Study on fluvoxamine maleate sustained-release pellets and its compression technology / 药学学报

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (24) Taguchi experiment. Using Minitab software to design a DOE experiment with 24 partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

Clinical Efficacy of Fuzheng Huaji Longbi Decoction in Treating Benign Prostatic Hyperplasia with Syndrome of Healthy Qi Deficiency and Blood Stasis / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy and safety of Fuzheng Huaji Longbi decoction in treating benign prostatic hyperplasia （BPH） in the patients with the syndrome of healthy Qi deficiency and blood stasis. MethodA total of 94 BPH patients were randomized into control and observation groups， with 47 patients in each group. The control group was treated with doxazosin mesylate sustained-release tablets， and the observation group with Fuzheng Huaji Longbi decoction on the basis of the therapy in the control group. After eight weeks， the international prostate symptom score （IPSS）， quality of life （QOL） score， residual urine volume （RUV）， maximum urinary flow rate （Qmax）， TCM syndrome score， TCM symptom score， electrocardiogram， and liver and kidney function were determined to evaluate the clinical efficacy and safety of the two groups. ResultAfter 8 weeks of treatment， the total response rate in the control group was 63.64% （28/44）， which was lower than that （84.44%， 38/45） in the observation group （χ2=5.026， P<0.05）. The clinical efficacy in the observation group was higher than that in the control group （Z=-2.17， P=0.030）. The treatment in both groups decreased the IPSS， QOL score， RUV， and TCM syndrome scores and increased the Qmax （P<0.05）. Moreover， the observation group had lower IPSS， QOL score， RUV， and TCM syndrome score （P<0.05） and higher Qmax than the control group after treatment （P<0.05）. The treatment in the observation group decreased all the TCM symptom scores （P<0.05）， while that in the control group only decreased the frequency of urination at night and the scores of dysuria， weak urine stream， and post-urinary drainage （P<0.05）. After treatment， the observation group had lower frequency of urination at night and lower scores of mental fatigue， cold limbs， lower abdominal discomfort， and loose stool than the control group （P<0.05）. No adverse events associated with the administration of Fuzheng Huaji Longbi decoction were observed during the treatment period. ConclusionFuzheng Huaji Longbi decoction is effective in treating BPH in the patients with the syndrome of healthy qi deficiency and blood stasis. It can relieve the clinical symptoms and improve the quality of life， being a safe and reliable choice for clinical application.

Trend analysis of hemagglutinin and ovalbumin content for influenza virus split vaccines in 2021 / 中国生物制品学杂志

@#Objective To analyze the trend of the hemagglutinin(HA) and ovalbumin contents in the lot release of influenza virus split vaccines in 2021,and evaluate the quality and quality control level of the vaccines.Methods The HA and ovalbumin content data of influenza virus split vaccines from two domestic enterprises in 2021 were collected and collated. The mean value and standard deviation were calculated according to the first 40 batches of data of the enterprise in the year,and the warning limit and action limit were established. The trend analysis of the above indexes was carried out to evaluate the stability and consistency of the product quality of the enterprise. Statistical data comparison and consistency analysis were made between the test results of the batch inspected by the lot release institution and the results of the enterprise.Results Through the retrospective data analysis of quadrivalent influenza virus split vaccines from two vaccine enterprises A and B,it was found that the content of H1N1 subtype HA and ovalbumin in the two enterprises and the content of Bv HA in the B enterprise had out of trend(OOT)situations,while the trend of other items was stable. The results of paired student's t test or Wilcoxon signed-rank test of the samples inspected by the lot release institution showed that except Bv subtype HA(t = 1. 094 and 0. 742 respectively)and ovalbumin(w =-64 and 36 respectively)contents showed no statistically significant difference(P > 0. 05),the HA contents of H1N1(t = 3. 862,w = 232),H3N2(t = 8. 225 and3. 473 respectively)and By(t = 5. 616 and 4. 934 respectively)of the two enterprises had significant differences(P <0. 05). The results of enterprises were generally higher than the lot release institution. Bland-Altman test analysis found that the consistency between the test data of enterprise A's HA content and the data of the lot release institution was better than that of enterprise B.Conclusion The stability and consistency of data trends of active ingredients and main impurity ingredients of quadrivalent influenza virus split vaccine batches in 2021 were generally good. The trend analysis can identify potential problems in vaccine production,and enterprises should carefully implement trend analysis and effectively monitor the product quality of vaccines.

