Characteristic Analysis of Imprinting Template of Flavonoid Clusters in Four Chinese Medicines to Lung Meridian and Establishment of Experimental Approach of Meridian Tropism in Vitro / 中国实验方剂学杂志

ObjectiveTo study the characteristics of imprinting template of flavonoid clusters in four Chinese medicines attributed to the lung meridian， and to establish an in vitro experimental approach for the study of the attribution of Chinese medicines to the lung meridian. MethodBased on 13 Chinese medicines， including Xanthii Fructus， Houttuyniae Herba， Fagopyri Dibotryis Rhizoma， Belamcandae Rhizoma and so on， which only belong to the lung meridian in Chinese Materia Medica（the 13th Five-Year planning textbook of general higher education）， we identified four representative Chinese medicines， namely Houttuyniae Herba， Fagopyri Dibotryis Rhizoma， Belamcandae Rhizoma and Mori Cortex， and set up their fingerprints by high performance liquid chromatography（HPLC） and calculated the molecular connectivity indices of various components in the four Chinese medicines， the similarity to their mean value was calculated by included angle cosine method， so as to establish the quantitative relationship of construction versus imprinting ability， and to determine the order of each component in the lung meridian. A total of 7 reference substances， including chlorogenic acid， rutin， quercetin， isoquercitrin， hyperoside， epicatechin， and iridin， were selected to validate the overall conformational relationships of flavonoids of the model， as well as its predictive ability. ResultHouttuyniae Herba， Fagopyri Dibotryis Rhizoma， Belamcandae Rhizoma and Mori Cortex contained a total of 437 chemical components with an average molecular connectivity index similarity of 0.995 6. The four Chinese medicines contained a total of 204 flavonoids with an average molecular connectivity index similarity of 0.978 0， which was second only to the alkaloids with 0.985 1. The retention time（tR） of the 7 reference substances showed a good conformational relationship with the similarity of the molecular connectivity index（tR=831.4×S-790.3， r=0.861 4， P<0.01）， which was applicable to the in vitro attribution study of the position， similarity， and relative similarity with tR of the cluster of 98.04% of flavonoids. Accordingly， the 1st position was kuwanon D， with a similarity of molecular connectivity index of 0.987 7 and a tR of 30.88 min， the 200th position was chlorogenic acid， with a similarity of molecular connectivity index of 0.958 2 and a tR of 6.36 min. The total first-order moment of the four Chinese medicines calculated by total statistical moment method of fingerprint was 24.26 min， ranked 21， which could characterize 99.19% of the whole， and the total first-order moment of the total peak area of the 7 reference substances in the four Chinese medicines was 20.00 min， with a rank of 46， which could characterize 98.68% of the whole. ConclusionFlavonoid clusters are suitable probes for the characterization of imprinting template for the study of the lung meridian， which can be established a quantitative imprinting method for meridian tropism of Chinese medicines in vitro.

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

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

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

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

Polymorphisms of host tropism relating amino acid sites in influenza A virus / 上海预防医学

ObjectiveTo discover and analyze single or several correlative key amino acid sites that influence the host tropism during the influenza A virus （IAV） infection based on complete internal protein gene segments of IAV strains， and to provide evidence for the study of human host-adaptive mutations of IAV. MethodsThe full-length nucleotide sequences of 43 671 IAV strains containing 6 complete internal gene segments were downloaded from the GISAID EpiFluTM database， and 698 human-tropic （HU） and 1 266 avian-tropic （AV） representative strains were included. The consensus coding sequences of the representative strains from the amphitropic category were compared by R script， and the differential amino acid sites and their polymorphisms were then obtained. The multi-site combination analysis of differential sites was conducted with R script. ResultsA total of 49 and 57 conserved differential sites were obtained from the consensus sequence comparison between AV and H1N1 （subtype from HU）， and comparison between AV and H3N2 （another subtype from HU）， separately. 79 and 65 multi-site combinations were found between HU and AV strains through 3 and 4 sites combination analysis， respectively， and a total of 11 conserved sites were involved： site 271 and 684 in PB2； site 336， 486， 581 and 621 in PB1； site 204 and 356 in PA； site 33， 305 and 357 in NP. No eligible differential sites were found in M1 and NS1. ConclusionSeveral conserved amino acid differential sites， between HU and AV strains of IAV， are found in PB2， PB1， PA and NP proteins. Instead of working as single units， these sites may have interactions， forming specific amino acid combinations that determine the host tropism of IAV collectively.

