Evaluation Of Therapeutic Effects Research Articles

Establishment of AML Mouse Model by Transplantation of Hematopoietic Cells from MLL-AF9 Transgenic Mice

To establish a leukemia mouse model induced by transplantation of hematopoietic cells from mixed lineage leukemia (MLL)-AF9 transgenic mice so as to provide the basis for the mechanism research and drug screening of acute myeloid leukemia (AML). MLL-AF9 knock-in mice were bred and identified. When the mice developed leukemia, white blood cell (WBC) count in peripheral blood, flow cytometry and morphology method were analyzed to identify the disease. When the WBC count in peripheral blood was more than 100×109/L, bone marrow cells and spleen cells were collected and cryopresevated. After resuscitation, the cells were injected into 4.5 Gy irradiated wild C57BL/6J mice through the tail vein to develop MLL-AF9 leukemia mouse model. Finally, the therapeutic effect was evaluated by positive drug on the model. The natural onset times of leukemia on MLL-AF9 knock-in mice were 22-28 weeks. The spleens of the transgenic mice enlarged and the bone marrow showed the immature forms of myeloid leukemia cells. Both the bone marrow and spleen cells highly expressed myeloid markers, CD11b and Gr-1. At least 0.5×106 bone marrow cells and 2.5×106 spleen cells could induce leukemia in all recipient mice, and the median survival times of mice were 20 days and 36 days, respectively. Experimental treatment was carried out on the leukemia mouse model transplanted with MLL-AF9 spleen cells, and it was found that the traditional chemotherapy drug cytarabine could delay the onset of leukemia and prolong the survival time of the mouse model. The leukemia model of hematopoietic cell transplantation based on MLL-AF9 transgenic mice is successfully established, which can be used for the study of the pathogenesis and evaluation of therapeutic effect of AML.

Evaluation of therapeutic effect of Premna herbacea in diabetic rat and isoverbascoside against insulin resistance in L6 muscle cells through bioenergetics and stimulation of JNK and AKT/mTOR signaling cascade

BackgroundPremna herbacea Roxb., a perennial herb is well documented for its therapeutic uses among the traditional health care-givers of Assam, India. Scientific validation on the traditional use of the medicinal plant using modern technology may promote further research in health care. PurposeThis study evaluates the therapeutic potential of methanolic extract of P. herbacea (MEPH) against type 2 diabetes mellitus (T2DM) and its phytochemical(s) in ameliorating insulin resistance (IR), thereby endorsing the plant bioactives as effective anti-hyperglycemic agents. MethodsThe anti-diabetic potential of the plant extract was explored both in L6 muscle cells and high fructose high fat diet (HF-HFD) fed male Sprague Dawley (SD) rats. Bioactivity guided fractionation and isolation procedure yielded Verbascoside and Isoverbascoside (ISOVER) as bioactive and major phytochemicals in P. herbacea. The bioenergetics profile of bioactive ISOVER and its anti-hyperglycemic potential was validated in vitro by XFe24 analyzer, glucose uptake assay and intracellular ROS generation by flourometer, FACS and confocal microscopy. The potential of ISOVER was also checked by screening various protein markers via immunoblotting. ResultsMEPH enhanced glucose uptake in FFA-induced insulin resistant (IR) L6 muscle cells and decreased elevated blood glucose levels in HF-HFD fed rats. Isoverbascoside (ISOVER) was identified as most bioactive phytochemical for the first time from the plant in the Premna genus. ISOVER activated the protein kinase B/AMP-activated protein kinase signaling cascades and enhanced glucose uptake in IR-L6 muscle cells. ISOVER decreased the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) and increased that of mammalian target of rapamycin (mTOR), thereby attenuating IR. However, molecular docking revealed that ISOVER increases insulin sensitivity by targeting the JNK1 kinase as a competitive inhibitor rather than mTOR. These findings were further supported by the bioenergetics profile of ISOVER. ConclusionThis study for the first time depicts the functional properties of ISOVER, derived from Premna herbacea, in ameliorating IR. The phytochemical significantly altered IR with enhanced glucose uptake and inhibition of ROS through JNK-AKT/mTOR signaling which may pave the way for further research in T2DM therapeutics.

