X-ray evaluation of pulp calcification in adult permanent teeth after pulpotomy / 北京大学学报(医学版)

OBJECTIVE@#To compare the clinical effects of pulpotomy with two kinds of calcium silicate materials, and to evaluate the formation of dentin bridge and pulp calcification after pulpotomy of adult permanent teeth.@*METHODS@#Patients who visited the General Department of Peking University School and Hospital of Stomatology from November 2017 to September 2019 and planned for pulpotomy on permanent premolars and molars with carious exposed pulp were selected. They were randomly divided into two groups. Bioceramic putty material iRoot BP (iRoot group, n=22) and mineral trioxide aggregate MTA (MTA group, n=21) were used as pulp capping agents, respectively. The patients were recalled after one year and two years. The clinical efficacy, dentin bridge index (DBI) and pulp calcification index (PCI) were recorded. Blinding method was used for the patients and evaluators.@*RESULTS@#There was no significant difference in gender, mean age, dentition and tooth position between the two groups (P>0.05). Seven cases were lost during the first year (4 cases in iRoot group and 3 cases in MTA group). In the iRoot group, 1 case had transient sensitivity at the time of 1-year follow-up. The cure rate of the two groups was 100% at the time of 2-year follow-up. The proportion of dentin bridge formation was 38.9% one year after operation, 55.6% two years after operation. The proportion of partial or even complete disappearance of root canal image was 5.6% before operation, 38.9% and 55.6% one and two years after operation, respectively. The difference was statistically significant by rank sum test (P < 0.05). There was no significant difference in dentin bridge formation and pulp calcification between the two groups (P < 0.05). DBI and PCI after operation was as the same as those before operation (44.4% cases of DBI and 25% cases of PCI) or gradually increased (55.6% cases of DBI and 75% cases of PCI). Spearman's nonparametric correlation analysis showed that age was positively correlated with preoperative pulp calcification index (PCI0, P < 0.05), but not with the dentin bridge index (DBI1, DBI2), pulp calcification index (PCI1, PCI2) and the degree of change (DBI2 vs. DBI1, PCI1 vs. PCI0, PCI2 vs. PCI0) 1-year and 2-year after operation (P>0.05).@*CONCLUSION@#According to this study, good clinical effects were obtained within 2-year after pulpotomy of adult permanent teeth with MTA and iRoot. In some cases, the root canal system had a tendency of calcification aggravation, and there was no statistical difference in the development of this trend between the two groups.

Actualización en fibrosis quística: uso de exacaftor/tezacaftor/ivacaftor/en pacientes con fibrosis quística port-trasplante pulmonar / Use of exacaftor/tezacaftor/ivacaftor in cystic patients post lung transplantation

El uso de moduladores de CFTR en pacientes con fibrosis quística post trasplante pulmonar es un tema todavía controversial. Varias publicaciones reportan los beneficios del modulador elexacaftor/tezacaftor/ivacaftor en los síntomas extrapulmonares de la fibrosis quística, especialmente enfermedad sinusal, síntomas gastrointestinales y diabetes. Un número alto de pacientes debe discontinuar el tratamiento por mala tolerancia, sin embargo, no se describen interacciones de importancia con el tratamiento inmunosupresor. Se debe considerar para su uso los riesgos versus beneficios en forma individual en cada paciente.

The use of CFTR modulators in patients with cystic fibrosis after lung transplantation is still a controversial issue. Several publications report the benefits of the use of the modulator elexacaftor/tezacaftor/ivacaftor on extrapulmonary symptoms of cystic fibrosis, especially sinus disease, gastrointestinal symptoms and diabetes. A high number of patients must discontinue treatment due to poor tolerance; however, no significant interactions with immunosuppressive treatment have been described. The individual risk-benefit of each patient should be considered for its use.

