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Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

《医学前沿（英文）》 2022年 第16卷 第5期   页码 815-826 doi: 10.1007/s11684-021-0891-0

摘要： Oral drugs such as ibrutinib play an important role in the treatment of mature B-cell lymphoma (BCL) due to their reliable efficacy, manageable safety, high accessibility, and convenience for use. Still, no guidelines or consensus focusing on oral drug therapies for BCL is available. To provide a reference of oral agent-based treatment for mature BCL, a panel of experts from the Lymphocyte Disease Group, Chinese Society of Hematology, Chinese Medical Association conducted an extensive discussion and reached a consensus on oral drugs for Chinese BCL patients on the basis of the current application status of oral drugs in China, combined with the latest authoritative guidelines in the world and current research reports. This consensus reviewed the application of oral drugs in the treatment of BCL and the latest research and provided appropriate recommendations on the use of oral drugs for indolent or aggressive BCL patients. With the deepening of research and the development of standardized clinical applications, oral medications will bring better treatment to BCL patients, enabling more patients to benefit from them.

关键词： B-cell lymphoma     oral drug     targeted therapy     immunotherapy     COVID-19 pandemic    

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Factors related to compliance with oral analgesic treatment of inpatients with chronic pain

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 374-379 doi: 10.1007/s11684-015-0411-1

摘要：

This study aimed to determine the relationship between the different factors of analgesic therapy and the compliance of chronic pain inpatients. We prospectively investigated 100 consecutive inpatients with non-cancer chronic pain who were hospitalized to receive oral analgesic treatment in the Pain Department of West China Hospital from May 2013 to October 2013. Patients who completed the treatment plan were recorded as good compliance, whereas patients who partly completed or even refused the treatment were recorded as moderate or non-compliance, respectively. A total of 73 (73.7%), 17 (17.1%), and 9 (9.2%) patients showed good, moderate, and non-compliance, respectively. Univariate analyses showed significantly better compliance among farmers, patients educated in college or above, with family income of<3000 CNY, and with severe or moderate pain than those employed and unemployed (P=0.02), patients educated below college (P=0.013), with family income of≥3000 CNY (P=0.025), and with mild pain (P<0.001), respectively. Logistic regression analysis showed that the family income of≥3000 CNY (OR: 2.50, 95%CI: 1.65–4.51, P=0.021) and mild pain (OR: 1.27, 95%CI: 1.03–3.31, P=0.016) were associated with moderate or non-compliance with oral analgesic treatment. In conclusion, the low compliance with oral treatment of analgesics was found in Chinese inpatients with chronic pain and compliance was negatively associated with family income and degree of pain of patients.

关键词： chronic pain     inpatient     oral paregoric drugs     compliance    

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Oral product input to the GI tract: GIS an oral product performance technology

Gordon L. Amidon, Yasuhiro Tsume

《化学科学与工程前沿（英文）》 2017年 第11卷 第4期   页码 516-520 doi: 10.1007/s11705-017-1658-7

摘要： The patient receives a pharmaceutical product, not a drug. The pharmaceutical products are formulated with a drug, an active ingredient to produce the maximum therapeutic effect after oral absorption. Therefore, it is the product we must optimize for the patients. In order to assure the safety and efficacy of pharmaceutical products, we need an predictive tool for oral product performance in patients. Currently, we are a surprisingly long way from accomplishing that objective. If the 20th century was the ‘age of the drug’, i.e., the ‘magic bullet’, the 21st century must become the ‘age of the guided missile’, i.e., the delivery system, including the form of the active pharmaceutical ingredient (API) (‘drug’). The physical form of the drug and the delivery system must be optimized to maximize the therapeutic benefits of pharmaceutical products for humans. Oral immediate release (IR) dosage forms cannot be optimal for all drugs or likely even any drugs (APIs). Still, the formulation of pharmaceutical products has to be optimized for patients. But how do we optimize oral delivery of drugs? It is usually through ‘trial and error’, in humans! We need a better way to optimize the oral dosage forms. We have suggested to select different dissolution methodologies for this optimization based on BCS Subclasses. In this article, we present the predicted drug dissolution profile of ketoconazole as a model drug from our laboratory utilizing a gastrointestinal simulator (GIS), which is an adaptation of the ASD system. GIS consists of three chambers representing stomach, duodenum, and jejunum, to create the human gastrointestinal tract-like environment and enable the control the gastric emptying rate. This dissolution system allows the monitoring of the drug dissolution phenomena and the observation of the supersaturation and the precipitation of pharmaceutical products, which is useful information to predict dissolution of pharmaceutical products. This system can provide the actual input needed to accurately predict the input into the systemic circulation required by many of the absorption prediction packages available today.

