntomas de la disfunción temporomandibular, incluidos el dolor y los chasquidos, empeoran durante los eventos estresantes, y los pacientes informan un aumento del dolor alrededor de la articulación temporomandibular. Los comportamientos relacionados con el estrés, como apretar y rechinar los dientes, suelen aumentar durante el estrés. La prevalencia de la disfunción temporomandibular y los comportamientos relacionados con el estrés se informa de manera diferente en la literatura. El estrés en la educación superior es común. El propósito de este estudio piloto fue investigar la prevalencia de la disfunción de la articulación temporomandibular y los comportamientos relacionados con el estrés entre los miembros del personal de una universidad local. El objetivo del estudio además fue explorar los patrones de dolor descritos por personas que experimentan disfunción de la articulación temporomandibular y la relación entre los comportamientos relacionados con el estrés y los síntomas de dolor experimentados. Además, en este estudio piloto se investigó el impacto del estrés en los síntomas que experimentan las personas con disfunción temporomandibular.

Protective effect of LW-AFC against fear sensitization induced by traumatic stress / 军事医学

Objective To investigate the protective effects and underlying mechanisms of Liuwei Dihuang Glucoside(LW-AFC)against fear sensitization induced by traumatic stress.Methods Mice were divided into naive,control,stressed and LW-AFC administration groups.The LW-AFC treated group received LW-AFC(1.6 g/kg daily)via oral gavage for two weeks following exposure to traumatic stress.The non-associative memory dependent fear sensitization responses in mice subjected to trauma were investigated,including behavior in novel environments,social interaction,and observational fear tests.Z-score normalization method was employed to integrate and assess multiple behavioral variables such as travel distance,freezing time,and corner time,and comprehensively examined fear sensitization behaviors across the groups.Additionally,serum concentrations of adrenocorticotropic hormone,corticosterone,aldosterone,renin,angiotensin Ⅱ,and aldosterone were measured using ELISA.Results Compared to the control group,stressed mice exhibited significantly reduced travel distance(P<0.0001)and increased freezing time(P<0.0001)in the new context test.Integrated Z-scores indicated a significant increase in fear behavior among stressed mice during the new context test(P<0.0001).In the social interaction test,stressed mice demonstrated significantly reduced travel distance(P<0.0001),increased freezing time(P<0.0001),increased corner time(P<0.05),and higher integrated Z-scores(P<0.0001).In the observational fear test,stressed mice showed significantly reduced travel distance(P<0.05),increased freezing time(P<0.001),increased corner time(P<0.05),and higher integrated Z-scores(P<0.0001).Compared to the stressed group,mice in the LW-AFC treated group displayed trends toward improvement in travel distance,freezing time,corner time,and integrated Z-scores in the new context tests,albeit without statistical significance.In the social interaction test,the LW-AFC treated group exhibited a significant reduction in freezing time(P<0.05)and integrated Z-scores(P<0.05).In the observational fear test,the LW-AFC treated group showed a significant reduction in freezing time(P<0.05)and integrated Z-scores(P<0.01).Compared to the naive group,control and stressed groups exhibited an increased trend in renin and aldosterone levels after the fear sensitization test.Although there were no significant differences between stressed and control groups,renin and aldosterone levels significantly increased between stressed and naive groups(P<0.05,P<0.05).Following LW-AFC treatment,serum renin levels showed no significant change,while aldosterone levels significantly decreased(P<0.05).Conclusion Stressed mice exhibited significant fear sensitization behavior in new context,social interaction,and observational fear tests,possibly associated with partial activation of the renin-angiotensin-aldosterone system(RAAS)system.LW-AFC treatment significantly mitigated fear sensitization behavior of stressed mice in social interaction and observational fear test,potentially due to its regulatory effects on the RAAS system in mice subjected to traumatic stress.