Histological, Immunohistochemical and Biochemical Evaluation of The Possible Therapeutic Effect of Pirfenidone on Bleomycin-Induced Pulmonary Fibrosis in Adult Male Albino Rats.

Histological, Immunohistochemical and Biochemical Evaluation of The Possible Therapeutic Effect of Pirfenidone on Bleomycin-Induced Pulmonary Fibrosis in Adult Male Albino Rats.

Analysis of the curative effect of a domestic ear orthosis system in the treatment of congenital auricle deformity

ObjectiveTo evaluate the therapeutic effect and determinants of jingle ear orthosis in the correction of infant ear malformation and to evaluate its clinical application value. MethodsIn this retrospective study, 156 patients with 233 ears who had used the beautiful ear orthosis system in Jiangxi Province in the last 3 years were included. The patients were grouped according to age at initial correction, sex, and type of deformity, and data on duration and age of orthotic use and complications were obtained. ResultsWe studied 156 paediatric cases with 233 ear deformities, 79 of which were single-ear deformities. In total, 77 cases had an ear shape deformity, and an implicit ear was the most common deformity. For a good therapeutic effect evaluation standard above 96.57%, the mean duration of follow-up was 1 month. The initial correction age was an important factor in the correction effect while gender had no obvious influence. The difference in the mean wearing time was not statistically significant (p = 0.233, p > 0.05). There was no statistically significant difference in the ratio of correcting effects between the 6 types of deformities that were excellent or good (p = 0.086, p > 0.05). ConclusionsDomestic auricle orthosis is an effective nonsurgical treatment for ear malformation. The correction effect is related to the initial correction age. The younger the child is, the better the treatment effect is, and the shorter the treatment time is. Complications are common in older infants. Therefore, prompt non-surgical correction performed can improve the effective rate of treatment.

Therapeutic effects evaluation of vitamin E alone and in combination with ranitidine in stress – induced gastric ulcers in rats

It is noteworthy to examine the morphologic and biochemical efficacies of vitamin E, and its combination with a histamine receptor type 2 blocker on stress gastric ulcers. Animals were divided into (6) groups; group 1 (normal control), group 2 (Cold – restraint stress; CRS), group 3 (ranitidine 20 mg/kg), group 4 (vitamin E 100 mg/kg), group 5 (ranitidine 10 mg/kg + vitamin E 50 mg/kg ), group 6 (ranitidine 5 mg/kg + vitamin E 50 mg/kg ). Rats received treatment orally for 7 consecutive days beginning 1 h after induction of the gastric injury . They were sacrificed for assessment of stomach damage using body weight loss, macroscopic changes, oxidative stress markers (MDA stomach content and SOD enzyme activity). Present findings showed that the combined treatment of vitamin E and ranitidine is dose-dependent, and significantly much more effective in management of stress-induced lesions than using vitamin E alone, which caused remarkable body weight decrease.

Evaluation of therapeutic effect of Psidium guajava root extract against the toxicity induced by Ricinus communis (castor oil) in rats

Evaluation of therapeutic effect of Psidium guajava root extract against the toxicity induced by Ricinus communis (castor oil) in rats

Animal Models for COVID-19: Hamsters, Mouse, Ferret, Mink, Tree Shrew, and Non-human Primates.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus causing acute respiratory tract infection in humans. The virus has the characteristics of rapid transmission, long incubation period and strong pathogenicity, and has spread all over the world. Therefore, it is of great significance to select appropriate animal models for antiviral drug development and therapeutic effect evaluation. Here, we review and compare the current animal models of SARS-CoV-2.

Recent Advances in Endosonography-Elastography: Literature Review.

