A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers / 药物分析学报

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid / 药物分析学报

Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of pneumonia.However,the pharmacological com-ponents of GC for pneumonia treatment are rarely explored.Gan An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many years.Therefore,GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia.We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days.Using the intelligent mass spectrometry data-processing technologies to analyze the meta-bolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in urine.After analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective components.The experimental results based on two animal pneumonia models and the in-flammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo.The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS.Thus,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.

The standard adapt-to-shape workflow for prostate cancer on MR-linac—Experience from National Cancer Institute/Cancer Hospital, Chinese Academy of Medical Sciences / 中华放射肿瘤学杂志

With aligned MR registration, the MR-Linac provides superior soft tissue resolution for prostate cancer. No fiducial markers or electromagnetic transponders insertion is needed to guarantee high-precision radiotherapy. The highly-recommended Adapt-To-Shape (ATS) workflow can resolve all the problems encountered during prostate cancer radiotherapy, including prostate volume changes and adjacent organs motion, both inter-fractionally and intra-fractionally. With all the above advantages, MR-Linac performs outstandingly than conventional linac in prostate cancer RT delivery, and probably helps us to reduce the CTV-PTV margin safely in the near future. Nevertheless, it is difficult to implement the ATS workflow in clinical practice. In this article, the standard ATS workflow for prostate cancer was summarized based on our own experience.

Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.

Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed

An automatic VMAT planning method for primary liver cancer radiotherapy based on predicting the feasibility DVH / 中华放射肿瘤学杂志

Objective:To establish an automatic planning method using volumetric-modulated arc therapy (VMAT) for primary liver cancer (PLC) radiotherapy based on predicting the feasibility dose-volume histogram (DVH) and evaluate its performance.Methods:Ten patients with PLC were randomly chosen in this retrospective study. Pinnacle Auto-Planning was used to design the VMAT automatic plan, and the feasibility DVH curve was obtained through the PlanIQ dose prediction, and the initial optimization objectives of the automatic plan were set according to the displayed feasible objectives interval. The plans were accessed according to dosimetric parameters of the planning target volume and organs at risk as well as the monitor units. All patients′ automatic plans were compared with clinically accepted manual plans by using the paired t-test. Results:There was no significant difference of the planning target volume D 2%, D 98%, D mean or homogeneity index between the automatic and manual plans ((58.55±2.81) Gy vs.(57.98±4.17) Gy, (47.15±1.58) Gy vs.(47.82±1.38) Gy, (53.14±0.95) Gy vs.(53.44±1.67) Gy and 1.15±0.05 vs. 1.14±0.07, all P>0.05). The planning target volume conformity index of the manual plan was slightly higher than that of the automatic plan (0.77±0.08 vs. 0.69±0.06, P<0.05). The mean doses of normal liver, V 30Gy, V 20Gy, V 10Gy, V 5Gy and V< 5Gy of the automatic plan were significantly better than those of the manual plan ((26.68±11.13)% vs.(28.00±10.95)%, (29.96±11.50)% vs.(31.89±11.51)%, (34.88±11.51)% vs.(38.66±11.67)%, (45.38±12.40)% vs.(50.74±13.56)%, and (628.52±191.80) cm 3vs.(563.15±188.39) cm 3, all P<0.05). The mean doses of the small intestine, the duodenum, and the heart, as well as lung V 10 of the automatic plan were significantly less than those of the manual plan ((1.83±2.17) Gy vs.(2.37±2.81) Gy, (9.15±9.36) Gy vs.(11.18±10.49) Gy, and (5.44±3.10) Gy vs.(6.25±3.26) Gy, as well as (12.70±7.08)% vs.(14.47±8.11)%, all P<0.05). Monitor units did not significantly differ between two plans ((710.67±163.72) MU vs.(707.53±155.89) MU, P>0.05). Conclusions:The automatic planning method using VMAT for PLC radiotherapy based on predicting the feasibility DVH enhances the quality for PLC plans, especially in terms of normal liver sparing. Besides, it also has advantages for the protection of the intestine, whole lung and heart.

