Establishment of a high-throughput screening platform based on drug repurposing targeting alpha-1-acid glycoprotein and discovery of potential weight loss drugs / 药学实践杂志

Objective Alpha-1-acid glycoprotein （ORM） was a new target for the development of weight loss drugs. To search for potential weight loss drugs that could target ORM from the compound library of already marketed drugs based on drug repurposing. Methods The pGL4.20-ORM1 promoter recombinant plasmid was contructed and validated, and then a lentiviral vector was utilized to establish stable AML12 cell lines expressing ORM1 promoter-LUC-PURO. This cell line was employed for high-throughput screening of compounds from the marketed drug library, and the luminescence value of the cells was characterized by enzyme marker. Results Primary screening and secondary screening of 1 470 compounds identified 42 compounds that increased ORM1 promoter expression and could be used for further weight loss effect assessment. Conclusion This study successfully constructed LV-AML12-ORM1 promoter-LUC-PURO stable expression cell lines using lentiviral vectors, laying a foundation for efficient and stable screening of weight loss drugs targeting ORM.

Concentration improvement test for athletes in archery training / Teste de melhoria de concentração para atletas em treino de tiro com arco / Prueba de mejora de la concentración para deportistas en el entrenamiento de tiro con arco

ABSTRACT Introduction: There is a correlation between competition performance with a concentration in competitive archery athletes. It is an essential theme in academia to improve the performance of archers, the belief that this goal can be achieved by increasing their concentration. Studies on concentration and relaxation in archery training have shown effective indicators to evaluate training intensity and athlete cognition, but there is still no scientific consensus. Objective: This study aims to analyze the impact of concentration on traditional archery and athlete performance during competition. Methods: Twenty traditional archers were selected as research volunteers. They underwent a battery of biometric tests, including an EEG system to perform group tests. A chi-square test was performed on concentration and relaxation data. The results were analyzed according to the influence of the above two factors on the athletes' performance. In parallel, this paper analyzed the relationship between the degree of relaxation and the archers' performance. Results: There was a positive correlation between concentration and performance. More focused athletes perform better. The data were statistically significant (P<0.05). There is a positive correlation between relaxation and performance. The data were statistically significant (P<0.05). Conclusion: The results of this article provide evidence that both concentration and relaxation can help improve archer performance. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Há uma correlação entre o desempenho na competição com a concentração nos atletas arqueiros competidores. É um tema essencial na academia para melhorar o desempenho dos arqueiros a crença de que esse objetivo pode ser alcançado aumentando a sua concentração. Estudos sobre a concentração e o relaxamento no treinamento de arco e flecha mostraram indicadores eficazes para avaliar a intensidade do treinamento e a cognição do atleta, porém ainda não há um consenso científico. Objetivo: Este estudo tem como objetivo analisar o impacto da concentração sobre o esporte de arco e flecha tradicional e o desempenho do atleta durante a competição. Métodos: Foram selecionados 20 arqueiros tradicionais como voluntários de pesquisa. Estes foram submetidos a uma bateria de testes biométricos, incluindo um sistema EEG para realizar testes em grupo. Realizou-se um teste qui-quadrado sobre os dados de concentração e relaxamento. Os resultados foram analisados segundo a influência dos dois fatores acima no desempenho dos atletas. Paralelamente, este artigo analisou a relação entre o grau de relaxamento e o desempenho dos arqueiros. Resultados: Houve correlação positiva entre a concentração e o desempenho. Atletas mais focados realmente têm melhor desempenho. Os dados foram estatisticamente significativos (P<0,05). Há uma correlação positiva entre relaxamento e desempenho. Os dados foram estatisticamente significativos (P<0,05). Conclusão: Os resultados deste artigo evidenciam que tanto a concentração quanto o relaxamento podem ajudar a melhorar o desempenho dos arqueiros. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Existe una correlación entre el rendimiento en la competición y la concentración en los atletas de tiro con arco de competición. Es un tema esencial en la academia para mejorar el rendimiento de los arqueros la creencia de que este objetivo se puede lograr mediante el aumento de su concentración. Los estudios sobre la concentración y la relajación en el entrenamiento de tiro con arco han mostrado indicadores eficaces para evaluar la intensidad del entrenamiento y la cognición del deportista, pero aún no hay consenso científico. Objetivo: Este estudio pretende analizar el impacto de la concentración en el deporte del tiro con arco tradicional y el rendimiento del atleta durante la competición. Métodos: Se seleccionaron veinte arqueros tradicionales como voluntarios para la investigación. Estos fueron sometidos a una batería de pruebas biométricas, incluyendo un sistema de EEG para realizar pruebas de grupo. Se realizó una prueba de chi-cuadrado con los datos de concentración y relajación. Los resultados se analizaron en función de la influencia de los dos factores mencionados en el rendimiento de los atletas. Paralelamente, este artículo analizó la relación entre el grado de relajación y el rendimiento de los arqueros. Resultados: Hubo una correlación positiva entre la concentración y el rendimiento. Los atletas más concentrados rinden más. Los datos fueron estadísticamente significativos (P<0,05). Existe una correlación positiva entre la relajación y el rendimiento. Los datos fueron estadísticamente significativos (P<0,05). Conclusión: Los resultados de este artículo demuestran que tanto la concentración como la relajación pueden ayudar a mejorar el rendimiento de los arqueros. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Solid Tumors With Cold Agglutinins:Report of Two Cases and Literature Review / 中国医学科学院学报

Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.

Clinicopathological Features and Prognosis of Patients Newly Diagnosed With Lung Adenocarcinoma With Both EGFR Mutation and C-MET Amplification / 中国医学科学院学报

Objective To explore the clinicopathological features and prognosis of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification.Methods The pathological sections were reviewed.EGFR mutation was detected by amplification refractory mutation system-quantitative real-time polymerase chain reaction,and C-MET amplification by fluorescence in situ hybridization.The clinicopathological features and survival data of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification were analyzed retrospectively.Results In 11 cases of EGFR mutation combined with C-MET amplification,complex glands and solid high-grade components were observed under a microscope in 10 cases except for one case with a cell block,the tissue structure of which was difficult to be evaluated.The incidence of lung adenocarcinoma in the patients with EGFR mutation combined with C-MET amplification at clinical stage Ⅳ was higher than that in the EGFR mutation or C-MET amplification group (all P<0.001),whereas the difference was not statistically significant between the EGFR mutation group and C-MET amplification group at each clinical stage (all P>0.05).There was no significant difference in the trend of survival rate between EGFR gene group and C-MET amplification group (χ2=0.042,P=0.838),while the survival of the patients with EGFR mutation combined with C-MET amplification was worse than that of the patients with EGFR mutation (χ2=246.72,P<0.001) or C-MET amplification (χ2=236.41,P<0.001).Conclusions The patients newly diagnosed with lung adenocarcinoma with EGFR mutation plus C-MET amplification demonstrate poor histological differentiation,rapid progress,and poor prognosis.The patients are often in the advanced stage when being diagnosed with cancer.Attention should be paid to this concurrent adverse driving molecular event in clinical work.With increasing availability,the inhibitors targeting C-MET may serve as an option to benefit these patients in the near future.

Association between Fruit and Vegetable Intake and Arterial Stiffness: The China-PAR Project / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the association between fruit and vegetable intake and arterial stiffness.@*METHODS@#We conducted a cohort-based study comprising 6,628 participants with arterial stiffness information in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. A semi-quantitative food-frequency questionnaire was used to assess baseline (2007-2008) and recent (2018-2021) fruit and vegetable intake. We assessed changes in fruit and vegetable intake from 2007-2008 to 2018-2021 in 6,481 participants. Arterial stiffness was measured using the arterial velocity-pulse index (AVI) and arterial pressure-volume index (API). Elevated AVI and API values were defined according to diverse age reference ranges.@*RESULTS@#Multivariable-adjusted linear regression models revealed that every 100 g/d increment in fruit and vegetable intake was associated with a 0.11 decrease in AVI ( B= -0.11; 95% confidence interval [ CI]: -0.20, -0.02) on average, rather than API ( B = 0.02; 95% CI: -0.09, 0.13). The risk of elevated AVI (odds ratio [ OR] = 0.82; 95% CI: 0.70, 0.97) is 18% lower in individuals with high intake (≥ 500 g/d) than in those with low intake (< 500 g/d). Furthermore, maintaining a high intake in the past median of 11.5 years of follow-up was associated with an even lower risk of elevated AVI compared with a low intake at both baseline and follow-up ( OR = 0.64; 95% CI: 0.49, 0.83).@*CONCLUSION@#Fruit and vegetable intake was negatively associated with arterial stiffness, emphasizing recommendations for adherence to fruit and vegetable intake for the prevention of arterial stiffness.