Research progress on the epidemiology of human adenovirus infections / 预防医学

Abstract@#Human adenovirus (HAdV), which is characterized by infectivity, complex pathogenesis and multiple target organs, causes multiple organ infections in the respiratory system, gastrointestinal system and eyes, which seriously endangers human health. Various subspecies of HAdV has different tissue tropism, which presents diverse clinical symptoms and epidemiological characteristics. Based on the molecule biological characteristics of HAdV, this review summarizes the clinical symptoms and epidemiological characteristics of HAdV infections depending on tissue tropism, and describes the trends in HAdV epidemiology, so as to provide insights into prevention and control of HAdV infections.

Meridian Tropism and Compatibility of Chinese Medicine from Theory of Brain Sweat Pore / 中国实验方剂学杂志

Since LIU Hejian proposed the concept of sweat pore， the theory of sweat pore has experienced accelerated development. Especially with the advances in modern human anatomy and physiology， the microscopic anatomy of sweat pore begins to focus on the intercellular space， ion channels and other membranous space with channels， pores， doors， etc.， which exert the functions of exchanging fluid， information， and energy inside and outside blood vessels and discharging metabolic wastes so as to maintain the normal operation of organs. Therefore， sweat pore is the structural basis for the movement of Qi and the central link of Qi-fluid exchange in the body. The brain， as the house of original spirit， is in charge of the spirit of five Zang-organs. The brain sweat pore is pivotal for the circulation of Qi， blood， and fluid in the brain， and it is the structural basis for the normal physiological functions of the brain. The dysfunction of the brain sweat pore will cause the stagnation of Qi and the abnormal transport of blood and fluid. It will cause the abnormal exchange of Qi， liquid and other material and information， which fail to nourish the original spirt and cause the loss of vital activity， eventually leading to consciousness and emotion disorders. The treatment should focus on opening the brain sweat pore， smoothing the exchange of Qi and fluid inside and outside the pore， and restoring the Qi movement， so as to cure encephalopathy. At present， western medicine treatment of encephalopathy needs to solve the problem of drug efflux from the blood-brain barrier and improve the effective concentration of drugs into the brain. The structure and function of brain sweat pore is similar to those of the blood-brain barrier. The aromatic resuscitative medicines and wind-extinguishing medicines can open the brain sweat pore. When being combined with other medicines， they can lead the medicine to enter the brain to restore the Qi movement of the brain sweat pore and enhance the therapeutic effect. Liver-pacifying wind-extinguishing medicines， insect medicines， tonifying medicines， heat-clearing toxin-removing medicines， and damp-draining medicines can treat pathological factors such as wind， phlegm， stasis， deficiency， toxin， and dampness， respectively. These medicines， combined with the medicines with the tropism to brain meridians， can open the brain sweat pore and guide the medicine into the brain to enhance the effective concentration of the medicine， thereby enhancing the efficacy against encephalopathy.

Sub-lineages of the Omicron variant of SARS-CoV-2: characteristic mutations and their relation to epidemiological behavior / Sub-linajes de la variante Ómicron del SARS-CoV-2: mutaciones características y su relación con el comportamiento epidemiológico

Abstract By the end of 2021, the Omicron variant of SARS-CoV-2, the coronavirus responsible for COVID-19, emerges, causing immediate concern, due to the explosive increase in cases in South Africa and a large number of mutations. This study describes the characteristic mutations of the Omicron variant in the Spike protein, and the behavior of the successive epidemic waves associated to the sub-lineages throughout the world. The mutations in the Spike protein described are related to the virus ability to evade the protection elicited by current vaccines, as well as with possible reduced susceptibility to host proteases for priming of the fusion process, and how this might be related to changes in tropism, a replication enhanced in nasal epithelial cells, and reduced in pulmonary tissue; traits probably associated with the apparent reduced severity of Omicron compared to other variants.

Resumen A finales de 2021 surge la variante Omicron del SARS-CoV-2, el coronavirus responsable de la COVID-19, causando preocupación inmediata, debido al aumento explosivo de casos en Suráfrica, y a su gran cantidad de mutaciones. Este estudio describe las mutaciones características de la variante Ómicron en la proteína de la Espiga (S) y el comportamiento de las sucesivas olas epidémicas asociadas a la circulación de sus sub-linajes en todo el mundo. Las mutaciones en la proteína S descritas están relacionadas con su capacidad para evadir la protección provocada por las vacunas actuales, así como su posible susceptibilidad reducida a las proteasas del hospedero para la preparación del proceso de fusión. Se infiere cómo esto podría estar relacionado con su cambio en el tropismo, con una replicación mayor en las células epiteliales nasales y menor en el tejido pulmonar, rasgos probablemente asociados a su aparente menor gravedad en comparación con otras variantes.

