LC-MS/MS method for the determination of an anti-tumor compound C17 in nude mice plasma and its application to a pharmacokinetic study / 药学学报

C17 is an orally available anti-tumor compound inhibiting cancer stem cell (CSC). In this study, a stable, sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated, and was further applied to a pharmacokinetic study in nude mice receiving C17 by gavage. Using propranolol as the internal standard, the plasma samples were pre-treated by precipitation with methanol and analyzed on an Intersil C8-3 column (100 mm × 2.1 mm, 3 μm), and gradient elution was performed with a mobile phase consisting of 0.1% formic acid aqueous and solution mixed up by 90% isopropanol and 10% acetonitrile. The analyte was detected by a triple quadrupole tandem mass spectrometer, and multiple reaction monitoring was employed to select C17 at m/z 439.3/247.1 and propranolol at m/z 260.2/116.2 in the positive ion mode. The calibration curves were linear (r > 0.995) over the range of 5-800 ng·mL-1. The intra- and inter-day precisions and accuracies were 7.42%-13.22% and -8.99%-8.81% respectively. The method was successfully applied to a PK study in nude mice administered with a single oral dose of 50 mg·kg-1 C17, and the PK data were analyzed with non-linear mixed effect model (NONMEM). Two separated absorption peaks were found in the PK curve of C17, and a two-compartment model with two sequential first-order absorption rate was utilized to describe the PK properties of C17, and the model could provide insights into the physiological process and exposure of C17 in nude mice. All animal experiments were in strict accordance with the regulations of the Biomedical Ethics Committee of Peking University.

A prospective cohort study on serum A20 as a prognostic biomarker of aneurysmal subarachnoid hemorrhage / 世界急诊医学杂志（英文）

@#BACKGROUND: A20 may be a neuroprotective factor. Herein, we aimed to investigate whether serum A20 levels were associated with disease severity, delayed cerebral ischemia (DCI), and outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this prospective cohort study containing 112 aSAH patients and 112 controls, serum A20 levels were quantified. At 90 d poststroke, Modified Rankin Scale (MRS) scores ≥3 were defined as a poor outcome. All correlations and associations were assessed using multivariate analysis. RESULTS: Compared with controls, there was a significant elevation of serum A20 levels in patients (median 123.7 pg/mL vs. 25.8 pg/mL; P<0.001). Serum A20 levels were independently correlated with Hunt-Hess scores (β 9.854; 95% confidence interval [95% CI] 2.481-17.227, P=0.009) and modified Fisher scores (β 10.349, 95% CI 1.273-19.424, P=0.026). Independent associations were found between serum A20 levels and poor outcome (odds ratio [OR] 1.015, 95% CI 1.000-1.031, P=0.047) and DCI (OR 1.018, 95% CI 1.001-1.035, P=0.042). Areas under the curve for predicting poor outcome and DCI were 0.771 (95% CI 0.682-0.845) and 0.777 (95% CI 0.688-0.850), respectively. Serum A20 levels ≥128.15 pg/mL predicted poor outcome, with a sensitivity of 73.9% and specificity of 74.2%, and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with 65.5% sensitivity and 89.2% specificity. Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores (both P>0.05). CONCLUSION: Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH, implying that serum A20 may be a potential prognostic biomarker for aSAH.

Curative effect of capreomycin in adjuvant treatment of multidrug-resistant pulmonary tuberculosis and its effect on quality of life and immune function / 中国热带医学

