Efficacy and safety analysis of anlotinib in the treatment of distant metastatic radioactive iodine-refractory differentiated thyroid cancer / 中华核医学与分子影像杂志

Objective:To investigate the efficacy and safety of anlotinib in distant metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC).Methods:Retrospective analysis was performed on 17 patients with distant metastatic RAIR-DTC (6 males, 11 females, age: 57.0(45.5, 63.0) years) from Affiliated Hospital of Qingdao University between October 2018 and February 2023, including 13 patients receiving first-line treatment and 4 patients receiving second-line treatment with anlotinib. The changes of serum thyroglobulin (Tg) during the treatment of anlotinib, the changes of maximum diameter of the target lesion at the last follow-up compared with the diameter at baseline, the imaging efficacy, and treatment-related adverse events were analyzed. The serological and imaging effects of the first-line treatment group and the second-line treatment group were compared. The Fisher exact test was used to analyze the differences between groups.Results:The follow-up time of 17 patients was 17.3(9.5, 21.4) months, and the objective response rate (ORR) and disease control rate (DCR) were 7/17 and 16/17, respectively. There were no significant differences of ORR (6/13 vs 1/4; P=0.603) and DCR (13/13 vs 3/4; P=0.235) between the first-line and second-line treatment groups. The change rates of serum Tg at 3, 6 weeks and the last follow-up were -30.2%(-61.2%, -15.5%), -64.8%(-90.6%, -32.3%), and -85.8%(-96.1%, -50.7%), respectively. At the last follow-up, the change rate of maximum diameter of target lesions was -20.0%(-45.0%, -5.2%). The incidence of treatment-related adverse reactions was 14/17, and 2 patients (2/17) had grade 3 or above adverse reactions. Conclusion:Anlotinib shows superior efficacy with tolerable toxicity in the first-line treatment of distant metastatic RAIR-DTC, and hopefully plays an important role in second-line treatment for RAIR-DTC resistant to sorafenib.

Predictive value of cellular immune status before initial 131I treatment for treatment response in young and middle-aged patients with papillary thyroid cancer / 中华核医学与分子影像杂志

Objective:To investigate the value of cellular immune status before initial 131I treatment for predicting treatment response in young and middle-aged patients with papillary thyroid cancer (PTC). Methods:From March 2018 to April 2019, 150 young and middle-aged patients with PTC (46 males, 104 females, age (40.0±9.8) years) who underwent total thyroidectomy and neck lymph node dissection in the Affiliated Hospital of Qingdao University were enrolled retrospectively. All patients underwent radioablation 1-2 months after operation, and the serum lymphocyte subsets (CD3 + , CD4 + , CD8 + , CD4/CD8) as well as natural killer (NK) cells were detected 1 d before the initial 131I treatment. Patients were divided into excellent response (ER) group and non-ER group according to the response of 6-12 months after 131I treatment. Clinicopathological characteristics, preablative stimulated thyroglobulin (psTg), initial 131I dose and lymphocyte subsets that might affect the response to 131I treatment were analyzed (independent-sample t test, Mann-Whitney U test, χ2 test, multiple logistic regression analysis). ROC curve analysis was used to evaluate the predictive value of significant factors for non-ER. Results:Of 150 patients, 84 cases were in ER group (56.00%), and 66 cases (44.00%) were in non-ER group. Age ( z=-2.86, P=0.004), M stage ( χ2=13.64, P<0.001), psTg ( z=-8.94, P<0.001), initial 131I dose ( z=-7.60, P<0.001), CD4 + ( t=2.50, P=0.014), CD4/CD8 ( z=-2.22, P=0.027) of the two groups were significantly different. Multivariate analysis showed that psTg (odds ratio ( OR)=1.27, 95% CI: 1.16-1.40, P<0.001) and CD4/CD8 ( OR=0.39, 95% CI: 0.15-0.99, P=0.048) were independent factors for predicting 131I treatment response. The cut-off values of psTg and CD4/CD8 for predicting non-ER were 6.78 μg/L and 1.67, respectively. Conclusions:Cellular immune status before initial 131I treatment may predict treatment response in young and middle-aged patients with PTC. It indicates non-ER response when Tg is higher than 6.78 μg/L and CD4/CD8 is lower than 1.67.

