Prescrição de benzodiazepínicos em Unidades Básicas de Saúde em uma comunidade com alta vulnerabilidade social / Prescription of benzodiazepines in Health Centers in a community with high social vulnerability

RESUMO Os benzodiazepínicos, medicamentos mais prescritos no mundo, são extremamente úteis no manejo de patologias relativas ao sistema nervoso central, porém, nem sempre sua prescrição está relacionada com uma patologia. Este estudo buscou identificar os fatores influenciadores na prescrição de benzodiazepínicos na Atenção Básica do Sistema Único de Saúde e suas consequências, em uma região com alta vulnerabilidade social. Foram utilizados os princípios de um estudo qualitativo com amostra intencional de médicos prescritores construída com a ajuda dos Informantes-Chave e com tamanho (n = 10) definido pelo princípio da saturação teórica. A coleta de dados ocorreu mediante entrevistas semiestruturadas nas unidades básicas onde os profissionais atuavam. Os temas identificados relativos aos motivos da prescrição foram: relativos ao paciente (demanda do paciente; problemas sociais); relativos ao medicamento (dependência); relativos ao prescritor (uso irracional). A prescrição do benzodiazepínico deu-se devido às baixas condições sociais dos usuários nessa região e as consequências dessa conjuntura (vulnerabilidade social, problemas angustiantes de difícil resolução). Educação permanente para profissionais, ações interprofissionais e integralidade do cuidado foram demandas dos profissionais. O problema extrapola a ação do médico, e são sugeridas políticas públicas que garantam, às populações com essas características, acesso a saúde, trabalho e educação.

ABSTRACT Benzodiazepines, the most prescribed medications in the world, are extremely useful in managing conditions related to the central nervous system, however, their prescription is not always related to a pathology. This study sought to identify the factors influencing the prescription of benzodiazepines in Primary Care of the Unified Health System and their consequences, in a region with high social vulnerability. The principles of a qualitative study with intentional sampling of prescribing physicians were used, constructed with the help of Key Informants and with a size (N=10) defined by the principle of theoretical saturation. Collection took place through semi-structured interviews in the basic units where the professionals worked. The themes identified regarding the reasons for prescription were Patient-related (patient demand; social problems); Relating to medication (dependence); Relative to the prescriber (irrational use). The prescription of benzodiazepine was due to the low social conditions of users in this region and the consequences of this situation (social vulnerability, distressing problems with difficult resolution). Continuous education for professionals, interprofessional actions, and comprehensive care were demands of the professionals. The problem goes beyond the doctor's scope of action, and public policies that guarantee such populations access to health, work, and education are suggested.

Prevalencia de la automedicación en odontología en adultos de Macas, Ecuador / Prevalence of self-medication in dentistry in adults in Macas, Ecuador

Introducción: el hecho de que una persona no puede acceder a un servicio de salud puede favorecer la automedicación, que es la administración de fármacos según la autopercepción del individuo sobre su posible diagnóstico y solución. Aunque es una situación considerada como problema de salud pública, por medio de la educación o futuras investigaciones que generen propuestas, se podrá erradicar las barreras al acceso de la salud oral. Objetivo: determinar la prevalencia de la automedicación en odontología en adultos de Macas, Ecuador, durante el año 2021. Material y métodos: estudio descriptivo, cuantitativo, documental, comunicacional y transversal actual, donde se trabajó sobre la población de edad adulta de Macas, Ecuador; los datos se recolectaron mediante una encuesta online, para luego ser analizados en prevalencia, frecuencia y chi cuadrado. Resultados: 49% de los encuestados respondió que se automedican, los analgésicos fueron el tipo de medicamento más consumido (44.2%); 27% de los individuos respondió que el dolor dental era una causa para tomar medicamentos sin receta, el principal motivo para automedicarse y no acudir al odontólogo fue por indicación del técnico de farmacia (26%). Conclusiones: los datos epidemiológicos obtenidos en esta investigación demuestran la marcada tendencia de las personas a consumir medicinas sin receta médica, por lo que, se deduce que existe una barrera para acceder a los servicios de salud oral; por ello, debería darse la importancia y atención oportuna (AU)

Introduction: the fact that a person cannot access a health service, may favor self-medication, which is the administration of drugs according to the individual's self-perception about their possible diagnosis and solution. Although, it is a situation considered as a public health problem, through education or future research that generates proposals, it will be possible to eradicate the barriers to oral health access. Objective: to determine the prevalence of self-medication in dentistry in adults in Macas, Ecuador, during the year 2021. Material and methods: a descriptive, quantitative, documentary, communicational and current cross-sectional study was carried out on the adult population of Macas, Ecuador; data were collected by means of an online survey and then analyzed in terms of prevalence, frequency and chi-square. Results: 49% of those surveyed responded that they self-medicate, analgesics were the most consumed type of medicine (44.2%), 27% of the individuals responded that dental pain was a cause for taking medicines without prescription, the main reason for self-medicating and not going to the dentist was because of the indication of the pharmacy technician (26%). Conclusions: the epidemiological data obtained in this investigation show us the marked tendency of people to take medicines without a medical prescription; therefore, it can be deduced that there is a barrier to accessing oral health services, and for this reason it should be given importance and timely attention (AU)