Research progress of sustained-release drug delivery system for uveitis / 国际眼科杂志(Guoji Yanke Zazhi)

Uveitis, a complex ocular disorder with numerous etiologies, can result from infection, autoimmune, and various physicochemical and mechanical injury factors. The treatment of this disease is difficult, and failure to receive timely and effective treatment can often lead to blindness. With the deepening of people's understanding of uveitis and its related mechanisms, various new sustained-release drug delivery systems for uveitis have been studied. However, due to the existence of various anatomical and physiological barriers in the eye, there are multiple obstacles to the sustained release treatment of uveitis. In this paper, the main research results in this field in recent years are reviewed, and the innovations and limitations of various new sustained-release drug delivery systems are discussed in order to provide new ideas for the sustained-release drug delivery treatment of uveitis in the future. These new sustained-release drug delivery systems will help to completely change the traditional treatment mode of uveitis with side effects and poor compliance in the future, bringing longer targeted sustained release and less toxic reactions.

Prevalência e fatores associados ao uso de cigarro eletrônico por estudantes universitários / Prevalence and factors associated with electronic cigarette use by university students / Prevalencia y factores asociados al uso de cigarrillos electrónicos por estudiantes universitarios

Este estudo objetivou estimar a prevalência do uso do cigarro eletrônico e a associação com fatores preditores. Trata-se de um estudo transversal, analítico, com amostra probabilística de universitários matriculados em um Centro Universitário de Montes Claros, Minas Gerais, Brasil no segundo semestre de 2022. A variável dependente referiu-se ao uso do cigarro eletrônico. As variáveis independentes referiram a fatores sociodemográficas, laborais e comportamentais. A associação entre as variáveis investigadas e a prevalência do uso do CE foi verificada pela análise bivariada e a regressão de Poisson. Foram entrevistados 730 universitários, com a média de idade de anos 22,56 (±6,25). Destes, 21,8 % faziam o uso cigarro eletrônico e após a análise multivariada manteve-se associado ao desfecho não ter companheiro (RP= 3,31; IC95% 1,04-10,48), morar com amigos/sozinho (RP=1,53; IC95% 1,07-2,18), ter histórico de usuários de cigarro eletrônico na residência (RP= 1,76; IC95%: 1,17- 1,89), consumir bebida alcoólica (RP= 3,07; IC95%: 1,72-5,49) e não praticar atividade física (RP= 3,37; IC95% 2,35-4,83). Conhecer sobre o cigarro eletrônico foi fator protetor (RP= 0,31 IC95% 0,20-0,46). Registrou-se elevada prevalência do uso do cigarro eletrônico, e manteve associados a fatores sociodemográficos e comportamentais. Esses achados chamam a atenção para a necessidade de novas medidas regulatórias, a fim de reduzir o uso desse dispositivo.

This study aimed to estimate the prevalence of e-cigarette use and the association with predictors. This is a cross-sectional, analytical study with a probabilistic sample of university students enrolled in a University Center of Montes Claros, Minas Gerais, Brazil in the second half of 2022. The dependent variable referred to the use of electronic cigarettes. The independent variables referred to sociodemographic, labor and behavioral factors. The association between the variables investigated and the prevalence of EC use was verified by bivariate analysis and Poisson regression. A total of 730 university students were interviewed, with a mean age of 22.56 (±6.25). Of these, 21.8% used electronic cigarettes and after multivariate analysis, it remained associated with the outcome of not having a partner (PR= 3.31; CI95% 1.04-10.48), living with friends/alone (PR=1.53; CI95% 1.07-2.18), having a history of e-cigarette users in the residence (PR= 1.76; CI95%: 1.17- 1.89), alcohol consumption (PR= 3.07; CI95%: 1.72-5.49) and not practicing physical activity (PR= 3.37; IC95% 2.35-4.83). Knowing about electronic cigarettes was a protective factor (PR= 0.31 CI95% 0.20-0.46). There was a high prevalence of e-cigarette use, and it was associated with sociodemographic and behavioral factors. These findings draw attention to the need for new regulatory measures in order to reduce the use of this device.

