O uso da proteína botulínica na correção do sorriso gengival / The use of botulinum protein in the correction of gingival smile

A sociedade está cada vez mais exigente e em busca de excelência quando o assunto é estética facial. O sorriso tem grande impacto na harmonia da face e, atualmente, os pacientes estão mais conscientes sobre a influência da gengiva na beleza do sorriso. A exposição da gengiva em excesso, conhecida como sorriso gengival, afeta a estética, podendo interferir na autoestima e nas relações sociais dos pacientes. Existem diversos procedimentos descritos para solucionar o problema e, para o planejamento do caso e escolha do método, é preciso determinar a etiologia e levar em consideração o desejo do paciente. A injeção da proteína botulínica é uma alternativa minimamente invasiva que está sedo cada vez mais utilizada para a correção do sorriso gengival. Com isso, o objetivo do presente trabalho monográfico foi realizar uma revisão de literatura sobre o uso da toxina botulínica na correção do sorriso gengival, analisando técnicas de injeção, identificando o efeito imediato e a longo prazo da toxina nos músculos elevadores do lábio superior, além de avaliar a relevância desse método na correção do sorriso gengival, sozinho ou em conjunto com outros procedimentos. Foi realizada uma revisão de literatura nas bases de dados PubMed e Scielo, buscando artigos dos anos de 2013 até 2022, utilizando os descritores "botulinum toxin", "botox", "gummy smile", "gingival display" e "gingival exposure". Essa revisão analisa 15 artigos que discorrem sobre o método, durabilidade e eficácia da aplicação de proteína botulínica para correção do sorriso gengival. Algumas variantes diferenciam as técnicas de aplicação, como a marca do produto e recomendações do fabricante, classificação do sorriso e extensão da exposição gengival. Com base na revisão de literatura, pôde-se concluir que, apesar de ser transitório, esse procedimento se mostrou eficaz, tanto ao ser realizado como método principal, quanto como coadjuvante no tratamento. Além de ser comprovadamente seguro, rápido, minimamente invasivo e ser o tratamento de preferência entre os pacientes, com alto índice de satisfação, são raras as complicações relacionadas a aplicação da proteína botulínica para esse fim.

Society is becoming increasingly demanding, seeking excellence in facial aesthetics. The smile greatly impacts facial harmony, and nowadays, patients are more aware of the influence of the gums on smile beauty. Excessive gum exposure, known as gummy smile, affects aesthetics and can interfere with patients' self-esteem and social relationships. There are various procedures described to address this issue, and for case planning and method selection, it is necessary to determine the etiology and take into account the patient's desires. The injection of botulinum protein is a minimally invasive alternative that is increasingly being used for gummy smile correction. Thus, the aim of this monographic work was to conduct a literature review on the use of botulinum toxin in gummy smile correction, analyzing injection techniques, identifying the immediate and long-term effects of the toxin on the upper lip elevator muscles, and evaluating the relevance of this method in gummy smile correction, either alone or in conjunction with other procedures. A literature review was conducted in the PubMed and Scielo databases, seeking articles from 2013 to 2022, using the descriptors "botulinum toxin", "botox", "gummy smile", "gingival display", and "gingival exposure". This review analyzes 15 articles that discuss the method, durability, and effectiveness of botulinum toxin application for gummy smile correction. Some variations differentiate the application techniques, such as the product brand and manufacturer's recommendations, smile classification, and extent of gum exposure. Based on the literature review, it was possible to conclude that, despite being temporary, this procedure proved to be effective, both when performed as the main method and as an adjunct in treatment. In addition to being proven safe, fast, minimally invasive, and the preferred treatment among patients, with a high satisfaction rate, complications related to botulinum toxin application for this purpose are rare.

Tratamento integrado para correção do sorriso gengival: relato de caso / Integrated treatment for correction of gingival smile: case report

O sorriso gengival possui inúmeras causas, podendo acontecer por motivos esqueléticos, musculares ou por alteração no desenvolvimento dos tecidos de suporte. No entanto, na atualidade, a estética vermelha e a branca têm se apresentado completamente passíveis de transformações e com uma gama de procedimentos cirúrgicos ou não cirúrgicos para sanar as queixas dos pacientes. O objetivo geral deste trabalho é mostrar o poder que a odontologia tem frente às questões estéticas, como, por exemplo, a vergonha de sorrir por não se sentir confortável com os dentes curtos e com uma grande faixa de gengiva sendo exposta. O método utilizado foi um relato de caso. Que descreve todos os passos clínicos do tratamento de um paciente de 40 anos, que estava insatisfeita com o seu sorriso por apresentar erupção passiva alterada juntamente com hiperatividade do lábio superior. O plano de tratamento escolhido foi de realizar a cirurgia de aumento de coroa clínica estético, seguido de clareamento dentário e posteriormente um reposicionamento labial, com ajuda da toxina botulínica. Finalizando, para ajudar na cicatrização, o uso de laserterapia. O resultado de todo o processo cirúrgico envolvido neste trabalho, é satisfação do paciente, materializando o sonho deste, devolvendo segurança e espontaneidade ao sorrir. Pôde-se observar que através da combinação de técnicas cirúrgicas periodontais para tratar o sorriso gengival, obtém-se êxito tanto no sentido científico quanto no biológico, alcançando um sorriso esteticamente mais atrativo(AU)