Vivencias y estrategias comunitarias de manejo del riesgo dentro de las prácticas chemsex: un estudio cualitativo / Community experiences and strategies of risk management within chemsex practices: a qualitative study

Resumen El auge en el estudio del uso sexualizado de drogas entre hombres gais, bisexuales u otros hombres que tienen sexo con hombres (HSH), conocido como chemsex, ha generado una multiplicidad de datos que contribuyen a su problematización en tanto cuestión de salud pública a través del vínculo con el VIH y las adicciones. El estudio de estas prácticas, desde un paradigma biomédico, se ha centrado en el riesgo y ha contribuido a su reducción como fenómeno único y cuantificable. Este estudio tiene como objetivo explorar la vivencia del riesgo en el transcurso de las prácticas, para conocer qué estrategias de manejo emplean frente a éste y de qué manera son generadas. Se realizaron entrevistas semiestructuradas a cinco practicantes de chemsex en el Área Metropolitana de Barcelona y, posteriormente se aplicó un análisis temático. Los hallazgos muestran cómo estos hombres detectan, asumen y enfrentan los riesgos presentes en estas prácticas, donde toman relevancia el tipo de relaciones que allí se dan y el círculo social del que disponen. Este estudio destaca también la creación de estrategias basadas en la experiencia y cómo la transmisión de estos saberes entre participantes facilita la toma de decisiones y el manejo del riesgo.

Abstract The rise in the study of sexualised drug use among gay, bisexual and other men who have sex with men (MSM), known as chemsex, has generated a multiplicity of data that contribute to its problematisation as a public health issue through the link with HIV and addictions. The study of these practices, from a biomedical paradigm, has focused on risk and has contributed to its reduction as a unique and quantifiable phenomenon. This study aims to explore the experience of risk in the course of the practices, to find out what management strategies they employ in the face of risk and how they are generated. Semi-structured interviews were conducted with five chemsex practitioners in the Metropolitan Area of Barcelona and, subsequently, a thematic analysis was applied. The findings show how these men detect, assume and confront the risks present in these practices, where the type of relationships that take place and the social circle available to them are relevant. This study also highlights the creation of strategies based on experience and how the transmission of this knowledge among participants facilitates decision-making and risk management.

Deprescribing psychotropic drugs in a geriatric psychiatry outpatient clinic

Objective: To describe the psychotropic drug deprescription process in older patients of a geriatric psychiatry outpatient clinic. Methods: We conducted a quasi-experimental study of people aged ≥ 60 years who were treated at Hospital São Lucas' Geriatric Psychiatry Outpatient Clinic, which is affiliated with Pontifícia Universidade Católica do Rio Grande do Sul, Brazil. Data on 150 older people were collected from March 2021 to August 2022 and were evaluated by the pharmacists. The inclusion criteria were age ≥ 60 years, being a patient of the hospital's Geriatric Psychiatry Outpatient Clinic, use of at least one psychotropic drug, and agreeing to participate in the study. Those unable to report their medications and those who only came to the first appointment were excluded. Results: Overall, deprescription of at least one psychotropic drug was indicated in 61.3% (n = 92) of the participants, and it was effectively implemented in 68.5% (n = 63) of this group. Deprescribing, which was more frequent in the youngest age group (60­69 years) (p = 0.049), was indicated for 37.4% (n = 136) of psychotropic drugs, 67.6% (n = 92) of which were effectively deprescribed. The main classes indicated for deprescription were hypnotics and sedatives (90.0%; n = 18) and anxiolytics (73.3%; n = 11). Conclusions: At least 1 psychotropic drug was indicated for deprescription in the majority of the patients, and in most cases it was effectively implemented. One-third of the prescribed psychotropic drugs were indicated for deprescription, and more than half were successfully deprescribed. (AU)

O uso de drogas e seus efeitos na cavidade oral

Objetivos: Descrever as principais manifestações bucais associadas ao uso das drogas lícitas e ilícitas mais utilizadas atualmente, bem como os cuidados que devem ser tomados durante o atendimento odontológico desses pacientes. Revisão de literatura: Na revisão foi abordada a classificação das substâncias químicas, as principais manifestações orais e os cuidados que o cirurgião-dentista deve ter durante o atendimento odontológico. As substâncias descritas foram álcool, tabaco, benzodiazepínicos, maconha, anfetaminas e cocaína/crack. As complicações de saúde bucal associadas ao abuso de drogas podem resultar da exposição direta dos tecidos orais às drogas durante o fumo ou ingestão, da interação biológica das drogas com a fisiologia normal da cavidade oral e dos efeitos das drogas na função cerebral que resultam em um espectro de comportamentos de dependência, como comportamento de risco, falta de higiene e descuido. Considerações finais: O consumo de substâncias psicoativas, seja a curto ou longo prazo, pode desencadear consequências, tanto na saúde geral como na saúde bucal do usuário. Sob essa perspectiva, o cirurgião-dentista deve estar ciente das manifestações orais e sistêmicas causadas pelas substâncias psicoativas e estar capacitado para diagnosticar, tratar ou também encaminhar o usuário, se necessário, visando um cuidado integral e multiprofissional.