Analysis of therapeutic mechanism of Liushen Wan against colitis-associated colorectal cancer based on network pharmacology and validation in mice / 南方医科大学学报

OBJECTIVE@#To explore the therapeutic mechanism of Liushen Wan (LSW) against colitis-associated colorectal cancer (CAC) by network pharmacology.@*METHODS@#TCMSP, BATMAN-TCM, CNKI, PubMed, Genecards, OMIM, and TTD databases were used to obtain the related targets of LSW and CAC. The common targets of LSW and CAC were obtained using Venny online website. The PPI network was constructed using Cytoscape 3.8.2 to screen the core targets of LSW in the treatment of CAC. GO and KEGG enrichment analysis were conducted using DAVID database. The therapeutic effect of LSW on CAC was evaluated in a C57BL/6J mouse model of AOM/DSS-induced CAC by observing the changes in body weight, disease activity index, colon length, and size and number of the tumor. HE staining and RT-qPCR were used to analyze the effect of LSW on inflammatory mediators. Immunohistochemistry and TUNEL staining were used to evaluate the effect of LSW on the proliferation and apoptosis of AOM/DSS-treated colon tumor cells. Immunohistochemistry and Western blotting were used to detect the effects of LSW on the expression of TLR4 proteins in CAC mice.@*RESULTS@#Network pharmacology analysis identified 69 common targets of LSW and CAC, and 33 hub targets were screened in the PPI network. KEGG pathway enrichment analysis suggested that the effect of LSW on CAC was mediated by the Toll-like receptor signaling pathway. In the mouse model of AOM/DSS-induced CAC, LSW significantly inhibited colitis-associated tumorigenesis, reduced tumor number and tumor load (P < 0.05), obviously improved histopathological changes in the colon, downregulated the mRNA levels of proinflammatory cytokines, and inhibited the proliferation (P < 0.01) and promoted apoptosis of colon tumor cells (P < 0.001). LSW also significantly decreased TLR4 protein expression in the colon tissue (P < 0.05).@*CONCLUSION@#LSW can inhibit CAC in mice possibly by regulating the expression of TLR4 to reduce intestinal inflammation, inhibit colon tumor cell proliferation and promote their apoptosis.

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease / 老年心脏病学杂志（英文版）

BACKGROUND@#Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers.@*METHODS@#A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death.@*RESULTS@#Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years.@*CONCLUSIONS@#Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Study on the substance basis of "property-taste-efficacy" of Liquorice and Rhizoma chinensis based on supramolecular system induced by weak bond / 药学学报

It is a common understanding that turbidity and precipitation of traditional Chinese medicine are easy to occur in the process of decocting. At present, our research group found that the cause of "multi-phase of traditional Chinese medicine decoction" mainly came from the interaction between the effective components of traditional Chinese medicine, especially the interaction of acid and base components. For example, the Liquorice and Rhizoma chinensis was a supramolecular system formed by a large number of active components in the decoction (>30%), and could stably exist in the decoction system. In this study, the supramolecular part was extracted, and the morphology of the supramolecular part was characterized by scanning electron microscopy and dynamic light scattering. It was observed that the supramolecular particles were uniform in size and regular in shape. The main components of supramolecular sites were identified by liquid mass spectrometry (LC-MSn). The results of UV and IR spectra showed that the chemical components of Liquorice and Rhizoma chinensis in the co-decocting process collided with each other, and weak bonds were formed between the functional groups of the molecules, which then induced the aggregation to form supramolecules. Thereafter, Through the diarrhea model of mice, sensory evaluation and antibacterial activity evaluation found that Liquorice and Rhizoma chinensis decocted together enhanced the antibacterial activity of Rhizoma, and compatibility "reconcile" Rhizoma "big bitter cold" property compared with single decoction group and interval administration group. All animal experiments were approved by the Animal Ethics Committee of Beijing University of Chinese Medicine, and the relevant regulations of Beijing University of Chinese Medicine on experimental animals were strictly followed. In this study, supramolecular chemistry method was used to preliminarily discuss the scientific connotation of "increasing efficiency and decreasing toxicity" of Liquorice and Rhizoma chinensis combined decoction from three perspectives of "property, efficacy and taste", and provide new ideas for the basic research of "reconcile" compatibility of Liquorice.