Este estudio tuvo como objetivo estimar la prevalencia del uso de cigarrillos electrónicos y la asociación con predictores. Se trata de un estudio analítico transversal con una muestra probabilística de estudiantes universitarios matriculados en un Centro Universitario de Montes Claros, Minas Gerais, Brasil, en el segundo semestre de 2022. La variable dependiente se refería al uso de cigarrillos electrónicos. Las variables independientes se refirieron a factores sociodemográficos, laborales y conductuales. La asociación entre las variables investigadas y la prevalencia de uso de CE fue verificada por análisis bivariado y regresión de Poisson. Fueron entrevistados 730 estudiantes universitarios, con una edad promedio de 22,56 (±6,25). De estos, 21,8% utilizaron cigarrillos electrónicos y después del análisis multivariado, se mantuvo asociado con el resultado de no tener pareja (RP= 3,31; IC95% 1,04-10,48), vivir con amigos/solo (RP=1,53; IC95% 1,07-2,18), con antecedentes de usuarios de cigarrillos electrónicos en la residencia (RP= 1,76; IC95%: 1,17- 1,89), consumo de alcohol (RP= 3,07; IC95%: 1,72-5,49) y no practicar actividad física (RP= 3,37; IC95% 2,35-4,83). El conocimiento de los cigarrillos electrónicos fue un factor protector (RP= 0,31 IC95% 0,20-0,46). Hubo una alta prevalencia de uso de cigarrillos electrónicos, y se asoció con factores sociodemográficos y de comportamiento. Estos hallazgos llaman la atención sobre la necesidad de nuevas medidas regulatorias para reducir el uso de este dispositivo.

Un « lâcher de ballons ¼ thoracique pas comme les autres / «A thoracic "balloon release" unlike any other¼

La neurofibromatose de type 1 ou maladie de Von Recklinghausen, maladie héréditaire la plus fréquente parmi les phacomatoses, caractérisée par la présence d'au moins deux critères diagnostiques, dont le neurofibrome. Nous rapportons le cas d'un patient de 37 ans, contact direct d'un patient tuberculeux, atteint de neurofibromatose dont la radiographie pulmonaire mimait des images en « lâcher de ballon ¼ coexistant avec une tuberculose pulmonaire. Nous insistons à travers ce cas et à la lumière d'une revue de la littérature sur l'importance d'avoir un esprit critique et un raisonnement diagnostic médical devant toute image ne correspondant pas à l'indication clinique.

Neurofibromatosis type 1 or Von Recklinghausen disease, most common hereditary disease of phacomatosis, which is characterized by the presence of at least two diagnostic criteria, including neurofibroma. We report the case of a 37-year-old patient, direct contact of a tuberculosis patient, suffering from neurofibromatosis whose chest X-ray mimicked images of "balloon release" coexisting with pulmonary TBC. We insist through this observation and in the light of a literature review on the importance of having a critical mind and medical diagnostic reasoning in front of any image that does not match the clinical indication.

Hydrogels in the Treatment of Degenerative Tendinopathy / Hidrogeles en el Tratamiento de la Tendinopatía Degenerativa

Abstract: Degenerative tendinopathy is a significant health problem, and its incidence increases yearly. This condition causes functional deficits in young and adult patients and sedentary or active individuals, resulting in health, social, and economic consequences. Due to limited blood supply, drug administration is complex for tendon diseases, such as degenerative tendinopathy. Biomaterials, such as hydrogels, have gained significant attention in designing drug delivery systems to treat musculoskeletal pathologies due to their attractive characteristics and the challenges posed by conventional drug delivery routes. This paper provides an overview of tendon pathology and discusses the use of hydrogels as drug carriers and release agents in emerging treatments.

Resumen: La tendinopatía degenerativa es un importante problema de salud, y su incidencia aumenta cada año en todo el mundo. Esta condición genera déficits funcionales en pacientes jóvenes o adultos, así como en personas sedentarias o activas, trayendo consigo repercusiones sanitarias, sociales y económicas. Debido al suministro de sangre limitado, la administración de medicamentos es compleja para las enfermedades de los tendones, como la tendinopatía degenerativa. El uso de biomateriales, como los hidrogeles, ha ganado una atención significativa en el diseño de sistemas de administración de fármacos para tratar patologías musculoesqueléticas debido a sus atractivas características y los desafíos que plantean las rutas convencionales de administración de fármacos. Este documento proporciona una descripción general de la patología del tendón y analiza el uso de hidrogeles como transportadores de fármacos y agentes de liberación en tratamientos emergentes.

Recent Advances in the development of Modified Release Tablets by amalgamating both Solubility Enhancement and Polymer Matrix Sintering Technologies.