Comparación del efecto de omeprazol como monoterapia y su combinación con bicarbonato de sodio en el tratamiento de la pirosis moderada a severa: ensayo clínico controlado, aleatorizado y doble ciego / Comparison of the effect of omeprazole monotherapy and its combination with sodium bicarbonate in the treatment of moderate to severe heartburn: a double-blind, randomized controlled clinical trial

Heartburn occurs in 75% of patients with digestive discomfort of any origin and is one of the main symptoms of gastroesophageal reflux disease. Treatment focuses on lifestyle modification and symptomatology management with various drugs; when heartburn is moderate to severe, a proton pump inhibitor is more suitable. Omeprazole (OMZ) combined with sodium bicarbonate (BC) has demonstrated significant and sustained suppression of acid secretion. The objective was to compare the effect of sequential OMZ/BC therapy compared to OMZ monotherapy for the improvement of heartburn in Mexican individuals. The study was a double-blind, randomized, controlled, multicenter clinical study including 277 subjects with moderate to severe heartburn. Patients received 7 days of OMZ/BC and 7 days of OMZ (OMZ/BC7) or 14 days of OMZ (OMZ14). The primary endpoint was defined as the change in the number of days a week that the patient has heartburn, it was evaluated at 14 days. Both treatments reduced time (days) with heartburn by less than 4 days (OMZ14 3.9 vs. 4.2 days OMZ/BC7), as well as duration, number of events and intensity of heartburn. The treatments improved the quality of life, and the control of the symptoms. The proportion of adverse events was lower with OMZ/BC. The non-inferiority of OMZ/BC7 with respect to OMZ14 was verified.

La pirosis se presenta en el 75% de los pacientes con molestias digestivas de cualquier origen y es uno de los principales síntomas de la enfermedad por reflujo gastroesofágico. El tratamiento se enfoca en la modificación del estilo de vida y el manejo de la sintomatología con diversos fármacos; cuando la pirosis es moderada a severa, un inhibidor de la bomba de protones es más adecuado. El omeprazol (OMZ) combinado con bicarbonato de sodio (BC) ha demostrado supresión significativa y sostenida de la secreción ácida. El objetivo fue comparar el efecto de la terapia secuencial de OMZ/BC en comparación con el tratamiento continuo de OMZ para la mejoría de la pirosis en individuos mexicanos. Estudio clínico multicéntrico, doble ciego, controlado, aleatorizado que incluyó 277 sujetos con pirosis moderada a severa. Los pacientes recibieron 7 días de OMZ/BC y 7 días de OMZ (OMZ/BC7) o 14 días de OMZ (OMZ14). La variable primaria fue definida como el cambio del número de días a la semana que el paciente presenta pirosis, se evaluó a los 14 días. Ambos tratamientos redujeron los días con pirosis en menos 4 días (OMZ14 3,9 vs. 4,2 días OMZ/BC7), así como la duración, el número de eventos e intensidad de la pirosis. Los tratamientos mejoraron los indicadores de calidad de vida, y el control del padecimiento. La proporción de eventos adversos fue menor con OMZ/BC. Se comprobó la no-inferioridad de OMZ/BC7 respecto OMZ14.

Eficácia e segurança da combinação Glicosamina e Condroitina comparada a medicamentos disponíveis no SUS para o tratamento de osteoartrite: revisão rápida / Effectiveness and safety of Glucosamine and Chondroitin combination compared to drugs available in Brazilian Public Health System for the treatment of Osteoarthritis: rapid review

Tecnologia: Combinação de glicosamina e condroitina. Indicação: Tratamento de osteoartrite em adultos. Pergunta: O tratamento com a combinação de glicosamina e condroitina é mais eficaz e seguro que os demais tratamentos para osteoartrite disponíveis no SUS? Métodos: Uma revisão rápida de evidências, uma revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2. Resultados: Foi selecionada uma revisão sistemática, que atendiam aos critérios de inclusão. Conclusão: A combinação de glicosamina com condroitina, comparados ao placebo, mostrou ser mais eficaz para tratamento da dor e função e alcançou o segundo lugar nas alternativas terapêuticas para tratamento da dor e função

Technology: Combination of glucosamine and chondroitin. Indication: Treatment of osteoarthritis in adults. Question: Is the treatment with the combination of glucosamine and chondroitin more effective and safer than the other treatments for osteoarthritis available in the Brazilian Public Health System? Methods: A rapid review of evidence, a overview of systematic reviews, with bibliographic search done in PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2. Results: A systematic review was selected, which met the inclusion criteria. Conclusion: The combination of glucosamine and chondroitin, compared to placebo, proved to be more effective for the treatment of pain and function and reached second place in therapeutic alternatives for the treatment of pain and function

Medication rules of Chinese herbal compound prescriptions for treating angina in national patent database based on multiple data mining / 中国中药杂志