@#Abstract: Objective To investigate the efficacy of capreomycin adjuvant therapy for multidrug-resistant pulmonary tuberculosis (MDR-TB) and its effect on quality of life and immune function. Methods Eighty-eight elderly pulmonary tuberculosis patients admitted to Affiliated Hospital of Hebei University from October 2019 to October 2020 were selected and divided into two groups according to the random number table method. The control group (n=44) used 4-6Am-Mfx（Lfx）-Pto-Cfz-Z-Hhigh-dose-E/5 Mfx（Lfx）-Cfz-Z-E, the research group (n=44) used capreomycin on the basis of the control group. The 6-Minute Walk Test (6MWT) measured value/predicted value and quality of life [36-Item Short Form Health Survey Questionnaire (SF-36)] scores, safety evaluation results, chest CT cavity and lesion absorption rate and sputum culture turned negative were compared between the two groups, and the serum procalcitonin (PCT) expression levels and immune function were detected before and after treatment. Results The 6MWT measured value/predicted value of the research group and control group before the treatment were (0.48±0.11) and (0.64±0.13), which were significantly higher than corresponding (0.51±0.12) and (0.58±0.14) after treatment (t=6.23, 2.520, P<0.05), the measured/expected value of 6MWT increased in both groups after treatment. Compared with the same group before treatment, the SF-36 scores for each dimension increased in both groups after treatment (P<0.01). The expression levels of serum PCT in the research group and control group before the treatment were (0.37±0.09) ng/mL and (0.12±0.03) ng/mL versus (0.36±0.11) ng/mL and (0.21±0.06) ng/mL after treatment (t=17.480, 7.940, P<0.01). Compared with the same group before treatment, serum PCT expression levels decreased in both groups after treatment. Compared with the same group before treatment, CD3+, CD4+ and CD4+/CD8+ were elevated in both groups after treatment (P<0.05 or P<0.01); after treatment, CD3+, CD4+, and CD4+/CD8+ were significantly higher in research group compared to the control group (t=4.21, 8.02, 2.04, P<0.05). The absorption rate of chest CT cavity and lesions and negative rate of sputum culture in the research group were 88.64% (39/44) and 81.82% (36/44), which were significantly higher than corresponding 63.64% (28/44) and 61.36% (27/44) in the control group (P<0.05). Conclusions　Capreomycin can improve the quality of life of MDR-TB patients, extend the 6-minute walking distance, and regulate serum PCT expression levels and immune function, to promote the absorption of chest CT cavity and lesions, and sputum culture to turn negative, and the security is acceptable.

A prospective study on application of human umbilical cord mesenchymal stem cells combined with autologous Meek microskin transplantation in patients with extensive burns / 中华烧伤杂志

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.

Effect of Yangqing Chenfei Formula on epithelial-mesenchymal transition in silicon dioxide-induced silicosis rats / 中国职业医学

@# Objective Yangqing Chenfei Formula - To investigate the effect of (YCF) on epithelial mesenchymal transition (EMT) Methods in lung tissues of silicosis model rats. Specific pathogen free adult male SD rats were randomly divided into control group, model group, tetrandrine group and YCF group, with eight rats in each group. The rats in the model group, tetrandrine group and YCF group were intratracheally injected with 1.00 mL of silica suspension with a mass concentration of 50.0 g/L, and the rats in the control group were given an equal volume of 0.9% sodium chloride solution. On the 15th day after modeling, the tetrandrine group was given tetrandrine at a dose of 27.0 mg/kg body weight, the YCF group was given YCF with a dose of 8.91 g/kg body weight, while both the control group and model group were given 2.00 mL 0.9% sodium chloride solution. Gavage wasperformed twice a day in the morning and evening for 14 days. On day 29 of the experiment, after evaluating the tidal volume, - functional residual volume (FRC) and vital capacity of rats in each group, lung tissues were collected, and hematoxylin eosin staining and Masson staining were performed to examine the histopathological changes, and the fibrosis score was evaluated. - - Hydroxyproline level was detected by colorimetry. The expression of type Ⅰ collagen (COL Ⅰ), type Ⅲ collagen (COL Ⅲ), - - - - - - E cadherin (E Cad), N cadherin (N Cad) and α smooth muscle actin (α SMA) protein was detected by immunohistochemistry. - The expression of epithelial cell adhesion molecule (EpCAM) and fibroblast specific protein 1 (FSP 1) was detected by Results immunofluorescence. The lung structure was intact and the alveolar structure was normal in the control group. The alveolar structure was destroyed, the alveolar wall was thickened, and cellular nodules were observed/n the model group. The lung tissue lesions of rats in the tetrandrine group and YCF group were reduced compared with that in the model group, and there was no difference in the degree of lesions between the two groups. The tidal volume, FRC and vital capacity of rats in model P< - P< group decreased (all 0.05), the relative expression of E Cad protein in lung tissue decreased ( 0.05), the fibrosis score and - - - - the level of hydroxyproline, the protein relative expression of COL Ⅰ, COL Ⅲ, N Cad and α SMA in lung tissue increased (all P< - 0.05), while the fluorescence intensity of EpCAM protein decreased, and that of FSP 1 protein increased compared with the P< control group. The tidal volume, FRC and vital capacity of rats in tetrandrine and YCF groups increased (all 0.05), the fibrosis - - - score and the level of hydroxyproline, the protein relative expression of COL Ⅰ, N Cad and α SMA in lung tissue decreased (all P< - P< 0.05), the relative expression of E Cad protein in lung tissues increased ( 0.05), while the EpCAM protein fluorescence - intensity increased and FSP 1 protein fluorescence intensity decreased compared with the model group. The relative expression - P< Conclusion of N Cad protein in lung tissues of YCF group was lower than that of the tetrandrine group ( 0.05). YCF can - improve the lung function, alleviate collagen deposition in lung tissues, and inhibit the epithelial mesenchymal transition in silicosis model rats, and then attenuates the progression of silicotic fibrosis.

Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein

ABSTRACT Purpose: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. Methods: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). Results: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. Conclusions: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

Vertical transmission of hepatitis B virus: propositions and future directions / 中华医学杂志(英文版)

Chronic hepatitis B virus (HBV) infection due to vertical transmission remains a critical concern with regards to eliminating HBV infection. Implementation of hepatitis B vaccine, the foundation to prevent perinatal and horizontal transmission, has reduced the prevalence of HBV by >80%. In countries where the hepatitis B immune globulin (HBIG) is available, such as China and the United States, the administration of HBIG and hepatitis B vaccine to the infants of mothers who are positive for hepatitis B surface antigen has become a standard practice and is effective in preventing vertical transmission. Accumulating evidence on the efficacy and safety of antiviral prophylaxis during pregnancy indicates the probability of attaining the goal of the World Health Organization to eliminate hepatitis by 2030. In this review, we discuss the transmission routes, diagnostic criteria, and preventive strategies for vertical transmission. A preventive program that includes screening before pregnancy, antiviral prophylaxis during pregnancy, and postpartum immunoprophylaxis provides "perfect strategies" to eliminate vertical transmission. However, there is still a notable gap between "perfect strategies" and real-world application, including insufficient coverage of timely birth dose vaccine and the efficacy and necessity of HBIG, especially in mothers who are negative for hepatitis B envelope antigen. In particular, there is a clear need for a comprehensive long-term safety profile of antiviral prophylaxis. Therefore, feasible and cost-effective preventive strategies need to be determined across regions. Access also needs to be scaled up to meet the demands for prophylaxis and prevalence targets.

Pharmacokinetic/pharmacodynamic modeling of the antitumor action of bispecific CD3/EpCAM antibody M701 in human colorectal cancer xenograft mice / 药学学报

M701 is a bispecific CD3/EpCAM T-cell engager antibody for the treatment of malignant ascites. We developed a population pharmacokinetic/pharmacodynamic (PK/PD) model to quantitatively describe and predict the antitumor effect of M701 in human colorectal cancer xenograft mice. We developed the M701 PK model based on plasma concentration data after i.v. administration. A tumor growth model for human colorectal cancer xenograft was developed to evaluate the antitumor effect of M701. We additionally simulated the inhibitory effect of M701 on tumor volume under different dose regimens based on a PK/PD model. A two-compartment model was developed to predict the PK in human colorectal cancer xenograft mice. The relationship between the M701 concentration and tumor growth inhibition was characterized by a combined Simeoni tumor growth/transit compartment model. The estimated pharmacodynamic parameters were related to the tumor growth characteristics λ0 (0.212 d-1) and λ1 (0.044 7 cm3·d-1), to the drug potency k2 (0.071 5 mL·ng-1·d-1), and to the kinetics of tumor cell death k1 (2×10-5 d-1). A model visual predictive check showed that both the PK model and the tumor growth model closely fit the observed data. Simulated tumor growth after administration of M701 (0.5 mg·kg-1 every 6 days and 0.25 mg·kg-1 every 3 days) could be effectively inhibited. This population PK/PD model of M701 provides insight into the antitumor effect of M701 and supports the further therapeutic development of M701.

