Milling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a“topedown”approach in the production of fine particles.Fine drug particulates are esp...Milling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a“topedown”approach in the production of fine particles.Fine drug particulates are especially desired in formulations designed for parenteral,respiratory and transdermal use.Most drugs after crystallization may have to be comminuted and this physical transformation is required to various extents,often to enhance processability or solubility especially for drugs with limited aqueous solubility.The mechanisms by which milling enhances drug dissolution and solubility include alterations in the size,specific surface area and shape of the drug particles as well as millinginduced amorphization and/or structural disordering of the drug crystal(mechanochemical activation).Technology advancements in milling now enable the production of drug micro-and nano-particles on a commercial scale with relative ease.This review will provide a background on milling followed by the introduction of common milling techniques employed for the micronization and nanonization of drugs.Salient information contained in the cited examples are further extracted and summarized for ease of reference by researchers keen on employing these techniques for drug solubility and bioavailability enhancement.展开更多
There has been a strong interest for controlled release solid dosage forms,and to achieve controlled release,coating of particulates is often attempted to modify drug release.Due to the disadvantages of coated single-...There has been a strong interest for controlled release solid dosage forms,and to achieve controlled release,coating of particulates is often attempted to modify drug release.Due to the disadvantages of coated single-unit dosage forms,such as occurrences of dose dumping and local irritation,coated multiparticulates are often preferred.However,coated multiparticulates are often filled into capsules.Compressed tablet dosage form is more desirable than capsules as the unit production costs of tablets are lower and tablet presses are more common.展开更多
Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique s...Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e.,classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm.The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.展开更多
Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes(NHs) for the management of behavioral and psychological symptoms of dementia continue to be emphasized and inte...Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes(NHs) for the management of behavioral and psychological symptoms of dementia continue to be emphasized and intervened by many. However, despite the numerous side effects and the recent blackbox warning by the United States Food and Drug Administration about the increased risks for stroke and sudden death associated with the use of antipsychotics in dementia, the prevalence of antipsychotic use in NHs remains high. While the use of antipsychotics appeared to have modest efficacy in reducing symptoms of aggression and psychosis in dementia, there is insufficient evidence to routinely recommend the use of alternative psychopharmacological treatments for these symptoms. Hence, clinicians have to balance the safety warnings against the need to treat these symptoms in order to prevent harm to the resident that may result from his/her dangerous behaviors. Although the use of antipsychotics may be warranted in some cases, organizational, resource and training support should be provided to encourage and equip NH staff to participate in interventions so as to minimize inappropriate use of these medicines in NHs. This review will discuss the place in therapy, the trend and appropriateness of antipsychotic use in NHs, as well as the effectiveness of current and future strategies for reducing antipsychotic use in the NHs.展开更多
BACKGROUND With advanced age and chronic illness,the life expectancy of a patient with colorectal cancer(CRC)becomes less dependent on the malignant disease and more on their pre-morbid condition.Justifying major surg...BACKGROUND With advanced age and chronic illness,the life expectancy of a patient with colorectal cancer(CRC)becomes less dependent on the malignant disease and more on their pre-morbid condition.Justifying major surgery for these elderly patients can be challenging.An accurate tool demonstrating post-operative survival probability would be useful for surgeons and their patients.AIM To integrate clinically significant prognostic factors relevant to elective colorectal surgery in the elderly into a validated pre-operative scoring system.METHODS In this retrospective cohort study,patients aged 70 and above who underwent surgery for CRC at Singapore General Hospital between 1 January 2005 and 31 December 2012 were identified from a prospectively maintained database.Patients with evidence of metastatic disease,and those who underwent emergency surgery or had surgery for benign colorectal conditions were excluded from the analysis.The primary outcome was overall 3-year overall survival(OS)following surgery.A multivariate model predicting survival was derived and validated against an equivalent external surgical cohort from Kyungpook National University Chilgok Hospital,South Korea.Statistical analyses were performed using Stata/MP Version 15.1.RESULTS A total of 1267 patients were identified for analysis.The median post-operative length of stay was 8[interquartile range(IQR)6-12]d and median follow-up duration was 47(IQR 19-75)mo.Median OS was 78(IQR 65-85)mo.Following multivariate analysis,the factors significant for predicting overall mortality were serum albumin<35 g/dL,serum carcinoembryonic antigen≥20μg/L,T stage 3 or 