Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer's Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice / 神经科学通报·英文版

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

Traditional Chinese Medicine Syndromes in Depressive Episodes of Bipolar Disorder Based on Cluster Analysis and Bayesian Network：A Cross-sectional Study / 中医杂志

ObjectiveTo explore the elements， distribution and characteristics of traditional Chinese medicine （TCM） syndromes in depressive episodes of bipolar disorder （BD）. MethodsBasic information， along with the four examination information， the Hamilton Depression Scale and Young Mania Rating Scale scores， were collected from 293 outpatients with BD at Beijing Anding Hospital， Capital Medical University. The four examination information with an occurrence rate greater than 12% were retained. The R language “dist” function was used to calculate the distances between samples using the Euclidean distance method. The hierarchical clustering of the four examination information was performed using the “hclust” function and the squared Euclidean distance method. A team of five researchers was formed to determine the nature and location of the essential elements of TCM syndrome in BD based on the clustering results. The PC algorithm was used to construct a Bayesian network model of the essential elements. The working group combined the essential elements of TCM syndromes in the Bayesian network according to the reference model results， and then extracted common TCM syndromes. The score of each patient based on the essential elements was matched with the common TCM syndromes to determine the syndrome type of each patient. The working group then performs conformity and revision based on this， obtaining the final distribution of TCM syndromes for the patients. ResultsThere were 77 common TCM symptoms in BD with a frequency greater than 12%. The top 15 symptoms with higher frequencies were slippery pulse， mental fatigue and lack of strength， wiry pulse， excessive rumination， preference for solitude， vexation， agitation and irritability， dry mouth， palpitations， profuse dreaming， unwarranted worries， chest oppression， thin white coating， amnesia， frequent sighing， and poor appetite. TCM syndrome elements of BD can be grouped into 11 categories. The nature of disease-related essential elements included fire， qi deficiency， blood deficiency， qi counterflow， yin deficiency， dampness， heat， fire from constraint， and phlegm. The location of disease-related essential elements included heart， liver， spleen， stomach， kidney， bladder channel， and gallbladder. By constructing a Bayesian network model and considering the opinions from the experts， six common syndromes of BD were identified， among which the highest proportion was heart-stomach heat accumulation， accounting for 27.99% （82 cases）， followed by heart-spleen deficiency （55 cases， 18.77%）， non-interaction between the heart and the kidney （49 cases， 16.72%）， liver constraint and blood deficiency （42 cases， 14.33%）， heart qi deficiency （37 cases， 12.63%）， and damp-heat in the liver and gallbladder （28 cases， 9.56%）. ConclusionsThe nature of disease-related elements of BD are predominantly fire and heat， while the location of disease-related essential elements are primarily associated with the heart， liver， and spleen. The most common TCM syndromes are heart-stomach heat accumulation and heart-spleen deficiency.

Clusters Espaço-Temporais de Alto Risco da Mortalidade Infantojuvenil em Mato Grosso, Brasil / High-risk space-time clusters of mortality in children 5 to 14 years of age in Mato Grosso state, Brazil

Resumo O objetivo deste estudo é detectar as áreas de maior risco para óbitos de crianças e adolescentes de 5 a 14 anos no estado de Mato Grosso entre os anos de 2009 e 2020. Estudo ecológico, tipo exploratório, cuja unidade de análise foram os municípios. Considerando dados de mortalidade do SIM e os demográficos do IBGE, o estudo utilizou a estatística multivariada para a identificação dos clusters espaço-temporais de sobrerrisco de mortalidade nesta faixa etária. Dos 5 aos 9 anos, dois clusters de alto risco de mortalidade foram detectados; o mais provável localizado na mesorregião sul (RR: 1,6; LRV: 8,53). Dentre os 5 clusters detectados na faixa etária dos 10 aos 14 anos, o principal foi localizado na mesorregião norte (RR: 2,26; LRV: 7,84). Foi identificada redução das taxas de mortalidade na faixa etária mais jovem e aumento destas taxas na faixa etária mais velha. A identificação destes clusters, cuja análise merece ser replicada a outras partes do território nacional, é a etapa inicial para a investigação de possíveis fatores associados à morbi-mortalidade deste grupo ainda pouco explorado e para o planejamento de intervenções adequadas.

Abstract The study aimed to detect high-risk areas for deaths of children and adolescents 5 to 14 years of age in the state of Mato Grosso, Brazil, from 2009 to 2020. This was an exploratory ecological study with municipalities as the units of analysis. Considering mortality data from the Mortality Information System (SIM) and demographic data from the Brazilian Institute of Geography and Statistics (IBGE), the study used multivariate statistics to identify space-time clusters of excess mortality risk in this age group. From 5 to 9 years of age, two clusters with high mortality risk were detected; the most likely located in the state's southern mesoregion (RR: 1.6; LRT: 8,53). Among the 5 clusters detected in the 10-14-year age group, the main cluster was in the state's northern mesoregion (RR: 2,26; LRT: 7,84). A reduction in mortality rates was observed in the younger age group and an increase in these rates in the older group. The identification of these clusters, whose analysis merits replication in other parts of Brazil, is the initial stage in the investigation of possible factors associated with morbidity and mortality in this group, still insufficiently explored, and for planning adequate interventions.