Progress in diagnosis and treatment of allergic fungal airway disease in children / 中华实用儿科临床杂志

Fungus is one of common allergens in allergic disease that affects the susceptibility, severity, and disease control of allergic airway disease in children.A spectrum of respiratory diseases associated with fungal sensitization has been described as allergic fungal airway disease (AFAD), including severe asthma with fungal sensitization, allergic bronchopulmonary aspergillosis, thunderstorm asthma, and allergic fungal rhinosinusitis.Glucocorticoids, biologics, antifungal therapy, and immunotherapy can reduce the airway inflammation, fungal burden, and tissue damage associated with AFAD.This review introduced fungus, the mechanism of fungal sensitization and the detection, as well as the scope and treatment of AFAD in children, aiming to improve the understanding of AFAD among pediatricians.

Dihydroartemisinin promotes radiotherapy sensitivity of nasopharyngeal carcinoma CNE-2Z cells by activating chloride channels / 中国病理生理杂志

AIM:To investigate the role of ClC-3 chloride channel in the promotion of radio sensitization of na-sopharyngeal carcinoma CNE-2Z cells by dihydroartemisinin(DHA).METHODS:MTT was used to detect the inhibito-ry effect of DHA on the viability of CNE-2Z cells and normal nasopharyngeal epithelial NP69-SV40T cells,the radio sensi-tization effect of DHA on CNE-2Z cells was detected by cloning assay,the expression of ClC-3 protein was detected by Western blot,the expression of ClC-3 protein was down-regulated by siRNA technology,and the chlorine current of cells was recorded by whole cell patch-clamp technology.RESULTS:(1)Compared with NP69-SV40T cells,DHA selective-ly inhibited the proliferation of CNE-2Z cells,with IC10 values of(13.020±4.831)μmol/L and(5.244±1.050)μmol/L,respectively(P＜0.01).(2)The results of clonal formation experiments showed that DHA had a radio sensitizing effect on CNE-2Z cells,with a radio sensitization ratio of 1.9.(3)DHA could activate the chlorine channel of CNE-2Z cells and produce an outward chlorine current,but had no effect on the chlorine channel of NP69-SV40T cells.(4)DHA promoted the expression of ClC-3 chloric channel protein in CNE-2Z cells(P＜0.01).(5)Chlorine channel blocker NPPB could in-hibit the radio sensitizing effect of DHA on CNE-2Z cells by 1.84 times,and also inhibited the chlorine current activated by DHA.(6)the down-regulation of CNE-2Z ClC-3 protein could inhibit the radio sensitization effect of DHA on CNE-2Z cells by 4.19 times,and the activation of chlorine current by DHA on CNE-2Z cells was no longer produced.CONCLU-SION:DHA has a radio sensitizing effect on nasopharyngeal carcinoma CNE-2Z cells,which is likely to be related to the activation of ClC-3 chloride channel.

Corticotropin releasing factor receptor 2 involves in pain sensitization and anxiety of chronic migraine mice / 中华神经医学杂志