An Investigation of the Effects of B7-H4 Gene rs10754339 and miR-125a Gene rs12976445 on Cancer Susceptibility / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the effects of the B7-H4 gene rs10754339 and miR-125a gene rs12976445 on cancer susceptibility through a case-control study and meta-analysis.@*METHODS@#A total of 1,490 cancer patients (lung/gastric/liver/: 550/460/480) and 800 controls were recruited in this case-control study. The meta-analysis was performed by pooling the data from previous related studies and the present study.@*RESULTS@#The results of this study showed that in the Hubei Han Chinese population, the rs10754339 gene was significantly associated with the risk of lung and gastric cancer but not liver cancer, and the rs12976445 gene was significantly associated with the risk of lung cancer but not liver or gastric cancer. The meta-analysis results indicated that rs10754339 and rs12976445 contributed to cancer susceptibility in the Chinese population and also revealed a significant association between rs10754339 and breast cancer risk, as well as between rs12976445 and lung cancer risk.@*CONCLUSION@#The B7-H4 gene rs10754339 and miR-125a gene rs12976445 may be the potential genetic markers for cancer susceptibility in the Chinese population, which should be validated in future studies with larger sample sizes in other ethnic populations.

Diagnosis of primary clear cell carcinoma of the liver based on Faster region-based convolutional neural network / 中华医学杂志(英文版)

BACKGROUND@#Distinguishing between primary clear cell carcinoma of the liver (PCCCL) and common hepatocellular carcinoma (CHCC) through traditional inspection methods before the operation is difficult. This study aimed to establish a Faster region-based convolutional neural network (RCNN) model for the accurate differential diagnosis of PCCCL and CHCC.@*METHODS@#In this study, we collected the data of 62 patients with PCCCL and 1079 patients with CHCC in Beijing YouAn Hospital from June 2012 to May 2020. A total of 109 patients with CHCC and 42 patients with PCCCL were randomly divided into the training validation set and the test set in a ratio of 4:1.The Faster RCNN was used for deep learning of patients' data in the training validation set, and established a convolutional neural network model to distinguish PCCCL and CHCC. The accuracy, average precision, and the recall of the model for diagnosing PCCCL and CHCC were used to evaluate the detection performance of the Faster RCNN algorithm.@*RESULTS@#A total of 4392 images of 121 patients (1032 images of 33 patients with PCCCL and 3360 images of 88 patients with CHCC) were uesd in test set for deep learning and establishing the model, and 1072 images of 30 patients (320 images of nine patients with PCCCL and 752 images of 21 patients with CHCC) were used to test the model. The accuracy of the model for accurately diagnosing PCCCL and CHCC was 0.962 (95% confidence interval [CI]: 0.931-0.992). The average precision of the model for diagnosing PCCCL was 0.908 (95% CI: 0.823-0.993) and that for diagnosing CHCC was 0.907 (95% CI: 0.823-0.993). The recall of the model for diagnosing PCCCL was 0.951 (95% CI: 0.916-0.985) and that for diagnosing CHCC was 0.960 (95% CI: 0.854-0.962). The time to make a diagnosis using the model took an average of 4 s for each patient.@*CONCLUSION@#The Faster RCNN model can accurately distinguish PCCCL and CHCC. This model could be important for clinicians to make appropriate treatment plans for patients with PCCCL or CHCC.

Probing bundle-wise abnormalities in patients infected with human immunodeficiency virus using fixel-based analysis: new insights into neurocognitive impairments / 中华医学杂志(英文版)