Perfiles de resiliencia asociados al engagement académico y al apoyo social en estudiantes universitarios / Coping profiles associated with resilience, academic engagement, and social support in university students

Resumen El objetivo de este estudio fue observar los estilos de resiliencia entre estudiantes de pregrado y explorar la forma en la que cada uno de ellos se encontraba asociado al engagement académico y a las redes de apoyo social al inicio de los estudios universitarios. La muestra correspondió a 371 estudiantes de pregrado del Caribe Colombiano evaluados a partir de un análisis estadístico de clústeres, por el método jerárquico aglomerativo. Posteriormente se clasificaron en grupos de acuerdo con sus similitudes en las 12 dimensiones de resiliencia y finalmente se compararon en términos de engagement y redes personales. Los resultados señalaron cuatro perfiles de estudiantes: (1) sujetos con baja-resiliencia, alto engagement y fuertes vínculos relacionales; (2) resilientes-en-proceso, con niveles intermedios de resiliencia, bajo engagement y redes sociales con poca cercanía; (3) resilientes-autónomos con altos puntajes de resiliencia, niveles intermedios de engagementy redes sociales débiles; y (4) resilientes-con-redes, exhibieron altos niveles de resiliencia, con alto engagement y amplias redes de apoyo. Se concluye que la mayor porción de jóvenes que comienzan la universidad muestra perfiles de baja resiliencia; sin embargo, los altos niveles de motivación por los estudios y los recursos sociales como las redes de apoyo de los compañeros son las condiciones que más permiten afrontar los obstáculos de la vida universitaria. Es importante notar que solamente el último perfil integró los elementos de alta resiliencia, alto engagement y fuertes redes de apoyo que permiten confirmar la íntima asociación entre estos constructos. Los otros perfiles representan casos en los cuales los rasgos de resiliencia son independientes de los niveles de engagement y de la composición de las redes de apoyo personal.

Abstract Adjustment of first-year students to university environments, as well as their academic success, is not exclusively related to their academic aptitude; instead, this adjustment is associated with psychological characteristics, personal and even social resources that help students cope with stressors and new circumstances. A comprehensive assessment of the students' adjustment to university environment must transcend preoccupation on academic performance, and instead explore associations among psychological, academic, and social elements that promote adaptation during the initial years of higher education (Marenco-Escuderos et al., 2021). In this line of research, the objective of this work was to inquire how internal characteristics of students (psychological and academic) interplay with external elements in their support systems to promote adaptation in a higher education environment. Associations were explored among resilience, academic engagement, and social support as determining elements in the adjustment to the demands of the university context. The sample consisted of 371 undergraduate students (60 % female), of low socioeconomic status, enrolled in public universities in the Caribbean region of Colombia. Firstly, the resilience of university students was explored, as the ability to respond to obstacles with a positive view of the world, of others, and of one's own abilities to cope with stressors (Saavedra-Guajardo et al., 2019). Second, the level of engagement that drives young students to concentrate their energies on academic activities was reviewed; and third, the role of peers, and friends as the close-support system that facilitates the overcoming of personal and academic difficulties was investigated (Fernández-Martínez et al., 2017). Based on a statistical cluster analysis, by the agglomerative hierarchical method, individuals were classified according to their similarities in the expression of 12 dimensions of resilience (SV-RES scale), and subsequently compared in terms of engagement (UWES-S scale), and personal support networks (UNICET software). The results showed four student profiles: (1) the largest group consisting of students with low-resilience, high engagement and strong support networks; (2) a resilient group with low levels of engagement and support networks with little intimacy; (3) a resilient group with high characteristics of autonomy, intermediate levels of engagement, and support networks with weak structure; and (4) a very resilient group, high engagement, and wide and strong social support networks. The results point out the fact that the greatest proportion of students who start college show profiles of low resilience, however, high levels of motivation for studies and social resources such as peer support networks are the conditions that mostly allow for coping with adversity in the first years of college. These results could point to cultural aspects specific to the Caribbean region, where social networks are of great importance for daily functioning (Marenco-Escuderos et al., 2021). Regarding the association among the studied variables, it is important to note that only the last profile gathered all elements of high resilience, high engagement, and strong support networks that allow for confirming the association among these constructs. The other three profiles represent cases in which the resilience traits are independent of the students' levels of engagement and the composition of their personal support networks. This study is valuable as it provides a differentiating picture of the relationship of resilience with other psychological and social constructs, and in that it allows to better understand resilience in association with other elements that mediate its interpretation. Important gender differences among the profiles are additionally discussed.

The B-cell non-Hodgkin’s lymphoma: An enigma to diagnose

Non-Hodgkin’s lymphoma is a heterogeneous group of malignancies characterized by an abnormal clonal proliferation of T-cells, B-cells, or both. Sometimes, tuberculosis and lymphoma presentation can share common symptoms and features. In this case report, we present the case of a 28-year-old female patient who came with a chief complaint of swelling on the right side of the face for the past 6 months. Initially, it was not associated with pain but gradually developed severe pain over the region and reduced salivary flow. The patient was planned for surgery with a differential diagnosis of salivary gland pathology. Post-operatively, the histopathological report showed atypical cells which were diffusely positive for cluster of differentiation (CD)20. Focally positive for CD45 and CD3 which was positive in reactive T lymphocytes. Immunohistochemistry pattern favors the diagnosis of B-cell type NHL. Through this case report, we want to share our experience in treating an aggressive tumor that mimics salivary gland pathology.

