Influence of the dilution method on the intraocular duration of C3F8 in vitrectomy for macular hole: a randomized clinical trial

ABSTRACT Purpose: To compare the injection of small amounts of undiluted C3F8 with the traditional gas injection in vitrectomy for macular hole treatment. Methods: This clinical trial included 26 individuals divided into two groups. Group 1 received an intravitreal injection of 0.9-1.0 mL of 100% C3F8, and Group 2 received 15-20 mL of 20% C3F8. Results: The median intraocular gas duration was 31 days in Group 1 and 34 in Group 2. The median letter gains in corrected distance visual acuity for the 26th postoperative week were 20 letters in Group 1 and 12.5 in Group 2. The median intraocular pressure was normal in both groups. Primary anatomical success was 11/13 in both groups. Conclusions: The use of C3F8 gas in a small undiluted volume is an alternative that slightly reduces the duration of the gas without negatively affecting the anatomical and visual response.

Intraoral administration of probiotics and postbiotics: An overview of microorganisms and formulation strategies

Abstract The last decade provided significant advances in the understanding of microbiota and its role in human health. Probiotics are live microorganisms with proven benefits for the host and were mostly studied in the context of gut health, but they can also confer significant benefits for oral health, mainly in the treatment of gingivitis. Postbiotics are cell-free extracts and metabolites of microorganisms which can provide additional preventive and therapeutic value for human health. This opens opportunities for new preventive or therapeutic formulations for oral administration. The microorganisms that colonize the oral cavity, their role in oral health and disease, as well as the probiotics and postbiotics which could have beneficial effects in this complex environment were discussed. The aim of this study was to review, analyse and discuss novel probiotic and postbiotic formulations intended for oral administration that could be of great preventive and therapeutic importance. A special attention has been put on the formulation of the pharmaceutical dosage forms that are expected to provide new benefits for the patients and technological advantages relevant for industry. An adequate dosage form could significantly enhance the efficiency of these products.

Textual Research on Principle of Dose Conversion in Ancient Famous Classical Formulas / 中国实验方剂学杂志

Due to the difference between the system of weights and measures， and the dosage of clinical prescriptions of traditional Chinese medicine in various historical periods， the dosage and conversion standard of prescriptions in past dynasties are different. Therefore， when discounting the dosage of famous classical formulas， the principles of inheriting the essence， making the past serve the present， linking the past and the present， and forming a consensus should be followed， firstly， the dosage of the prescription was converted according to the weights and measures system of the past dynasties. If the converted dosage significantly exceeds the provisions of the 2020 edition of Chinese Pharmacopoeia， then on the premise of ensuring that the proportion of the original prescription drug dosage remains unchanged， the conversion shall be based on expert consensus and drug safety evaluation. For drugs measured in non-standard units， a conversion range is provided based on comprehensive literature analysis and physical measurements. For the conversion of service volume， the original text was used as the basis for the conversion with reference to the measurement standards of different eras. If the original dosage is not clear， the converted dosage will be determined based on the historical evolution of the formula， referring to relevant ancient books， and combining modern applications. Eventually， the converting standard for famous classical formulas was determined as follows：during the Han and Tang dynasties， one Liang（两） was equivalent to 13.8 g and one Sheng（升） was equivalent to 200 mL， in the Tang dynasty， one Fen（分） was equivalent to 3.45 g， during the Song， Jin and Yuan dynasties， one Qian（钱） was equivalent to 4.13 g and one Zhan（盏） was equivalent to 300 mL， during the Ming and Qing dynasties， one Qian（钱） was equivalent to 3.73 g， and one Bei（杯） and one Zhong（盅） were equivalent to 200 mL. For drugs recorded in non-standard units of measurement， it is necessary to conduct actual measurements to determine their conversion standards based on comprehensive analysis to determine their origin. If necessary， different records of the dosage of drugs with the same or similar efficacy and indications in medical books of similar ages can be used to assist in determining the conversion standards. The analysis of the principle of dosage conversion for Chinese medicine is helpful for the clinical application and development of famous classical formulas.

