Optimization of on-site supervision strategy based on big data of quality risk in drug enterprises / 中国药房

On-site supervision is a risk-based regulatory system that requires the scientific development of supervision plans for quality risks and hidden dangers in pharmaceutical enterprises， the rational allocation of supervision resources based on their risk levels， and the implementation of classified supervision measures. In this study， the quality risk monitoring business support system is set up for pharmaceutical enterprises by establishing the quality risk expert database and quality risk monitoring index system for pharmaceutical enterprises based on the difficulty analysis of on-site drug supervision. Based on this support system， the quality risk classification method， the differentiated spot check strategy and business auxiliary visualization system are established. This support system is used to learn the risk level of pharmaceutical enterprises， so as to innovate supervision methods and optimize monitoring strategies. Taking Jiangxi Province as an example， it is verified that the support system can guide the risk assessment of sample enterprises， can improve the targeting of on-site drug supervision in the process of technical review， scheme editing， on-site implementation and comprehensive evaluation， and can effectively improve the quality and efficiency of supervision.

Niveles de referencia diagnósticos en equipos de radiografía dental en Bogotá, Colombia

Introducción: Las radiografías dentales son una de las exposiciones médicas más frecuentes a la radiación ionizante. El uso de radiación ionizante está asociado a un riesgo probable de desencadenar efectos biológicos adversos y posibles daños a la salud del paciente. Para evitar que los pacientes reciban dosis innecesariamente altas durante estas exposiciones, la Comisión Internacional de Protección Radiológica recomienda la utilización de los niveles de referencia para diagnóstico, como una herramienta efectiva de ayuda a la optimización de la protección radiológica de los pacientes. Objetivo: Estimar los niveles de referencia para diagnóstico en radiografía dental intraoral y panorámica en la ciudad de Bogotá, D. C. Metodología: Se evaluaron los parámetros de exposición radiográficos de los equipos y la calidad de imagen en 68 equipos de radiografía dental periapical y 23 equipos de radiografía panorámica. Se estimaron las magnitudes dosimétricas de kerma incidente en aire (Kai) en equipos intraorales para la radiografía de un maxilar molar de un adulto y el producto kerma aire-área (PKA) en equipos de radiografía panorámica en un examen de un adulto estándar. Resultados: El tercer cuartil de la distribución de kerma incidente en aire para radiografía intraoral fue de 3,3 mGy y del producto kerma aire-área para radiografía panorámica fue de 103,9 mGycm2. En la distribución de frecuencias de kerma incidente en aire para radiografía intraoral, el porcentaje más alto de equipos estuvo en el rango de 2,0-3,0 mGy. En la distribución de frecuencias del producto kerma aire-área para los equipos de radiografía panorámica, el porcentaje más alto de equipos estuvo en el rango de 60 a 80 mGycm2. Discusión: Las instituciones consideradas para establecer los Niveles de Referencia para Diagnóstico en este estudio contaron con una adecuada calidad de la imagen evaluada con un maniquí dental, pero las variaciones en las dosis de radiación entre instituciones señalan la necesidad de implementar herramientas que contribuyan a la optimización de las prácticas. Conclusiones: Se recomienda usar los valores de los niveles de referencia para diagnóstico encontrados en esta investigación para optimizar la protección radiológica en las exposiciones radiológicas dentales, y se espera que este estudio sirva de base para nuevas investigaciones en las demás ciudades del país.

Introduction: Dental X-rays are one of the most frequent medical exposures to ionizing radiation. The use of ionizing radiation is associated with a probable risk of triggering adverse biological effects and possible damage to the patient's health. To prevent patients from receiving unnecessarily high doses during these exposures, the International Commission on Radiological Protection recommends the use of diagnostic reference levels as an effective tool to help optimize radiological protection for patients. Objective: To estimate diagnostic reference levels in intraoral and panoramic dental radiography in the city of Bogotá, D.C. Methodology: In 68 periapical dental radiography equipment and 23 panoramic radiography equipment, the radiographic exposure parameters of the equipment and image quality were evaluated. The dosimetric magnitudes of incident air kerma (Ka,i) in intraoral equipment for the radiography of a maxillary molar of an adult and the air kerma-area product (PKA) in panoramic radiography equipment in a standard adult examination were estimated. Results: The third quartile of the incident air kerma distribution for intraoral radiography was 3,3 mGy and the air kerma-area product for panoramic radiography was 103,9 mGycm2. In the frequency distribution of incident air kerma for intraoral radiography, the highest percentage of equipment was in the range of 2,0-3,0 mGy, and in the frequency distribution of the air kerma-area product for equipment of panoramic radiography, the highest percentage of the equipment was in the range of 60 to 80 mGy cm2. Discussion: The institutions considered to establish the diagnostic reference levels in this study had an adequate quality of the image evaluated with a dental phantom, but the variations in radiation doses between institutions indicate the need to implement tools that contribute to the optimization of the practices. Conclusions: It is recommended to use the values of the diagnostic reference levels found in this research to optimize radiological protection in dental radiological exposures, and it is expected that this study will serve as a basis for further research in other cities of the country.