Meridian Tropism of Components in Bupleuri Radix Based on Nonalcoholic Steatohepatitis Model and Principal Component Analysis / 中国实验方剂学杂志

ObjectiveTo explore the meridian tropism of components in Bupleuri Radix （Chaihu， CH） based on the model of nonalcoholic steatohepatitis （NASH） and clarify the substance basis of the meridian tropism of CH in Xiaoyaosan （XYS） by means of principal component analysis. MethodEighty SPF male C57BL/6 mice were randomly assigned into 8 groups， with 10 mice in each group. Except that the blank group was fed with the methionine choline-sufficient （MCS） diet， the other mice were fed with methionine choline-deficient （MCD） diet for 4 weeks to establish the nonalcoholic steatohepatitis （NASH） model. After the established model was confirmed by hematoxylin-eosin （HE） staining， the mice were administrated with corresponding drugs by gavage once a day for 4 weeks. Specifically， the 8 groups were XYS group （2.874 g·kg-1）， XYS-CH group （2.445 g·kg-1）， XYS-CH+volatile oils （Vol， 0.163 mg·kg-1） group， XYS-CH+polysaccharides （Pol， 24.067 mg·kg-1） group， XYS-CH+flavones （Fla， 2.241 mg·kg-1） group， and XYS-CH+saponins （Sap， 2.746 mg·kg-1） group. The model group and the blank group were administrated with the same volume of normal saline. After the last administration， the mice were sacrificed for the collection of blood and liver tissue. The pathological changes of liver were observed by HE staining and oil red O staining. Enzyme linked immunosorbent assay （ELISA） kits were used to determine the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL） in serum as well as malondialdehyde （MDA）， superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） in liver. SPSS Statistics 23 was used for principal component analysis and comprehensive evaluation to determine the substance basis of the meridian tropism of CH in NASH mice. ResultCompared with the blank control group， the modeling led to hepatocyte swelling， increased fat vacuoles， and appearance of inflammatory cells. Further， the modeling elevated the levels of ALT， AST， TG， TC， and LDL and lowered the HDL level in serum， and it increased the MDA level and decreased the SOD， CAT， and GSH-Px levels in liver. Compared with the model group， the administration of XYS and XYS-CH in combination with the components of CH alleviated the oxidative damage in liver （P<0.05）. The comprehensive score of the pharmacological efficacy was in a descending order as follows： XYS > XYS-CH+Sap > XYS-CH+Fla > XYS-CH+Pol > XYS-CH+Vol > XYS-CH. Among the chemical components of CH， Sap had the best effect. ConclusionSap lowers the blood lipid level， regulates the abnormal lipid metabolism， and alleviates the oxidative damage of liver， which is the substance basis for CH to exert the meridian tropism in liver.

Mechanism of Toxic Chinese Medicinals Against Esophageal Cancer： A Review / 中国实验方剂学杂志

Esophageal cancer ranks the seventh and sixth in morbidity and mortality among the malignant tumors， respectively. In traditional Chinese medicine， toxic medicinals are commonly used to enhance the efficacy on esophageal cancer. In recent years， as natural drugs have become the focus of research on anti-tumor drugs， toxic Chinese medicinals have received wide attention. It has been found that a variety of toxic Chinese medicinals have significant anti-esophageal cancer effect. In this study， articles on the treatment of esophageal cancer were retrieved from SinoMed， China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP， and the toxic Chinese medicinals in the articles were summarized. It was found that the toxic Paridis Rhizoma， Gekko， Cremastrae Pseudobulbus Pleiones Pseudobulbus， Scolopendra， Hirudo， Sophorae Tonkinesis Radix et Rhizoma， Scorpio， and Bufonis Corium were mainly used for the treatment of this cancer. They can be classified into the heat-clearing and toxin-removing medicinals， toxin-counteracting medicinals， phlegm-resolving medicinals， and blood-activating and stasis-resolving medicinals. Most of them were pungent （19，52.78%） or bitter （17，47.22%）. The majority had the meridian tropism toward liver （25， 69.44%）， spleen （13， 36.11%）， and lung （12， 33.33%）. According to the research on the above commonly used toxic Chinese medicinals， most of them have anti-tumor effect and some have been reported to have anti-esophageal cancer effect. The mechanism is mainly the inhibition of proliferation. To be specific， they exert the anti-cancer effect by suppressing the proliferation， migration， and differentiation of cancer cells， inducing cell cycle arrest， and activating B-cell lymphoma/leukemia-2 （Bcl-2）-associated X protein （Bax）/Bcl-2/Caspase signaling pathway to induce apoptosis. In this paper， the commonly used toxic Chinese medicinals for the treatment of esophageal cancer were statistically analyzed， and the mechanisms were summarized， in order to provide a reference for the clinical rational use of toxic Chinese medicinals and the research on the mechanisms for their efficacy.

