Medicine and Health Sciences Commons^™

Novel Small Molecule Antifungals For Invasive Fungal Infections, Emily Dennis

Theses and Dissertations--Pharmacy

Human fungal pathogens cause a range of diseases from benign skin conditions (i.e., ringworm) to thrush, mucosal membrane infections, and life-threatening systemic infections including bloodstream infections (i.e., aspergillosis and candidiasis) and Cryptococcal meningitis. These systemic infections occur most often in immunocompromised individuals and have high mortality rates. Current antifungal agents used in the clinic belong to three main classes: the polyenes (e.g., amphotericin B (AmB)), the echinocandins (e.g., caspofungin (CFG)), and the azoles (e.g., fluconazole (FLC)). In addition, the antimetabolite pyrimidine analogue flucytosine is used in combination with AmB. The …

Characterization And Engineering Of Interrupted Adenylation Domains, Taylor A. Lundy

Theses and Dissertations--Pharmacy

Nature has historically served as a prolific source of biologically active molecules produced by plants, fungi, and bacteria termed natural products (NPs). These NPs often serve as therapeutic leads due to their structural diversity and unique mechanisms of action. However, many need modifications to make them more effective or safer for human use. This can be a daunting and complicated task to do via traditional organic chemistry because of their complexity, copious stereocenters, and a multitude of reactive functional groups. For this reason, enzymatic modification of these NP during their biosynthesis is an appealing option. One major class of NPs …

Opioid Use In Vulnerable Populations, Gyeon Oh

Theses and Dissertations--Epidemiology and Biostatistics

Opioid-related negative health outcomes, such as substance use disorder, misuse, and overdose deaths, have risen as long-term opioid use has increased. The benefit of using long-term opioids for pain is yet to be established. The Centers for Disease Control and Prevention provides guidelines for opioid prescribing in chronic pain, but detailed recommendations on opioid prescribing for vulnerable populations are missing due to lack of evidence-based studies. The purpose of this dissertation is to describe patterns and predictors of opioid use and assess outcomes related to prescribing opioid medications in vulnerable populations, specifically older adults with various levels of cognitive function, …

Nsu Sharks Rx_Winter 2020, Nova Southeastern University

NSU Sharks Rx

Newsletter

Gynecologic Large Cell Neuroendocrine Carcinoma: A Review, Grant Burkeen, Aman Chauhan, Rohitashva Agrawal, Riva Raiker, Jill M. Kolesar, Lowell B. Anthony, B. Mark Evers, Susanne Arnold

Internal Medicine Faculty Publications

Large cell neuroendocrine carcinomas (LCNEC) are rare, aggressive high-grade neuroendocrine neoplasms within the neuroendocrine cell lineage spectrum. This manuscript provides a detailed review of published literature on LCNEC of gynecological origin. We performed a PubMed search for material available on gynecologic LCNEC. We analyzed 104 unique cases of gynecologic LCNECs, of which 45 were cervical primary, 45 were ovarian, 13 were uterine, and 1 was vaginal. A total of 45 cases of cervical LCNEC were identified with a median age of 36 years. Median overall survival was 16 months. We identified 45 ovarian LCNEC cases in the published literature with …

340b Program Utilization In Rural Us Clinics, William Finley, Heather M. Kruel

Theses, Dissertations and Capstones

Introduction: The 340B program was an effective strategy in reaching more potential patients, providing more comprehensive services, and limiting the gap between affordability and healthcare. The uninsured and underprivileged often are unable to receive medications at the high market price due to the financial situation they face and inflation. The 340B program seeked to mend this issue to help the public and healthcare organizations. The main purpose of this research was to search and evaluate if the 340B program lived up to its purpose of decreasing the cost of medications in rural based clinics.