He-Wei Granule enhances anti-tumor activity of cyclophosphamide by changing tumor microenvironment / 中草药·英文版

Objective: He-Wei Granule (HWKL) is a modern product derived from the modified formulation of traditional Chinese medicine Banxia Xiexin Decoction (BXD), which remarkedly enhanced the anti-proliferation activity of cyclophosphamide (CTX) on HepG2 and SGC-7901 cell lines in vitro in our previous research. The aim of the study was to investigate the synergistic effects of HWKL and CTX using a transplanted H22 hepatocellular carcinoma mouse model. Methods: The CTX-toxic-reducing efficacy of HWKL was evaluated by hematology indexes, organ indexes and marrow DNA detection. To investigate the underlying mechanisms, histopathology test, immunohistochemistry test and TUNEL staining were conducted. The efficacy of HWKL on the micro-vessel density (MVD) in tumor tissue was also evaluated by measuring CD34 level. Results: High dose HWKL (6.75 g/kg) markedly attenuated CTX-induced hepatotoxicity and myelosuppression while significantly enhanced CTX anticancer efficacy in vivo. Further mechanism investigation suggested that high dose HWKL significantly increased cleaved Caspase 3 level and promoted apoptosis in tumor tissue by up-regulating Bax expression and down-regulating Bcl-2 and FasL expressions. Compared with CTX alone group, the decrease in LC-3B and Beclin 1 levels suggested that the autophagy in H22 carcinoma was significantly inhibited with addition of high dose HWKL. ELISA assay results indicated that the autophagy inhibition was achieved by decreasing p53 expression, blocking PI3K/AKT/mTOR pathway and recovering Th1/Th2 cytokine balance. In addition, CD34 and EGFR immunohistochemistry assay suggest that high dose HWKL could significantly decrease micro-vessel density (MVD) and inhibit angiogenesis in H22 carcinoma. Conclusion: It can be concluded that high-dose HWKL enhanced CTX efficacy by promoting apoptosis, inhibiting autophagy and angiogenesis in tumor tissue while significantly alleviated CTX-induced toxicity, and could be applied along with CTX in clinical treatment as a supplement agent.

Human genetic resources management of the Investigator-Initiated Clinical Trials / 中华医学科研管理杂志

Objective:To encourage the innovation of medical science and technology, regulate the Investigator Initiated Clinical Trials (IIT), this paper analyzed the problems faced by the management of human genetic resources in medical institution, and the corresponding management measures.Methods:Existing problems of human genetic resource management in IIT were discussed and summarized, taking into consideration of regulatory requirements and daily practices in the hospital.Results:Problems identified include imperfect supervision mechanism, incomplete policy interpretation, insufficient understanding of human genetic resources management policies by researchers, and how to support innovation with human gentic resources and so on.Conclusions:Medical institutions should establish and improve the supervision system and strengthen the whole process management of IIT. Accurately interpret regulatory requirements to improve application efficiency. Improve researchers′ recognition of human genetic resources to avoid omission and misrepresentation. Build a biobank to encourage legal and compliant use of human genetic resources to carry out high-quality IIT.