Optimization Method of Whole Wheat Flour, Soybean Flour, Oyster Meat Powder for Nutrient- Dense Composite Flour

Aim: To study the production of Nutrient – Dense Composite Flour from the blends of whole wheat flour, soybean flour (full fat) and oyster meat powder. Study Design: The study was design using the D-optimal combination design of Response Surface Methodology (RSM). Place and Duration of Study: The study was carried out at Department of Food, Nutrition and Home Science, University of Port Harcourt (Processing of raw materials) and the Department of Food Technology, Federal Institute of industrial research Oshodi, Lagos (Analysis of raw materials) between October 2021 and August 2022. Methodology: The raw materials were each processed to have wholesome flours, and then they were combined according to the matrix generated, which had ranges of 70 – 100%, 0 – 22%, and 0 – 8% for whole wheat flour (WWF), soybean flour (SBF) and oyster meat powder (OMP) respectively. Results: The design was used to assess the significance (5% probability) of the moisture, fat, and protein content, which ranged from 8.09 to 11.37%, 1.80 to 8.52% and 9.70 to 19.07% respectively; the water absorption (72.00 - 79.10BU), dough stability (9.3 - 17.5BU) and mixing tolerance index (25 - 50BU); and lightness and yellowness, which ranged from 65.48 - 83.2 and 13.77 - 23.58 respectively, of the flour blends. Protein content, water absorption dough stability, and mixing tolerance index were prioritized while moisture content, fat content, and yellowness were minimized for the numerical optimization of the responses. This study highlights the possibilities of utilizing non-conventional raw materials in the production of composite flour with balance nutritional and baking qualities. Conclusion: The best flour combination was 72.51% whole wheat flour, 19.63% soybean flour, and 7.86% oyster meat powder.

Mejoramiento de un método no comercial para la extracción de ADN de moscas de interés médico-legal

La obtención de ADN de moscas de interés médico-legal es de relevancia para una variedad de aplicaciones. Aunque existen métodos de extracción comerciales de ADN, su uso rutinario es limitado, en algunos escenarios. En este contexto, el uso de métodos no comerciales constituye una alternativa; sin embargo, su optimización es clave para mejorar el flujo de trabajo y los resultados. Este trabajo evaluó el impacto de variaciones a un método de precipitación salina sobre la concentración y la pureza del ADN recuperado. No se encontraron diferencias significativas en la concentración de ADN extraído entre los diferentes tiempos de incubación, probados durante la fase de extracción, mientras que el incremento en el volumen de etanol absoluto, en la fase de precipitación de ADN, mejoró significativamente la concentración de ADN obtenido. Las modificaciones propuestas reducen el tiempo de ejecución y la concentración de ADN obtenido comparado con el protocolo original.

Obtaining DNA from flies of medico-legal interest is relevant for a variety of applications. Although commercial extraction methods offer optimal DNA, their routine use is limited in some settings. In this context, the use of non-commercial methods constitutes an alternative in laboratories with limited resources however, its optimization is key to improving the workflow and the results. This work evaluated the impact of variations to a saline precipitation method on the concentration and purity of the recovered DNA. No significant differences were found in the concentration of extracted DNA between the different incubation times tested during the extraction phase. In contrast, the increased volume of absolute ethanol in the DNA precipitation phase significantly improved the concentration of DNA obtained. The proposed modifications reduce the runtime and DNA concentration obtained compared with the original protocol.

Cirugía en horario extendido: una visión de los actores involucrados / Extended hours surgery: a vision of the actors involved

Introducción. Las listas de espera para cirugía de alta prevalencia son producto de una limitada oferta ante una elevada demanda de jornadas quirúrgicas. Tienen un impacto sobre las condiciones médicas de los pacientes y la consulta por urgencias. Como respuesta, se han incorporado los espacios quirúrgicos adicionales en horarios no convencionales. Su creciente implementación, aunque controversial, se reconoce cada vez más como una nueva normalidad en cirugía. Hay una limitada documentación de la efectividad de la medida, debido a la complejidad e intereses de los participantes. Métodos. Se analizó desde una posición crítica y reflexiva la perspectiva de los actores involucrados en un programa de cirugía en horario extendido, estableciendo las posibles barreras y los elementos facilitadores de una política enfocada a procedimientos en horario no convencional. Asimismo, se describen posibles oportunidades de investigación en el tema. Discusión. Los programas quirúrgicos en horarios no convencionales implican un análisis de los determinantes de su factibilidad y éxito para establecer la pertinencia de su implementación. La disponibilidad de las salas de cirugía, una estandarización de los procedimientos y una cultura de seguridad institucional implementada por la normativa vigente, favorecen estas acciones operacionales. Los aspectos económicos del prestador y del asegurador inciden en la planeación y ejecución de esta modalidad de trabajo. Conclusión. La realización segura y el éxito de un programa de cirugía en horario no convencional dependen de la posibilidad de alinear los intereses de los actores participantes en el proceso

