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1.
Acta Pharmaceutica Sinica ; (12): 25-34, 2024.
Article in Chinese | WPRIM | ID: wpr-1005435

ABSTRACT

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.

2.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 134-142, 2024.
Article in Chinese | WPRIM | ID: wpr-1005262

ABSTRACT

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.

3.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 290-298, 2024.
Article in Chinese | WPRIM | ID: wpr-1003791

ABSTRACT

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.

4.
Rev. Finlay ; 13(3)sept. 2023.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1514826

ABSTRACT

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.

5.
Indian Pediatr ; 2023 Jun; 60(6): 447-452
Article | IMSEAR | ID: sea-225424

ABSTRACT

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.

7.
Arq. Asma, Alerg. Imunol ; 7(2): 222-224, 20230600. ilus
Article in English, Portuguese | LILACS | ID: biblio-1509869

ABSTRACT

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.


Subject(s)
Humans , Male , Middle Aged
8.
Indian J Biochem Biophys ; 2023 Apr; 60(4): 331-338
Article | IMSEAR | ID: sea-221643

ABSTRACT

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.

9.
Article | IMSEAR | ID: sea-218015

ABSTRACT

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.

10.
Indian J Exp Biol ; 2023 Mar; 61(3): 151-158
Article | IMSEAR | ID: sea-222580

ABSTRACT

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.

11.
Rev. cuba. med ; 62(1)mar. 2023.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1450003

ABSTRACT

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.

12.
Article | IMSEAR | ID: sea-220313

ABSTRACT

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.

13.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 185-191, 2023.
Article in Chinese | WPRIM | ID: wpr-953939

ABSTRACT

Renal fibrosis is the main pathological foundation of chronic kidney diseases progressing to end-stage renal diseases. With complex pathogenic factors and prolonged disease course, it threatens the quality of life of patients and brings about heavy financial burden to medical care. In the instance of intestinal flora disturbance, the internal homeostasis is broken, resulting in various "imbalances". The "combination of state and target" endows the syndrome differentiation-based treatment of renal fibrosis with new connotation from the perspective of intestinal flora reconstruction and microbial diversity restoration. In addition, traditional Chinese medicine (TCM)-targeted intervention of intestinal microecology has unique advantages under the principle of "treating different diseases with the same method", which can guide the diagnosis and treatment of renal fibrosis. To be specific, TCM emphasizes macroscopic regulation of state and microscopic targeting. In view of the inflammatory response, accumulation of endotoxin, and excessive deposition of extracellular matrix (ECM) in the process of renal fibrosis, the strategies for treating this disease have been developed, such as alleviating dampness,removing turbid toxin, and relieving deficiency and stasis. Famous prescriptions in ancient books or compound Chinese medicine prescriptions, classical formulas, Chinese medicine monomers, or active components of Chinese medicine target intestinal microecology. Therefore, from the perspective of common pathogenic factors of renal diseases (renal fibrosis) or pathological product-intestinal microecological imbalance, this article combines TCM basic theory with modern medical pathogenesis, and summarizes the research on TCM intervention of renal fibrosis by regulating intestinal microecology and the scientific connotation of renal fibrosis, which is expected to provide ideas and methods for the product development and related preparations and in-depth molecular biological research.

14.
Journal of Pharmaceutical Analysis ; (6): 640-659, 2023.
Article in Chinese | WPRIM | ID: wpr-991171

ABSTRACT

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after long-term use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saiko-saponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-KB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RB-induced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to sai-kogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NF-κB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosa-ponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

15.
Journal of Pharmaceutical Analysis ; (6): 603-615, 2023.
Article in Chinese | WPRIM | ID: wpr-991168

ABSTRACT

Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents.To overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier.Herein,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a pep-tide and a small molecular compound.In this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97-110 amino acids of apoptin(AP)(AA@G))was con-structed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle.As expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma cell.This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced com-bination therapy.

16.
Chinese Journal of Endocrine Surgery ; (6): 117-119, 2023.
Article in Chinese | WPRIM | ID: wpr-989907

ABSTRACT

The incidence of thyroid cancer has continued to increase. Most thyroid cancer patients have good prognosis, but there are still some patients who will develop into the middle or late stage. The status of cytotoxic treatment in thyroid cancer treatment is controversial. Chemotherapy, as a classical malignant tumor treatment, has its unique significance for the special type and the special period of thyroid cancer. Chemotherapy can be an option for systemic treatment if no other treatment is available for patients of differentiated thyroid carcinoma refractory to radiodine in rapid progression and life-threatening period. For patients of anaplastic thyroid cancer in progression period, chemotherapy can be selected if there are no other treatments in clinical trials. And "Chemical therapy plus" treatment model might play an important role in thyroid treatment, because with the development of targeted drugs and immunotherapy, chemotherapy combined with other treatments can reduce the dosage of chemotherapy drugs to reduce the toxic side effect, and can improve other therapeutic effects.