This study explored the medication rules of Chinese herbal compound prescriptions for the treatment of angina based on the Chinese herbal compound patents in the patent database of the China National Intellectual Property Administration. The data of eligible Chinese herbal compound patents for the treatment of angina were collected from the patent database of the China National Intellectual Property Administration from database inception to November 10, 2022, and subjected to data modeling, analysis of main syndromes, medication frequency analysis, cluster analysis, association rule analysis, and data visualization by using Excel 2021, IBM SPSS Statistics 26.0, IBM SPSS Modeler 18.0, Cytoscape 3.9.1, and Rstudio R 4.2.2.2 to explore the medication rules for angina. The study included 636 pieces of patent data for angina that met the inclusion criteria, involving 815 drugs, with a total frequency of 6 586. The most common main syndromes were blood stasis obstructing the heart syndrome(222, 34.91%) and Qi deficiency and blood stasis syndrome(112, 17.61%). The top 10 most frequently used drugs were Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoginseng Radix et Rhizoma, Astragali Radix, Angelicae Sinensis Radix, Carthami Flos, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Borneolum Syntheticum, and Corydalis Rhizoma. High-frequency drugs included blood-activating and stasis-resolving drugs(1 197, 18.17%) and deficiency-tonifying drugs(809, 12.28%). Cluster analysis identified eight drug combinations, including five new prescriptions suitable for clinical use and new drug development, and three drug pairs. The core drug combination of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Carthami Flos was identified through the complex co-occurrence network analysis of Chinese medicines. Association rule analysis yielded a total of 17 rules, including 13 drug pairs and 4 tripartite combinations. Common drug pairs included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma(support degree 25.79%, confidence coefficient 69.49%, lift 1.30) and Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma(support degree 22.01%, confidence coefficient 61.95%, lift 1.16). Common tripartite combinations included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix(support degree 10.85%, confidence coefficient 73.40%, lift 1.37) and Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Notoginseng Radix et Rhizoma(support degree 10.69%, confidence coefficient 79.07%, lift 1.48). The results showed that the underlying pathogenesis of angina involved blood stasis obstructing the heart and Qi deficiency and blood stasis. The overall nature of the disease was characterized as asthenia in origin and sthenia in superficiality. In the prescription formulation, blood-activating and stasis-resolving drugs, such as Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Carthami Flos were often used to resolve the excess manifestation, which were combined with tonifying drugs such as Astragali Radix, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, and Ginseng Radix et Rhizoma to reinforce the deficiency. The syndrome, pathogenesis, disease nature, and medication were consistent with clinical practice. Additionally, the new compound prescriptions and drug combinations derived from the multiple data mining in this study could provide references and insights for the clinical diagnosis and treatment of angina and the development of new drugs.

Prescription and medication rules of traditional Chinese medicine for prevention and treatment of diabetic microangiopathy based on literature mining / 中国中药杂志

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

Perfiles de hipoglicemiantes e insulinas en pacientes con diabetes mellitus tipo 2 y su efecto en control metabólico, hipoglicemia y otros efectos adversos / Profile of glucose lowering drug use in outpatients with type 2 diabetes mellitus

BACKGROUND: The use of glucose lowering agents with favorable weight profile is a growing practice in Diabetology. AIM: To characterize medication combinations in patients with type 2 Diabetes (T2D) and their effect on metabolic control. MATERIAL AND METHODS: Review of medical records of 249 outpatients with T2D with a median age of 66 years, cared for at a medical network. Clinical characteristics, glycated hemoglobin (HbA1c), details of Diabetes treatment (types of drugs or insulin), renal function, lipids and B12 vitamin levels were registered. RESULTS: The median disease duration was 16 years. The most recent HbA1c was 7.4%. No patient was using sulfonylureas, 45 were using Dipeptidyl peptidase 4 inhibitors, 113 were using Sodium-glucose Cotransporter-2 (SGLT2i) Inhibitors, 21 used Glucagon-like Peptide-1 Receptor Agonists (GLP1ra), 158 used basal insulin and 61 on basal plus bolus insulin. The use of SGLT2i or GLP1ra was associated with a metabolic control similar to those patients not using them, while patients on rapid insulin had a significantly worse metabolic control and a tendency to greater body mass index. The use of basal insulin and rapid insulin was significantly associated with more hypoglycemia events. CONCLUSIONS: The use of SGLT2i and GLP1ra in patients with T2D is associated with better metabolic control than rapid insulin with less risk of hypoglycemia. The use of these therapies should be prioritized in the future.

