Comparative of Forensic DNA Identification Using Cell Lysis Method and Magnetic Beads Method / 法医学杂志

OBJECTIVES@#To compare the effects of cell lysis method and magnetic beads method in forensic DNA identification and to explore these two methods in forensic DNA identification.@*METHODS@#The genome DNA of THP-1 cells in different quantities was extracted by the cell lysis method and magnetic beads method, and the DNA content was quantified by real-time quantitative PCR. The cell lysis method and magnetic beads method were used to type the STR of human blood with different dilution ratios.@*RESULTS@#When the numbers of THP-1 cell were 100, 400 and 800, the DNA content extracted by cell lysis method were (1.219±0.334), (5.081±0.335), (9.332±0.318) ng, respectively; and the DNA content extracted by magnetic beads method were (1.020±0.281), (3.634±0.482), (7.896±0.759) ng, respectively. When the numbers of THP-1 cells were 400 and 800, the DNA content extracted by the cell lysis method was higher than that by the magnetic beads method. The sensitivity of cell lysis method and magnetic beads method was similar in STR typing of human blood at different dilution ratios. Complete STR typing could be obtained at 100, 300 and 500-fold dilutions of blood samples, but could not be detected at 700-fold dilution. STR typing of undiluted human blood could not be detected by cell lysis method.@*CONCLUSIONS@#The cell lysis method is easy to operate and can retain template DNA to the maximum extend. It is expected to be suitable for trace blood evidence tests.

The practical path of constructing the "Curriculum Ideological and Political System" in nursing specialty / 中华医学教育探索杂志

With the comprehensive quality of nursing undergraduates cultivation as the core, the construction of "Curriculum Ideological and Political System" follows the law of ideological work, the rules of teaching and the rules of student growth, to change according to the events, to progress according to the period, and to update according to the situation. This paper attempts to instruct the ways of building the first class with multiple ways, building the second-class education by three platform and three integrations, and establishing a multi-time, multi-dimensional and multi-way evaluation system for the educational effect, so as to promote the quality of nursing professionals to higher level.

Effect of Yudantong decoction on intestinal flora and intestinal barrier function in mice with cholestasis induced by α-naphthyl isothiocyanate / 临床肝胆病杂志

Objective To investigate the therapeutic effect of Yudantong decoction in mice with α-naphthyl isothiocyanate (ANIT)-induced cholestasis, as well as its targets and mechanism based on intestinal flora and intestinal barrier function. Methods A total of 24 C57BL/6 mice were randomly divided into control group, model group, Yudantong decoction group (YDTF group), and ursodeoxycholic acid (UDCA) group, with 6 mice in each group. The mice in the model group, the YDTF group, and the UDCA group were given ANIT 35 mg/kg/day by gavage on days 1, 4, 7, 10, and 13, and those in the YDTF group and the UDCA group were given Yudantong decoction or UDCA by gavage for 15 consecutive days; related samples were collected on day 16. Liver histopathology was observed, and liver function parameters were measured; immunohistochemistry was used to measure the protein expression levels of caspase-1, interleukin-1β (IL-1β), and FXR in the liver, and flow cytometry was used to measure the percentages of CD11b + , CD86 + , and CD45 + immune cells in the liver; 16S rDNA sequencing and information analysis were performed for fecal microorganisms; immunohistochemistry was used to measure the protein expression of the intestinal FXR/NLRP3 pathway, and immunofluorescence assay was used to measure the protein expression of intestinal E-cadherin and occludin. A one-way analysis of variance was used for comparison of continuous data with homogeneity of variance between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Welch test was used for comparison of data with heterogeneity of variance between multiple groups, and the Games-Howell test was used for further comparison between two groups. Results HE staining showed that the model group had partial hepatocyte fatty degeneration, massive necrosis of hepatocytes in hepatic lobules, damage of lobular structure, and massive inflammatory cell infiltration, and the YDTF group and the UDCA group had alleviation of hepatocyte fatty degeneration and hepatocyte necrosis in hepatic lobules, with a reduction in inflammatory cells. Compared with the control group, the model group had significantly higher serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), and total bile acid (TBA) (all P < 0.05); compared with the model group, the YDTF group had significant reductions in the serum levels of ALT, AST, GGT, ALP, TBil, DBil, and TBA (all P < 0.05), and the UDCA group had significant reductions in the serum levels of GGT, TBil, DBil, and TBA (all P < 0.05). Compared with the control group, the model group had significant increases in the levels of caspase-1 and IL-1β and a significant reduction in the expression of FXR in the liver (all P < 0.05); compared with the model group, the YDTF group had significant reductions in the levels of caspase-1 and IL-1β in the liver and the UDCA group had a significant reduction in the level of IL-1β in the liver, and both the YDTF group and the UDCA group had a significant increase in the expression level of FXR in the liver (all P < 0.05). The model group had a significant change in the composition of intestinal flora compared with the control group ( P < 0.05); there was a significant difference in the structure of intestinal flora between the YDTF group and the model group ( P < 0.05), and there was also a significant difference in the composition of intestinal flora between the UDCA group and the control/model groups ( P < 0.05). Compared with the control group, the model group had a significant increase in the abundance of intestinal Akkermansia muciniphila and a significant reduction in the abundance of Lactobacillus johnsonii (both P < 0.05); compared with the model group, both the YDTF group and the UDCA group had a significant reduction in the abundance of intestinal Akkermansia muciniphila , and the YDTF group had a significant increase in the abundance of Lactobacillus murinus , while the UDCA group had significant increases in the abundance of Lactobacillus murinus and Bifidobacterium pseudolongum (all P < 0.05). Compared with the control group, the model group had a significant reduction in the protein expression of intestinal FXR, a significant increase in the protein expression of intestinal NLRP3, and significant reductions in the expression of intestinal E-cadherin and occludin (all P < 0.05); compared with the model group, both the YDTF group and the UDCA group had a significant increase in the protein expression of intestinal FXR, a significant reduction in the protein expression of intestinal NLRP3, and significant increases in the expression of intestinal E-cadherin and occludin (all P < 0.05). Conclusion Yudantong decoction can alleviate liver injury in mice with ANIT-induced cholestasis, possibly by improving intestinal flora and enhancing intestinal barrier function.