Methodology: The research strategy developed …

Producing Urban Aerobiological Risk Map For Cupressaceae Family In The Sw Iberian Peninsula From Lidar Technology, Raúl Pecero‐Casimiro, Santiago Fernández‐Rodríguez, Rafael Tormo‐Molina, Inmaculada Silva‐Palacios, Ángela Gonzalo‐Garijo, Alejandro Monroy‐Colín, Juan Francisco Coloma, José María Maya‐Manzano

Articles

Given the rise in the global population and the consequently high levels of pollution, urban green areas, such as those that include plants in the Cupressaceae family, are suitable to reduce the pollution levels, improving the air quality. However, some species with ornamental value are also very allergenic species whose planting should be regulated and their pollen production reduced by suitable pruning. The Aerobiological Index to create Risk maps for
Ornamental Trees (AIROT), in its previous version, already included parameters that other indexes did not consider, such as the width of the streets, the height of buildings and the geographical …

Biopharmaceutical Revolution In Saudi Arabia: Progress And Development, Rihana Alzahran, Elaine Harris

Articles

Purpose This paper aimed to analyze the situation of the biopharmaceutical industry in Saudi Arabia to improve the situation in a way that achieves high levels of development similar to those in Europe, the United States of America (USA), and Japan. Methods To achieve the objective of the study, the authors surveyed 18 out of 21 Saudi pharmaceutical companies that have received licensing for manufacturing from the Saudi Food and Drug Authority (SFDA) to diagnose the situation of manufacturing in relation to biopharmaceuticals. An interview with SFDA officials was carried out as a supplement to the survey. Results Findings revealed …

Dietary Xanthones, Dina M. El-Kersh, Mohamed A. Farag, Hesham R. Elseedi, Omar M. Khattab

Pharmacy

Xanthones, polyphenolic compounds, are one of the most important classes in natural products, as they exhibit variety of pharmacological and health benefits, i.e., anti-obesity, antidiabetic, antioxidant, anti-Alzheimer, anti-inflammatory, and anticancer. Xanthones can be found in higher plants that are used as food sources.

Sickle Cell Disease, Vibhu Bhargava, Dr. Sandeep Barve

Digital Journal of Clinical Medicine

No abstract provided.

A Case Of Mixed Anxiety Depression In The Covid-19 Lockdown, Dr Hrishikesh Solunke, Dr Kishor M

Digital Journal of Clinical Medicine

No abstract provided.

Tuberculoma Presenting As Paradoxical Iris In A Hiv Positive Patient, Dr. Supritha Chintamaneni, Dr.Rajendra Prasad S, Dr.Bhanukumar M, Dr.Adarsh L S

Digital Journal of Clinical Medicine

No abstract provided.

Naming Convention, Interchangeability, And Patient Interest In Biosimilars, Mariana P. Socal, Jace B. Garrett, William B. Tayler, Ge Bai, Gerard F. Anderson

Faculty Publications

Although biosimilars may offer cost savings over their comparable biologics, use of biosimilars in the United States remains relatively low. This study investigates two barriers to uptake of biosimilars in the United States. First, the U.S. Food and Drug Administration requires that four-letter suffixes be added to the nonproprietary names of all biosimilars, as well as to the nonproprietary names of all biologics approved after March 2020. Second, biosimilars are not interchangeable with their reference biologic product at the pharmacy counter; a new prescription is needed for the biosimilar to be dispensed in place of the biologic. We conducted two …

Evaluating The Impact Of Verigene® Organism Identification On Antimicrobial Stewardship Recommendations, Rebecca Gerske

Undergraduate Honors Thesis Collection

Verigene® is one of many commercially available rapid diagnostic tests (RDT) for organism identification in blood culture. Community Health Network (CHNw) utilizes this system to identify blood cultures and guide antimicrobial therapy. As antibiotic resistance becomes more and more prevalent, limiting exposure to broad-spectrum antibiotic therapy is of paramount importance. RDT provides more timely information to providers, which if utilized appropriately, can result in the patient receiving appropriate antibiotic therapy in a shorter time and further limits unnecessary antibiotic exposure. This study was a three-part, retrospective chart review to determine the microbiological accuracy of Verigene® within CHNw and evaluate the …

Development Of Gamma-Aminobutyric Acid Nanoemulsions For Dermal Delivery, Kamonwan Singpanna

Chulalongkorn University Theses and Dissertations (Chula ETD)

The aims of this work were to study the effect of the penetration enhancer on physical properties of GABA-loaded nanoemulsions, to evaluate their physical and chemical stabilities and to compare in vitro skin permeability between GABA loaded-nanoemulsions with and without the penetration enhancer. In this study, 1,8-cineole was used as a penetration enhancer. The nanoemulsions were prepared by using the Microfluidizer. The oil phase consists of 10% w/w soybean oil and 5% w/w surfactant(s). Type of nanoemulsions was confirmed by dilution test. The average droplet size and size distribution (PDI) were measured by dynamic light scattering Zetasizer Nano ZS™. The …

