Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Exploration on Optimizing "Five-sphere" Medical Humanistic Care Service in Medical and Nursing Institutions / 中国医学伦理学

The combination of medical care and nursing is an important measure of health care for the aged, and it is also an important part of aging work. Under the background of increasing aging, and under the background of changing from disease-centered and patient-centered medical model to health-centered "big medicine" model, medical humanities are particularly important for how to make the elderly spend their old age in peace and make the road of combining medical care with nursing care wider. Based on the practice of combination of medical care and nursing, under the guidance of the concept of great health, this paper discussed the establishment of a "Five-sphere" all-round humanistic care concept integrating medical care, nutrition care, sports care, mental care and other convalescent health care factors, and provided a series of comprehensive multi-angle humanistic care service measures from physiology to psychology for elderly patients with chronic diseases, which has achieved good results.

Content measurement of doxorubicin hydrochloride and lonidamine by HPLC / 药学实践杂志

Objective To establish a method for the simultaneous determination of DOX·HCl and LND. Methods HPLC was performed on Agilent 5 HC-C18（2） （4.6 mm × 250 mm, 5 µm） column. The mobile phase was methanol-0.1% TFA aqueous solution, and the gradient elution procedure were: 0 to 3 min, 65% methanol; 3 to 7 min, 65%→90% methanol; 7 to 13 min, 90% methanol; 13 to 15 min, 90%→65% methanol; 15 to 20 min, 65% methanol. The collection time was 20 min, the balance time was 3 min, the UV detection wavelengths were 205 nm and 253 nm. The flow rate was 1.0 ml/min and the column temperature was 35℃. The amount of inlet was 10 µl. Results The method was highly specific, and both DOX·HCl and LND exhibited good linearity in the concentration range of 1-40 µg/ml and 6-240 µg/ml, respectively. The two compounds’ precision, stability, and recovery satisfied the requirements of the method. Conclusion This study established a HPLC method that was suitable for the simultaneous detection of DOX·HCl and LND. This method’s high level of specificity, accuracy, and reliability .

Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine：Aural Vertigo / 中国实验方剂学杂志

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.

Erectile Dysfunction and Premature Ejaculation Comorbidity Diagnosis and Treatment by Integrated Traditional Chinese and Western Medicine Chinese Expert Consensus / 中国实验方剂学杂志

At present，there is a lack of consensus on the diagnosis， treatment and management of erectile dysfunction（ED）/premature ejaculation（PE） comorbidity in China. To develop a clinical diagnosis and treatment strategy for ED/PE comorbidity， according to the guidelines for ED/PE comorbidity published in China and abroad in recent years and combined with the clinical practice of many urology and andrology research units in China，the clinical experts organized by the Branch of Sexology of Traditional Chinese Medicine， China Sexology Association formed this consensus through consensus drafting， academic review， expert correspondence interview and full discussion at the review meeting based on the existing evidence-based medical evidence. Based on the clinical experience of doctors，research evidence，patients' wishes and living environment factors，this consensus comprehensively evaluates the diagnosis and treatment norms of ED/PE comorbidity with integrated traditional Chinese and Western medicine，aiming at the diagnosis and treatment orientation and value of integrated traditional Chinese and Western medicine，so as to benefit the whole process management of more patients. Traditional Chinese medicine diagnosis pays attention to the collection of four diagnostic information of inspection， auscultation， inquiry and palpation， and carries out pattern differentiation of six meridians， pattern differentiation of Wei-defence， Qi， Ying nutrients and blood， and pattern differentiation of zang-fu organs as described in the Shanghanlun （《伤寒论》）. Based on the synergy of traditional Chinese and Western medicine， the advantages of the overall regulation of traditional Chinese medicine are brought into play， and the individualized treatment of integrated traditional Chinese and Western medicine is implemented. Internal treatment of traditional Chinese medicine is based on the pattern differentiation of yin and yang described in Section Ⅱ， Chapter Ⅳ Syndrome Differentiation of Surgical Diseases in Surgery of Traditional Chinese Medicine. As stated in Leijing： Yinyanglei （《类经·阴阳类》）， "Human diseases ... must have their roots， either in Yin or in Yang. Although there are many pathological changes， their roots are one." Huangdineijing：Suwen： Yinyangyingxiangdalun（《黄帝内经·素问·阴阳应象大论》） states that "Those who are good at diagnosis should look at the color and pulse， and differentiate Yin and Yang syndromes first." This consensus describes the yang and yin syndromes according to the principle that "Yin and Yang syndromes differentiation should be the priority in the pattern differentiation by the eight principles." In addition， for the syndromes of ED/PE comorbidity， based on the same treatment of different diseases， Chaihu Guizhitang， Wenjingtang and Buzhong Yiqitang are used， which can be referred to.

Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. Here, we describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy. VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload. Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation. The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory. Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

The evolution and application progress of non-modified drug target discovery CETSA technology / 药学学报

Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

Establishment and Evaluation of Animal Model of Acute Myocardial Infarction with Syndrome of Qi and Yin Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the establishment and evaluation methods of the rat model of acute myocardial infarction （AMI） in coronary heart disease with the syndrome of Qi and Yin deficiency by sleep deprivation （SD） combined with isoproterenol （ISO） and preliminarily explore its biological basis. MethodForty SD rats were assigned into normal （no treatment）， SD （treatment in modified multi-platform water environment for 96 h）， ISO （subcutaneous injection of ISO at 100 mg·kg-1 once every other day for a total of 2 times）， and SD+ISO （injection of 100 mg·kg-1 ISO after SD for 72 h and 96 h） groups. The cardiac function was detected by small animal echocardiography. The serum levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， and cardiac troponin T （cTnT） were measured by biochemical methods. The pathological changes of the myocardial tissue were observed by hematoxylin-eosin staining. The general state， body weight， grip strength， body temperature， behaviors in open field test， serum levels of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， cAMP/cGMP ratio， red （R）， green （G）， blue （B） values of the tongue surface， and pulse amplitude were observed and measured to evaluate the modeling results. Enzyme-linked immunosorbent assay was employed to determine the serum levels of interleukin-18 （IL-18）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， malondialdehyde （MDA）， corticotropin-releasing factor （CRF）， adrenocorticotropic hormone （ACTH）， triiodothyronine （T3）， tetraiodothyronine （T4）， cluster of differentiation 4 （CD4）， and cluster of differentiation 8 （CD8）. ResultIn terms of disease indicators， the ISO and SD+ISO groups had lower cardiac function indicators than the normal group （P<0.01）. The levels of CK， CM-MB， LDH and cTnT elevated in each model group compared with the normal group （P<0.01）. The pathological changes of myocardial tissue were obvious in the ISO and SD+ISO groups. In terms of syndrome indicators， compared with the normal group， the SD and SD+ISO groups showed decreased body weight at each time point （P<0.01）， and the ISO group showed decreased body weight at the time points of 48 h and 72 h （P<0.05， P<0.01）. The paw temperature and rectal temperature increased in the SD group （P<0.01）. The model groups showed weakened grasp strength， lowered R， G， and B values of the tongue surface （P<0.01）， prolonged immobility time （P<0.01）， reduced total distance and number of entering the central area （P<0.01）， decreased average speed （P<0.05， P<0.01）， and increased cAMP and cGMP （P<0.05， P<0.01）. The cAMP/cGMP ratio was increased in the SD+ISO group （P<0.01）， and the pulse amplitude was decreased in the SD and SD+ISO groups （P<0.01）. In terms of serological indicators，compared with the normal group， the levels of IL-18， TNF-α， SOD and MDA were significantly increased in the ISO and SD+ISO groups （P<0.01）， the CRF， ACTH， CORT， T3， T4， CD4 and CD8 in the model groups were increased （P<0.05， P<0.01）. ConclusionSleep deprivation for 96 h combined with high-dose ISO can successfully establish a rat model of acute myocardial infarction in coronary heart disease with the syndrome of Qi and Yin deficiency. The model evaluation system can be built with disease indicators of western medicine， histopathological indicators， macroscopic indicators of traditional Chinese medicine， and serological indicators.