Gummy smile has numerous causes, which can occur for skeletal or muscular reasons or due to changes in the development of supporting tissues. However, nowadays, the red and white aesthetics have been completely capable of transformation and with a range of surgical or non-surgical procedures to resolve patients' complaints. The general objective of this work is to show the power that dentistry has in the face of aesthetic issues, such as, for example, the shame of smiling due to not feeling comfortable with short teeth and a large strip of gum being exposed. The method used was a case report. Which describes all the clinical steps of the treatment of a 40-year-old patient, who was dissatisfied with her smile due to an altered passive eruption together with hyperactivity of the upper lip. The chosen treatment plan was to perform aesthetic clinical crown augmentation surgery, followed by tooth whitening and later lip repositioning, with the help of botulinum toxin. Finally, to help with healing, the use of laser therapy. The result of the entire surgical process involved in this work is patient satisfaction, materializing the patient's dream, restoring security and spontaneity when smiling. It was observed that through the combination of periodontal surgical techniques to treat gummy smile, success is achieved both in the scientific and biological sense, achieving a more aesthetically attractive smile(AU)

Reshaping smiles: A successful clinical case with botulinum toxin for gummy smile reduction / Remodelación de sonrisas: un caso clínico de éxito con toxina botulínica para la reducción de la sonrisa gingival

Abstract The use of botulinum toxin (BTX) represents an effective and safe approach in treating the gummy smile, reducing excessive gum exposure during smiling. This minimally invasive procedure can yield remarkable aesthetic results and contribute to an increase in the patient's self-confidence. The aim of this study is to report a clinical case of a female patient undergoing treatment to correct a gummy smile. The case study involves a 21-year-old patient with excessive gum exposure (5mm when smiling) who sought dental treatment. The origin of her gummy smile was mixed, and the treatment involved the application of 6 units of BTX type A at three specific points on the face. No complications were observed during the three-month follow-up period. Based on the case report, it can be concluded that BTX application for gummy smile treatment proved to be effective, safe, and comfortable in terms of recovery. The BTX approach to correcting a gummy smile is considered safe and entails straightforward recovery, producing satisfactory results that contribute to the improvement of aesthetics and the patient's well-being.

Resumen El uso de toxina botulínica (BTX) representa un enfoque eficaz y seguro para el tratamiento de las sonrisas gingivales, reduciendo la exposición excesiva de las encías durante la sonrisa. Este procedimiento mínimamente invasivo puede producir resultados estéticos notables y contribuir a aumentar la confianza del paciente en sí mismo. El objetivo de este estudio es presentar el caso clínico de una paciente que se sometió a un tratamiento para corregir una sonrisa gingival. Se trata de una paciente de 21 años con una exposición gingival excesiva (5mm al sonreír) que solicitó tratamiento odontológico. El origen de su sonrisa gingival era mixto y el tratamiento consistió en la aplicación de 6 unidades de BTX tipo A en tres puntos concretos de la cara. No se observaron complicaciones durante los tres meses de seguimiento. Basándonos en el informe del caso, se puede concluir que la aplicación de BTX para el tratamiento de la sonrisa gingival demostró ser eficaz, segura y cómoda en términos de recuperación. El enfoque de BTX para la corrección de la sonrisa gingival se considera seguro y de fácil recuperación, y produce resultados satisfactorios que contribuyen a mejorar la estética y el bienestar del paciente.

Oromandibular dystonia as a cause of temporomandibular disorder (Case report) / Distonia oromandibular como causa de disfunção temporomandibular (Relato de caso)

Temporomandibular disorders (TMD) can have multiple etiologies, including oromandibular dystonia (OMD). However, in a few cases, the OMD can evolve from cervical dystonia (CD), leading to severe bone degeneration. The purpose of this case report of a 64-year-old woman presenting to the Outpatient Neurology Clinic of the Federal University of Bahia is to illustrate the development of oromandibular dystonia with temporomandibular joint (TMJ) dysfunction after 10 years of cervical dystonia. Clinical examination showed bone degeneration of the mandibular ramus and right TMJ click, a prevalent sound in patients with temporomandibular disorders when they open their mouths or chew. After onabotulinum toxin type A injections in the right lateral pterygoid muscle, the patient improved in swallowing and pain. This case highlights the importance of close follow-up of cervical dystonia patients to identify new dystonic muscles. In our patient, lateral pterygoid muscle involvement was followed by several comorbidities, such as dysphagia and jawbone abnormalities.

Os distúrbios temporomandibulares (DTM) podem ter múltiplas etiologias, incluindo a distonia oromandibular (DO). No entanto, em raros casos, a DO pode evoluir a partir da distonia cervical (DC) e raramente pode levar a degeneração óssea. O objetivo deste relato de caso de uma mulher de 64 anos atendida no Ambulatório de Neurologia da universidade Federal da Bahia é ilustrar o desenvolvimento de distonia oromandibular com disfunção da articulação temporomandibular (ATM) após 10 anos de distonia cervical. O exame clínico mostrou degeneração óssea do ramo mandibular e clique na ATM direita, um som prevalente em pacientes com distúrbios temporomandibulares quando abrem a boca ou mastigam. Após injeções de toxina botulínica tipo A no músculo pterigoideo lateral direito, a paciente apresentou melhora na deglutição e na dor. Este caso destaca a importância do acompanhamento próximo de pacientes com distonia cervical para identificar novos músculos distônicos. Em nossa paciente, o envolvimento do músculo pterigoide lateral foi seguido por várias comorbidades, como disfagia e anormalidades ósseas da mandíbula.

