Schizophrenia is a severe and chronic psychiatric disorder with a lifetime prevalence of approximately 0.7％-1％worldwide[1].Ari-piprazole is widely used for schizophrenia treatment,and known as a dopamine system stabilizer due to its partial agonist activity as the dopamine-2(D2)and serotonin 5-hydroxytryptamine 1A(5-HT1A)receptors,as well as antagonist action at the 5-HT2A receptors[2].
Objective:To evaluate the cost-effectiveness of dupilumab plus background therapy compared with omalizumab plus background therapy in the treatment of severe asthma from the perspective of Chinese health system.Methods:A Markov model was established.The clinical efficacy,health benefit and cost data were obtained from the randomized controlled trials,published literatures and clinical expert consultation results.Lifetime disease outcomes,effectiveness,and costs under each intervention were calculated.With incremental cost-effectiveness ratio(ICER)as the index,the economy of each intervention was evaluated under the threshold of 2 times GDP per capita(178 716 yuan in 2023).Scenario analysis,one way sensitivity analysis and probability sensitivity analysis were carried out to verify the robustness of the results.Results:The total costs were 679 459 and 615 213 CNY in the groups of dupilumab and omalizumab,respectively.Total quality-adjusted life year(QALY)were 13.11 and 12.68.Compared with omalizumab,dupilumab increased costs by 64 246 CNY and QALY by 0.43.ICER was 149661 CNY per QALY,which was lower than the 2 times per-capita GDP threshold,indicating that dupilumab was cost-effective compared with omalizumab.In the two scenarios set in the study,the group of dupilumab was more economical than the group of omalizumab.In the three scenarios set in the study,the group of dupilumab was more economical.If the negotiated price of dupilumab in the 2024 edition of the National Medical Insurance Drug List is used,the group of dupilumab is obviously superior.Sensitivity analysis verified the robustness of the above results.Conclusion:Under the threshold of 2-time Chinese GDP per capita,dupilumab is more cost-effective than omalizumab in the treatment of severe asthma patients.
Rheumatoid arthritis is a common immune disease with early symptoms of joint swelling, morning stiffness, pain, and swelling. It could develop into a joint deformity as the disease progresses, resulting in the loss of normal joint function and seriously affecting the patient’s quality of life. Methotrexate is the “anchor drug” for rheumatoid arthritis treatment, which has an immunosuppressive effect and could effectively prevent the abnormal activation of B cells in vivo, inhibit the abnormal generation of cytokines, and relieve related symptoms. However, in some cases, methotrexate alone is not ideal and often needs to be combined with other drugs like xianlinggubao capsules. This study has provided an experimental basis for the combined efficacy of methotrexate and xianlinggubao capsules for female patients with moderate to severe rheumatoid arthritis and their impact on ovarian function.
Lung cancer is one of the most common cancers worldwide.As reported in 2020,there were approximately 2.2 million new cases of lung cancer worldwide,accounting for 11.4%of newly diagnosed malignant tumors.Additionally,there were 1.8 million deaths resulting from lung cancer in 2020,representing about 18%of all cancer-related deaths globally.Lung cancer remains the leading cause of cancer-associated morbidity and mortality in China.Despite the increasing popularity of immunotherapy and targeted therapy,chemotherapy remains one of the most dominant treatment modalities for lung cancer(particularly for small-cell lung cancer).However,chemotherapeutic drugs in clinical practice lack specificity and kill normal cells while killing tumor cells,especially cells that are relatively active in proliferation or metabolism.Chemotherapy-induced myelosuppression(CIM)is the most common dose-limiting and potentially fatal complication in cancer therapy and a key factor affecting the course and dose of chemotherapy,and nearly 90%of chemotherapeutic drugs may be associated with myelosuppression.Myelosuppression is the biggest obstacle to cancer chemotherapy.Myelosuppression seriously affects the life quality of cancer patients,reduces patient compliance,delays treatment,and even threatens the lives of patients,which we should pay attention to in clinical practice.At present,the main treatment regimens for bone marrow suppression are those follows,such as drugs promoting neutrophils,red blood cells,thrombopoietic drugs and blood transfusion.As the world's first approved CDK4/6 inhibitor with full myeloprotection,the use of trilaciclib before chemotherapy is effective in reducing the incidences of CIM.This review aims to summarize the relevant research progress in recent years from the mechanism of bone marrow suppression,related treatment measures of bone marrow suppression after chemotherapy for lung cancer,and provides further ideas and clinical basis for clinical application,monitoring and management of CIM.