Ultrasonographic elastography is a modality used to visualize the elastic properties of tissues. Technological advances in ultrasound equipment have supported the evaluation of elastography (EG) in endosonography (EUS). Currently, the usefulness of not only EUS-strain elastography (EUS-SE) but also EUS-shear wave elastography (EUS-SWE) has been reported. We reviewed the literature on the usefulness of EUS-EG for various diseases such as chronic pancreatitis, pancreatic solid lesion, autoimmune pancreatitis, lymph node, and gastrointestinal and subepithelial lesions. The importance of this new diagnostic parameter, “tissue elasticity” in clinical practice might be applied not only to the diagnosis of liver fibrosis but also to the elucidation of the pathogeneses of various gastrointestinal diseases, including pancreatic diseases, and to the evaluation of therapeutic effects. The most important feature of EUS-EG is that it is a non-invasive modality. This is an advantage not found in EUS-guided fine needle aspiration (EUS-FNA), which has made remarkable progress in the field of diagnostics in recent years. Further development of artificial intelligence (AI) is expected to improve the diagnostic performance of EUS-EG. Future research on EUS-EG is anticipated.

Cardiorenal Syndrome: Emerging Role of Medical Imaging for Clinical Diagnosis and Management.

Cardiorenal syndrome (CRS) concerns the interconnection between heart and kidneys in which the dysfunction of one organ leads to abnormalities of the other. The main clinical challenges associated with cardiorenal syndrome are the lack of tools for early diagnosis, prognosis, and evaluation of therapeutic effects. Ultrasound, computed tomography, nuclear medicine, and magnetic resonance imaging are increasingly used for clinical management of cardiovascular and renal diseases. In the last decade, rapid development of imaging techniques provides a number of promising biomarkers for functional evaluation and tissue characterization. This review summarizes the applicability as well as the future technological potential of each imaging modality in the assessment of CRS. Furthermore, opportunities for a comprehensive imaging approach for the evaluation of CRS are defined.

Relevance of diffusion-weighted imaging with background body signal suppression for staging, prognosis, morphology, treatment response, and apparent diffusion coefficient in plasma-cell neoplasms: A single-center, retrospective study.

Accurate staging and evaluation of therapeutic effects are important in managing plasma-cell neoplasms. Diffusion-weighted imaging with body signal suppression magnetic resonance imaging (DWIBS-MRI) allows for acquisition of whole-body volumetric data without radiation exposure. This study aimed to investigate the usefulness of DWIBS-MRI in plasma-cell neoplasms. We retrospectively analyzed 29 and 8 Japanese patients with multiple myeloma and monoclonal gammopathy of undetermined significance, respectively, who underwent DWIBS-MRI. We conducted a histogram analysis of apparent diffusion coefficient values. The correlations between each histogram parameter and staging, cell maturation, prognosis, and treatment response were evaluated. We found that the apparent diffusion coefficient values in patients with monoclonal gammopathy of undetermined significance were lower than those in patients with multiple myeloma. Pretreatment apparent diffusion coefficient values of immature myeloma were lower than those of mature myeloma. Moreover, these values decreased in proportion to stage progression in Durie-Salmon classification system but showed no significant correlation with other staging systems or prognosis. Patients were stratified as responder, stable, and non-responder based on the International Myeloma Working Group criteria. The magnitude of changes in apparent diffusion coefficients differed significantly between responders and non-responders (0.154 ± 0.386 ×10–3 mm2/s vs. -0.307 ± 0.424 ×10–3 mm2/s, p = 0.003). Although its usefulness has yet to be established, DWIBS-MRI combined with apparent diffusion coefficient measurement allowed for excellent response evaluation in patients with multiple myeloma. Furthermore, apparent diffusion coefficient analysis using DWIBS-MRI may be useful in predicting cell maturation and total tumor volume.