4,moderate tumor cell differentiation or worse,mucinous histology,rectal tumors,and pre-existing chronic obstructive lung disease.Advanced age alone was not found to be significant.The Korean cohort consisted of 910 patients.The Singapore cohort exhibited a poorer OS,likely due to a higher proportion of advanced cancers.Despite the clinicopathologic differences,there was successful validation of the model following recalibration.An interactive online calculator was designed to facilitate post-operative survival prediction,available at http://bit.ly/sgh_crc.The main limitation of the study was selection bias,as patients who had undergone surgery would have tended to be physiologically fitter.CONCLUSION This novel scoring system generates an individualized survival probability following colorectal resection and can assist in the decision-making process.Validation with an external population strengthens the generalizability of this model.展开更多
Diagnosis and treatment of breast cancer have been improved during the last decade; however, breast cancer is still a leading cause of death among women in the whole world. Early detection and accurate diagnosis of th...Diagnosis and treatment of breast cancer have been improved during the last decade; however, breast cancer is still a leading cause of death among women in the whole world. Early detection and accurate diagnosis of this disease has been demonstrated an approach to long survival of the patients. As an attempt to develop a reliable diagnosing method for breast cancer, we integrated support vector machine (SVM), k-nearest neighbor and probabilistic neural network into a complex machine learning approach to detect malignant breast tumour through a set of indicators consisting of age and ten cellular features of fine-needle aspiration of breast which were ranked according to signal-to-noise ratio to identify determinants distinguishing benign breast tumours from malignant ones. The method turned out to significantly improve the diagnosis, with a sensitivity of 94.04%, a specificity of 97.37%, and an overall accuracy up to 96.24% when SVM was adopted with the sigmoid kernel function under 5-fold cross validation. The results suggest that SVM is a promising methodology to be further developed into a practical adjunct implement to help discerning benign and malignant breast tumours and thus reduce the incidence of misdiagnosis.展开更多
Pharmaceutical solid dosage forms are commonly coated to modify the release of drugs. Due to the disadvantages of coated single-unit dosage forms, such as occurrences of dose dumping and local irritation, coated multi...Pharmaceutical solid dosage forms are commonly coated to modify the release of drugs. Due to the disadvantages of coated single-unit dosage forms, such as occurrences of dose dumping and local irritation, coated multi-particulates are preferred.Coated multi-particulates can eventually be filled into capsules or compressed into tablets.展开更多
OBJECTIVE To establish a small compound library via a versatile synthetic route for the investigation of natural-inspiring compounds containing N-hydroxypyridones motif as potential anti-plasmodial,anti-bacterial and ...OBJECTIVE To establish a small compound library via a versatile synthetic route for the investigation of natural-inspiring compounds containing N-hydroxypyridones motif as potential anti-plasmodial,anti-bacterial and iron(Ⅱ)-chelating agents.METHODS An amidation/cyclization approach was adopted to synthesize a library of N-hydroxyquinolinones.The anti-plasmodial susceptibility of lab clone 3D7 P.falciparum was measured using aprotocol modified from the WHO microtest.The minimum bactericidal concentration(MBC)values were determined against Escherichia coli and Staphylococcus arueus.Nine compounds were selected to test their iron(Ⅱ)-chelating abilities.The iron(Ⅱ)-chelating ability was determined by measuring the absorbance of ferrozine-iron complex at 562 nm.RESULTS A new route for the facile synthesis of a library of N-hydroxyquinolinones based on one-pot palladium catalyzed C-N amidation/dehydrocyclizationsequence was implemented.Four compounds show anti-plasmodial activities with the range of 1.1-1.4μmol·L-1,50% chelation abilities of the nine selected compounds were shown to be 0.24-0.29mmol·L-1.CONCLUSION Alibrary of N-hydroxyquinolinones was synthesized via a novel synthetic route.The anti-plasmodial and anti-bacterial activities of these compounds were evaluated.Four compounds show potent anti-plasmodial activities Nine compounds were examined for their propensities to undergo iron chelation and these compounds were shown to be promising iron(Ⅱ)chelators as compared to EDTA.展开更多
Photodynamic therapy(PDT)is a novel therapeutic approach for combating various cancers.PDT involves the administration of a photosensitizer which generates singlet oxygen after light activation.FosPeg■ is the liposom...Photodynamic therapy(PDT)is a novel therapeutic approach for combating various cancers.PDT involves the administration of a photosensitizer which generates singlet oxygen after light activation.FosPeg■ is the liposomal formulation of mTHPC.In this in vitro study,the photodynamic efficacy of FosPeg■ on a human colon cancer cell line(HT29)was investigated via studying the cellular uptake of FosPeg■,FosPeg■ PDT mediated photocytotoxicity and the cell death mechanism were triggered.FosPeg■ PDT demonstrated its antitumor effect in a drug and light dose-dependent manner in HT-29 cells.Lethal dose(LD50)was achieved with 0.4g/mL of drug and 3 J/cm^(2) of light dose.FosPeg■ PDT triggered apoptotic cell death via activating caspase cascade and regulating cell cycle progression.In conclusion,FosPegr-PDT is an effective measure to combat human colon cancer cells.展开更多