Research progress in the route of administration and corresponding dosage form of triamcinolone acetonide / 中国药房

As a glucocorticoid drug with wide clinical application， triamcinolone acetonide can be administered by multiple routes， such as eye， nose， joint cavity， and skin， for the treatment of various local diseases such as arthritis， macular edema， rhinitis， and urticaria. As a drug with extremely low solubility in water， the dose form of triamcinolone acetonide is closely correlated with administration route and site. The dosage form of triamcinolone acetonide administered via injection（including joint cavity injection， vitreous injection， suprachoroidal injection， intramuscular injection） is mainly suspension， and the representative drugs include Kenalog-40®， Zilretta®， Triesence®， Xipere®， etc.； the dosage forms of nasal mucosal administration are mostly sprays， and the representative drug is Nasacort®； the dosage forms of oral mucosal administration are mostly patches， ointments and creams， and the representative drug is Oracort®； the dosage forms for transdermal administration are mostly ointments， creams and lotions， and the representative drugs include Trianex®， Teva-Triacomb®， etc. At present， the research on dosage forms of triamcinolone acetonide by various administration routes mainly focuses on the construction of delivery carriers， the addition of cosolvents or the use of new delivery tools.

Usage and Dosage Analysis and Countermeasures for Development of Compound Preparations of Han Dynasty Famous Classical Formulas / 中国实验方剂学杂志

In order to provide a reference basis for the development of relevant compound preparations， this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives， and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics， decoction methods， administration and dosage， and combining conversion methods of weights and measures by ancient medical practitioners， along with the dosage and administration of the listed Han dynasty famous classical formulas， it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents［13.8 g per Liang（两）］， ensuring the safe and effective medication of these formulas. After combing， it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty， the administration is flexible. The crude drug amount per administration serves as the foundational dose， with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study， it is recommended that when developing compound formulations of famous classical formulas in Han dynasty， the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose， with the frequency of administration described within a range（1 to N times per day， where N is the maximum number of administrations as per the original text）. The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies， where the dosage per administration serves as the basis for toxicity research， and the toxicity profile at the maximum administration frequency should be observed， providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.

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.

Dosis de radiación por radiografías y factores asociados en neonatos de la Unidad de Recién Nacidos del Hospital Universitario San Ignacio, Bogotá, Colombia / X-ray radiation dose and associated factors in neonates from the newborn unit of Hospital Universitario San Ignacio, Bogotá, Colombia

Introducción. Las radiografías continúan usándose ampliamente, subestimando los riesgos. Esto sucede, especialmente, en las unidades de cuidado neonatal, lo que implica que los neonatos reciben una dosis de radiación ionizante mayor que los adultos. Objetivo. Cuantificar las dosis de radiación recibidas al tomar radiografías y evaluar los posibles factores asociados con el aumento de la dosis. Materiales y métodos. Se llevó a cabo un estudio observacional de 160 neonatos de la Unidad de Recién Nacidos del Hospital Universitario San Ignacio, Bogotá, Colombia. Se consideró como variable dependiente la dosis de entrada en piel por cada radiografía. Se hizo la caracterización de los pacientes, seguida de un análisis multivariado con regresión lineal múltiple para identificar factores asociados. Resultados. Se analizaron 160 pacientes y 492 radiografías en total. Entre los hallazgos más frecuentes, se encuentran: pacientes de sexo masculino (n=87; 54,4 %), nacimiento por cesárea (n=122; 76,3 %) e indicación de toma de radiografías por dificultad respiratoria (n=123; 24,9 %). El 1,8 % (n=9) de los pacientes no tenían una indicación para la toma de la radiografía. La radiografía más frecuente fue la de tórax (n=322; 65,4 %). La mayoría de las radiografías se tomaron con el equipo computarizado (n=352; 71,5 %) y no con el digital (n=140, 28,4 %). La mediana de la dosis de entrada en piel con el equipo computarizado fue de 0,112 mGy (0,022; 0,134 mGy) y, con el equipo digital, de 0,020 mGy (0,019, 0,022 mGy). Conclusiones. Se cuantificaron las dosis de radiación absorbida en neonatos, general y específica, con el equipo computarizado y el digital. Se identificaron mayores dosis con el equipo computarizado. Se reconoció la interacción entre el equipo computarizado con menores edades gestacionales corregidas como principal factor para el aumento de la dosis. Además, se reconoció la relación entre el equipo computarizado y una menor edad gestacional corregida, como principal factor para una mayor dosis.

