Central auditory processing and aphasia: A scoping review / Processamento auditivo central e afasia: uma revisão de escopo

ABSTRACT Purpose: to report scientific evidence on the impact of aphasia on central auditory processing and map the contribution of auditory training to aphasic individuals. Methods: a scoping review approaching national and international databases (SciELO, LILACS, PubMed, Scopus, and Cochrane Library) and the gray literature (Google Scholar and Open Grey). The inclusion criteria covered articles that addressed the interface between central auditory processing and aphasia, excluding duplicates, literature reviews, and scientific abstracts. Literature Review: the review comprised 13 articles that met the eligibility criteria for this study. Seven of the selected articles assessed central auditory processing, four used electrophysiological examinations (such as auditory brainstem response and long-latency auditory evoked potentials) to assess the auditory pathway, and only one analyzed the intervention in aphasic individuals with auditory training. Conclusion: scientific evidence points to an important change in aphasic people's central auditory processing, with impaired figure-ground, auditory closure, temporal resolution and ordering, and binaural integration. Moreover, it is relevant to assess auditory processing, given the contribution of auditory training in speech-language-hearing therapy for a better prognosis in the rehabilitation of aphasia.

RESUMO Objetivo: reportar as evidências científicas do impacto da afasia no Processamento Auditivo Central e mapear a contribuição do Treinamento Auditivo para a população afásica. Métodos: trata-se de uma revisão de escopo realizada nas bases de dados nacionais e internacionais: Scielo, Lilacs, Pubmed, Scopus, Cochrane Library e com uma busca adicional à literatura cinzenta no Google Scholar e Open Grey. Os critérios de inclusão abrangeram artigos que abordassem a interface do processamento auditivo central e afasia, excluindo-se as duplicações, artigos de revisão da literatura e resumos científicos. Revisão de Literatura: selecionaram-se 13 artigos que cumpriram os critérios de elegibilidade deste estudo. Dos artigos selecionados, sete apresentaram a avaliação do Processamento Auditivo Central, quatro apresentaram os exames eletrofisiológicos - como os exames de Potencial Evocado Auditivo de Tronco Encefálico (PEATE) e Potencial Evocado Auditivo de Longa Latência (PEALL) - para avaliação da via auditiva e apenas um estudo analisou a intervenção dos indivíduos afásicos por meio do treinamento auditivo. Conclusão: as evidências científicas apontam importante alteração no Processamento Auditivo Central dos afásicos, apresentando prejuízos nas habilidades auditivas de figura-fundo, fechamento auditivo, resolução e ordenação temporal e integração binaural. Ainda, demonstra-se como relevante a avaliação do processamento, devido à contribuição do Treinamento Auditivo nas terapias fonoaudiológicas para um melhor prognóstico na reabilitação das afasias.

Signaling Pathways Related to Renal Interstitial Fibrosis in Diabetic Kidney Disease Regulated by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic kidney disease （DKD） is a common microvascular complication of diabetics mellitus （DM） and the leading cause of end-stage renal disease （ESRD）. Renal interstitial fibrosis （RIF） is the primary pathological basis for DKD progression to ESRD， which significantly increases the mortality rate of DKD patients and burdens patients and society， and it is thus a clinical problem that needs to be solved urgently. The pathogenesis of RIF is complex and mainly associated with excessive deposition of extracellular matrix （ECM）， epithelial-mesenchymal transition （EMT）， oxidative stress， inflammation， and autophagy. Multiple signaling pathways such as transforming growth factor-β1/Smad （TGF-β1/Smad）， nuclear transcription factor-κB （NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， secretory glycoprotein/β-catenin （Wnt/β-catenin）， mammalian target of rapamycin （mTOR）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， neurogenic site-gap homologous protein （Notch）， and nuclear factor E2-associated factor 2 （Nrf2） mediate the development of RIF， which are currently novel targets for DKD therapy. Due to the complexity of its pathogenesis， the current Western medical treatment mainly focuses on essential treatment to improve metabolism， which has poor efficacy and is difficult to prevent the progression of DKD， so it is significant to find new treatment methods clinically. In recent years， many studies have proved that traditional Chinese medicine can alleviate oxidative stress， inhibit inflammatory response， and regulate cellular autophagy by modulating relevant signaling pathways， so as to treat RIF in DKD， which has the advantages of multi-pathway， multi-targeting， multi-linking， and significant therapeutic efficacy. However， there is still a lack of relevant summary. By reviewing the latest research reports in China and abroad， this article examines the roles of the signaling pathways mentioned above in the occurrence and development of RIF in DKD and the recent research progress in the intervention of RIF in DKD by traditional Chinese medicine via these pathways， aiming to provide new ideas and references for further scientific research and clinical practice.