Mucormicosis periostomal posoperatoria, a propósito de un caso / Mucormycosis periostomal: case report

Resumen Introducción: La mucormicosis en una enfermedad infrecuente y oportunista que afecta, principalmente, a pacientes inmunocomprometidos. Pocas veces se han reportado casos de afectación periostomal. Clínicamente puede ser confundida con otras patologías, pudiendo tener una evolución fulminante, por lo que un adecuado y pronto diagnóstico son necesarios para una instauración precoz del tratamiento. Caso Clínico: Se presenta el caso de una paciente de 62 años inmunocomprometida, que tras complicaciones quirúrgicas evoluciona con mucormicosis periostomal de la pared abdominal. A pesar de un tratamiento quirúrgico con múltiples resecciones de tejido asociado a antifúngico local y sistémico, la paciente fallece, concordante a la letalidad expresada en la literatura.

Introduction: Mucormycosis is a rare and opportunistic disease that mainly affects immunocompromised patients. Few cases of peristomal involvement have been reported. Clinically it can be confused with other pathologies and may have a fulminant evolution, so an adequate and prompt diagnosis is necessary for an early establishment of treatment. Clinical Case: We present the case of a 62-year-old immunocompromised patient who, after surgical complications, evolves with periostomal mucormycosis of the abdominal wall. Despite surgical treatment with multiple tissue resections, associated with local and systemic antifungal agents, the patient died, consistent with the lethality expressed in the literature.

Eficacia y seguridad de la combinación de tixagevimab y cilgavimab (Evusheld) contra la COVID-19 / Efficacy and safety of the combination of tixagevimab and cilgavimab (Evusheld) against COVID-19

ANTECEDENTES: Este informe se efectúa en atención a la solicitud la jefatura del Instituto Nacional de Salud (INS). El 8 de diciembre de 2021, la FDA emitió la autorización de uso de emergencia de la combinación de anticuerpos monoclonales tixagevimab y cilgavimab (Evusheld) como profilaxis pre exposición (prevención) en cierta población de adultos y niños (personas inmunocomprometidas y antecedentes de reacciones adversas severas a las vacunas contra COVID-19) (1). La EMA continua con el proceso de revisión de la eficacia y seguridad (2). El objetivo es sintetizar la evidencia científica publicada respecto a la eficacia y seguridad de la combinación de tixagevimab y cilgavimab (EvusheldTM) contra la COVID-19. MÉTODOS: Pregunta PICO: ¿En población con COVID-19, cuál es la eficacia y seguridad de la combinación de de tixagevimab y cilgavimab (Evusheld)? Criterios de elegibilidad: Los criterios de selección de los estudios fueron los siguientes: Ensayos clínicos aleatorizados o revisiones sistemáticas que reporten resultados para al menos uno de los desenlaces. En ausencia de resultados de eficacia para alguno de los desenlaces, se considerará los resultados de efectividad a partir de estudios de cohorte o test negativo. Estudios publicados en idioma inglés y español. Se excluyeron cartas al editor, revisiones narrativas, estudios preclínicos (estudios in vitro o en modelos animales), artículos de opinión y manuscritos no revisados por pares. Métodos para la búsqueda e identificación de la evidencia: Los ensayos clínicos fueron identificados desde las siguientes fuentes (búsqueda realizada el 3 de febrero de 2022): Plataforma Living Overview of the Evidence (L·OVE) de la Fundación Epistemonikos (https://www.epistemonikos.org/en/). Bases de datos electrónicas: MEDLINE/Pubmed, Embase y Cochrane Library. Registro de Ensayos Clínicos de Estados Unidos (https://clinicaltrials.gov/ct2/home) y la Plataforma Internacional de Registro de Ensayos Clínicos de la OMS (https://trialsearch.who.int/). Páginas institucionales de la Food and Drug Administration (FDA) de Estados Unidos (https://www.fda.gov/) y la European Medicines Agency (EMA) (https://www.ema.europa.eu/en). RESULTADOS: No se encontraron ECA o RS en las bases de datos seleccionadas que muestren resultados de eficacia o seguridad de la combinación de tixagevimab y cilgavimab (Evusheld). En cambio, se encontraron 8 protocolos de ECA que están en progreso. CONCLUSIONES: La presente nota técnica tiene como objetivo sintetizar la evidencia disponible sobre la eficacia y seguridad de la combinación de tixagevimab y cilgavimab (Evusheld) para la prevención de la infección por SARS-CoV-2. En la búsqueda de información, no se encontraron ECA o RS publicados en revistas científicas que mostraran información sobre la eficacia y seguridad de la combinación de tixagevimab y cilgavimab (Evusheld). En cambio, se encontró una revisión de la FDA de la ECA PROVENT que evaluó la eficacia y seguridad de la combinación de tixagevimab y cilgavimab (Evusheld). La combinación de tixagevimab y cilgavimab (Evusheld) fue evaluada en población que fue candidata a inmunización pasiva con anticuerpos, en este grupo se incluyeron las personas que tuvieron una respuesta deficiente a vacunas o personas con riesgo incrementado a infección por SARS-CoV-2. Según el informe, combinación de tixagevimab y cilgavimab (Evusheld) mostró una reducción del riesgo relativo en la infección sintomática por SARS-CoV-2 (confirmado por RT-PCR) de 76.7%. La combinación de tixagevimab y cilgavimab (Evusheld) mostró una reducción del riesgo relativo de muerte por cualquier causa de 68.8%. Se ha reportado eventos adversos asociados a tratamiento en el grupo intervención (8%) y en el grupo placebo (7%). Se ha reportado eventos adversos con desenlace de muerte en el grupo AZD7442 (0.12%) y placebo (0.23%), los detalles de estos desenlaces no están disponibles en el reporte. Los eventos adversos de especial interés fueron reportados en el grupo AZD7442 (3%) y en el grupo placebo (2%).