Introduction. Waiting lists for high-prevalence surgeries are the product of limited supply due to a high demand for surgical days. They have an impact on patients' medical conditions and emergency consultation. In response, additional surgical spaces have been incorporated at unconventional times. Its growing implementation, although controversial, is increasingly recognized as a new normal in surgery. There is limited documentation of the effectiveness of the measure due to the complexity and interests of the participants. Methods. The perspective of the actors involved in an extended hours surgery program was analyzed from a critical and reflective position, establishing the possible barriers, and facilitating elements of a policy focused on procedures during unconventional hours. Possible research opportunities on the topic are also described. Discussion. Surgical programs at unconventional times involve an analysis of the determinants of their feasibility and success to establish the relevance of implementation. The availability of operating rooms, a standardization of procedures and a culture of institutional security implemented by current regulations, favor these operational actions. The economic aspects of the provider and the insurer affect the planning and execution of this type of work. Conclusion. The safe realization and success of a surgical program in unconventional hours depend on the possibility of aligning the interests of the actors involved in the process

Optimization of Growth Parameters for Enhancing the Production of Biosurfactants from Pediococcus pentosaceus S-2

Numerous Lactic acid bacteria (LAB) have been found to be capable of synthesizing surface-active compounds i.e biosurfactants. These are amphiphilic compounds produced by microorganisms on their cell surface or secreted extracellularly that have a tendency to reduce surface and interfacial tension. In the present study, different process parameters including nitrogen and carbon source, pH, temperature, aeration and agitation were optimized to maximize the production of biosurfactants from Pediococcus pentosaceus S-2. Xylose (1.5%) and yeast extract (1.5%) act as better carbon and nitrogen sources respectively for the production of biosurfactants. Maximum biosurfactant yield was observed at pH 6, a temperature of 35o C, an agitation rate of 200 rpm and with inoculum size of 3%. The high yield of biosurfactants produced from Pediococcus pentosaceus S-2 by utilizing media supplemented with whey under optimized conditions.

Prueba de microneutralización para la detección de anticuerpos contra el virus dengue serotipo 2

Objetivo: Optimizar la prueba de microneutralización (MNT) para detección de anticuerpos neutralizantes contra el virus dengue serotipo 2 (DENV-2) en la línea celular Vero-76. Materiales y métodos: Se evaluaron diferentes concentraciones celulares (0.6 x105 cel/mL, 0.9 x105 cel/mL, 1.2 x105 cel/mL), porcentajes de 2 %, 3 % y 4 % de suero bovino fetal (SBF), número de pasajes del stock de virus y los días de incubación. La semilla viral se confirmó por RT-qPCR. El DENV-2 se propagó realizando 5 pasajes en células Vero-76, seguidamente se tituló el virus en placas de 96 pozos y se evaluaron 2 métodos de infección celular: monocapa y células en suspensión, además se determinó el día óptimo de coloración de las células. Obtenidos los resultados, se procesaron mediante MNT para DENV-2 las siguientes muestras: 5 sueros negativos a DENV-2 y YFV (Virus de la Fiebre Amarilla), 5 sueros negativos de anticuerpos a DENV-2 y positivos de anticuerpos a YFV y 5 sueros positivos de anticuerpos a DENV-2 seleccionados mediante la prueba de neutralización por reducción de placas (PRNT). Resultados: El método óptimo para MNT utilizó células en suspensión (0.9 x 105 cel/mL), 2 % de SBF y semilla viral pasaje 5. La mínima dilución capaz de diferenciar una muestra positiva a DENV-2 fue 1:40 y el tiempo de incubación para la MNT para DENV-2 fue de 10 días. Conclusión: La MNT con el método de células en suspensión y medio de cultivo con 2 % de SBF permite detectar anticuerpos neutralizantes IgG contra DENV-2 con resultados confiables, pudiendo analizar un mayor número de muestras con ahorro de materiales.