Association between triglyceride glucose index and impairment of renal function in community-dwelling middle-aged and elderly population / 中华全科医师杂志

Objective:To explore the relationship between the triglyceride glucose (TyG) index and impairment of renal function in community-dwelling middle-aged and elderly population.Methods:A total of 4 988 residents aged ≥45 years undergoing health check-up in Yongshun Health Service Center from January 2016 to December 2021 were enrolled and followed up. According to the quartile of the baseline TyG index, all subjects were divided into Q1, Q2, Q3 and Q4 groups. The medical history, physical examination and laboratory test results were documented. Participants were followed up through regular health check-up until March 31, 2023. The outcomes were rapid decline of estimated glomerular filtration rate (eGFR) (a loss in eGFR>3 ml·min -1·1.73 m -2 per year) and the new-onset of chronic kidney disease (CKD) during the follow-up period. Linear regression model, multivariate logistic regression model, restricted cubic spline fitting logistic regression model and ROC curve analysis were used to analyze the association between the TyG index and the impairment of renal function. Results:Among 4 988 residents, 1 396 (28.0%) were males and the age was (59.76±6.28) years. There were 1 247 participants in Q1, Q2, Q3 and Q4 groups, respectively. After 56 months of follow-up, the incidence of rapid eGFR decline and new-onset CKD was 21.9% (1 294/4 988) and 4.0% (200/4 988), respectively. Multivariate logistic regression model analysis showed that TyG index was correlated positively with rapid eGFR decline and new-onset of CKD ( OR=1.34, 95%CI: 1.17-1.52, P<0.001, and OR=1.57, 95%CI:1.19-2.06, P=0.001). Taking group Q1 as a reference, higher levels of TyG index ( Q2, Q3 and Q4 groups) was an independent risk factor for rapid eGFR decline ( P<0.05), which has a dose-response relationship (for trend P=0.002). Compared with the lowest quartile, the adjusted OR of new-onset CKD in the highest quartile was 1.85 ( 95%CI:1.13-3.03, P=0.014). The results of restricted cubic spline fitting logistic regression analysis showed a linear association between TyG index and both outcomes (both P>0.05). The area under ROC curve ( AUC) of the TyG index for predicting the two adverse outcomes were 0.536 ( 95%CI: 0.516-0.556, P<0.001) and 0.588 ( 95%CI:0.548-0.627, P<0.001), respectively. Conclusion:The elevated levels of TyG index may be used as an independent predictor of rapid eGFR decline and new-onset CKD.