Eficacia y seguridad de la combinación de nirmatrelvir y ritonavir (PaxlovidTM) contra la COVID-19 / Efficacy and safety of the combination of nirmatrelvir and ritonavir (PaxlovidTM) against COVID-19

ANTECEDENTES: Este informe se efectúa en atención a la solicitud la jefatura del Instituto Nacional de Salud (INS). En un comunicado de prensa (publicado el 5 de noviembre de 2021), Pfizer indicó que, a través de un análisis provisional de su ECA fase 2/3, su nuevo antiviral candidato a tratamiento contra la COVID-19 (Paxlovid™) reduce el riesgo de hospitalización o muerte en un 89%, en comparación de las personas que recibieron placebo, en adultos no hospitalizados con COVID-19 (1). El comunicado menciona también que Pfizer planea enviar los datos a la FDA para su uso de emergencia, tan pronto como sea posible. El 16 de diciembre de 2021, la EMA emite recomendaciones sobre el uso de Paxlovid™ para el tratamiento de la COVID-19 (2) y el 19 de noviembre la EMA solicitó una opinión científica sobre los datos preclínicos, clínicos y de calidad disponibles sobre el potencial uso de Paxlovid™ para el manejo de pacientes con COVID-19 (el reporte se publicó el 10 de enero) (3). El 22 de diciembre de 2021, la FDA comunicó que autorizó el uso de emergencia de la combinación de nirmatrelvir y ritonavir (Paxlovid™) contra los casos leves y moderados de COVID-19 en adultos y población pediátrica de 12 a más años (que pesen de 40 Kg a más) (4). El 28 de enero del 2022, la EMA otorgó autorización comercial condicional a Paxlovid™ (5). El objetivo es sintetizar la evidencia científica publicada respecto a la eficacia y seguridad de la combinación de nirmatrelvir y ritonavir (Paxlovid™) contra la COVID-19. MÉTODOS: Pregunta PICO: ¿En población con COVID-19, cuál es la eficacia y seguridad de la combinación de nirmatrelvir y ritonavir (Paxlovid™)? Criterios de elegibilidade: Los criterios de selección de los estudios fueron los siguientes: Ensayos clínicos aleatorizados o revisiones sistemáticas que reporten resultados para al menos uno de los desenlaces. En ausencia de resultados de eficacia para alguno de los desenlaces, se considerará los resultados de efectividad a partir de estudios de cohorte o test negativo. Estudios publicados en idioma inglés y español. Se excluyeron cartas al editor, revisiones narrativas, estudios preclínicos (estudios in vitro o en modelos animales), artículos de opinión y manuscritos no revisados por pares. Métodos para la búsqueda e identificación de la evidencia: Los ensayos clínicos fueron identificados desde las siguientes fuentes (búsqueda realizada en 26 de enero de 2022): Plataforma Living Overview of the Evidence (L·OVE) de la Fundación Epistemonikos (https://www.epistemonikos.org/en/). Bases de datos electrónicas: MEDLINE/Pubmed, Embase y Cochrane Library. Registro de Ensayos Clínicos de Estados Unidos (https://clinicaltrials.gov/ct2/home) y la Plataforma Internacional de Registro de Ensayos Clínicos de la OMS (https://trialsearch.who.int/). Páginas institucionales de la Food and Drug Administration (FDA) de Estados Unidos (https://www.fda.gov/) y la European Medicines Agency (EMA) (https://www.ema.europa.eu/en). RESULTADOS: En la búsqueda bibliográfica no se encontraron ECA o