Effect of radiotherapy on ovarian function in patients undergoing radical surgery for cervical cancer / 中华放射肿瘤学杂志

Objective@#The correlation between dosimetric parameters of transposed ovary and different clinical ovarian functional status was assessed in young patients with cervical cancer who needed adjuvant radiotherapy after radical resection of the ⅠB1-ⅡA2 phase of preserved and transposed ovaries.@*Methods@#The function of transposed ovary and relevant clinical symptoms in 86 patients before and 2 years after treatment between 2015 and 2017 were retrospectively analyzed, and the correlation between the dosimetric parameters and functional status of transposed ovaries during radiotherapy was evaluated. Different in vitro measures were adopted to protect the transposed ovaries during postoperative radiotherapy including 68 cases of IMRT or VMAT and 18 cases of two-dimensional and other central radiotherapy.@*Results@#The nearest distance between ovary and PTV was negatively correlated with the ovarian dose ≥V5 Gy (P=0.025). V8 Gy and Dmean were positively correlated with FSH after treatment (P=0.011, 0.020). The larger the volume of V8 Gy and the large Dmean, the higher the FSH, the worse the ovarian function. In two-dimensional technology, the ovarian dose ≥V5 Gy was significantly lower than that in three-dimensional technique. The average age of those with normal ovarian function after treatment was 33.4 years, whereas the average age of women with ovarian failure was 39.6 years (P=0.007). The number of preserved ovaries and whether synchronous chemotherapy was delivered were similar in patients with different ovarian status, which were correlated with the levels of FSH and E2 (Estradiol) before treatment, that is, the higher the level of FSH before treatment, the lower the E2 of ovarian FSH after treatment, and the higher the level of FSH after treatment, the lower the level of ovarian E2. Patients who retained their ovaries before treatment but suffered from ovarian failure received neoadjuvant chemotherapy with a slightly higher age.@*Conclusions@#Age, V8 Gy and Dmean of the transposed ovary, the shortest distance between transposed ovary and PTV, whether neoadjuvant chemotherapy was delivered before surgery and radiotherapy technique affect the protection of the function of transposed ovary.

Effect of radiotherapy on ovarian function in patients undergoing radical surgery for cervical cancer / 中华放射肿瘤学杂志

Objective The correlation between dosimetric parameters of transposed ovary and different clinical ovarian functional status was assessed in young patients with cervical cancer who needed adjuvant radiotherapy after radical resection of the Ⅰ B1-Ⅱ A2 phase of preserved and transposed ovaries.Methods The function of transposed ovary and relevant clinical symptoms in 86 patients before and 2 years after treatment between 2015 and 2017 were retrospectively analyzed,and the correlation between the dosimetric parameters and functional status of transposed ovaries during radiotherapy was evaluated.Different in vitro measures were adopted to protect the transposed ovaries during postoperative radiotherapy including 68 cases of IMRT or VMAT and 18 cases of two-dimensional and other central radiotherapy.Results The nearest distance between ovary and PTV was negatively correlated with the ovarian dose ≥ V5 Gy (P=0.025).Vs Gy and D were positively correlated with FSH after treatment (P=0.011,0.020).The larger the volume of Vs Gy and the large D the higher the FSH,the worse the ovarian function.In two-dimensional technology,the ovarian dose ≥ V5 Gy was significantly lower than that in three-dimensional technique.The average age of those with normal ovarian function after treatment was 33.4 years,whereas the average age of women with ovarian failure was 39.6 years (P=0.007).The number of preserved ovaries and whether synchronous chemotherapy was delivered were similar in patients with different ovarian status,which were correlated with the levels of FSH and E2 (Estradiol) before treatment,that is,the higher the level of FSH before treatment,the lower the E2 of ovarian FSH after treatment,and the higher the level of FSH after treatment,the lower the level of ovarian E2.Patients who retained their ovaries before treatment but suffered from ovarian failure received neoadjuvant chemotherapy with a slightly higher age.Conclusions Age,V8 Gy and D of the transposed ovary,the shortest distance between transposed ovary and PTV,whether neoadjuvant chemotherapy was delivered before surgery and radiotherapy technique affect the protection of the function of transposed ovary.

A method of describing the characteristics of flattening filter-free photon beam / 中华放射肿瘤学杂志

Objective To establish a novel method of describing the off-axis ratio (OAR) characteristics of the flattening filter-free (FFF) beam.Methods The OAR curves at a depth of 1.5,5,10 and 20 cm were measured for Varian Edge,Elekta VersaHD and Tomotherapy using the water tank.The second derivatives of the OAR in the positive and negative directions were calculated.The center of the line connecting the maximum and minimum second derivatives was defined as the field edge.The distance between the left and right field edges was defined as the dosimetric field size.The OAR curve within the 80％ of dosimetric field size was fitted using the gaussian function and the fitting parameters were adopted to describe the shape of OAR.Results The calculated field size error was less than 0.11 cm and the central axis position error was less than 0.05 cm.The fitting correlation coefficient was greater than O.998.The fitting maximum error of OAR curve did not significantly alter with the depth,whereas slightly increased over the increased field size.The maximum error for a field size of 10,20,30 and 40 cm was 0.49％,0.67％,1.25％ and 2.52％,respectively.Conclusions A method which can independently and accurately describe the OAR characteristics of FFF photon beam is established for the first time,which can calculate the field size of FFF beam and fit the OAR curve of FFF beam using the gaussian function.