Association of cardiometabolic index and traditional body fat evaluation indicators with metabolic syndrome in urban population over 40 years old in Guiyang city: A cross-sectional study / 中华内分泌代谢杂志

Objective:To explore the association of cardiometabolic index(CMI) and other body fat evaluation indicators [body mass index(BMI), waist circumference(WC), waist to height ratio(WHtR), lipid accumulation index(LAP)] with the prevalence of metabolic syndrome(MS) as well as the predictive value of the above indicators for MS.Methods:A total of 10 140 residents over 40 years old in Guiyang city who participated in the " Epidemiological study on tumor risk of type 2 diabetes patients in China" in 2011 were recruited. The 2005 International Diabetes Federation diagnostic criteria were used to identify MS. Logistic regression was used to analyze the association of CMI and other body fat evaluation indicators with MS. Receiver operating characteristic(ROC) curve was used to evaluate the predictive value and the optimal cut-off point of different indicators. Taking the best cut-off point value of each index as the boundary, the prevalence of MS was evaluated again by Chi square test.Results:The prevalence of MS in the study population was 39.81%(27.23% for men and 44.39% for women). Logistic regression analysis showed that the risk of MS increased with increasing CMI and quartile level of other body fat evaluation indicators in both men and women( P<0.05). The risks of MS in CMI Q4 group were 17.15(95% CI 11.64-25.27) for male and 45.14(95% CI 37.07-54.96) for female compared with Q1 group. In male, the area under curve(AUC) of MS by predicted CMI was 0.761(sensitivity 79.8%, specificity 63.2%, optimal cut-off point 0.71). WC displayed the highest value of AUC among the body fat evaluation indicators. In women, the AUC value of MS predicted by CMI was 0.831(sensitivity 76.8%, specificity 75.7%, optimal cut-off point 0.65), higher than those of BMI and WHtR while lower than those of WC and LAP. Further calculating the prevalence of MS with the best cut-off point value of each index as the boundary, WC was still the best predictor for male, while CMI was only secondary to LAP for women. Conclusion:CMI and other body fat evaluation indicators are significantly associated with MS. CMI could be used to predict MS.

Cardiometabolic index and metabolic syndrome in the population over 40 years old in Guiyang city: A prospective cohort study / 中华内分泌代谢杂志

Objective:To investigate the relationship between cardiometabolic index and metabolic syndrome in people aged 40 and beyond in Guiyang city.Methods:A total of 4 506 residents over 40 years(including 3 067 females and 1 439 males) were enrolled in the analysis from those who participated in the epidemiological study of cancer risk in Chinese patients with type 2 diabetes in 2011 in Guiyang City. The cardiometabolic index (CMI) is calculated by triglycerides(TG)/high-density lipoprotein-cholesterol(HDL-C)×waist-to-height ratio (WHtR). Multivariable logistic regression was used to analyze the correlation between cardiometabolic index and metabolic syndrome, and ROC was used to analyze the predictive ability of CMI on the incidence of metabolic syndrome. Results:The average follow-up period was 3 years. According to the International Diabetes Federation (IDF) diagnostic criteria for metabolic syndrome in 2005, 985 patients (774 women and 211 males) had metabolic syndrome. The incidence rate of metabolic syndrome in the general population was 21.86%, the incidence rate of male metabolic syndrome was 14.66%, and that of women was 25.24%, and the incidence of CMI increased with the increase of the number of women. After multivariable logistic regression analysis, the odds ratio of CMI for metabolic syndrome in women is 1.303(95% CI 1.263-1.344) and 1.724(95% CI 1.162-2.558) in men, respectively. ROC results showed that CMI had a good ability to predict the incidence (AUC: 0.759 for men and 0.852 for women). Conclusion:CMI is positively associated with the incidence of metabolic syndrome. It supports CMI as a useful method to screen metabolic syndrome in China′s general population.

Nitric Oxide Produced by the Antioxidant Activity of Verapamil Improves the Acute Wound Healing Process