Background: The fact that about 90 % of newly discovered API’s or new molecular entity(NME) have little or no aqueous solubility, causes a significant protest to the initialization of development and their scale up of dosage form in the Pharma Industry. Aqueous solubility of API’s has critical role in drug dissolution or availability of drug at the site of action or bioavailability, when a dosage form is administered orally.Objective: The object of this study is to formulate a modified release tablet dosage form of a poorly aqueous soluble drug, which not only have higher aqueous solubility or bioavailability but also have sustained release characteristics with high mechanical strength &their commercial viability. Numerous techniques are available for the solubility enhancement but all individual techniques have its own limitations for commercialization.Method: Aqueous solubility of drugs is improved by the known Solubility enhancement techniques like Micronization &Solid dispersions. After successful solubility enhancement, sustained release or modified release tablets of poorly aqueous soluble drug can be easily formulated into a suitable shape or size by using a known Polymer Matrix Sintering Technology with commercial feasibility. Micronization of poorly water-soluble drugs can be performed by Air Jet Mill or Ball Mill. Whereas Solid dispersion technique involves, molecular dispersion of poorly soluble drug in a suitable inert carrier, to form an amorphous and highly soluble compounds. Sintering Technology is defined as the bonding of adjacent particle surfaces in a mass of powder, or in compact, by the application of heat. Conventional sintering technique involves the heating of compact at a temperature below the melting point of the solid constituents in a controlled environment under atmospheric pressure.Results: Enhanced solubility of poorly soluble API’s by these proposed techniques is due to either conversion of crystalline compound in to amorphous form or reduction of particle size to its molecular level by the application of Micronization or solid dispersion techniques. The developed modified release tablets will show a sustained release characteristic due to Sintering aspect and provides enhanced solubility of BCS class II or IV drugs.Conclusion: Novel modified release tablets have been designed through consolidation of Solubility enhancement and Polymer Matrix Sintering technologies. Simultaneous exploitation of well-known and established approaches- Micronization (optimum particle size reduction) or solid dispersion, optional surfactant and Polymer Matrix Sintering Technique in the recent concept, produces significant enhancement of solubility of poorly water soluble API’s without compromising the content uniformity of dosage form and also provide a modified or sustained release characteristics with high mechanical strength. The release profile of drug can be easily tailored by using combination of both techniques where challenges of low solubility are prominent.

Autopercepção dos benefícios da mobilização miofascial em praticantes de exercício físico: um estudo transversal / Self-perception of the benefits of myofascial mobilization in physical exercise practitioners: a cross-sectional study

A mobilização miofascial vem sendo utilizada com frequência no meio esportivo como forma de melhorar as restrições da fáscia que surgem com as atividades físicas. Objetivo: Analisar e comparar os benefícios da mobilização miofascial para praticantes adultos de exercício físico regular, verificando os métodos e técnicas utilizados, assim comparando a maior eficácia segundo a percepção dos praticantes. Métodos: Trata-se de um estudo transversal onde foi aplicado um questionário online a 160 pessoas de ambos os sexos, com o intuito de analisar informações de técnicas aplicadas e sua eficácia. Os dados foram analisados por meio da estatística descritiva. Resultados: Os resultados demonstraram que a satisfação e benefícios foram predominantes, e o uso da técnica manual foi a de maior escolha entre os praticantes, ressaltando que a maioria foi aplicada por fisioterapeutas. Conclusões: Quem utiliza a técnica, independente da forma executada, os resultados são considerados satisfatórios e trazem bem-estar e benefícios à saúde dos praticantes de exercício físico

Myofascial mobilization has been frequently used in sports as a way to improve fascia restrictions that arise with physical activities. Objective: To analyze and compare the benefits of myofascial mobilization for adult practitioners of regular physical exercise, verifying the methods and techniques used, thus comparing the greater effectiveness according to the practitioners' perception. Methods: This is a cross-sectional study where an online questionnaire was applied to 160 people of both sexes, with the aim of analyzing information on applied techniques and their effectiveness. Data were analyzed using descriptive statistics. Results: The results showed that satisfaction and benefits were predominant, and the use of the manual technique was the most preferred among practitioners, emphasizing that most were applied by physiotherapists. Conclusion: Those who use the technique, regardless of the way it is performed, the results are considered satisfactory and bring well-being and benefits to the health of practitioners of physical exercise.

Analysis of pH, calcium ion release, and energy dispersive spectroscopy of a bioceramic root canal dressing

Abstract This study compared the pH and calcium ion release of calcium silicate- (Bio-C Temp) and calcium hydroxide-based (Ultracal XS) medications. Intracanal remnants of both medications were also evaluated using SEM-EDS after the removal protocol. Thirty-five bovine teeth were prepared. Fifteen were filled with Bio-C Temp and 15 with Ultracal XS. Five remained without intracanal medication (control group). Five samples from each experimental time (i.e.. 24, 72, and 168 hours) were used to measure pH and calcium ions release using a digital pH meter and microplate reader, respectively. Afterward, the peaks of the chemical elements composing both medications were analyzed in SEM-EDS. One-way ANOVA and Tukey's post hoc test analyzed the pH and calcium ion release data. Student's t-test compared the medications in each experimental time. SEM-EDS described the percentage of chemical elements in the samples. Bio-C Temp and Ultracal XS showed a significant pH increase from 24 to 168 hours (p<0.05). Ultracal XS showed a higher pH value at 24 hours than Bio-C Temp (p<0.05) but were similar at 72 and 168h (p > 0.05). Calcium ion release did not depend on the experimental period (p > 0.05). Bio-C Temp showed lower calcium ions release than Ultracal XS at 24 hours (p<0.05). SEM-EDS analyses showed the remains of both medications, but the concentration of Si, Al, and W ions was present only in the calcium silicate-based medication. Bio-C Temp presented alkaline pH and a satisfactory calcium ion release over the time. The remaining of both medications were present after the protocols for paste removal.