In nursing homes, antipsychotic prescribing decisions (APDs) for managing behavioral and psychological symptoms of dementia (BPSD) depend on the nursing staff’s feedback. Inappropriate APDs can result in the lack of ...In nursing homes, antipsychotic prescribing decisions (APDs) for managing behavioral and psychological symptoms of dementia (BPSD) depend on the nursing staff’s feedback. Inappropriate APDs can result in the lack of timeliness, objectivity and important clinical information when nursing staff’s feedback on residents’ behavior and pharmacotherapy outcomes. Currently, there are no reported interventions for improving psychiatrists’ APDs through nursing staff’s monitoring and feedback processes. This one-group pre-and-post pilot study aimed to evaluate the feasibility and impact of implementing a newly-developed Psychotropic Use Monitoring (PUM) program for improving the appropriateness of APDs in a 50-bed dementia ward of a nursing home. The PUM intervention involved 16 pharmacist-trained nursing staff, who monitored and reported residents’ BPSD changes and psychotropic side effects for 24 weeks, while carrying out their routine care duties. A face-to-face interview was then administered to determine the nursing staff’s perceptions of PUM. Data of 51 residents were collected from hardcopy individual patient records to evaluate the changes in APDs and the number of resident falls before and after implementing PUM. The nursing staff reported increases in their knowledge, awareness, confidence, and actual frequency of monitoring for side effects, as well as their ability in differentiating and managing BPSD (p < 0.05). After PUM, there was a significant increase in the number of APDs due to side effect-related reasons (4 versus 16) (p < 0.031). Although not significant, the number of APDs with no documented reasons (5 versus 9) and the number of resident falls (7 versus 15) appeared to be lesser after PUM. This study demonstrated the nursing staff’s positive participation in PUM intervention, specifically in monitoring and feedback of side effects. Furthermore, a potential exists for PUM to encourage more judicious APDs, which may be useful in settings with heavy patient load, limited human resources and dependence on foreign nursing staff from differing cultural backgrounds.展开更多
Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk...Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.展开更多
Biochars were prepared by the pyrolysis of various H_(3)PO_(4) activated agricultural biomasses at 600℃and subsequently used as adsorbents for the removal of ciprofloxacin(CIP)from aqueous solution.Peanut shell-based...Biochars were prepared by the pyrolysis of various H_(3)PO_(4) activated agricultural biomasses at 600℃and subsequently used as adsorbents for the removal of ciprofloxacin(CIP)from aqueous solution.Peanut shell-based biochar(PSBC),corncob-based biochar(CCBC)and cotton-based biochar(CTBC)had high surface areas(571.0-1006.3 m^(2)/g),well-developed pore structures(mesopores with large pore volumes)and available adsorption functional groups(C=C,C-N and C-O-C).The CIP adsorption onto the biochars was investigated by batch experiments(kinetics,isotherms,thermodynamics,pH,etc.).Thermodynamics calculations showed the spontaneous(ΔG^(θ)<0)and endothermic(ΔH^(θ)>0)nature of the mechanism.In particular,CCBC exhibited high adsorption capacity(120.6 mg/g)of CIP in real lake water and it also had significant removal efficiency of other common pharmaceutical contaminants from real lake environ-ment,and even in a coexisting quintuple system.Finally,multiple interaction mechanisms of CIP adsorption onto aromatized biochar were explored combining characterization analysis and theoretical calculations.Elucidation of the mechanism of CIP adsorption onto biochar provides new insights into the assessment of the removal of pharmaceuticals from the aqueous environment.展开更多
Background:Despite therapeutic advances,treatment of patients with axial spondyloarthritis(axSpA)continue to pose as a challenge as many do not respond well to conventional Western medications,such as nonsteroidal ant...Background:Despite therapeutic advances,treatment of patients with axial spondyloarthritis(axSpA)continue to pose as a challenge as many do not respond well to conventional Western medications,such as nonsteroidal anti-inflammatory drugs(NSAIDs)and biologic diseasemodifying antirheumatic drugs(bDMARDs).Hence,acupuncture is a possible alternative.Some studies found electroacupuncture to be better than manual acupuncture,though no trials have been conducted in patients with axSpA.This clinical trial aims to evaluate the clinical efficacy,safety,and cost-effectiveness of electroacupuncture compared to manual acupuncture for patients with axSpA.Methods/Design:This randomized controlled trial will recruit 100 patients diagnosed with axSpA,who have active disease despite NSAIDs and bDMARDs.Eligible patients will be randomized to receive either electroacupuncture or manual acupuncture in a 1:1 ratio.All participants will receive standard rheumatologic care in addition to 20 acupuncture sessions.The mean difference in Bath Ankylosing Spondylitis Disease Activity Index score between the 2 groups over 12 weeks will serve as the primary outcome.Secondary outcomes include improvements in other clinical,quality of life,and economic outcomes over 24 weeks.All adverse events will be recorded.Discussion:Results from this trial may provide evidence regarding the clinical effectiveness,safety,and cost-effectiveness of electroacupuncture compared to manual acupuncture for patients with axSpA,and guide implementation into clinical practice.Limitations of this trial include the lack of patient blinding,use of a repeated measures design,and possible variation in acupuncture technique amongst the various Traditional Chinese Medicine practitioners.展开更多