Mechanism of Traditional Chinese Medicine in Treatment of Neurodegenerative Diseases by Regulating Polarization Balance of Microglia： A Review / 中国实验方剂学杂志

Neuroinflammation is a common pathological feature of neurodegenerative diseases （NDs）. Microglia （MG）， a resident macrophage in the brain with a unique developmental origin， is the core driver of neuroinflammation. It can participate in the occurrence and development of NDs through different polarization states and play a key role in regulating neurogenesis and synapse shaping and maintaining homeostasis. MG can be divided into M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype according to its function. The inflammatory mediators released by the M1 phenotype can lead to nerve degeneration and myelin sheath damage， while the activation of the M2 phenotype is required to inhibit the inflammatory response and promote tissue repair. With the advantages of multi-pathway， multi-target， and bidirectional regulation， traditional Chinese medicine can regulate the polarization balance of MG and has dual effects on NDs such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis. The active components of traditional Chinese medicine and its compound can inhibit the activation of MG by regulating phosphatidylinositol-3-kinases/protein kinase B（PI3K/Akt）， NOD-like receptor thermal protein domain associated protein 3（NLRP3）， signal transducer and activator of transcription factor1（STAT1）， nuclear transcription factor kappa B（NF-κB）， and other pathways， promote the polarization of M1 phenotype to M2 phenotype， reduce the expression of interleukin（IL）-6， tumor necrosis factor-α（TNF-α）， and other pro-inflammatory factors， and increase the secretion of IL-10， arginase-1（Arg-1）， and other anti-inflammatory factors. It can also reduce β-amyloid deposition and tau protein expression in Alzheimer's disease， alleviate dopaminergic neuronal damage in Parkinson's disease， and relieve demyelination， inflammatory cell infiltration， and related clinical symptoms of multiple sclerosis. The bidirectional regulation of the M1/M2 polarization balance of MG by traditional Chinese medicine is a potential strategy for the treatment of NDs. This paper focused on the targets of the regulation of MG polarization balance by traditional Chinese medicine monomer and its compound in the treatment of NDs， so as to further study and summarize the existing research results and provide ideas and basis for the future treatment of NDs.

Validation of qrs-polarity algorithm with special emphasis in parahisian pathways / Validación del algoritmo de la polaridad del qrs con especial énfasis en vías parahisianas

Abstract Background: In 1996 Iturralde et al. published an algorithm based on the QRS polarity to determine the location of the accessory pathways (AP), this algorithm was developed before the massive practice of invasive electrophysiology. Purpose: To validate the QRS-Polarity algorithm in a modern cohort of subjects submitted to radiofrequency catheter ablation (RFCA). Our objective was to determinate its global accuracy and its accuracy for parahisian AP. Methods: We conducted a retrospective analysis of patients with Wolff-Parkinson-White (WPW) syndrome who underwent an electrophysiological study (EPS) and RFCA. We employed the QRS-Polarity algorithm to predict the AP anatomical location and we compared this result with the real anatomic location determined in the EPS. To determine accuracy, the Cohen's kappa coefficient (k) and the Pearson correlation coefficient were used. Results: A total of 364 patients were included (mean age 30 years, 57% male). The global k score was 0.78 and the Pearson's coefficient was 0.90. The accuracy for each zone was also evaluated, the best correlation was for the left lateral AP (k of 0.97). There were 26 patients with a parahisian AP, who showed a great variability in the ECG features. Employing the QRS-Polarity algorithm, 34.6% patients had a correct anatomical location, 42.3% had an adjacent location and only 23% an incorrect location. Conclusion: The QRS-Polarity algorithm has a good global accuracy; its precision is high, especially for left lateral AP. This algorithm is also useful for the parahisian AP.

Resumen Antecedentes: En 1996 Iturralde y colaboradores publicaron un algoritmo basado en la polaridad del QRS para determinar la ubicación de las vías accesorias (VA), este algoritmo fue desarrollado antes de la práctica masiva de la electrofisiología invasiva. Objetivo: Validar el algoritmo de la polaridad del QRS en una cohorte moderna de sujetos sometidos a ablación con catéter por radiofrecuencia (ACRF). Nuestro objetivo fue determinar su precisión global y su precisión para las VA parahisianas. Métodos: Realizamos un análisis retrospectivo de pacientes con síndrome de Wolff-Parkinson-White (WPW) a los que se les realizó estudio electrofisiológico (EEF) y ACRF. Empleamos el algoritmo de la polaridad del QRS para predecir la ubicación anatómica de la VA y comparamos este resultado con la ubicación anatómica real determinada en el EEF. Para determinar la precisión se utilizaron el coeficiente kappa de Cohen (k) y el coeficiente de correlación de Pearson. Resultados: Se incluyeron un total de 364 pacientes (edad media 30 años, 57 % varones). La puntuación k global fue de 0,78 y el coeficiente de Pearson de 0,90. También se evaluó la precisión para cada zona, la mejor correlación fue para las VA laterales izquierdas (k de 0.97). Hubo 26 pacientes con VA parahisianas, que mostraron una gran variabilidad en las características del ECG. Empleando el algoritmo de la polaridad del QRS, el 34,6 % de los pacientes tenía una ubicación anatómica correcta, el 42,3 % tenía una ubicación adyacente y solo el 23 % una ubicación incorrecta. Conclusión: El algoritmo de la polaridad del QRS tiene una buena precisión global; su precisión es alta, especialmente para VA lateral izquierdo. Este algoritmo también es útil para la VA parahisiana.