Objective: to describe the main oral manifestations associated with the use of the most commonly used licit and illicit drugs today, as well as the care that should be taken during the dental care of these patients. Literature review: The review covered the classification of chemical substances, the main oral manifestations and the care that dentist should take during dental care. The substances described were alcohol, tobacco, benzodiazepines, marijuana, amphetamines and cocaine/crack. Oral health complications associated with drug abuse can result from direct exposure of oral tissues to drugs during smoking or ingestion, from the biological interaction of drugs with the normal physiology of the oral cavity, and from the effects of drugs on brain function that result in a spectrum of addictive behaviors, such as risk behavior, poor hygiene and carelessness. Final considerations: The consumption of psychoactive substances, whether in the short or long term, can have consequences for both the general health and the oral health of the user. From this perspective, the dentist must be aware of the oral and systemic manifestations caused by psychoactive substances and be able to diagnose, treat or also refer the user, if necessary, aiming for comprehensive, multi-professional care.

Perfil de las víctimas mortales por intoxicaciones agudas en Costa Rica del 2012 al 2021 asociadas al consumo de sustancias psicoactivas y drogas de abuso: etanol, metanol, benzodiacepinas, anfetaminas, heroína, cocaína y mixto / Profile of fatalities due to acute intoxications in Costa Rica from 2012 to 2021 associated with the consumption of psychoactive substances and drugs of abuse: ethanol, methanol, benzodiazepines, amphetamines, heroin, cocaine and mixed

Resumen Introducción: La mortalidad por intoxicaciones agudas de sustancias psicoactivas representa un problema de salud pública, especialmente en personas jóvenes. El objetivo del estudio fue crear un perfil de las víctimas mortales por intoxicación aguda en Costa Rica entre los años 2012 y 2021 asociado al consumo de sustancias psicoactivas y drogas de abuso. Materiales y métodos: Se recopilaron datos de Sección de Patología Forense del Departamento de Medicina Legal en Costa Rica, con los cuales se realizó una revisión de las víctimas mortales por intoxicaciones agudas a partir del 1 de enero de 2012 hasta el 31 de diciembre de 2021. La revisión incluyó las siguientes variables: variables epidemiológicas: sexo, edad, nacionalidad, ocupación, estado civil, provincia, consumo frecuente asociado, manera de muerte, tipo de sustancia y lugar de intoxicación. Resultados: De los 456 casos de muertes asociados a intoxicaciones agudas por etanol, metanol, benzodiacepinas, anfetaminas, heroína, cocaína y mixtas; reportados entre el 1 de enero de 2012 y el 31 de diciembre de 2021: el año que más casos reportó fue 2020; 82% de las víctimas fueron hombres y 18% mujeres; las principales edades de las personas reportadas abarcan entre 41 y 60 años. 80% de las personas eran costarricenses; San José fue la provincia con mayor número de casos de intoxicación letal, siendo el domicilio el sitio más frecuente. 14% de las víctimas eran desempleadas; 77% de las personas presentaban algún trastorno de la adicción o consumo frecuente de alguna de las sustancias estudiadas. La mayoría de muertes fueron de manera accidental. Conclusiones: El perfil predominante de las víctimas fue: masculino, entre 41 y 60 años, costarricense, de estado civil indeterminado o soltero, desempleado, que muere de manera accidental, en su domicilio, por intoxicación aguda con alcohol o mixta (alcohol y cocaína).

Abstract Introduction. Mortality from acute poisoning of psychoactive substances represents a public health problem, especially in young adults. The purpose of the study was to create a profile of fatalities due to acute poisoning in Costa Rica between 2012 and 2021 associated with the consumption of psychoactive substances and drugs of abuse. Materials and methods. Data were collected from the Forensic Pathology Section of the Legal Medicine Department in Costa Rica, then a review of fatalities due to acute poisoning was carried out from January 1, 2012 to December 31, 2021. The review included the following epidemiological variables: sex, age, nationality, occupation, marital status, province, consumption associated, manner of death, type of substance, and place of intoxication. Results. Out of the 456 reported cases of deaths associated with acute intoxication with ethanol, methanol, benzodiazepines, amphetamines, heroin, cocaine, and mixed substances between January 1, 2012, and December 31, 2021: the year with the highest number of cases reported was 2020; 82% of the victims were male, and 18% were female; the main age group of reported victims ranged from 41 to 60 years old. 80% of the victims were Costa Rican, and San Jose was the province with the highest number of lethal intoxication cases, with the home being the most frequent site. 14% of the victims were unemployed, and 77% of the individuals had some addiction disorder or frequent consumption of one of the studied substances. The majority of deaths were accidental. Conclusion. The main profile of the victims was male, between 41 and 60 years old, Costa Rican, of indeterminate or single marital status, unemployed, who died accidentally, at home, due to acute intoxication with alcohol or a mixture of substances (alcohol and cocaine).

