Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively characterizing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear timeinvariant dynamical model.It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

Paricalcitol in hemodialysis patients with secondary hyperparathyroidism and its potential benefits

BACKGROUND Secondary hyperparathyroidism(SHPT)is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients.SHPT can increase bone fragility and calcification of blood vessels and soft tissues,which greatly increases the risk of death.AIM To discuss the outcome,safety and other potential benefits of paricalcitol injection in hemodialysis patients with SHPT.METHODS We recruited 40 patients who received hemodialysis at our hospital for chronic renal failure with SHPT between March and December 2019.They received paricalcitol injection for 24 wk(starting dose,0.06–0.08μg/kg),three times per week.They were followed up at the baseline(week 0),week 4,week 12 and week 24.The primary outcome indicator was the percentage of patients with a>30%decrease in intact parathyroid hormone(iPTH)levels at week 24 compared with the baseline.The secondary outcome indicators included percentage decrease in iPTH levels at week 24,standard-reaching rate of iPTH(percentage of patients with iPTH down to 130–585 pg/mL),changes in serum levels of calcium(Ca),phosphate(P),Ca×P product,alkaline phosphatase(ALP),creatinine(Cre),hemoglobin(Hb),and C-reactive protein(CRP),and incidence of adverse events(AEs).RESULTS After 24 wk of treatment,iPTH levels decreased significantly(598.88±381.29 pg/mL vs 888.84±376.88 pg/mL,P<0.05).More than 30%decrease of iPTH was found in 21 of 36(58.33%)patients.The average decrease in iPTH levels was 32.16±4.33%;the standard-reaching rate of iPTH levels was 66.67%(24/36);and ALP levels decreased significantly compared with the baseline(113.72±41.73 IU/L vs 133.45±56.86 IU/L)(t=2.798,P<0.05).There were no significant differences in the serum levels of calcium,Hb,Cre and CRP compared with the baseline(P>0.05).After 24 wk of treatment,serum P levels decreased compared with the baseline(1.91±0.40 mmol/L vs 2.16±0.66 mmol/L)(t=2.830,P<0.05).Ca×P product decreased significantly compared with the baseline(56.38±13.22 mg2/dL2 vs 63.97±20.30 mg2/dL2)(t=2.717,P<0.05).No serious adverse events occurred.CONCLUSION Paricalcitol was a safe and effective treatment for hemodialysis patients with SHPT.It decreased serum levels of iPTH,ALP and P and maintained stability of serum Ca levels.

Management of functional dyspepsia: Unsolved problems and new perspectives

The common characteristic criteria of all functional gastrointestinal(GI)disorders are the persistence and recurrence of variable gastrointestinal symptoms that cannot be explained by any structural or biochemical abnormalities. Functional dyspepsia (FD) represents one of the important GI disorders in Western countries because of its remarkably high prevalence in general population and its impact on quality of life. Due to its dependence on both subjective determinants and diverse country-specific circumstances, the definition and management strategies of FD are still variably stated.Clinical trials with several drug classes (e.g., proton pump inhibitors, H2-blockers, prokinetic drugs) have been performed frequently without validated diseasespecific test instruments for the outcome measurements.Therefore, the interpretation of such trials remains difficult and controversial with respect to comparability and evaluation of drug efficacy, and definite conclusions can be drawn neither for diagnostic management nor for efficacious drug therapy so far. In view of these unsolved problems, guidelines both on the clinical management of FD and on the performance of clinical trials are needed. In recent years, increasing research work has been done in this area. Clinical trials conducted in adequately diagnosed patients that provided validated outcome measurements may result in better insights leading to more effective treatment strategies.Encouraging perspectives have been recently performed by methodologically well-designed treatment studies with herbal drug preparations. Herbal drugs, given their proven efficacy in clinical trials, offer a safe therapeutic alternative in the treatment of FD which is often favored by both patients and physicians. A fixed combination of peppermint oil and caraway oil in patients suffering from FD could be proven effective by well-designed clinical trials.

Saturation Effects on Immunopathogenic Mechanism of Psoriasis:A theoretical approach

Psoriasis vulgaris is a common chronic autoimmune inflammatory skin disease characterized by T-cell mediated hyper proliferation of keratinocytes.This type of skin disorder is characterized by macroscopic and also microscopic skin alterations.It was observed that,psoriatic lesions are sharply demarcated,red and slightly raised lesions along with silver whitish scales.The striking feature of T-cell mediated chronic psoriatic lesions are the epidermal infiltration of predominantly oligoclonal CD8^+T-cells and probably also of CD4^+T-cells in the dermis.In this research article we proposed a mathematical model for the chronic disease,psoriasis,consisting a set of differential equations, involving T-Lymphocytes cells,Dendritic cells and the epidermal Keratinocytes,incorporating half saturation constant through the T lymphocyte cells and also in that sense,it has been infiltrated in the activation process of keratinocytes in the course of the plaque of psoriasis.Cell biological research on psoriasis has been established the suppression of epidermal T-cell density.Here we are interested to know how the cell biological system changes for introducing the half saturation constant in presence of suppression taking place DCs on the model dynamics.Our analytical and numerical result reveal that due to control effect,the macrophages population density does not impede for the interaction between T-cell and keratinocytes.T-cell and keratinocyte population ultimately become stable after a certain period of time span.