Network-based Toxicogenomics Approach to Unraveling the Influence of Lead and Cadmium Mixture on the Development and Progression of Hypertension

Heavy metals, generally characterized by high densities and atomic weights, are ubiquitous in the environment and are a public health concern due to the several health issues they pose to humans. Of all heavy metals, lead and cadmium among others are known to be capable of inducing multiple health effects even at a low rate of exposure. Hypertension (HYP), a major cause of death and a risk factor for other cardiovascular diseases, is known to be caused by both lead and cadmium. While the mechanism underlying the development of HYP induced by independent exposure to lead and cadmium has been well studied, the mechanism underlying the induction and progression of HYP upon lead and cadmium co-exposure remains mildly explored. Hence, this study aimed to elucidate the mechanism using a toxicogenomic approach. The set of genes affected by both heavy metals was identified using the comparative toxicogenomics database (CTD) while HYP targets were retrieved from the Gene Cards database. The shared genes between the heavy metals and the disease were identified and subjected to further analysis. The results of our analysis revealed the signaling pathways that are dysregulated by lead and cadmium co-exposure while oxidative stress, inflammation, and endothelial dysfunction were revealed as processes pertinent to the induction and progression of HYP by lead and cadmium co-exposure. Biomarkers that could be used for prognosis evaluation were also identified. Ultimately, this study supports and advances the growing body of finding on the roles played by lead and cadmium co-exposure in inducing HYP.

Preoperative clinical management of patients who are candidates for facial transplantation / Manejo clínico pré-operatório de pacientes candidatos ao transplante facial

Introduction: Face transplantation has gained recognition, changing the clinicalsurgical scenario for restoring complex facial defects, as it attributes functional and aesthetic recovery to patients who have suffered serious accidents. At the time of writing this article, in official publications, 43 patients had already undergone facial transplantation worldwide. Face transplantation has numerous pieces of evidence that can irrefutably provide improvements to the patient. For this, preoperative care for the patient must be carefully established so that there is good surgical performance. Case Report: Male patient, 46 years old, reports that, at the age of 6, he had burns due to exposure to gasoline, with 72% of his body surface burned, showing sequelae of burns and surgical reconstructions on the face, with redundant and ptotic skin flap on the left cheek, absence of upper and lower lip and exposure of lower teeth. Conclusion: It is important to publicize this innovative procedure in different medical specialties and preoperative care through a thorough investigation, which attributes better surgical effectiveness, allowing the rescue of their facial identity, once stigmatized.

Introdução: O transplante de face adquiriu reconhecimento, alterando o panorama clínico-cirúrgico para a restauração de defeitos faciais complexos, visto que atribui recuperação funcional e estética a pacientes que sofreram acidentes graves. Até o momento da redação deste artigo, em publicações oficiais, 43 pacientes já haviam realizado o transplante facial em todo mundo. O transplante de face possui inúmeras evidências que podem fornecer melhorias ao paciente de forma irrefutável. Para isso, cuidados pré-operatórios ao paciente devem ser cuidadosamente estabelecidos para que haja um bom desempenho cirúrgico. Relato de Caso: Paciente sexo masculino, 46 anos, relata que, aos 6 anos de idade, teve queimadura por exposição à gasolina, com 72% de superfície corporal queimada, apresentando sequelas de queimaduras e reconstruções cirúrgicas na face, com retalho cutâneo redundante e ptótico em bochecha esquerda, ausência de lábio superior e inferior e exposição dos dentes inferiores. Conclusão: Ressalta-se a importância da divulgação desse procedimento inovador em diferentes especialidades médicas e dos cuidados pré-operatórios através de uma investigação minuciosa, que atribuem uma melhor eficácia cirúrgica, possibilitando o resgate de sua identidade facial, uma vez estigmatizada.

A systematic review of metabolomic studies on the mechanism of myopia / 中华实验眼科杂志

Myopia has become a global public health concern with its increasing prevalence.It is the interaction result of genetic and environmental factors.Exploration of the changes of metabolites in myopia is helpful to know new clues about its pathogenic mechanism.Metabolomics focuses on the integral analysis of all small molecular metabolites (relative molecular mass <1 000) which form a biological system and it is used as an effective tool to discover potential biomarkers.Metabolomic analysis of the myopic population could discover the metabolic changes related to myopia and screen the markers with potential biological significance, which can be used in the early diagnosis and treatment of myopia.It has been found that metabolites related to oxidative stress and inflammation play an important role in the development of myopia.Abnormal energy metabolism and amino acid metabolism are associated with myopic fundus changes.In addition, classical myopia-associated metabolites such as retinoic acid, dopamine and vitamin D, other metabolites such as melatonin, cyclic adenosine monophosphate and 5-hydroxy indole acetic acid, as well as multiple metabolic pathways such as fatty acid metabolism and mitochondrial metabolism are all closely related to myopia.This article systematically reviewed metabolomics researches on myopia, providing clues for better prevention and control of myopia in the future.