BACKGROUND@#Verapamil is used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, hypertrophic scars, and keloids to block transmembrane calcium ion flux. Verapamil has antioxidant activity, which enhances the production of nitric oxide (NO). NO promotes the proliferation of fibroblasts, keratinocytes, endothelial cells, and epithelial cells during wound healing. In this study, we investigated the effect of verapamil and its antioxidant properties on the enhancement of acute wound healing via NO. @*METHODS@#A full-thickness wound healing model was created on the rat dorsal with a silicone ring. The wound closure rate was estimated every 2 days for 14 days. A histological study was performed to evaluate wound healing.Immunofluorescence staining was analyzed for angiogenesis. The expressions of collagen type I (COL I), collagen type III (COL III), and vascular endothelial growth factor (VEGF) were assessed by Western blot. Real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of endothelial NO synthase and inducible NO synthase, which are related to antioxidant activity in the process of wound healing. @*RESULTS@#The wound closure rate was faster in the verapamil group compared to the control and silicone groups.Histologic analysis revealed capillaries and stratum basale in the verapamil group. Immunofluorescence staining was shown vessel formation in the verapamil group. Western blot and qRT-PCR analysis revealed high expression levels of COL I, VEGF, eNOS, and FGF in the verapamil. @*CONCLUSION@#Verapamil’s antioxidant activity enhances NO production in acute wound healing. We suggest that verapamil can be used to promote acute wound healing.

NOX4/Src regulates ANP secretion through activating ERK1/2 and Akt/GATA4 signaling in beating rat hypoxic atria

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 µM) and BQ788 (0.3 µM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 µM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 µM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxiaactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 µM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 µM) and LY294002 (10.0 µM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

Immunogenicity of Whole / 生物医学与环境科学（英文）

Objectives@#To evaluate the immunogenicity of @*Methods@#Protein extracts from @*Results@#Immunization with @*Conclusion@#This is the advanced study to investigate the immunogenicity of

Based on weak bond chemistry, the interaction mechanism between glycyrrhiza protein and berberine in water decocting process of Rhizoma Coptidis and Liquorice was investigated / 药学学报

The purpose of this study was to explore the interaction mechanism between glycyrrhiza protein and berberine in the decocting process of Rhizoma Coptidis and Liquorice and its effect on the pharmacodynamic effect. In this experiment, licorice crude protein was obtained from licorice decoction pieces, and it was found that licorice crude protein and berberine could form spherical supramolecular particles after decocting together. Morphological characterization was carried out by using Malvin particle size analyzer and emission scanning electron microscopy, and the supramolecular particles were observed to be nanoscale, which was significantly different from the morphology of licorice protein and berberine. The results of ultraviolet, infrared and fluorescence spectroscopy showed that the mechanism of molecular interaction was induced by weak bonds such as electrostatic attraction and hydrophobic interaction. Furthermore, the antimicrobial activity of berberine was significantly affected by the supramolecular particles of licorice protein-berberine, which were significantly different from the mechanical mixture. This study reveals the pharmacological value of macromolecular substances such as proteins in the decoction of licorice and Coptis chinensis from a new perspective, which is helpful to promote the secondary development of clinical effective prescriptions, especially the research on the pharmacological substance basis of classic famous prescriptions.

Value of 99Tc m-MIBI SPECT/CT imaging in preoperative diagnosis of primary hyperparathyroidism and its influencing factors / 中华核医学与分子影像杂志