Association between plasma uric acid and hypertension and the gender difference in community-dwelling middle-aged and elderly population / 中华全科医师杂志

Objective:To investigate the association between plasma uric acid and hypertension and the gender difference in community-dwelling middle-aged and elderly population.Methods:A community-based cross-sectional study was conducted in Beijing Tongzhou Yongshun Community Health Service Center from June to December 2021, among residents aged 45 years or older selected by cluster sampling method. According to plasma uric acid (UA) level in quartiles, the subjects were divided into 4 groups; and stratified by gender, the subjects were further divided into subgroups. Multivariate logistic regression model was used to analyze the related factors of hypertension, and restricted cubic spline fitting logistic regression model was used to analyze the nonlinear association between uric acid and hypertension and the cut-off values of uric acid.Results:A total of 6 229 residents with the age of (63.2±7.3) years were enrolled in the study. In 1 874 male participants (30.1%), 946 participants (50.5%) had hypertension, and the uric acid level was 359 (309, 418)μmol/L; in 4 355 female participants (69.9%), 2 003 participants (46.0%) had hypertension, and the uric acid level was 306 (261, 359)μmol/L. Multivariate logistic regression analysis showed that after adjusting for factors that were statistically significant in univariate analyses or potentially clinically relevant (including age, body mass index, diabetes mellitus, coronary heart disease, cerebrovascular disease, albumin, estimated glomerular filtration rate, and cholesterol), uric acid was independently associated with hypertension ( P<0.001), for total participants the risk of hypertension in Q4 group was 1.33 times of that in Q1 group ( OR=1.33,95% CI 1.13-1.56, P=0.001); while for females the risk of hypertension in Q4 group was 1.38 times of that in Q1 group ( OR=1.38,95% CI 1.13-1.68, P=0.002), but no significant association was observed for males ( P>0.05). The results of restricted cubic spline fitting logistic regression analysis showed that there was a linear association between uric acid level and hypertension in the total population and males, and the risk of hypertension increased with uric acid level ( P<0.001 for the total population, P=0.016 for male). However, there was a non-linear association in females. When uric acid>307 μmol/L in females, the risk of hypertension increased significantly as the level of uric acid increased ( P<0.001). Conclusions:Uric acid level was independently associated with hypertension in the community-dwelling middle-aged and elderly population, and there was a gender difference in the correlation. The association was nonlinear in females and the cut-off value of uric acid in females was 307 μmol/L.

Meta-Analysis of the Diagnostic Efficacy of the Luminex xTAG Respiratory Viral Panel FAST v2Assay for Respiratory Viral Infections

Purpose@#Acute respiratory viral infections pose significant morbidity and mortality, making it essential to diagnose respiratory viral infections rapidly. In this study, the diagnostic efficacy of the Luminex xTAG Respiratory Virus Panel (RVP) FAST v2 test was evaluated on respiratory viral infections. @*Materials and Methods@#Information was retrieved from electronic databases, including Embase, Web of Science, PubMed, and Cochrane Library, for systematic review. Studies that fulfilled predefined inclusion criteria were included. After the extraction of information, statistical software was utilized for quality evaluation, data analysis, and assessment of publication bias. @*Results@#Eighty groups in fourfold tables from nine articles were included to perform statistical analyses. Therein, the mean specificity and mean sensitivity of Luminex xTAG RVP FAST v2 test for the detection of respiratory viral infections were 0.99 (0.98–0.99) and 0.88 (0.87–0.90), respectively. Additionally, the negative and positive likelihood ratios were 0.14 (0.11–0.19) and 87.42 (61.88– 123.50), respectively. Moreover, the diagnostic odds ratio and area under the curve of summary receiver operating characteristic were 714.80 and 0.9886, respectively. @*Conclusion@#The Luminex xTAG RVP FAST v2 test could be a reliable and rapid diagnostic method for multiple respiratory viral infections.

Statistical methods for relative risk estimation and applications in case-cohort study / 中华流行病学杂志