Asociación del consumo de drogas ilícitas en mujeres embarazadas y sífilis congénita en un Hospital Público de México / Association of illicit drug use in pregnant women and congenital syphilis in a public hospital in Mexico

Resumen Realizamos un estudio de casos y controles anidado en una cohorte con el objetivo de estudiar la asociación del consumo de drogas ilícitas y sífilis congénita (SC). Los casos se diagnosticaron mediante pruebas treponémicas y no treponémicas en la madre y el recién nacido (RN). Se realizó un análisis multivariado con regresión logística. Se registraron 6.171 nacimientos con edad gestacional promedio 37,8 semanas y se diagnosticaron 62 eventos de SC (incidencia: 10,5 eventos/1.000 RN). Los factores maternos asociados fueron el uso de drogas ilícitas (OR = 14,08; IC 95% = 1,19-166,6), menos de cinco consultas en el control prenatal (OR = 2,9; IC 95% = 1,12-7,53), más de dos parejas sexuales (OR = 3,76; IC 95% = 1,62-8,71) y estudios universitarios (OR = 0,06; IC 95% = 0,005-0,85). Entre las madres de los casos, la prevalencia del consumo de drogas ilícitas fue de 22,6% y las más frecuentes fueron las metanfetaminas y la marihuana.

Abstract We conducted a nested case-control study within a cohort with the aim of studying the association between illicit drug use and congenital syphilis (CS). Cases were diagnosed based on treponemal and non-treponemal tests conducted both in the mother and the newborn (NB). Multivariate analysis with logistic regression was performed. A total of 6171 births with a mean gestational age of 37.8 weeks were recorded and 62 CS events were diagnosed (incidence 10.5 events/1000 NB). Associated maternal factors were illicit drug use (OR 14.08, 95% CI 1.19-166.6), <5 prenatal visits (OR 2.9, 95% CI 1.12-7.53), more than two sexual partners (OR 3.76, 95% CI 1.62-8.71) and professional education level (OR 0.06, 95% CI 0.005-0.85). Among the mothers of the cases presented, the prevalence of illicit drug use was 22.6% and the most frequent drugs were methamphetamines and cannabis.

Acute kidney injury and hypercalcemia associated with veterinary supplements applications in adult man / Injúria renal aguda e hipercalcemia associadas a aplicações de suplementos veterinários em homem adulto

The compound "ADE" is an injectable oil for veterinary use which contains large amounts of vitamins A, D and E. The parenteral application in humans leads to a granuloma reaction which triggers hypercalcemia. A 42-year-old man was admitted with lower limb pain, nephrolithiasis and nephrocalcinosis. Laboratory tests revealed creatinine 4.59 mg/dl, calcium 13.3 mg/dl and parathormone 13.8 pg/ml. He underwent an ureterolithotripsy, stent placement, intravenous crystalloid fluids, and corticosteroid. He improved symptoms, kidney function and normalized serum calcium. The "ADE"-induced hypercalcemia diagnosis can be challenging. The early diagnosis may avoid negative outcomes.

O composto "ADE'' é um óleo veterinário injetável que contém grandes quantidades de vitaminas A, D e E. A aplicação parenteral causa reação granulomatosa e hipercalcemia. Um homem de 42 anos foi admitido com dor no membro inferior, nódulos musculares endurecidos, nefrolitíase e nefrocalcinose. O laboratório revelou creatinina 4,59 mg/dl, cálcio 13,3 mg/dl e paratormônio 13,8 pg/ml. Foi tratado com ureterolitotripsia, cateter duplo-J, cristaloide intravenoso e corticoterapia. Ele apresentou melhora dos sintomas, função renal e normalizou cálcio. O diagnóstico da hipercalcemia pelo "ADE'' pode ser desafiador. O diagnóstico precoce pode evitar desfechos negativos.

Research advances in traditional Chinese medicine regulation of programmed cell death in intervening against hepatic fibrosis / 临床肝胆病杂志

Hepatic fibrosis （HF） is a pathological process of abnormal repair of liver tissue structure caused by chronic liver injury， and its pathogenesis has not been fully clarified. Related studies have shown that programmed cell death may be associated with the onset of HF， and traditional Chinese medicine （TCM） has a significant effect in regulating programmed cell death to intervene against HF. This article reviews the main mechanism of the influence of programmed cell death on HF and discusses the possible mechanism of TCM regulation of programmed cell death in improving HF， which provides new ideas for TCM prevention and treatment of HF.