Spatial point pattern analysis of hemorrhagic fever with renal syndrome in Jingzhou, Hubei Province, 2017 / 中华疾病控制杂志

Objective To analyze the spatial point pattern distribution characteristics of hemorrhagic fever with renal syndrome (HFRS) in Jingzhou city, Hubei province during the two seasons spring- summer and autumn-winter of 2017, to discuss its high incidence area and reason, and to provide basis for the resource allocation of public health. Methods The analytical data was collected from Infectious Disease Reporting Information System in China, and the spring-summer season was from March to August of 2017, while the autumn-winter was from the September of 2017 to the February of 2018. The Ripley's K-function and kernel density estimation were applied to analyze the spatial point pattern distribution and compare the distribution characteristics of spatial point pattern between the two seasons. Results In 2017, 133 cases of HFRS were reported in Jingzhou city, including the spring- summer and autumn-winter two pick incidences. The strongest aggregation distance was 17.77km in spring-summer season, and 14.40 km in autumn-winter season. The spatial gathering center was located in the north of Jianli County in spring-summer, and it moved to the south of Jiangling County and Shashi District in autumn-winter. Conclusions The key areas for the prevention and control of HFRS in Jingzhou City are Jiangling County, the southern part of Shashi District and the northern part of jianli county. The key groups are the residents of the urban-rural junction in the southern part of Shashi City, residents along the route of large-scale projects, and farmers engaged in agricultural planting or crayfish breeding in the gathering areas.

Heart rate variability in neonates with non-benign tachyarrhythmia / 中国当代儿科杂志

OBJECTIVE@#To study heart rate variability (HRV) in neonates with non-benign tachyarrhythmia (NNTA) and the role of automatic nervous system (ANS) in NNTA.@*METHODS@#The neonates who were admitted to the Department of Neonatology, the Second Xiangya Hospital of Central South University, from January 2010 to June 2018 and were diagnosed with NNTA were enrolled as the NNTA group, and the neonates with sinus rhythm or accidental premature beats on ambulatory electrocardiography were enrolled as the control group. Each group was further subdivided into preterm and term subgroups. A retrospective analysis was performed for their clinical data.@*RESULTS@#A total of 27 NNTA neonates were enrolled, accounting for 0.28% (27/9 632) of all neonates hospitalized during the same period of time, and 53 neonates were enrolled in the control group. Compared with the preterm and term control subgroups, the preterm NNTA and term NNTA subgroups had a significant increase in the standard deviation of average RR interval (P<0.05).@*CONCLUSIONS@#Immature and unbalanced ANS function may play an important role in the development and progression of NNTA.

Protective effect and regulating effect on FXR/SHP gene of electroacupuncture preconditioning on myocardial ischemia-reperfusion injury in rats / 中国针灸

OBJECTIVE@#To explore the protective mechanism of electroacupuncture preconditioning on myocardial ischemia-reperfusion injury in rats.@*METHODS@#A total of 88 SPF-grade Wistar male rats were randomized into a normal group, a sham-operation group, a model group and an electroacupuncture (EA) group, 22 rats in each one. The rats in the normal group received normal diet and no intervention was given for 7 d. The rats in the sham-operation and the model group were bound for 20 min, once a day for 7 d. In the EA group, EA, continuous wave, 2 Hz and 1 mA, was applied at "Neiguan" (PC 6), "Zusanli" (ST 36) and "Guanyuan" (CV 4) for 20 min, once a day for 7 d. In the 8th day, the blood was collected by abdominal aortic method 60 min after intraperitoneal injection of 10% urethane anesthesia by 10 mL/kg in the normal group, and then the tissue of heart was collected. In the model group and the EA group, ligating the left anterior descending coronary artery (LAD) was adopted for 20 min and reperfusion was applied for 40 min, then the samples were collected. The rats in the sham-operation group recevied open-chest operation and no other intervention, the samples were collected in 60 min. Nitro Blue Tetrazolium Chloride monohydrate (NBT) stain was used to detected myocardial infarct size and weight, ELISA was used to measured myocardial injury markers and inflammatory factors (LDH、CK、cTnI), and the fluorescent quantitative PCR method was used to determine the expressions of FXR and SHP gene.@*RESULTS@#①There was no significant difference between the normal group and the sham-operation group in myocardial infarct size and weight (>0.05) .Compared with the normal group, myocardial infarct size and weight were higher in the model group (0.05). Compared with the normal group, the serum contents of LDH、CK、cTnI were higher in the model group (<0.05). Compared with the model group, the serum contents of LDH、CK、cTnI were lower in the EA group (<0.05). ③The expressions of FXR and SHP gene in the model group were higher than those in the normal group (<0.05). The expressions of FXR and SHP gene in the EA group were lower than those in the model group (<0.05).@*CONCLUSION@#Electroacupuncture preconditioning could significantly improve cardiac function of rats with myocardial ischemia-reperfusion, reduce infarct size and inflammatory factors, and down-regulate the expressions of FXR and SHP gene. The protective effect may generate based on regulation of FXR/SHP apoptosis signal pathway.