Objective: To systematically introduce the design of case-cohort study and the statistical methods of relative risk estimation and their application in the design. Methods: First, we introduced the basic principles of case-cohort study design. Secondly, Prentice's method, Self-Prentice method and Barlow method were described in the weighted Cox proportional hazard regression models in detail, finally, the data from the Shanghai Women's Health Study were used as an example to analyze the association between obesity and liver cancer incidence in the full cohort and case-cohort sample, and the results of parameters from each method were compared. Results: Significant association was observed between obesity and risk for liver cancer incidence in women in both the full cohort and the case-cohort sample. In the Cox proportional hazard regression model, the partial regression coefficients of the full cohort and the case-cohort sample fluctuated with the adjustment of confounding factors, but the hazard ratio estimates of them were close. There was a difference in the standard error of the partial regression coefficient between the full cohort and the case-cohort sample. The standard error of the partial regression coefficient of the case-cohort sample was larger than that of the full cohort, resulting in a wider 95% confidence interval of the relative risk. In the weighted Cox proportional hazard regression model, the standard error of the partial regression coefficient of Prentice's method was closer to the parameter estimates from full cohort than Self-Prentice method and Barlow method, and the 95% confidence interval of hazard ratio was closer to that of the full cohort. Conclusions: Case-cohort design could yield parameter results closer to the full cohort by collecting and analyzing data from sub-cohort members and patients with the disease, and reduce sample size and improve research efficiency. The results suggested that Prentice's method would be preferred in case-cohort design.

Synthesis and antibacterial activity of synephrine sulfonamide derivatives containing tetrazole and sulfuryl groups / 药学学报

Synephrine is a natural small-molecule alkaloid found in Aurantii fructus immaturus with versatile biological activities, but its derivatives have been rarely studied so far. Based on the multi-target drug design strategy, the phenolic hydroxyl and secondary amino group of synephrine were modified structurally by the molecular splicing method in this study and thus five intermediates and fifteen target molecules were designed and synthesized. These compounds were evaluated with certain human pathogenic bacteria and fungi, and found that the inhibitory activities of IM4 and IM5 against E.coli are comparable to those of eight fluoroquinolones; TM1n showed stronger inhibitory activity against drug-resistant C. trobicans and drug-resistant C. albicans than the positive control drug fluconazole. TM1d and TM1f against C. albicans ATCC90023, TM1o and TM1f against drug-resistant C. albicans, and TM1f against C. parapsilosis ATCC22019 are all comparable to fluconazole, all of which have the potential for in-depth research. In this study, synephrine derivatives with strong inhibitory activities against human pathogenic fungi were discovered for the first time, which provided a new idea for the further study of synephrine.

Risk factors analysis and prediction model establishment of neovascular glaucoma after central retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the risk factors of neovascular glaucoma(NVG)after central retinal vein occlusion(CRVO), and to construct a predictive model.<p>METHODS: The clinical data of 483 patients(527 eyes)with CRVO admitted to the Department of Ophthalmology of our hospital from February 2016 to March 2020 were retrospectively selected and followed up until June 2021. CRVO combined with NVG were counted.The risk prediction model of NVG after CRVO was constructed according to the regression coefficient of risk factors, and the Hosmer-Lemeshow(<i>H-L</i>)test and receiver operating characteristic(ROC)curve method were used to evaluate the prediction model.<p>RESULTS: Fifteen patients(23 eyes)were followed up with 35(15-64)mo. NVG was happened in 70 patients(86 eyes)(NVG group)and no NVG was happened in 398 patients(418 eyes)(non-NVG group). Regression analysis showed that ischemic CRVO, IOP≥18mmHg at the first visit, hypertension,relative afferent pupillary defect(RAPD)≥0.75logU at the first visit, uncorrected visual acuity(UCVA)>0.30(LogMAR)at the first visit were risk factors for NVG after CRVO(<i>P</i><0.01), and anti-vascular endothelial growth factor(VEGF)therapy were protective factors for NVG after CRVO(<i>P</i><0.01). The risk prediction model for NVG after CRVO had good consistency(<i>H-L</i> test <i>P</i>>0.05)and discrimination(area under the curve was 0.877, 95%<i>CI</i>:0.830-0.924, sensitivity was 84.3%, specificity was 88.9%). The predictive scoring model was further constructed, and the critical value of NVG after CRVO was 5 points,the area under the curve was 0.844(95%<i>CI</i>:0.790-0.898), sensitivity was 78.6%, and specificity was 87.4%.<p>CONCLUSION: Ischemic CRVO, IOP≥18mmHg at the first visit,hypertension,RAPD≥0.75logU at the first visit, UCVA>0.30(LogMAR), and anti-VEGF therapy are closely related to NVG after CRVO, and the predictive model established on this basis has good predictive efficacy.