Objective: To optimize the microneutralization test (MNT) for the detection of neutralizing antibodies against serotype 2 of dengue fever virus (DENV-2) in a Vero-76 cell line. Materials and methods: Different cell concentrations were assessed (0.6 X 105 cells/mL, 0.9 X 105 cells/mL, and 1.2 x 105 cells/mL) with 2%, 3%, and 4% fetal bovine serum, virus stock passage number, and incubation days. Viral particles were confirmed using RT-qPCR. DENV-2 disseminated with 5 passages in Vero-76 cells, then, the virus was titrated in 96-well plaques, and two methods for cell infection were evaluated: single layer, and suspended cells. Also, the optimum day for cell staining was determined. Once results were obtained, the following samples were processed using MNT for DENV-2: five sera negative for DENV-2 and yellow fever virus (YFV), five sera negative for antibodies against DENV-2 and positive for antibodies against YFV, and five sera positive for antibodies against DENV-2 that were selected using the plate reduction neutralization test. Results: The optimum method for MNT used suspended cells (0.9 X 105 cells/mL), 2% fetal bovine serum, and viral particles at the 5th passage. The minimal dilution able to differentiate a positive sample for DENV2 was 1:40, and the MNT incubation time for DENV-2 was ten days. Conclusion: MNT with the cell suspension method and a culture medium with 2% fetal bovine serum allows the detection of IgG neutralizing antibodies against DENV-2 with reliable results, so that larger sample sizes may be assessed, saving materials to be used.

Simultaneous detection of thirteen exons of dystrophin gene by optimized multiplex PCR assay to screen Duchenne/Becker muscular dystrophy

Advancements in Polymerase Chain Reaction (PCR) technology and other techniques like Deoxyribonucleic acid (DNA)signal and target amplification have become key procedures in molecular diagnostics. PCR enables the synthesis of nucleic acids in vitro through which a DNA segment can be specifically replicated in a semiconservative way that sets forth deletion and mutation analysis. Multiplex PCR (M-PCR) is beneficial over standard and long PCR as this can amplify more than one locus using the respective primer sets. In harmony with this, the present study aimed to optimize M-PCR followed by its chemistry and condition to screen Duchenne Muscular Dystrophy (DMD) [OMIM #310200] and Becker Muscular Dystrophy (BMD) [OMIM #300376]. Muscular Dystrophies (MDs) are a broad group of hereditary, progressive, and degenerative disorders of muscles. X-linked recessive D/BMD are caused by mutation/s in the dystrophin gene [OMIM #300377] that encodes for dystrophin protein [UniProt#P11532]. As dystrophin is the human metagene with 79 exons, mutational analysis is very challenging. Chamberlain set (10 plex), Beggs set (9 Plex), and Kunkel set (7 Plex) is used for many years to diagnose this condition. However, in this study, Beggs set is customized with 13 exons to screen DMD gene mutation in a single reaction. Optimization of M-PCR was designed with many physicochemical parameters. According to the literature and after many appraisals the present study demonstrated the most sufficient concentration of various chemical components and optimal cycling conditions to optimize the modified Beggs set (13 Plex). 50 µL PCR reaction includes primer(s) (0.3–0.5 µM each), dNTP mixture (160 µM each), Dream Taq buffer (1X), Taq DNA polymerase (6U/50 µL), DNA template (250 ng/50 µL), BSA (0.4 µg/µL), and MgCl2 (1.4 mM). To get the most effective results cyclic conditions obtained were 10 min initial denaturation at 94°C, 62°C annealing temperature, and 35 PCR cycles at 72°C extending temperature. Consequently, the study successfully formulated a less expensive and simple approach for >3000 bp that was used to screen D/BMD. Finally, a developed M-PCR mix with a unique combination of specificity and sensitivity coupled with great flexibility has led to a true revolution in molecular diagnostics.

Optimización del control interno de calidad de RT-PCR en tiempo real para detección cualitativa de SARS-CoV-2

Objetivo: Optimizar el control interno de calidad de RT-PCR en tiempo real para detección cualitativa de SARS-CoV-2, utilizando los valores Cq de controles negativos y positivos. Material y método: Estudio prospectivo-longitudinal. La muestra estuvo constituida por 143 valores Cq para los controles negativos de alicuotado y extracción, así como para el control positivo. Se analizó la distribución normal de los valores Cq mediante la prueba de Anderson-Darling (AD) y se aplicaron pruebas de aleatoriedad. Se calculó límites de control a partir de 51 valores Cq, para luego, mediante gráficas de control, monitorizar 92 valores Cq obtenidos desde noviembre del 2020 hasta marzo del 2021. Se evaluó aceptación de lote e índices Cpk como indicadores de optimización. Los cálculos se hicieron con el programa Minitab. Resultados: Se aceptaron los lotes de valores Cq y se obtuvieron índices Cpk superiores a 1.33 para los tres tipos de control. Discusión: No existen estudios publicados que apliquen control estadístico de calidad a la detección cualitativa de SARS-CoV-2. Conclusiones: Es posible utilizar los valores Cq de los controles para optimizar el control interno de calidad de RT-PCR en tiempo real para detección cualitativa de SARS-CoV-2, como si se tratara de una técnica de tipo cuantitativo.