Bortezomib, Liposome Doxorubicin and Dexamethasone (PDd) Is Superior in Safety and Not Inferior in Efficiency to Bortezomib, Doxorubicin and Dexamethasone (PAd) As Induction Therapy in New-Diagnosed Multiple Myeloma Patients: An Interim Report from China's Multicenter Study

Purpose:Bortezomib, doxorubicin and dexamethasone (PAd) and bortezomib, liposome doxorubicin and dexamethasone (PDd) are widely used as induction chemotherapy regimens in china in the new-diagnosed multiple myeloma patients before autologous stem cell transplantation or other consolidation therapy. There was no data on the comparison in safety and efficiency between that two regimens, so we design this open-label, randomized, multicenter clinical trial in China's 16 sites. Here is our interim report.Method:Until April 15th 2017, 18 cases with PDd and 22 cases with PAd have finished the whole induction therapy. Incidence of adverse reaction, therapeutic effect evaluation is compared here.Results:There is no significant difference in age, gender, ISS stage, R-ISS stage, D-S stage between the two groups. There is also no differences in the incidence of the M-protein type between the two groups except for IgA type more often in PAd group than PDd group (7/22 vs 1/18, p=0.0537). As the 40 patients finished the 4-cycle induction therapy, effect evaluation by morphology, IFE and FLC shows no difference in sCR, CR, VGPR, PR, SD, PD, as well as in ORR. And minimal residual disease tested by flow-cytometry is also no difference between the two groups. The incidence of leukocytopenia (III-IV°) (1/18 vs 9/22, p=0.0126) and thrombocytopenia (III-IV°)(2/11 vs 11/22, p=0.0162) is lower in PDd group than in PAd group, and no difference is observed in other adverse reactions such as active infection, neutropenia, anemia, febrile neutropenia, hepatic and renal impairment, herpes, ect.Conclusion:There is no difference in the efficiency after 4-cycle induction chemotherapy between the PDd group and PAd group, and PDd regimen show advantages in less incidence in leukocytopenia and thrombocytopenia. DisclosuresNo relevant conflicts of interest to declare.

Dye-Sensitized Rare Earth-Doped Nanoparticles with Boosted NIR-IIb Emission for Dynamic Imaging of Vascular Network-Related Disorders.

Real-time dynamic vascular network imaging can provide accurate hemodynamic and anatomical information, facilitating the diagnosis of blood circulatory system-related diseases and achieving precise evaluation of therapeutic effects. In vivo luminescence imaging in the NIR-IIb biological window (1500-1700 nm) has developed into a next generation of optical imaging method with significantly improved temporal-spatial resolution and penetration depth. Unfortunately, an imaging contrast agent capable of emitting NIR-IIb luminescence with sufficient brightness in this region is lacking. Herein, we designed and proposed a type of dye-sensitized rare earth-doped nanoparticle (RENPs@Alk-pi) with obviously boosted NIR-IIb emission and high biocompatibility, which can be used to realize the real-time NIR-IIb luminescence imaging with high temporal-spatial resolution and contrast. The dye sensitization process provides a 40-fold enhanced brightness of the NIR-IIb emission at 1525 nm of Er3+. Consequently, the RENPs@Alk-pi was not only able to depict a vascular network but also applicable in noninvasively monitoring the dynamic vascular processes and changes in the vascular anatomy of two blood circulatory system-related disorders, including hindlimbs ischemia and atherosclerosis. Our research provides a powerful tool for evaluating vascular network-related dysfunction and physiological processes.