Clinical characteristics and prognosis of young children with idiopathic arthritis combined with lung injury / 中华实用儿科临床杂志

Objective:To explore clinical manifestations, imaging features and prognosis of juvenile idiopathic arthritis (JIA) combined with lung injury, aiming to improve the understanding of the disease.Methods:Clinical data from 464 children with JIA who were hospitalized in Beijing Children′s Hospital from January 2016 to September 2019 were retrospectively analyzed.Their clinical manifestations, high resolution CT (HRCT) features, lung function and follow-up of children with lung injury were analyzed.Results:Among 464 children with JIA, 40 cases (8.62%) combined with lung injury.There were no significant differences in the age and sex between JIA children either combined with lung injury or not (all P>0.05). Among them, there were 125 cases of systemic-onset juvenile idiopathic arthritis (SoJIA) and 28 cases (22.4%) of JIA combined with lung injury, accounting for the highest proportion (70%, 28/40 cases) in JIA children combined with lung injury.Among 40 JIA children combined with lung injury, 22 cases (55.0%) had respiratory symptoms and 7 cases (17.5%) had obvious hypoxia.HRCT examination was performed in them, and the imaging findings included high-density strip or strip flocculation (75.0%, 30/40 cases), pleural thickening (45.0%, 18/40 cases), ground glass shadow (22.5%, 9/40 cases), nodular lesion (20.0%, 8/40 cases), vesicles or cystic emphysema (15.0%, 6/40 cases). Lung function was detected in 12/20 children with varying degrees of pulmonary function abnormalities, most of which were mixed ventilation dysfunction, and 2 cases still had pulmonary function abnormalities after treatment.During the follow-up for 3 months to 3.5 years, 4 cases (10%) JIA combined with lung injury died.A total of 29 children were re-examined by pulmonary CT in the follow-up visit, including 14 (48.28%) improved, 8 cases (27.58%) with no significant improvement, and 7 cases (24.14%) with repeated disease. Conclusions:JIA is a common rheumatic immune disease in children and all subtypes can be combined with lung injury, manifesting as interstitial lung disease mainly.The age and sex of JIA children combined with lung injury are not specific factors.The proportion of lung injury in SoJIA is significantly higher than that in other subtypes.SoJIA combined with macrophage activation syndrome can lead to respiratory failure, respiratory distress syndrome, and even death, which is one of the main factors leading to poor prognosis of JIA.HRCT is more sensitive to the diagnosis of lung injury.Lung function detection is a simple and easy method to evaluate and monitor lung injury.The prognosis of JIA children combined with lung injury is poor, which should be well concerned.

Advances in understanding the role of sphingosine kinase-2 in tumorigenesis and its inhibitors / 药学学报

In recent years the role of sphingosine kinase 2 (SphK2), a key enzyme in the sphingolipid pathway, in the process of tumorigenesis has gradually been elucidated. Recent research has shown that SphK2 inhibitors can be used as anticancer drugs alone or in combination with existing drugs to increase the therapeutic sensitivity of drug-resistant tumors. Among them, one selective SphK2 inhibitor, ABC294640, shows excellent oral bioavailability and biodistribution in vivo and has now entered Phase II clinical research. Therefore, developing innovative drugs based on SphK2 is of great interest. Herein, we discuss progress in understanding the role of SphK2 in tumorigenesis and review the recent development of inhibitors of SphK2.

Development and validation of radiomics model built by incorporating machine learning for identifying liver fibrosis and early-stage cirrhosis / 中华医学杂志(英文版)

BACKGROUND@#Liver fibrosis (LF) continues to develop and eventually progresses to cirrhosis. However, LF and early-stage cirrhosis (ESC) can be reversed in some cases, while advanced cirrhosis is almost impossible to cure. Advances in quantitative imaging techniques have made it possible to replace the gold standard biopsy method with non-invasive imaging, such as radiomics. Therefore, the purpose of this study is to develop a radiomics model to identify LF and ESC.@*METHODS@#Patients with LF (n = 108) and ESC (n = 116) were enrolled in this study. As a control, patients with healthy livers were involved in the study (n = 145). Diffusion-weighted imaging (DWI) data sets with three b-values (0, 400, and 800 s/mm) of enrolled cases were collected in this study. Then, radiomics features were extracted from manually delineated volumes of interest. Two modeling strategies were performed after univariate analysis and feature selection. Finally, an optimal model was determined by the receiver operating characteristic area under the curve (AUC).@*RESULTS@#The optimal models were built in plan 1. For model 1 in plan 1, the AUCs of the training and validation cohorts were 0.973 (95% confidence interval [CI] 0.946-1.000) and 0.948 (95% CI 0.903-0.993), respectively. For model 2 in plan 1, the AUCs of the training and validation cohorts were 0.944, 95% CI 0.905 to 0.983, and 0.968, 95% CI 0.940 to 0.996, respectively.@*CONCLUSIONS@#Radiomics analysis of DWI images allows for accurate identification of LF and ESC, and the non-invasive biomarkers extracted from the functional DWI images can serve as a better alternative to biopsy.