Establishment of a high-throughput screening platform based on drug repurposing targeting alpha-1-acid glycoprotein and discovery of potential weight loss drugs / 药学实践与服务

Objective Alpha-1-acid glycoprotein （ORM） was a new target for the development of weight loss drugs. To search for potential weight loss drugs that could target ORM from the compound library of already marketed drugs based on drug repurposing. Methods The pGL4.20-ORM1 promoter recombinant plasmid was contructed and validated, and then a lentiviral vector was utilized to establish stable AML12 cell lines expressing ORM1 promoter-LUC-PURO. This cell line was employed for high-throughput screening of compounds from the marketed drug library, and the luminescence value of the cells was characterized by enzyme marker. Results Primary screening and secondary screening of 1 470 compounds identified 42 compounds that increased ORM1 promoter expression and could be used for further weight loss effect assessment. Conclusion This study successfully constructed LV-AML12-ORM1 promoter-LUC-PURO stable expression cell lines using lentiviral vectors, laying a foundation for efficient and stable screening of weight loss drugs targeting ORM.

Research progress on the antitumor effects of platinum-based chemo-immunotherapies / 中国药科大学学报

@#Abstract: As potential immunomodulators, platinum-based drugs could trigger immunogenic cell death (ICD). Hence, combination of platinum-based chemotherapy and immunotherapy could have better synergistic anticancer effect. Pt(II)-based drugs are the most common chemotherapeutic agents in cancer treatment yet with limited clinical application due to their toxic side-effects and drug resistance. Pt(IV) complexes have been widely investigated in the past decades due to their kinetic inertness and unique mechanisms . This article summarizes the progress in the pharmacological activities and mechanisms of Pt(IV) antitumor complexes via introducing different immunomodulators into chemotherapeutic agents in literature over recent years and highlights the potential targets and molecular signaling pathways so as to provide some reference for further development and potential clinical application of platinum-based chemo-immunotherapeutic agents.

Application of double-layer soft tissue suture closure technique in the surgical treat-ment of patients with mandible medication-related osteonecrosis of the jaw of early and medium stages / 北京大学学报(医学版)

Objective:To investigate the clinical application effect of double-layer soft tissue(DLST)suture closure technique in patients with mandible medication-related osteonecrosis of the jaw(MRONJ)of early and medium stages resulted in application of anti-bone-resorptive drugs.Methods:Early to me-dium stage mandible MRONJ patients who underwent surgical treatment in the fourth ward of Peking Uni-versity School and Hospital of Stomatology from October 2021 to September 2022 were included.Clinical information of the patients were collected,including primary disease,concomitant disease,medication regimen(drug type,duration of medication),MRONJ stage,clinical symptoms,imaging manifestations,etc.During surgery,after using marginal mandibulae resection to remove the necrotic bone,the wound was closed using DLST closure technique.Regular post-operative follow-up was performed to evaluate the therapeutic effect and complications of the DLST technique,the pain score and functional status of the patiens were evaluated.Results:This study totally included 13 patients,12 women and 1 man,aged(66.69±13.14)years.Seven patients had osteoporosis,2 had lung cancer,3 had breast cancer and 1 had prostate cancer among their primary diseases;7 had no concomitant diseases,2 had diabetes melli-tus,2 had cardiovascular disease and 1 had dry syndrome.Intravenous zoledronic acid were used in 9 patients,the average duration was(37.7±20.0)months,and other drugs,such as letrozole tablets were taken in 7 patients at the same time;Denosumab injection was used in 3 patients for an average of(10.3±11.9)months;Alendronate sodium tablets were taken in 5 patients for an average of(55.20± 27.20)months,and prednisone acetate tablets or acarbose tablets were taken to varying degrees in 2 pa-tients.The average post-operative follow-up was 11.9 months(9 to 17 months),and all the 13 patients were cured without complications,such as pus overflow and so forth.The pre-operative score of Karnof-sky performance status(KPS)in the patients was 68.46±14.05,and the post-operative score was 82.31±15.36,and the difference was statistically significant(P＜0.05).The pre-operative score of visual analogue scale(VAS)in the patients was 5.77±0.73 and the post-operative score was 0.38±0.51,and the difference had statistical significance(P＜0.001).Conclusion:The double-layer soft tissue suture closure technique can achieve good clinical results in patients with MRONJ of the man-dible using anti-bone-resorptive drugs alone,and can provide clinical treatment ideas for MRONJ patients with more complicated drug use.

Advances in the treatment of spinal muscular atrophy / 国际儿科学杂志

Spinal muscular atrophy（SMA），an autosomal recessive genetic disease characterized by progressive weakness and atrophy of the proximal limbs caused by degeneration of motor neurons in the anterior horn of the spinal cord，can affect multiple systems such as respiratory，digestive，and skeletal systems. Untreated children with severe type 1 SMA usually die within 2 years of age. In recent years，the treatment of SMA has developed rapidly，and a variety of drugs have been approved to benefit patients. However，none of the existing therapeutic drugs or regimens can achieve a complete cure. Therefore，the combination of different therapeutic drugs and the research and development of new drugs may be the way forward for the treatment of SMA. The latest progress of therapeutic drugs and combination therapy in SMA are summarized in this review，which may be helpful for guiding the treatment of SMA.