Research progress of Chinese materia medica in inhibiting malignant biological behavior of lung cancer stem cells / 国际中医中药杂志

Chinese materia medica can inhibit the proliferation, invasion, migration and expression of drug-resistant proteins of lung cancer stem cells (LCSCs), and induce apoptosis and delay self-renewal, as well as exert anti-tumor effects by interfering with their ecological niche, immune microenvironment and aerobic glycolysis, etc. The biomarkers involved mainly include CD133, CD44, ALDH and ABCG2, while the related signaling pathways are Wnt/β-catenin, Hedgehog, and Notch. The research on the intervention of LCSCs by Traditional Chinese Medicine (TCM) is generally few, mostly concentrated in basic research, and the selected experimental indicators have a high repetition rate, involving fewer cell types and signaling pathways; there is a relative lack of clinical trials, which lack an organic connection with basic experiments. In the future, the quality of research is expected to be improved, and in-depth study of TCM with anti-lung cancer stem cell effect should be carried out, with the purpose to promote the precise treatment of lung cancer.

Analysis on Metabolites and Metabolic Pathways of Limonin in Rats by UHPLC-Q-Orbitrap HRMS / 中国实验方剂学杂志

ObjectiveUltra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UHPLC-Q-Orbitrap HRMS） was used to identify the metabolites of limonin in rats， and to explore the gender differences in the distribution of prototype components and metabolites in rats after single dose intragastric administration of limonin， as well as to speculate the metabolic pathways. MethodThe separation was performed on a Thermo Scientific Accucore™ C18 column（3 mm×100 mm， 2.6 μm） with 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） as mobile phase in a gradient elution mode（0-1 min， 5%B； 1-6 min， 5%-20%B； 6-18 min， 20%-50%B； 18-23 min， 50%-80%B； 23-25 min， 80%-95%B； 25-30 min， 95%B） at a flow rate of 0.3 mL·min-1 and a column temperature of 30 ℃. MS data of biological samples were collected under the positive ion mode of electrospray ionization（ESI） and in the scanning range of m/z 100-1 500. Plasma， tissues（heart， liver， spleen， lung， kidney， stomach and small intestine）， urine and fecal samples were collected and prepared after intragastric administration， and the prototype component and metabolites of limonin were identified. ResultThe prototype component of limonin were detected in the feces， stomach， small intestine of female and male rats， and in the heart， liver， spleen， lung and kidney tissues of female rats. A total of 23 metabolites related to limonin were detected in rats， of which 2， 1， 5， 4， 23 metabolites were detected in liver， stomach， small intestine， urine and feces， respectively， and the main metabolic pathways were hydrolysis， reduction， hydroxylation and methylation， etc. The distribution of some metabolites differed between male and female rats. ConclusionThe prototype component of limonin are mainly distributed in the stomach and small intestine in rats， and the distribution of prototype component and some metabolites are different by gender. Limonin is mainly excreted through feces with phase Ⅰ metabolites as the main ones. The results of this study can provide a reference for further elucidation of the effect of gender differences on the metabolism of limonin in vivo and its mechanism of action.

Research Progress of the Effect of Microgravity on Cellular Senescence / 医用生物力学

Microgravity is a typical feature of the space. A large number of space flights and foundation simulation experiments have shown that cells show typical biological characteristics of aging, such as reduced cell proliferation and cell cycle arrest under microgravity or simulated microgravity. However, the molecular mechanism by which microgravity or simulated microgravity affects cellular senescence is not well understood. Understanding the mechanism controlling cellular senescence induced by microgravity environment is helpful for exploring anti-aging strategies and targeted interventions in space. In recent years, domestic and foreign scholars have carried out a number of researches and explorations on the effect of microgravity and simulated microgravity on cellular senescence as well as the related mechanisms. In this review, the latest research progress of this filed was summarized.

Signaling Pathways Related to Diabetic Peripheral Neuropathy Treated by Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy （DPN） is one of the common complications of diabetes. The disease has a long course with nerve pain and other symptoms， seriously affecting the quality of life of patients. DPN is related to high glucose in vivo， inflammation， oxidative stress， apoptosis， and autophagy， involving phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， nuclear factor-κB （NF-κB）， mitogen-activated protein kinase （MAPK）， and other signaling pathways. At present， the treatment of DPN mainly focuses on symptomatic treatments such as blood glucose control and neurotrophic therapy， but the effect is not ideal. Therefore， it is particularly important to select a reasonable and effective drug to prevent and treat DPN. In recent years， Chinese medicine has played an important role in the treatment of DPN. Many studies have explored the mechanism of Chinese medicine in the treatment of DPN， and it has been found that some Chinese medicine monomers and compounds can regulate signaling pathways to prevent and treat DPN. This paper reviewed the research results of signaling pathways involved in DPN and the regulation of related pathways by Chinese medicine， aiming to provide references for the clinical treatment of DPN.