Artesunate Combined with Other Medications and Action Mechanism： A Review / 中国实验方剂学杂志

A sesquiterpene natural substance called artemisinin was discovered in Artemisia annua. One of its derivatives， artesunate （ART）， has the properties of economy， immediate effect， low toxicity， and good tolerance. Since it has a quick and powerful killing effect on plasmodium in the erythrocyte phase and can quickly handle clinical seizure and symptoms， it is currently mostly utilized to treat cerebral malaria and other severe instances of malaria. In addition， it has antitumor， antivirus， anti-hepatic fibrosis， anti-inflammatory， antibacterial， hepatocyte protection， immunological modulation， and other pharmacological properties and can inhibit cell proliferation， induce cell apoptosis， and reduce the incidence of sepsis. In many countries， artemisinin-based combination therapies （ACTs）， such as artemether-benflumetol， artesunate-amodiaquine， and artemether-lumefantrine， are the first-line treatments for malaria. Recent research on artesunate by Chinese and international scholars has revealed that compared with monotherapy， artesunate combination therapy offers more benefits in terms of improving pharmacological effects， shortening the duration of medicine， and minimizing adverse effects. Through systematic retrieval of Web of Science Core Collection and integration through CiteSpace （6.2.1） software， this article reviewed the mechanism of artesunate combined with other medications with regard to antimalarial， antitumor， antibacterial， and antiviral features in the previous five years， so as to provide some theoretical basis for rational development and utilization of ART and new drug research and development.

Comportamiento de la anemia por toxicidad a la quimioterapia en pacientes con cáncer de pulmón

Fundamento: la anemia constituye una de las toxicidades más frecuentes con factores de riesgo intrínsecos en el paciente. La anemia por toxicidad debido a la quimioterapia se considera una disfunción hematopoyética de una sola estirpe de causa iatrogénica por su relación al tratamiento. Objetivo: caracterizar el comportamiento de la anemia por toxicidad a la quimioterapia en los pacientes con cáncer de pulmón. Método: se realizó un estudio descriptivo y retrospectivo en pacientes con cáncer de pulmón que recibieron tratamiento con quimioterapia en el Hospital Provincial Docente Oncológico María Curie de la provincia Camagüey, en el período de enero del 2020 a diciembre del 2022. La población objeto de estudio estuvo constituida por 101 pacientes que cumplieron con los criterios de inclusión. Las variables estudiadas fueron: edad, sexo, estadiamiento, condición al egreso y anemia por toxicidad. Se empleó como método el análisis documental, a través de la revisión de las historias clínicas. Resultados: predominó el sexo masculino con 73,3 % de los casos de cáncer de pulmón, no se evidenciaron diferencias en cuanto a la edad acorde al sexo. La mayor parte de los pacientes se encontraron en los estadios IIIA 36,6 % y IIIB 33,6 %. El 56,4 % egresaron en condición de vivo y el 21,8 % de los pacientes que recibieron quimioterapia desarrollaron anemia por toxicidad. Conclusiones: predominó el sexo masculino, la mayoría de los pacientes se encontraron en los estadios IIIA y IIIB, el mayor porciento de pacientes egresó vivo y un número considerable de los que recibieron quimioterapia desarrollaron anemia por toxicidad.

Foundation: anemia constitutes one of the most frequent toxicities with intrinsic risk factors in the patient. Anemia due to toxicity due to chemotherapy is considered a single-line hematopoietic dysfunction of iatrogenic cause due to its relationship to treatment. Objective: to characterize the behavior of anemia due to toxicity to chemotherapy in patients with lung cancer. Method: a descriptive and retrospective study was carried out in patients with lung cancer who received chemotherapy treatment at the María Curie Provincial Teaching Oncology Hospital in Camagüey province, from January 2020 to December 2022. The population under study the study consisted of 101 patients who met the inclusion criteria. The variables studied were: age, sex, staging, condition at discharge and anemia due to toxicity. Documentary analysis was used as a method, through the review of medical records. Results: the male sex predominated with 73.3 % of the cases of lung cancer, there were no differences in terms of age according to sex. Most of the patients were found in stages IIIA 36.6 % and IIIB 33.6 %. 56.4 % were discharged alive and 21.8 % of the patients who received chemotherapy developed anemia due to toxicity. Conclusions: the male sex predominated, most of the patients were in stages IIIA and IIIB, the highest percentage of patients were discharged alive and a considerable number of those who received chemotherapy developed anemia due to toxicity.