Introduction. Radiographs are still widely used, underestimating the risks. This situation is frequent in neonatal care units, generating radiation doses than in adults. Objective. To quantify the received radiation doses when performing radiographs on neonates and the possible factors associated with higher doses. Materials and methods. We performed an observational study of 160 neonates from the newborn unit of the Hospital Universitario San Ignacio, Bogotá, Colombia. We considered the input dose of each radiograph as the dependent variable. Patients were characterized and a multivariate analysis with multiple linear regression was performed to identify associated factors. Results. We analyzed 160 newborns and 492 radiographs. The most frequent findings were male patients (n=87, 54.4%), cesarean delivery (n=122, 76.3%), and radiograph indication for respiratory distress (n=123, 24.9%). One-point eight percent of the patients (n=9) did not have radiograph indication. The most frequently taken radiograph was chest (322, 65.4%). Most radiographs were taken with a computerized equipment (n=352, 71.5%), compared to a digital one (n=140, 28.4%). The median input dose with computerized equipment was 0.112 mGy (0.022, 0.134 mGy), and with the digital equipment was 0.020 mGy (0.019, 0.022 mGy). Conclusions. The general and specific absorbed radiation doses were measured in neonates with a computerized and a digital equipment. We identified higher doses with the computerized equipment. In addition, it was recognized the correlation between computerized radiography equipment with lower corrected gestational ages as the main factor for dose increase.

Prospective evaluation of the effectiveness of combined treatment of macular edema secondary to retinal vein occlusion with intravitreal bevacizumab and dexamethasone implants / Estudo intervencionista prospectivo para avaliar a eficácia da associação do bevacizumabe intravítreo ao implante de dexametasona para edema macular secundário à oclusão da veia retiniana

ABSTRACT Purpose: To evaluate the effectiveness of in­­­travitreal bevacizumab injections following a single dexamethasone implant in the treatment of macular edema secondary to branch and central retinal vein occlusion. Methods: This was a prospective interventional non-comparative study, 44 eyes of patients with naïve macular edema related to branch and central retinal vein occlusion were treated with a dexamethasone implant. Patients were followed-up at four-week intervals from the second to the sixth month. If persistent or recurrent macular edema occurred during this period, the patient was treated with intravitreal bevacizumab injections on an as-needed basis. The outcome measures were best-corrected visual acuity and central macular thickness changes. Results: The mean best-corrected visual acuity changed from 0.97 ± 0.33 LogMAR at baseline to 0.54 ± 0.40 at the six-month post-implant examination (p<0.00001). Improvement ≥3 Snellen lines were seen in 20 eyes (45.54%). The mean central macular thickness at baseline was 670.25 ± 209.9 microns. This had decreased to 317.43 ± 112.68 microns at the six-month follow-up (p<0.00001). The mean number of intravitreal bevacizumab injections received in the six months post-implant was 2.32. The mean time from dexamethasone implant to first anti-VEGF injection was 3.45 months. Conclusions: Intravitreal bevacizumab injections following a single dexamethasone implant were found to improve best-corrected visual acuity and central macular thickness in patients with macular edema due to branch and central retinal vein occlusion at six months, with few intravitreal injections required.

RESUMO Objetivo: Avaliar a eficácia da combinação de in­jeções intravítreas de bevacizumabe em olhos com edema macular secundário à oclusão de ramo e da veia central da retina após um único implante de dexametasona. Métodos: Foi realizado um estudo prospectivo intervencionista não comparativo com 44 olhos de pacientes com edema macular relacionado à oclusão de ramo e veia central da retina, sem tratamento prévio e tratados com um único implante de dexametasona, que foram acompanhados em intervalos de quatro semanas do segundo ao sexto mês. Se fosse constatado edema macular persistente ou recorrente durante esse período, os pacientes eram tratados com injeções intravítreas de bevacizumabe em um regime ajustado conforme a necessidade. Foram estudadas a melhor acuidade visual corrigida e alterações da espessura macular central. Resultados: A média da melhor acuidade visual corrigida mudou de 0,97 ± 0,33 LogMAR iniciais para 0,54 ± 0,40 no exame de 6 meses (p<0,00001). Vinte olhos (45,54%) melhoraram 3 linhas de Snellen ou mais. A média da espessura macular central inicial foi de 670,25 ± 209,9 μm e diminuiu para 317,43 ± 112,68 μm na visita de 6 meses (p<0,00001). O número médio de injeções intravítreas de bevacizumabe em 6 meses foi de 2,32 e o tempo médio entre o implante de dexametasona e a primeira injeção de anti-VEGF foi de 3,45 meses. Conclusão: Injeções intravítreas de bevacizumabe após um único implante de dexametasona podem proporcionar um aumento da melhor acuidade visual corrigida e diminuição da espessura macular central aos 6 meses em pacientes com edema macular devido à oclusão de ramo e da veia central da retina, com poucas injeções intravítreas.