estudios observacionales publicados o en proceso de publicación (in press) o sin revisión por partes (preprint) que hayan evaluado la eficacia y seguridad de la combinación de nirmatrelvir y ritonavir (Paxlovid™) contra la COVID-19. En cambio, se encontraron 3 ECA en proceso, sin resultados preliminares publicados en Clinical Trials (Tabla 1). Se encontró 1 evaluación realizada por la EMA de los datos del ECA de Paxlovid™ (NCT04960202) (3). El ensayo clínico es de tipo aleatorizado, en fase 2/3, doble ciego, controlado con placebo en adultos con COVID-19 sintomáticos y no hospitalizados que se encuentran en riesgo incrementado de progresar a enfermedad severa. El objetivo del ECA fue determinar la eficacia, seguridad y tolerabilidad de la combinación de nirmatrelvir (PF-07321332) y ritonavir (Paxlovid™) comparado con placebo en pareamiento 1:1. Las características del ECA se resumen en la Tabla 2. Con un análisis provisional de datos, con 45% de los participantes que completaron el seguimiento al día 28, se reportó una reducción absoluta del 6.317% (CI95%: -9.041%, -3.593%; p<0.0001). La EMA mencionó que no está completamente claro en qué medida los subgrupos de pacientes con COVID-19 leve y moderado están representados y adecuadamente balanceados en ambos grupos. Asimismo, hay una pobre representación de los pacientes con factores de riesgo (enfermedad pulmonar crónica, enfermedades cardiovasculares, enfermedades inmunosupresivas, etc.). Además, la EMA indicó que la falta de información de la actividad de nirmatrelvir (FP-07321332) contra la variante Omicron in vitro puede ser una advertencia crítica. CONCLUSIONES: El objetivo de la nota técnica fue sintetizar la evidencia científica publicada respecto a la eficacia y seguridad de la combinación de nirmatrelvir y ritonavir (Paxlovid™) contra la COVID-19. No se encontraron ECA o estudios observacionales publicados o en proceso de publicación (in press) o sin revisión por partes (preprint) que hayan evaluado la eficacia y seguridad de la combinación de nirmatrelvir y ritonavir (Paxlovid™) contra la COVID-19. Se encontraron 3 ECA en proceso, sin resultados preliminares publicados en Clinical Trials. Se encontró una evaluación de la EMA a un ECA de Pfizer (NCT04960202) que tuvo como objetivo evaluar la eficacia y seguridad de la combinación de nirmatrelvir y ritonavir (Paxlovid™) contra la COVID-19. Con un análisis provisional de datos, con 45% de los participantes que completaron el seguimiento al día 28, se reportó una reducción absoluta de la proporción de hospitalizaciones relacionadas a COVID-19 o muertes por cualquier causa en 6.317% (CI95%: -9.041%, -3.593%; p<0.0001) respecto de placebo. Según la ficha técnica de la FDA de Paxlovid™ y la información de la EMA, las reacciones adversas más frecuentes son disgeusia, diarrea, hipertensión y mialgias. No se reportaron muertes en el grupo Paxlovid™. Los datos sobre la eficacia de la combinación de nirmatrelvir y ritonavir (Paxlovid™) deben tomarse con precaución. La EMA señaló que no está completamente claro la representatividad de los grupos según grado de severidad y presencia de factores de riesgo. Además, existe falta de información sobre la actividad del Paxlovid contra la variante Omicron in vitro.