Development Of Reimbursement Policy For Knee Osteoarthritis Treatment In Thailand, Parnnaphat Luksameesate

Chulalongkorn University Theses and Dissertations (Chula ETD)

Purpose : Osteoarthritis (OA) is the most common type of joint disease. The treatments are included oral non-steroidal anti-inflammatory drugs (NSAIDs), Symptomatic Slow-Acting Drugs for Osteoarthritis (SYSADOA), intra-articular steroid injection, and surgery. Each of treatments was a difference in benefit and risk. In addition to variation of reimbursement policy among three health insurance schemes in Thailand. The objective of this study was 1.) to conduct an economic evaluation of knee OA treatments in Thailand 2.) to investigate Thai patients’ preferences and their willingness-to-pay (WTPs) for knee OA treatments. Methods : A cost-utility analysis was conducted to compare among treatment options …

Variability In Antibacterial Activity In The Caribbean Sponge Amphimedon Compressa, Mackenzie Reilly

Honors Theses

Coral reefs are essential ecosystems that provide an abundance of natural resources. Sponges, common reef inhabitants, produce a diversity of secondary metabolites that are known to serve as chemical defenses. Secondary metabolites often have ecological functions, such as antipredator and antibacterial activities. I studied the common Caribbean sponge species, Amphimedon compressa, which is known to be chemically defended. Samples were collected from three sites in Belize, two sites in Grand Cayman, and three sites in St. Croix, U.S. Virgin Islands. To determine whether antibacterial activity varied across broad or local geographic scales, sponge extracts were tested against four bacterial strains …

The Interplay Of Progestins, Matrix Metalloproteinases, And The Aging Brain, Keyana Nicole Porter

Graduate Theses, Dissertations, and Problem Reports (ETD)

Progestins are synthetic hormones that are designed to mimic the biological actions of progesterone. They, however, possess other pharmacological actions and properties, in addition to their progestational activities. Medroxyprogesterone Acetate (MPA) is a progestin used globally in the hormonal contraceptive, Depo Provera®, by women in their reproductive prime and is a major compound found in hormone therapy (HT) formulations used by menopausal women. MPA is used by approximately 1 in 5 adolescents and adult women in the United States who are sexually active. Globally, nearly 48 million women utilize injectable contraceptives to prevent pregnancy, with most users utilizing MPA as …

Evaluation Of Rational Drug Use Project, Under The Support Of National Health Security Office, On Drug Utilization And Drug Management In Community Care Clinics In Bangkok, Dararat Samretwit

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: "The Network of Rational Drug Use Clinic (RDU Clinic)" campaign implemented in August 2015 to promote rational drug use in community caring clinic operated under National Health Security Office (NHSO) in Bangkok. The intervention composed of various measures such as education, managerial intervention, regulatory, and financial incentive. The purpose of the project is to evaluate and monitor the program effectiveness. Objectives: The purpose of the study is to evaluate the impact of RDU project on the quality of drug use in community care clinics in Bangkok using an interrupted time-series intervention analysis Methods: Quasi-experimental study using interrupted time series …

อิทธิพลของระดับความอิ่มตัวของทรานส์เฟอร์รินต่อดัชนีการดื้อยาอีริโทรโพอิตินในผู้ป่วยโรคไตเรื้อรังระยะที่ 4-5, อิ่มจิต บุญอำนวย

Chulalongkorn University Theses and Dissertations (Chula ETD)