Radiation safety measures in diagnostic nuclear medicine, based on the potential radiation dose emitted by radioactive patients / Cuidados de radioproteção em medicina nuclear diagnóstica baseados no potencial de dose de radiação emitida por pacientes radioativos

Abstract Objective: To measure the potential radiation dose emitted by patients who have recently undergone diagnostic nuclear medicine procedures, in order to establish optimal radiation safety measures for such procedures. Materials and Methods: We evaluated the radiation doses emitted by 175 adult patients in whom technetium-99m, iodine-131, and fluorine-18 radionuclides were administered for bone, kidney, heart, brain, and whole-body scans, as measured with a radiation detector. Those values served as the basis for evaluating whole-body radiopharmaceutical clearance, as well as the risk for the exposure of others to radiation, depending on the time elapsed since administration of the radiopharmaceutical. Results: The mean time to clearance of the radiopharmaceuticals administered, expressed as the effective half-life, ranged from 1.18 ± 0.30 h to 11.41 ± 0.02 h, and the mean maximum cumulative radiation dose at 1.0 m from the patients was 149.74 ± 56.72 µSv. Even at a distance of 0.5 m, the cumulative dose was found to be only half and one tenth of the limits established for exposure of the general public and family members/caregivers (1.0 mSv and 5.0 mSv per episode, respectively). Conclusion: Cumulative radiation doses emitted by patients immediately after diagnostic nuclear medicine procedures are considerably lower than the limits established by the International Commission on Radiological Protection and the International Atomic Energy Agency, and precautionary measures to avoid radiation exposure are therefore not required after such procedures.

Resumo Objetivo: O objetivo deste trabalho foi levantar o potencial de dose de radiação emitida por pacientes em procedimentos diagnósticos, visando a estabelecer cuidados de radioproteção mais otimizados. Materiais e Métodos: Taxas de dose de radiação emitidas por 175 pacientes administrados com os radionuclídeos 99mTc, 131I e 18F para cintilografias óssea, renal, cardíaca, cerebral e corpo inteiro, foram mensuradas com um detector de radiação, servindo para avaliar o clareamento do radiofármaco no organismo e risco de exposição após administração dos radiofármacos. Resultados: O clareamento, representado pela meia-vida efetiva, variou de 1,18 ± 0,30 h até 11,41 ± 0,02 h e a dose de radiação máxima acumulada oferecida pelos pacientes a 1,0 m foi de 149,74 ± 56,72 µSv. Mesmo para distâncias de 0,5 m, as doses estimadas foram, respectivamente, duas e dez vezes inferiores ao nível de restrição para o público geral (1,0 mSv) e exposição médica (5,0 mSv/episódio). Conclusão: Doses de radiação oferecidas por pacientes em procedimentos diagnósticos são inferiores aos níveis de restrição recomendados pela International Commission on Radiological Protection e International Atomic Energy Agency, e assim, cuidados de radioproteção são geralmente desnecessários.

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

Gas tamponade followed by laser treatment for macular retinal detachment secondary to optic pit / Tamponamento com gás seguido de laser para descolamento de retina secundário à fosseta de disco óptico