Bioinformatics-based screening for ferroptosis-related DEGs of EGFR-TKIs resistance in non-small cell lung cancer / 国际检验医学杂志

Objective To screen for ferroptosis-related differentially expressed genes(DEGs)of epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs)resistance in non-small cell lung cancer(NSCLC).Methods The gene sequencing dataset GSE117846 of NSCLC EGFR-TKIs resistant cells was se-lected from the Gene Expression Omnibus data base(GEO)and screened for DEGs with P＜0.05 and | log2 FC |1.Ferroptosis-related genes were collected using the FerrDb database and jvenn was used to intersected the DEGs screened from GSE117846 dataset with the ferroptosis-related genes obtained from FerrDb database.GO function and KEGG pathway enrichment analysis of intersection genes were performed,and protein-pro-tein interaction(PPI)network was drawn.The score of intersection genes was calculated by using Cytohubba plug-in in Cytoscape software,and the top 10 genes were used for Hub genes screening.ULCAN and GEPIA2 databases were used to analyze the expression of Hub genes in NSCLC and its effect on the survival prognosis of patients.Real-time fluorescence quantitative PCR(qPCR)was used to detect the relative expression levels of Hub gene mRNA in NSCLC patients'cancer tissues,adjacent tissues and in vitro cells to verify the results of bioinformatics analysis.Results A total of 60 ferroptosis-related DEGs of EGFR-TKIs resistance in NSCLC were screened out,including 30 up-regulated genes and 30 down-regulated genes.The 60 genes were mainly enriched in P53 signaling pathway,ferroptosis pathway and FoxO signaling pathway.There were 57 nodes and 99 edges in the PPI network,with an average clustering coefficient of 0.377 and PPI enrichment P＜0.01.The Hub gene screened out by Cytohubba plug-in was tumor protein P63(TP63).ULCAN and GE-PIA2 database analysis showed that the expression of TP63 in lung adenocarcinoma tissue was significantly lower than that in normal tissue,while the expression of TP63 in lung squamous cell carcinoma tissue was sig-nificantly higher than that in normal tissue,and the differences were statistically significant(P＜0.05).In pa-tients with lung adenocarcinoma,there was no significant difference in the survival prognosis between TP63 high and low expression groups(P＞0.05),while in patients with lung squamous cell carcinoma,the survival prognosis of TP63 low expression group was better,and the difference was statistically significant(P＜0.05).QPCR showed that TP63 mRNA highly expressed in lung squamous cell carcinoma tissue and lowly expressed in lung adenocarcinoma tissue compared with adjacent tissues(P＜0.05).The expression of TP63 mRNA was down-regulated in gefitinib-resistant PC9/GR cells(P＜0.05),which was consistent with the re-sults of bioinformatics analysis.Conclusion TP63 may be an important gene linking NSCLC EGFR-TKIs re-sistance to ferroptosis.

Review on the registration of herbal drugs in north America and Europe / 国际中医中药杂志

International registration of herbal drugs is a necessary prerequisite for the internationalization of Chinese materia medica. North America and European Union occupy an important position in the world herbal drugs market, and their drug administration and quality supervision requirements are relatively complete and progressiveness. By summarizing the definition of herbal drugs in North America and European Union, combing and interpreting the relevant laws, regulations and policy documents, this article constructed the registration path of herbal drugs, and discussed the current status of market registration of herbal drugs in North America and European Union based on the examples of successful marketing of herbal drugs under current application and approval in overseas markets. This article believed that in the future, an internationally matched TCM quality standard evidence system should be built, clinical trials of TCM products in line with international standards should be carried out, standards that are the same or higher than international mainstream GMP should be developed, the registration path of TCM compounds should be explored, and professionals to establish an international registration application team should be recruited to provide theoretical and practical support for China's overseas registration of Chinese TCM products, promote TCM products to enter the world mainstream market, and achieve high-quality development of TCM internationalization.

Clinical applications of abnormal DNA methylation in chronic myeloid leukemia / 中南大学学报(医学版)

DNA methylation,a crucial biochemical process within the human body,fundamentally alters gene expression without modifying the DNA sequence,resulting in stable changes.The changes in DNA methylation are closely related to numerous biological processes including cellular proliferation and differentiation,embryonic development,and the occurrence of immune diseases and tumor.Specifically,abnormal DNA methylation plays a crucial role in the formation,progression,and prognosis of chronic myeloid leukemia(CML).Moreover,DNA methylation offers substantial potential for diagnosing and treating CML.Accordingly,understanding the precise mechanism of DNA methylation,particularly abnormal changes in the methylation of specific genes in CML,can potentially promote the development of novel targeted therapeutic strategies.Such strategies could transform into clinical practice,effectively aiding diagnosis and treatment of CML patients.