Anaphylaxis associated with intracavernous penile injection of prostaglandin E1 in combination with papaverine and phentolamine / Anafilaxia associada à injeção intracavernosa peniana de prostaglandina E1 em combinação com papaverina e fentolamina

Total radical prostatectomy for advanced prostate cancer may lead to sexual impotence, since it is associated with severe erectile dysfunction. A widely recommended treatment for this disabling condition is intracavernous penile injection of a mixture of prostaglandin E1, papaverine, and phentolamine. To our knowledge, we present the first case of anaphylaxis associated with intracavernous penile injection of prostaglandin E1 in combination with papaverine and phentolamine.

A prostatectomia radical total para câncer de próstata avançado pode levar à impotência sexual, associada a uma disfunção erétil grave. Um tratamento amplamente recomendado para esta condição incapacitante é a injeção intracavernosa no pênis de uma mistura de prostaglandina E1, papaverina e fentolamina. Até onde sabemos, estamos apresentando o primeiro caso de anafilaxia associada à injeção intracavernosa peniana de prostaglandina E1 em combinação com papaverina e fentolamina.

Desmopressin Plus Tolterodine vs Desmopressin Plus Indomethacin for Refractory Pediatric Enuresis: An Open-label Randomized Controlled Trial

Objective: To compare the efficacy of desmopressin plus tolterodine (D+T) with desmopressin plus indomethacin (D+I) for treating enuresis in children. Design: Open-label randomized controlled trial. Setting: Bandar Abbas Children’s Hospital, a tertiary care children’s hospital in Iran, from March 21, 2018, to March 21, 2019. Participants: 40 children older than five years with monosymptomatic and non-monosymptomatic primary enuresis resistant to desmopressin monotherapy. Intervention: Patients were randomized to receive either D+T (60 µg sublingual desmopressin and 2 mg tolterodine) or D+I (60 µg sublingual desmopressin and 50 mg indomethacin) every night before bedtime for five months. Outcome: Reduction in the frequency of enuresis was evaluated at one, three, and five months, and response to treatment at five months. Drug reactions and complications were also noted. Results: After adjustment for age, consistent incontinence from toilet training, and non-monosymptomatic enuresis, D+T was significantly more efficacious than D+I; mean (SD) percent in nocturnal enuresis reduction at 1 [58.86 (7.27)% vs 31.18 (3.85) %; P<0.001], 3 [69.78 (5.99)% vs 38.56 (3.31)%; P<0.000], and 5 [84.84(6.21)% vs 39.14 (3.63)%; P<0.001] months showing a large effect. At 5 months, complete response to treatment was only observed with D+T, while treatment failure was significantly higher with D+I (50% vs 20%; P=0.047). None of the patients in either group developed cutaneous drug reactions or central nervous system symptoms. Conclusion: Desmopressin plus tolterodine appears to be superior to desmopressin plus indomethacin for treating pediatric enuresis resistant to desmopressin.

Sequential analysis of erythrocyte aggregation in P. falciparum malaria with and without ASAQ therapy by optical signal and image analysis

The aggregation of erythrocytes is an important mechanism for blood flow through the cardiovascular system. In malaria, this is complicated by infection caused by P. falciparum and is further complicated by the severity of parasitemia. Hence analysis of this micro-mechanism is essential to know the changes in blood not only in diseased conditions but also after artemisinin combination therapy (ASAQ) to alleviate suffering. For analysis purposes, aggregation of erythrocytes was determined by LED laser aggregometer, represented in terms of various parameters related to the changes in laser transmitted intensity. Formed aggregates are further analyzed by imaging and image-processing methods. For this study blood samples from young adults (18 – 40 years old) infected with P. falciparum (n= 80), without any other serious illness, were performed. These samples were selected based on the severity of parasitemia, and were divided into low (LP), medium1 (MP1), medium 2 (MP2), and high (HP) parasitemia. For three days, the selected individuals were treated with artemisinin-based combination therapy ASAQ (Artesunate 4 mg/kg and amodiaquine 10 mg base/ kg once a day). Healthy subjects (n=20) without any history of the disease were selected as a control group. The results, as obtained by various parameters, show a significant elevation of aggregation of erythrocytes (P< 0.05) in P. falciparum malaria with the increase of parasitemia level. There was a decrease in the aggregation after treatment on day four tending towards normal. Thus the current study shows the potential beneficial role of ASAQ on erythrocytes aggregation, which may contribute to reducing the harmful effects on various organs in P. falciparum-infected blood.