Prognosis impact of perineural invasion in advanced stage oral squamous cell carcinoma / Impacto do prognóstico da invasão perineural no carcinoma espinocelular de boca em estágio avançado

Apesar de pesquisas recentes mostrarem baixa sobrevida em pacientes oncológicos que tiveram invasão perineural (IPN), pouco se sabe sobre a força do IPN relacionada à sobrevida do carcinoma espinocelular (CEC) de boca e em relação a suas variáveis clínico-patológicas. Os objetivos específicos do estudo foram medir o impacto do IPN na sobrevida do CEC de boca, bem como a correlação entre as características clínico-patológicas do paciente diagnosticado com CEC de boca com o IPN em pacientes tratados cirurgicamente. Foi realizado um estudo retrospectivo envolvendo 101 pacientes submetidos ao tratamento cirúrgico com ou sem associação de terapia adjuvante entre os anos de 1994 e 2016. Todas as variáveis foram inseridas simultaneamente no modelo de cox para cada modelo de sobrevida e na tabulação cruzada para avaliar a relação do IPN com as variáveis do CEC de boca. A significância estatística para o estudo foi estabelecida em um valor de P inferior a 0,05. A variável de interesse IPN provou ser preditora de sobrevida global (HR, 3,38; IC 95%, 0,139-0,624; P = 0,004) e sobrevida específica da doença (HR, 2,95; IC 95% 0,137-0,810; P=0,019). O IPN também mostrou relação com tratamento (P = 0,011) na análise de correlação. A invasão perineural foi considerada uma variável independente na sobrevida específica e global de pacientes com CEC de boca. Outros fatores relacionados à sensibilidade da avaliação do padrão de invasão perineural no CEC de boca ainda permanecem desconhecidos(AU)

Despite recent research showing low survival in cancer patients who had perineural invasion (PNI), little is known about the strength of the PNI related to oral squamous cell carcinoma (OSCC) survival and in relation to its clinicopathological variables. The specific objectives of the study were to measure the impact of the PNI on the survival of oral SCC, as well as the correlation between the clinicopathological characteristics of the patient diagnosed with OSCC of the mouth with the PNI in surgically treated patients. A retrospective study was carried out involving 101 patients who underwent surgical treatment with or without the association of adjuvant therapy between the years 1994 and 2016. All variables were entered simultaneously in the cox model for each survival model and in the cross-tabulation to evaluate the relationship between the PNI and the OSCC by mouth variables. Statistical significance for the study was established at a P value of less than 0.05. The PNI variable of interest proved to be a predictor of overall survival (HR, 3.38; 95% CI, 0.139-0.624; P = 0.004) and disease-specific survival (HR, 2.95; 95% CI 0.137-0.810; P =0.019). The PNI also showed a relationship with treatment (P = 0.011) in the correlation analysis. Perineural invasion was considered an independent variable in the specific and overall survival of patients with OSCC. Other factors related to the sensitivity of the assessment of the perineural invasion pattern in OSCC of the mouth still remain unknown(AU)

SARS-CoV-2: mucho más que un virus respiratorio / SARS-COV-2: more than a respiratory virus

RESUMEN Fundamento: el virus SARS-CoV-2 es responsable de la segunda pandemia del siglo XXI. Desde su aparición en China a finales de 2019, se asocia a neumonía y considera como un virus respiratorio más. Sin embargo, durante su diseminación global demuestra su capacidad para producir daño a otros órganos con manifestaciones clínicas nunca antes descritas para otros virus respiratorios. Objetivo: describir la evidencia científica que respalde el daño extrapulmonar directo producido por el virus SARS-CoV-2 en etapas tardías de la infección, que apoyan su naturaleza bifásica y distinta frente a otros virus respiratorios. Métodos: se realizó una búsqueda de artículos referente al tema en las bases de datos MEDLINE accedido desde PubMed, SciELO y LILACS. También se tuvieron en cuenta artículos publicados en los repositorios de preimpresión como medRxiv, BioRxiv. Mediante el gestor de búsqueda y administrador de referencias Mendeley, se eliminaron los duplicados y aquellos que no se ajustaban al objetivo del estudio, se seleccionaron 63 artículos para la revisión. Resultados: la evidencia sugiere que el SARS-CoV-2 tiene tropismo no solo limitado a las vías respiratorias. La progresión clínica de la COVID-19 presenta un curso bifásico, con manifestaciones de tipo gripal en la primera fase y episodios postagudos y persistentes en la fase tardía, ocasionados por el daño directo al sistema nervioso central, cardiovascular, endocrino y renal. Conclusiones: la infección por SARS-CoV-2 no debe considerarse solo como una infección aguda y circunscrita a las vías respiratorias.