Signaling Pathways Related to Irritable Bowel Syndrome Treated by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Irritable bowel syndrome （IBS） is a functional gastrointestinal disease， but it often causes extreme gastrointestinal discomfort and prolonged illness， which seriously affects the quality of life of patients. The global incidence rate is increasing year by year. Clinically， western medicine mainly uses oral antispasmodics， secretagogues， and antidepressants， but there are many disadvantages such as adverse reactions and poor long-term efficacy. Therefore， finding an efficient and safe treatment method is an urgent problem to be solved. A large number of studies have shown that traditional Chinese medicine has definite curative and long-lasting effects on the treatment of IBS， which has become a hot research direction in recent years. By searching Chinese and foreign literature， it is found that electroacupuncture， moxibustion， Chinese medicine monomers， and compound decoctions are the main methods in the mechanism research of traditional Chinese medicine in the treatment of IBS-related pathways， and their signaling pathways involve nuclear transcription factor kappa B （NF-κB）， transient receptor potential vanillin subfamily 1 （TRPV1）， 5-hydroxytryptamine （5-HT）， mitogen-activated protein kinase （MAPK）， and so on. Traditional Chinese medicine can repair intestinal inflammation， reduce visceral sensitivity， enhance intestinal mucosal barrier， and regulate intestinal motility by regulating this series of signaling pathways， thereby playing an important role in the treatment of IBS with multi-level， multi-link and multi-target characteristics. Based on the cell signaling pathways， this paper reviewed the research progress on the mechanism of traditional Chinese medicine in the treatment of IBS， hoping to provide theoretical support and diagnosis and treatment ideas for the clinical treatment of IBS with traditional Chinese medicine.

Research progress on targeted drugs for vascular malformations / 口腔疾病防治

@#Vascular malformations, which mainly occur in the head and neck region, are a group of congenital disorders that cannot involute and dilate gradually as patients grow. Traditional therapeutic strategies for vascular malformations include laser therapy, sclerotherapy, interventional embolization, surgical resection, etc. However, for some cases with a relatively larger range of lesions, traditional therapeutic strategies might fall short of the goals. With the development of molecular genetics, gene mutations are currently recognized as the root cause of the occurrence of vascular malformations. The progression of vascular malformation lesions is further promoted by the activation of related pathways. Low-flow vascular malformations mainly involve activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, whereas high-flow vascular malformations mainly involve activation of the rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MAPKK)/extracellular-signal regulated protein kinase (ERK) pathway. Targeted drugs against relevant gene mutations and signaling pathways have also been applied in the treatment of vascular malformations, and previous studies have shown that the mTOR inhibitor rapamycin is effective and now widely used in the treatment of low-flow vascular malformations. The PI3K inhibitor alpelisib is also promising in the treatment of venous malformations, and the MAPKK inhibitor trametinib has shown good results in the treatment of arteriovenous malformations. Therefore, traditional therapies supplemented by targeted drugs may bring new breakthroughs to the treatment of vascular malformations.

Mechanism of tonifying kidney and activating blood therapy for premature ovarian failure:a review / 中国中药杂志

Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-β/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.

Rapid characterization and identification of non-volatile constituents in Pogostemonis Herba by UPLC-Q-TOF-MS combined with UNIFI and an in-house library / 中国中药杂志

This study aimed to characterize and identify the non-volatile components in Pogostemonis Herba by using ultra-perfor-mance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with UNIFI and an in-house library. The chemical components in 50% methanol extract of Pogostemonis Herba were detected by UPLC-Q-TOF-MS in both positive and negative MS~E continuum modes. Then, the MS data were processed in UNIFI combined with an in-house library to automatically characterize the metabolites. Based on the multiple adduct ions, exact mass, diagnostic fragment ions, and peak intensity of compounds and the fragmentation pathways and retention behaviors of reference substances, the structures identified by UNIFI were further verified and those of the unidentified compounds were tentatively elucidated. A total of 120 compound structures were identified or tentatively identified, including flavonoids, phenylpropanoids, phenolic acids, terpenes, fatty acids, alkaloids, and phenylethanoid glycosides. Sixteen of them were accurately identified by comparison with reference substances, and 53 compounds were reported the first time for Pogostemonis Herba. This study systematically characterized and identified the non-volatile compounds in Pogostemonis Herba for the first time. The findings provide a scientific basis for revealing the pharmacodynamic material basis, establishing a quality control system, and developing products of Pogostemonis Herba.