Resumo Este estudo comparou o pH e a liberação de íons cálcio de medicações intracanais a à base de silicato de cálcio (Bio-C Temp) e à base de hidróxido de cálcio (Ultracal XS). Remanescentes de ambas as medicações também foram avaliados usando microscopia eletrônica de varredura e espectroscopia de dispersão de energia após o protocolo de remoção. Trinta e cinco dentes bovinos foram preparados. Quinze dentes foram preenchidos com Bio-C Temp e 15 com Ultracal XS. Cinco permaneceram sem medicação intracanal (grupo controle). Cinco amostras de cada tempo experimental (ou seja, 24, 72 e 168 horas) foram usadas para medir o pH e a liberação de íons de cálcio usando um medidor de pH digital e um leitor de microplacas, respectivamente. Em seguida, os picos dos elementos químicos que compõem os dois medicamentos foram analisados ​​em microscopia eletrônica de varredura e por espectroscopia de dispersão de energia. Os testes One-way ANOVA e post hoc de Tukey analisaram os dados de pH e liberação de íons cálcio. O teste t de Student comparou as medicações em cada tempo experimental. A microscopia eletrônica de varredura e a espectroscopia de dispersão de energia descreveu a porcentagem de elementos químicos nas amostras. O Bio-C Temp e o Ultracal XS mostraram um aumento significativo de pH de 24 a 168 horas (p<0,05). O Ultracal XS apresentou um valor de pH mais alto em 24 horas do que o Bio-C Temp (p<0,05), mas foi semelhante em 72 e 168h (p > 0,05). A liberação de íons cálcio não dependeu do período experimental (p> 0,05). O Bio-C Temp apresentou menor liberação de íons de cálcio do que Ultracal XS em 24 horas (p<0,05). As análises de microscopia eletrônica de varredura e espectroscopia de dispersão de energia mostraram remanescentes de ambas as medicações, mas a concentração de íons Si, Al e W estavam presentes apenas na medicação à base de silicato de cálcio. O Bio-C Temp apresentou pH alcalino e maior liberação de íons cálcio. Remanescentes de ambas as medicações estiveram presentes após os protocolos de remoção da pasta.

COVID-19 in the nervous system: physiopathology and neurological manifestations / Covid-19 no sistema nervoso: fisiopatologia e manifestações neurológicas

Abstract Background Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although respiratory manifestations have received greater visibility during the pandemic caused by this virus, numerous neurological complaints related to coronavirus 2 infection have been documented in several countries. These records suggest that this pathogen presents neurotropism, and it can cause different neurological conditions of varying intensity. Objective To investigate the ability of coronavirus 2 to invade the central nervous system (CNS) and its neurological clinical outcomes. Methods The present study consists in a comprehensive literature review of the records available in the PubMed, SciELO, and Google Scholar databases. The descriptors COVID-19, brain and physiopathology, associated with the Boolean operator AND, were used in the search. Regarding the inclusion and exclusion criteria, we selected the papers published since 2020 with the highest number of citations. Results We selected 41 articles, most of them in English. The main clinical manifestation associated with COVID-19 patients was headache, but cases of anosmia, hyposmia, Guillain-Barré syndrome, and encephalopathies were also described with considerable frequency. Conclusion Coronavirus-2 presents neurotropism, and it can reach the CNS by hematogenous dissemination and by direct infection of the nerve endings. It causes brain injuries through several mechanisms, such as cytokine storm, microglial activation, and an increase in thrombotic factors.