ABSTRACT Background: the SARS-CoV-2 virus is responsible for the second pandemic of the 21st century. Since its appearance in China at the end of 2019, it has been associated with pneumonia and considered to be just another respiratory virus. However, during its global spread, it shows its ability to damage other organs with clinical manifestations never before described for other respiratory viruses. Objective: to describe the scientific evidence that supports the direct extra-pulmonary damage produced by the SARS-CoV-2 virus in late stages of infection, which supports its biphasic nature and different from other respiratory viruses. Methods: a search of the articles was carried out in the MEDLINE databases accessed from PubMed, SciELO and LILACS. Articles published in prepress repositories such as medRxiv, BioRxiv were also taken into account. Using the Mendeley reference manager and search manager, duplicates and those that did not meet the objective of the study were eliminated, selecting 63 articles for the present review. Results: the evidence suggests that SARS-CoV-2 has a tropism not only limited to the respiratory tract. The clinical progression of COVID-19 presents a biphasic course, with flu-like manifestations in the first phase and post-acute and persistent episodes in the late phase, caused by direct damage to the central nervous, cardiovascular, endocrine and renal systems. Conclusions: SARS-CoV-2 infection should not be considered only as an acute infection limited to the respiratory tract.

Host metabolism dysregulation and cell tropism identification in human airway and alveolar organoids upon SARS-CoV-2 infection

The coronavirus disease 2019 (COVID-19) pandemic is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we showed that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids which covered the complete infection and spread route for SARS-CoV-2 within lungs. The infected cells were ciliated, club, and alveolar type 2 (AT2) cells, which were sequentially located from the proximal to the distal airway and terminal alveoli, respectively. Additionally, RNA-seq revealed early cell response to virus infection including an unexpected downregulation of the metabolic processes, especially lipid metabolism, in addition to the well-known upregulation of immune response. Further, Remdesivir and a human neutralizing antibody potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection and to discover and test therapeutic drugs for COVID-19.

Unstable Non-isthmic Spondylolisthesis Following Unilateral Biportal Endoscopy Assisted Unilateral Laminotomy for Bilateral Decompression: A Case Report

@#Lumbar decompressive laminectomy is a standard treatment for degenerative lumbar spinal stenosis, but in some cases, can lead to iatrogenic spondylolysis and delayed segmental instability. Iatrogenic spondylolysis occurs in most cases in pars interarticularis, but rare cases have also been reported, pediculolysis in pedicle and laminolysis in lamina. Minimally invasive spine surgery (MIS) is known to have a low risk of developing these iatrogenic spondylolyses, and unilateral biportal endoscopy is the MIS that has been drawing attention. We present a case of a 72-year-old female who was diagnosed with L4-5 unstable non-isthmic spondylolisthesis and severe right central disc extrusion 10 weeks after UBE assisted unilateral laminotomy for bilateral decompression (ULBD) at the consecutive segments of L3-4 and L4-5. Pre-operative imaging studies revealed severe central stenosis without spondylolisthesis at L3-L4 and L4- L5 along with L4-L5 facet tropism. She was managed by anterior lumbar interbody fusion and cement augmented pedicle screw fixation, which resulted in the complete resolution of her clinical and neurologic symptoms.

The assessment of pain, flexibility and daily activity level in the patients who had facet tropism

Vernal keratoconjunctivitis(VKC)is a chronic bilateral inflammation of the conjunctiva, commonly associated with a personal or family history of atopy. It is characterized by severe itching, foreign body sensation, thick ropy discharge, photophobia and conjunctival injection. VKC has palpebral, limbal and mixed forms. The classical conjunctival sign in palpebral VKC is the presence of giant papillae, which are predominantly seen on the superior tarsal conjunctiva. The limbal form occurs in dark skinned individuals and the papillae tend to occur at the limbus and have a thick gelatinous appearance. Clinical findings and laboratory investigations support the presence of IgE mediated type1 hypersensitivity reaction. Involvement of CD4 T helper (Th2) driven type IV hypersensitivity has also been confirmed. There has been an increase in the prevalence of allergic disorders in recent years and exaggerated manifestations of these diseases have been recognized in patients living with Human immunodeficiency virus

Active constituents and mechanisms of Respiratory Detox Shot, a traditional Chinese medicine prescription, for COVID-19 control and prevention: Network-molecular docking-LC-MS analysis / 中西医结合学报