Obesogenic behavior clusters associated with weight status among Brazilian students: a latent class analysis / Agrupamentos de comportamentos obesogênicos associados com status de peso em estudantes brasileiros: uma análise de classe latente

Abstract This study aimed to examine the association between clusters of physical activity (PA), diet, and television viewing (TV) with weight status among a representative sample of Brazilian students. Data from the National Health School-based Survey (PeNSE) 2015 were analyzed (n = 16,521; mean age 14.8, standard deviation 0.03 year). PA (minutes/week spent in leisure-time, and commuting to/from school), TV (hours/day), and weekly consumption of deep-fried empanadas, candies, sodas, ultra-processed foods, fast foods, green salads or vegetables, and fruits were self-reported on the validated PeNSE questionnaire. Latent class analysis defined behavior classes, and binary logistic regression assessed the association between clustering and weight status. Six classes' types with positive and negative behaviors were identified. Adolescents belonging to the "low TV time and high healthy diet" class had higher chances of being overweight (including obesity) compared to their peers in the "moderate PA and mixed diet" class. No associations were found in the other clusters. Mixed classes with healthy and unhealthy behaviors characterized adolescents' lifestyles and these profiles were related to weight status.

Resumo O estudo objetivou examinar a associação entre agrupamentos de atividade física (AF), dieta e tempo de televisão (TV) com o status do peso em uma amostra representativa de estudantes brasileiros. Foram analisados ​​dados da Pesquisa Nacional de Saúde do Escolar (PeNSE) 2015 (n = 16.521; idade média 14,8, desvio padrão de 0,03 ano). AF (minutos/semana no lazer e deslocamento para/da escola), assistir televisão (TV) (horas/dia), consumo semanal de doces, refrigerantes, alimentos ultraprocessados/fast-foods, saladas/vegetais e frutas foram coletadas por questionário validado. Análise de classes latentes definiu os perfis de comportamento e a regressão logística binária a associação entre agrupamento e status de peso. Foram identificadas seis classes com comportamentos positivos e negativos. Adolescentes pertencentes à classe "baixo tempo de TV e alta alimentação saudável" apresentaram maior probabilidade de ter sobrepeso/obesidade em comparação com seus pares na classe "AF moderada e dieta mista". Não foram encontradas associações nos outros perfis. Classes com comportamentos saudáveis ​​e não saudáveis ​​caracterizaram o estilo de vida dos adolescentes e estiveram relacionadas com o status de peso.

Cluster de doenças crônicas não transmissíveis e multimorbidade em trabalhadores da atençãoprimária à saúde / Cluster of chronic non-communicable diseases and multimorbidity in primary healthcare workers

Objetivo: Investigar a agregação das DCNT e a sua associação com as características sociodemográficas e os aspectos ocupacionais dos trabalhadores da APS. Métodos: Tratou-se de um estudo epidemiológico transversal que analisou os dados parciais de uma coorte retrospectiva realizada em Vitória da Conquista (BA) e em São Geraldo da Piedade (MG) no mês de janeiro de 2022 com 105 trabalhadores da Estratégia Saúde da Família (ESF), que preencheram um questionário eletrônico específico autoaplicável. As variáveis analisadas foram: sociodemográficas, caracterização do trabalho, presença de DCNT e de multimorbidade. Foram aplicados os seguintes procedimentos estatísticos: análise descritiva, análise de cluster, teste de qui-quadrado de Pearson e regressão logística binária. Resultados:As cinco DCNT mais prevalentes foram a rinite/sinusite (30,5%), a cefaleia/enxaqueca (26,7%), o colesterol alto (26,7%), a gastrite (19,0%) e a hipertensão arterial sistêmica (19,0%). A prevalência de multimorbidade foi de 26,7% e foram encontradas 11 combinações de cluster (34,4%), sendo o maior escore na combinação das cinco doenças mais prevalentes. Foi identificada a associação entre a presença de multimorbidade e o sexo, sendo a prevalência 24% menor entre os homens, e com a escolaridade, sendo a prevalência 26% maior nos indivíduos que não possuem ensino superior. Conclusão: Foram identificadas associações entre a presença de multimorbidade e o sexo feminino, e indivíduos que não concluíram o ensino superior. Observou-se, ainda, uma associação simultânea das cinco principais DCNT deste estudo com o nível de escolaridade (AU).

Objectives: Investigate the aggregation of NCDs and their association with sociodemographic characteristics and occupational aspects in primary healthcare workers. Methods: A cross-sectional study analyzed partial data from a cohort profile conducted in Vitória da Conquista (BA) and in São Geraldo da Piedade (MG) in January 2022 with 105 workers of "Estratégia de Saúde da Família (ESF)" who answered a self-report electronic questionnaire. The variables of this research were: sociodemographic characteristics, job aspects, and the presence of NCDs and multimorbidity. Data were analyzed with descriptive statistics, cluster analysis, chi-square test, and binary logistic regression. Results: The five NCDs more prevalent were: rhinitis/sinusitis (30,5%), headache/migraine (26,7%), hypercholesterolemia (26,7%), gastritis (19,0%), and hypertension (19,0%). The prevalence of multimorbidity was 26,7%, and 11 cluster combinations were found (34,4%) since the higher score was identified in the aggregation of the five more prevalent diseases. There was an association between the presence of multimorbidity and the sex (the prevalence is 24% smaller for men) and between the presence of multimorbidity and the level of education (the prevalence is 26% higher in people without a college degree). Conclusion: The prevalence of multimorbidity was associated with the female sex and with people without a college degree. Furthermore, an association was observed between the five more prevalent NCDs in this study and the level of education (AU).