Drug resistance characteristics and treatment strategies of TB patients in three age groups in Guangdong Province from 2014 to 2020 / 实用医学杂志

Objective To evalute the drug resistance characteristics of tuberculosis(TB)patients of all ages in Guangdong Province during 2014-2020,and provide prevention and treatment strategies of tuberculosis.Method We used 39,048 clinical isolates of Mycobacterium tuberculosis(MTB)belonging to patients with confirmed TB from 2014 to 2020,from 32 TB drug-resistant surveillance sites in Guangdong Province,and we retrospectively analyzed the laboratories data of patients with drug-resistant TB,and grouped patients by age and region,to explore the trend of drug-resistance of MTB clinical isolates,the trend and incidence differences of multi-resistant TB(including monodrug-resistant TB(MR-TB),polydrug-resistant TB(PDR-TB),multidrug-resistant TB(MDR-TB)and exten-sively drug-resistant TB(XDR-TB)),and resistance characteristics of MTB clinical isolates to drugs in focus(rifam-picin and ofloxacin).Result The differences in the resistance rates of MTB clinical isolates to nine antituberculosis drugs among patients at 32 TB drug resistance surveillance sites in Guangdong Province from 2014 to 2020 were not statistically significant(P>0.05).The rates of MR-TB,PDR-TB,MDR-TB,XDR-TB,and total resistance isolates of MTB clinical isolates were 14.46%,5.16%,5.16%,4.58%,and 1.29%,respectively.he pediatric group had a higher MR rate(15.4%)than the adult and geriatric groups,while the adult and geriatric groups had higher MDR rates(5.0%and 5.0%,respectively).The geriatric group also had a higher XDR rate(2.1%),with statistically significant differences(P<0.001).The rates of MR-TB(14.8%),PDR-TB(5.3%),MDR-TB(4.7%),XDR-TB(1.4%),ofloxacin resistance(11.33%)and rifampicin resistance(6.92%)of MTB clinical isolates were higher in patients from the Pearl River Delta than in other regions of Guangdong Province,with statistically significant differ-ences(P<0.001).Conclusion According to the data from the surveillance sites,the epidemiological trend of drug-resistant TB in Guangdong Province is leveling off during the period 2014-2020.However,the incidence of drug-resistant TB is higher in specific populations(e.g.children and the elderly),and the incidence of drug-resistant TB and the rate of drug resistance to drugs in focus are higher in the Pearl River Delta than in other regions of Guang-dong Province,necessitating further investigation and the development of novel prevention and control strategies.

Gut microbiota and drug-associated osteonecrosis:a two-sample Mendelian randomization study / 中国组织工程研究

BACKGROUND:Osteonecrosis due to drugs is a serious adverse reaction occurring after the application of such drugs.Increasing evidence suggests that the gut microbiota composition is associated with osteonecrosis due to drugs.However,the causal relationship of the gut microbiota to osteonecrosis due to drugs is still unclear. OBJECTIVE:To evaluate the potential causal relationship between the gut microbiota and the risk of osteonecrosis due to drugs using the Mendelian randomization method. METHODS:A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis(n=13 266)conducted by the MiBioGen consortium as well as the summary statistics of osteonecrosis due to drugs obtained from the FinnGen consortium R9 release data(264 cases and 377 013 controls).Inverse variance weighted,MR-Egger,weighted median,weighted model and simple model were used to examine the causal association between gut microbiota and osteonecrosis due to drugs.Sensitivity analysis was used to test whether the results of the Mendelian randomization analysis were reliable.Reverse Mendelian randomization analysis was performed on all the bacteria as an outcome for effect analysis and sensitivity analysis. RESULTS AND CONCLUSION:Inverse variance weighted estimates suggested that Lentisphaerae(phylum),Lentisphaeria(class),Melainabacteria(class),Gastranaerophilales(order),Rhodospirillales(order),Victivallales(order)and Bifidobacterium(genus)had protective causal effects on osteonecrosis due to drugs.Methanobacteria(class),Bacillales(order),Methanobacteriaceae(family),Lachnospiraceae(family),Methanobacteriales(order),Holdemania(genus),Holdemania(UCG010 group)(genus),Odoribacter(genus)and Tyzzerella3(genus)had negative causal effects on osteonecrosis due to drugs.According to the results of reverse Mendelian randomization analysis,Clostridiaceae1(family),Peptostreptococcaceae(family),Streptococcaceae(family),Clostridiumsensustricto1(genus)and Streptococcus(genus)showed negative causal effects on osteonecrosis due to drugs.However,Eisenbergiella(genus)showed protective causal effects on osteonecrosis due to drugs.None of the bidirectional sensitivity analysis revealed heterogeneity or horizontal pleiotropy.When gut microbiota were used as exposure and osteonecrosis due to drugs as the outcome,Mendelian randomization analysis found that seven bacterial traits were positively correlated to osteonecrosis due to drugs,nine bacterial traits were negatively related to osteonecrosis due to drugs.When osteonecrosis due to drugs were used as exposure and gut microbiota as the outcome,reverse Mendelian randomization analysis found a negative correlated relationship with five bacterial traits and a positive causal relationship with one bacterial trait.By changing the diversity and composition of gut microbiota,it is expected to improve the incidence and prognosis of osteonecrosis due to drugs,providing new ideas for the study of orthopedic diseases.