Objective:To explore the role of corticotrophin releasing factor receptor 2 (CRFR2) in regulating pain sensitization and anxiety and its mechanism in chronic migraine mice.Methods:Forty-eight C57BL/6J mice were randomly divided into control group, model group, NBI35965 group and K41498 group ( n=12); chronic migraine models in the later 3 groups were established by intraperitoneally administrating 10 mg/kg nitroglycerin on the 1 st, 3 rd, 5 th, 7 th and 9 th d; mice in the NBI35965 group and K41498 group were injected with 100 nL NBI35965 or K41498 solution into the bilateral trigeminal nucleus caudalis on the 2 nd, 4 th, 6 th and 8 th d, and mice in the control group were injected with same volume of normal saline. Von frey fiber was used to detect the orbitofrontal mechanical pain threshold 2 h after intraperitoneal injection on the 1 st, 3 rd, 5 th, 7 th and 9 th d, and at 11 a.m. on the 10 th d. Elevated plus maze was used to detect the anxiety-like behaviors at 11 a.m. on the 11 th d. Western blotting was performed to detect the protein expressions of corticotrophin releasing factor (CRF), corticotrophin releasing factor receptor 1 (CRFR1), CRFR2 in the trigeminal nucleus caudalis. Real-time quantitative PCR (RT-qPCR) was used to detect the CRFR1 and CRFR2 mRNA expressions in the trigeminal nucleus caudalis. Immunofluorescent staining was used to detect the protein expressions of calcitonin gene-related peptide (CGRP), immediate-early gene c-fos, glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1) in the trigeminal nucleus caudalis. Results:Compared with the control group, the model group, NBI35965 group and K41498 group had significantly decreased orbitofrontal mechanical pain thresholds 3, 5, 7, 9, and 10 d after intraperitoneal injection ( P<0.05); compared with model group, the K41498 group had significantly increased orbitofrontal mechanical pain thresholds 7, 9, and 10 d after intraperitoneal injection ( P<0.05). Compared with control group, the model group, NBI35965 group and K41498 group had significantly decreased entries and shorter time in opened arms ( P<0.05); compared with the model group, the K41498 group had significantly increased entries and shorter time in opened arms ( P<0.05). Compared with the control group, the model group, NBI35965 group and K41498 group had significantly higher CRF and CRFR2 protein expressions in the trigeminal nucleus caudalis ( P<0.05); compared with the model group, the K41498 group had statistically lower CRF protein expression in the trigeminal nucleus caudalis ( P<0.05). Compared with the control group, the model group, NBI35965 group and K41498 group had significantly higher CRFR2 mRNA expression in the trigeminal nucleus caudalis ( P<0.05). Compard with the control group, the model group, NBI35965 group and K41498 group had significantly increased CGRP, c-fos, Iba-1 and GFAP protein expressions in the trigeminal nucleus caudalis ( P<0.05); compared with the model group, the K41498 group had significantly decreased CGRP and c-fos protein expressions in the trigeminal nucleus caudalis ( P<0.05). Conclusion:CRFR2 can alter the orbitofrontal pain sensitization and anxiety-like behaviors in chronic migraine mice by regulating neuronal activation and CGRP release in the trigeminal nucleus caudalis.

Clinical management strategies for recipients with renal graft loss / 器官移植

With the maturity of kidney transplantation, introduction of new immunosuppressive drugs and improvement of immunosuppressive regimen, the short-term survival rate of kidney transplant recipients has been significantly improved, whereas the long-term survival rate has not been significantly elevated. Kidney transplant recipients may have the risk of renal graft loss. Clinical management after renal graft loss is complicated, including the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy. These management procedures directly affect clinical prognosis of patients with renal graft loss. Nevertheless, relevant guidelines or consensuses are still lacking. Clinical management of patients after renal graft loss highly depend upon clinicians’ experience. In this article, the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy were reviewed, aiming to provide reference for prolonging the survival and improving the quality of life of these patients.

Regulatory Mechanism of Radiation Therapy for Lung Cancer with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Lung cancer is the fastest-growing cancer type in terms of incidence and mortality worldwide， posing a huge threat to the health and life of the population. Radiation therapy is one of the main methods for treating lung cancer， and there is a clear dose-effect relationship between the radiation dose and local control rate of lung cancer. However， the lung is a radiation dose-limiting organ， and the radiation resistance of lung cancer tissues and the radiation damage to normal tissues limit the radiation efficacy for lung cancer. The pathogenesis of lung cancer in traditional Chinese medicine （TCM） is characterized by an initial deficiency in vital Qi， followed by the internal invasion and gradual accumulation of pathogenic Qi. After radiation therapy for lung cancer， the body's vital Qi becomes weaker， and syndromes of phlegm coagulation， Qi stagnation， and static blood blocking collaterals become more severe， leading to radiation resistance of lung cancer tissues. Therefore， the key issue to better clinical efficacy of radiation therapy for lung cancer patients is to use drugs to enhance the radiation sensitivity of lung cancer cells and improve the radiation tolerance of normal lung tissues. TCM can be used as a radiation sensitizer by regulating the cell cycle to increase the proportion of cells in the radiation-sensitive phase， promoting upregulation of pro-apoptotic genes and downregulation of anti-apoptotic genes to induce cell apoptosis， enhancing DNA damage caused by radiation and inhibiting damage repair， improving blood circulation and tissue oxygen supply， and so on， to enhance the sensitivity of tumor cells to radiation and amplify the toxicity of radiation to tumor tissues. TCM can also be used as a radiation protector by inhibiting cell damage， regulating cytokines and immune balance， reducing the release of inflammatory and fibrotic factors， and inhibiting the activation of related signaling pathways to prevent and treat radiation-induced lung injury. This article systematically reviewed the research results of TCM on radiation sensitization and radiation protection in lung cancer in recent years， aiming to elucidate the mechanism of TCM in regulating the effect of radiation therapy for lung cancer and provide more theoretical and practical basis for TCM to participate in improving the prognosis of lung cancer patients undergoing radiation therapy.