Research progress on stimulator of interferon genes agonists for cancer immunotherapy / 中国药科大学学报

@#In recent years, tumor immunotherapy has become a new hot spot in the field of cancer treatment. Besides the great success of immunological checkpoint inhibitors and cellular immunotherapy, small molecule immunotherapy has also attracted more and more attention. As a key signal transduction molecule involved in the innate immune response, stimulator of interferon genes plays an important role in defending against viral and intracellular bacterial infections, mediating type I IFN production and regulating the production of spontaneous anti-tumor immune responses in vivo. This paper briefly introduces the biological mechanism of STING signaling pathway and reviews the research progress of STING agonists based on the structural classification, so as to provide some reference for the design and discovery of STING agonist drugs.

Effect of Tanshinonne ⅡA preconditioning on nuclear factor kappa B signaling pathway in N9 cells subjected to oxygen-glucose deprivation and restoration / 中华麻醉学杂志

Objective To evaluate the effect of TanshinonneⅡA preconditioning on nuclear factor kappa B ( NF-κB ) signaling pathway in N9 cells subjected to oxygen-glucose deprivation and restoration ( OGD∕R) . Methods N9 cells cultured in vitro were divided into 4 groups ( n=16 each) by using a ran-dom number table method: control group ( C group) , OGD∕R group, vehicle group ( V group) and Tanshi-none ⅡA preconditioning group ( TP group) . N9 cells were subjected to O2-glucose deprivation for 4 h fol-lowed by restoration of O2-glucose supply for 24 h to establish the OGD∕R model. Group C receive no treat-ment. In group TP, N9 cells were cultured in medium containing Tanshinone ⅡA ( final concentration 5 mg∕L) for 24 h before the model was established. Dimethyl sulfoxide was added to the culture medium in group V. At the 24 h of reoxygenation, the level of lactate dehydrogenase ( LDH) and nitric oxide ( NO) in culture medium was detected by spectrophotometry, cell apoptosis was assessed by using TUNEL, and the expression of NF-κB in nucleus was detected by Western blot. The apoptosis rate was calculated. Results Compared with group C, the levels of LDH, IL-β, TNF-α and NO in culture medium and apoptosis rate were significantly increased, and the expression of NF-κB in nucleus was up-regulated in OGD∕R, V and TP groups ( P<0. 05) . Compared with group OGD∕R, the levels of LDH, IL-β, TNF-αand NO in culture me-dium and apoptosis rate were significantly decreased, and the expression of NF-κB in nucleus was down-reg-ulated in group TP ( P<0. 05) , and no significant change was found in the parameters mentioned above in group V ( P>0. 05 ) . Conclusion The mechanism by which Tanshinonne ⅡA preconditioning reduces OGD∕R injury to N9 cells is related to inhibiting NF-κB signaling pathway.

Cardiac Fibroblast-Specific Activating Transcription Factor 3 Promotes Myocardial Repair after Myocardial Infarction / 中华医学杂志(英文版)