Quantitative Assessment of Age-dependent Changes in Porphyrins from Fluorescence Images of Ultraviolet Photography by Image Processing

BackgroundSkin is the first line of defense against harmful external environmental factors. Skin flora living on the skin surface impact skin health and skin disease. Bacteria, form part of the unique and complex skin micro-ecological system. For example, Propionibacterium acnes (P. acnes) is a member of the anaerobic organisms and is involved in the induction of skin acne. It produces porphyrins that absorb ultraviolet light and emit red fluorescence in response. As a result, fluorescence surveillance of the skin can be important in both the diagnosis of skin acne and the evaluation of therapeutic effects. Many different measurement methods for single skin biophysical properties have been reported.. This study focused on the age-dependent changes in porphyrins for normal skin, and developed a novel algorithm to evaluate porphyrins using the fluorescence images by image processing quantitatively. Materials and methodsAn extraction algorithm was proposed for the segmentation of porphyrin fluorescence images in OpenCV. The algorithm consisted primarily of preprocessing, conversion from RGB color space to HSV color space, and classification of fluorescence. There are 3595 healthy Japanese aged 16–85 years enrolled in the study and fluorescence images were acquired from their cheek sites under 375 nm UV-LED excitation. Age-related fluorescence variation was conducted applying the algorithm implemented. ResultsA new extraction algorithm has been proposed with fluorescence image input and three indexes output, including the number of fluorescence, area of fluorescence, and mean intensity of fluorescence. Proposed algorithm was verified by three parameters, the accuracy, sensitivity, and precision, which refer to the ability of algorithm to detect the number of fluorescence correctly and repeatedly. The verification results were 71%, 72%, and 88% respectively, taking a validly fundamental step for skin health record and analysis. Furthermore, large-scale fluorescence image segmentation results revealed that similar trends were coming out for all three indexes in cheek as people get older. All the fluorescence number, area and mean intensity arrived at the highest at 30 years old and fell off since then. ConclusionThe number, area, and fluorescence intensity of porphyrins can be extracted well from fluorescence images with the proposed algorithm in the study, which has the potential to aid in thediagnosis of skin acne and predict skin conditions as an assisted tool. It is implicated that fluorescence status is influenced by age, which rises to the peak around 30 years old for normal cheek's skin.

Objective Evaluation of Therapeutic Effects of ADHD Medication by Analyzing Movements Using a Smart Chair with Piezoelectric Material

Attention-deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in schoolchildren. Several methods are available to evaluate ADHD therapeutic effects, including the Swanson, Nolan, and Pelham (SNAP) questionnaire, the Vanderbilt ADHD Diagnostic Rating Scale, and the visual analog scale. However, these scales are subjective. In this study, a piezoelectric material was applied to a medical chair to objectively evaluate the therapeutic effect of ADHD medication before and after treatment. A total of 22 patients (18 boys and 4 girls) with ADHD were enrolled. During the appointment, the patients’ movements were recorded by the piezoelectric material before being analyzed. The variance, zero-crossing rate, and high energy rate of movements were used to analyze the signal in this study. The results showed the variance, zero-crossing rate, and high energy rate in patients with ADHD all decreased significantly after 1 month of methylphenidate use. Although the hyperactivity subscales of SNAP obtained from parents and teachers demonstrated significant decreases after 1 month of medication, the reduction rate of the three aforementioned measurements decreased more than hyperactivity subscales. This suggests that the use of a smart chair equipped with a piezoelectric material is an objective and useful method for evaluating the therapeutic effects of ADHD medication.

Evaluation of Therapeutic Effect of Mg doped ZnS Nano Particle and Bougainvillea glabra Flower Fraction on HepG2 Cell Lines

Diabetes mellitus is chronic disease which causes ill effects on human health. Over many years, a number of research works undergone to control diabetes mellitus among humans. Most of the researchers contributed various drugs for controlling diabetes mellitus. It is observed that drugs either causing side effects or efficiency is very less. Hence, the present study is formulated to find out efficient drug to control diabetes mellitus, which is free from side effects. Zinc has potential antioxidant activity. Hence it is selected as drug delivery agent as in the form of Mg doped ZnS nanoparticle. Herbal formulations always showed potential biological activities. and herbal delivery with nanoparticle showed enhanced antidiabetic activity. The Mg doped ZnS nanoparticle and Bougainvillea glabra flower fraction were evaluated for their cytotoxic nature against HepG2 cell lines. Glucose uptake activity and α-Glucosidase activity were also estimated. The results showed potential antidiabetic activity and antioxidant activity with negligible cytotoxicity, signifying that Mg doped ZnS nano particle and Bougainvillea glabra flower fraction as potential candidate for the treatment of diabetes.