Film coating process of Xianqu Tablets based on concept of quality by design / 中草药

Objective To investigate the film coating process of Xianqu Tablets based on the concept of quality by design (QbD), and improve the coating efficiency and stability. Methods Using the QbD as an experimental guidance and the Design-Expert software as a tool, the critical quality attributes affecting Xianqu film coating targets were first determined as the response values, and the process parameters of influencing critical quality attributes were selected as the key factors. Then the Box- Behnken design was used to optimize the process parameters and establish a control space. Finally, the design space were verified by measuring the hygroscopicity of Xianqu Tablets. Results The results showed that the design space was optimized to reduce the actual error by 95% confidence interval, the best range of process parameters were obtained as follow: bed temperature 37-43 ℃, coating solution concentration 9%-11%, coating weight gain 4%-5%. After the Xianqu Tablets were coated under the given conditions, the hygroscopicity of Xianqu Tablets, which had a smooth surface and uniform color, was significantly reduced. Conclusion The desired effects by using a reasonable experimental design concept of QbD were efficiently achieved, it provides a predictive model for the film coating process of Xianqu Tablets through constructing reasonable design space, which not only enhances the flexibility and applicability of the coating process, but also ensures the stable product quality.

Effect of low-temperature preparation on the biological characteristics of adipose-derived mesenchymal stem cells / 中国组织工程研究

BACKGROUND: Adipose-derived mesenchymal stem cells (ADSCs) that are manufactured in good manufacturing practice (GMP) clean rooms should be made into stem cell preparations before administration. Low-temperature preparation has many advantages over cryopreservation preparation; however, little is reported on the effect of short-term low-temperature storage on the biological characteristics of stem cells. OBJECTIVE: To evaluate the effect of 24-hour low-temperature storage using multiple electrolytes containing 5% human serum albumin on the biological characteristics of ADSCs.METHODS: ADSCs at passages 3-6 at a concentration of 5×109/L were suspended in multiple electrolytes containing 5% human serum albumin. Cell suspension was transferred into cryogenic vials, and then these vials were placed in a cold chain shipping box for 2-8 ℃ low-temperature storage for 24 hours. Cell morphology, adhesion ability, cell viability, cell diameters and cell immunophenotyping before and after the storage were observed. RESULTS AND CONCLUSION: (1) After low-temperature storage of ADSCs for 24 hours, the number of dead cells increased. Although cell viability decreased significantly, it was still higher than 80%. Cell diameters of living cells increased significantly. (2) After low-temperature storage of ADSCs for 24 hours, few cells which were circle-shaped lost adhesion ability, and most cells could adherently grow, with the spindle-shaped morphology similar to the cells before preservation. (3) After low-temperature storage of ADSCs for 24 hours, HLA-DR, CD34 and CD45 were negatively expressed with a positive rate lower than 2%; CD29, CD73 and CD105 were positively expressed with a positive rate higher than 95%. However, the cell cluster was clearly divided into two parts after the preservation. Cells with enlarged diameters moved right in the FSC/SSC dot-plot. These results show that low-temperature preparation storage has no significant effect on the stemness of ADSCs, such as adhesion ability, cell viability and cell immunophenotype.