Chinese Medicine Monomers Against Pancreatic Cancer： A Review / 中国实验方剂学杂志

Pancreatic cancer is a disease with a high fatality rate， with a five-year survival rate of no more than 10% and a significantly increasing annual mortality rate. The common pathogenesis factors of pancreatic cancer are family inheritance， diet， pancreatitis， obesity， etc.， among which， family inheritance of pancreatic cancer is the main reason， and about 7%-10% of patients have family inheritance. Surgery is an effective way to treat pancreatic cancer in patients and improve their survival， but most people are diagnosed with pancreatic cancer at intermediate and advanced stages and lose the opportunity for surgical treatment. Therefore， radiotherapy， interventional therapy， supportive treatment， immunotherapy， and other treatments are used clinically to relieve symptoms and prolong the survival of patients. The commonly used clinical drug is gemcitabine. Although it can inhibit tumor growth and improve the condition， it can bring side effects such as bone marrow suppression， rash， digestive tract side effects， and drug resistance. The damage of these side effects to the human body is systemic. Chinese medicine can be used alone or in combination with other treatment methods to reduce the toxic and side effects of chemotherapy， restore the physical energy of patients， and reduce its related complications. Chinese medicine contains a large number of active ingredients， including alkaloids， flavonoids， saponins， phenolic acids， and organic acids， with anti-inflammatory， anti-viral， anti-tumor， and other curative effects. Many clinical studies of traditional Chinese medicine （TCM） on cancers have verified that TCM plays a positive role in tumor prevention and treatment， especially in improving and controlling clinical symptoms， and also plays a good detoxification effect on radiotherapy and chemotherapy， with good results achieved in improving bone marrow suppression， improving immunity， improving quality of life， and prolonging survival. This paper reviewed the anti-pancreatic cancer mechanism of Chinese medicine monomers based on literature in China and abroad， aiming to provide new potential drug candidates for the treatment of pancreatic cancer.

Myocardial insulin resistance and systemic arterial hypertension / Resistência insulinica miocárdica e hipertensão arterial sistêmica

Background: Low availability of Glut-4 transporters in the sarcolemma of cardiac cells characterizes myocardial insulin resistance (MIR), which is triggered separately from generalized insulin resistance. Insulin receptors are quite evident in the heart muscle and vessels, and mitochondrial activity performs a significant role in MIR preserving cellular homeostasis through cell reproduction, cells livelihoods, and energy generation. Objective: To evaluate the MIR mechanism and its association with hypertension by signaling pathways design. Methods: PubMed database was employed to search for reviews publications with MIR. The referenced data of the signaling pathway was chosen by aggregating references from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. A signaling pathway was designed based on MIR research manuscripts, where we show several mechanisms included in the MIR. The KEGG server was employed to exploit the interrelationship protein-protein, and elaborate signaling pathway diagram. The signaling pathway mapping was carried out with PathVisio software. Results: We selected 42 articles from a total of 450 articles in the PubMed database that presented a significant association between the terms "insulin resistance myocardial" AND "signaling pathway" AND "systemic arterial hypertension". Founded on database-validated research papers, we chose well-founded pathways and we succeeded in representative description of these pathways. The reproduction contigs taken from the KEGG database designed the signaling pathway of the bio-molecules that lead to MIR. Thus, the acting among multiple mechanisms releases factors that participate in the development of MIR. Conclusion: The interaction among various mechanisms and molecular interactions are important factors in developing MIR (AU).

Introdução: A baixa disponibilidade de transportadores Glut-4 no sarcolema das células cardíacas caracteriza a resistência à insulina miocárdica (MIR), que é desencadeada separadamente da resistência generalizada à insulina. Os receptores de insulina são bastante evidentes no músculo cardíaco e nos vasos, e a atividade mitocondrial desempenha uma função significativa no MIR, preservando a homeostase celular pela reprodução celular, subsistência das células e geração de energia. Objetivo: Avaliar o mecanismo MIR e sua associação com hipertensão por meio do desenho de vias de sinalização. Métodos: A base de dados PubMed foi empregada para pesquisar publicações de revisões com MIR. Os dados referenciados da via de sinalização foram escolhidos agregando referências do banco de dados Kyoto Encyclopedia of Genes and Genomes (KEGG). Uma via de sinalização foi projetada com base em manuscritos de pesquisa MIR, onde mostramos vários mecanismos incluídos no MIR. O servidor KEGG foi empregado para explorar a inter-relação proteína-proteína e elaborar o diagrama de vias de sinalização. O mapeamento das vias de sinalização foi realizado com o software PathVisio. Resultados: Foram selecionados 42 artigos de um total de 450 artigos na base de dados PubMed que apresentavam associação significativa entre os termos "insulin resistance miocárdio" AND "signalingway" AND "systemic arterial hypertension". Com base em trabalhos de pesquisa validados por banco de dados, escolhemos caminhos bem fundamentados e conseguimos uma descrição representativa desses caminhos. Os contigs de reprodução retirados do banco de dados KEGG desenharam a via de sinalização das biomoléculas que levam ao MIR. Assim, a atuação entre múltiplos mecanismos libera fatores que participam do desenvolvimento da MIR. Conclusão: A interação entre vários mecanismos e interações moleculares são fatores importantes no desenvolvimento de MIR (AU).