关键词： GIS     in vivo predictive dissolution     ketoconazole     BCS subclassification     supersaturation    

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Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region

Zhiyuan Zhang

《医学前沿（英文）》 2011年 第5卷 第4期   页码 401-413 doi: 10.1007/s11684-011-0161-7

摘要： Clinical imperatives for the reconstruction of jaw bone defects or resorbed alveolar ridge require new therapies or procedures instead of autologous/allogeneic bone grafts. Regenerative medicine, based on stem cell science and tissue engineering technology, is considered as an ideal alternative strategy for bone regeneration. In this paper, we review the current choices of cell source and strategies on directing the osteogenic differentiation of stem cells. The preclinical animal models for bone regeneration and the key translational points to clinical success in oral and maxillofacial region are also discussed. We propose comprehensive strategies based on stem cell and tissue engineering researches, allowing for clinical application in oral and maxillofacial region.

关键词： bone regeneration     animal models     translational strategies     oral and maxillofacial region    

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Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous

Huining HE, Junxiao YE, Jianyong SHENG, Jianxin WANG, Yongzhuo HUANG, Guanyi CHEN, Jingkang WANG, Victor C YANG

《化学科学与工程前沿（英文）》 2013年 第7卷 第1期   页码 9-19 doi: 10.1007/s11705-013-1306-9

摘要： Oral insulin delivery has received the most attention in insulin formulations due to its high patient compliance and, more importantly, to its potential to mimic the physiologic insulin secretion seen in non-diabetic individuals. However, oral insulin delivery has two major limitations: the enzymatic barrier that leads to rapid insulin degradation, and the mucosal barrier that limits insulin’s bioavailability. Several approaches have been actively pursued to circumvent the enzyme barrier, with some of them receiving promising results. Yet, thus far there has been no major success in overcoming the mucosal barrier, which is the main cause in undercutting insulin’s oral bioavailability. In this review of our group’s research, an innovative silica-based, mucoadhesive oral insulin formulation with encapsulated-insulin/cell penetrating peptide (CPP) to overcome both enzyme and mucosal barriers is discussed, and the preliminary and convincing results to confirm the plausibility of this oral insulin delivery system are reviewed. In vitro studies demonstrated that the CPP-insulin conjugates could facilitate cellular uptake of insulin while keeping insulin’s biologic functions intact. It was also confirmed that low molecular weight protamine (LMWP) behaves like a CPP peptide, with a cell translocation potency equivalent to that of the widely studied TAT. The mucoadhesive properties of the produced silica-chitosan composites could be controlled by varying both the pH and composition; the composite consisting of chitosan (25 wt-%) and silica (75 wt-%) exhibited the greatest mucoadhesion at gastric pH. Furthermore, drug release from the composite network could also be regulated by altering the chitosan content. Overall, the universal applicability of those technologies could lead to development of a generic platform for oral delivery of many other bioactive compounds, especially for peptide or protein drugs which inevitably encounter the poor bioavailability issues.

关键词： insulin     cell penetrating peptide     mucoadhesive composites     oral delivery    

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Taking advantage of drug resistance, a new approach in the war on cancer

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 490-495 doi: 10.1007/s11684-018-0647-7

摘要：

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit. We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.

关键词： cancer     drug resistance     genetic screens     senescence     targeted therapy    

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Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems

Ranvijay KUMAR, Kaushlendra SHARMA

《化学科学与工程前沿（英文）》 2013年 第7卷 第1期   页码 116-122 doi: 10.1007/s11705-013-1310-0

摘要： Polymethacrylic acid (PMA) was synthesized on the backbone of psyllium (Psy) by a microwave assisted method to prepare polymeric grafted materials designated as (Psy- -PMA). Various grades of Psy- -PMA were prepared by changing the degree of grafting from 35%–58% and the materials were then made into tablets. Swelling and biodegradability studies of the tablets were carried out. Acetyl salicylic acid was incorporated in the various Psy- -PMA samples and tablets were prepared to study the in vitro drug release in acidic (pH= 4), neutral (pH= 7), and basic (pH= 9) media. In the acidic medium, the swelling was more than 1300%. In addition, the biodegradable Psy- -PMA had the highest drug release in the acidic medium. This may be attributed to Fickian diffusion since the drug and the medium in which it was released have the same acidic nature.