Objective: To optimize the internal quality control of real-time RT-PCR for the qualitative detection of SARS-CoV-2, using the Cq values ​​of negative and positive controls. Material and method : Prospective-longitudinal study. The sample consisted of 143 Cq values for the negative aliquot and extraction controls, as well as for the positive control. The normal distribution of Cq values ​​was analyzed using the Anderson-Darling (AD) test and randomness tests were applied. Control limits were calculated from 51 Cq values, and then, using control charts, to monitor 92 Cq values ​​obtained from November 2020 to March 2021. Lot acceptance and Cpk indices were evaluated as optimization indicators. The calculations were made with the Minitab program. Results: The batches of Cq values ​​were accepted and Cpk indices higher than 1.33 were obtained for the three types of control. Discussion : There are no published studies that apply statistical quality control to the qualitative detection of SARS-CoV-2. Conclusions : It is possible to use the Cq values ​​of the controls to optimize the internal quality control of real-time RT-PCR for qualitative detection of SARS-CoV-2, as if it were a quantitative technique.

Effect of dwell time deviation constraint on the three-dimensional brachytherapy plans for cervical cancer / 中华放射肿瘤学杂志

Objective:To investigate the effect of dwell time deviation constraint of inverse optimization on the quality and position error robustness of three-dimensional (3D) brachytherapy plans for cervical cancer.Methods:A total of 20 patients with cervical cancer receiving 3D brachytherapy treatment in Xiangya Hospital Central South University from August 2020 to August 2021 were retrospectively selected. All plans were designed using the Eclipse treatment planning system, and the dwell time deviation constraint parameter smooth value in the system were set to 0.00, 0.25, 0.50, 0.75, and 1.00, respectively. An inverse dose volume optimization algorithm was used to generate plans with various smooth values, and the optimization conditions were the same as the original clinical plans. Key dosimetric metrics and total dwell time differences were comparatively analyzed. The applicators were intentionally subjected to position errors (0.2-1.0 cm) in 6 directions (left-right, anterior-posterior, head-foot), and the effect of various smooth values on plan quality and robustness was assessed. There were 133 plans per case and 2 660 plans for 20 patients. The results were statistically analyzed using the Wilcoxon signed-rank nonparametric test.Results:As the smooth value was increased, the modulation factor was gradually decreased and the D 2 cm3 of the bladder and rectum was increased. Plans with smooth values of 0.25, 0.50, 0.75, 1.00 had modulation factors of 0.72±0.09, 0.63±0.08, 0.55±0.08, 0.51±0.06, respectively, lower than 0.75±0.05 of the plan with the smooth value of 0.00, and all differences were statistically significant ( P=0.004, 0.002, 0.002, 0.002). The bladder D 2 cm3 of plans with smooth values of 0.50, 0.75, 1.00 were (475.4±41.0) cGy, (483.7±46.2) cGy, and (489.0±46.8) cGy, respectively, higher than (469.8±41.8) cGy of the plan with the smooth value of 0.00, with statistically significant differences (all P=0.002). The rectum D 2 cm3 of plans with smooth values of 0.50 and 0.75 plans were (413.2±93.3) cGy and (418.6±96.4) cGy, both higher than (410.2±91.5) cGy of the plan with the smooth value of 0.00, with statistically significant differences ( P=0.006, 0.010). When positional errors were introduced, the high risk clinical target volume (HR-CTV) D 90% was close for different smooth plans at most positional errors, and the differences were not statistically significant. The organs at risk D 2 cm3 of plans with the smooth value of 0.00 was lower than those of plans with other smooth values, and for the bladder and rectum, the differences were statistically significant at most positional errors (all P<0.01). Conclusions:The dwell time deviation constraint parameter exerts significant effect on the plan quality, and the smaller the value of the constraint parameter, the higher quality of the plan. The dwell time deviation constraint parameter has slight impact on the positional error robustness of dosimetric indices of targets and key organs at risk.