Repositioning of FDA-approved drugs for the treatment of methicillin-resistant Staphylococcus aureus infection: Structure-based virtual screening and in vitro assay

Background: Computer-aided repositioning of approved drugs is an increasingly popular strategy for the discovery of effective therapies. The potency of the newly repositioned drugs can be optimized using them as a component of an effective drug combination, thereby achieving the desired therapeutic effect at a lower and more tolerable drug concentration. Aim and Objectives: The aim of the study was to perform structure-based virtual screening and repurposing of FDA-approved drugs for the treatment of methicillin resistance by Staphylococcus aureus (SA) and perform an in vitro validation of the prediction. Materials and Methods: Following ethical clearance at the Department of Pharmacology and Therapeutics, College of Health Sciences, Usmanu Danfodiyo University Sokoto, molecular docking was performed against 5 validated protein targets involved in the development of methicillin resistance by SA and an in vitro validation of the prediction was done using 3 of the top-ranking drug candidates against methicillin-resistant vancomycin-susceptible strain of the pathogen (ATCC 43300). Results: Desmopressin and docetaxel, two of the 20 top-ranking repurposed drugs discovered through virtual screening, enhanced the inhibitory effect of oxacillin against the ATCC 43300 SA strain in a ratio-dependent manner, although each of the two drugs singly was only weakly effective against the bacterial strain. The standard drug, vancomycin (also among the top-scoring candidates), alone, was effective against ATCC 43300 strain and in combination with oxacillin, the two drugs produced a ratio-dependent synergistic effect against the bacterial strain. Conclusion: These findings suggest that oxacillin-based combinations with desmopressin, docetaxel, and the standard drug vancomycin, three of the 20 top-ranking drugs, at optimum ratios, may be beneficial in reversing the resistance of the ATCC 43300 SA strain to oxacillin, thus supporting the prediction of the molecular docking results.

Obtener un mejor tratamiento para el paciente con hipotiroidismo

Introducción: El hipotiroidismo es una entidad de visita frecuente al endocrinólogo, establecer el mejor tratamiento es un desafío, a pesar del manejo adecuado y de un control hormonal óptimo, en ocasiones los pacientes continúan con los síntomas que afectan su calidad de vida, por lo que el tratamiento debe ser individualizado, basado en la mejor evidencia. Objetivo: Establecer las mejores opciones terapéuticas en las diferentes formas de presentación del hipotiroidismo. Métodos: Se realizó una búsqueda bibliográfica no sistemática en las bases de datos de PubMed, Medline, LILACS, EMBASE, Redalyc y guías internacionales. Los criterios de inclusión fueron publicaciones en inglés y español, en las que el título, palabras clave o resumen incluyen información pertinente al objetivo de estudio, periodicidad no mayor a los 5 años a excepción de las guías que son las últimas revisiones. En la búsqueda se obtuvieron 30 artículos de los cuales fueron 14 seleccionados. Conclusiones: Se establecieron las opciones terapéuticas con el fin de obtener un mejor tratamiento para el paciente hipotiroideo que debe ser individualizado y basado en la mejor evidencia, para alcanzar un control adecuado de su enfermedad, mejorar la calidad de vida y evitar complicaciones relacionadas con esta patología.