Therapeutic Advances in Tendinopathy Quantified Microscopically Using Bonar Score, with a Special Reference to PRP Therapy—A Systematic Review of Experimental Studies

(1) Background: The Bonar scoring system serves in the microscopic evaluation of tendon pathology. However, it can be easily adapted to investigate decreasing degeneration after treatment and quantify the healing progress. We believe that there is an actual need for a connection between clinical observations and tissue alterations arising during the treatment process, to gain superior functional outcomes. Herein, we perform a systematic review of the Bonar score’s application in the histopathological assessment of therapeutic advances in tendinopathy, with special reference to PRP therapy. (2) Methods: A systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The searching strategy was conducted across major databases: PubMed, Cochrane Central, ScienceDirect, SciELO, and Web of Science. The risk-of-bias assessment was made using the Cochrane Collaboration’s Risk of Bias Tool and SYRCLE. (3) Results: The searching strategy produced 807 articles, and after selection, 22 studies were included. We collected 21 animal studies (n = 472) and 1 human study (n = 45). Three types of tendons were taken into account: 14 Achilles tendons, 7 supraspinatus tendons (SST), and in 1 case, Achilles and patellar tendons simultaneously. A variety of therapeutic methods were used—from intra-tendinous substance injections to surgical procedures or mechanical stimuli—but platelet-rich plasma (PRP) therapy dominated among them and was present in six studies. Most of the collected studies included an assessment of the tendons’ histopathology based on the classical Bonar score (with four variables and one observer). The staining protocol was based on the hematoxylin and eosin technique. An evaluation of therapeutic effects showed 15 positive results, 6 negative results, and 1 neutral result of treatments. (4) Conclusions: To understand the tendinopathy phenomenon, a link between histopathology and clinical observations in chronic tendon disorders is required due to the possibility of functional outcome improvements. The Bonar scoring system is well established in tendon pathology assessment and could also be adopted to assess therapeutic results in tendon disorders. Studies that included the PRP application showed Bonar-scoring-system-based evidence of superior tendinous tissue healing related to improved clinical results.

Intraductal carcinoma of the retromolar trigone found with elevated serum CEA and CA19-9 levels: a case report

Intraductal carcinoma (IDC) is a rare salivary gland tumor, classified according to the 4th WHO Classification of Head and Neck Tumors in 2017. The tumor affects the parotid gland much more frequently than the minor salivary glands. It’s often asymptomatic. We report a case of IDC of the left retromolar trigon occurring in an 81-year-old woman. She was diagnosed with high serum CEA and CA19-9 at a medical examination. Examinations of her gastrointestinal tract, lungs, and mammary glands were conducted, resulting in no abnormal findings. FDG-PET showed abnormal uptake only in the left retromolar trigon, and a painless mass was observed. A biopsy of this tumor indicated it was likely a low-grade salivary gland tumor. The tumor was completely removed, along with sufficient margins. Histological examination revealed that the lesion was composed of alveolar nests showing an expanded duct-like structure surrounded by an intact myoepithelial layer, with no evidence of infiltration. The final diagnosis was IDC. The postoperative course was uneventful and the patient’s serum CEA and CA19-9 levels decreased to within normal range. We believe that serum CEA and CA19-9 levels could be used for the diagnosis and evaluation of therapeutic effect for this tumor.