Effect of Shenmai Injection on Long-Term Prognosis of Patients with Chronic Heart Failure: A Multicenter, Large Sample Capacity, Long-Term Follow-Up Retrospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Shenmai Injection (SMI) on the long-term prognosis of patients with chronic heart failure (CHF).@*METHODS@#The Hospital Information System was used to extract data of CHF patients, and the retrospective cohort study was conducted for analysis. In non-exposed group, standardized Western medicine treatment and Chinese patent medicine or decoction were applied without combination of SMI while in the exposed group, SMI were applied for more than 7 days. Evaluation indicators are followed with New York Heart Association functional classification (NYHA classification), left ventricular ejection fraction (LVEF), N-terminal brain natriuretic peptide precursor (NT-ProBNP), cardiogenic death and heart failure (HF) readmission. Statistical analysis includes Kaplan-Meier analysis and Cox regression which are used to explore the relationship between SMI and outcome events.@*RESULTS@#A total of 1,211 eligible CHF patients were involved and finally 1,047 patients were followed up successfully. After treatment, the cases of NYHA classification decline in the exposed and non-exposed groups accounted for 64.30% and 43.45%, respectively; the improvement values of LVEF were 8.89% and 7.91%, respectively; the improvement values of NT-ProBNP were 909 pg/mL and 735 pg/mL, respectively. After exposure on SMI, the rates of cardiogenic death and HF readmission reduced from 15.43% to 10.18% and 38.93% to 32.37%. According to Kaplan-Meier analysis, the log-rank P value of SMI and cardiogenic death was 0.014, while the counterpart of SMI and HF readmission was 0.025. Cox regression analysis indicated that for cardiogenic death, age, cardiomyopathy, diabetes, and NYHA classification were risk factors while β-blockers, aldosterone receptor antagonists, Chinese patent medicine/decoction and SMI were protective factors. Likewise, for HF readmission, age, cardiomyopathy, and NYHA classification were risk factors while SMI was a protective factor.@*CONCLUSION@#Combination with SMI on the standardized Western medicine treatment can effectively reduce cardiogenic mortality and readmission rate in CHF patients, and thereby improve the long-term prognosis.

~1H-qNMR quantification of total ginsenosides in Shenmai Injection / 中国中药杂志

A content determination method based on ~1H-qNMR was developed for the determination of total ginsenosides in Shenmai Injection. The parameters were optimized with CD_3OD as the solvent, dimethyl terephthalate as the internal standard, the peak at δ 8.11 as the internal standard peak, and the peaks at δ 1.68 and δ 0.79 as quantitative peaks of total ginsenosides. The developed ~1H-qNMR-based method was validated methodologically. The results showed that the method could achieve accurate measurement of total ginsenosides in Shenmai Injection in the range of 0.167 6-3.091 1 mmol·L~(-1). The developed ~1H-qNMR-based method for total ginsenosides is simple in operation, short in analysis time, strong in specificity, independent of accompanying standard curve, and small in sample volume, which can serve as a reliable mean for the quality control of Shenmai Injection. This study is expected to provide new ideas for the development of quantification methods of total ginsenosides.

Fingerprint of Shenmai Injection based on ~1H-NMR technique / 中国中药杂志

Shenmai Injection is a Chinese medicinal injection prepared from Ginseng Radix et Rhizoma Rubra and Ophiopogonis Radix, which is widely used in clinical practice for the treatment and adjuvant therapy of cardiovascular diseases with significant pharmacological effects. Proton nuclear magnetic resonance spectroscopy(~1H-NMR) has the advantages of simple and nondestructive sample pretreatment, fast analysis, abundant chemical information, quantification and no need to follow the standard curve. It is widely used in the analysis and research of complex mixtures of traditional Chinese medicine, clinical blood and urine samples. In this study, the ~1H-NMR fingerprint of Shenmai Injection was established. Thirty-two chemical components were identified, including seven amino acids, eight small molecular organic acids, one alkaloid, four sugars, two nucleosides, seven saponins, and three other components. Pearson's correlation coefficient and multivariate analysis of variance(principal component analysis combined with hierarchical cluster analysis) were applied based on the ~1H-NMR fingerprint to evaluate the quality consistency. The results showed high-quality consistency of 82 batches of Shenmai Injection. This study confirms that the ~1H-NMR fingerprint has great potential in the application of quality control of Chinese medicinal injection.