The investigation shows that malignant tumor is one of the major diseases threatening human health and life safety.In recent years,the cancer prevalence and mortality rate remain high,making anti-tumor drug research a hot field of drug research and development.For a better understanding of the industry development situation and to grasp the latest development of antitumor drug patent applications,Derwent Innovations Index was used for mining and analysis on the patent document against cancer drugs.At the same time,we complemented public patent data in recent years,as well as the overall intelligence information updates,statistics,analysis,and visualization,in order to provide information reference and decision support for the research and development of anti-tumor drugs and medicine.
Objective:To study the cytotoxicity effect of NK cells on breast cancer cells in vitro,and the cytotoxicity and possible mechanism of NK cells combined with low concentration lapatinib on breast cancer cells.Methods:CCK-8 method was used to detect the effect of different concentrations of lapatinib on the proliferation of breast cancer cells for 24 h,48 h and 72 h.LDH Assay Kit was applied to detect cytotoxicity of NK cells and NK cells combined with lapatinib on tumor cells.Changes of HER-2 expression on the surface of MDA-MB-231 and BT549 breast cancer cells before and after treatment with lapatinib and the ligand expression of NK cell activated and inhibitory receptors on breast cancer cell surface were both evaluated by flow cytometry.Results:The inhibitory effect of lapatinib on the proliferative activity of breast cancer cells was proportional to the time and concentration of action.The inhibitory rate on the proliferation of HER-2 high-expression breast cancer cells was greater than that of HER-2 low-expression breast cancer cells.NK cells had certain cytotoxicity against breast cancer cells,and lapatinib(The final concentration of lapatinib was 0.1 μmol·L-1 in HER-2 high-expression breast cancer cells MDA-MB-453 and BT474 and 3.125 μmol·L-1 in HER-2 low-expression breast cancer cells MDA-MB-231 and BT549)combined with NK cells could significantly improve the killing efficiency of NK cells against breast cancer cells.Lapatinib(3.125 μmol·L-1)could increase the expression level of HER-2 on the surface of HER-2 low-expression breast cancer cells after interacting with HER-2 low-expression breast cancer cells.Conclusion:Lapatinib improves the killing activity of NK cells against breast cancer cells in vitro,and its synergistic mechanism may be related to the increased expression of HER-2 on the surface of breast cancer cells by lapatinib.
Tumor therapy has always been the focus of study.Due to the variability of tumor cells,the complexity of the tumor microenvironment and other factors,the problems such as multidrug resistance of tumors,reduced drug delivery efficiency are obtained.In recent years,increasing attention has been paid to biomimetic vectors,in which cancer cell membrane(CCM)is a new type of nano-carrier with the characteristics of homologous targeting,immune escape and penetrating biological barrier.Using CCM as a bionic carrier to coat different types of nanoparticles(NPs)can achieve effective tumor targeting and advantages in tumor therapy.This review introduces the biomimetic vector of CCM,briefly describes the preparation process of NPs coated with CCM,summarizes the research of CCM in tumor drug delivery and tumor vaccine,and discusses the future development prospects of CCM.