Trajetórias assistenciais de usuários com COVID-19: das medidas preventivas à reabilitação / Trayectorias asistenciales de usuarios con el COVID-19: de las medidas preventivas a la rehabilitación / Care trajectories of COVID-19 patients: from preventive measures to rehabilitation

O objetivo deste trabalho é analisar as trajetórias assistenciais, relativas ao uso e acesso às redes de atenção à saúde (RAS), de usuários diagnosticados, internados e em reabilitação decorrente da COVID-19. Foi realizado estudo avaliativo, qualitativo, com base em entrevistas com usuários, no Município de Niterói, Rio de Janeiro, Brasil. As trajetórias assistenciais, a partir da análise temática, foram reconstituídas em três momentos que expressam as experiências com a rede de saúde e apoio durante a pandemia: medidas de prevenção, apoio e diagnóstico; a experiência da internação; cuidados, reabilitação e apoio pós-COVID-19. Os resultados apontam que a principal fonte de informação sobre a doença foram os telejornais; as medidas preventivas de higienização, as mais adotadas; e a família foi a principal rede de apoio. Não houve tempos de espera para internação no hospital municipal de referência. A internação foi muito bem avaliada em função do acolhimento, cuidado multiprofissional, visitas virtuais e contato diário do médico com os familiares. Identificou-se, porém, "vácuo assistencial" pós-alta, com ausência de seguimento pela atenção primária à saúde (APS) e demais serviços públicos. Foi frequente a busca espontânea por planos populares e pagamento direto para acesso aos serviços especializados no pós-COVID-19, até a implantação do serviço de reabilitação. Em síntese, trajetórias assistenciais solitárias e descontínuas de indivíduos e famílias revelam diversos desafios ao sistema de saúde, entre os quais a garantia de acesso e coordenação dos cuidados pela APS, ampliação da oferta de serviços públicos especializados e de reabilitação em redes, alinhados aos princípios do cuidado humanizado, além da manutenção das medidas de apoio social.

Este artículo tiene por objetivo analizar las trayectorias asistenciales de usuarios diagnosticados, hospitalizados y en rehabilitación por el COVID-19 en cuanto al uso y acceso a las redes de atención a la salud (RAS). Se realizó un estudio cualitativo, evaluativo, a partir de entrevistas con usuarios en el municipio de Niterói, Rio de Janeiro, Brasil. A partir del análisis temático, las trayectorias asistenciales se reconstituyeron en tres momentos que expresan las experiencias con la red de salud y de apoyo durante la pandemia: las medidas de prevención, apoyo y diagnóstico; la experiencia de hospitalización; y los cuidados, rehabilitación y apoyo post-COVID-19. Los resultados muestran que los telediarios fueron la principal fuente de información sobre el COVID-19. Las medidas preventivas más adoptadas fueron las de higiene. La familia fue la principal red de apoyo. No hubo tiempo de espera para el ingreso en el hospital municipal de referencia. La hospitalización fue muy bien evaluada debido a la recepción, atención multidisciplinaria, visitas virtuales y contacto diario del médico con los familiares. Se identificó un "vacío asistencial" posterior al alta, sin seguimiento por parte de la atención primaria de salud (APS) y otros servicios públicos. Hubo una frecuente búsqueda espontánea de planes populares y pago directo para acceder a servicios especializados post-COVID-19 hasta la implementación del servicio de rehabilitación. Por lo tanto, las trayectorias asistenciales solitarias y discontinuas de individuos y familias revelan varios desafíos para el sistema de salud, entre ellos la garantía de acceso y coordinación de la atención por parte de la APS, la ampliación de la oferta de servicios públicos especializados y la rehabilitación en redes, combinada con los principios de cuidado humanizado, además del mantenimiento de las medidas de apoyo social.

This study aims to analyze the care trajectories of patients diagnosed with COVID-19 who were hospitalized and are currently undergoing rehabilitation regarding their use of and access to the healthcare network (HN). An evaluative, qualitative study was carried out based on interviews with patients in the city of Niterói, Rio de Janeiro State, Brazil. The care trajectories were reconstructed at three different occasions that express their experiences with the healthcare and support network during the pandemic: prevention, support and diagnosis measures; hospitalization; post-COVID-19 care, rehabilitation and support. The results indicate that the main source of information about COVID-19 was TV newscasts. Preventive hygiene measures were the most widely adopted. The family was the main support network. There was no waiting time for admission to the municipal referral hospital. Hospitalization was very well evaluated in terms of user embracement, multidisciplinary care, virtual visits and daily contact between doctor and family members. A post-discharge "care vacuum" was identified, with no follow-up by primary health care (PHC) and other public services. Low-cost health insurance plans and private specialized post-COVID-19 services were frequently and spontaneously sought until the implementation of the rehabilitation service. In summary, solitary and discontinuous care trajectories of individuals and families shed light on several challenges to the health system, including guaranteed access to coordinated PHC and expanded offer of specialized public services and rehabilitation, aligned with the principles of humanized care, in addition to the maintenance of social support measures.