17.
International Journal of Traditional Chinese Medicine ; (6): 766-771, 2023.
Article in Chinese | WPRIM | ID: wpr-989703

ABSTRACT

Objective:To explore the core syndrome type and Chinese herbal medicine combination in Ulcerative Colitis (UC) remission phase based on the real and effective clinical data of the outpatient information system of the hospital.Methods:Medical records of patients with UC in remission who received Traditional Chinese Medicine (TCM) oral intervention from August 1, 2018 to October 31, 2021 in Jiangsu Provincial Hospital of Traditional Chinese Medicine were collected. Medcase V3.2 data record mining system was used, and the enhanced FPGrowth algorithm was used to build a strengthened association rule data mining model. Xminer Operation Tool was used for mining and logical analysis, and Medcase Chart was used for deconstruction analysis and graphical representation of quantitative trend data. Based on the statistical analysis results, the core syndrome types, pathogenesis evolution rules, and core TCM compatibility law in remission stage of UC were explored.Results:A total of 302 patients were collected. Diarrhea, bloody stool, mucus stool, fatigue, light tongue, fine pulse, paroxysmal abdominal pain, and colonoscopy found intestinal polyps were the core symptoms in UC remission phase. Spleen Qi Deficiency Syndrome, Spleen Deficiency and Dampness Syndrome, Spleen Deficiency and Toxin Accumulation Syndrome were the core syndrome type. In Spleen Qi Deficiency Syndrome, the core drug combinationed Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Poria, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Amomi Fructus, Angelicae Sinensis Radix, and Paeoniae Radix Alba. In Spleen Deficiency and Dampness Syndrome, the core drug combinationed Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Poria, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Coptidis Rhizoma, Amomi Fructus, and Saposhnikoviae Radix. In Spleen Deficiency and Toxin Accumulation Syndrome, the core drug combinationed Codonopsis Radix, Astragali Radix, Atractylodis Macrocephalae Rhizoma, Citri Reticulatae Pericarpium, Mume Fructus, Sophorae Flos, Coptidis Rhizoma, and Saposhnikoviae Radix.Conclusion:Spleen deficiency was the core syndrome type in UC remission phase. The Chinese herbal medicine treatment options included replenishing qi supplemented with harmonizing the stomach, promoting blood circulation, stopping bleeding, removing dampness, clearing heat, and relieving depression.

18.
International Journal of Traditional Chinese Medicine ; (6): 95-99, 2023.
Article in Chinese | WPRIM | ID: wpr-989598

ABSTRACT

Objective:To analyze the application and regularity of acupoint selection of Sanyinjiao (SP 6) based on data mining.Methods:Search for literatures in CNKI, Wanfang, VIP, and Pubmed, the clinical researches of acupuncture on Sanyinjiao (SP 6) point were selected, according to the inclusion and exclusion criteria, and the retrieval period was from database construction to September 30th, 2021. Excel 2016, SPSS Statistics 25.0, SPSS Modeler 18.0 were used to perform descriptive analysis, association analysis and cluster analysis.Results:After literature screening, a total of 261 literatures were included, involving 73 kinds of diseases, mainly including mental and behavioral disorders, genitourinary diseases, endocrine and nutritional metabolism diseases and nervous system diseases. The most frequently used acupoints in Sanyinjiao (SP 6) compatibility are Zusanli (ST 36), Baihui (GV 20), Guanyuan (CV 4) and Taichong (LR 3), most of which focus on stomach meridian, conception channel, governor channel and bladder meridian. Seven categories were extracted among high-frequency acupoints by cluster analysis. The association rule analysis showed that the commonly used combination of Sanyinjiao (SP 6) were Zusanli (ST 36)-Sanyinjiao (SP 6), Baihui (GV 20)-Sanyinjiao (SP 6), and Guanyuan (CV 4)-Sanyinjiao (SP 6).Conclusions:Sanyinjiao (SP 6) is widely used in clinical application, and it is always compatible with stomach meridian, conception vessel, governor channel acupoints, especially those acupoints on the outer and inner meridians and the upper and lower parts. Sanyinjiao (SP 6) combined with other acupoints can treat diseases of multiple systems, such as insomnia, stroke, anxiety and depression, dysmenorrhea, infertility, etc. Clustering and association analysis found the core compatibility law of Sanyinjiao (SP 6), which can be used as a reference for clinical acupoint selection.

19.
Journal of International Oncology ; (12): 362-367, 2023.
Article in Chinese | WPRIM | ID: wpr-989572

ABSTRACT

Compared with single therapy, radiotherapy combined with chemotherapy, endocrine therapy, molecular targeted therapy and immunological therapy can not only shorten the treatment cycle, but also improve the local control rate and prolong the survival of patients. However, the safety of combined therapy still needs to be further clarified to comprehensively evaluate the feasibility. Therefore, exploring the efficacy and safety of radiotherapy combined with systematic therapy will provide evidence for clinical benefits.

20.
Journal of Leukemia & Lymphoma ; (12): 343-347, 2023.
Article in Chinese | WPRIM | ID: wpr-988991

ABSTRACT

Objective:To investigate clinical efficacy and safety of venetoclax (VEN)-based regimens in the treatment of acute myeloid leukemia (AML).Methods:The clinical data of 41 AML patients treated with venetoclax-based regimens from January 2021 to December 2021 in Ruijin Hospital North of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The treatment regimens included VEN+demethylating drugs ± gene mutation inhibitors or VEN+chemotherapy with a median number of 2 courses (1- 5 courses).Results:The median age of all patients was 60 years (18-73 years), and there were 24 males and 17 females. After 1 course of VEN-based therapy, 22 (53.7%) patients achieved complete remission (CR) or morphological complete remission without complete blood count recovery (CRi), including 5 patients achieving minimal residual disease (MRD) negative. After 2 courses of treatment, of 17 patients available for efficacy evaluation, 7 patients achieved MRD negative. Among 20 relapsed/refractory AML patients, 9 cases achieved CR/CRi after 1 course of treatment, of which 1 patient had MRD negative. Among 21 patients initially treated and re-treated, 13 cases achieved CR/CRi and 1 case achieved partial remission after 1 course of treatment, of which 4 cases had MRD negative.Conclusions:VEN-based treatment regimens for AML have a high remission rate and tolerable adverse effects.

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