Inyección local de toxina botulínica para la prevención de cicatrices hipertróficas y queloides: un protocolo para una revisión panorámica

Introducción: Las cicatrices hipertróficas (CH) y queloides (QU) corresponden al resultado de una cicatrización patológica en la piel, que afectan la calidad de vida de quienes las presentan. Su tratamiento considera diversas intervenciones, muchas de las cuales son de alto costo y/o poco predecibles. Entre ellas, la toxina botulínica (TB) podría tener un efecto a nivel preventivo, aunque los resúmenes de evidencia presentan resultados disímiles. Por esto, proponemos sintetizar la evidencia proveniente de revisiones sistemáticas (RS) y metaanálisis (MA) de ensayos clínicos aleatorizados (ECA) sobre los efectos de la inyección local de TB en la prevención de CH y QU en pacientes que recibieron o recibirán un trauma quirúrgico en la piel. Métodos y análisis: Revisión panorámica siguiendo la declaración PRIOR. Ejecutaremos la búsqueda en la base de datos Epistemonikos. Realizaremos la selección de estudios, extracción de datos y evaluación de la calidad de las RS por duplicado. Compararemos las revisiones a través de matrices de evidencia, incluyendo las RS que aborden una pregunta similar y los ECA incluidos en estas. Estimaremos la superposición entre revisiones mediante el método de área cubierta y área cubierta corregida. Ética y difusión: No se requiere aprobación ética. Esta revisión se publicará después de un proceso de revisión por pares. Sus resultados podrían ser utilizados por personal de salud para informar decisiones individuales y por tomadores de decisión de servicios de salud para guiar la asignación de recursos.

Introduction: Hypertrophic scars (HS) and keloids (KE) result from an aberrant reparative process in the skin, impacting the quality of life of those who are affected by them. Their treatment consists of different interventions, many of which are costly and/or have unpredictable results. Among them, botulinum toxin (BT) might have a preventive effect, although current evidence summaries show varying results. Therefore, we aim to synthesize the evidence coming from systematic reviews (SRs) and meta-analyses (MA) of randomized controlled trials (RCTs) on the effects of local injection of TB in the prevention of HS and KE formation in patients after a surgical wound of the skin. Methods and analysis: This will be an overview of SRs following PRIOR statement. We will conduct the search in Epistemonikos Database. Two reviewers will independently conduct the screening of articles for inclusion, quality appraisal and data extraction. We will compare the SRs using an evidence matrix, including SRs that address this topic, and the RCTs included in them. We will estimate the overlap between them using the covered area method and corrected covered area index. Ethics and dissemination: Ethics approval is not required. This review will be published after a peer-review process. The results will inform areas of future research and could be used by health personnel to make individual decisions, and by healthcare managers, administrators, and policymakers to guide resource allocation.

Relationship between Botulinum Toxin and Temporomandibular Dysfunction: a Literature Review / Relação Entre Toxina Botulínica e Disfunção Temporomandibular: uma Revisão Bibliográfica

Temporomandibular dysfunction (TMD) encompasses several conditions affecting the temporomandibular joint and jaw muscles, leading to orofacial pain and other symptoms. Botulinum toxin is a potential therapy for relieving pain, improving jaw function, and reducing the use of analgesics. This study aims to systematically illustrate the application of botulinum toxin in the therapeutic context of TMD. This study took the form of a literature review, in which an analysis of knowledge repositories was conducted, including Medline (U.S. National Library of Medicine), accessed via PubMed, as well as Lilacs (Latin American and Caribbean Literature in Health Sciences), Scielo (Scientific Electronic Library Online), and Google Scholar. The selection involved the inclusion of studies published from 2015 to 2023. The literature review identified botulinum toxin as an effective and safe therapeutic alternative for TMD patients. The manifestation of side effects, when reported, was predominantly mild and transient in nature, granting botulinum toxin the prospect of establishing itself as a promising therapeutic option in refractory cases to conventional approaches. However, it is important to emphasize the need for further studies and clinical trials to further consolidate the efficacy and safety associated with the use of botulinum toxin as a treatment for TMD. (AU)

A disfunção temporomandibular (DTM) engloba várias condições que acometem a articulação e os músculos da mandíbula, causando dor orofacial e outros sintomas. A toxina botulínica é uma potencial terapia para aliviar a dor, melhorar a função mandibular e reduzir o uso de analgésicos. Este estudo visa ilustrar de forma sistemática a aplicação da toxina botulínica no contexto terapêutico da DTM. Este estudo assumiu a forma de uma revisão bibliográfica, na qual foi realziado uma análise de repositórios de conhecimento, incluindo o Medline (Biblioteca Nacional de Medicina dos Estados Unidos), acessado por meio do PubMed, assim como o Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), o SciELO (Scientific Electronic Library Online) e o Google Scholar. A seleção envolveu a inclusão de estudos publicados no período de 2015 a 2023. A revisão bibliográfica identificou a toxina botulínica como uma alternativa terapêutica eficaz e segura para pacientes com DTM. A manifestação de efeitos colaterais, quando relatados, revelou-se predominantemente de natureza branda e transitória, outorgando à toxina botulínica a perspectiva de se consagrar como um recurso terapêutico promissor em situações refratárias às abordagens convencionais. No entanto, é importante enfatizar a necessidade de estudos prévios e ensaios clínicos para uma maior consolidação da eficácia e segurança associadas à utilização da toxina botulínica como tratamento para a DTM. (AU)