วัตถุประสงค์: เพื่อศึกษาความสัมพันธ์ของระดับความอิ่มตัวทรานส์เฟอร์ริน (TSAT) กับดัชนีการดื้อยาอีริโทรโพอิติน (ERI) ในผู้ป่วยโรคไตเรื้อรังระยะที่ 4-5 วิธีการวิจัย: ในการศึกษาเชิงวิเคราะห์จากเหตุไปหาผลแบบย้อนหลังนี้ ผู้ป่วยโรคไตเรื้อรังระยะที่ 4-5 ที่ได้รับยาอีริโทรโพอิตินและมีการตรวจวัด TSAT ที่โรงพยาบาลบุรีรัมย์ ในช่วง ม.ค. 2560 ถึง ธ.ค. 2562 ถูกแบ่งออกเป็น 2 กลุ่มด้วยค่ามัธยฐานของระดับ TSAT (median TSAT) เพื่อเปรียบเทียบค่า ERI ที่คำนวณมาจากขนาดยาอีริโทรโพอิตินที่ใช้ต่อน้ำหนักตัวต่อสัปดาห์ (IU/kg/week) หารด้วยระดับฮีโมโกลบิน (g/dl) ระหว่างผู้ป่วย 2 กลุ่ม ผลการวิจัย: ผู้ป่วย 502 คนที่เข้าร่วมในการศึกษา มีค่ามัธยฐานของ TSAT เท่ากับร้อยละ 26.0 [IQR: ร้อยละ 17.9, ร้อยละ 36.0] และมัธยฐานของ ERI เท่ากับ 16.42 [IQR: 11.26, 21.25] IU/kg/week per g/dl มีผู้ป่วยในกลุ่มที่มี TSAT สูงกว่าค่ามัธยฐาน (>median TSAT) 246 คน และกลุ่ม TSAT ต่ำกว่าหรือเท่ากับค่ามัธยฐาน (≤median TSAT) 256 คน พบว่า ค่า ERI ในผู้ป่วยกลุ่ม >median TSAT ต่ำกว่ากลุ่ม ≤median TSAT อย่างมีนัยสำคัญทางสถิติ (15.04 [IQR: 9.74, 20.25] เทียบกับ 17.06 [IQR: 12.12, 22.50] IU/kg/week per g/dl ตามลำดับ, P= 0.003) สรุปผลการวิจัย: ผู้ป่วยโรคไตเรื้อรังระยะที่ …

เภสัชจลนศาสตร์ประชากรของยาเมอโรพีเนมในผู้ป่วยทารกขั้นวิกฤต, วัลย์ลิกา ยนต์วิเศษ

Chulalongkorn University Theses and Dissertations (Chula ETD)

วัตถุประสงค์: เพื่อวิเคราะห์หาค่าพารามิเตอร์และปัจจัยที่มีผลต่อค่าพารามิเตอร์ทางเภสัชจลนศาสตร์ของยาเมอโรพีเนมในผู้ป่วยเด็กทารกขั้นวิกฤต วิธีดำเนินการศึกษา: การศึกษาเชิงวิเคราะห์แบบเก็บข้อมูลไปข้างหน้า ในผู้ป่วยเด็กทารกขั้นวิกฤตอายุ 1 เดือน ถึง 2 ปี ที่ได้รับยาเมอโรพีเนมในการรักษา ณ โรงพยาบาลจุฬาลงกรณ์ สภากาชาดไทย ระหว่างวันที่ 4 กุมภาพันธ์ พ.ศ. 2563 ถึง 4 กุมภาพันธ์ พ.ศ. 2564 จำนวน 35 ราย ข้อมูลระดับยาในรูปอิสระของเมอโรพีเนมในเลือด จำนวน 160 ตัวอย่าง ถูกวิเคราะห์ด้วยเครื่อง high-performance liquid chromatography with ultraviolet (HPLC-UV) และนำมาสร้างแบบจำลองทางเภสัชจลนศาสตร์ประชากรโดยใช้โปรแกรม nonlinear mixed-effects modeling (NONMEM) ทดสอบความถูกต้องของแบบจำลองโดยการทดสอบภายในด้วยวิธี bootstrap analysis และวิเคราะห์กราฟ prediction-corrected visual predictive check (pcVPC) เพื่อประเมินความถูกต้อง แม่นยำในการทำนายของแบบจำลองสุดท้าย ผลการศึกษา: แบบจำลองทางเภสัชจลนศาสตร์แบบ one-compartment model with first-order elimination มีความเหมาะสมกับการศึกษานี้ อัตราการกำจัดยาและปริมาตรการกระจายยาของประชากรมีค่าเท่ากับ 1.33 ลิตรต่อชั่วโมง และ 2.27 ลิตร ตามลำดับ ปัจจัยที่มีผลต่ออัตราการกำจัดของยาเมอโรพีเนม คือ น้ำหนัก และอัตราการกำจัดของครีเอตินิน ส่วนปัจจัยที่มีผลต่อปริมาตรการกระจายของยาเมอโรพีเนม คือ น้ำหนัก ค่าความผันแปรระหว่างบุคคลของอัตรากำจัดยาและปริมาตรการกระจายยาเปรียบเทียบระหว่างแบบจำลองพื้นฐานและแบบจำลองสุดท้าย พบว่า มีค่าลดลงอย่างมีนัยสำคัญทางสถิติ ผลการประเมินแบบจำลอง พบว่า แบบจำลองสุดท้ายมีความถูกต้อง แม่นยำ และสามารถนำมาทำนายได้ดี สรุปผลการศึกษา: การศึกษานี้ได้พัฒนาและทดสอบความถูกต้องของแบบจำลองทางเภสัชจลนศาสตร์ประชากรของยาเมอโรพีเนมในผู้ป่วยเด็กทารกขั้นวิกฤต โดยพบว่า น้ำหนัก และอัตราการกำจัดของครีเอตินิน เป็นปัจจัยร่วมที่มีผลต่อค่าพารามิเตอร์ทางเภสัชจลนศาตร์ของยาเมอโรพีเนมอย่างมีนัยสำคัญทางสถิติ แบบจำลองทางเภสัชจลนศาสตร์ประชากรที่ได้จากการศึกษานี้สามารถนำมาเป็นแนวทางในการปรับขนาดยาเมอโรพีเนมให้เหมาะสมกับผู้ป่วยแต่ละรายในกลุ่มประชากรผู้ป่วยเด็กทารกขั้นวิกฤตที่มีลักษณะประชากรใกล้เคียงกับการศึกษานี้