ABSTRACT Purpose: The study aimed to describe anatomic and visual outcomes associated with perfluoropropane intravitreal injection followed by laser treatment for macular retinal detachment secondary to optic disc pit. Methods: A single-center, retrospective study. Medical records of all patients treated at a tertiary retina referral center were evaluated between 2011 and 2018 for congenital optic disc pit-associated macular detachment with 0.3 ml 100% perfluoropropane intravitreal injection followed by retinal laser photocoagulation along the temporal optic disc margin as the initial treatment. Results: Six patients with optic disc pit-associated macular detachment were identified, with postoperative follow-up ranging from 13 to 52 months (mean: 28 months). Spectral domain optical coherence tomography (SD-OCT) showed complete fluid resolution without recurrence in five of the six cases. Four cases showed complete reabsorption after Intravitreal perfluoropropane plus laser, one patient needed an extra procedure (pars plana vitrectomy with inner limiting membrane peeling and pedicle flap inversion over the temporal optic disc margin) to achieve complete fluid reabsorption, and one patient had persistent intraretinal fluid and denied additional surgeries. The time between the initial procedure and total fluid reabsorption varied from 6.5 to 41 months (mean: 19.5 months). Best-corrected visual acuity improved after surgery on the last follow-up visit in all cases. Conclusion: 100% perfluoropropane intravitreal injection followed by photocoagulation along temporal optic disc margin was associated with anatomic and visual improvement in most cases, representing an alternative treatment approach for optic disc pit-associated macular detachment.

RESUMO Objetivo: Descrever os resultados anatômicos e visuais associados à injeção intravítrea de perfluoropropano seguida de tratamento a laser para descolamento de retina macular secundário à fosseta do disco óptico. Métodos: Estudo retrospectivo em um único centro. Foram revisados os prontuários médicos dos pacientes com descolamento macular associado a fosseta do disco óptico congênito em um centro de referência terciário de retina entre 2011 e 2018. Todos receberam como estratégia de tratamento inicial injeção intravítrea de perfluoropropano 100% seguido por fotocoagulação a laser ao longo da margem temporal do disco óptico. Resultados: Foram identificados seis pacientes com descolamento macular associado a fosseta do disco óptico durante o período do estudo. O seguimento pós-operatório variou de 13 a 52 meses, com média de 28 meses. SD-OCT demonstrou resolução completa do fluido em cindo dos seis casos, sem recorrência. Quatro casos apresentaram reabsorção completa após perfluoropropano intravítreo associado a laser, e um paciente necessitou de procedimento adicional (vitrectomia via pars plana com peeling da membrana limitante interna e inversão do retalho do pedículo sobre a margem temporal do disco óptico) para obter reabsorção completa de fluidos. Um paciente apresentou fluido intrarretiniano persistente e negou tratamentos adicionais. O tempo entre o procedimento inicial e a resolução completa do fluido variou entre 6,5 a 41 meses, com média de 19,5 meses. A acuidade visual corrigida melhorou após a cirurgia, considerando a última consulta de acompanhamento em todos os casos. Conclusão: A injeção intravítrea de perfluoropropano 100% seguida de fotocoagulação ao longo da margem temporal da margem do disco óptico foi associada à melhora anatômica e visual na maioria dos casos e representa uma abordagem terapêutica alternativa para o descolamento macular associado a fosseta do disco óptico.

Bleaching gel volume influences hydrogen peroxide diffusion, inflammation, and the presence of nitric oxide in the pulp tissue: in vitro and in vivo model

Abstract Objective To assess whether bleaching gel volume influences chromatic changes, hydrogen peroxide (HP) diffusion, inflammation, and oxidative stress in the pulp tissue. Methodology A total of 60 bovine teeth were divided into four groups, according to bleaching gel volume (n=15): without gel (WG); V30 (30 µL of 35% HP); V60 (60 µL); and V120 (120 μL). HP diffusion analysis was performed in the first session (T1). Chromatic changes (ΔE, ΔE00, and WID) were assessed after the first (T1), second (T2), third (T3) sessions, and 15 d (T4) after the end of treatment. Moreover, 20 rats were randomly divided into four groups (n=10) and their upper first molars were treated with different gel volumes: control (no treatment); V2 (2 μL of 17.5% HP); V4 (4 μL); and V8 (8 μL). After 24 h, rats were euthanized and the specimens processed for histological and immunohistochemical (nitric oxide synthase) evaluation. Data were analyzed using the Wilcoxon and Mann-Whitney tests (p<0.05). Results In vitro (bovine teeth), chromatic changes were not influenced by bleaching gel volume, showing similar values in all groups and sessions, except for the control group (p<0.05). The V120 group had the highest HP diffusion values (p<0.05). In vivo (pulp tissue), the V4 and V8 groups showed the highest inflammatory infiltrate in the pulp and significant oxidative stress (p<0.05). Conclusion The adverse effects on the dental pulp related to HP diffusion, pulp inflammation, and oxidative stress depend on bleaching gel volume, while the bleaching effect is not proportional to the volume used.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅰ): classification of processing routes / 中国中药杂志