Development and Verification of a Traditional Chinese Medicine Diagnostic Scale for Type 2 Diabetes Mellitus with Turbid-Toxin Accumulation Syndrome / 中医杂志

To develop a traditional Chinese medicine （TCM） diagnostic scale for type 2 diabetes mellitus with turbid-toxin accumulation syndrome and to validate the performance of the scale. A candidate pool was established through literature review and expert consultation， and a clinical case information collection form was developed accordingly. Patients with type 2 diabetes mellitus admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from July 2021 to January 2022 were investigated， and 312 valid clinical case information collection forms were obtained， which were randomly divided into 235 cases in the study group and 77 cases in the validation group. Four statistical methods， namely， differentiation analysis， Cronbach's coefficient， correlation coefficient， and stepwise regression， were used to screen out the candidate items， and Logistic regression analysis and factor analysis were used to assign weights to the items， and the final diagnostic model was determined by the receiver operating characteristic （ROC） curve， and the diagnostic thresholds were calculated for the Yoden index. The final TCM diagnostic scale for type 2 diabetes mellitus was composed of 8 items： turbid dirt coating （with a weight value of 23， the same below）， sticky stools （16）， fullness in the epigastrium and abdomen （12）， dark complexion （12）， irritability （11）， brown spots on the skin （11）， heaviness of head （10）， and chest stuffiness （5）， and the degree score was 0， 0.5， 1.0， and 1.5 points corresponding to no， mild， moderate and severe symptoms， respectively. The total score was the sum of the degree score multiplied by the weighted value of each item， and when the total score reached 33 points， it is diagnosed as the turbid-toxin accumulation syndrome. The established scale was tested and evaluated in the study group and the validation group， and the results showed that the sensitivity of the study group and the validation group was 89.38% and 89.47%， with the specificity of 95.90% and 89.74%， the Yoden index of 0.85 and 0.79， the positive predictive value of 95.28% and 89.47%， the negative predictive value of 90.70% and 89.74%， the diagnostic advantage ratios of 198.18 and 72.67， and the Kappa values of 0.86 and 0.79， which indicated that the TCM diagnostic scale for turbid-toxin accumulation syndrome of type 2 diabetes mellitus showed good diagnostic ability.

Preparation of rabbit polyclonal antibody and development and identification of quantitative ELISA detection method for pertussis toxin / 中国生物制品学杂志

@#Objective To prepare rabbit polyclonal antibodies against pertussis toxin(PT) and develop a double antibody sandwich ELISA for quantitative determination of PT antigen,identify and apply the method.Methods The rabbit polyclonal antibody against PT was prepared by immunizing Chinchilla rabbit with PT using traditional method.The reaction conditions of ELISA system were optimized,the double antibody sandwich ELISA method for quantitative determi-nation of PT was developed,and the specificity,linearity,accuracy,precision and sensitivity were verified.The developed method was used to detect PT antigen content in fimbriae proteins(FIM) stock solution of samples during detoxification and other purification process of pertussis antigen.Results The working condition of double antibody sandwich ELISA for detection of PT antigen content was the coating concentration of PT rabbit polyclonal antibody of 1 μg/mL,and the enzyme-labeled antibody dilution of 1:8 000.This detection system showed specific reaction with PT purified protein,but had no cross reaction with filamentous hemagglutinin,diphtheria toxoid and tetanus toxoid;the linear detection range of the developed double antibody sandwich ELISA was within 25—400 ng/mL;the recovery rates of PT at high,moderate and low concentrations were 103.27%,91.48% and 103.52%,respectively;both the intra-and inter-coefficients of variation(CVs)were less than 10%;the sensitivity of the method was 20.719 ng/mL,and the detection limit was 41.438 ng/mL.Thirty-five batches of samples were detected under five different detoxification process conditions and at different sampling time points,and the changes of antigen content were all consistent with the trend of detoxification reaction.Conclusion The PT rabbit polyclonal antibody was successfully prepared,and a double antibody sandwich ELISA with high precision and accuracy was developed for the quantitative determination of PT antigen content,which can be used for the antigen content detection of chemically detoxified samples in the production process of component DPT vaccines.

Feasibility of Tetramethylpyrazine in Prevention and Treatment of Alzheimer's Disease Based on Theory of 'Toxin Damaging Brain Collaterals' / 中国实验方剂学杂志

With intensified aging， Alzheimer's disease has become a serious problem in China's health field. In the field of traditional Chinese medicine （TCM）， Alzheimer's disease mainly describes cognitive deficits such as dementia and amnesia. After the inheritance and summary by medical experts of successive generations， the theory of "toxin damaging brain collaterals" has become a mature pathogenesis hypothesis of this disease. Blood stasis， as one of the main viral pathogens， is also closely related to the theory of Alzheimer's disease in modern pharmacology. Chuanxiong Rhizoma is used frequently in clinical prescriptions for Alzheimer's disease. As the main component of Chuanxiong Rhizoma， tetramethylpyrazine has a series of pharmacological effects on the cardiovascular system such as vasodilation， anti-platelet aggregation， anti-atherosclerosis， and anti-myocardial ischemia， which reflects the effects of Chuanxiong Rhizoma in activating blood circulation and removing blood stasis. However， few studies have focused on the effect of tetramethylpyrazine on the pathogenesis of Alzheimer's disease. From the perspective of TCM theory and modern pharmacology， this article discussed the effects of tetramethylpyrazine on the pathology and pathogenesis of Alzheimer's disease from the aspects of cardiovascular function， oxidative stress， inflammatory response， mitochondrial function， and cholinergic system and made prospects for the future application of tetramethylpyrazine to prevent and treat Alzheimer's disease.