Efficacy Of Cpap Compared To Standard Pharmacotherapy In Reducing Cognitive Impairment Symptoms In Patients With Alzheimer's Disease, Nicholas Moylan

Capstone Showcase

This review analyzed the following question: In adults age 65 years old or older diagnosed with Alzheimer’s Disease (P), is nightly use of CPAP (I) more effective in reducing cognitive impairment symptoms (O) than standard pharmacotherapy options (C)? A literature search conducted through Google Scholar and PubMed granted six relevant articles that provided data for this review. No current studies compared CPAP treatment with pharmacotherapy, and each study used unique measures of cognitive function, making direct comparison of the two therapies difficult. Results demonstrated that first line pharmacotherapy can improve cognitive function, but only in limited way and only in …

Oral Contraceptives As Possible Acl Injury Prevention Method, Haley Schweizer

Capstone Showcase

ABSTRACT

Introduction: Anterior Cruciate Ligament (ACL) injuries are an upsetting setback for many athletes that require a long and costly recovery process. The injury rates are four times greater in women than men. Preventative measures that help to prevent ACL injuries are limited to stretching and strengthening. Therefore, this review aims to investigate if oral contraceptive [I] usage provides a possible new avenue for prevention of ACL injury [O] in young female athletes (ages 18-30) [P] compared to those that do not take oral contraceptives [C].

Methods: A literature review was performed though PubMed, Google Scholar, SCOPUS Database, and ClinicalKey …

Qualitative Research In Pharmacy Education: An Exploration Of Pharmacy Education Researchers' Perceptions And Experiences Conducting Qualitative Research, Antonio A. Bush, Mauriell Amechi, Adam Persky

Educational Leadership & Workforce Development Faculty Publications

Objective. To investigate pharmacy education researchers’ experiences in conducting qualitative research and their perceptions of qualitative research in pharmacy education

Methods. A phenomenological approach was used to conduct one-time, in-depth interviews with 19 participants from 12 schools and colleges of pharmacy. Interview transcripts were coded and themes were identified using a modified form of the Sort and Sift, Think and Shift method of data analysis.

Results. Faculty members were the largest subgroup in the sample, followed by graduate students, postdoctoral fellows/scholars, and residents. Pharmacy education researchers had varying levels of training in conducting qualitative research and some had none at …

Community Pharmacists’ And Residents’ Decision Making And Unmet Information Needs When Completing Comprehensive Medication Reviews, Kacie L. Mcpherson, Omolola A. Adeoye-Olatunde, Jayna M. Osborne, William R. Doucette, Stephanie A. Gernant, Heather Jaynes, Shobha Phansalkar, Alissa L. Russ-Jara, Margie E. Snyder

Department of Pharmacy Practice Faculty Publications

Objective

To (1) characterize community pharmacists’ and community pharmacy residents’ decision making and unmet information needs when conducting comprehensive medication reviews (CMRs) as part of medication therapy management and (2) explore any differences between community pharmacists and community pharmacy residents in CMR decision making and unmet information needs.