Introduction: Hypothyroidism is an entity that is frequently seen at the endocrinologist´s. establishing the best treatment is a challenge, despite proper management and optimal hormonal control, sometimes patients continue with symptoms which affect their quality of life, therefore that treatment should be individualized, based on the best evidence. Objective: To establish the best therapeutic options in hypothyroidism different forms of presentation. Methods: A non-systematic bibliographic search was carried out in PubMed, Medline, LILACS, EMBASE, Redalyc databases and in the international guidelines. The inclusion criteria were publications in English and Spanish, in which the title, keywords or abstract include relevant information to the objective of the study, with a periodicity of no more than 5 years, except for the guidelines that the latest revisions were used. In the search, 30 articles were retrieved, 14 which were selected. Conclusions: The therapeutic options were established in order to find better treatment for hypothyroid patients, which must be individualized and based on the best evidence, to achieve adequate control of the disease, to improve the quality of life and to avoid related complications.

Effect of combination treatment of protocatechuic acid with 5-fluorouracil and oxaliplatin on colon cancer Caco-2 cell line

Among the most common antitumor drugs used in the treatment of colon cancer are 5-fluorouracil and oxaliplatin (5-FU and OXA). However, both these drugs have many side effects, and hence there is a need for new treatment\approach to reduce the side effects aas well as drug concentration. In this context, here, we investigated the effect of addition of protocatechuic acid (PCA) onto either monotherapies or combination therapies of 5-FU and OXA on the human colon cancer (Caco-2) cell line. In addition, we did evaluate the synergistic effect of PCA with 5-FU and OXA. Further, we determined the suppressive effects of different doses of PCA alone or in combination with 5-FU/OXA on cell proliferation after 24 and 48 hours. We identified a suppressive effect of PCA on cell viability at 48 h starting from the dose of 50 µM Matrix metalloproteinase-2 (MMP-2) and MMP-9 gene expression levels and apoptotic effects showed significant increases and decreases depending on the dose and time applied in the experimental groups. The highest synergistic activity was seen at 2:1 concentration of 5-FU+ PCA. Our findings indicate the presence of the cytotoxic and apoptotic effects of PCA in Caco-2 cells at 48 h, increasing with a dose- and time-dependent manner.

Efficacy and Safety of Fixed-Dose Combination of Efonidipine and Telmisartan in Stage II Hypertensive Patients: Results from Randomized Clinical Trial

Aim: The aim of this study was to evaluate the anti-hypertensive efficacy of a fixed-dose combination (FDC) of Efonidipine 40 mg and Telmisartan 40 mg in Stage II hypertensive patients. Study Design: Multicentric, randomized, double-blind, parallel, comparative Phase III clinical trial. Methodology: This clinical trial was conducted at six geographically distributed sites across India and enrolled 240 Stage II hypertensive patients. They were randomized into two groups in a ratio of 1:1 using computer-generated block randomization to receive E+T (FDC of Efonidipine 40 mg + Telmisartan 40mg) or C+T (FDC of Cilnidipine 10 mg + Telmisartan 40 mg) group intervention once daily for a period of 90 days. The study site staff, investigator and patients were blinded to the treatment allocation. The primary endpoint of the study evaluated the mean reduction in sitting systolic BP (SBP) and diastolic BP (DBP) from baseline to day 90 whereas the secondary endpoints assessed were mean reduction in BP from baseline to day 30 & 60, patients achieving target BP (<140/90 mmHg) and the safety and tolerability of the investigational products based on the incidences of adverse events (AEs) reported. Results: A total of 118 subjects were randomized to the E+T group wherein the mean (±SD) SBP and DBP at baseline was 167.25 ± 4.68/107.26 ± 5.19 mmHg. After 30 days of treatment with the E+T group, the mean reduction in SBP/DBP of 29.37/18.06 mmHg was observed whereas at Day 60 reduction of 38.55/22.69 mmHg was seen from the baseline. At Day 90, SBP/DBP decreased to 119.41±14.99/81.67±4.29 mmHg with a mean reduction of 47.94/25.89 mmHg in the E+T group. During the study period, the difference in systolic blood pressure between the treatments with E+T and C+T was -0.48 mmHg, with the two-sided 95% confidence interval (CI) ranging from -4.54 to 3.58?mmHg. The corresponding difference in diastolic blood pressure was -0.77 (95% CI: -2.60 to 1.06) mm?Hg. The upper boundary of the 95% CI was below the margin of 10?mmHg, confirming the non-inferiority of E+T to C+T. A total of 92% of patients who had been assigned to E+T treatment achieved their target BP goal. Only one patient reported an adverse event with E+T treatment. No unexpected AEs were reported in the E+T group suggesting its good safety and tolerability. Overall, the E+T treatment was effective, safe and well-tolerated by the patients for 90 days. Conclusion: It was concluded that the FDC of Efonidipine 40 mg and Telmisartan 40 mg was efficacious in the management of Stage II hypertension.