Objective:To investigate the preoperative diagnostic value of 99Tc m-methoxyisobutylisonitrile (MIBI) planar imaging and SPECT/CT imaging for primary hyperparathyroidism (PHPT), and analyze the relevant factors affecting the imaging results. Methods:From June 2016 to September 2019, a total of 62 patients (15 males, 47 females, age range: 27-80 years) confirmed as PHPT by postsurgical pathology in Affiliated Hospital of Qingdao University were retrospectively enrolled. The diagnostic efficacies of 99Tc m-MIBI planar imaging and SPECT/CT imaging were compared using χ2 test. The differences of preoperative serum parathyroid hormone (PTH), Ca and the maximum diameter of lesion between the positive and negative groups of planar imaging were analyzed using independent-sample t test and Mann-Whitney U test. The region of interest (ROI) method was applied to calculate the uptake ratio of lesions to normal tissues at the early phase (T/Ne) and delayed phase (T/Nd) in positive cases of planar imaging. Pearson or Spearman correlation analysis was used to evaluate the correlation of T/Ne, T/Nd with preoperative serum PTH, Ca and the maximum diameter of lesion. The receiver operating characteristic (ROC) curves of preoperative serum PTH, Ca and positive planar imaging were drawn and the cut-off values were obtained. Results:The sensitivity of planar imaging and SPECT/CT imaging was 69.35%(43/62) and 87.10%(54/62) respectively ( χ2=5.729, P=0.017). The preoperative serum PTH, Ca levels and the maximum diameter of lesion in patients with positive planar imaging (253.32(107.00, 331.70) ng/L, 2.78(2.51, 2.87) mmol/L, (2.01±0.88) mm) were higher than those with negative planar imaging ((111.86±44.29) ng/L, (2.59±0.21) mmol/L, (1.42±0.55) mm; z values: -2.802, -1.978, t=3.300, all P<0.05). T/Ne was positively correlated with preoperative serum PTH ( rs=0.511, P<0.001) and the maximum diameter of lesion ( r=0.381, P=0.012), and T/Nd was positively correlated with preoperative serum PTH ( rs=0.538, P<0.001), Ca ( rs=0.348, P=0.022) and the maximum diameter of lesion ( r=0.463, P=0.002). The area under the ROC curve between preoperative serum PTH, Ca and planar imaging was 0.725 and 0.646, respectively. Preoperative serum PTH had a better predictive value with the optimal cut-off value of 150.4 ng/L. Conclusions:Preoperative serum PTH, Ca and the maximum diameter of lesion are positively correlated with 99Tc m-MIBI uptake in PHPT patients with positive planar imaging results. When preoperative serum PTH is lower than 150.4 ng/L, planar imaging is prone to false negative. SPECT/CT imaging has a significant value in preoperative diagnosis and the combination of PTH and CT can improve the positive rate.

Nitric Oxide Produced by the Antioxidant Activity of Verapamil Improves the Acute Wound Healing Process

BACKGROUND@#Verapamil is used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, hypertrophic scars, and keloids to block transmembrane calcium ion flux. Verapamil has antioxidant activity, which enhances the production of nitric oxide (NO). NO promotes the proliferation of fibroblasts, keratinocytes, endothelial cells, and epithelial cells during wound healing. In this study, we investigated the effect of verapamil and its antioxidant properties on the enhancement of acute wound healing via NO. @*METHODS@#A full-thickness wound healing model was created on the rat dorsal with a silicone ring. The wound closure rate was estimated every 2 days for 14 days. A histological study was performed to evaluate wound healing.Immunofluorescence staining was analyzed for angiogenesis. The expressions of collagen type I (COL I), collagen type III (COL III), and vascular endothelial growth factor (VEGF) were assessed by Western blot. Real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of endothelial NO synthase and inducible NO synthase, which are related to antioxidant activity in the process of wound healing. @*RESULTS@#The wound closure rate was faster in the verapamil group compared to the control and silicone groups.Histologic analysis revealed capillaries and stratum basale in the verapamil group. Immunofluorescence staining was shown vessel formation in the verapamil group. Western blot and qRT-PCR analysis revealed high expression levels of COL I, VEGF, eNOS, and FGF in the verapamil. @*CONCLUSION@#Verapamil’s antioxidant activity enhances NO production in acute wound healing. We suggest that verapamil can be used to promote acute wound healing.

NOX4/Src regulates ANP secretion through activating ERK1/2 and Akt/GATA4 signaling in beating rat hypoxic atria

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 µM) and BQ788 (0.3 µM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 µM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 µM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxiaactivated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 µM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 µM) and LY294002 (10.0 µM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

Optimal Condition of Isolation from an Adipose Tissue-Derived Stromal Vascular Fraction for the Development of Automated Systems