Relationship between statin drugs and bone density:a drug target-mediated Mendelian randomization study / 中国组织工程研究

BACKGROUND:Observational studies have suggested that statin drugs may have a protective effect on bone density,making them a potential treatment option for osteoporosis. OBJECTIVE:To evaluate the causal relationship between drug target-mediated lipid phenotypes and bone mineral density(BMD)using Mendelian randomization methods. METHODS:We obtained single nucleotide polymorphismsrelated to statin drugs and BMD data from the IEU Open GWAS database.The primary analysis method was the inverse variance weighted method,and we also used weighted median,simple median,weighted mode,and MR-Egger regression.We usedβ values and 95%confidence intervals(CI)to assess the causal relationship between statin drugs and BMD.Additionally,we conducted sensitivity analyses to validate the results,assessed heterogeneity using Cochran's Q test,examined for horizontal pleiotropy using the MR-Egger intercept test,and performed leave-one-out analyses to determine if individual or multiplesingle nucleotide polymorphism influenced the results. RESULTS AND CONCLUSION:There was a significant association between the statin target of action,3-hydroxy-3-methyl glutaryl coenzyme A reductase-mediated low-density lipoprotein cholesterol,and heel bone BMD(β=-0.086,95%CI:-0.117 to-0.055,P=5.42×10-8)and whole-body BMD(β=-0.193,95%CI:-0.288 to-0.098,P=7.35×10-5).The findings of this study support the protective effect of statin drugs on BMD.These findings not only deepen our understanding of the relationship between cholesterol-related genes and bone health but also reveal potential therapeutic targets for improving BMD.

Efficacy of mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for hepatocellular carcinoma with Vp4 portal vain tumor thrombus / 中华消化外科杂志

Objective:To investigate the efficacy of mFOLFOX7 regimen systemic chemo-therapy combined with camrelizumab and apatinib for hepatocellular carcinoma (HCC) with Vp4 portal vain tumor thrombus (PVTT).Methods:The single-arm, open, exploratory clinical study was conducted. The clinicopathological data of 15 HCC patients with Vp4 PVTT who were admitted to the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2021 to October 2023 were collected. There were 14 males and 1 female, aged 48(range, 33-67)years. All patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. Observa-tion indicators: (1) clinical efficacy; (2) survival of patients. Measurement data with skewed distribution were represented as M(rang), and count data were described as absolute numbers or percentages. Results:(1) Clinical efficacy. All 15 patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. According to the response evaluation criteria in solid tumors version 1.1, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 10/15, 1/15, 9/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. According to the modified response evaluation criteria in solid tumors, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 12/15, 6/15, 6/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. Of the 15 patients, 7 cases were successfully treated with conversion therapy with the surgical conversion rate as 7/15, and all of them achieved R 0 resection. The other 6 cases were failed in conversion therapy, and there were 2 cases still undergoing conversion therapy. Of the 7 patients with successful conver-sion therapy, 5 cases achieved complete pathological remission, 1 case achieved major pathological remission with 90% of tumor tissue necrosis, and 1 case achieved complete remission through imaging examination, but new liver lesions appeared in multiple locations during further observation which were surgically removed. Results of histopathology examination on the patient confirmed multiple liver metastases. The proportion of treatment-associated adverse reactions in 15 patients was 13/15, with 7/15 having ≥grade 3 adverse reactions, including diarrhea (3/15), neutropenia (2/15), thrombo-cytopenia (2/15), and elevated aspartate aminotransferase (2/15). One patient may experience ≥1 adverse reaction. All patients were improved after symptomatic treatment. (2) Survival of patients. All 15 patients were followed up for 13.0(range, 2.0-31.0)months. During the follow-up period, 3 patients died. One case died of upper gastrointestinal bleeding after achieving partial remission, with a survival time of 7.5 months. One case died of multiple liver metastases of tumor, with tumors accounting for over 70% volume of liver and a survival time of 9.5 months. One case with multiple liver tumors and bilateral lung metastasis died due to disease progression after achieving partial remission, with a survival time of 13.5 months. The postoperative follow-up time for 7 patients undergoing surgical treatment was 14.0(range, 2.0-25.0)months. Of the 7 patients, 1 case experien-ced tumor recurrence 20.0 months after surgery, and 6 cases had no recurrence at last time of the follow-up (3 cases completed treatment and entered follow-up observation). The longest survival time was 31.0 months. Conclusion:The mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for HCC with Vp4 PVTT is safe and feasible.