对humanether-a-gò-gò related genes(HERG)钾离子通道(钾通道)抑制剂,计算了表征分子组成、电荷分布、拓扑、几何结构及物理化学性质等特征的1559个分子描述符,采用Fischer Score(F-Score)排序过滤和MonteCarlo模拟退火法相...对humanether-a-gò-gò related genes(HERG)钾离子通道(钾通道)抑制剂,计算了表征分子组成、电荷分布、拓扑、几何结构及物理化学性质等特征的1559个分子描述符,采用Fischer Score(F-Score)排序过滤和MonteCarlo模拟退火法相结合从中筛选与HERG钾通道抑制剂分类相关的分子描述符.采用支持向量机(SVM)方法,分别以IC50=1.0、10.0μmol·L-1为分类标准,建立了三个分类预测模型.对367个训练集分子,用五重交叉验证,得到正、负样本的平均预测精度分别为84.8%-96.6%、80.7%-97.7%,其总的平均预测精度为87.1%-97.2%,优于其它文献报道结果.对97个外部测试集分子,所建三个模型的总样本预测精度在67.0%-90.1%之间,接近或优于其它文献报道结果.展开更多
In a recent single cell transcriptomic investigation of the peripheral immune responses of the patients with severe COVID-19[1],no substantial expression of pro-inflammatory cytokines has been identified in the periph...In a recent single cell transcriptomic investigation of the peripheral immune responses of the patients with severe COVID-19[1],no substantial expression of pro-inflammatory cytokines has been identified in the peripheral monocytes and lymphocytes,while these peripheral immune cells exhibit phenotypes of heterogeneously expressed interferon-stimulated genes in certain COVID-19 patients.These genes may contribute to the inhibitory response to the viral entry,translation,replication and egress.Questions remain regarding why the peripheral cytokine production is constrained,what additional roles these peripheral immune cells may play in COVID-19 pathophysiology,and which potential targets can be explored for facilitating COVID-19 therapeutics.展开更多
In this study,we sought to investigate the expression of the transcription factor E2F1 in chicken pulmonary arterial smooth muscle cells upon hypoxia exposure,as well as the role that E2F1 played in the regulation of ...In this study,we sought to investigate the expression of the transcription factor E2F1 in chicken pulmonary arterial smooth muscle cells upon hypoxia exposure,as well as the role that E2F1 played in the regulation of cell proliferation.Isolated chicken pulmonary arterial smooth muscle cells were subjected to hypoxia or normoxia for indicated time points.Cell viability,DNA synthesis,cell cycle profile,and expression of E2F1 were analyzed.The results showed that hypoxia promoted cell proliferation and DNA synthesis which was accompanied by an increased S phase entry and upregulation of E2F1 at mRNA and protein levels.Using siRNA technology,we demonstrated that gene inactivation of endogenous E2F1 abolished hypoxia-induced cell proliferation,DNA synthesis,and S phase entry compared with negative siRNA transfected cells.These results suggest that hypoxia-induced proliferation is mediated by inducing E2F1 in chicken pulmonary arterial smooth muscle cells.展开更多
The incidence of prostate cancer is rising in the Asia-Pacific region as well as other countries. Androgen-ablation therapy is clinically useful in the androgen-dependent phenotype however, many patients progress to h...The incidence of prostate cancer is rising in the Asia-Pacific region as well as other countries. Androgen-ablation therapy is clinically useful in the androgen-dependent phenotype however, many patients progress to hormone refractory prostate cancer that is difficult to treat and needs newer interventions that are more effective. The objective of this study was to determine functionally-relevant biological networks, to appreciate the potential crosstalk between signaling members, and to identify biomarker signatures in prostate cancer. We used microarray analyses to identify key genes that were upregulated or down regulated at least five-fold in human prostate cancer and constructed canonical interaction networks that are important in prostate cancer through metabolomics analyses. Our prostate cancer network architecture revealed several key biomarkers including ERK1/2, JNK, p38, MEK, PI3 K, NFκB, AP-1, 14-3-3, VEGF, PDGF, Rb, WNT8 A, WNT10 A, CD44, ESR2, FSH and LH. Furthermore, the top ten transcription factors identified by TFBS-association signature analysis in the regulatory elements of co-regulated biomarkers were delineated, which may crosstalk with upstream or downstream genes elicited in our network architecture. Taken together, our results demonstrate that the regulatory interaction networks in prostate cancer provide a universal view of crosstalk between important biomarkers, i.e., key players in the pathogenesis of this disease. This will facilitate more rapid screening of functional biomarkers in early/intermediate drug discovery.展开更多
文摘Milling involves the application of mechanical energy to physically break down coarse particles to finer ones and is regarded as a“topedown”approach in the production of fine particles.Fine drug particulates are especially desired in formulations designed for parenteral,respiratory and transdermal use.Most drugs after crystallization may have to be comminuted and this physical transformation is required to various extents,often to enhance processability or solubility especially for drugs with limited aqueous solubility.The mechanisms by which milling enhances drug dissolution and solubility include alterations in the size,specific surface area and shape of the drug particles as well as millinginduced amorphization and/or structural disordering of the drug crystal(mechanochemical activation).Technology advancements in milling now enable the production of drug micro-and nano-particles on a commercial scale with relative ease.This review will provide a background on milling followed by the introduction of common milling techniques employed for the micronization and nanonization of drugs.Salient information contained in the cited examples are further extracted and summarized for ease of reference by researchers keen on employing these techniques for drug solubility and bioavailability enhancement.