Clustering of cardiovascular disease risk factors among first-year students at the University of Ibadan, Nigeria: a cross-sectional study

ABSTRACT BACKGROUND: Cardiovascular disease (CVD) is the second leading cause of death in sub-Saharan Africa. Globally, there is substantial evidence that modifiable risk factors for CVD are increasing in adolescents. Unfortunately, there is a paucity of information on the prevalence and clustering of these risk factors in adolescents. OBJECTIVES: This study explores the modifiable risk factors for CVD among first-year students at the University of Ibadan, Nigeria. DESIGN AND SETTING: This cross-sectional study was conducted at the University of Ibadan, Nigeria. METHODS: A total of 546 newly admitted students at the University of Ibadan, Nigeria, were recruited using stratified random sampling. An interviewer-administered questionnaire was used to obtain information from study participants between January and February 2016. RESULTS: The mean age of respondents was 19 ± 2.2 years with a male-to-female ratio of 1:1. The reported risk factors for CVD were smoking (1.6%), abdominal obesity (3.3%), alcohol consumption (3.7%), overweight/obesity (20.7%), unhealthy diet (85.3%), and physical inactivity (94.5%). Clustering of ≥ 2 risk factors was reported in 23.4% of students. Female students were twice as probably overweight/obese as male students (adjusted odds ratio [AOR] = 2.2; confidence interval [CI] = 1.41-3.43). Students whose fathers were skilled workers were 3.5 times more likely to be physically inactive (AOR = 1.7; CI = 0.97-2.96). The clustering of ≥ 2 risk factors was significantly higher among women and Muslims in bivariate analysis, whereas no significant association was found in multivariate analysis. CONCLUSIONS: Public health strategies to prevent CVD risk factors should begin in schools and extend to the entire community.

Transnasal endoscopy-guided percutaneous access to the sphenopalatine ganglion for neurostimulation in the treatment of primary headache: operative technique and feasibility

Abstract Objectives: Cluster headache is considered a trigeminal autonomic cephalalgia and may present with characteristic symptoms of sympathetic/parasympathetic activation on the affected side of the face, such as nasal discharge, tearing, and conjunctival injection. Invasive therapies targeting the sphenopalatine ganglion have been performed in these headache syndromes and can have a medication-sparing effect, especially in refractory, difficult-to-manage cases. The gate control theory of pain suggests that electric pulses delivered to nerve tissues can modulate neuronal activity, thus aiding in management of nociceptive or neuropathic pain, and studies have demonstrated the efficacy and safety of sphenopalatine ganglion neurostimulation. Within this context, we sought to assess the feasibility of a new surgical technique for neurostimulation of the sphenopalatine ganglion in a cadaver dissection model. Methods: The technique was developed through dissection of two cadaver heads. We divided the procedure into two stages: an endonasal endoscopic approach to expose the sphenopalatine ganglion and confirm electrode placement, and a cervicofacial approach to introduce the electrode array and position the internal pulse-generator unit. Computed tomography was performed to confirm implant placement at the end of the procedure. Results: The pulse-generator unit was successfully placed through a retroauricular incision, as is already standard for cochlear implant placement. This should reduce the incidence of perioperative sequelae, especially pain and swelling in the oral region, which are a common complication of previous approaches used for this purpose. Control imaging confirmed proper electrode placement. The device used in this study allows the patient to modulate the intensity of the stimulus, reducing or even obviating the need for drug therapy. Conclusion: The novel technique described herein, based on percutaneous access guided by transmaxillary endoscopy, can provide great precision in electrode array positioning and decreased perioperative morbidity, combining the advantages of endoscopic approaches with those of the retroauricular route. Level of evidence: 3.

Os perfis de gamers adultos pagantes: uma análise sobre os valores preferidos em jogos / The profiles of paying adult gamers: an analysis of the preferred values in games

Os indivíduos constantemente tomam decisões de consumo, que também impactam na cadeia que participa direta ou indiretamente para a criação daquele produto ou serviço. Assim, compreender melhor os perfis dos consumidores de jogos digitais auxiliam os desenvolvedores locais a produzir jogos que despertem e mantenham o interesse desses gamers, tornando esse, o principal objetivo desta pesquisa. Para tal, utilizou-se a Análise de Clusters, através do método K-means para variáveis categóricas, onde foram encontradas quatro personas. Os grupos com mais idade e com renda mensal de R$ 2.200,01 a R$ 4.400,00 expressou um comportamento prudente em relação aos gastos com jogos (gastaram de 0 a 100 reais, nos últimos 6 meses). Os outros dois grupos restantes, mais jovens, apresentaram características financeiras distintas: o de menor renda mensal (até R$ 1.100,00) não foi o que menos gastou com jogos eletrônicos nos últimos 6 meses (101 a 250 reais). A pesquisa também concluiu que "autonomia para seguir vários caminhos" foi bastante valorizada pelos 4 perfis, nomeados de "jogador retraído", "jogador apaixonado", "jogador nostálgico" e "jogador vontade", refletindo as características principais de cada perfil.

Individuals constantly make consumption decisions, which impact not only the consumer, but also the entire chain that participates directly or indirectly in the creation of that product or service. Thus, there is a need to better understand the profiles of consumers of digital entertainment games, so that local developers can produce games that arouse and maintain the interest of these gamers, making this the main objective of this research. For this, Cluster Analysis was used, through the K-means method for categorical variables, where four personas were found, which were translated by their reference profiles (detailed in D descriptions), and represented a set of similar profiles in the sample space of the respondents, with homogeneous characteristics to this "focal profile". The groups composed of the oldest age group (31 ­ 40 years old) and with a monthly income of BRL 2,200.01 to BRL 4,400.00 expressed a prudent behavior in relation to spending on games (they spent from BRL 0.00 to BRL 100.00 in the last 6 months). The other two remaining groups, formed by the younger age group (21 ­ 30 years), had different financial characteristics: the one with the lowest monthly income (up to BRL 1,100.00) was not the one who spent the least on electronic games in the last 6 months. (BRL 101.00 to BRL 250.00). The survey also concluded that "autonomy to follow several paths" was highly valued by the 4 profiles, named "withdrawn player", "passionate player", "nostalgic player" and "willing player"" to reflect the main characteristics of each profile.