Objective:To excavate and analyze signals of immune checkpoint inhibitors(ICIS)related adverse events of acute kidney injury through data mining methods based on the big data of FAERS,and to provide a reference for the safe clinical use of ICIS drugs.Methods:Case reports were collected from April 2011 to March 2021 with immune checkpoint inhibitors(ICIS)as the first suspected drug and acute kidney injury(AKI)as the preferred term.Reporting odds ratio(ROR),proportional reporting ratio(PRR),Bayesian confidence propagation neural network(BCPNN)and multi-item gamma Poisson shrinker(MGPS)were used to study the relationship between ICIS and acute kidney injury.The incidence time,mortality and hospitalization rate of acute kidney injury were further studied.Results:1 528 cases of acute kidney injury were included.The proportion of people aged over 65 was the highest,reaching 65.38%.Males were about twice as large as females(64.66%vs 31.87%).Patients with chest cancer reported the most acute kidney injury(32.98%),followed by skin cancer(26.11%)and urogenital cancer(18.72%).Acute kidney injury was most reported in nivolumab monotherapy(54.78%).Cimepritimab had the strongest signal in immune checkpoint inhibitor monotherapy,which may be related to the patient population.The median onset time of acute kidney injury was 49 days in immune checkpoint inhibitor monotherapy regimens(interquartile range[IQR]1～1 720).Conclusions:The mechanism of action of immune checkpoint inhibitors differs from traditional cytotoxic and targeted drugs.The proper balance between activation and inhibition of immune molecule function is the key to a strong immune response,and sufficient attention should be given to its efficacy and safety.
Small-cell lung cancer(SCLC)is one of the most malignant subtypes of lung cancer with rapid tumor progression and a poor prognosis,and also one of the malignancies most difficult to cure in clinical practice.Currently,platinum-based chemotherapy remains the first-line standard treatment for extensive-stage small cell lung cancer(ES-SCLC).Full-dose chemotherapy is warranted for the best efficacy,and the effective rate of first-line treatment is 60%～80%(full-dose),while chemotherapy-induced myelosuppression(CIM)is the main reason hindering adequate chemotherapy.Granulocyte colony-stimulating factor(G-CSF)is commonly used to deal with neutropenia in clinical practice,while this traditional treatment may even cause the depletion of bone marrow hematopoietic reserve function and damage to the normal bone marrow hematopoietic function of patients.Currently,trilaciclib has been approved for the prevention of myelosuppression in ES-SCLC,which can protect hematopoietic stem cells/progenitor cells(HSPCs)fundamentally.In this paper,we report a case of a patient with ES-SCLC treated in our department receiving bone marrow protection with trilaciclib combined with chemotherapy,aiming to provide reference and basis for further research.
Chemotherapy-induced myelosupression(CIM)is the most common toxicity of chemotherapy drugs.Usually,more than 80%of chemotherapy drugs lead to myelosuppression,and CIM is usually characterized by neutropenia,thrombocytopenia and erythrocytopenia.Dose reduction and delayed administration of chemotherapy drugs by CIM seriously reduce the life quality of patients and the overall anti-tumor effect of chemotherapy.As the first drug approved for bone marrow protection,trilaciclib is a highly effective,selective and reversible cyclin-dependent kinase(CDK)4/6 inhibitor,which can temporarily block cell cycle of hematopoietic stem/progenitor cells and immune cells in G1 phase,so as to reduce the damage caused by chemotherapy and protect bone marrow protection.In April 2021,trilaciclib was approved by FDA as a myelo preservation in the United States.In July 2022,trilaciclib was approved by the National Medical Products Administration for marketing in China,and the first indication of trilaciclib in China was for patients with extensive stage small-cell lung cancer.In this review,the mechanisms of action,pharmacokinetics,drug interaction mechanism,clinical evaluation,safety and other related research progress of trilaciclib are systematically reviewed,aiming to provide further reference and basis for clinical practice.