文摘There has been a strong interest for controlled release solid dosage forms,and to achieve controlled release,coating of particulates is often attempted to modify drug release.Due to the disadvantages of coated single-unit dosage forms,such as occurrences of dose dumping and local irritation,coated multiparticulates are often preferred.However,coated multiparticulates are often filled into capsules.Compressed tablet dosage form is more desirable than capsules as the unit production costs of tablets are lower and tablet presses are more common.
基金the funding support for this study from GEA-NUS PPRL (N-148-000-008-001)SERC Grant No. 102 169 0049 (R-148-000-157-305)partial support from the NSF through the NNIN program
文摘Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e.,classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm.The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.
文摘Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes(NHs) for the management of behavioral and psychological symptoms of dementia continue to be emphasized and intervened by many. However, despite the numerous side effects and the recent blackbox warning by the United States Food and Drug Administration about the increased risks for stroke and sudden death associated with the use of antipsychotics in dementia, the prevalence of antipsychotic use in NHs remains high. While the use of antipsychotics appeared to have modest efficacy in reducing symptoms of aggression and psychosis in dementia, there is insufficient evidence to routinely recommend the use of alternative psychopharmacological treatments for these symptoms. Hence, clinicians have to balance the safety warnings against the need to treat these symptoms in order to prevent harm to the resident that may result from his/her dangerous behaviors. Although the use of antipsychotics may be warranted in some cases, organizational, resource and training support should be provided to encourage and equip NH staff to participate in interventions so as to minimize inappropriate use of these medicines in NHs. This review will discuss the place in therapy, the trend and appropriateness of antipsychotic use in NHs, as well as the effectiveness of current and future strategies for reducing antipsychotic use in the NHs.
文摘BACKGROUND With advanced age and chronic illness,the life expectancy of a patient with colorectal cancer(CRC)becomes less dependent on the malignant disease and more on their pre-morbid condition.Justifying major surgery for these elderly patients can be challenging.An accurate tool demonstrating post-operative survival probability would be useful for surgeons and their patients.AIM To integrate clinically significant prognostic factors relevant to elective colorectal surgery in the elderly into a validated pre-operative scoring system.METHODS In this retrospective cohort study,patients aged 70 and above who underwent surgery for CRC at Singapore General Hospital between 1 January 2005 and 31 December 2012 were identified from a prospectively maintained database.Patients with evidence of metastatic disease,and those who underwent emergency surgery or had surgery for benign colorectal conditions were excluded from the analysis.The primary outcome was overall 3-year overall survival(OS)following surgery.A multivariate model predicting survival was derived and validated against an equivalent external surgical cohort from Kyungpook National University Chilgok Hospital,South Korea.Statistical analyses were performed using Stata/MP Version 15.1.RESULTS A total of 1267 patients were identified for analysis.The median post-operative length of stay was 8[interquartile range(IQR)6-12]d and median follow-up duration was 47(IQR 19-75)mo.Median OS was 78(IQR 65-85)mo.Following multivariate analysis,the factors significant for predicting overall mortality were serum albumin<35 g/dL,serum carcinoembryonic antigen≥20μg/L,T stage 3 or 4,moderate tumor cell differentiation or worse,mucinous histology,rectal tumors,and pre-existing chronic obstructive lung disease.Advanced age alone was not found to be significant.The Korean cohort consisted of 910 patients.The Singapore cohort exhibited a poorer OS,likely due to a higher proportion of advanced cancers.Despite the clinicopathologic differences,there was successful validation of the model following recalibration.An interactive online calculator was designed to facilitate post-operative survival prediction,available at http://bit.ly/sgh_crc.The main limitation of the study was selection bias,as patients who had undergone surgery would have tended to be physiologically fitter.CONCLUSION This novel scoring system generates an individualized survival probability following colorectal resection and can assist in the decision-making process.Validation with an external population strengthens the generalizability of this model.