Exploration on Syndrome Differentiation Thinking for Stress Sensitization-induced Depression from the Perspective of"Deficient Qi with Stagnation and Heat" / 中国中医药信息杂志

TCM proposes that the core pathological mechanism of depression is"deficient qi with stagnation and heat",with the following pathogenic characteristics and evolution patterns:"deficient qi"as the nature,and deficiency in nature is in spleen,and deficiency in superficiality is in brain;"stagnation"is the superficiality,and qi stagnation,phlegm stagnation,and blood stagnation are in the brain collaterals;"heat"fires the brain collaterals,depression raised the heat,and excessive heat accumulated to stagnation.Based on the understanding of the pathogenesis of depression caused by stress sensitization in modern medicine,this article explored the potential association between this mechanism and the core pathogenesis of"deficient qi with stagnation and heat".It proposed that tonifying deficiency,promoting circulation,and clearing heat are the basic treatment principles for depression.By inhibiting inflammatory reactions and improving the stress sensitization state of neurons and glial cells,TCM compound formulas can exert multi-target and multi-dimensional therapeutic characteristics.

Basic and clinical research progress in carbon ion therapy for colorectal cancer / 中华放射肿瘤学杂志

Colorectal cancer is a common clinical malignant tumor. As the main therapeutic method of colorectal cancer, radiotherapy has a good inhibitory effect on tumor progression. In recent years, because of its good physical and biological advantages, carbon ion has shown better clinical efficacy than traditional radiotherapy in the treatment of local recurrence or distant metastasis of colorectal cancer. In this article, basic and clinical studies related to the efficacy of carbon ion therapy for the recurrence of colorectal cancer in recent years were reviewed, aiming to provide theoretical basis for preventing and reducing adverse reactions after radiotherapy and prolonging the survival of colorectal cancer patients.

Poly sensibilisation dans le cadre d'un eczéma de contact des mains chez une aide-ménagère dans le nord du Bénin / Poly sensitization in the context of hand contact eczema in a household helper in northern Benin

L'eczéma des mains est fréquent. Son étiologie est souvent multifactorielle comprenant les facteurs environnementaux et des facteurs individuels prédisposants. Il pose des problèmes de diagnostic étiologique en particulier dans un contexte de poly sensibilisation. Observation Il s'est agi d'une employée de maison âgée de 17 ans sans antécédents allergiques connus. Elle a développé un eczéma bilatéral des mains six mois après embauche. Le patch test avec la batterie standard européenne a montré une poly sensibilisation à plusieurs allergènes contenus dans les détergents et désinfectants. Le patch test aux gants est revenu négatif mais n'exclut pas son implication dans la survenue des lésions devant le caractère bilatéral et symétrique des lésions. Une réorientation professionnelle a été proposée devant le jeune âge de la travailleuse Conclusion La connaissance des allergènes en cause au cours d'un eczéma est un atout pour une meilleure prise en charge du patient mais leur identification n'est pas toujours aisée. La réorientation professionnelle lorsqu'elle est possible assure la guérison.