Progress in the clinical application and correlation between glucose transporter-1 and 18F-FDG PET/CT imaging for non-small cell lung cancer

Because of the unobvious early symptoms and low 5-year survival rate, the early diagnosis and treatment is of great significance for patients with non-small cell lung cancer. Glucose transporter-1 is the most widely distributed glucose transporters in various tissue cells in the human body, whose expression in non-small cell lung cancer is closely related to the histological types, lymph node metastasis, degree of differentiation, progression and prognosis. 18F-FDG PET/CT imaging, a molecular imaging diagnostic method, is based on the characteristics of glucose metabolism in malignant tumors, which has been widely applied in the cancer diagnosis, stage division, evaluation of therapeutic effects and prognosis evaluation. Glucose transporter-1 is regulated and influenced by many factors, and it is closely related to 18F-FDG PET/CT imaging. This article briefly reviews the progress in the clinical application and correlation between glucose transporter-1 and 18F-FDG PET/CT imaging for non-small cell lung cancer, in order to improve the diagnosis and treatment of lung cancer.

An experimental evaluation of therapeutic effect of Rosa damascena in hepatotoxicity induced by isoniazid

Objectives: Hepatotoxicity occurs as a side effect of first line anti-tubercular drug such as Isoniazid. The aim of the present study was to evaluate therapeutic potential of ethanolic extract of Rosa damascene flowers (RDEE) in isoniazid induced hepatotoxicity in rats. Methods: Rats were given orally isoniazid (50 mg/kg) for 28 days. Silymarin (50 mg/kg) was administered, as standard drug. From 29th to 43rd day of the study, isoniazid was stopped and therapeutic agents such as normal saline, silymarin, RDEE 1.5g/kg and 3g/kg were given orally in different animal groups respectively. On 44th day, blood samples were collected for biochemical analysis and liver tissue was subjected to histopathological examination. Results: The rats administered RDEE showed significant reduction in the liver marker enzymes and total bilirubin treated as compared to negative control group. There was also significant improvement in antioxidant levels and histopathological scores in RDEE treated group in comparison to the negative control group. Conclusion: This study demonstrates the beneficial effect of ethanolic extract of Rosa damascene flowers (RDEE) as a therapeutic agent in hepatotoxicity induced by isoniazid in a dose dependant manner. Keywords: Rosa damascene, Hepatoprotective, Isoniazid, Silymarin, Tuberculosis, Hepatotoxicity.

Cost-Effectiveness of Alirocumab for the Secondary Prevention of Cardiovascular Events after Myocardial Infarction in the Chinese Setting.

Background: Proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduce ischemic events; however, the cost-effectiveness remains uncertain. This study sought to evaluate its economic value in patients with myocardial infarction (MI) from the Chinese healthcare perspective. Methods: A state-transition Markov model was developed to determine the cost-effectiveness of alirocumab for preventing recurrent MI, ischemic stroke and death. Preventative effect of the therapy was gathered from ODYSSEY OUTCOMES trial and absolute reduction of low-density lipoprotein cholesterol (LDL-C) in ODYSSEY EAST trial, respectively. The primary outcome was the incremental cost-effectiveness ratio (ICER), defined as incremental cost per quality-adjusted life-year (QALY) gained. Results: Compared with statin monotherapy, the ICER of alirocumab therapy at its present discounted price [34,355 Chinese yuan (CNY) annually, 33% rebate] based on clinical follow-up efficacy was 1,613,997 CNY per QALY gained. A willingness-to-pay threshold of 212,676 CNY per QALY would be achieved when the annual cost of alirocumab was reduced by 88% from the full official price to 6071 CNY. The therapeutic effect evaluation estimated by the magnitude of LDL-C reduction was superior to the results of clinical follow-up, but this medication was still far from cost-effective. Multiple vulnerable subgroup analyses demonstrated that the ICER for patients with polyvascular disease in 3 vascular beds was 111,750 CNY per QALY gained. Conclusion: Alirocumab is not cost-effective in general MI population based on current discounted price. High long-term costs of alirocumab may be offset by health benefit in patients with polyvascular disease (3 beds).