Discussion on the syndrome of toxin and blood stasis in myelodysplastic syndrome from Xuanfu theory / 国际中医中药杂志

Myelodysplastic syndrome (MDS) is a malignant hematologic tumor, which is currently difficult to cure. The theory of Xuanfu was proposed by Liu Wansu, which is unique in the clinical evidence of Chinese medicine and is less frequently applied to hematological diseases. The application of Xuanfu theory in myelodysplastic syndrome provides new ideas for the treatment of the disease. The abnormal flow of Qi, blood and fluids caused by the occlusion of the Xuanfu is the cause of toxic stasis obstruction, which is the pathogenesis of toxic stasis obstruction. Thus, the method of dispersion of Bone from Xuanfu, the external treatment of Xuanfu, and regulation of liver qi and Xuanfu help to return to normal of opening and closing function of Xuanfu, and release toxic stasis. In this paper, we analyzed the evidence of toxin-stasis obstruction in myelodysplastic syndrome from the theory of Xuanfu, aiming to provide a feasible theoretical basis for clinical treatment of the disease.

Clinical Characteristics of Stasis-Toxin Pathogenesis in Patients with Non-small Cell Lung Cancer of Blood Stasis and Qi Stagnation Syndrome and the Interventional Mechanism of Adjuvant Therapy with Bufei Huayu Decoction / 广州中医药大学学报

Objective To investigate the clinical characteristics of stasis-toxin pathogenesis in patients with non-small cell lung cancer(NSCLC)of blood stasis and qi stagnation type,and to explore the interventional mechanism of adjuvant therapy with Bufei Huayu Decoction.Methods Seventy-eight patients with NSCLC of blood stasis and qi stagnation type admitted to the Department of Respiratory Medicine of Liu'an Hospital of Traditional Chinese Medicine from January 2021 to September 2022 were selected as the NSCLC group,and 71 volunteers who underwent physical examination during the same period served as the healthy control group.The clinical characteristics of stasis-toxin pathogenesis in the NSCLC group were observed,and the differences in the indicators of coagulation function were compared between NSCLC group and the healthy control group.According to the therapy,the NSCLC patients were divided into Bufei Huayu Decoction group(40 cases)and conventional treatment group(38 cases).The conventional treatment group was treated with conventional chemotherapy,while Bufei Huayu Decoction group was treated with Bufei Huayu Decoction together with conventional chemotherapy.Three weeks constituted one course of treatment,and the treatment lasted for 2 courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,coagulation function,immune function,serum nitric oxide(NO),vascular endothelial growth factor(VEGF)level in Bufei Huayu Decoction group and conventional treatment group were observed before and after treatment.Moreover,the clinical efficacy of the two groups and the occurrence of adverse reactions were compared during the treatment period.Results(1)NSCLC patients were classified into the clinical stages Ⅲ and Ⅳ and the pathological types of squamous carcinoma and adenocarcinoma,had the high proportion of KPS scores lower than 70,and were scored with high TCM syndrome scores,suggesting that the illness condition of patients with NSCLC was serious.Compared with the healthy control group,plasminogen time(PT)and thrombin time(TT)in NSCLC patients were significantly shortened,and levels of fibrinogen(FIB)and D-dimer(D-D)were significantly increased,and the differences were statistically significant(P＜0.01).(2)After 6 weeks of treatment,the total effective rate and total stability rate of Bufei Huayu Decoction group were 32.50%(13/40)and 85.00%(34/40),which were significantly superior to those of the conventional treatment group[versus 13.16%(5/38)and 60.53%(23/38)],and the differences were statistically significant(P＜0.05).(3)After 3 weeks of treatment,obvious improvement was presented in the scores of all the TCM symptoms of fatigue,chest distress and shortness of breath,stabbing pain in the chest,and blood stasis in the vessels and collaterals of Bufei Huayu Decoction group and in the scores of the fatigue,chest distress and shortness of breath of the conventional treatment group when compared with those before treatment(P＜0.05).After 6 weeks of treatment,all of the TCM syndrome scores of the two groups were improved compared with those before treatment and after three weeks of treatment(P＜0.05).The intergroup comparison showed that except for the scores of chest distress and shortness of breath after 3 weeks of treatment,the effect on improving all of the TCM syndrome scores in Bufei Huayu Decoction group was significantly superior to that in the conventional treatment group after 3 and 6 weeks of treatment(P＜0.05 or P＜0.01).(4)After 6 weeks of treatment,the levels of coagulation function indicators of PT,TT,FIB and D-D in the Bufei Huayu Decoction group were significantly improved compared with those before treatment(P＜0.05),while only FIB and D-D in the conventional treatment group were improved compared with those before treatment(P＜0.05).The intergroup comparison showed that Bufei Huayu Decoction group had stronger effect on improving the levels of PT,FIB and D-D than the conventional treatment group(P＜0.05).(5)After 6 weeks of treatment,the serum NO and VEGF levels in both groups were significantly lower than those before treatment(P＜0.05),and the effect on lowering serum NO and VEGF levels of the Bufei Huayu Decoction group was significantly superior to that of the conventional treatment group(P＜0.01).(6)After 6 weeks of treatment,the immune function parameters of CD3+,CD4+ levels and CD4+/CD8+ ratio in the Bufei Huayu Decoction group were increased(P＜0.05)and CD8+level was decreased(P＜0.05)as compared with those before treatment,whereas CD3+,CD4+ levels and CD4+/CD8+ ratio in the conventional treatment group were decreased(P＜0.05)and CD8+ level was increased(P＜0.05).The intergroup comparison showed that the effect of Bufei Huayu Decoction group on the increase of CD3+,CD4+ levels and CD4+/CD8+ ratio and the effect on the decrease of CD8+ level were significantly superior to those of the conventional treatment group(P＜0.01).(7)In terms of the quality of life,the KPS scores of patients in the two groups after 6 weeks of treatment were significantly higher than those before treatment(P＜0.05),and the effect of Bufei Huayu Decoction group on the increase of KPS scores was significantly superior to that of the conventional treatment group(P＜0.01).(8)During the course of treatment,the incidence of adverse reactions such as gastrointestinal reactions and alopecia in the two groups was not statistically significant(P＞0.05),while the incidence of hepatic and renal impairment,bone marrow suppression,and toxicity of oral mucosa in Bufei Huayu Decoction group was significantly lower than that of the conventional treatment group(P＜0.05 or P＜0.01),suggesting that Bufei Huayu Decoction group reduced the adverse reactions induced by chemotherapy to a certain extent.Conclusion Patients with NSCLC of blood stasis and qi stagnation type generally have advanced disease progression and high blood coagulation,which is consistent with the stasis-toxin pathogenesis in TCM.The use of Bufei Huayu Decoction against the stasis-toxin pathogenesis can significantly improve patients'TCM syndrome scores and coagulation function,down-regulate the levels of serum NO and VEGF,and improve the immune function,which brings about the enhancement of clinical efficacy and quality of life,and the reduction of adverse reactions caused by chemotherapy,with a high safety.