BACKGROUND@#Changes in white matter (WM) underlie the neurocognitive damages induced by a human immunodeficiency virus (HIV) infection. This study aimed to examine using a bundle-associated fixel-based analysis (FBA) pipeline for investigating the microstructural and macrostructural alterations in the WM of the brain of HIV patients.@*METHODS@#This study collected 93 HIV infected patients and 45 age/education/handedness matched healthy controls (HCs) at the Beijing Youan Hospital between January 1, 2016 and December 30, 2016.All HIV patients underwent neurocognitive evaluation and laboratory testing followed by magnetic resonance imaging (MRI) scanning. In order to detect the bundle-wise WM abnormalities accurately, a specific WM bundle template with 56 tracts of interest was firstly generated by an automated fiber clustering method using a subset of subjects. Fixel-based analysis was used to investigate bundle-wise differences between HIV patients and HCs in three perspectives: fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). The between-group differences were detected by a two-sample t -test with the false discovery rate (FDR) correction ( P <0.05). Furthermore, the covarying relationship in FD, FC and FDC between any pair of bundles was also accessed by the constructed covariance networks, which was subsequently compared between HIV and HCs via permutation t -tests. The correlations between abnormal WM metrics and the cognitive functions of HIV patients were explored via partial correlation analysis after controlling age and gender.@*RESULTS@#Among FD, FC and FDC, FD was the only metric that showed significant bundle-wise alterations in HIV patients compared to HCs. Increased FD values were observed in the bilateral fronto pontine tract, corona radiata frontal, left arcuate fasciculus, left corona radiata parietal, left superior longitudinal fasciculus III, and right superficial frontal parietal (SFP) (all FDR P <0.05). In bundle-wise covariance network, HIV patients displayed decreased FD and increased FC covarying patterns in comparison to HC ( P <0.05) , especially between associated pathways. Finally, the FCs of several tracts exhibited a significant correlation with language and attention-related functions.@*CONCLUSIONS@#Our study demonstrated the utility of FBA on detecting the WM alterations related to HIV infection. The bundle-wise FBA method provides a new perspective for investigating HIV-induced microstructural and macrostructural WM-related changes, which may help to understand cognitive dysfunction in HIV patients thoroughly.

Acupuncture of revised acupoint combination around the skull base for post-stroke mild cognitive impairment: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of acupuncture of revised acupoint combination around the skull base in treating post-stroke mild cognitive impairment (PSMCI), and preliminary explore its action mechanism.@*METHODS@#A total of 76 PSMCI patients were randomly divided into an observation group (38 cases, 4 cases dropped off) and a control group (38 cases, 3 cases dropped off, 1 case was removed). In the observation group, acupuncture of revised acupoint combination around the skull base (bilateral Fengchi [GB 20], Wangu [GB 12], Tianzhu [BL 10] and Yamen [GV 15], Baihui [GV 20]) was used for treatment. In the control group, 8 non-meridian and non-acupoint points at the distal end were selected for shallow puncture treatment. Retaining the needles of 30 min, once every other day,3 times a week for 4 weeks in both groups. The scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), Barthel index (BI) and serum levels of cystatin C (Cys-C) and homocysteine (Hcy) were compared in the two groups before and after treatment, and the clinical efficacy was evaluated.@*RESULTS@#After treatment, the scores of MoCA were increased compared with those before treatment in the two groups (P<0.05), and the score in the observation group was higher than that in the control group (P<0.05). The scores of MMSE and BI were increased compared with those before treatment in the observation group (P<0.05), and the score of MMSE in the observation group was higher than that in the control group (P<0.05). After treatment, the serum levels of Cys-C and Hcy were decreased compared with those before treatment in the observation group (P<0.05), and lower than those in the control group (P<0.05). After treatment, the serum level of Cys-C was increased compared with that before treatment in the control group (P<0.05). The total effective rate of the observation group was 88.2% (30/34), which was higher than 32.4% (11/34) of the control group (P<0.05).@*CONCLUSION@#Acupuncture of revised acupoint combination around the skull base can improve cognitive function and daily living ability of PSMCI patients, which may be related to the down regulation of serum levels of Cys-C and Hcy.

Radiation environment monitoring and analysis of exempted X-ray devices / 中国辐射卫生

Objective To propose specific suggestions for exemption management of X-ray devices applying for exemption management. Methods The weight analysis of influence of shielding thickness and tube voltage on the radiation dose leakage of low-energy X-ray devices was carried out through test analysis, and the radiation status of 50 X-ray devices applied for end-user exemption in Shenzhen, China was investigated. Results There was no significant correlation between the ambient dose equivalent rate and the tube voltage and tube current of the X-ray device. The ambient dose equivalent rate of 50 X-ray devices was 0.16-1.20 μSv/h. Among them, 8 X-ray devices had radiation dose leakage, that is, the ambient dose equivalent rate was greater than 0.36 μSv/h; the ambient dose equivalent rate of one X-ray device was 1.2 μSv/h, exceeding exemption management requirements. Conclusion Applications for exemption management and filing of X-ray devices should be treated differently, and their own shielding effect and inherent safety have a greater impact on radiation safety, which should be focused on.