Preoperative chemotherapy versus upfront surgery for advanced gastric cancer: a propensity score matching analysis / Quimioterapia pré-operatória versus cirurgia de princípio para câncer gástrico avançado: análise por escore de propensão

ABSTRACT BACKGROUND: Surgical resection remains the main curative therapeutic modality for advanced gastric cancer. Recently, the association of preoperative chemotherapy has allowed the improvement of results without increasing surgical complications. AIMS: To evaluate the surgical and oncological outcomes of preoperative chemotherapy in a real-world setting. METHODS: A retrospective review of gastric cancer patients who underwent gastrectomy was performed. Patients were divided into two groups for analysis: upfront surgery and preoperative chemotherapy. The propensity score matching analysis, including 9 variables, was applied to adjust for potential confounding factors. RESULTS: Of the 536 patients included, 112 (20.9%) were referred for preoperative chemotherapy. Before the propensity score matching analysis, the groups were different in terms of age, hemoglobin level, node metastasis at clinical stage- status, and extent of gastrectomy. After the analysis, 112 patients were stratified for each group. Both were similar for all variables assigned in the score. Patients in the preoperative chemotherapy group had less advanced postoperative p staging (p=0.010), postoperative n staging (p<0.001), and pTNM stage (p<0.001). Postoperative complications, 30- and 90-days mortality were similar between both groups. Before the propensity score matching analysis, there was no difference in survival between the groups. After the analysis, patients in the preoperative chemotherapy group had better overall survival compared to upfront surgery group (p=0.012). Multivariate analyses demonstrated that American Society of Anesthesiologists III/IV category and the presence of lymph node metastasis were factors significantly associated with worse overall survival. CONCLUSIONS: Preoperative chemotherapy was associated with increased survival in gastric cancer. There was no difference in the postoperative complication rate and mortality compared to upfront surgery.

RESUMO RACIONAL: A ressecção cirúrgica continua sendo a principal modalidade terapêutica curativa para o câncer gástrico avançado. Recentemente, a associação de quimioterapia pré-operatória tem permitido a melhora dos resultados sem aumentar as complicações cirúrgicas. OBJETIVOS: Avaliar os resultados cirúrgicos e oncológicos da quimioterapia pré-operatória em um cenário do mundo real. MÉTODOS: Realizou-se uma revisão retrospectiva de pacientes com câncer gástrico submetidos à gastrectomia. Os pacientes foram divididos em dois grupos para análise: cirurgia inicial e quimioterapia pré-operatória. A análise por escore de propensão, incluindo 9 variáveis, foi aplicada para ajustar possíveis fatores de confusão. RESULTADOS: Dos 536 pacientes incluídos, 112 (20,9%) foram encaminhados para quimioterapia pré-operatória. Antes da análise por escore de propensão, os grupos eram diferentes em termos de idade, nível de hemoglobina, status de node metastasis at clinical stage e extensão da gastrectomia. Após a análise, 112 pacientes foram estratificados para cada grupo. Ambos foram semelhantes para todas as variáveis atribuídas no escore. O grupo da quimioterapia pré-operatória apresentou estágios postoperative p staging (p=0,010), postoperative n staging (p<0,001) e pTNM menos avançados (p<0,001). As complicações pós-operatórias e a mortalidade em 30 e 90 dias foram semelhantes entre os grupos. Antes da análise por escore de propensão, não houve diferença na sobrevida entre os dois grupos. Após a análise, o grupo da quimioterapia pré-operatória apresentou melhor sobrevida global em comparação ao grupo da cirurgia inicial (p=0,012). As análises multivariadas demostraram que a categoria American Society of Anesthesiologists III/IV e a metástase linfonodal foram fatores significativamente associados à pior sobrevida global. CONCLUSÕES: A quimioterapia pré-operatória foi associada à maior sobrevida no câncer gástrico. Não houve diferença na taxa de complicações pós-operatórias e mortalidade em comparação com a cirurgia inicial.