The feasibility of individualized primary CTV for lateralized nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective:To investigate the feasibility of individualized primary clinical target volume (CTV) delineation in intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC).Methods:Clinical data of 87 consecutive patients newly diagnosed with lateralized NPC in Jiangsu Cancer Hospital between October 2016 and February 2018 were retrospectively analyzed. Lateralized NPC is defined as tumor invasion not exceeding the contralateral wall. According to the tumor spread, the primary CTV was optimized as follows: CTV2 only covered the medial part of the contralateral pterygopalatine fossa, whereas the contralateral foramen oval was not included; on the level of parapharyngeal space, the contralateral side of CTV only covered the posterior lateral lymph nodes, whereas the contralateral internal jugular vein was not regularly covered. Failure patterns and 5-year survival [local control rate (LCR), progression-free survival (PFS) and overall survival (OS)] were evaluated by Kaplan-Meier method. Paired t-test and rank-sum test were used to analyze the dose variation in the optimized region and adverse reactions. Results:The median follow-up time was 59.5 months. The 5-year LCR, PFS, and OS were 98.9%, 86.5% and 92.1%, respectively. There was no local recurrence in the optimized area of CTV. Dosimetric comparison results showed that the doses of parotid gland, temporal lobe, cochlea and middle ear on the contralateral side were reduced by 13.45%, 9.14%, 38.83%, and 29.36%, respectively. Four cases (4.6%) developed grade 3 hearing loss, all on the ipsilateral side. The optimized scheme significantly alleviated the hearing loss on the contralateral side compared to that on the ipsilateral side ( P<0.001). Other grade 3 late adverse reactions included cranial nerve injury, subcutaneous fibrosis in the neck and visual impairment, with 1 case each. Conclusion:Individualized primary CTV for lateralized NPC is feasible and safe, with obvious dosimetric advantages and reduced adverse reaction rate, which is worthy of clinical promotion.

Application of the second derivative-based small monitor unit beam deletion optimization to CyberKnife planning of heads / 中华放射医学与防护杂志

Objective:To investigate the effects of different small monitor unit (MU) beam deletion optimization method in the CyberKnife treatment planning system on the calculated planned dose to brain tumors.Methods:A total of 17 patients with brain metastases treated in our hospital from June, 2021 to February, 2022 were selected for this study. A treatment plan was designed for each patient using the multiPlan system in the CyberKnife VSI system as the group without optimization. To improve the efficiency, the generated original plans should be optimized first by deleting some small MUs, forming an experience group and an optimization group for each patient. For the experience group, beams below 30 MU were deleted according to experience. For the optimization group, beams below the MU value calculated based on the second derivative method were deleted. Finally, the parameters of the two groups were statistically compared. The main evaluation parameters included the node number, the beam number, the total number of MUs, the estimated treatment duration, doses to 2% and 95% planning target volumes (PTV D2 and PTV D95), average dose to PTV ( Dmean), average dose to brain tissue ( Dmean-Brain), conformity index (CI), new conformity index (nCI), gradient index (GI), coverage, and the maximum doses to the brainstem and left and right lens ( Dmax-BS, Dmax-LL, and Dmax-RL), and the average doses to the dose shells 20 mm and 40 mm away from PTV (Shell20 and Shell40). Results:The two optimization method met the requirements for the prescription dose delivery to more than 98% PTV. There were statistical differences in the node number ( H = 7.97, P< 0.05) and estimated treatment duration ( H = 6.60, P < 0.05) among the group without MP optimization, the experience group, and the optimization group, with the estimated treatment duration and node number of the optimization group less than those of the group without MP optimization ( P < 0.05). There were no statistically significant differences in other parameters among the three groups ( P > 0.05). The PTV was moderately positively correlated with the treatment duration ( r=0.79, P < 0.01) and beam number ( r=0.78, P < 0.01) of the experience group, and was also moderately positively correlated with the treatment duration ( r=0.69, P < 0.01) and beam number ( r=0.71, P < 0.01) of the optimization group. Conclusions:For the CyberKnife planning of heads, the small MU beam deletion optimization method based on the second derivative can further shorten the treatment duration while ensuring no significant differences in the distribution of doses to organs at risk and targets. Moreover, this method is more effective in optimizing the plans for a large PTV volume.

A metaheuristics-based automatic planning method for intensity-modulated radiation therapy / 中华放射医学与防护杂志