Non-alcoholic fatty liver disease(NAFLD)is a common chronic metabolic disease characterized by the accumulation of fat in the liver.The onset and progression of NAFLD are associated with a variety of metabolic abnormalities,including obesity,diabetes mellitus,and hyperlipidemia.Due to its high prevalence and risk worldwide,NAFLD has become an important issue in public health.However,to date,treatments for NAFLD are very limited,with no relevant drugs approved for marketing in Europe,America,or China and clinical trials of new drugs have gained no progress in recent years.This paper reviews the therapeutic targets,clinical research progress of new drugs,and new treatment strategies for NAFLD,in addition to summarizing the reasons for the high failure rate of NASH clinical trials and proposing corresponding solutions,aiming at providing ideas and reference for new drug development.
To analyze the pattern,characteristics and causes of protocol violation in anti-tumor drug clinical trials from the perspective of ethical review.The number and categories of violation projects were retrospectively analyzed and compared in different departments and the area of clinical trials(domestic or international).The impact of protocol violation on clinical trials carried out in our hospital from 2018 to 2021 was also analyzed.From 2018 to 2021,1256 protocol violation cases occurred in clinical trials of anti-tumor drugs carried out in our hospital.The number of continuous protocol violations(318,25.32%)was the largest,and the number of researchers'failure to cooperate with supervision/audit(6,0.50%)was the fewest.The difference in the number of protocol violation between internal and surgical,domestic and global clinical trials were both statistically significant(P<0.01).The proportion of protocol violations affecting the safety,rights of subjects and trials results were 5.81%,4.78%and 5.41%,respectively.Various protocol violations may occur during clinical trials of anti-tumor drugs.In order to improve the quality of clinical trials,it can be effectively avoided by strengthening quality control and conducting targeted training for the research team and subjects.
Molecular targeted therapy has become a research hotspot in the field of cancer therapy in recent years.Regorafenib belongs to the multi-target tyrosine kinase inhibitor class of antitumor drug developed by Bayer company,which was approved by NMPA in March 2017.This article introduces the status of regorafenib-related Chinese patent applications and focuses on combing and analyzing the development context of patent technology,in order to provide reference for the drug R&D and patent portfolio for relevant domestic pharmaceutical companies.
Immunotherapy combined with chemotherapy has been established as the standard first-line treatment in advanced esophageal cancer(EC).Myelosuppression is the most common side effects of chemotherapy,and severe myelosuppression often leads to prolonged cycles of chemotherapy and reduced doses of chemotherapy,thereby reducing the intensity and potential anti-tumor efficacy of chemotherapy.At present,granulocyte-stimulating factor(G-CSF)is widely used to stimulate the differentiation of bone marrow hematopoietic progenitor cells to treat chemotherapy-induced myelosuppression(CIM).Trilaciclib is a short-acting and reversible CDK4/6 inhibitor,which can provide systemic protection of bone marrow hematopoiesis,and was approved by NMPA in July 2022 for the prophylactic treatment of myelosuppression in extensive-stage small cell lung cancer(ES-SCLC).However,trilaciclib has not been widely used in clinical practice.Therefore,this paper reports a case of one patient with advanced EC who was treated by trilaciclib to prevent CIM in our department,aiming to provide further reference and basis for further investigation.
Control of cell cycle progression plays a significant role in tumor development.The cyclin-dependent kinase(CDK)family governs cell cycle progression,and the activations of CDK4 and CDK6 allow cells to transit from G1 phase to S phase to start mitosis.Overactivation of CDK4/6 is closely related to tumor progression,thus CDK4/6 can be used as a potential target of oncotherapy.CDK4/6 inhibitors can not only arrest the tumor cells at G1 phase to prevent tumor overgrowth,but also affect the tumor microenvironment and enhance immune activity.Trilaciclib is a small-molecule CDK4/6 inhibitor,which is highly efficient,selective and reversible.Trilaciclib administrated before chemotherapy can temporarily block the hematopoietic stem cells and progenitor cells in bone marrow at G1 phase to reduce the cytotoxic damage caused by chemotherapy,thus protecting bone marrow and the immune system.Trilaciclib was first approved by FDA in the United States in February 2021 for extensive stage small cell lung cancer(ES-SCLC)before platinum/etoposide or topotecan chemotherapy to reduce the incidences of myelosuppression in adult patients.In July 2022,National Medical Products Administration(NMPA)also approved the administration of trilaciclib in patients with ES-SCLC who had not previously received systemic chemotherapy.In addition,the positive effects of trilaciclib on overall survival(OS)were observed in patients with triple-negative breast cancer(TNBC)treated with chemotherapy.Other clinical studies related to trilaciclib were still ongoing.This review summarizes the anti-tumor mechanisms of trilaciclib and the relative preclinical and clinical studies,aiming to provide further reference for clinical application and future research.