我国非国家组织药品集中采购模式比较

目的比较分析我国各省市的药品集中采购方案及相关政策,探讨各地非国家组织药品集中采购模式的特点。方法围绕采购内容、采购规则等比较分析各地的非国家组织药品集中采购模式的特点,以及采购内容、采购环境、采购规则之间的内在关系。结果我国目前的非国家组织药品集中采购模式可划分为药品集中采购组织(group purchasing organization,GPO)、非过评仿制药带量采购、专项药品带量采购、带量议价以及分类采购框架下的带量采购5种。我国非国家组织药品集中采购的特点是分品种、分批次,以政府主导为主,执行机构主要为医疗保障局。结论目前,各地的非国家组织药品集中采购仅覆盖了部分品种的药品,对非过评仿制药进行集中采购是未来的重要趋势,建立公平、科学的质量分组规则是非国家组织药品集中采购亟待解决的重要技术问题。

Study on Effect of Chinese Herbal Medicine for Enhancing Therapeutic Efficacy on Refractory Drug Resistant Leukemia

The so-called multidrug resistance （MDR） of leukemic cells means the cross resistance of leukemic cells against multiple anti-tumor agents with different constitution and acting mechanism, which takes place simultaneous after resistance to a single contacted drug has been produced. Tumor cells with MDR would now show a low sensitivity to anti-tumor agents, making chemotherapy ineffective or of little effect. Moreover, MDR is one of the pathogenetic factors for inducing refractory leukemia.

Regulatory evaluation of efficacy and safety of new drugs in China

Accessibility, availability, and rational use of medicines are widely recognized priorities for guaranteeing equity in health care. Commercial pressure can twist health policy if pharmaceutical companies are allowed to promote and impose their products beyond clear public-health interest. National regulatory

Efficacy of praziquantel in the treatment of Schistosoma haematobium infection among school-age children in rural communities of Abeokuta, Nigeria

Background:Chemotherapy with praziquantel(PZQ)has been the cornerstone of schistosomiasis control over the last two decades.Being the only available drug for the treatment of over 200 million people worldwide,continuous monitoring of PZQ efficacy under the pressure of widespread use is therefore advocated.Methods:The efficacy of taking two doses of oral PZQ for the treatment of Schistosoma haematobium was examined among school children in Nigeria.Urine specimens were collected from 350 school children and examined using the filtration technique.Blood was collected for packed cell volume(PCV)estimation,and the weight and height of each child were estimated.S.haematobium egg positive pupils were treated with two oral doses of PZQ at 40 mg/kg with a four-week interval in between.Drug efficacy was determined based on the egg reduction rate(ERR).Results:Among 350 school children,245(70.0%)-of which 132 were males and 113 were females,with an age range of 4 to 15 years-were diagnosed with S.haematobium.All the 245 infected children received a single oral dose of 40 mg/kg PZQ twice with a four-week interval in between and were followed up for 12 weeks.At four,eight and twelve weeks post treatment,the ERR was 57.1%,77.6%and 100%,respectively.The ERR was significantly higher among the children with a light infection compared to those with a heavy infection.One hundred and twenty-one children were egg negative at four weeks post treatment,among which 1(6.3)and 120(52.4%)had heavy and light infections,respectively.Following the second round of treatment,the cure rate at eight weeks and twelve weeks was 85.3%and 100%,respectively.Conclusion:This study demonstrated the efficacy of taking two doses of oral PZQ for the treatment of urinary schistosomiasis among school children in Nigeria.

Omics in schizophrenia:current progress and future directions of antipsychotic treatments

Schizophrenia is a life-long,complex mental illness that still lacks satisfactory treatments.In recent years,increasing numbers of candidate biomarkers of schizophrenia occurrences and drug responses to schizophrenia therapies have been successfully identified by many omics studies.This review discusses the latest discoveries regarding effective drug targets and relevant drug classifications in schizophrenia.It also assesses our understanding of biomarkers for drug efficacy and adverse drug reactions in current schizophrenia treatments using omics technologies.Future applications in clinical practice have been proposed based on these new findings,and are now considered highly promising strategies to better treat schizophrenia.Finally,we explore several novel approaches that aim to reveal additional genetic signatures of schizophrenia using multi-omics data,which are hoped to improve the diagnosis and treatment of this illness in the future.

Simultaneous and Spatial Quantification of Telomerase Activity and DNA Methylation in Living Cells by a Deformable Satellite Nanocapsule

Telomerase plays an essential role in many biological processes.DNA methylation regulates the expression of many genes,including telomerase.Here,we propose a deformable satellite nanocapsule fluorescein isothiocyanate(FITC)-hollowbowl mesoporous organicsilica@gold nanoparticles-methyl-CpG-binding protein 2(MECP 2)-silver nanoclusters(FHBMO@AMA),for simultaneous quantitative detection of both cytoplasmic telomerase activity and the degree of DNA methylation.This strategy enabled spatial-based detection in cells.The total cytoplasmic telomerase activity was detected by fluorescence energy resonance transfer(FRET)between FHBMO and gold nanoparticles(Au NPs),while the DNA methylation in the nucleus was detected by enhanced fluorescence of silver nanoclusters(Ag NCs).Furthermore,FHBMO@AMA could intuitively distinguish between the differences in telomerase expression in cells during the DNA synthesis period at the mitotic phase(S/M)of the cell cycle.Interestingly,the ratio of the two detections(telomerase activity/DNA methylation)significantly correlated with the efficacy of anticancer drugs.At the same time,there was no apparent linear relationship between any single detection target and the efficacy of the anticancer drugs.Therefore,based on the relationship between telomerase activity and DNA methylation,our newly developed approach serves as new and feasible method for evaluating the efficacy of anticancer drugs,thereby,extending the technology toolbox for precision in medical and pharmaceutical analysis of drug potency.