Design

Thirty-to 60-minute semistructured interviews framed using a clinical decision-making model (CDMM) were conducted with community pharmacists and residents.

Setting and participants

Participants were recruited from practice-based research networks and researchers’ professional networks. Eligible participants had completed or supported the completion of at least 2 CMRs in the last 30 days.

Outcome …

Clinical Risk Assessment In Early Pregnancy For Preeclampsia In Nulliparous Women: A Population Based Cohort Study, Anna Sandstrom, Jonathan Snowden, Jonas Höijer, Matteo Bottai, Anna-Karin Wikström

OHSU-PSU School of Public Health Faculty Publications and Presentations

Objective

To evaluate the capacity of multivariable prediction of preeclampsia during pregnancy, based on detailed routinely collected early pregnancy data in nulliparous women.

Design and setting

A population-based cohort study of 62 562 pregnancies of nulliparous women with deliveries 2008–13 in the Stockholm-Gotland Counties in Sweden.

Methods

Maternal social, reproductive and medical history and medical examinations (including mean arterial pressure, proteinuria, hemoglobin and capillary glucose levels) routinely collected at the first visit in antenatal care, constitute the predictive variables. Predictive models for preeclampsia were created by three methods; logistic regression models using 1) pre-specified variables (similar to the Fetal Medicine …

Benchmarking Machine Learning Methods For Molecular Property Prediction, Govinda Bahadur Kc

Open Access Theses & Dissertations

Machine learning (ML) techniques have been widely applied in a variety of areas ranging from pattern recognition, natural language processing, and computer games to self-driving cars, clinical diagnostics, and molecular structure prediction easing day to day life of human beings. Drug discovery is an expensive, complex, and time taking process. Currently, the pharma industry is hoping to leverage machine learning methods in expediting the drug discovery process. Molecular property prediction is one of the most important tasks in drug discovery. While developing a new drug relies on a proper understanding of molecular properties, there has been great interest in the …

Eecp Improves Markers Of Functional Capacity Regardless Of Underlying Ranolazine Therapy, Sanaz Ziad, Jamil Malik, Obinna Isiguzo, Lang Xu, Leqi Chen, Annette Cox, Sachin Shah

School of Pharmacy Faculty Articles

OBJECTIVE: Enhanced external counterpulsation (EECP) and ranolazine are approved treatments for patients with chronic stable angina by the United States Food and Drug Administration (FDA). Whether EECP offers clinical benefits regardless of underlying ranolazine therapy needs further investigation.

METHODS: This was a retrospective evaluation of patients referred to a specialized EECP center. Patients having data on 6-Minute Walk Distance (6MWD) or Duke Activity Status Index (DASI) were categorized into two groups (EECP with ranolazine or EECP only). The primary endpoints were change in 6MWD and DASI before and after a full course of EECP within each of the two groups. …

Modulation Of K V 7 Channel Deactivation By Pi(4,5)P 2, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The activity of K_V7 channels critically contributes to the regulation of cellular electrical excitability in many cell types. In the central nervous system, the heteromeric K_V7.2/K_V7.3 channel is thought to be the chief molecular entity giving rise to M-currents. These K⁺-currents as so called because they are inhibited by the activation of Gq protein-coupled muscarinic receptors. In general, activation of Gq protein-coupled receptors (GqPCRs) decreases the concentration of the phosphoinositide PI(4,5)P₂ which is required for K_V7 channel activity. It has been recently reported that the deactivation rate of K …

Enhancing Chemosensitivity Of Lung Cancers By Manipulating The Tumor Microenvironment: Local Lung Delivery And Nanocarrier-Based Therapies, Hanming Zhang

Theses and Dissertations

Cancer is the second leading cause of death in United States causing an estimated six hundred thousand death in 2019. Among different types of cancer, lung cancer is the leading cause of cancer related death in both male and female. While targeted therapy and immunotherapy have shown promising clinical outcomes, currently there remain a significant proportion of patients who do not benefit from these strategies or who cannot tolerate them, making Pt based doublet chemotherapy still an indispensable component in almost all stages of treatment. However, partially due to the poor tumor distribution of small molecule drug, the development of …