Chemotherapy still plays pivotal roles in the comprehensive treatment of tumors.Chemotherapy-induced myelosuppression(CIM)is the most common adverse event of chemotherapy,which has posed serious impacts on the anti-tumor efficacy of chemotherapy and the quality of patients'lives,and also resulted in increased treatment burden of patients and more medical resources at the same time.Trilaciclib is a highly potent,selective,reversible cyclin-dependent kinase 4/6(CDK4/6)inhibitor.Clinical data showed that trilaciclib could temporarily arrest bone marrow cells in G1 phase to reduce the incidences of CIM and the proportion of chemotherapy dose adjustment and delay,increasing the tolerance of chemotherapy and reducing the economic burden.This article systematically elaborates on the CIM-caused hazards,clinical prevention,and current status of treatment of CIM,as well as the roles of trilaciclib in the prevention of CIM and its economic value,aiming to provide scientific reference for patients to select reasonable prevention and therapeutic treatment regimens of CIM.
Objective:To investigate the in vivo and in vitro antibacterial activity of doxycycline combined with levofloxacin on carbapenem-resistant Klebsiella pneumoniae(CRKP).Methods:Eight clinically isolated CRKP strains were collected in Yichun People's Hospital,and the minimum inhibitory concentration(MIC)of 8 CRKPs was determined using microbroth dilution method in vitro.The antibacterial effect of the two drugs was judged by checkerboard dilution method.The time-sterilization curve was further applied to evaluate the combined bactericidal effect of the two drugs.Crystal violet staining semi-quantitative biofilm method was used to determine the inhibitory effect and elimination effect of the combination of two drugs on biofilm formation.In vivo,a model of acute lung infection of mice was established by nasal instillation of CRKP bacteria,and the mental state of mice was recorded.The bacterial load of lung tissues,the levels of serum inflammatory factor C-reactive protein(CRP),IL-6 and pathological morphological changes were evaluated and analyzed.Results:The MIC of doxycycline to 8 CRKP strains was 4～256 ug·mL-1,levofloxacin to 8 strains of CRKP MIC of 16～256 ug·mL-1.The checkerboard method showed that doxycycline combined with levofloxacin had an 80%synergistic or additive effect on 8 CRKP strains.The time-sterilization curve showed that after the treatment of doxycycline combined with levofloxacin on CRKP2 and CRKP7 for 24 hours,the number of bacteria decreased by≥2 lg CFU·mL-1 compared with the initial bacterial number,showing bacteriostatic or bactericidal effects.The results of crystal violet staining showed that the combination of doxycycline and levofloxacin had inhibitory and destructive effects on CRKP biofilms.Animal experiments showed that compared with the model group,the combined group mice had a good mental state,and the loading levels of lung tissue,C-reactive protein(CRP)and IL-6 significantly reduced(P<0.001).The results of HE staining showed that the alveolar structure was clear,the inflammatory cells reduced,and the hyperemia area reduced in the drug administration group compared with the model group,and the differences were statistically significant(P<0.001).Conclusion:In vitro experiments show that doxycycline combined with levofloxacin has a synergistic antibacterial or bactericidal effect on CRKP,and in vivo experiments show that doxycycline combined with levofloxacin can reduce inflammatory indexes,effectively treat bacterial infections in lung tissue,exerting good antibacterial effect in vivo.