关键词： psyllium     acetyl salicylic acid     in-vitro drug release     swelling     biodegradation    

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Meta-analysis of the risk factors of breast cancer concerning reproductive factors and oral contraceptive

Qiong DAI MD, Bei LIU MD, Yukai DU MM,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 452-458 doi: 10.1007/s11684-009-0080-z

摘要： The authors performed a meta-analysis of case-control studies that addressed whether reproductive factors and oral contraceptive use were associated with breast cancer by searching the MEDLINE, PubMed, Proquest, Embase, ScienceDirect, African Healthline, BMJ Health Intelligence and Chinese Periodical net databases for all English-language and Chinese-language papers published from January 1, 1997 to December 31, 2007. A total of 15 studies calculating pool ORs indicated that menopausal age >50yr [odds ratio (OR), 1.39; 95% confidence interval (CI), 1.22―1.57] and oral contraceptive use (OR, 2.12*, “*”: summary OR was adjusted; 95% CI, 1.24―3.62) were correlated with the increase in breast cancer risk while the summary OR based on number of full-term pregnancies ≥1 (OR, 0.63*; 95% CI, 0.60―0.68) and breast-feeding (OR, 0.76; 95% CI, 0.64―0.90) indicated no association with breast cancer risk. The correlation was statistically significant. Menopausal age >50yr and oral contraceptive use are positively correlated with an increase in breast cancer risk while breast-feeding and number of full-term pregnancies ≥1 are protective factors.

关键词： meta-analysis     breast cancer     risk factors     reproductive factors     oral contraceptive use    

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Protein microspheres for pulmonary drug delivery

Yongda SUN,

《化学科学与工程前沿（英文）》 2010年 第4卷 第1期   页码 82-86 doi: 10.1007/s11705-009-0307-1

摘要： A new supercritical fluid (SCF) technique was developed for the preparation of microspheres for pulmonary drug delivery (PDD). This technique, based on the anti-solvent process, has incorporated advanced engineering design features to enable improved control of the particle formation process. Human recombinant insulin (HRI) was used as a model compound to evaluate the efficiency of this SCF process. An aqueous solution of HRI with a co-solvent was sprayed into high pressure carbon dioxide that extracted the solvent and water, leading to a dry fine powder with good particle size distribution and near ideal morphology for pulmonary drug delivery.

关键词： advanced engineering     improved     pressure     aqueous     technique    

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Semi-solid materials for controlled release drug formulation: current status and future prospects

Michelle TRAN,Chun WANG

《化学科学与工程前沿（英文）》 2014年 第8卷 第2期   页码 225-232 doi: 10.1007/s11705-014-1429-7

摘要： Semi-solid materials represent an important category of inactive ingredients (excipients) of pharmaceutical products. Here we review several common semi-solid polymers currently used in the controlled release formulations of many drugs. These polymers are selected based on their importance and broad scope of application in FDA-approved drug products and include several polysaccharides (cellulose, starch, chitosan, alginate) and carbomers, a group of mucoadhesive synthetic polymers. Glyceride-based polymers used in self-emulsifying drug delivery systems (SEDDS) will also be discussed for its importance in formulating poorly water-soluble drugs. Unique features and advantages of each type of semi-solid materials are discussed and examples of their use in oral delivery of drugs are provided. Finally, future prospects of developing new and better semi-solid excipients are discussed with the objective of facilitating clinical translation.

关键词： controlled release     drug delivery     semi-solids     polymer     excipient    

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Nanostructured hollow spheres of hydroxyapatite: preparation and potential application in drug delivery

Xiaojing ZHANG, Weixin ZHANG, Zeheng YANG, Zhao ZHANG

《化学科学与工程前沿（英文）》 2012年 第6卷 第3期   页码 246-252 doi: 10.1007/s11705-012-1299-9

摘要： A solvothermal method has been successfully used to prepare nanostructured hydroxyapatite (HA) hollow spheres with average diameters of about 500 nm and shell thicknesses of about 100 nm in a glycerin/water mixed solvent. Transmission electron microscopy (TEM) and field-emission scanning electron microscopy (FESEM) images show that the shells of the HA hollow spheres are actually composed of nanosheets with thicknesses of about 10 nm. By tuning the glycerin/water volume ratio, two other kinds of HA solid spheres with average diameters of about 6 or 20 μm were assembled from nanoflakes. The properties of the different kinds of spheres as drug delivery carriers were evaluated. Ibuprofen (IBU) was chosen as the model drug to load into the HA samples. The nanostructured HA samples showed a slow and sustained release of IBU. The HA hollow spheres exhibited a higher drug loading capacity and more favorable release properties than the HA solid spheres and thus are very promising for controlled drug release applications.