Comparación de dos tipos de clasificación en dispepsia funcional; distrés postprandial o dolor epigástrico vs. un análisis multidimensional por conglomerados utilizando aprendizaje no supervisado

Los métodos de inteligencia artificial utilizando herramientas de aprendizaje no supervisado pueden apoyar la resolución de problemas al establecer patrones de agrupación o clasificación no identificados, que permiten tipificar subgrupos para manejos más individualizados. Existen pocos estudios que permiten conocer la influencia de síntomas digestivos y extradigestivos en la tipificación dispepsia funcional; esta investigación realizó un análisis de aprendizaje no supervisado por conglomerados basándose en dichos síntomas, para discriminar subtipos de dispepsia y comparar con una de las clasificaciones actualmente más aceptadas. Se realizó un análisis exploratorio de conglomerados en adultos con dispepsia funcional según síntomas digestivos, extradigestivos y emocionales. Se conformaron patrones de agrupación de tal manera que dentro de cada grupo existiera homogeneidad en cuanto a los valores adoptados por cada variable. El método de análisis de conglomerados fue bietápico y los resultados del patrón de clasificación se compararon con una de las clasificaciones más aceptadas de dispepsia funcional. De 184 casos, 157 cumplieron con criterios de inclusión. El análisis de conglomerados excluyó 34 casos no clasificables. Los pacientes con dispepsia de tipo 1 (conglomerado uno), presentaron mejoría al tratamiento en el 100% de los casos, solo una minoría presentaron síntomas depresivos. Los pacientes con dispepsia de tipo 2 (conglomerado dos) presentaron una mayor probabilidad de falla al tratamiento con inhibidor de bomba de protones, padecieron con mayor frecuencia trastornos de sueño, ansiedad, depresión, fibromialgia, limitaciones físicas o dolor crónico de naturaleza no digestiva. Esta clasificación de dispepsia por análisis de clúster establece una visión más holística de la dispepsia en la cual características extradigestivas, síntomas afectivos, presencia o no de trastornos de sueño y de dolor crónico permiten discriminar el comportamiento y respuesta al manejo de primera línea.

Artificial intelligence methods using unsupervised learning tools can support problem solving by establishing unidentified grouping or classification patterns that allow typing subgroups for more individualized management. There are few studies that allow us to know the influence of digestive and extra-digestive symptoms in the classification of functional dyspepsia. This research carried out a cluster unsupervised learning analysis based on these symptoms to discriminate subtypes of dyspepsia and compare with one of the currently most accepted classifications. An exploratory cluster analysis was carried out in adults with functional dyspepsia according to digestive, extra-digestive and emotional symptoms. Grouping patterns were formed in such a way that within each group there was homogeneity in terms of the values adopted by each variable. The cluster analysis method was two-stage and the results of the classification pattern were compared with one of the most accepted classifications of functional dyspepsia. Of 184 cases, 157 met the inclusion criteria. The cluster analysis excluded 34 unclassifiable cases. Patients with type 1 dyspepsia (cluster one) presented improvement after treatment in 100% of cases, only a minority presented depressive symptoms. Patients with type 2 dyspepsia (cluster two) presented a higher probability of failure to treatment with proton pump inhibitor, suffered more frequently from sleep disorders, anxiety, depression, fibromyalgia, physical limitations or chronic pain of a non-digestive nature. This classification of dyspepsia by cluster analysis establishes a more holistic vision of dyspepsia in which extradigestive characteristics, affective symptoms, presence or absence of sleep disorders and chronic pain allow discriminating behavior and response to first-line management.

Radix Tetrastigme Polysaccharide Promotes Antitumor Immune Response in Lewis Lung Cancer Mice / 中国肺癌杂志

BACKGROUND@#Lung cancer has a high incidence and mortality rate, but the treatment of lung cancer still lacks low toxicity and efficient anti-tumor drugs. Polysaccharide from radix tetrastigme has development value in anti-tumor treatment methods. This study was to observe the effect of polysaccharide from radix tetrastigme on immune response of Lewis lung cancer mice and explore its molecular mechanism.@*METHODS@#Lewis lung cancer mouse models were established and randomly grouped. The spleen polypeptide group was intragastric with 50 mg/kg spleen polypeptide, and the radix tetrastigme polysaccharide low, medium and high dose groups were intragastric with 62.5, 125 and 250 mg/kg radix tetrastigme polysaccharide, respectively, and the model group and the control group were intragastric with equivolume normal saline. Tumor formation and metastasis were compared. Haematoxylin-eosin (HE) staining was used to observe the pathological changes of tumor cells. Macrophage phagocytosis, apoptosis, M1/M2 polarization, T cell subsets and cytokine levels in peripheral blood were detected by flow cytometry. The proliferation activity of macrophages was detected by methyl thiazolyldiphenyl tetrazolium (MTT) assay. Dendritic cell (DC) antigen presenting function was detected by chlorophenol red-β-D-galactopyranoside (CPRG) method. Tumor tissue differentiation antigen cluster 47 (CD47) mRNA and protein expression and macrophage signal regulatory protein α (SIRRP α) expression were detected by real time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB).@*RESULTS@#The tumor inhibition rates and anti-metastasis rates in the 3-dose radix tetrastigme polysaccharide group and the spleen polypeptide group were higher than those in the model group, and the pathological injury of tumor tissue were severer, and the positive rate of phagocytosis of ink by macrophages and the efficiency of phagocytosis of tumor cells were increased; the apoptosis rate of macrophages was decreased; the proliferation activity of macrophages, polarization ratio of macrophages to M1 type, DC antigen presenting ability, CD4+, CD4+/CD8+ levels were increased; the level of serum tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and the expression of tumor tissue CD47, macrophage SH2-containing protein tyrosine phosphatase 1 (SHP-1), SH2-containing protein tyrosine phosphatase 2 (SHP-2), and phosphorylation signal regulatory protein α (p-SIRPα) were decreased, and the differences were statistically significant (P<0.05). There were no significant differences in the above indexes between low-dose radix tetrastigme polysaccharide group and spleen polypeptide group (P>0.05), and the effects of radix tetrastigme polysaccharide were dose-dependent.@*CONCLUSIONS@#Radix tetrastigme polysaccharide can inhibit tumor growth, metastasis and immune response in Lewis lung cancer mice, and its mechanism may be related to inhibiting SIRP/CD47 signaling pathway.