Clinical Study on LUO's Nephropathy Recipe Ⅲ Combined with Conventional Western Medicine in Treating Stage 3-5 Non-dialysis Chronic Kidney Disease of Spleen-Kidney Deficiency with Turbidity-Toxin-Stasis Obstruction Type / 广州中医药大学学报

Objective To investigate the clinical effect of LUO's Nephropathy Recipe Ⅲ(composed of Sargassum,Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Rehmanniae Radix Praeparata,calcined Ostreae Concha,Houttuyniae Herba,Schizonepetae Spica,etc.)combined with conventional western medicine in treating stage 3-5 non-dialysis chronic kidney disease(CKD)of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type.Methods A total of 180 patients with stage 3-5 non-dialysis CKD of spleen-kidney deficiency with turbidity-toxin-stasis obstruction type were randomly divided into observation group and control group,with 90 cases in each group.The control group was given conventional western medicine for symptomatic treatment,and the observation group was treated with LUO's Nephropathy RecipeⅢon the basis of treatment for the control group.The course of treatment for the two groups covered one month.Before and after treatment,the levels of serum inflammatory factors,renal function indicators and urine protein parameters in the two groups were observed.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)After one month of treatment,the total effective rate in the observation group was 95.56%(86/90)and that in the control group was 81.11%(73/90).The intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the serum levels of inflammatory factors of transforming growth factor β1(TGF-β1),monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor α(TNF-α)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the levels of renal function indicators of blood urea nitrogen(BUN),serum creatinine(Scr),blood uric acid(UA),and cystatin C(Cys-C)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the levels of 24-hour urine protein quantification and urine microalbumin in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(5)The incidence of adverse reactions in the observation group was 4.44%(4/90),which was significantly lower than that of 15.56%(14/90)in the control group,and the difference was statistically significant between the two groups(P＜0.05).Conclusion LUO's Nephropathy Recipe Ⅲ combined with conventional western medicine exerts satisfactory efficacy in treating stage 3-5 non-dialysis CKD patients with spleen-kidney deficiency with turbidity-toxin-stasis obstruction syndrome type,and the therapy can significantly alleviate the inflammatory response,improve the renal function,decrease the urinary protein excretion of the patients,with high safety profile.

Research progress in biological toxins / 军事医学

Biological toxins are toxic molecules produced by specific microorganisms,plants or animals.Due to their wide range of sources and high toxicity,the availability of protein and non-protein toxins is becoming increasingly important,some of which are used for military purposes and developed as biotoxin warfare agents.In this paper,the classification and mechanism of action of biological toxins are discussed.In addition,the strategies for prevention and control of biological toxins as well as their therapeutic applications are reviewed.