Analysis method based on the gene-panel sequencing data / 上海交通大学学报（医学版）

Objective· To establish an integrative method for the gene-panel sequencing data to automatically complete quality control, detection of gene mutation and visualization. Methods · Integrate several methods, e.g. FastQC, preprocessing and information of sequences (Prinseq) to develop an R package that can be used to visualize and control the quality of the raw sequencing reads and final mutations result. The sequencing reads mapped against to the reference genome using Burrows-Wheeler Alignment Tool (BWA)/Torrent Mapping Alignment Program (TMAP). Lofreq, Varscan2, the Genome Analysis Toolkit (GATK) and Torrent Variant Caller (TVC) were used to detect gene mutation and get the variant call format (VCF) format file. Annotate the gene mutation sites using Annovar. Results · Thirty-six cases of acute myeloid leukemia sequencing from Ion Torrent Personal Genome Machine (PGM) platform were passed by this analysis tool.Ten mutation sites of 2 demo data were found in DNMT3A,TET2,JAK2,PHF6,ASXL1,NPM1 and CEBPA which were validated by sanger sequencing. Conclusion · The analysis method that integrated and developed several tools for gene-panel sequencing data analysis can accomplish the gene-panel sequencing data analysis effectively. Besides, it can reduce the false positive ratio and improve the sensitivity of gene mutation detection that provides support for the analysis of gene-panel sequencing data.

Fluorous Solid-Phase Extraction Assisted New Methods for Analysis of Biomolecules with Mass Spectrometry / 分析化学

Fluorous solid-phase extraction ( FSPE ) is a solid-phase extraction technique based on fluorous affinity between perfluorous compounds. It requires derivatization on analytes with fluorous tags and further specific separation accomplished by perfluorinated solid phase. This technique has extended to various research fields with broad application including organic synthesize, catalysis, chemical and biological analysis. Recently, owing to its good compatibility with mass spectrometry, new analytic techniques relying on FSPE coupled to biological mass spectrometry have received wide attention. This review briefly introduced the principle of FSPE and emphasized on its application for the analysis of biomolecules with mass spectrometry, as well as its outlook of future development.

Population pharmacokinetics and its application in new drug research / 药学学报

Population pharmacokinetics is an emerging discipline developed from the combination of classical pharmacokinetic compartment model and statistics principles, which has been received more and more attention in recent years. Population pharmacokinetics plays important roles in all stages of new drug research. In the early preclinical phase, population pharmacokinetic analysis can help to achieve the preliminary prediction of parameters from animal to human, optimize clinical trial designs, and shorten the time required for new drugs from laboratory to clinical trials. In clinical trials and applications stage, population pharmacokinetic research can help researchers investigate the related covariates that affecting pharmacokinetic behavior of patients comprehensively, and find potential drug-drug interactions in clinical. In addition, population pharmacokinetics has a unique advantage in pediatric drug development due to its strong analysis ability of sparse data. This paper provides a summary on the history and methods of population pharmacokinetics, and the application in new drug discovery and development.

Using the cumulative odds Logit model to explore the application of the questionnaire derived from PANSS / 药学学报

Currently, aripiprazole, olanzapine and risperidone are three anti-psychiatry agents commonly used in the treatment of schizophrenia. Although the efficacy of these drugs is good, schizophrenia cannot be completely cured yet. Patients need long-term medication. The family members of patients may play a key role to understand the disease status of patients after patient discharge from hospital. PANSS is a commonly used scale in the clinic to evaluate the disease status and drug effects of anti-psychiatry agents. It was professionally written, and is not user friendly to amateurs. In the previous study, we developed a questionnaire for patient's family members to monitor the disease status. In this study, we explored the correlations between the results of questionnaire and 5 kinds of disease state corresponding to different PANSS score interval using the cumulative odds Logit model. The final results show that the model had relatively good prediction ability for aripiprazole, olanzapine and risperidone, suggesting that the questionnaire has an extensive prospect of clinical applications.