Objective:To establish a metaheuristics-based automatic radiotherapy treatment planning method (ATP-STAR) and verify its effectiveness.Methods:The main process of the ATP-STAR method was as follows. First, the optimization parameters were vectorized for encoding and corrected using Gaussian convolution. Then, the candidate optimization parameter vector set was selected through simulated annealing. Finally, the optimal combination of optimization parameters was determined by combining the field fluence optimization to achieve automatic trial-and-error. Twenty cases with large individual differences in tumors were selected for testing. Clinical physicists with more than five years of experience were invited to perform manual planning. Both the manual and ATP-STAR plans were made utilizing the matRad open source software for radiation treatment planning, with the fields and prescribed doses consistent with those of the clinical treatment plans. The dosimetric differences of target volumes and organs at risk between the ATP-STAR and manual plans for different diseases were analyzed.Results:For the target volumes, the ATP-STAR plans showed superior homogeneity compared with the manual plans (brain tumors: z = 2.28, P = 0.022; lung cancers: z = 2.29, P = 0.022; liver cancers: z = 2.11, P = 0.035). The conformability of the ATP-STAR plans was comparable to that of the manual plans for brain tumors and liver cancer and was slightly lower than that of the manual plans for lung cancer ( z = 2.29, P = 0.022). The comparison result of doses to organs at risk (OARs) between the manual plans and STAR plans were as follows. For OARs of brain tumors, the ATP-STAR plans decreased the mean left lens Dmean from 2.19 Gy to 1.76 Gy ( z = 2.28, P = 0.022), decreased left optic nerve Dmean from 11.36 Gy to 10.22 Gy ( z = 2.28, P = 0.022), decreased right optic nerve Dmax from 32.92 Gy to 29.97 Gy ( z = 2.10, P = 0.036), and decreased pituitary Dmax from 39.53 Gy to 35.21 Gy ( z = 2.29, P = 0.022). For OARs of lung cancer, the ATP-STAR plans decreased the mean spinal cord Dmax from 38.00 Gy to 31.17 Gy ( z = 2.12, P = 0.034), decreased the bilateral lungs Dmean from 8.51 Gy to 8.07 Gy ( z = 2.29, P = 0.022), and decreased cardiac Dmean from 3.21 Gy to 2.69 Gy ( z =2.29, P = 0.022). For OARs of liver cancer, the ATP-STAR plans decreased spinal cord Dmax from 18.19 Gy to 14.76 Gy ( z = 2.11, P = 0.035), decreased liver Dmean from 15.61 Gy to 14.45 Gy ( z = 2.11, P = 0.035), and decreased kidneys Dmean from 4.76 Gy to 4.04 Gy ( z = 2.10, P = 0.036). Conclusions:The proposed ATP-STAR method relies little on the experience of manual planning and thus is easy to be widely applied. This method is expected to improve the quality and consistency of IMRT plans and save clinical labor and time costs.

Research progress on the biological activity of pyrrole 1,2-α indole alkaloids / 中国基层医药

Pyrrole [1,2-α] indole is a novel fused heterocyclic skeleton, which is also the basic structural unit and synthetic intermediate of many natural active products and drugs. Pyrrole [1,2-α] indole heterocyclic derivatives have attracted much attention in organic synthesis and medicinal chemistry because of their extensive and marked biological activities. Plant extracts have always been an important source of active compounds. At present, the alkaloids based on the pyrrole [1,2-α] indole heterocyclic structure discovered and isolated from plant extracts include isatisine, isoborreverine, flinderoles, polyavolensin and yuremamine. This paper reviews the research progress on the biological activity of pyrrole [1,2-α] indole heterocyclic derivatives and has found that pyrrole [1,2-α] indole heterocyclic derivatives have a good development prospect in screening active compounds and developing candidate drugs.

Design and practice of a blended teaching mode based on SPOC: taking the teaching of medical statistics as an example / 中华医学教育探索杂志

Simply relying on the introduction of online teaching resources on the platforms such as Chinese University Massive Open Online Course (MOOC) to carry out online teaching, it is easy to encounter problems that the teaching resources are inconsistent with the learning situation and teaching syllabus of the students majoring in medical statistics of Binzhou Medical University, the lack of interaction among students, and the untimely teaching feedback. Therefore, on the basis of integrating the MOOC resources, we established asynchronous small private online course (SPOC) online curriculum resources for medical statistics that were suitable for the students of our school. The blended teaching mode of "SPOC+QQ living broadcast" was carried out. Before and after the implementation, two rounds of questionnaires were conducted to understand students' teaching and learning needs and teaching effect evaluation of online teaching, and then the teaching mode was optimized. The results show that the blended teaching mode of "SPOC + QQ living broadcast" designed in this study has the advantages of rich teaching resources, high enthusiasm of students, flexible teaching interaction, timely teaching feedback, and diversified teaching evaluation, which provides a reference for the better development of online and offline blended teaching reform in the future.

Overall planning and optimization: characteristics analysis of the medical doctoral supervisor and consideration of the current situation of enrollment / 中华医学教育探索杂志

This study has combed and analyzed the characteristics of medical doctoral supervisors and the enrollment status from 2015 to 2018 in Tongji University School of Medicine. The results show that the distribution of doctoral supervisors' age, gender and professional title is relatively balanced. The enrollment situation shows the clustering trend. There are obvious differences in enrollment among clinical medical disciplines, and the scales of doctoral supervisors and doctoral students are not matched and unevenly distributed. It is essential to give an overall consideration in discipline resources and optimize enrollment allocation, for improving the construction of doctoral supervisors and the quality of doctoral training.