Oral solid dosage(OSD) occupies a key position in the market of Chinese patent medicines and new traditional Chinese medicines. Processing route is the foundation for the research and development of traditional Chinese medicine OSDs. On the basis of prescriptions and preparation methods of 1 308 traditional Chinese medicine OSDs recorded in the Chinese Pharmacopoeia, we summarized the patterns of processing routes of both modern dosage forms(tablets, granules, and capsules) and traditional dosage forms(pills and powder) and constructed a manufacturing classification system(MCS) based on the processing routes. Based on the MCS, statistical analyses were conducted respectively on medicinal materials, pharmaceutical excipients, extraction solvents in the pretreatment process, crushed medicinal materials, methods of concentration and purification, and methods of drying and granulation, aiming to uncover the process features. The results showed that each dosage form can be prepared via different routes with different processing methods of decoction pieces and raw materials for dosage preparation. The raw materials for dosage form preparation of traditional Chinese medicine OSDs included total extract, semi-extract, and total crushed powder, which accounted for different proportions. The raw materials for traditional dosage forms are mainly decoction pieces powder. Semi-extracts are the main raw materials for tablets and capsules, which account for 64.8% and 56.3%, respectively. Total extracts are the main raw materials for granules, with a proportion of 77.8%. Compared with tablets and capsules, traditional Chinese medicine granules with dissolubility requirements had a larger proportion of water extraction process, a higher proportion of refining process(34.7%), and a lower proportion of crushed medicinal mate-rials in semi-extract granules. There are four ways to add volatile oil to the modern dosage forms of traditional Chinese medicine. In addition, some new technologies and processes have been used in concentration, filtration, and granulation processes of traditional Chinese medicine OSDs, and the application of pharmaceutical excipients is diversified. The results of this study are expected to provide reference for the processing route design and upgrading of OSDs for new traditional Chinese medicines.

Conversion of traditional Chinese medicine (TCM) into nanomedicine:application of theory of unification of medicines and excipients / 中国中药杂志

In recent years, the use of active substances as excipients or as substitutes for other excipients in the design of modern drug delivery systems has received widespread attention, which has promoted the development of the theory of unification of medicines and excipients in the design of traditional Chinese medicine(TCM) preparations. Adopting the theory of unification of medicines and excipients to design drug delivery systems can reduce the use of excipients and thus the cost of preparations, reduce drug toxicity, increase drug solubility and biocompatibility, enhance synergistic effect, and realize targeted delivery and simultaneous delivery of multiple components. However, the research on the application of this theory in the modern drug delivery system of TCM preparations is still insufficient, with few relevant articles. In addition, the TCM active substances that can be used as the excipients remain to be catalogued. In this paper, we review the types and applications of the drug delivery systems with TCM active substances as excipients and describe their common construction methods and mechanisms, aiming to provide references for the in-depth research on the modern drug delivery systems for TCM preparations.

External Application Characteristics of Roots and Rhizomes of Chinese Herbal Medicines in Chinese Materia Medica / 中国实验方剂学杂志

ObjectiveTo collect and analyze the properties and application characteristics of external use of roots and rhizomes of Chinese herbal medicines in the Chinese Materia Medica（《中华本草》） to provide data references for the research on clinical external use of Chinese medicine， in order to provide data reference for clinical external use of traditional Chinese medicine（TCM）. MethodThe Chinese herbal medicines included in the Chinese Materia Medica were systematically screened. The inclusion criterion was the explicit mention of terms like "root", "rhizome", "root bark", "tuber", "tuberous root", etc. under the "Source" in the Chinese Materia Medica. Information on properties, flavors, meridian tropism, medicinal parts, fresh use, toxicity, efficacies and indications, and dosage of roots and rhizomes of Chinese herbal medicines was collected. The information was then entered into an Excel spreadsheet for statistical analysis. ResultThe Chinese Materia Medica records 2 662 roots and rhizomes of Chinese herbal medicines, of which 1 653 are suitable for external use. The predominant properties and flavors are cool, cold, bitter, pungent, and sweet. These Chinese herbal medicines mainly act on the liver, lung, and spleen meridians. The primary medicinal parts used include root, rhizome, and root bark. More than half of the roots and rhizomes of Chinese herbal medicines can be used in their fresh form. The main efficacies include clearing heat, removing toxins, resolving stasis, dispersing accumulation, resolving blood stasis and stopping bleeding, reducing swelling and alleviating pain, dispelling dampness and relieving pain. The main indications are skin sores, traumatic injuries, and rheumatic diseases. Common external application methods include poultice, decoction for washing, and applying powdered form. Most of these Chinese herbal medicines lack specific dosage guidelines for external use, with an emphasis on using an appropriate amount. ConclusionThe Chinese Materia Medica contains a wide range of roots and rhizomes of Chinese herbal medicines suitable for external use, with definite therapeutic effects, providing a broad perspective for the application of Chinese medicine externally. However, there are still problems such as unclear dosages and limited research. Further studies are necessary to better utilize the advantages of the external use of Chinese medicine.