Introduction: Hand eczema is common. Its etiology is often multifactorial, including environmental factors and individual predisposing factors. It poses problems of etiological diagnosis, particularly in the context of poly sensitization. Observation: This case involved a 17-year-old domestic worker with no known allergic history. She developed bilateral hand eczema six months after hiring. The patch test with the standard European battery showed poly-sensitization to several allergens contained in detergents and disinfectants. The glove patch test came back negative, but did not rule out its involvement in the lesions, given the bilateral and symmetrical nature of the lesions. In view of the young age of the worker, a vocational reorientation was carried out. Conclusion: Knowledge of the allergens involved in eczema is an asset for better patient management, but identifying them is not always easy. When possible, professional reorientation ensures recovery

Aeroallergen sensitization patterns among patients with chronic rhinitis with or without concomitant asthma

Abstract Objectives The aim of this study was to explore the differences in the pattern of allergen sensitization in CR individuals without or with asthma, according to asthma severity. Methods A total of 1066 adults were evaluated. Asthma and chronic⁄allergic rhinits were identified by specialists, questionnaries and skin-prick test. The phenotypic characterization was avaliable from skin-prick test to an aeroallergen extended panel, total IgE and pulmonary function. Using questionnaires and clinical evaluation, participants were classified into the groups: chronic rhinitis alone (CRA) and chronic rhinitis + asthma, the latter subdivided into CR + mild asthma (CRMA) and CR + moderate to severe asthma (CRMSA). Aerollergen sensitization was defined by a positive prick test to one or more allergens associated with nasal symptoms and/or asthma. The association between CR and asthma was evaluated by multivariable logistic regression. The evidence of effect modification of pattern of sensitization in CR on the association with asthma severity and outcomes was examined by introducing interactions terms in the logistic regression models adjusting for confounders. Results Frequency of sensitization to aeroallergens was higher in association with asthma in comparison to CRA (CRMA 70.4%; CRMSA 65.0%; CRA 47.0%; p= 0.000). Similarly, the presence of asthma was associated to aeroallergen multiple sensitization (51.5%) (OR = 2.10, 95% CI 1.27-3.50). Additionally, the sensitization to mites, cockroaches, animal epithelium, grasses, and molds, were higher in asthma (56.8%, 24.3%, 12%, 7.13% and 10.3%, respectively). Sensitization to Alternaria alternata, Cladosporium herbarum and dog epithelium was exclusive in asthma groups. A concomitant asthma diagnosis was directly associated with a positive allergen sensitization at least one allergen (62.7%, OR = 2.45, 95% CI 1.80-3.34) and polissensitization (51.5%, OR = 2.10, 95% CI 1.27-3.50). Conclusion Asthma is associated with multiple allergen sensitization among patients with CR. Some unique profiles of aeroallergen sensitization were observed in patients with CR and asthma. Nevertheless, no difference was found in the sensitization in relation to asthma severity, which suggest atopy is not the main underlying mechanism for asthma severity among patients with CR. Level of evidence: Level 3.

Central sensitization in adults with chronic neck pain: cross-cross study exploring differences by gender / Sensibilização central em adultos com dor cervical crônica: estudo transversal explorando as diferenças por sexo

ABSTRACT BACKGROUND AND OBJECTIVES: The presence of central sensitization (CS) in people with chronic neck pain requires clarification, as does the possible disparities between genders. Therefore, this study aimed to evaluate the presence of CS in chronic neck pain according to gender. METHODS: Cross-sectional study with the participation of 260 adults (18-59 years old) with chronic neck pain, carried out between September 2022 and September 2023. Instruments were applied to collect sociodemographic profile, pain characteristics, cervical functional disability and presence of SC. The software SPSS 23.0 was used for comparative analyzes. RESULTS: Regarding disparities between genders, there were no differences in the intensity of pain and cervical functional disability (p=0.134 and p=0.277, respectively). However, SC was higher in women (43.5 ± 14.0; p=0.003). In females, CS was related to "pain interference" in the aspects of walking (r=0.311; p=0.001), relationships with people (r=0.309; p=0.001), appreciation of life (r=0.321; p= 0.001) and with cervical functional disability (r=0.570; p=0.001). In males, CS was related to "pain interference" in aspects such as general activity (r=0.311; p=0.008), mood (r=0.376; p=0.001), walking (r=0.313; p= 0.007), relationships with people (r=0.477; p=0.001), sleep (r=0.321; p=0.006), appreciation of life (r=0.427 p=0.001) and functional disability (r=0.667; p<0.001). CONCLUSION: Women with chronic neck pain showed a greater presence of CS, while CS in men was related to a variety of aspects that negatively affect life. Given this, differences between genders could be considered in the management of patients with chronic neck pain.