Construction of the pore-forming toxin gene exlA knock-out mutant of Pseudomonas aeruginosa and its basic characteristics / 军事医学

Objective To construct a non-trace deletion mutant of exlA in Pseudomonas aeruginosa strain NY8755(NY8755ΔexlA)and investigate the basic characteristics of pore-forming toxin ExlA.Methods The NY8755ΔexlA was constructed using the secondary homologous recombination method.C57BL/6J female mice ages 6 to 8 weeks were infected with NY8755 and NY8755 ΔexlA via aerosolized intratraheal inoculation respectively.Within 7 days of infection,the survival and weight changes of the mice were observed and recorded before the proinflammatory cytokines in the bronchoal-veolar lavage fluid(BALF)of the infected mice in the two groups were detected.Results The sequencing results showed that NY8755 ΔexlA was constructed.After 1×107 CFU NY8755 and NY8755 ΔexlA were infected,all the mice in the wild-type strain group died within 48 hours,while those in the mutant strain group began to die after 48 hours,and 40%of them remained alive 7 days later.The weight of surviving mice in the mutant strain group decreased but recovered gradually.After 12 hours of infection,there were more bloody exudates(redder in color)in the BALF of the wild-type strain group than in the mutant strain group,and the contents of proinflammatory cytokines interleukin-1β(IL-1β)and interleukin-17A (IL-17A)were significantly different. Conclusion Pseudomonas aeruginosa pore-forming toxin ExlA is the key pathogenic virulence factor of the exlA-positive Pseudomonas aeruginosa,which can significantly affect the survival status of mice and cause obvious inflammation in mice. Very little information is available on the action mechanisms of ExlA. In this study, The NY8755ΔexlA and the C57BL/6J mouse models infected with NY8755 and NY8755ΔexlA have been constructed that may be used for the investigation of pathogenesis of exlA-positive Pseudomonas aeruginosa.

Efficacy and safety of botulinum toxin type A combined with pulsed radiofrequency in the treatment of postherpetic neuralgia / 实用医学杂志

Objective Exploring the efficacy and safety of botulinum toxin type A(BTX-A)combined with pulsed radiofrequency(PRF)in the treatment of postherpetic neuralgia(PHN).Methods A total of 80 patients with PHN were collected.They were randomly divided into experimental group(Group B)and control group(Group C),Group B was treated with BTX-A intradermal injection combined with PRF,and Group C was treated with lidocaine intradermal injection combined with PRF.Numeric pain score(NRS),Simplified McGill Pain Questionnaire(SF-MPQ)and Sleep Quality Score(QS)were used to assess the patients'pain level and sleep quality preoperatively,1,3,and 7 days postoperatively,and 1,2,and 3 months postoperatively.The patients'postoperative adverse reac-tions were collected.Interleukin-1β(IL-1β)and calcitonin gene-related peptide(CGRP)levels in patients'serum were measured preoperatively and 3 days postoperatively.Results The NRS scores,SF-MPQ scores,and QS scores of group B and group C were significantly lower at all postoperative time points compared to preoperative ones(P<0.05).The NRS and SF-MPQ score were significantly lower in group B at 1,2,and 3 months postoperatively compared with group C(P<0.05);and group B had significantly lower QS scores at 2 and 3 months postoperatively(P<0.05).The effective rate of pain relief at 3 months postoperatively in group B(90%)was statistically signifi-cant(P<0.05)compared with group C(56.7%).No serious adverse reactions occurred in either group.The levels of IL-1β and CGRP in serum of patients in both groups were significantly decreased at 3 days after surgery compared with the preoperative period,and the degree of decrease of IL-1β and CGRP in group B was more significant than that in group C(P<0.05).Conclusion BTX-A combined with PRF treatment for PHN can effectively reduce its pain level,improve the quality of sleep,and is safe.

Discussion on the Treatment of Chronic Liver Disease from"Toxin" / 中国中医药信息杂志

The connotation of theory of"toxin"in TCM is rich,and"toxin"is closely related to the occurrence and development of chronic liver disease.Treatment from"toxin"is an important treatment for chronic liver disease.In this article,by summarizing the ancient and modern literature to explain the theory of"toxin",and combined with clinical experience,it concluded that"toxin"has the pathogenic characteristics of strong bias,lingering nature,complex and changeable in chronic liver disease.The authors put forward the view that"toxin leads to disease occurrence and accelerates disease progression",and explored the idea of treating chronic liver disease from"toxin",including tracing the source of toxins,clarifying the nature of toxins,identifying changes of toxins,strengthening the body and eliminating toxins,in order to provide ideas for the clinical treatment of chronic liver disease.

Exploration on Scientific Connotation of Pathogenesis Theory of Gastric Cancer"Spleen Deficiency and Stasis Toxin"Based on the Reprogramming of Glucose Metabolism in Tumor-associated Macrophages / 中国中医药信息杂志

The pathogenesis theory of"spleen deficiency and stasis toxin"in gastric cancer holds that spleen is the source of generation and transformation of qi and blood,that spleen deficiency is the internal basis of disease and throughout the disease.Stasis toxin is based on spleen deficiency,which is the fundamental pathogenesis of gastric cancer.In the pathological process of gastric cancer,a variety of metabolic substances in tumor cells and tumor microenvironment,mainly glucose metabolic reprogramming,undergo metabolic changes to reconstruct the phenotype and function of tumor-related macrophages,which is consistent with the pathogenesis theory of"spleen deficiency and stasis toxin".Therefore,this article focused on the reprogramming of glucose metabolism in tumor microenvironment to drive the phenotypic remodeling of tumor-related macrophages,explored the scientific connotation of the pathogenesis theory of"spleen deficiency and stasis toxin"of gastric cancer,and provided references for the theoretical and clinical research on the treatment of gastric cancer by TCM.