Small cell lung cancer(SCLC)is characterized by a high degree of malignancy,with poor prognosis and high-growth fraction.About two-thirds of patients have developed distant metastasis at the time of diagnosis with rapid disease progression and high recurrence rates.Currently,topotecan-based chemotherapy remains the standard second-line treatment of SCLC with unfavorable disease remission,and less than one-fourth of patients have benefited from its efficacy.Chemotherapy-induced myelosuppression(CIM)is the most common toxicity in cancer chemotherapy,and severe CIM will reduce the dose intensity and anti-tumor efficacy of chemotherapy.Trilaciclib is a short-acting intravenous cyclin-dependent kinase 4/6(CDK4/6)inhibitor administered prior to chemotherapy to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy,which has been approved by NMPA for prevention of CIM in SCLC in July 2022.Previous results showed that trilaciclib yielded favorable bone marrow protection during chemotherapy,but its anti-tumor effects in second-line treatment of SCLC have not been determined.This paper reports a case of a patient with advanced small-cell lung cancer with multiple metastases who obtained progression-free survival time of more than 1 year using trilaciclib combined with topotecan as second-line treatment.
目的:探究系统性红斑狼疮(SLE)患者他克莫司血药谷浓度(C0)与疗效相关性,获得他克莫司在该人群治疗的有效浓度阈值,为临床用药的安全性和有效性提供参考.方法:回顾性收集我院2016年1月—2021年12月间应用他克莫司治疗的SLE患者的临床及实验室检查数据,包括人口统计学信息(性别、年龄、身高、体重)、病程、实验室检查结果、用药情况、血药浓度监测数据及临床反应,并进行疗效和安全性评价.分析C0与疗效相关性,受试者工作特征曲线(ROC)确定他克莫司有效浓度阈值.结果:本研究共纳入符合标准患者72例,收集176例次C0监测数据(0.1～10.3 ng·mL-1).他克莫司日剂量与C0间存在弱相关性(r=0.326);随着他克莫司用药时间的延长C0无显著性变化;补体C3在不同血药浓度组间存在差异(P<0.05),其他生化指标并未显现出显著差异.有效浓度研究分析了长期用药(他克莫司用药时间>3个月)的59例患者的124例次血药浓度监测结果,根据临床表现和生化指标分为有效组(76例次)和无效组(48例次).二元logistics回归分析结果表明,C0对患者疗效有显著性影响(P<0.001).ROC曲线下面积AUC为0.763(P<0.001,95％CI:0.674～0.851).此时对应的截点为1.55 ng·mL-1,提示当C0>1.55 ng·mL-1时,临床疗效阳性概率较高.结论:本研究表明药物剂量可影响SLE患者的他克莫司血药浓度;他克莫司血药浓度与疗效存在相关性,ROC曲线分析初步确定其有效浓度的阈值为1.55 ng·mL-1.
目的:对使用肿瘤坏死因子抑制剂的乙肝感染相关的类风湿关节炎患者进行乙肝再激活风险的Meta分析.方法:对目标数据库进行检索,对符合要求的文献进行收集整理,确定纳入文献后提取相关的数据进行数据分析.结果:本研究共纳入14 篇相关研究,涉及534 例乙肝相关的类风湿关节炎患者,其整体综合乙肝再激活率为0.0175(95%CI:0.0054,0.0340),I2 =67%,P<0.01.在亚组分析中,使用糖皮质激素得到的乙肝再激活率为0.0676(95%CI:0.0396,0.1012),I2 =89%,P<0.01.未使用糖皮质激素得到的乙肝再激活率为0.045 7(95%CI:0.016 4,0.084 6),I2 =69%,P<0.01.结论:乙肝感染相关的类风湿关节炎患者在使用肿瘤坏死因子抑制剂后具有一定的乙肝再激活率.在亚组分析中,目标人群的乙肝再激活率呈现出较为明显的地区分布,且使用糖皮质激素的亚组乙肝再激活率高于未使用糖皮质激素亚组.