OBJECTIVE@#Lung-toxin Dispelling Formula No. 1, referred to as Respiratory Detox Shot (RDS), was developed based on a classical prescription of traditional Chinese medicine (TCM) and the theoretical understanding of herbal properties within TCM. Therapeutic benefits of using RDS for both disease control and prevention, in the effort to contain the coronavirus disease 2019 (COVID-19), have been shown. However, the biochemically active constituents of RDS and their mechanisms of action are still unclear. The goal of the present study is to clarify the material foundation and action mechanism of RDS.@*METHODS@#To conduct an analysis of RDS, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, and cluster analysis; further, the hub genes involved in the disease-related pathways were identified, and the their corresponding compounds were used for in vitro validation of molecular docking predictions. The presence of these validated compounds was also measured in samples of the RDS formula to quantify the abundance of the biochemically active constituents. In our network pharmacological study, a total of 26 bioinformatic programs and databases were used, and six networks, covering the entire Zang-fu viscera, were constructed to comprehensively analyze the intricate connections among the compounds-targets-disease pathways-meridians of RDS.@*RESULTS@#For all 1071 known chemical constituents of the nine ingredients in RDS, identified from established TCM databases, 157 passed drug-likeness screening and led to 339 predicted targets in the constituent-target network. Forty-two hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-constituent-disease network. Twelve disease pathways attributed to the Lung-Large Intestine meridians, with six and five attributed to the Kidney-Urinary Bladder and Stomach-Spleen meridians, respectively. One-hundred and eighteen candidate constituents showed a high binding affinity with SARS-coronavirus-2 3-chymotrypsin-like protease (3CL), as indicated by molecular docking using computational pattern recognition. The in vitro activity of 22 chemical constituents of RDS was validated using the 3CL inhibition assay. Finally, using liquid chromatography mass spectrometry in data-independent analysis mode, the presence of seven out of these 22 constituents was confirmed and validated in an aqueous decoction of RDS, using reference standards in both non-targeted and targeted approaches.@*CONCLUSION@#RDS acts primarily in the Lung-Large Intestine, Kidney-Urinary Bladder and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all nine ingredients. In the context of TCM meridian theory, the multiple components and targets of RDS contribute to RDS's dual effects of health-strengthening and pathogen-eliminating. This results in general therapeutic effects for early COVID-19 control and prevention.

Discussion on the academic system of "theory, method, recipe and degree" in s infantile Chinese massage of the western part of Hunan province / 中国针灸

The theory and technique of s infantile Chinese massage of the western part of Hunan province are reviewed in clinical diagnosis and treatment and the core theoretical system is refined. Based on clinical experiences and in consideration of the analysis on relevant literature, the academic system of s infantile Chinese massage of the western part of Hunan province is summarized as four aspects, named "theory, method, recipe and degree". "Theory" refers to the four diagnostic methods and eight principle in terms of diagnosis and treatment and the therapeutic emphasis on the main disorders of organs in children. "Method" refers to promotion and restriction of five elements, meridian tropism in treatment. "Recipe" refers to the selection of acupoints, optimization of therapeutic techniques and the key in the composition of the herbs with different roles considered, named monarch herb, minister herb, assistant herb and guiding herb. "Degree" refers to the strength and intensity of manipulation to ensure the optimal effect. All of the aforementioned reviews provide the reference to theoretic study on this Chinese massage school.

Analysis on Medication Rules of Traditional Chinese Medicine for Treatment of Diabetic Peripheral Neuropathy Based on Clinical Literature / 中国实验方剂学杂志

Objective:To investigate the medication rules of traditional Chinese medicine (TCM) for the treatment of diabetic peripheral neuropathy (DPN).Method:The literature published in China Knowledge Resource Integrated Database (CNKI), Wanfang Database, China Biomedical Literature Service System (SinoMed), VIP Database and PubMeb from 2008 to 2019 were retrieved by setting the topics of diabetic peripheral neuropathy and TCM. After screening, a database was established to analyze the medication rules (efficacy, frequency, flavor and meridian tropism, common couplet medicinals and core medicines) of TCM by frequency statistics, association rules and data statistical methods of constructing complex networks.Result:A total of 461 papers for treatment of DPN were included in this study, including 275 kinds of TCM and a total frequency of 6 361 times. Astragali Radix had the highest frequency. Among all kinds of medicinal materials, activating blood circulation and removing stasis was the most commonly used medicine, followed by Qi-invigorating medicine. Flavor of medicines was mainly sugariness and warm, and most of their meridian tropism was liver meridian. After the analysis by association rules, the couplet medicinals with the highest support was Astragali Radix-Angelicae Sinensis Radix. The core medicines obtained by complex network analysis were Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, Spatholobi Caulis, Cinnamomi Ramulus, Carthami Flos, Pheretima, Paeoniae Radix Rubra, Salviae Miltiorrhizae Radix et Rhizoma and Persicae Semen.Conclusion:This study comprehensively analyzes the medication rules of TCM clinical treatment of DPN. The main treatment methods of TCM for DPN are invigorating Qi and blood, activating blood circulation and removing stasis, activating meridians to stop pain, which can provide guidance for the TCM clinical use and new Chinese medicines research and development of DPN.