Syndrome Differentiation and Treatment of Thyroid Carcinoma Based on the Theory of Cancer Toxin Pathogenesis / 中国中医药信息杂志

On the basis of inheriting the cancer toxin theory of Zhou Zhongying,a national TCM master,Professor Cheng Haibo's team proposes the theory of cancer toxin pathogenesis.This theory believes that thyroid carcinoma is caused by pathogenic surroundings,emotional injury,irregular diet and other factors,which cause the accumulation of qi stagnation,phlegm coagulation,blood stasis and cancer toxin in the neck.The main pathological factors of thyroid carcinoma are"qi,phlegm,stasis and toxin".The disease is located in front of the neck and is greatly related to liver,spleen and kidney."Liver-qi stagnation,phlegm and stasis containing toxin"is its core pathogenesis.The nature of the disease is mostly a mixture of deficiency and excess,and in the later stage of the disease,qi and yin are always depleted.The general principle of treatment in clinic is"anti-cancer and detoxification,strengthening vital energy and dispelling pathological factors".In view of the rise and fall of cancer toxin and the characteristics of different stages of the disease,it is recommended to soothe liver and regulate qi,dissolve phlegm and disperse lumps,reduce stasis and detoxify,benefit qi and nourish yin in the clinical treatment of thyroid carcinoma.Based on the theory of cancer toxin pathogenesis,the pathogenesis evolution and relevant treatment is discussed,in order to provide new ideas for the syndrome differentiation and treatment of thyroid carcinoma.

Pertussis toxin in involves the development of interstitial lung disease in an experimental autoimmune myositis mice modelby inducing the formation of neutrophil extracellular traps / 中华风湿病学杂志

Objective:To test the hypothesis that Pertussis toxin (PTX) can promote the occurrence of interstitial lung disease (ILD) in experimental autoimmune myositis (EAM) model and clarify the potential pathogenic mechanism.Methods:EAM mice model were induced by Skeletal muscle thomogenate with or without PTX, and the relationship between ILD phenotypes and neutrophil extracellular traps (NETs) infiltration was analyzed by histopathological and serological studies in EAM with PTX group and EAM without PTX group. Healthy mice were given PTX alone intraperitoneally to clarify whether NETs formation could be induced in vivo, and neutrophils separated from healthy human blood were intervened with PTX to induce NETs formation in vitro. The data was tested for normality using Shapiro-Wilk. Statistical methods and were analyzed using t-test or ANOVA, and multiple comparisons between different groups were tested using Tukey test. Results:Compared with EAM without PTX group, lung tissues in EAM with PTX group had multiple pathological changes similar to polymyositis/dermatomyositis-related ILD. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the main pathological types. The pulmonary interstitial lesions were accompanied by significant infiltration of NETs; and serum NETs markers levels were obviously elevated in EAM with PTX group, compared with the control group [ n=5, (87±10) ng/ml], cfDNA levels were statistically significantly elevated in both the EAM without PTX group [ n=4, (115±27) ng/ml] and the EAM with PTX group [ n=7, (150±50) ng/ml] ( F=4.24, P=0.038); Cit-H3-DNA levels were elevated in the EAM without PTX group ( n=4, 0.24±0.09), and in the EAM EAM with PTX group ( n=6, 0.33±0.11) compared with the control group ( n=4, 0.13±0.02) ( F=6.21, P=0.016). After PTX intervention, serum cfDNA levels were higher in the PTX group [ n=3, (100±40) ng/ml] than in the control group [ n=3, (45±12) ng/ml, t=2.27, P=0.086]; PTX also induced neutrophils to form NETs in vitro. Conclusion:PTX may promote the development of ILD in EAM mice model by inducing the formation of NETs, indicating that EAM mice can serve as a model for targeting NETs to study the pathogenesis ILD.

Explore the Diagnosis and Treatment of Gastric Cancer Accompanied by Depression Based on"Depression Caused by Illness"and"Illness Caused by Depression" / 浙江中医药大学学报

[Objective]To discuss the occurrence and gastric cancer accompanied by depression from the perspective of"depression caused by illness"and"illness caused by depression",and provide theoretical support for the treatment by traditional Chinese medicine(TCM).[Methods]By consulting the ancient and modern literature of TCM,and collecting the academic views of some doctors on the theory of"depression caused by illness"and"illness caused by depression"of gastric cancer,combined with clinical practice experience,it discusses the diagnosis and treatment of gastric cancer accompanied by depression.[Results]The etiology and pathogenesis of gastric cancer accompanied by depression can be summarized as follows:loss of middle Qi,the rise and fall of surly for its root;cementation of stasis and toxin,seven emotions disorder is its root;tumor gathering locally,poison overflowing into the blood vessels,illness and depression intermingled as its symptom,and it accordingly points out that the treatment of gastric cancer accompanied by depression should mediate middle Qi and smooth the Qi transformation of spleen and stomach;regulate Qi and open depression,regulate the rise and fall of Qi of the body;remove blood stasis and detoxify,dredge the body's Qi,blood and body fluid;form and spirit in tune,restore the complex of the five viscera of the human body.[Conclusion]Stasis,toxin and depression are important pathological factors affecting the occurrence,development and outcome of gastric cancer accompanied by depression.These three factors often affect each other as causation.Discussion of gastric cancer accompanied by depression from the perspective of"depression caused by illness"and"illness caused by depression"is not only helpful to improve the etiological and pathogenesis theory of gastric cancer accompanied by depression,but also helpful to provide theoretical reference for its clinical treatment.