关键词： hydroxyapatite     hollow spheres     synthesis     drug release    

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Relative expression of PTTG and bFGF in oral squamous cell carcinoma and Tca8113

Yumei DING BM , Lili CHEN MD , Bo CHENG PhD , Handong ZHANG MM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 357-362 doi: 10.1007/s11684-009-0046-1

摘要： The purpose of this study was to investigate the expression of pituitary tumor transforming gene (PTTG) and basic fibroblast growth factor (bFGF) in oral squamous cell carcinoma (OSCC) and tongue cancer cell line Tca8113, as well as their effects on each other. We detected PTTG protein and bFGF in OSCC tissues from 56 cases using the streptavidin-biotin peroxidase (S-P) method; additionally, after being treated with different concentrations of anti bFGF or PTTG antibody, PTTG or bFGF expression in Tca8113 was examined by immunocytochemistry. The results were as follows: (1) Positive rates of PTTG protein and bFGF were 78.2% and 67.3% in OSCC, respectively, which were significantly higher than those in normal mucosal tissues (<0.05). PTTG protein was significantly up-regulated in poorly and moderately differentiated tumors compared to well differentiated tumors (<0.05), and there was also a significant difference between tumors with lymph node metastasis and tumors without lymph node metastasis (<0.05). PTTG protein expression was positively correlated with bFGF ( = 0.382, <0.05); (2) PTTG protein emitted strong fluorescence in Tca8113, and it decreased after being treated with anti-bFGF antibody. Anti-PTTG antibody also had an inhibitive effect on bFGF expression. In summary, the overexpression of PTTG protein is closely related with OSCC differentiation and lymph node metastasis. PTTG protein expression conforms to bFGF in OSCC tissues and Tca8113 cells. Detection of both PTTG and bFGF may help to judge the degree of malignancy and prognosis of patients with OSCC.

关键词： carcinoma     squamous cell     pituitary tumor transforming gene (PTTG) protein     basic fibroblast growth factor    

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A Double-Layer Polysaccharide Hydrogel (DPH) for the Enhanced Intestine-Targeted Oral Delivery of Probiotics

Wen-Can Huang,Wenjie Wang,Wei Wang,Yanan Hao,Changhu Xue,Xiangzhao Mao,

《工程（英文）》 doi: 10.1016/j.eng.2023.05.024

摘要： Transplantation of probiotics to the intestine can positively regulate the gut microbiota, thereby promoting the immune system and treating various diseases. However, the harsh gastrointestinal environment and short retention time in the gastrointestinal tract significantly limit the bioavailability and intestinal colonization of probiotics. Herein, we present a double-layer polysaccharide hydrogel (DPH) in the form of a double-layer structure composed of a carboxymethyl cellulose (CMCL) supramolecular inner layer and a dialdehyde alginate (DAA) cross-linked carboxymethyl chitosan (CMCS) outer layer. This double-layer structure allows DPH to encapsulate and deliver probiotics in a targeted manner within the body. In the stomach, the cage structure of the DPH is closed, and the outer layer absorbs surrounding liquids to form a barrier to protect the probiotics from gastric fluids. In the intestine, the cage structure opens and disintegrates, releasing the probiotics. Thus, DPH endows probiotics with excellent intestine-targeted delivery, improved oral bioavailability, enhanced gastrointestinal tract tolerance, and robust mucoadhesion capacity. The encapsulated probiotics exhibit almost unchanged bioactivity in the gastrointestinal tract before release, as well as improved oral delivery. In particular, probiotics encapsulated by DPH exhibit 100.1 times higher bioavailability and 10.6 times higher mucoadhesion than free probiotics in an animal model 48 h post-treatment. In addition, with a remarkable ability to survive and be retained in the intestine, probiotics encapsulated by DPH show excellent in vitro and in vivo competition with pathogens. Notably, DAA-mediated dynamic crosslinking not only maintains the overall integrity of the hydrogels but also controls the release timing of the probiotics. Thus, it is expected that encapsulated substances (probiotics, proteins, etc.) can be delivered to specific sites of the intestinal tract by means of DPH, by controlling the dynamic covalent crosslinking.