<p><b>Background</b>Myocardial ischemia injury is one of the leading causes of death and disability worldwide. Cardiac fibroblasts (CFs) have central roles in modulating cardiac function under pathophysiological conditions. Activating transcription factor 3 (ATF3) plays a self-protective role in counteracting CF dysfunction. However, the precise function of CF-specific ATF3 during myocardial infarction (MI) injury/repair remains incompletely understood. The aim of this study was to determine whether CF-specific ATF3 affected cardiac repair after MI.</p><p><b>Methods</b>Fifteen male C57BL/6 wild-type mice were performed with MI operation to observe the expression of ATF3 at 0, 0.5, 1.0, 3.0, and 7.0 days postoperation. Model for MI was constructed in ATF3TGfl/flCol1a2-Cre+ (CF-specific ATF3 overexpression group, n = 5) and ATF3TGfl/flCol1a2-Cre- male mice (without CF-specific ATF3 overexpression group, n = 5). In addition, five mice of ATF3TGfl/flCol1a2-Cre+ and ATF3TGfl/flCol1a2-Cre- were subjected to sham MI operation. Heart function was detected by ultrasound and left ventricular remodeling was observed by Masson staining (myocardial fibrosis area was detected by blue collagen deposition area) at the 28 day after MI surgery in ATF3TGfl/flCol1a2-Cre+ and ATF3TGfl/flCol1a2-Cre- mice received sham or MI operation. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect cell proliferation/cell cycle-related gene expression in cardiac tissue. BrdU staining was used to detect fibroblast proliferation.</p><p><b>Results</b>After establishment of an MI model, we found that ATF3 proteins were increased in the heart of mice after MI surgery and dominantly expressed in CFs. Genetic overexpression of ATF3 in CFs (ATF3TGfl/flCol1a2-Cre+ group) resulted in an improvement in the heart function as indicated by increased cardiac ejection fraction (41.0% vs. 30.5%, t = 8.610, P = 0.001) and increased fractional shortening (26.8% vs. 18.1%, t = 7.173, P = 0.002), which was accompanied by a decrease in cardiac scar area (23.1% vs. 11.0%, t = 8.610, P = 0.001). qRT-PCR analysis of CFs isolated from ATF3TGfl/flCol1a2-Cre+ and ATF3TGfl/flCol1a2-Cre- ischemic hearts revealed a distinct transcriptional profile in ATF3-overexpressing CFs, displaying pro-proliferation properties. BrdU-positive cells significantly increased in ATF3-overexpressing CFs than control CFs under angiotensin II stimuli (11.5% vs. 6.8%, t = 31.599, P = 0.001) or serum stimuli (31.6% vs. 20.1%, t = 31.599, P = 0.001). The 5(6)-carboxyfluorescein N-hydroxysuccinimidyl ester assay showed that the cell numbers of the P2 and P3 generations were higher in the ATF3-overexpressing CFs at 24 h (P2: 91.6% vs. 71.8%, t = 8.465, P = 0.015) and 48 h (P3: 81.6% vs. 51.1%, t = 9.029, P = 0.012) after serum stimulation. Notably, ATF3 overexpression-induced CF proliferation was clearly increased in the heart after MI injury.</p><p><b>Conclusions</b>We identify that CF-specific ATF3 might contribute to be MI repair through upregulating the expression of cell cycle/proliferation-related genes and enhancing cell proliferation.</p>

Preventive and therapeutic effects of rhEGF gel on radiation-induced oral mucositis:A clinical observation / 医学研究生学报

Objective Few studies are reported on the prevention and management of oral mucositis(OM) induced by post-operative radiotherapy in patients with oral cavity cancer.This study aimed to investigate the therateutic effect of the recombinant human epidermal growth factor(rhEGF) gel on radiation-induced OM. Methods Sixty-eight cases of radiation-induced OM after surgery for oral cavity cancer were randomly divided into an experimental and a control group of equal number,the former treated with rhEGF gel while the latter with borax mouthwash. Comparisons were made between the two groups of patients in the severity of oral cavity mucous membrane injury,the intensity of radiation-induced oral pain,the in-cidence of oral cavity infection, and the duration of radiotherapy. Results At 3 weeks of radiotherapy,the patients of the experimental group showed mainly mild and moderate OM while the controls chiefly moderate and severe OM,and at 6 weeks,the former exhibited mainly moderate while the latter chiefly severe OM, with statistically significant differences in the incidence rate between the two groups (P<0.01). The experimental group, compared with the controls, had a significantly higher incidence rate of grade-Ⅰ radiation-induced pain (47.1% vs 20.6%,P<0.01),but lower rates of grade-Ⅱ(17.6% vs 32.4%,P<0.01) and grade-Ⅲpain(2.9% vs 20.6%,P<0.01).The rates of oral infection and antibiotics medication were remarkably lower in the experimental group than in the controls(23.5% vs 38.2% and 11.8% vs 26.5%,P<0.05),and the duration of radiotherapy was markedly shorter in the former than in the latter ([42.37±3.14] d vs [48.47±4.39] d, P<0.05). Conclusion The rhEGF gel can significantly reduce the severity of radiation-induced oral mucositis,improve its symptoms,and shorten the time of postoperative radiotherapy for patients with oral cavity cancer.