Dosimetric comparison of intensity-modulated photon radiotherapy and intensity-modulated proton radiotherapy for non-small cell lung cancer / 肿瘤研究与临床

Objective:To investigate the difference of dose distribution between intensity-modulated photon radiotherapy (IMRT) and intensity-modulated proton radiotherapy (IMPT) in patients with non-small cell lung cancer.Methods:The clinical data of 8 patients with stage Ⅱ-Ⅲ non-small cell lung cancer who received radiotherapy in Ion Medical center of the First Affiliated Hospital of University of Science and Technology of China from November 2020 to April 2022 were retrospectively analyzed. IMRT and IMPT radiotherapy plans were created for each patient separately, the main evaluation indicators were targeted area dose distribution parameters [homogeneity index (HI), conformity index (CI) and the percent volume of volume wrapped by 95% and 100% of prescription dose profile in the targeted area (V 95% and V 100%)], and the average dose (D mean) to the organ at risk and the percent volume of a certain relative biological effect (RBE) dose exposure [D mean, V 5 Gy(RBE) and V 20 Gy(RBE) of ipsilateral lung, D mean, V 5 Gy(RBE) and V 20 Gy(RBE) of bilateral lung, D mean, V 30 Gy(RBE) and V 40 Gy(RBE) of heart, maximum dose (D max) of spinal cord, and D mean of esophageal]. Results:In comparison with IMRT, IMPT reduced the levels of dose parameters in bilateral lung, ipsilateral lung, spinal cord, esophagus, and heart with statistically significant differences (all P < 0.05), especially in D mean of bilateral lung [(4.1±1.8) Gy (RBE) vs. (6.9±1.9) Gy (RBE)], V 5 Gy(RBE) [(15.9±7.1) % vs. (28.5±8.6)%], V 20 Gy(RBE) [(7.4±3.5)% vs. (10.1±3.5)%], and D mean of ipsilateral lung [(9.1±4.5) Gy (RBE) vs. (11.9±3.3) Gy (RBE)], all decreased significantly (all P < 0.001), but the differences in the levels of targeted area dose distribution parameters between them were not statistically significant (all P > 0.05). Conclusions:For patients with non-small cell lung cancer, IMPT is superior to IMRT in the protection of bilateral lung, ipsilateral lung, spinal cord, esophagus and heart.

Effects of different moxibustion time on knee cartilage morphology and the expression of TNF-α and IL-10 in rats with knee osteoarthritis / 针灸推拿医学（英文版）