Effect evaluation of meticulous nursing management in patients with recurrent acute pancreatitis / 中华胰腺病杂志

Objective To evaluate the application effect of nursing management in the follow-up of patients with recurrent acute pancreatitis (RAP).Methods During January 2016 and January 2017,the clinical data of RAP patients admitted in Changhai Hospital of Navy Medical University was collected.Selfcontrol method was used to establish a prospective cohort study.Meticulous nursing management mode was applied to follow up the patients for 12 months.Patients' compliance,symptom improvement,patients' satisfaction and other markers are evaluated using questionnaires to assess the effect of meticulous nursing management once every 3 months.The data over 12 months were collected.Results Sixty-four RAP patients were finally included.The average follow-up period was 19.7 ±3.4 months.Before admission,the average disease course was(4.21 ± 3.95) years.30 patients (46.9％)had a history of drinking;33 patients (51.6％)had a history of smoking.25 patients (39.1％) had abnormal blood lipid and 40 patients (62.5％) had the dietary habit of high lipid and high protein.The etiology included alcohol (n =10,15.6％),high lipid (n =7,10.9％),biliary diseases (n =1,1.6％),idiopathic causes (n =46,71.9％) and abnormal BMI (n =49,76.6％).After the meticulous nursing management,the frequency of pancreatitis,VAS score of pain and alcohol intake situation was obviously lower than before intervention [(0.50 ±0.85) times/year vs(2.77 ±2.52)times/year;(1.84 ±2.54)vs(6.47 ±2.15);2 cases vs 30 cases].The number of patients who took medicine on time and BMI were obviously decreased[(52 cases vs 13 cases;(23.26 ± 3.85) kg/m2 vs (21.92 ± 4.27)kg/m2)],and the differences were statistically significant (P ＜0.01).Patients' satisfaction with this nursing model was 4.90 ± 0.56.Conclusions The implementation of the new meticulous nursing management model can effectively alleviate patient's symptom condition and improve the compliance behavior and life quality of the patients.

Investigation of the nursing interns'knowledge about emergency medications / 中国实用护理杂志

Objective To check the nursing interns′ knowledge about emergency medications. Methods A self-designed questionnaire was used to investigate the knowledge of emergency medications (including dosage, indications and usage) and learning demands in 258 nursing interns. Results The mean score of all students was 18.06 ± 3.35,accounting for 82.2%(212/258)nursing interns expected to obtain the knowledge by the clinical teachers.Both different education backgrounds and training periods didn′t have significant influence on the scores of emergency medications. There were significant differences in total scores among practice nurses from different areas (F=2.87, P<0.05). Conclusion Generally,the nursing interns are not qualified enough to know emergency medications.We should focus on training nursing interns in pharmacological knowledge and the ability of their knowledge management cognition.

Research in predialysis education for dialysis timing in patients with end-stage renal disease / 中国实用护理杂志

Objective To investigate the predialysis education on dialysis timing of patients with end-stage renal disease (ESRD). Methods 129 patients with chronic renal failure (CRF) and serum creatinine(Scr)＞442μmol/L, endogenous creatinine clearance rate (Ccr)＜20 ml/min were randomly divided into the experimental group(70 cases) and the control group(59 cases), the experimental group received predialysis education, the control group received routine care.The basic situation, dialysis timing, depression and quality of life on the 6th,12th months after dialysis were assessed. Results There was no significant difference in age, sex, education background, health care payment manners, employment, serum creatinine, endogenous creatinine clearance rate before education.For the timing of dialysis, Ccr for the experimental group was (9.49 ± 0.77)ml/min, Ccr for the control group was (4.54 ±1.79) ml/min,the difference was significant, depression and quality of life between two groups after 6,12 months of dialysis was also statistically different. Conclusions Strengthening predialysis education is conducive to a timely start of dialysis and can effectively improve the quality of life in patients with ESRD.