Meridian tropism of Scutellaria baicalensis based on molecular thermodynamic characteristics / 药学学报

The property of medicine is the "identity card" of traditional Chinese medicine (TCM), and the key to crack the theory of property of TCM. Based on molecular thermodynamics, the effects of interaction between TCM and organs in vitro were studied from the perspective of micro-energy release and absorption in order to construct a new idea of characterizing meridian theory. Scutellaria baicalensis, for example, application of isothermal titration calorimetry (ITC) were used to determine the energy changes during the interaction of Scutellaria baicalensis and its main active ingredient baicalin with brain, heart, lung, spleen and kidney in vitro, comparison including the association constant (Ka) and disassociation constant (Kd), combined with thermodynamic parameters, such as stoichiometry ratio (n), enthalpy change (ΔH), entropy change (ΔS), Gibbs free energy (ΔG), it is found that the interaction intensity between Scutellaria baicalensis and lung is significantly stronger than that of other organs, which is consistent with the theory of the return of Scutellaria baicalensis in ancient books. In addition, baicalin, the main active ingredient, showed the same action pattern as Scutellaria baicalensis. The thermodynamic parameters analysis showed that the action was a weak bond-induced spontaneous chemical binding reaction driven by both entropy and enthalpy. The results of specific curl measurement further proved the interaction between baicalin and lung, and were consistent with the results of ITC titration, indicating that ITC could be used to characterize the meridian tropism of TCM. Therefore, based on ITC, it is scientific and feasible to characterize the meridian of TCM by the energy change of the interaction between the decoction of TCM and its active components and the in vitro tissues respectively. This experiment provides a new idea for the discussion of meridian of TCM.

Pegivirus humano: potencial patogénico y riesgo de desarrollo de linfoma no Hodgkin / Human Pegivirus: pathogenic potential and non-Hodgkin lymphoma development risk

Resumen El pegivirus humano (HPgV) es un virus ARN que fue identificado en el año 1995. Actualmente se encuentra clasificado dentro de la familia Flaviviridae, género Pegivirus, relacionado filogenéticamente con el virus de la hepatitis C (VHC). El HPgV es un virus linfotrópico, con replicación en médula ósea, tejidos linfoides, y en células mononucleares de sangre periférica. Este virus se transmite por vía parenteral y sexual. Según estimaciones realizadas, en el mundo existen alrededor de 750 millones de personas infectadas por este agente. Se ha evidenciado que hasta en 25% de los casos se presenta una infección persistente, y aunque se considera que el HPgV es un virus no patogénico, existen evidencias epidemiológicas que sugieren una relación con el desarrollo de desórdenes linfoproliferativos, particularmente linfoma no Hodgkin (LNH). Algunos estudios han reportado una alta prevalencia de HPgV en pacientes con LNH comparado con donantes de sangre y/o pacientes con enfermedades hematológicas no malignas, lo que se asocia a un incremento en el riesgo relativo para el desarrollo de LNH en personas infectadas. De otra parte, existen estudios epidemiológicos que contradicen esta asociación, por lo que el rol de HPgV en la aparición de desórdenes lifoproliferativos es un tema actual de debate. En el presente manuscrito se discute el potencial patogénico derivado de los mecanismos de infección persistente del HPgV, así como las principales evidencias sobre la relación entre el HPgV y el riesgo de desarrollo de LNH.

The human pegivirus (HPgV), classified in the Flaviviridae family - Pegivirus genus, is an RNA virus identified in 1995. HPgV is a lymphotrophic virus, with replication sites in bone marrow and lymphoid tissue, as well as in peripheral blood mononuclear cells (PBMCs). Transmission is through sexual and parenteral routes, and recent estimations suggest nearly 750 million people are infected with HPgV worldwide. Almost 25% of infected individuals can develop persistent infection. Until now, HPgV has been considered a non-pathogenic virus; however, epidemiological studies suggest a potential role in lymphoproliferative diseases, particularly in the development of non-Hodgkin lymphoma (NHL). The evidence of this is controversial and the role of HPgV in lymphomagenesis has not yet been demonstrated. Several studies report a high prevalence of HPgV infection in patients with NHL compared to controls and patients with other hematological diseases. Therefore, analytic studies show that HPgV could be related to an increased risk of NHL development. Conversely, other studies indicate no association between HPgV and NHL, so the role of HPgV in lymphomagenesis is not clear. This review summarizes the main findings related to HPgV's pathogenic potential and association with NHL.