Ebola outbreak in Guinea, 2021: Clinical care of patients with Ebola virus disease

Background: Experience from the Zaire Ebolavirus epidemic in the eastern Democratic Republic of the Congo (2018­2020) demonstrates that early initiation of essential critical care and administration of Zaire Ebolavirus specific monoclonal antibodies may be associated with improved outcomes among patients with Ebola virus disease (EVD). Objectives: This series describes 13 EVD patients and 276 patients with suspected EVD treated during a Zaire Ebolavirus outbreak in Guinea in 2021. Method: Patients with confirmed or suspected EVD were treated in two Ebola treatment centres (ETC) in the region of N'zérékoré. Data were reviewed from all patients with suspected or confirmed EVD hospitalised in these two ETCs during the outbreak (14 February 2021 ­ 19 June 2021). Ebola-specific monoclonal antibodies, were available 2 weeks after onset of the outbreak. Results: Nine of the 13 EVD patients (age range: 22­70 years) survived. The four EVD patients who died, including one pregnant woman, presented with multi-organ dysfunction and died within 48 h of admission. All eight patients who received Ebola-specific monoclonal antibodies survived. Four of the 13 EVD patients were health workers. Improvement of ETC design facilitated implementation of WHO-recommended 'optimized supportive care for EVD'. In this context, pragmatic clinical training was integrated in routine ETC activities. Initial clinical manifestations of 13 confirmed EVD patients were similar to those of 276 patients with suspected, but subsequently non confirmed EVD. These patients suffered from other acute infections (e.g. malaria in 183 of 276 patients; 66%). Five of the 276 patients with suspected EVD died. One of these five patients had Lassa virus disease and a coronavirus disease 2019 (COVID-19) co-infection. Conclusion: Multidisciplinary outbreak response teams can rapidly optimise ETC design. Trained clinical teams can provide WHO-recommended optimised supportive care, including safe administration of Ebola-specific monoclonal antibodies. Pragmatic training in essential critical care can be integrated in routine ETC activities. Contribution: This article describes clinical realities associated with implementation of WHO-recommended standards of 'optimized supportive care' and administration of Ebola virus specific treatments. In this context, the importance of essential design principles of ETCs is underlined, which allow continuous visual contact and verbal interaction of health workers and families with their patients. Elements that may contribute to further quality of care improvements for patients with confirmed or suspected EVD are discussed.

Chemical Components Distribution and Transcriptome Analysis of Different Tissues from Codonopsis pilosula / 中国实验方剂学杂志

ObjectiveThe transcriptome characteristics of different tissues of Codonopsis pilosula were analyzed to illustrate the genetic basis of the accumulation of active ingredients in the root of C. pilosula， and to provide theoretical basis for its high-quality production and cultivation. MethodDifferent tissues of C. pilosula at flowering stage were selected as experimental materials， and the contents of tangshenoside Ⅰ， lobetyolin and atractylenolide Ⅲ were detected by high performance liquid chromatography（HPLC）. RNA-Seq was used to perform transcriptome sequencing of different tissues， and the differentially expressed genes were screened and analyzed by Gene Ontology（GO） and Kyoto Gene and Encyclopedia of Genes and Genomes（KEGG） enrichment analysis， in order to explore the characteristics of active compound distribution and the transcriptional profiles. ResultThe contents of polysaccharides and tangshenoside Ⅰ in the root of C. pilosula were significantly higher than those in other tissues. The transcriptional profiles of the root were significantly different from those of stem， leaf and flower. Cluster analysis， GO and KEGG enrichment analysis of differential gene expression showed that the differential expression genes were mainly enriched in flavonoid and phenylpropanoid biosynthesis， sucrose-starch metabolism， plant hormone signal transduction， plant-pathogen interaction， mitogen-activated protein kinase（MAPK） cascade signal transduction， Adenosine triphosphate（ATP）-binding cassette（ABC） transporter and other pathways. The expression of genes related to biosynthesis of phenylpropanoid compounds were significantly up-regulated in the roots and flowers， and ABC transporter proteins were mostly highly expressed in the flowers. The expression of key enzyme genes for polysaccharide synthesis， such as sucrose：sucrose 1-fructosyltransferase（1-SST） and fructan 1-exohydrolase（1-Feh）， were significantly up-regulated in the roots， and a large number of stress-responsive genes closely related to the accumulation of secondary metabolites were significantly up-regulated in the roots. ConclusionThe active compound content and transcriptional profiles in C. pilosula roots were significantly different from those in stem， leaf， flower and other tissues， showing tissue specificity. Meanwhile， the genes related to stress response and biosynthesis of active compound， such as fructan and phenylpropanoid compounds， were up-regulated in roots of C. pilosula.