RESUMO JUSTIFICATIVA E OBJETIVOS: A presença de sensibilização central (SC) em pessoas com dor cervical crônica carece de esclarecimentos, bem como as possíveis disparidades entre os sexos. Portanto, objetivou-se avaliar a presença de SC na dor cervical crônica de acordo com o sexo. MÉTODOS: Estudo transversal com a participação de 260 adultos (18-59 anos) com dor cervical crônica, realizado entre setembro de 2022 e setembro de 2023. Foram aplicados instrumentos para coletar perfil sociodemográfico, características da dor, incapacidade funcional da cervical e presença de SC. Para análises comparativas foi utilizado o SPSS 23.0. RESULTADOS: Nas disparidades entre os sexos, não houve diferenças na intensidade da dor e incapacidade funcional cervical (p=0,134 e p=0,277, respectivamente). No entanto, a SC foi mais elevada nas mulheres (43,5 ± 14,0; p=0,003). No sexo feminino, a SC apresentou relação com a "interferência da dor" nos aspectos: caminhar (r=0,311; p=0,001), relacionamento interpessoal (r=0,309; p=0,001), apreciação da vida (r=0,321; p=0,001) e com incapacidade funcional da cervical (r=0,570; p=0,001). Já no sexo masculino, a SC teve relação com a "interferência da dor" em aspectos como atividade geral (r=0,311; p=0,008), humor (r=0,376; p=0,001), caminhar (r=0,313; p=0,007), relacionamento interpessoal (r=0,477; p=0,001), sono (r=0,321; p=0,006), apreciação da vida (r=0,427 p=0,001) e incapacidade funcional (r=0,667; p<0,001). CONCLUSÃO: Mulheres com dor cervical crônica mostraram maior presença da SC, enquanto nos homens a SC esteve relacionada a uma variedade de aspectos que afetam negativamente a vida. Diante disso, as diferenças entre os sexos poderiam ser consideradas no gerenciamento de pacientes com dor cervical crônica.

Study on the antidepressant activity of (2R,6R; 2S,6S)-Hydroxynorketamine (HNK) and its derivatives

Abstract Objective: This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects. Methods: Four HNK compounds were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization test, and conditioned location preference test were used to screen the antidepressant activity of the synthesized target compounds. Results: In the case of 10 mg HNK treatment, compared with saline, the immobile time of mice in the HNK group, I5 group and I6 group at 1 h and 7 days had statistical significance. In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different. In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day. In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group. Conclusion: The results of the forced swimming test, locomotor sensitization test, and conditioned location preference test showed that compounds C and D may have certain anti-depressant activity. However, HNK exerts a rapid and significant antidepressant effect within 1 week, but the duration is short.

Salmonella-mediated blood‒brain barrier penetration, tumor homing and tumor microenvironment regulation for enhanced chemo/bacterial glioma therapy

Chemotherapy is an important adjuvant treatment of glioma, while the efficacy is far from satisfactory, due not only to the biological barriers of blood‒brain barrier (BBB) and blood‒tumor barrier (BTB) but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as up-regulation of P-glycoprotein (P-gp). To address these limitations, we report a bacteria-based drug delivery strategy for BBB/BTB transportation, glioma targeting, and chemo-sensitization. Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment, including macrophages repolarization and neutrophils infiltration. Specifically, tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin (DOX)-loaded bacterial outer membrane vesicles (OMVs/DOX). By virtue of the surface pathogen-associated molecular patterns derived from native bacteria, OMVs/DOX could be selectively recognized by neutrophils, thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect. Moreover, the P-gp expression on tumor cells was silenced by bacteria type III secretion effector to sensitize the efficacy of DOX, resulting in complete tumor eradication with 100% survival of all treated mice. In addition, the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk, and cardiotoxicity of DOX was also avoided, achieving excellent compatibility. This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.