Analysis of Medication Rules of Traditional Chinese Medicine for Malaria Treatment Based on Data Mining / 中国医学科学杂志(英文版)

Objective To analyze the medication rules of traditional Chinese medicine (TCM) for malaria treatment.Methods Statistical analysis was conducted on the basic attributes of TCM drugs with regard to property, therapeutic methods, flavor, and meridian tropism. A complex network of TCM drug associations was constructed. Cluster analysis was applied to obtain the core drugs for malaria treatment. The Apriori algorithm was applied to analyze the association rules of these core drugs.Results A total of 357 herbs were used 3,194 times in 461 prescriptions for malaria treatment. Radix Glycyrrhizae (), Rhizoma Pinelliae (), Radix Bupleuri (), and Radix Dichroae () were the frequently used herbs through supplementing, exterior-releasing, heat-clearing, qi-rectifying, and damp-resolving therapeutic methods. Such herbs had warm, natural, and cold herbal properties; pungent, bitter, and sweet flavors; and spleen, lung, and stomach meridian tropisms. Cluster analysis showed 61 core drugs, including Radix Glycyrrhizae, Rhizoma Pinelliae, Radix Bupleuri, and Radix Scutellariae (). Apriori association rule analysis yielded 12 binomial rules (herb pairs) and 6 trinomial rules (herb combinations). Radix Bupleuri plus Radix Scutellariae was the core herbal pair for treating malaria. This pair could be combined with Rhizoma Atractylodis Macrocephalae () for treating warm or cold malaria, combined with Pericarpium Citri Reticulatae () or Radix Dichroae () for treating miasmic malaria, or combined with turtle shells () for treating malaria with splenomegaly.Conclusions TCM can be used to classify and treat malaria in accordance with the different stages of development. As the core herbal pair, Radix Bupleuri and Radix Scutellariae can be combined with other drugs to treat malaria with different syndrome types.

Differences in chemical components in processing of dried ginger-steamed, sand-fried, and rice swill water-bleached Aconiti Lateralis Radix Praeparata pieces in "Jianchang" faction based on UPLC-MS/MS / 中国中药杂志

This study compared the changes in chemical components during the processing of different types of Aconiti Lateralis Radix Praeparata(ALRP) in "Jianchang" faction, i.e., dried ginger-steamed ALRP pieces(Yin-FP), sand-fried ALRP pieces(Yang-FP), and rice swill water-bleached ALRP pieces(DFP), and provided a scientific basis for the mechanism in toxicity reduction and efficacy enhancement from a compositional perspective. Samples were collected during the processing of the three types of ALRP pieces, yielding raw ALRP pieces, water-bleached Yin-FP, ginger juice-moistened Yin-FP, steamed Yin-FP, water-bleached Yang-FP, sand-fried Yang-FP, water-bleached DFP, rice swill water-bleached DFP, and roasted DFP. Aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconine, aconine, mesaconine, hypaconine, salsolinol, fuziline, and higenamine in the extracts were determined by UPLC-MS/MS, and then content analysis and cluster heatmap analysis were performed on 11 sets of samples. During the processing of the three types of ALRP pieces, bleaching significantly reduced the content of 12 alkaloids; steaming, stir-frying, and roasting significantly reduced the content of diester-type alkaloids(aconitine, mesaconitine, and hypaconitine) and significantly increased the content of monoester-type alkaloids(benzoylaconine, benzoylmesaconine, and benzoylhypaconine) and aminoalcohol-type alkaloids(aconine, mesaconine, and hypaconine). During the processing of Yin-FP, the diester-type alkaloids continuously decreased, while the monoester-type and aminoalcohol-type alkaloids showed an initial decrease followed by an increase. During the processing of Yin-FP, Yang-FP, and DFP, the diester-type alkaloids continuously decreased, while the monoester-type and aminoalcohol-type alkaloids showed an initial decrease followed by an increase. Steamed Yin-FP showed a higher increase in content than fried Yang-FP and roasted DFP. Comprehensive analysis of content differences in toxic and therapeutic components in three ALRP pieces suggests that the distinctive processing methods in "Jianchang" faction can indeed achieve detoxification and efficacy enhancement on ALRP. This study provides references for understanding the mechanisms of action of the three processing methods.