Background@#The stromal vascular fraction (SVF) isolated from adipose tissue, which contains stem cells as well as other cell types, has been applied in various research fields. Although different enzymatic concentrations and treatment durations have been applied to isolate the SVF, optimal conditions have not been established. Thus, we aimed to establish the optimal conditions for isolation of the SVF from adipose tissue by automated systems. @*Methods@#The SVF was collected from removed adipose tissues of five donors during surgery. The SVF was treated with 0.1% or 0.2% collagenase type I for 20, 40, or 60 min. Then, colony forming unit (CFU) assays and flow cytometry were performed to characterize the adipose stem cells (ASCs). A cytokine array was used to investigate the correlation between colony-formation ability and the secretion of isolated ASCs. @*Results@#Treatment with 0.1% collagenase type I for 60 min resulted in a higher SVF yield, whereas treatment with 0.1% collagenase for 40 min resulted in higher CFU values. In addition, expression of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 in the SVF was higher in the high-CFU group than in the low-CFU group. @*Conclusion@#The optimal conditions for isolation of the SVF from adipose tissue were treatment with 0.1% collagenase type I for 40 min. We identified the conditions required for efficient SVF isolation based on high CFU values, and our results will facilitate the development of automated systems.

A new quantitative 16S rRNA amplicon sequencing method / 生物工程学报

In recent years, 16S rRNA amplicon sequencing technology has been widely used to study human gut microbiota and to detect unknown pathogens in clinical samples. However, its resolution to bacterial population can only reach the relative abundance of genus level, and different factors affect the final bacterial profile, such as sample concentrations, PCR cycle numbers and amplification primers. In order to solve these problems, we developed a quantitative 16S rRNA amplicon sequencing method by combining random tag and internal marker method. The new methods improved the accuracy of human gut microbiota, reduced the impact of experimental operation on the results, and improved the comparability between sequencing and other molecular biological methods.

Clinical Analysis for Patients with AML Treated after Allo-HSCT / 中国实验血液学杂志

OBJECTIVE@#To analyze risk factors that affect survival and relapse of AML patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to investigate the therapy choices after AML relapse.@*METHODS@#Clinical data of 180 AML patients achieved complete remission (CR) before HSCT from January 2009 to December 2018 treated in our center were analyzed retrospectively. Risk factors for survival and relapse after allo-HSCT were analyzed by COX regression.@*RESULTS@#Among 180 AML patients, 134 survived (74.4%), 46 patients died (25.6%), and 40 patients relapsed (22.2%). The rate of overall survival (OS), event-free survival (EFS) and cumulative rate of relapse in 5-years was 74.3%、42.5% and 25.0%, respectively. High-risk, adverse cytogenetics, CR at HSCT and no cGvHD were independent risk factors that affect OS. CR at HSCT, high-risk were independent risk factors that affect EFS. High-risk, MRD after one course of induction therapy, adverse cytogenetics and no cGVHD were independent risk factors that affect relapse. The OS rate of relapse patients could be improved by the usage of hypomethylation agents combined with G-CSF mobilized donor lymphocyte infusion (DLI), and 2-year OS rate was 62.5%.@*CONCLUSION@#The survival rate of AML is greatly improved by allo-HSCT, but relapse is still one of the most important factors that influence survival of the AML patients. The maintenance therapy of hypomethylation agents combined with DLI may be a new effective treatment option for patients who relapse after HSCT.

Identification of Peripheral Blood and Menstrual Blood Based on the Expression Level of MicroRNAs and Discriminant Analysis / 法医学杂志

Objective To construct a discriminant analysis model based on the differential expression of multiple microRNAs （miRNAs） in two kinds of blood samples （peripheral blood and menstrual blood） and three non-blood samples （saliva, semen and vaginal secretion）, to form an identification solution for peripheral blood and menstrual blood. Methods Six kinds of miRNA （miR-451a, miR-144-3p, miR-144-5p, miR-214-3p, miR-203-3p and miR-205-5p） were selected from literature, the samples of five kinds of body fluids commonly seen in forensic practice （peripheral blood, menstrual blood, saliva, semen, vaginal secretion） were collected, then the samples were divided into training set and testing set and detected by SYBR Green real-time qPCR. A discriminant analysis model was set up based on the expression data of training set and the expression data of testing set was used to examine the accuracy of the model. Results A discriminant analysis statistical model that could distinguish blood samples from non-blood samples and distinguish peripheral blood samples from menstrual blood samples at the same time was successfully constructed. The identification accuracy of the model was over 99%. Conclusion This study provides a scientific and accurate identification strategy for forensic fluid identification of peripheral blood and menstrual blood samples and could be used in forensic practice.