Prevalence of antifolate drug resistance markers in Plasmodium vivax in China / 医学前沿

The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax, as antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009-2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.

Shengmai San for Treatment of Cardiotoxicity from Anthracyclines: A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines.@*METHODS@#Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software.@*RESULTS@#Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group.@*CONCLUSION@#Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.

Evaluation of bioceramic putty repairmen iRoot and mineral trioxide aggregate in mature permanent teeth pulpotomy / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the clinical characteristics and effectiveness of pulpotomy in mature permanent teeth with bioceramic putty repairmen iRoot and mineral trioxide aggregate (MTA).@*METHODS@#Pulpotomy was performed on mature permanent premolars and molars with carious exposures at the Department of General Dentistry of Peking University School and Hospital of Stomatology, from November 2017 to September 2019. The patients were randomly divided into 2 groups, Group iRoot (n=22) and Group MTA (n=21). In Group iRoot, bioceramic putty repairmen iRoot was used as pulp capping agent, while in Group MTA, mineral trioxide aggregate was used as pulp capping agent. All the patients had signed informed consent forms. The clinical efficacy was evaluated by clinical examinations (temperature and electrical activity test) and imaging examinations 3, 6, and 12 months after surgery. Blinding was used for the patients and evaluators, but due to the obvious differences in the properties of the two pulp capping agents, the blinding method was not used for the treatment provider (the attending physician).@*RESULTS@#There was no significant difference in gender, average age, dentition and tooth position distribution between the two groups (P>0.05). In the study, 7 cases were lost to follow-up 12 months after operation (4 cases in Group iRoot, and 3 cases in Group MTA). One case in each of the two groups had transient sensitivity at the end of the 3-month follow-up, and the pulp vitality was normal at the end of the 6-month follow-up. One case in Group iRoot showed sensitivity at the end of the 12-month follow-up. The success rates of the two groups at the end of 12-month follow-up were 100%, and the cure rates were 94.4% (Group iRoot) and 100% (Group MTA), respectively, and the difference was not statistically significant (P>0.05). No cases in Group iRoot had obvious crown discoloration, while 3 cases in Group MTA had.@*CONCLUSION@#The clinical characteristics and effectiveness of pulpotomy in mature permanent teeth with bioceramic putty repairmen iRoot were similar with MTA. Bioceramic putty repairmen iRoot is an acceptable material when used in pulpotomy of mature permanent teeth. Because it is not easy to cause tooth discoloration after treatment and is convenient to operate, bioceramic putty repairmen iRoot has a better clinical application prospect.

A new combination of naringin and trimetazidine protect kidney Mitochondria dysfunction induced by renal Ischemia / Reperfusion injury in rat

Abstract Ischemia/reperfusion (IR) injury leads to overproduction of Reactive Oxygen Species (ROS), and disrupts membrane potential that contributes to cell death. The aim of this study was to determine if naringin (NAR), trimetazidine (TMZ) or their combination, protect the kidney mitochondrial from IR injury. Forty rats were randomly allocated into five groups, harboring eight rats each: Sham, IR, NAR (100 mg/kg), TMZ (5 mg/kg) and NAR plus TMZ. Ischemia was induced by obstructing both renal pedicles for 45 min, followed by reperfusion for 4 hours. The mitochondria were isolated to examine the ROS, Malondialdehyde (MDA), Glutathione (GSH), mitochondrial membrane potential (MMP) and mitochondrial viability (MTT). Our findings indicated that IR injury resulted in excessive ROS production, increased MDA levels and decreased GSH, MMP and MMT levels. However, NAR, TMZ or their combination reversed these changes. Interestingly, a higher protection was noted with the combination of both, compared to each drug alone. We speculate that this combination demonstrates a promising process for controlling renal failure, especially with the poor clinical outcome, acquired with NAR alone. This study revealed that pretreatment their combination serves as a promising compound against oxidative stress, leading to suppression of mitochondrial stress pathway and elevation of GSH level.