Advances of n-3 polyunsaturated fatty acids in food allergy / 中华实用儿科临床杂志

Food allergy is a common allergic disease threatening the growth and development of infants and children.n-3 polyunsaturated fatty acids (PUFAs) are common nutrients in the diet, which have important structural functions and immunomodulatory effects.Their protective effect in food allergy has gradually become a potential research hotspot.This review highlights the function and immune regulation of PUFAs, the regulation of n-3 PUFAs on immunological indexes, the mechanism of food allergy, and the relationship between food allergy, and the impact of n-3 PUFAs on other allergic diseases.

Effect of Acupuncture on Sensitization of Zusanli(ST36)in Rats with Different Functional States / 世界科学技术-中医药现代化

Objective To investigates the effect of acupuncture on sensitization of Zusanli(ST36)in rats with different functional states by using healthy and knee osteoarthritis model rats.Methods Male SD rats were randomly divided into control,model,model-acupuncture and blank-acupuncture group,with 7 rats in each group.KOA rat model was prepared by intra-articular injection of 1 mg·50 μL-1 monoiodoacetic aci(MIA)in model group and model-acupuncture group.On the second day of modeling,acupuncture treatment was performed on the left Zusanli of the model acupuncture group and the blank-acupuncture group,once everyday for 20 min,5 times as a course of treatment,2 days between courses.The general condition,knee joint diameter,plantar thermal pain threshold and Lequesne MG score of rats was observed before modeling and after acupuncture.Observing the morphology of knee joint cartilage to judge whether the model is successful,measuring the mechanical pain threshold of Zusanli to investigate the acupoint sensitization,observing and counting the morphology of skin mast cells in the acupoint area,and detecting the expression of skin calcitonin gene-related peptide(CGRP)in the acupoint area.Results The mechanical pain threshold of Zusanli after acupuncture in model group and blank-acupuncture group decreased significantly after modeling(P<0.01,P<0.05),compared with the control group,the change rate of mechanical pain threshold in model group and blank-acupuncture group increased significantly(P<0.05),compared with the model group,the mechanical pain threshold of Zusanli in the model-acupuncture group decreased significantly(P<0.01).Compared with the control group,the fluorescence intensity of CGRP protein in the skin tissue of Zusanli in the model group increased significantly(P<0.01),MC degranulation rate increased significantly(P<0.05),and there was no significant difference in the fluorescence intensity of CGRP protein of Zusanli in the blank-acupuncture group(P>0.05),MC degranulation rate increased obviously(P<0.01),CGRP protein of Zusanli in the model-acupuncture group was significantly reduced compared with the model group(P<0.01),and there was no significant difference in the degranulation rate of MC(P>0.05).Conclusion Acupoint sensitization can occur in different functional states of rats.Zusanli(ST36)of KOA model rats can be sensitized,and acupuncture stimulation can make Zusanli sensitization caused by disease disappear.Under physiological conditions,acupuncture stimulation can induce similar sensitization phenomenon.

Gardner-Diamond syndrome / 中华皮肤科杂志

Gardner-Diamond syndrome is a rare skin disease characterized by recrudescent, spontaneous and tender ecchymoses, and mostly affects psychologically disturbed adult women. The positive autoerythrocyte sensitization test has noticeable diagnostic significance. Currently, there is no specific therapy for Gardner-Diamond syndrome. This review summarizes advances in the pathogenesis, clinical features, diagnosis and treatment of this disease.

