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.

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.

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.

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.

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.

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.

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.

A combined regimen based on bortezomib and glucocorticoids for 6 patients with recurrent/refractory immune thrombotic thrombocytopenic purpura / 中华血液学杂志

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.

Effect of Huatan Tongluo Prescription on Vulnerability of Carotid Atherosclerotic Plaque in Hypertension / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Huatan Tongluo prescription on the vulnerability of atherosclerotic plaques in the carotid arteries of patients with hypertension of phlegm-stasis combination syndrome. MethodA total of 132 eligible patients were randomly divided into an observation group （66 cases） and a control group （66 cases）. The control group received oral atorvastatin calcium tablets and enteric-coated aspirin tablets， while the observation group received Huatan Tongluo prescription in addition to the treatment received by the control group. The treatment duration was 6 months. A carotid artery ultrasound examination was performed to record the number of plaques， the maximum plaque area， the maximum plaque cross-sectional thickness， and the intima-media thickness （IMT） of the carotid artery. Crouse score， plaque vulnerability score， and phlegm-stasis combination syndrome score were assessed. Blood lipid levels ［total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C）］， inflammatory markers ［neutrophil-to-lymphocyte ratio （NLR）， monocyte-to-lymphocyte ratio （MLR）， interleukin-6 （IL-6）， and high-sensitivity C-reactive protein （hs-CRP）］， vascular endothelial function ［endothelin-1 （ET-1）， von Willebrand factor （vWF）， and nitric oxide （NO）］， and relevant proteins ［pentraxin 3 （PTX3） and galectin-3 （Gal-3）］ levels were measured. Safety evaluation was conducted， and comparisons were made in terms of carotid artery stenosis rate， plaque regression efficacy， and traditional Chinese medicine （TCM） syndrome efficacy. ResultCompared with the results before treatment， both groups showed significant reductions in IMT， plaque number， maximum plaque area， and maximum plaque cross-sectional thickness （P<0.05）. After treatment， the observation group exhibited more significant reductions in the above indicators compared with the control group （P<0.05）. After treatment， Crouse scores， plaque vulnerability scores， and phlegm-stasis combination syndrome scores in both groups were lower than those before treatment （P<0.05）. After treatment， the observation group had lower scores in these indicators than the control group （P<0.05）. In terms of blood lipid levels， both groups showed decreases in TC， TG， and LDL-C levels， and an increase in HDL-C levels after treatment compared to those before treatment （P<0.05）. The observation group exhibited greater improvements in these lipid parameters than the control group （P<0.05）. Inflammatory markers NLR， MLR， IL-6， and hs-CRP significantly decreased in both groups after treatment compared with those before treatment （P<0.05）. The observation group showed more significant reductions in these markers than the control group after treatment （P<0.05）. After treatment， both groups demonstrated decreases in levels of ET-1， vWF， PTX3， and Gal-3， along with an increase in NO levels compared with those before treatment （P<0.05）. The observation group showed more significant improvements in these markers than the control group after treatment （P<0.05）. After treatment， the observation group had a lower carotid artery stenosis rate than the control group （P<0.05）. The plaque regression efficacy rate was 51.72% （30/58） in the observation group， and the total effective rate of TCM syndrome was 84.48% （49/58）， both of which were higher than 18.64% （11/59） and 52.54% （31/59） in the control group （χ²=10.061， 13.799， P<0.05）. No adverse reactions related to the Huatan Tongluo prescription were observed during the treatment period. ConclusionIn addition to statin therapy， Huatan Tongluo prescription can effectively reverse carotid artery atherosclerotic plaques in patients with hypertension and carotid artery stenosis， reduce plaque vulnerability， exhibit lipid-lowering and anti-inflammatory effects， and improve vascular endothelial function. The treatment demonstrates favorable clinical efficacy and safety. Therefore， it is very worthy of clinical promotion and application.

Feasibility of Combination of Antagonism Chinese Medicinals based on the Theory of “Eighteen Antagonisms” / 中医杂志

The “eighteen antagonisms” of Chinese medicinals have been regarded as taboos in the field of traditional Chinese medicine （TCM）， and the connotations have gradually been narrowed down in the development of TCM. From the historical perspective， “eighteen antagonisms” are not an absolute taboo in terms of the combination of medicinals， and the existing types of antagonism medicinals are also worth further discussion. From the perspective of toxicological effects， the toxicology of the “eighteen antagonisms” mainly comes from the enhancement of the toxic and side effects of a certain herb， rather than the combination of two herbs. From the perspective of pharmacodynamic actions， the combination of some antagonism medicinals can achieve therapeutic effects that cannot obtained by conventional medicinals， which is feasible and reasonable in clinical practice. Therefore， it is believed that the application of combining some antagonism medicinals based on “eighteen antagonisms” is of positive significance. Moreover， strict combination， processing and decoction methods should be noted in the use of antagonism medicinals. All mentioned above will provide reference for the correct recognition and use of the combination of “eighteen antagonisms”， and broaden the combination thinking for the treatment of clinical diseases with TCM.