基金Joint Research Project Between Chongqing University and National University of Singapore (No. ARF-151-000-014-112)the Basic Research & Applied Basic Research Program of Chongqing University (No.71341103)Natural Science Foundation of Chongqing S & T Committee(No. CSTC,2006BB5240)
文摘Diagnosis and treatment of breast cancer have been improved during the last decade; however, breast cancer is still a leading cause of death among women in the whole world. Early detection and accurate diagnosis of this disease has been demonstrated an approach to long survival of the patients. As an attempt to develop a reliable diagnosing method for breast cancer, we integrated support vector machine (SVM), k-nearest neighbor and probabilistic neural network into a complex machine learning approach to detect malignant breast tumour through a set of indicators consisting of age and ten cellular features of fine-needle aspiration of breast which were ranked according to signal-to-noise ratio to identify determinants distinguishing benign breast tumours from malignant ones. The method turned out to significantly improve the diagnosis, with a sensitivity of 94.04%, a specificity of 97.37%, and an overall accuracy up to 96.24% when SVM was adopted with the sigmoid kernel function under 5-fold cross validation. The results suggest that SVM is a promising methodology to be further developed into a practical adjunct implement to help discerning benign and malignant breast tumours and thus reduce the incidence of misdiagnosis.
文摘Pharmaceutical solid dosage forms are commonly coated to modify the release of drugs. Due to the disadvantages of coated single-unit dosage forms, such as occurrences of dose dumping and local irritation, coated multi-particulates are preferred.Coated multi-particulates can eventually be filled into capsules or compressed into tablets.
基金The project supported by the Agency for Science Technology and Research(A*STAR)(JCO-10/03/FG/06/02)
文摘OBJECTIVE To establish a small compound library via a versatile synthetic route for the investigation of natural-inspiring compounds containing N-hydroxypyridones motif as potential anti-plasmodial,anti-bacterial and iron(Ⅱ)-chelating agents.METHODS An amidation/cyclization approach was adopted to synthesize a library of N-hydroxyquinolinones.The anti-plasmodial susceptibility of lab clone 3D7 P.falciparum was measured using aprotocol modified from the WHO microtest.The minimum bactericidal concentration(MBC)values were determined against Escherichia coli and Staphylococcus arueus.Nine compounds were selected to test their iron(Ⅱ)-chelating abilities.The iron(Ⅱ)-chelating ability was determined by measuring the absorbance of ferrozine-iron complex at 562 nm.RESULTS A new route for the facile synthesis of a library of N-hydroxyquinolinones based on one-pot palladium catalyzed C-N amidation/dehydrocyclizationsequence was implemented.Four compounds show anti-plasmodial activities with the range of 1.1-1.4μmol·L-1,50% chelation abilities of the nine selected compounds were shown to be 0.24-0.29mmol·L-1.CONCLUSION Alibrary of N-hydroxyquinolinones was synthesized via a novel synthetic route.The anti-plasmodial and anti-bacterial activities of these compounds were evaluated.Four compounds show potent anti-plasmodial activities Nine compounds were examined for their propensities to undergo iron chelation and these compounds were shown to be promising iron(Ⅱ)chelators as compared to EDTA.
基金This study was supported by The Hong Kong Polytechnic University Central Research Grant (G-YJ67 and G-U737).
文摘Photodynamic therapy(PDT)is a novel therapeutic approach for combating various cancers.PDT involves the administration of a photosensitizer which generates singlet oxygen after light activation.FosPeg■ is the liposomal formulation of mTHPC.In this in vitro study,the photodynamic efficacy of FosPeg■ on a human colon cancer cell line(HT29)was investigated via studying the cellular uptake of FosPeg■,FosPeg■ PDT mediated photocytotoxicity and the cell death mechanism were triggered.FosPeg■ PDT demonstrated its antitumor effect in a drug and light dose-dependent manner in HT-29 cells.Lethal dose(LD50)was achieved with 0.4g/mL of drug and 3 J/cm^(2) of light dose.FosPeg■ PDT triggered apoptotic cell death via activating caspase cascade and regulating cell cycle progression.In conclusion,FosPegr-PDT is an effective measure to combat human colon cancer cells.