Analysis on the Phenomenon and Regularity of Acupoint Sensitization for Major Depressive Disorder / 浙江中医药大学学报

[Objective]To explore the phenomenon and regularity of acupoint sensitization for major depressive disorder(MDD)based on bibliometric methodology and data mining technology,and to provide scientific ideas for the clinical diagnosis and treatment of MDD.[Methods]Eight electronic databases and one ancient book were comprehensively searched and available literature was retrieved.Bibliometric methodology and data mining technology were applied to summarize the phenomenon and regularity of acupoint sensitization for MDD,and to explore the related theoretical mechanisms.[Results]A total of 29 literature related to acupoint sensitization of MDD was included.Acupoint sensitization of MDD involved in multiple forms,including heat sensitization,chemical sensitization,pain sensitization,and so on,and the testing means were diverse.The most common sensitized acupoint was Baihui(GV20).Among these acupoints,sensitization often simultaneously occurred in Baihui(GV20)and Neiguan(PC7),Baihui(GV20)and Taichong(LR3).The acupoints and sensitization could be divided into 4 effective clusters.The meridian involved with high sensitization frequency was governor vessel.Sensitization mainly occurred in the head-face-neck area.[Conclusion]The sensitization phenomenon of MDD has many types,However,there are few related studies at present.The phenomenon of acupoint sensitization involving acupoint,meridians,and location are relatively broad.There might be a close relationship between high-frequency sensitized acupoints and common acupoints for clinical treatment,which may be related to the effect of different acupoints and the etiology and pathogenesis of MDD.

Role and mechanism of PKCs in midazolam-induced relaxation of aortic smooth muscle in spontaneously hypertensive rats / 中国药理学通报

Aim To investigate the effect of protein kinase C (PKCs) on midazolam-induced relaxation of aortic smooth muscle in spontaneously hypertensive rats (SHR) and the underlying mechanism. Methods U-sing the isolated vessel tension measurement system, the relaxant effect of midazolam on aortic smooth muscle of SHR and Wistar-Kyoto (WKY) rats was observed. After preincubation with GF109203X (GF, a broad-spectrum inhibitor of PKCs), LY333531 (LY, PKCp2 specific inhibitor) and PKC6 pseudo-substrate inhibitor (PPS), the changes of midazolam-induced relaxation amplitude were observed. Western blot was used to detect the effect of midazolam on the phosphorylation level of PKC [32 in SHR aortic smooth muscle. The effect of midazolam, LY, GF and PPS on the phosphorylation level of the key proteins (CPI-17/ MYPT1/MLC) in calcium sensitization pathway in SHR aortic smooth muscle was also examined. Results Midazolam concentration-dependently relaxed aortic smooth muscle in SHR and WKY. GF significantly inhibited midazolam-induced relaxation amplitude of SHR and WKY aortic smooth muscle. LY and PPS had no significant effect on midazolam-induced relaxation amplitude of WKY aortic smooth muscle. In contrast, LY markedly inhibited midazolam-induced relaxation amplitude of SHR aortic smooth muscle. Midazolam significantly inhibited the phosphorylation level of PKC [32 enhanced by NE in SHR aortic smooth muscle. Midazolam, LY and GF all evidently inhibited the phosphorylation level of the key proteins in calcium sensitization pathway enhanced by NE in SHR aortic smooth muscle. Conclusions Midazolam induces excessive relaxation of SHR aortic smooth muscle by inhibiting calcium sensitization pathway mediated by PKC [32.

The role of bacteria and its derived biomaterials in cancer radiotherapy

Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics. It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors, especially when combined with traditional therapy, such as radiotherapy. According to their different biological characteristics, bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues. Moreover, genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy. In this review, we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years, expounding that the bacteria, bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment (TME) and immune effects. Furthermore, some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory, anti-oxidation and apoptosis inhibition. In conclusion, the prospect of bacteria in radiotherapy will be very extensive, but its biological safety and mechanism need to be further evaluated and studied.