Influence of facet tropism on the location of lumbar disc herniation / A influência do tropismo facetário sobre a localização da hérnia discal lombar / Influencia del tropismo facetario en la ubicación de la hernia de disco lumbar

ABSTRACT Objective: To correlate facet tropism with the side and location of the intervertebral disc in which the lumbar disc herniation occurred. Methods: A retrospective descriptive study that evaluated Magnetic Resonance Imaging of 255 patients with lumbar disc herniation undergoing surgical treatment with the Spine Group of the Hospital Ortopédico de Passo Fundo between 2002 and 2014. The total patient number was stratified according to the side affected by the herniated disc (right or left), location of the hernia in the intervertebral disc (central, centrolateral, foraminal and extraforaminal) and demographic data, such as age, gender etc. The degree of facet joint tropism was measured by the Karakan method and classified as mild (difference less than 7º); moderate (between 7º and 15º) and severe (difference greater than 15º). Results: A statistical significant relationship (p= 0.023) was observed between the facet joint tropism and the side where the lumbar disc herniation occurred. No correlation was found between facet joint tropism and location of the herniation on the intervertebral disc. Conclusions: The degree of facet tropism presents a statistical significant correlation with the side of the intervertebral disc in which the lumbar disc herniation will develop. Level of Evidence: II. Type of study: Retrospective study.

RESUMO Objetivo: Correlacionar o tropismo facetário com o lado e local do disco intervertebral no qual ocorreu a hérnia discal lombar. Métodos: Estudo retrospectivo descritivo, no qual foram avaliados exames de Ressonância Nuclear Magnética de 255 pacientes com hérnia discal lombar submetidos a tratamento cirúrgico pelo Grupo de Coluna do Hospital Ortopédico de Passo Fundo, entre os anos de 2002 e 2014. Estratificou-se o total de pacientes pelo lado acometido pela hérnia discal (direito ou esquerdo), localização da hérnia no disco intervertebral (central, centro-lateral, foraminal e extra-foraminal) e por dados epidemiológicos, como idade, sexo etc. O grau de tropismo facetário foi mensurado pelo método de Karakan e classificado entre leve (diferença menor que 7º), moderado (entre 7º e 15º) e grave (diferença maior que 15º). Resultados: Foi verificada relação estatisticamente significativa (p= 0,023) entre o tropismo facetário e o lado em que ocorreu a hérnia discal lombar. Não foi encontrada correlação entre tropismo facetário e localização da hérnia discal no disco intervertebral. Conclusão: O grau de tropismo facetário apresenta correlação estatisticamente significativa com o lado do disco intervertebral no qual irá se desenvolver a hérnia discal. Nível de Evidência: II. Tipo de Estudo: Estudo retrospectivo.

RESUMEN Objetivo: Correlacionar el tropismo facetario con el lado y local del disco intervertebral en el cual ocurrió la hernia del disco lumbar. Métodos: Estudio retrospectivo descriptivo, en el fueron evaluados exámenes de resonancia magnética nuclear de 255 pacientes con hernia discal lumbar sometidos a tratamiento quirúrgico por el Grupo de Columna Vertebral del Hospital Ortopédico de Passo Fundo, entre los años 2002 y 2014. El número total de pacientes fue estratificado de acuerdo con el lado acometido por la hernia discal (izquierda o derecha), localización de la hernia en el disco intervertebral (central, centro-lateral, foraminal o extra-foraminal) y datos epidemiológicos como edad, sexo etc. El grado de tropismo facetario fue medido por el método de Karakan y clasificado como leve (diferencia menor que 7º), moderado (entre 7º y 15º) y grave (diferencia mayor que 15º). Resultados: Se verificó una relación estadísticamente significativa (p = 0,023) entre el tropismo facetario y el lado en que ocurrió la hernia discal lumbar. No se encontró correlación entre el tropismo facetario y la localización de la hernia en el disco intervertebral. Conclusiones: El grado de tropismo facetario presenta correlación estadísticamente significativa con el lado del disco intervertebral en el cual se desarrollará la hernia discal lumbar. Nivel de evidencia: II. Tipo de Estudio: Estudio retrospectivo.