Seasonal characteristics and etiologic features of the cluster of fever in Pudong New Area of Shanghai in 2013-2021 / 公共卫生与预防医学

Objective To understand the seasonal and etiological characteristics of the epidemic situation of cluster fever in Pudong New Area, Shanghai, and to provide a scientific basis for the formulation of prevention and control strategies. Methods The epidemic data of cluster fever in Pudong New Area of Shanghai from 2013 to 2021 were collected, and the data were analyzed by concentration degree and circular distribution methods. Results From 2013 to 2021, there were 109 cases of cluster fever reported in Pudong New Area, with primary schools reporting the most cases, 77 cases (70.64%). The M value was 0.59. Circular distribution results showed that angle dispersion index r value was 0.54, the average angle was 357.32°, and the average angle of Rayleigh’s test Z value was 32.07. The peak day was December 28, and the peak period was from October 25 to March 3 of the following year. The cluster of fever in Pudong New Area was mainly caused by influenza virus. Most cases were single pathogen infection, and some were double pathogen infection. Influenza A virus had the highest detection rate in both single pathogen infection and double pathogen infection. Conclusion Primary schools are the focus of prevention and control of the cluster of fever in Pudong New Area. The epidemic situation of cluster fever has a strong seasonal characteristic, and the peak of incidence is from late October to early March of the next year. Respiratory pathogens such as influenza virus are the main causes of the epidemic situation.

HPLC Fingerprint Analysis of Benchmark Sample of Yanghetang / 中国实验方剂学杂志

ObjectiveTo establish a high performance liquid chromatography（HPLC） fingerprint of Yanghetang benchmark sample， and evaluate its quality with chemometric methods， so as to provide a reference for the quality control of this benchmark sample. MethodHPLC was used to establish the fingerprint of Yanghetang benchmark sample with ZORBAX SB-C18 column（4.6 mm×250 mm， 5 μm）， the mobile phase was consisted of acetonitrile（A） -0.05% phosphoric acid aqueous solution （containing 0.05% triethylamine solution）（B） for gradient elution（0-5 min， 2%-3%A； 5-15 min， 3%-5%A； 15-65 min， 5%-30%A； 65-90 min， 30%-70%A）， the flow rate was 1.0 mL·min-1， the column temperature was 35 ℃， and the detection wavelength was 210， 260 nm. Traditional Chinese Medicine（TCM） Chromatographic Fingerprint Similarity Evaluation System （2012 edition） combined with cluster analysis， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） were used to evaluate the quality differences between different batches of Yanghetang benchmark samples， and to find the main chemical components responsible for the quality differences. ResultHPLC fingerprint of Yanghetang benchmark sample was established， 13 common peaks were identified and attributed to each common peak， including peaks 2 and 8 from Rehmanniae Radix Praeparata， peaks 10 and 11 from Cinnamomi Cortex， peaks 1， 3-6 from fried Sinapis Semen， peak 13 from Ephedrae Herba， and peaks 7， 9， 12 from Glycyrrhizae Radix et Rhizoma. Eight of them were identified by comparing with control substance， which were 5-hydroxymethylfurfural（peak 2）， sinapine thiocyanate（peak 4）， glycyrrhizin（peak 7）， verbascoside（peak 8）， cinnamic acid（peak 10）， cinnamaldehyde（peak 11）， glycyrrhizic acid（peak 12） and ephedrine hydrochloride（peak 13）. The similarities of the HPLC fingerprints of 15 batches of Yanghetang benchmark samples with the control fingerprint were all greater than 0.80. The three chemometric methods could classify the samples into two categories. Eight differential components were screened out， among which 5-hydroxymethylfurfural， sinapine thiocyanate， verbascoside and ephedrine hydrochloride were identified. ConclusionThe established fingerprint analysis method is accurate， stable and reproducible， which basically reflects the overall chemical composition of Yanghetang benchmark sample， and can provide a basis for establishment of quality standards for compound preparations of this famous classical formula.

Epidemiological characterization of a cluster of COVID-19 caused by SARS-CoV-2 Omicron variant at a construction site in Qingpu District， Shanghai / 上海预防医学

ObjectiveTo determine the epidemiological characteristics of a cluster of SARS-CoV-2 Omicron variant at a construction site and provide evidence for further COVID-19 prevention and control. MethodsDemographic data of all COVID-19 cases at a construction site in Qingpu District， Shanghai， and basic information of the construction site were retrospectively collected through filed investigation. Descriptive epidemiology was used for the analysis. Basic reproduction number （R0） and time-dependent reproduction number （Rt） were calculated using R program. ResultsDuring April 12 and May 8， 2022， a total of 314 cases were reported at the construction site， with an attack rate of 60.62%. The attack rate significantly differed between workers and managers （χ2=10.868， P<0.001）， whereas did not differ statistically by gender （χ2=0.358， P=0.550） or by vaccination status （χ2=2.861， P=0.091）. The age of all cases ranged from 5 months of age to 68 years， with a media age of 49.0 years （interquartile range： 39.8， 54.0）. In all cases， male was predominant （83.44%）. Moreover， the epidemic was mainly concentrated in the workers’ dormitory area， with infected cases identified in all buildings of each dormitory area. The attack rate ranged between 33.33% and 87.50% across the buildings. Symptoms and signs were observed among 43.0% of all cases， of which major clinical manifestations included cough （33.33%）， fever （30.37%） and headache （17.04%）. Clinical manifestations did not differ by gender （χ2=1.275， P=0.259） or by vaccination status （χ2=0.186， P=0.666）. Additionally， R0 was estimated to be 6.08 （95% confidence interval： 4.49‒8.02）. The Rt showed a decline in the beginning， followed by an increase and a re-decline. ConclusionThe cluster epidemic of COVID-19 caused by Omicron variant at the construction site is highly contagious， spreads rapidly and quietly， causes mild symptoms， which finally resulted in a large number of infected cases. It warrants rapid and strict containment when an epidemic occurs at construction sites.