Research progress of nuclear factor erythroid 2-related factor 2 in pulmonary fibrosis / 中国临床药理学与治疗学

Pulmonary fibrosis is a common chronic interstitial lung disease. It is characterized by excessive deposition of extracellular matrix and remodeling of lung tissue structure, resulting in severe impairment of lung function. The cause of its pathogenesis is still unclear. Therefore, it is urgent to explore its pathogenesis and find new targets to combat pulmonary fibrosis. Studies have shown that nuclear factor erythroid 2-related factor 2 can maintain the body's redox homeostasis by regulating antioxidant genes and combining antioxidant response components, thereby protecting tissues and cells from oxidative stress. In recent years, many studies have proved that nuclear factor erythroid 2 -related factor 2 can play an anti-fibrotic role by alleviating oxidative stress, inhibiting macrophage polarization, activating autophagy, inhibiting ferroptosis, and blocking epithelial-mesenchymal transition. This paper provides a brief review of the association and research progress of nuclear factor erythroid 2-related factor 2 with pulmonary fibrosis, with the aim of providing a new direction for the precise treatment of pulmonary fibrosis.

Research progress of metformin in the pathogenesis of pulmonary fibrosis / 中国临床药理学与治疗学

Pulmonary fibrosis is a chronic, progressive and irreversible respiratory disease characterized by hyperposition of extracellular matrix leading to inflammation and extensive lung remodeling. There is currently no effective treatment. Multiple studies have shown that metformin is a classic antiglycemic drug with antifibrotic potential. However, at present, there is no consensus on the specific mechanism of metformin's anti-fibrosis effect, and this paper reviews the research progress of metformin in the field of pulmonary fibrosis in recent years, mainly from IGF-1/IGF-1R/PI3K signaling, AMPK/mTOR signaling, TGF-β/Smad signaling pathway, and intervening in myofibroblast proliferation and apoptosis, improving oxidative stress, inhibiting epithelial interstitial transformation and transglutaminase. In order to be able to more deeply and comprehensively understand the antifibrosis mechanism and clinical application scope of metformin in the future, and provide new ideas for the treatment of pulmonary fibrosis.

Effectss of hyperoside on traumatic brain injury rats by regulating RhoA/ROCK signaling pathway / 中国临床药理学与治疗学

AIM: To investigate the effects of hyperoside on traumatic brain injury (TBI) rats by regulating the Ras homolog gene family, member A (RhoA)/Rho-associated coiled coil-forming kinase (ROCK) signal pathway. METHODS: The TBI rat model was established by modified Feeney free fall hit method, and was randomly divided into model group, low-dose hyperoside (60 mg / kg) group, high-dose hyperoside (120 mg / kg) group, high-dose hyperoside (120 mg / kg) + no load group, and high-dose hyperoside (120 mg / kg) + RhoA overexpression group, with 10 rats in each group, another 10 healthy rats were set as sham operation group, after hyperoside and plasmid were grouped, the nerve injury was detected by modified neurological deficit score (mNSS) and dark avoidance test; Evans blue (EB) quantitative method was used to detect the permeability of blood brain barrier in rats; ultrastructural damage of blood-brain barrier was observed by transmission electron microscopy; the levels of tumor necrosis factor- α (TNF- α), interleukin-8 (IL-8), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and brain tissue of rats were measured with the kit; and the expression of RhoA/ROCK pathway related proteins in rat brain was detected by Western blot. RESULTS: Compared with the sham operation group, the blood brain barrier structure of the model group rats was damaged, the step-through latency and SOD level decreased obviously (P0.05). CONCLUSION: Hyperoside can inhibit neuroinflammation and oxidative stress in TBI rats by down-regulating RhoA / ROCK signal pathway, thereby reducing the damage of blood brain barrier and repairing its neural function.