关键词： Polysaccharides     Chitosan     Hydrogels     Oral delivery     Intestine-targeted    

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Prevalence of antifolate drug resistance markers in in China

《医学前沿（英文）》 2022年 第16卷 第1期   页码 83-92 doi: 10.1007/s11684-021-0894-x

摘要： The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax and antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009–2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.

关键词： drug resistance     antifolates     molecular markers     Plasmodium vivax     China    

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Clinical analysis of 275 cases of acute drug-induced liver disease

LI Lei, JIANG Wei, WANG Jiyao

《医学前沿（英文）》 2007年 第1卷 第1期   页码 58-61 doi: 10.1007/s11684-007-0012-8

摘要： In order to analyze the causative drugs, clinical manifestation and pathological characteristics of the patients with acute drug-induced liver disease, from January 2000 to December 2005, 275 cases diagnosed as acute drug-induced liver diseases according to Maria Criterion and hospitalized in Zhongshan Hospital of Fudan University were retrospectively reviewed. Each was determined by drug history, clinical symptoms and signs, laboratory tests and therapeutic effects. In 41 cases, the diagnosis was confirmed by liver biopsy. The proportion of acute drug-induced liver disease among all of the acute liver injuries was annually increased. The most common drugs which induced acute liver injuries were traditional Chinese herb medicine (23.3%, 64/275 cases), antineoplastics (15.3%, 42/275), hormones and other immunosuppressant agents (13.8%, 38/275), antihypertensive drugs and other cardiovascular drugs (10.2%, 28/275), NSAIDs (8.7%, 24/275) respectively. Hepatocellular injury was the predominant type in these cases (132 cases, 48%). The principal clinical manifestation included nausea (54.8%), fatigue (50.2%), jaundice (35.6%). 27.9% patients were asymptomatic. Most patients were cured with good prognosis. The total effective rate was 94.2% after treatment. The clinicians should pay attention to the prevention, diagnosis and therapy of drug-induced liver disease.
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标题 作者 时间 类型 操作

Chinese expert consensus on oral drugs for the treatment of mature B-cell lymphomas (2020 edition)

期刊论文

Factors related to compliance with oral analgesic treatment of inpatients with chronic pain

null

期刊论文

Oral product input to the GI tract: GIS an oral product performance technology

Gordon L. Amidon, Yasuhiro Tsume

期刊论文

Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region

Zhiyuan Zhang

期刊论文

Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous

Huining HE, Junxiao YE, Jianyong SHENG, Jianxin WANG, Yongzhuo HUANG, Guanyi CHEN, Jingkang WANG, Victor C YANG

期刊论文

Taking advantage of drug resistance, a new approach in the war on cancer

null

期刊论文

Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems

Ranvijay KUMAR, Kaushlendra SHARMA

期刊论文

Meta-analysis of the risk factors of breast cancer concerning reproductive factors and oral contraceptive

Qiong DAI MD, Bei LIU MD, Yukai DU MM,

期刊论文

Protein microspheres for pulmonary drug delivery

Yongda SUN,

期刊论文

Semi-solid materials for controlled release drug formulation: current status and future prospects

Michelle TRAN,Chun WANG

期刊论文

Nanostructured hollow spheres of hydroxyapatite: preparation and potential application in drug delivery

Xiaojing ZHANG, Weixin ZHANG, Zeheng YANG, Zhao ZHANG

期刊论文

Relative expression of PTTG and bFGF in oral squamous cell carcinoma and Tca8113

Yumei DING BM , Lili CHEN MD , Bo CHENG PhD , Handong ZHANG MM ,

期刊论文

A Double-Layer Polysaccharide Hydrogel (DPH) for the Enhanced Intestine-Targeted Oral Delivery of Probiotics

Wen-Can Huang,Wenjie Wang,Wei Wang,Yanan Hao,Changhu Xue,Xiangzhao Mao,

期刊论文

Prevalence of antifolate drug resistance markers in in China

期刊论文

Clinical analysis of 275 cases of acute drug-induced liver disease

LI Lei, JIANG Wei, WANG Jiyao

期刊论文