Hsa-miRNA-143-3p Reverses Multidrug Resistance of Triple-Negative Breast Cancer by Inhibiting the Expression of Its Target Protein Cytokine-Induced Apoptosis Inhibitor 1 In Vivo / 한국유방암학회지

PURPOSE: Multidrug resistance (MDR) remains a major obstacle in the treatment of triple-negative breast cancer (TNBC) with conventional chemotherapeutic agents. A previous study demonstrated that hsa-miRNA-143-3p plays a vital role in drug resistance of TNBC. Downregulation of hsa-miRNA-143-3p upregulated the expression of its target protein cytokine-induced apoptosis inhibitor 1 (CIAPIN1) in order to activate MDR, while upregulation of hsa-miRNA-143-3p effectively enhances the sensitivity of drug-resistant TNBC cells to chemotherapeutics. The present study aimed to further verify these findings in vivo. METHODS: We established a hypodermic tumor nude mice model using paclitaxel-resistant TNBC cells. We expressed ectopic hsa-miRNA-143-3p under the control of a breast cancer-specific human mammaglobin promoter that guided the efficient expression of exogenous hsa-miRNA-143-3p only in breast cancer cells. Thereafter, we overexpressed hsa-miRNA-143-3p in xenografts using a recombinant virus system and quantified the expression of hsa-miRNA-143-3p, CIAPIN1 protein, and proteins encoded by related functional genes by western blot. RESULTS: We successfully completed the prospective exploration of the intravenous virus injection pattern from extensive expression to targeted expression. The overexpression of hsa-miRNA-143-3p significantly alleviated chemoresistance of TNBC by inhibiting viability. In addition, we observed that the expression of CIAPIN1 as a hsa-miRNA-143-3p target protein was remarkably decreased. CONCLUSION: We partly illustrated the mechanism underlying the hsa-miRNA-143-3p/CIAPIN1 drug resistance pathway. HsamiRNA-143-3p as a tumor suppressive microRNA may be a novel target to effectively reverse MDR of TNBC in vivo.

Effect of Celecoxib capsules on the biological behavior of LoVo cell of human colorectal cancer / 中国生化药物杂志

Objective To investigate the effects of Celecoxib capsules on the proliferation, invasion and other biological behaviors of LoVo cells in human rectal cancer. Methods Cell proliferation was tested by CCK 8 method, the change of cell cycle was detected by using flow cytometry, cell apoptosis in each group was tested by TUNEL staining method, cell migration ability was detected through the scratch healing experiment. Results The results of CCK-8 test showed that the proliferation of LoVo cells of the intervention group was inhibited and the apoptosis rate was increased (P<0.05). The results of flow cytometry showed that the cell cycle of the intervention group was blocked in G0/G1 phase, and the number of cells decreased in S stage. The results of the scratch healing experiment showed that the migration of LoVo cells in the intervention group was decreased, compared with the control group. Conclusion Celecoxib capsules played an important role in inhibiting tumor proliferation and promoting apoptosis in treatment of rectal cancer, it may be a new method to prevent and treat rectal cancer.

Effect of Celecoxib capsules on the biological behavior of LoVo cell of human colorectal cancer / 中国生化药物杂志

Objective To investigate the effects of Celecoxib capsules on the proliferation, invasion and other biological behaviors of LoVo cells in human rectal cancer. Methods Cell proliferation was tested by CCK 8 method, the change of cell cycle was detected by using flow cytometry, cell apoptosis in each group was tested by TUNEL staining method, cell migration ability was detected through the scratch healing experiment. Results The results of CCK-8 test showed that the proliferation of LoVo cells of the intervention group was inhibited and the apoptosis rate was increased (P<0.05). The results of flow cytometry showed that the cell cycle of the intervention group was blocked in G0/G1 phase, and the number of cells decreased in S stage. The results of the scratch healing experiment showed that the migration of LoVo cells in the intervention group was decreased, compared with the control group. Conclusion Celecoxib capsules played an important role in inhibiting tumor proliferation and promoting apoptosis in treatment of rectal cancer, it may be a new method to prevent and treat rectal cancer.

Preparation of Epalrestat Solid Dispersion by Hot-Melt Extrusion Technique / 中国药学杂志

OBJECTIVE: To prepare epalrestat (EP) solid dispersion by holt-melt extrusion (HME) technique in order to enhance its dissolution rate. METHODS: Optimal formula was obtained by screening the carrier type and drug proportion. The dispersion state of EP in the solid dispersion and physical mixture were studied with differential X-ray diffraction (X-RD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) analysis techniques. RESULTS: Poloxamer 188 was selected as the carrier with the optimal ratio of Poloxamer188 to EP of 1∶3. The final solid powder product was homogeneous dispersion in light yellow color without any agglomerate. CONCLUSION: The carrier of EP solid dispersion has significant impact on the dissolution behavior and state of EP. Using Poloxamer 188 as the carrier, holt-melt extrusion is an effective technology for improving the in vitro dissolution of EP.