Resumo Antecedentes A doença do coronavírus 2019 (coronavirus disease 2019, Covid-19, em inglês) é uma infecção viral provocada pelo coronavírus 2 da síndrome respiratória aguda grave (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, em inglês). Embora as manifestações respiratórias tenham recebido maior visibilidade ao longo da pandemia provocada por esse vírus, inúmeras queixas neurológicas relacionadas à infecção pelo coronavírus 2 foram documentadas em diversos países. Tais registros sugerem que esse patógeno apresenta neurotropismo, e é capaz de provocar quadros neurológicos diversos e de intensidade variáveis. Objetivo Investigar a capacidade de invasão do sistema nervoso central (SNC) pelo coronavírus 2 e seus principais desfechos clínicos neurológicos. Métodos O presente estudo consiste em uma ampla revisão de literatura a partir dos registros das bases de dados PubMed, SciELO e Google Acadêmico. Nesse contexto, os descritores COVID-19, cérebro e fisiopatologia, associados com o operador booleano AND, foram utilizados na busca. Quanto aos critérios de inclusão e exclusão, selecionou-se os trabalhos publicados a partir de 2020 com o maior número de citações. Resultados Foram selecionados 41 artigos, a maioria na língua inglesa. A principal manifestação clínica associada a pacientes acometidos pela COVID-19 foi a cefaleia, mas casos de anosmia, hiposmia, síndrome de Guillain-Barré e encefalopatias também foram descritos com frequência considerável. Conclusão O coronavírus 2 apresenta neurotropismo, e é capaz de alcançar o SNC por disseminação hematogênica e por infecção direta das terminações nervosas. Ele provoca injúria cerebral por meio de variados mecanismos, como tempestade de citocinas, ativação da micróglia e aumento dos fatores trombóticos.

Ghost ileostomy release down: our initial experience

Background: Many publications describe the advantages of the creation of ghost ileostomy (GI) to prevent the need for formal covering ileostomy in more than 80% of carcinoma rectum patients. However, none of the papers describes exactly how to ultimately remove the GI in these 80% of patients in whom it doesn't need formal maturation. Aim: To describe and evaluate the ghost ileostomy release down (GIRD) technique in terms of feasibility, complications, hospital stay, procedure time etc. in patients with low anterior resection/ultra-low anterior resection (LAR/uLAR) with GI for carcinoma rectum. Method: The present was a prospective cohort study of patients with restorative colorectal resections with GI for carcinoma rectum, Postoperatively the patients were studied with respect to ease and feasibility of the release down of GI and its complications. The data was collected, analyzed and inference drawn. Results: A total of 26 patients needed the GIRD and were included in the final statistical analysis of the study. The procedure was done between 7th to 16th postoperative days (POD) and was successful in all patients without the need of any additional surgical procedure. None of the patients required any local anesthetic injection or any extra analgesics. The average time taken for procedure was 5-minutes and none of the patients had any significant difficulty in GI release. There were no immediate postprocedure complications. Conclusion: The GIRD technique is a simple, safe, and quick procedure done around the 10th POD that can easily be performed by the bedside of patient without the need of any anesthesia or additional analgesics. (AU)

Formulation and evaluation of Buccal mucoadhesive tablets of diclofenac sodium using 23 factorial designs

Buccal tablets

Diclofenac sodium

Drug release

Mucoadhesion

Mucoadhesive tablets

Release kinetics

An elevated HScore is associated with poor clinical outcomes in COVID-19 / Un HScore elevado se asocia a mal pronóstico en pacientes con COVID-19

BACKGROUND: Patients with Coronavirus Disease 2019 (COVID-19) frequently experience a hyperinflammatory syndrome leading to unfavorable outcomes. This condition resembles Secondary Hemophagocytic Lymphohistiocytosis (sHLH) described in neoplastic, rheumatic and other infectious diseases. A scoring system (HScore) that evaluates underlying immunosuppression, temperature, organomegaly, cytopenias, ferritin, triglycerides, fibrinogen and AST was validated for sHLH, and recently proposed to evaluate hyperinflammation in COVID-19. AIM: To assess the presence of sHLH among patients with COVID-19 admitted for hospitalization and to evaluate Hscore as a prognostic tool for poor outcomes. MATERIAL AND METHODS: One hundred forty-three patients aged 21-100 years (64% males) admitted because of COVID-19 were enrolled in a prospective study. HScore was calculated within 72 hours admission. The incidence of sHLH during hospitalization was evaluated. Additionally, the relationship between a HScore ≥ 130 points and either the requirement of mechanical ventilation or 60-days mortality was explored. RESULTS: The median HScore was 96 (33-169). A SHLH was diagnosed in one patient (incidence 0.7%), whose HScore was 169. After adjusting for age, sex, comorbidities and obesity, HScore ≥ 130 was independently associated with the composite clinical outcome (Hazard rartio 2.13, p = 0.022). CONCLUSIONS: sHLH is not frequent among COVID-19 patients. HScore can be useful to predict the risk for poor outcomes.