Value of generalized equivalent uniform dose optimization in radiotherapy for chest malignant tumors / 中国辐射卫生

Objective To explore the value of generalized equivalent uniform dose (gEUD) optimization in radiotherapy for chest malignant tumors. Methods Sixty patients with chest malignant tumors who were treated in Center for Tumor Radiotherapy, Chizhou Municipal People’s Hospital, Anhui Province, China from October 2021 to June 2022 were enrolled; each patient underwent tumor localization with a conventional fixed computed tomography scan. The patients were divided into two groups using the same field direction and weight in the Varian Eclipse 15.6 planning system. The first group was planned using the conventional physical dose-volume objective function plus the Upper gEUD objective function, with organs at risks (OARs) optimized with the EUD values suggested by the Varian Eclipse 15.6 planning system. The second group only adopted the conventional physical dose-volume objective function for OARs optimization. The two groups were compared for the radiation doses delivered to the OARs. Results Compared with the conventional physical dose-volume objective function alone, the addition of Upper gEUD objective function resulted in no significant difference in lung V5Gy, but resulted in significant reductions in V20Gy and mean dose in the lungs; some reductions in V30Gy, V40Gy, and mean dose in the heart; and significant reductions in the maximum dose in the spinal cord. Conclusion The gEUD objective optimization can effectively protect the normal tissue in the radiotherapy for chest malignant tumors and thus is recommended in radiotherapy planning.

Optimization of the preparation process of Soft-shelled turtle blood lyophilized powder using Box-Behnken response surface methodology / 中国药房

OBJECTIVE To optimize the preparation process of Soft-shelled turtle blood lyophilized powder （STBLP）， and to provide a reference for improving the availability and quality stability of soft-shelled turtle blood （STB）. METHODS STBLP was prepared with vacuum freeze-drying. Taking the solubility as the index， the preparation process parameters of STBLP were optimized by single factor experiment and Box-Behnken response surface method. RESULTS The optimal freeze-drying process for STBLP was obtained： pre-freezing time of 4 h， total drying time of 13 h （before at 0 ℃）， and resolution drying temperature of 25 ℃. The average solubility of 3 batches of STBLP prepared according to the optimal process was 95.72% （RSD＝0.68%， n＝3）， the relative error of which was －0.97% to the theoretical solubility （96.66%）. CONCLUSIONS Optimized lyophilization process in this study are stable and feasible， the solubility of the prepared sample is high.

Application practice of drug clinical comprehensive evaluation thinking in management of temporary drug purchase in hospital / 中国药房

OBJECTIVE To explore the construction of a new scientific management model for temporary drug purchase，and to provide a reference for hospitals to improve the level of rational drug use. METHODS Guided by clinical diagnosis and treatment needs and patient medication safety， our hospital carried out the whole process management practice of temporarily purchased drugs by optimizing the review process， creating a review team， formulating pre-audit and post follow-up evaluation standards based on comprehensive drug evaluation， and evaluated the practice effect through the number of temporary purchase applications， implementation rate， drug structure optimization and other indicators. RESULTS Since January 2021， our hospital had implemented a new mode of temporary drug purchase management. By December 2022， clinical pharmacists had reviewed 111 temporary drug procurement applications， effectively intercepted 13 irrational drug use applications （11.71%）， reduced the overall implementation rate of temporary drug procurement by 8.36%，and proposed five batches of drug structure optimization suggestions； 24 drugs were successively introduced such as camrelizumab，sorafenib，busulfan. After optimizing the management mode，the number of temporary drug procurement applications decreased by more than half from 133 in 2019 and 138 in 2020 to 66 in 2021 and 45 in 2022. CONCLUSIONS The model is helpful to optimize the hospital drug catalog， strengthen rational drug use，ensure the safety of patients’ drug use， and fully reflects the professional value of clinical pharmacists in hospital pharmacy management and rational drug use.

Optimization and simulation of maneuverability and stability of electric wheelchair based on three degrees of freedom model / 中国康复理论与实践

ObjectiveTo propose a three-degree-of-freedom model of electric wheelchair, to optimize the steering stability of the wheelchair. MethodsBased on the two degrees of freedom vehicle model and considering the influence of body inertia and lateral wind, the wheelchair roll angle was introduced to establish the three degrees of freedom steering model of wheelchair. The lateral velocity, centroid sideslip angle, yaw rate and body roll angle response of the motor angular velocity input under different working conditions were simulated and analyzed respectively. Taking KS2 electric wheelchair as an example, the wheelchair steering experiment was designed to verify the rationality and feasibility of the model, and the optimization effect of the model algorithm on the wheelchair handling and stability. ResultsThe maneuverability and stability of the electric wheelchair with three degrees of freedom model algorithm were significantly improved, and the response curve was smoother. The smaller the |VL-VR|/t was, the better the handling stability was when the left and right motors of the wheelchair had the same steering direction. When |VL-VR|/t was the same, the steering maneuverability was better on the reverse rotation of the motor, but the handling stability also decreased. ConclusionThe simulation analysis is in good agreement with the experimental results, which verifies that the model is reasonable and feasible. The model algorithm can better optimize the handling stability of electric wheelchairs, and can be generally applied to study and analyze the handling stability of different wheelchairs when they turn.