文摘In nursing homes, antipsychotic prescribing decisions (APDs) for managing behavioral and psychological symptoms of dementia (BPSD) depend on the nursing staff’s feedback. Inappropriate APDs can result in the lack of timeliness, objectivity and important clinical information when nursing staff’s feedback on residents’ behavior and pharmacotherapy outcomes. Currently, there are no reported interventions for improving psychiatrists’ APDs through nursing staff’s monitoring and feedback processes. This one-group pre-and-post pilot study aimed to evaluate the feasibility and impact of implementing a newly-developed Psychotropic Use Monitoring (PUM) program for improving the appropriateness of APDs in a 50-bed dementia ward of a nursing home. The PUM intervention involved 16 pharmacist-trained nursing staff, who monitored and reported residents’ BPSD changes and psychotropic side effects for 24 weeks, while carrying out their routine care duties. A face-to-face interview was then administered to determine the nursing staff’s perceptions of PUM. Data of 51 residents were collected from hardcopy individual patient records to evaluate the changes in APDs and the number of resident falls before and after implementing PUM. The nursing staff reported increases in their knowledge, awareness, confidence, and actual frequency of monitoring for side effects, as well as their ability in differentiating and managing BPSD (p < 0.05). After PUM, there was a significant increase in the number of APDs due to side effect-related reasons (4 versus 16) (p < 0.031). Although not significant, the number of APDs with no documented reasons (5 versus 9) and the number of resident falls (7 versus 15) appeared to be lesser after PUM. This study demonstrated the nursing staff’s positive participation in PUM intervention, specifically in monitoring and feedback of side effects. Furthermore, a potential exists for PUM to encourage more judicious APDs, which may be useful in settings with heavy patient load, limited human resources and dependence on foreign nursing staff from differing cultural backgrounds.
基金supported by the National Natural Science Foundation of China(82373808)Chongqing Natural Science Foundation(cstc2021jcyj-bshX0125)+1 种基金Fundamental Research Funds for the Central Universities(SWURC2020001)the project for Chongqing University Innovation Research Group,Chongqing Education Committee(CXQT20006).
文摘Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.
基金supported by grants from the National Natural Science Foundation of China(grant Nos.22068002,22178054 and 22176032)Training plan for academic and technical leaders of major disciplines in Jiangxi Province-youth talent project(grant No.20212BCj23001)Natural Science Foundation of Jiangxi Province(grant No.20212ACB203002).
文摘Biochars were prepared by the pyrolysis of various H_(3)PO_(4) activated agricultural biomasses at 600℃and subsequently used as adsorbents for the removal of ciprofloxacin(CIP)from aqueous solution.Peanut shell-based biochar(PSBC),corncob-based biochar(CCBC)and cotton-based biochar(CTBC)had high surface areas(571.0-1006.3 m^(2)/g),well-developed pore structures(mesopores with large pore volumes)and available adsorption functional groups(C=C,C-N and C-O-C).The CIP adsorption onto the biochars was investigated by batch experiments(kinetics,isotherms,thermodynamics,pH,etc.).Thermodynamics calculations showed the spontaneous(ΔG^(θ)<0)and endothermic(ΔH^(θ)>0)nature of the mechanism.In particular,CCBC exhibited high adsorption capacity(120.6 mg/g)of CIP in real lake water and it also had significant removal efficiency of other common pharmaceutical contaminants from real lake environ-ment,and even in a coexisting quintuple system.Finally,multiple interaction mechanisms of CIP adsorption onto aromatized biochar were explored combining characterization analysis and theoretical calculations.Elucidation of the mechanism of CIP adsorption onto biochar provides new insights into the assessment of the removal of pharmaceuticals from the aqueous environment.
基金Reverie Rheumatology Research Fund,Spondyloarthritis:Excelling in Research for best Outcomes(SPERO)。
文摘Background:Despite therapeutic advances,treatment of patients with axial spondyloarthritis(axSpA)continue to pose as a challenge as many do not respond well to conventional Western medications,such as nonsteroidal anti-inflammatory drugs(NSAIDs)and biologic diseasemodifying antirheumatic drugs(bDMARDs).Hence,acupuncture is a possible alternative.Some studies found electroacupuncture to be better than manual acupuncture,though no trials have been conducted in patients with axSpA.This clinical trial aims to evaluate the clinical efficacy,safety,and cost-effectiveness of electroacupuncture compared to manual acupuncture for patients with axSpA.Methods/Design:This randomized controlled trial will recruit 100 patients diagnosed with axSpA,who have active disease despite NSAIDs and bDMARDs.Eligible patients will be randomized to receive either electroacupuncture or manual acupuncture in a 1:1 ratio.All participants will receive standard rheumatologic care in addition to 20 acupuncture sessions.The mean difference in Bath Ankylosing Spondylitis Disease Activity Index score between the 2 groups over 12 weeks will serve as the primary outcome.Secondary outcomes include improvements in other clinical,quality of life,and economic outcomes over 24 weeks.All adverse events will be recorded.Discussion:Results from this trial may provide evidence regarding the clinical effectiveness,safety,and cost-effectiveness of electroacupuncture compared to manual acupuncture for patients with axSpA,and guide implementation into clinical practice.Limitations of this trial include the lack of patient blinding,use of a repeated measures design,and possible variation in acupuncture technique amongst the various Traditional Chinese Medicine practitioners.