Intraperitoneal chemotherapy for gastric cancer with peritoneal carcinomatosis: study protocol of a phase ii trial / Quimioterapia intraperitoneal para o câncer gástrico com carcinomatose peritoneal: protocolo de estudo de um ensaio de fase ii

ABSTRACT BACKGROUND: Peritoneal carcinomatosis in gastric cancer is considered a fatal disease, without expectation of definitive cure. As systemic chemotherapy is not sufficient to contain the disease, a multimodal approach associating intraperitoneal chemotherapy with surgery may represent an alternative for these cases. AIMS: The aim of this study was to investigate the role of intraperitoneal chemotherapy in stage IV gastric cancer patients with peritoneal metastasis. METHODS: This study is a single institutional single-arm prospective clinical trial phase II (NCT05541146). Patients with the following inclusion criteria undergo implantation of a peritoneal catheter for intraperitoneal chemotherapy: Stage IV gastric adenocarcinoma; age 18-75 years; Peritoneal carcinomatosis with peritoneal cancer index<12; Eastern Cooperative Oncology Group 0/1; good clinical status; and lab exams within normal limits. The study protocol consists of four cycles of intraperitoneal chemotherapy with paclitaxel associated with systemic chemotherapy. After treatment, patients with peritoneal response assessed by staging laparoscopy undergo conversion gastrectomy. RESULTS: The primary outcome is the rate of complete peritoneal response. Progression-free and overall survivals are other outcomes evaluated. The study started in July 2022, and patients will be screened for inclusion until 30 are enrolled. CONCLUSIONS: Therapies for advanced gastric cancer patients have been evaluated in clinical trials but without success in patients with peritoneal metastasis. The treatment proposed in this trial can be promising, with easy catheter implantation and ambulatory intraperitoneal chemotherapy regime. Verifying the efficacy and safety of paclitaxel with systemic chemotherapy is an important progress that this study intends to investigate.

RESUMO RACIONAL: A carcinomatose peritoneal no câncer gástrico é considerada uma doença fatal, sem expectativa de cura definitiva. Como a quimioterapia sistêmica não é suficiente para conter a doença, uma abordagem multimodal associando a quimioterapia intraperitoneal à cirurgia pode representar uma alternativa para esses casos. OBJETIVOS: Investigar o papel da quimioterapia intraperitoneal em pacientes com câncer gástrico estágio IV com metástases peritoneais. MÉTODOS: Trata-se de um ensaio clínico prospectivo unicêntrico, braço único, fase II (NCT05541146). Pacientes com os seguintes critérios de inclusão serão submetidos à implantação de cateter peritoneal para quimioterapia intraperitoneal: adenocarcinoma gástrico estágio IV; idade 18-75 anos; carcinomatose peritoneal com índice de câncer peritoneal<12; ECOG 0/1; bom estado clínico e exames laboratoriais dentro da normalidade. O protocolo do estudo consiste em 4 ciclos de quimioterapia intraperitoneal com Paclitaxel associado à quimioterapia sistêmica. Após o tratamento, os pacientes com resposta peritoneal avaliada por laparoscopia serão submetidos à gastrectomia de conversão. RESULTADOS: O desfecho primário é a taxa de resposta peritoneal completa. A sobrevida livre de progressão e global são outros desfechos avaliados. O estudo foi iniciado em julho de 2022 e os pacientes serão selecionados para inclusão até que 30 sejam inscritos. CONCLUSIONS: Terapias para pacientes com câncer gástrico avançado foram avaliadas em ensaios clínicos, mas sem sucesso em pacientes com metástase peritoneal. O tratamento proposto neste estudo pode ser promissor, com fácil implantação do cateter e regime de quimioterapia intraperitoneal ambulatorial. Verificar a eficácia e segurança do Paclitaxel associado à quimioterapia sistêmica é um progresso importante que o presente estudo pretende investigar.