Objective:To observe the effects of different moxibustion time on cartilage morphology,tumor necrosis factor(TNF)-α and interleukin(IL)-10 of the knee joint in rats with knee osteoarthritis(KOA),and to explore the best treatment time of moxibustion for KOA.Methods:Healthy male Wistar rats were randomly divided into a blank group,a model group,a 15-minute-moxibustion group,a 30-minute-moxibustion group,and a 60-minute-moxibustion group,with 10 rats in each group.Except for the blank group,the KOA model was established in all groups by injecting sodium iodoacetate solution into the knee joint cavity of rats.Rats in the 15-minute-moxibustion group,the 30-minute-moxibustion group,and the 60-minute-moxibustion group were all treated with mild moxibustion intervention for 15 min,30 min,and 60 min,respectively at Neixiyan(EX-LE4)and Dubi(ST35)points near the patella,3 times a week for 4 weeks,12 times in total.Rats in the blank group and the model group were fixed for 30 min without moxibustion intervention.Macroscopic observation for the smoothness of knee cartilage surface was performed after the intervention.Hematoxylin-eosin staining,toluidine blue staining,and Mankin score were used to evaluate the pathological changes in the cartilage.The expression levels of TNF-α and IL-10 in the serum were detected by enzyme-linked immunosorbent assay.Results:Compared with the blank group,the articular cartilage surface in the model group was rough,the chondrocyte arrangement was irregular,the Mankin score and the serum TNF-α expression were significantly increased(P＜0.05),while the expression of serum IL-10 was significantly decreased(P＜0.05).Compared with the model group,the articular cartilage surface was smoother,the chondrocytes were arranged neatly,the Mankin score and serum TNF-α expression level were significantly lower in the three moxibustion intervention groups(P＜0.05);the serum IL-10 level in the 30-minute-moxibustion group and the 60-minute-moxibustion group was increased significantly(P＜0.05).Compared with the 15-minute-moxibustion group,the articular cartilage surface in the 30-minute-moxibustion group and the 60-minute-moxibustion group was smoother,the chondrocyte arrangement was more regular,the Mankin score and the serum TNF-α level were decreased significantly(P＜0.05),and the serum IL-10 level was increased(P＜0.05).There was no significant difference in the serum TNF-α or IL-10 level between the 30-minute-moxibustion group and the 60-minute-moxibustion group(P＞0.05).Conclusion:Moxibustion can obviously improve the morphology and structure of KOA articular cartilage,protect articular cartilage,inhibit cartilage inflammation,and delay KOA cartilage degeneration.Moxibustion's effect is closely related to moxibustion time;the therapeutic effect of the 30-minute-moxibustion and the 60-minute-moxibustion is better than that of the 15-minute-moxibustion.

Efficacy and safety of rivaroxaban in different doses for the treatment of isolated distal deep vein thrombosis / 中华普通外科杂志

Objective:To evaluate the efficacy and safety of of rivaroxaban for different doses in the treatment of isolated distal deep vein thrombosis.Methods:The clinical data of 853 patients of isolated distal deep vein thrombosis attending Nanjing Drum Tower Hospital from Jan 2018 to Dec 2020 was retrospectively analyzed.Results:Thrombotic recurrence rate increased with increasing follow-up in the standard and low dose groups, and it was significantly lower in the standard dose group than in the low dose group (HR=0.44, 95% CI: 0.25-0.78, P=0.005) with most thrombosis occurring within the first year of follow-up. There was no statistical difference between the two groups in terms of major bleeding events (HR=1.70,95%CI 0.56-5.14, P=0.530) and the incidence of clinically relevant non-major bleeding events was significantly higher in the standard dose group than in the low dose group (HR=2.36, 95%CI 1.26-4.44, P=0.020). Subgroup analysis on anticoagulation duration found when anticoagulation duration was longer than 1.5 months, the risk of thrombosis was lower in the standard dose group than the low dose group (1.5-3 months:HR=0.11, 95%CI 0.01-0.87, >3 months: HR=0.19, 95%CI 0.04-0.95), there was an interaction between anticoagulation duration and dose ( P=0.007). Conclusions:Based on the risk of thrombosis recurrence and bleeding events, the standard dose of rivaroxaban (20 mg qd) is recommended for patients with isolated distal deep vein thrombosis, and the anticoagulant duration should be maintained for 1.5 months or more.

Reasonable selection of antiviral agents for herpes zoster / 中华皮肤科杂志

Antiviral treatment is the core part in the treatment of herpes zoster. Based on the latest studies, consensus and guidelines, this article aims to provide a basis and reference for clinicians to make a reasonable choice of types and doses of antiviral agents. Valacyclovir, a precursor of acyclovir with high oral bioavailability and great convenience of administration, is generally the first choice of oral antiviral agents; for some special cases, such as immunocompromised patients, intravenous drips of acyclovir should be selected when appropriate. Brivudine is often a better choice for patients with severe renal insufficiency; famciclovir or other antiviral agents should be considered for patients resistant to acyclovir; for immunocompromised patients resistant to acyclovir, intravenous drips of foscarnet sodium can be an option. Oral antiviral agents should be administered at adequate doses. Selecting appropriate antiviral agents and their doses can effectively relieve acute symptoms of patients and reduce the probability of postherpetic neuralgia.