The impact of mindfulness on nurses' professional quality of life / 中国实用护理杂志

Objective To provide a scientific basis for nursing managers to promote the professional quality of life of nurses.Methods Totally 373 nurses from three general hospitals in Jinan by convenience sampling technique were recruited and assessed with the Professional Quality of Life Scale Version 5 (ProQOL-V) and the Five Facet Mindfulness Questionnaire.The relationship between professional quality of life and mindfulness was analyzed.Results The average score of compassion satisfaction was (29.71±6.61) points,the average score of compassion fatigue was (52.82±8.04) points,which were in the middle level of them.Compassion satisfaction was correlated with mindfulness,observation,description,non-reactiveness and non-judgment (P ＜ 0.05).Compassion fatigue was correlated with mindfulness,observation,awareness of the action,non-reactiveness and non-judgment (P ＜ 0.05).Multiple regression analysis showed that the three dimensions (observation,non-reactiveness and non-judgment) of mindfulness could predict 15％ variance of compassion satisfaction and the three dimensions (observation,awareness of the action and non-judgment) of mindfulness could predict 34.1％ variance of compassion fatigue after controlling demographic variables.Conclusions Mindfulness can effectively predict nurses' professional quality of life.Nursing managers should take some mindfulness training in order to improve their professional quality of life.

Treatment effect of Qi ming granule in preventing macular edema after phacoemulsification in diabetes / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the clinical therapeutic efficacy of the Qi ming granule for macular edema ( ME ) in diabetic patients after phacoemulsification. METHODS:In this was a prospective clinical comparison study, 57 diabetic patients ( 76 eyes ) who underwent phacoemulsification were recruited and divided into two groups:treatment group (34 eyes) and control group (42 eyes) . All the patients in treatment group were given oral administration Qi ming granule (4. 5g, tid) and vitamin C ( 0. 1g, tid ) for 6mo postoperatively, while vitamin C ( 0.1g, tid ) for the controls. General clinical examinations, including blood glucose and glycated hemoglobin, as well as comprehensive standardized ophthalmic examinations were performed. Optical coherence tomography ( OCT ) were used to detect macular edema incidence and measure central field retinal thickness. RESULTS: No significant difference was found in the levels of blood glucose, glycated hemoglobin, course of disease, and macular thickness between the two groups during the initial visits. At the 6th month, 2 eyes ( 6%) eyes had clinically apparent macular edema in treatment group, while 6 ( 14%) eyes had clinically apparent macular edema in control group (P=0. 285). The central subfield retinal thickness values were significantly lower in the treatment group ( 211. 76±41. 21μm ) than those in control group (278. 36±48. 94μm) (P CONCLUSION:Qi ming granule can significantly reduce the incidences of macular edema and suppresses increasing retinal thickening after phacoemulsification in patients with diabetes mellitus.

Effect of overexpression of hypoxia-inducible factor-1α induced by hyperoxia in vivo in LNCaP tumors on tumor growth rate

OBJECTIVE@#To study effect of overexpression of hypoxia-inducible factor-1α induced by hyperoxia in vivo in LNCaP tumors on tumor growth rate.@*METHODS@#The prostate cancer LNCaP cells were inoculated in the abdomen of mice. All the mice were randomly placed in the gas chamber with different oxygen content. The groups were divided as follows: twelve mice in hypoxia group, sixteen mice in normoxia group, ten mice in hyperoxia group. After 28 d of treatment, the mice were weighed, the blood samples were taken from the left ventricle, and the tumor was isolated and weighed. Tumor growth, angiogenesis and vascularization, HIF-1α expression and intracellular signal transduction molecules expression in each group of xenografts were detected and analyzed by using Western blotting and immunofluorescence and determination of hemoglobin.@*RESULTS@#Comparison of the growth of xenografts in each group showed that, the xenografts growth of hypoxia group was more quickly than that of normoxia group. The difference was statistically significant (P = 0.004). The difference in xenografts growth between hyperoxia group compared and normoxia group was not statistically significant (P > 0.05). The expressions of HIF-1α, VEGF and VEGF-R of xenografts in hyperoxia group were significantly higher than those of normoxia group (P < 0.05). The expression of HIF-1α of xenografts in hypoxia group and normoxia group were similar. The blood growth rate of xenografts in hypoxia group (170%) was significantly higher than that of normoxia group (40%) (P < 0.05). The expression of Nrf2 of xenografts in hyperoxia group was significantly higher than that of normoxia group (P < 0.05).@*CONCLUSIONS@#When hyperoxia induces the overexpression of HIF-1α in LNCaP tumor, it will not affect tumor growth. It provides a new ideas and theoretical basis for the clinical treatment of prostate cancer.