Dietary patterns of preschool children based on factor analysis combined with cluster / 公共卫生与预防医学

Objective To investigate the dietary intake of preschool children in Northwest China, and provide scientific basis for studying the dietary patterns and characteristics of preschool children and formulating targeted dietary interventions. Methods Using the self-designed “Semi-quantitative Food Frequency Questionnaire for Preschool Children in Northwest China“, a convenient sampling method was used to investigate the dietary intake of children aged 3 to 7 years in Northwest China. The factor analysis combined with the cluster method was used to extract the dietary pattern. Results Through factor analysis of the average daily food intake of preschool children, the results show that the KMO test value was 0.82, Bartlett’s test value was 4 528.97, and the associated probability was <0.001, so factor analysis can be performed. In order to obtain more typical factor components so that the results were easier to explain, under the guidance of nutrition experts, the first 4 common factors were finally retained for analysis, and the cumulative variance contribution rate was 62.17%. On this basis, the number of clusters was 4, and the K-means cluster analysis method was used to cluster the factor scores of various foods for preschool children. According to the proportions of various foods and the characteristics of the foods, The dietary patterns of preschool children can be divided into staple food-based dietary patterns, high-protein dietary patterns, healthy dietary patterns, and high-sugar dietary patterns. Conclusion Using factor analysis method, the scores of each food factor of preschool children were continuous variables, and the results were highly repeatable, and subsequent analysis can be carried out. The factor analysis combined with cluster analysis method extracting the dietary pattern of preschool children that had certain degree of science. According to the characteristics of the four dietary patterns extracted in this study, children's dietary interventions can be targeted to promote children's physical and mental health.

Study on UPLC fingerprint and content determination of mangiferin of Gentiana rhodantha / 中国药房

OBJECTIVE To provide reference for quality control of Gentiana rhodantha. METHODS Taking 52 batches of G. rhodantha as subject， ultra-high performance liquid chromatography （UPLC） fingerprint was adopted. The similarity of 52 batches of medicinal materials samples was evaluated by the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine （2004A edition）； the content of mangiferin was determined； chemometric analyses [cluster analysis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）] were performed. RESULTS UPLC fingerprints of 52 batches of G. rhodantha were established， 17 common peaks were identified， and 6 of them were identified， which were loganic acid （peak 1）， neomangiferin （peak 3）， swertiamarin （peak 5）， dangyin （peak 6）， mangiferin （peak 7） and isoorientin （peak 9）. The similarities of 52 batches of medicinal materials samples were all greater than 0.9； cluster analysis showed that S1-S46， S48-S52 clustered into one class， and S47 alone； PCA results showed that the cumulative variance contribution rate of the first six principal components was 82.928%； OPLS-DA results showed that the corresponding components of swertiamarin， mangiferin and chemical composition represented by peak 4， 14， 15， 16 were the main iconic components affecting the quality differences of G. rhodantha medicinal materials. The contents of mangiferin in 52 batches of medicinal material samples ranged from 18.2 to 101.0 mg/g， mostly in accordance with 2020 edition of Chinese Pharmacopoeia. CONCLUSIONS The established UPLC fingerprint and chemometric analysis methods combined with content determination method of mangiferin can comprehensively evaluate the quality of G. rhodantha.

Macroscopic Clinical Medication Pattern of Traditional Chinese Medicine for Esophageal Cancer in Recent Ten Years Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo explore the macroscopic medication pattern of traditional Chinese medicine （TCM） in treating esophageal cancer （EC） and provide medication references for the clinical application of TCM in EC treatment. MethodRelevant literature on TCM treatment of EC was retrieved from three major Chinese databases： China National Knowledge Infrastructure （CNKI）， Wanfang Data， and VIP. Information about Chinese herbal medicines was entered into Excel to establish a prescription database for EC. The data were standardized， summarized， and subjected to frequency analysis， association rules， and cluster analysis of medication in the prescriptions. Based on the TCM classification of EC syndromes， clinical indications corresponding to each syndrome were identified， and high-frequency drugs and drug pairs were analyzed correspondingly with syndromes. ResultA total of 136 prescriptions containing 240 Chinese herbal medicines were screened， with a cumulative frequency of 1 853 times. The top 5 frequently used Chinese herbal medicines were Glycyrrhizae Radix et Rhizoma， Poria， Atractylodis Macrocephalae Rhizoma， Astragali Radix， and Pinelliae Rhizoma. In terms of functions， the Chinese herbal medicines were mainly deficiency-tonifying， urination-promoting and dampness-draining， deficiency-tonifying， deficiency-tonifying， and phlegm-resolving and cough and dyspnea-relieving ones. The statistical analysis of flavor， property， and meridian tropism showed that Chinese herbal medicines were mainly bitter and sweet， warm， cold， and neutral， and acted on the spleen， lung， and stomach meridians. Association rule analysis yielded nine potential drug combinations， and cluster analysis of high-frequency drugs resulted in four combination categories. The four TCM syndromes for EC corresponded to respective clinical indications， treatment drugs， and drug pairs. ConclusionTonifying deficiency， reinforcing healthy Qi， descending adverse Qi， resolving phlegm， activating blood， and resolving stasis are the basic principles of TCM treatment for EC， which are supplemented by clearing heat and dissipating mass while focusing on regulating and smoothing the qi movement. The drug combinations obtained from high-frequency drug and association rule analysis provide references for different TCM syndrome treatments of EC， offering valuable insights for clinical medication.