ANTECEDENTES: Los pacientes con Enfermedad por Coronavirus 2019 (COVID-19), experimentan frecuentemente un síndrome hiperinflamatorio que lleva a resultados desfavorables. Esta situación se asemeja al Síndrome Hemofagocítico Secundario (sHLH) descrito en enfermedades neoplásicas, reumatológicas y por otros agentes infecciosos. Un sistema simple de puntaje (HScore) que evalúa inmunosupresión, temperatura organomegalia, citopenias, ferritina, triglicéridos, fibrinógeno y AST ha sido validado para el diagnóstico de sHLH y ha sido propuesto recientemente para evaluar la hiperinflamación en COVID-19. OBJETIVO: Medir la frecuencia de sHLH entre pacientes con COVID-19 hospitalizados, y evaluar a HScore como una herramienta pronóstica. MATERIAL Y MÉTODOS: Ciento cuarenta y tres pacientes de 21 a 100 años (64% hombres) fueron ingresados en este estudio de cohorte prospectivo, unicéntrico. Se calculó HScore dentro de las primeras 72 horas desde el ingreso, y se midió la incidencia de sHLH durante la hospitalización. Adicionalmente, se evaluó la relación entre HScore ≥ 130 puntos y un desenlace compuesto de ventilación mecánica o muerte a los 60 días. RESULTADOS: La mediana de HScore fue 96 (33-169) puntos. Un paciente fue diagnosticado con sHLH (incidencia 0,7%). Luego de ajustar por edad, sexo, comorbilidades y obesidad, un HScore ≥ 130 se asoció de manera independiente con el desenlace compuesto. CONCLUSIONES: El sHLH no es frecuente en los pacientes con COVID-19. El uso de HScore puede ser útil para predecir el riesgo de desenlaces clínicos desfavorables.

Physicochemical properties of a novel chiral self-assembling peptide R-LIFE-1 and its controlled release to exosomes / 生物医学工程学杂志

This research aims to investigate the encapsulation and controlled release effect of the newly developed self-assembling peptide R-LIFE-1 on exosomes. The gelling ability and morphological structure of the chiral self-assembling peptide (CSAP) hydrogel were examined using advanced imaging techniques, including atomic force microscopy, transmission electron microscopy, and cryo-scanning electron microscopy. The biocompatibility of the CSAP hydrogel was assessed through optical microscopy and fluorescent staining. Exosomes were isolated via ultrafiltration, and their quality was evaluated using Western blot analysis, nanoparticle tracking analysis, and transmission electron microscopy. The controlled release effect of the CSAP hydrogel on exosomes was quantitatively analyzed using laser confocal microscopy and a BCA assay kit. The results revealed that the self-assembling peptide R-LIFE-1 exhibited spontaneous assembly in the presence of various ions, leading to the formation of nanofibers. These nanofibers were cross-linked, giving rise to a robust nanofiber network structure, which further underwent cross-linking to generate a laminated membrane structure. The nanofibers possessed a large surface area, allowing them to encapsulate a substantial number of water molecules, thereby forming a hydrogel material with high water content. This hydrogel served as a stable spatial scaffold and loading matrix for the three-dimensional culture of cells, as well as the encapsulation and controlled release of exosomes. Importantly, R-LIFE-1 demonstrated excellent biocompatibility, preserving the growth of cells and the biological activity of exosomes. It rapidly formed a three-dimensional network scaffold, enabling the stable loading of cells and exosomes, while exhibiting favorable biocompatibility and reduced cytotoxicity. In conclusion, the findings of this study support the notion that R-LIFE-1 holds significant promise as an ideal tissue engineering material for tissue repair applications.

Progress of research on chitosan-based microspheres in oral tissue lesions / 口腔医学

@#Chitosan-based microspheres use chitosan as the main material to obtain particles with special structures through microsphere processing technology. They have the ability of slow and controlled release of drugs and the role of scaffolding, which have great application prospect in stomatology, but the application of chitosan-based microspheres is still in the research stage and has not yet been applied in clinical practice. This article reviews progress of domestic and foreign research on chitosan-based microspheres, in aspects of treatment of oral and jawbone tissue defects, periodontal diseases, dental pulp diseases and nerve tissue injury, in order to provide reference for follow-up research.