文摘对humanether-a-gò-gò related genes(HERG)钾离子通道(钾通道)抑制剂,计算了表征分子组成、电荷分布、拓扑、几何结构及物理化学性质等特征的1559个分子描述符,采用Fischer Score(F-Score)排序过滤和MonteCarlo模拟退火法相结合从中筛选与HERG钾通道抑制剂分类相关的分子描述符.采用支持向量机(SVM)方法,分别以IC50=1.0、10.0μmol·L-1为分类标准,建立了三个分类预测模型.对367个训练集分子,用五重交叉验证,得到正、负样本的平均预测精度分别为84.8%-96.6%、80.7%-97.7%,其总的平均预测精度为87.1%-97.2%,优于其它文献报道结果.对97个外部测试集分子,所建三个模型的总样本预测精度在67.0%-90.1%之间,接近或优于其它文献报道结果.
基金support received from the Scientific Research Grant of Ningbo University(215-432000282)Ningbo Top Talent Project(215-432094250).
文摘In a recent single cell transcriptomic investigation of the peripheral immune responses of the patients with severe COVID-19[1],no substantial expression of pro-inflammatory cytokines has been identified in the peripheral monocytes and lymphocytes,while these peripheral immune cells exhibit phenotypes of heterogeneously expressed interferon-stimulated genes in certain COVID-19 patients.These genes may contribute to the inhibitory response to the viral entry,translation,replication and egress.Questions remain regarding why the peripheral cytokine production is constrained,what additional roles these peripheral immune cells may play in COVID-19 pathophysiology,and which potential targets can be explored for facilitating COVID-19 therapeutics.
基金supported by the Yangtze River Scholar and Innovation Research Team Development Program(Project No.IRT0945)grants from the National Natural Science Foundation of China(NO.30700576,31172225,31272451)State Key Laboratory of Animal Nutrition(Project No.2004DA125184-0807)
文摘In this study,we sought to investigate the expression of the transcription factor E2F1 in chicken pulmonary arterial smooth muscle cells upon hypoxia exposure,as well as the role that E2F1 played in the regulation of cell proliferation.Isolated chicken pulmonary arterial smooth muscle cells were subjected to hypoxia or normoxia for indicated time points.Cell viability,DNA synthesis,cell cycle profile,and expression of E2F1 were analyzed.The results showed that hypoxia promoted cell proliferation and DNA synthesis which was accompanied by an increased S phase entry and upregulation of E2F1 at mRNA and protein levels.Using siRNA technology,we demonstrated that gene inactivation of endogenous E2F1 abolished hypoxia-induced cell proliferation,DNA synthesis,and S phase entry compared with negative siRNA transfected cells.These results suggest that hypoxia-induced proliferation is mediated by inducing E2F1 in chicken pulmonary arterial smooth muscle cells.
基金RO1 CA 094828 to Prof. Ah-Ng Tony Kong and in part by R21 CA133675 to Dr.Li Cai both from the National Institutes of Health(NIH)
文摘The incidence of prostate cancer is rising in the Asia-Pacific region as well as other countries. Androgen-ablation therapy is clinically useful in the androgen-dependent phenotype however, many patients progress to hormone refractory prostate cancer that is difficult to treat and needs newer interventions that are more effective. The objective of this study was to determine functionally-relevant biological networks, to appreciate the potential crosstalk between signaling members, and to identify biomarker signatures in prostate cancer. We used microarray analyses to identify key genes that were upregulated or down regulated at least five-fold in human prostate cancer and constructed canonical interaction networks that are important in prostate cancer through metabolomics analyses. Our prostate cancer network architecture revealed several key biomarkers including ERK1/2, JNK, p38, MEK, PI3 K, NFκB, AP-1, 14-3-3, VEGF, PDGF, Rb, WNT8 A, WNT10 A, CD44, ESR2, FSH and LH. Furthermore, the top ten transcription factors identified by TFBS-association signature analysis in the regulatory elements of co-regulated biomarkers were delineated, which may crosstalk with upstream or downstream genes elicited in our network architecture. Taken together, our results demonstrate that the regulatory interaction networks in prostate cancer provide a universal view of crosstalk between important biomarkers, i.e., key players in the pathogenesis of this disease. This will facilitate more rapid screening of functional biomarkers in early/intermediate drug discovery.