Research progress in sodium calcium exchanger and heart failure with preserved ejection fraction / 中国临床药理学与治疗学

Sodium calcium exchanger (NCX) is encoded by the SCL8 family genes and belongs to the cation/Ca

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project / 老年心脏病学杂志（英文版）

BACKGROUND@#The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).@*METHODS@#A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.@*RESULTS@#A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).@*CONCLUSIONS@#Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Structural repurposing of SGLT2 inhibitor empagliflozin for strengthening anti-heart failure activity with lower glycosuria

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC50 > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling / 中国结合医学杂志

OBJECTIVE@#To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro.@*METHODS@#Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor β (TGF-β)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed.@*RESULTS@#High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFβ R1, TGFβ R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01).@*CONCLUSIONS@#Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

Recent Research Progress on CircRNA in Hematological Malignancies--Review / 中国实验血液学杂志

Most hematological tumors have high-grade malignancy and low cure rate, requiring new molecular markers for detection and evaluation. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed-loop structures, which participate in gene transcription and translation by binding to microRNAs and proteins. In recent years, with the deepening research on circRNAs, circRNAs have been found to play an important role in hematological malignancies. In this review, the latest research progress on the function and molecular mechanism of circRNAs in hematological malignancies was systematically summarized, and it was found that circRNAs may be potential new biomarkers and therapeutic targets in hematological malignancies.

Preparation of silk fibroin/hyaluronic acid composite hydrogel based on thiol-ene click chemistry / 浙江大学学报·医学版

OBJECTIVES@#To design and prepare silk fibroin/hyaluronic acid composite hydrogel.@*METHODS@#The thiol modified silk fibroin and the double-bond modified hyaluronic acid were rapidly cured into gels through thiol-ene click polymerization under ultraviolet light condition. The grafting rate of modified silk fibroin and hyaluronic acid was characterized by 1H NMR spectroscopy; the gel point and the internal microstructure of hydrogels were characterized by rheological test and scanning electron microscopy; the mechanical properties were characterized by compression test; the swelling rate and degradation rate were determined by mass method. The hydrogel was co-cultured with the cells, the cytotoxicity was measured by the lactate dehydrogenase method, the cell adhesion was measured by the float count method, and the cell growth and differentiation on the surface of the gel were observed by scanning electron microscope and fluorescence microscope.@*RESULTS@#The functional group substitution degrees of modified silk fibroin and hyaluronic acid were 17.99% and 48.03%, respectively. The prepared silk fibroin/hyaluronic acid composite hydrogel had a gel point of 40-60 s and had a porous structure inside the gel. The compressive strength was as high as 450 kPa and it would not break after ten cycles. The water absorption capacity of the composite hydrogel was 4-10 times of its own weight. Degradation experiments showed that the hydrogel was biodegradable, and the degradation rate reached 28%-42% after 35 d. The cell biology experiments showed that the cytotoxicity of the composite gel was low, the cell adhesion was good, and the growth and differentiation of the cells on the surface of the gel were good.@*CONCLUSIONS@#The photocurable silk fibroin/hyaluronic acid composite hydrogel can form a gel quickly, and has excellent mechanical properties, adjustable swelling rate and degradation degree, good biocompatibility, so it has promising application prospects in biomedicine.

Sex Estimation of Medial Aspect of the Ischiopubic Ramus in Adults Based on Deep Learning / 法医学杂志

OBJECTIVES@#To investigate the reliability and accuracy of deep learning technology in automatic sex estimation using the 3D reconstructed images of the computed tomography (CT) from the Chinese Han population.@*METHODS@#The pelvic CT images of 700 individuals (350 males and 350 females) of the Chinese Han population aged 20 to 85 years were collected and reconstructed into 3D virtual skeletal models. The feature region images of the medial aspect of the ischiopubic ramus (MIPR) were intercepted. The Inception v4 was adopted as the image recognition model, and two methods of initial learning and transfer learning were used for training. Eighty percent of the individuals' images were randomly selected as the training and validation dataset, and the remaining were used as the test dataset. The left and right sides of the MIPR images were trained separately and combinedly. Subsequently, the models' performance was evaluated by overall accuracy, female accuracy, male accuracy, etc.@*RESULTS@#When both sides of the MIPR images were trained separately with initial learning, the overall accuracy of the right model was 95.7%, the female accuracy and male accuracy were both 95.7%; the overall accuracy of the left model was 92.1%, the female accuracy was 88.6% and the male accuracy was 95.7%. When the left and right MIPR images were combined to train with initial learning, the overall accuracy of the model was 94.6%, the female accuracy was 92.1% and the male accuracy was 97.1%. When the left and right MIPR images were combined to train with transfer learning, the model achieved an overall accuracy of 95.7%, and the female and male accuracies were both 95.7%.@*CONCLUSIONS@#The use of deep learning model of Inception v4 and transfer learning algorithm to construct a sex estimation model for pelvic MIPR images of Chinese Han population has high accuracy and well generalizability in human remains, which can effectively estimate the sex in adults.