Sorting and Elaborating on the Combination Theory of Herb Pairs / 中医杂志

As the smallest combination unit of Chinese medicinals， herbal pairs serve as the bridge between medicinals and formulas， whose combination theory reflects the basic characteristics of Chinese medicinals combination and the core essence of prescription composition. Simultaneously， as a key combination of medicinals in clinical treatment of diseases， syndromes， and symptoms， herbal pairs are the main form of clinical medication in traditional Chinese medicine （TCM） as well as the characteristic advantage of treating diseases. This article summarized that “mutual complement of medicinals of same or antagonism flavor and nature” theory is the theoretical origin， and efficacy-enhancement and toxicity-attenuation is the core purpose of the combination of herbal pairs. The property theory of Chinese medicinals and the thought of differentiation and treatment are the main basis of the combination of herbal pairs， and pertinence and flexibility are the key points in clinical application. All mentioned above are expected to provide theoretical guidance for the clinical use and modern research of herbal pairs.

Short-term efficacy and safety analysis of TACE combined with TKI and PD-1 inhibitors in the treatment of initially unresectable hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To evaluate the efficacy and safety of transhepatic arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKI) and programmed death-1 (PD-1) inhibitors in the treatment of patients with initially unresectable hepatocellular carcinoma.Methods:The clinical data of 42 patients with initially unresectable hepatocellular carcinoma who were admitted to the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were included. There were 31 males and 11 females, with a median age of 56 years old (range, 45-72 years old). All patients received TACE+ TKI+ PD-1 inhibitor combined treatment. The systemic treatment cycles were calculated by the regimen of immunotherapy. The timing of local treatment depends on tumor size, blood supply and treatment response. Patients were followed up through hospitalization, outpatient visits and telephone review. The Kaplan-Meier curves were obtained for survival analysis.Results:The dosing cycle to achieve optimal imaging response in the patients was 4 (3, 7) [ M( Q1, Q3)], with a systemic treatment time of 141 (65, 194) d [ M( Q1, Q3)] and 2 (1, 3) times [ M( Q1, Q3)] of local treatments. All patients were evaluated by modified response evaluation criteria in solid tumors criteria after treatment, including nine patients with complete response (CR), 21 with partial response, eight with stable disease, and four with progressive disease. Objective response rate and disease control rate were 71.4% (30/42) and 90.5% (38/42), respectively. Treatment-related adverse reactions occurred in 85.7% (36/42) of patients and grade Ⅲ or Ⅳ adverse reactions occurred in 16.7% (7/42). There was no level Ⅳ adverse reactions. All adverse reactions were controlled after dose reduction and symptomatic treatment. Thirteen patients (31.0%, 13/42) redeemed resectable after treatment and underwent radical surgery. Seven patients had pathological CR after surgery. In two patients, the pathological residual cancer tissue was less than 10%. The cumulative overall survival rates of the 42 patients at 6 months, 1 year, 1.5 years after treatment were 100%, 91.7%, and 65.0%, respectively. The postoperative 1-year survival rate of patients undergoing surgery after successful conversion was 83.3%. Conclusion:This study preliminarily showed the safety and efficacy of TACE, TKI, and PD-1 inhibitor combined therapy in patients with initially unresectable hepatocellular carcinoma.

Hot topics in perioperative immune combination therapy for liver cancer / 中华肝胆外科杂志

Most patients with primary hepatocellular carcinoma (HCC) are already in advanced stage when they are diagnosed, with a short survival period and an extremely poor prognosis. HCC seriously threatens the life and health of Chinese people. In recent years, breakthroughs have been made in systemic treatment of HCC, especially in immunotherapy represented by immune checkpoint inhibitors, which has broken the single therapy situation of molecular targeted drugs. And the strategy of immunotherapy combined with anti-angiogenic therapy has shown superiority and profoundly changed the treatment strategy of HCC. This article focuses on several hotspots of immune checkpoint inhibitors combined with anti-angiogenic targeted drugs in the perioperative scenario of HCC, and takes stock of the latest research progress of immunotherapy combined with anti-angiogenic drugs regimens in the perioperative application of HCC.

Advances and the status of radiotherapy in advanced esophageal cancer / 中华放射肿瘤学杂志

Radiotherapy plays an important role in the treatment of advanced esophageal cancer. Under the premise of effective systemic treatment, selecting patients who may benefit from local radiotherapy can effectively relieve symptoms and improve quality of life, and it is expected to prolong the survival time of patients. Moreover, immunotherapy plays an increasingly significant role in advanced esophageal cancer, and the efficacy of radiotherapy combined with immunotherapy is promising.

Research progress on tumor treating fields combined with radiation therapy in the treatment of glioblastoma / 中华放射肿瘤学杂志

For patients with newly diagnosed glioblastoma, tumor treating fields (TTF) combined with temozolomide after radiation therapy is currently one of the standard therapeutic regimens. Recently, TTF has been increasingly applied in combination with radiation therapy since it can delay tumor DNA repair and increase DNA replication stress. The efficacy of TTF has been proven in clinical studies. However, no consensus has been reached regarding the theoretical basis, radiation dose, actual clinical operation, patients' benefit and safety, which remain controversial. In this article, research progress on these topics was reviewed.