Bioequivalence of metformin hydrochloride sustained-release tablets under fed condition in healthy subjects / 中国药科大学学报

@#To evaluate bioequivalence and safety of two kinds of metformin hydrochloride sustained-release tablets (test preparation vs reference preparation) under the condition of fed and single administration.A single center, randomized, open, single-dose, two-period, two-sequence, and double-crossover design was used.32 healthy subjects took 0.5 g of test preparation or reference preparation under fed and single-dose administration.4 mL of venous blood was collected from before administration (0 h) to 1, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 15, 24, 36 and 48 h after administration.The concentration of metformin in plasma samples was detected, and then the pharmacokinetic parameters were calculated by WinNonlin 7.0 software.When the 90% confidence intervals of cmax, AUC0-t and AUC0-∞ geometric mean ratio of test preparation and reference preparation were within 80.00%-125.00% equivalent intervals respectively, the bioequivalence of the two preparations was proved.One subject fell off due to adverse events.The main pharmacokinetic parameters of test preparation and reference preparation as follows: cmax were (0.68 ± 0.14) and (0.65 ± 0.11) mg/L, AUC0-t were (7.33 ± 1.65) and (7.00 ± 1.89) h·mg/L, AUC0-∞ were (7.39 ± 1.67) and (7.06 ± 1.91) h·mg/L, respectively.The 90% confidence intervals of the geometric mean ratio of the two main pharmacokinetic parameters were 101.45%-109.14%, 100.08%-112.32% and 100.24%-112.28%, respectively, which fell within the bioequivalence interval of 80.00%-125.00%.There were no serious adverse events and unexpected adverse events during the trial.The results show that test preparation and reference preparation are bioequivalent under fed and single-dose administration, safe and well tolerated in healthy subjects.

Early application of tacrolimus extended-release capsule after kidney transplantation / 器官移植

Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m2) vs. (60±15) mL/(min·1.73 m2), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure.

Research progress on antimicrobial peptides in terms of the prevention and treatment of dental caries / 口腔疾病防治

@#Antimicrobial peptides have antibacterial effects on various pathogenic microorganisms, including natural antimicrobial peptides and synthetic antimicrobial peptides. According to the structure of natural antimicrobial peptides, synthetic antimicrobial peptides can be obtained by recombining different functional domains, adjusting the original amino acid sequence, or completely redesigning the peptides from scratch. Antimicrobial peptides can inhibit the growth of various cariogenic microorganisms and the formation of microbial biofilms. They also reduce acid production and acid resistance of microorganisms. Natural antimicrobial peptide genes can be used as genetic susceptibility markers for predicting the development of caries, thus, showing potential applications in the prevention and treatment of dental caries. The instability of natural antimicrobial peptides and the inability to achieve targeted sustained release limit their application in the prevention and treatment of oral caries. Synthetic antimicrobial peptides can enhance their stability and the antibacterial effect. Synthetic antimicrobial peptides can also be polymerized with common oral adhesives to reduce the incidence of microleakage after filling treatment for caries and to prevent the occurrence of secondary caries. The pH-sensitive antimicrobial peptides are slowly released to promote remineralization in the process of caries. However, the safety and biocompatibility of synthetic antimicrobial peptides are worse than those of natural antimicrobial peptides. Moreover, the combined effect of antibacterial peptides and anticaries drugs, such as fluoride, is still uncertain. Therefore, in this paper, we will review the design methods, application and underlying mechanisms of antimicrobial peptides to introduce novel methods and ideas for the prevention and treatment of dental caries.

Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of Miao medicinal crossbow acupuncture therapy as adjuvant treatment for lung cancer pain based on oxycodone hydrochloride extended-release tablet.@*METHODS@#A total of 60 patients with lung cancer pain were randomized into an observation group (30 cases, 1 case dropped off) and a control group (30 cases). In the control group, oxycodone hydrochloride extended-release tablet was given orally, 10 mg a time, once every 12 hours. On the basis of the treatment in the control group, Miao medicinal crossbow acupuncture therapy was applied once every other day in the observation group. The treatment of 14 days was required in the two groups. Before and after treatment, the numerical rating scale (NRS) score, number of break-out pain and Karnofsky performance status (KPS) score were observed in the two groups. The equivalent oxycodone consumption and rate of adverse reactions were recorded, the analgesic effect was evaluated in the two groups.@*RESULTS@#Compared before treatment, the NRS scores and number of break-out pain were decreased while the KPS scores were increased after treatment in the two groups (P<0.01). After treatment, the NRS score and number of break-out pain in the observation group were lower than the control group (P<0.01), the KPS score in the observation group was higher than the control group (P<0.05). The equivalent oxycodone consumption of whole course and the rate of adverse reactions i.e. constipation, drowsiness, nausea and vomiting in the observation group were lower than the control group (P<0.05). The analgesic effect rate was 93.1% (27/29) in the observation group, which was superior to 63.3% (19/30) in the control group (P<0.05).@*CONCLUSION@#On the basis of oxycodone hydrochloride extended-release tablet, Miao medicinal crossbow acupuncture therapy as adjuvant treatment can effectively relieve the pain degree, reduce the number of break-out pain and improve the health status and quality of life in patients with lung cancer pain, enhance the efficacy of medication and reduce its adverse reactions.