Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Objective:To learn about the status quo and hotspots in the field of health policy research under the concept of One Health.Methods:The Web of Science Core Collection (WoS) database and China National Knowledge Infrastructure (CNKI) database from 2001 to 2020 were searched for publications in the field of health policy research under the concept of One Health. A total of 3 515 publications in English and 42 in Chinese were included, CiteSpace 5.6.R3 software was used to analyze the number of publications, countries, institutions, authors, and keywords, and to draw visual maps.Results:The number of publications in WoS database was 52 in 2001 and 500 in 2020, with an overall upward trend in the number of publications; the first relevant publication in CNKI database was published in 2009, and the number of publications increased to 13 by 2020, but the total number was still low (42). Among the countries, the USA had the highest number of publications (1 385), total citations (48 780) and highly cited (≥10 citations) publications (671). Switzerland had the highest citations per publication (89.72). China ranked 5th in the number of publications (160) and 8th in total citations (4 643) and citations per publication (29.02), with fewer highly cited publications (82). The English author partnership had a large collaborative team led by Chris Degeling at the University of Sydney; the Chinese author partnership had a large research team led by Lu Jiahai at the School of Public Health, Sun Yat-sen University. In terms of country cooperation, French node had the largest centrality (0.30), the centrality of Chinese nodes was 0.01. Emerging infectious diseases, zoonose, and antibiotic resistance were high-frequency keywords in the English publications, while COVID-19, zoonose, antibiotic resistance, and food safety were high-frequency keywords in the Chinese publications.Conclusions:From 2001 to 2020, the overall trend of the number of publications in health policy research under the concept of One Health worldwide is on the rise. Emerging infectious diseases, zoonose, antibiotic resistance, and food safety are the current research hotspots in this field.

Schizophrenia is a serious mental disease. The diagnosis of schizophrenia so far relies heavily on subjective evidence, including self-reported experiences by patients, manifestations described by relatives, and abnormal behaviors assessed by psychiatrists. The diagnosis, monitoring of the disease progression and therapy efficacy assessment are challenging due to the lack of established laboratory biomarkers. Based on the current literature, clinical consensus, guidelines, and expert recommendations, this review highlighted evidence-based potential laboratory biomarkers for the diagnosis of schizophrenia, including genetic biomarkers, neurotransmitters, neurodevelopmental-related proteins, and intestinal flora, and discussed the potential future directions for the application of these biomarkers in this field, aiming to provide an objective basis for the use of these biomarkers in the early and accurate diagnosis, treatment, and prognosis and rehabilitation assessment of schizophrenia.

Objective:To analyze the influencing factors of early miscarriage after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatment.Methods:From January 2015 to August 2018, 461 cases of pregnant women who received mid luteal phase ovulation induction in Beijing Obstetrics and Gynecology Hospital, Capital Medical University were retrospectively analyzed.According to the pregnancy outcome, the patients were divided into early miscarriage group (54 cases) and delivery group (407 cases). The general situation and ovulation induction outcome of the two groups were compared, and the related factors of early spontaneous miscarriage were analyzed.Results:There was no significant difference in age, pre pregnancy body mass index, type of infertility, history of abortion, thyrotropin, basal endocrine level, number of antral follicles, daily hormone level of hCG injection, and number of oocytes retrieved between early miscarriage group and delivery group (all P>0.05). Logistic regression analysis showed that age and basal follicle stimulating hormone were risk factors for early miscarriage.The risk of early miscarriage in patients with age ≥ 35 years old was 1.854 times higher than that in patients younger than 35 years old, 95% CI 1.027-3.347, P=0.041; the risk of early abortion in patients with basal FSH ≥ 10 U/L was 1.499 times higher than that in patients with basal FSH<10 U/L, 95% CI 0.776-2.895, P=0.048. Conclusion:Age and basal follicle stimulating hormone are risk factors for early miscarriage after long protocol assisted pregnancy in mid luteal phase.

Objective:To investigate the relationship between the levels of vascular endothelial growth factor (VEGF) and homocysteine (Hcy) in serum and diabetic retinopathy (DR) and diabetic nephropathy (DN).Methods:A total of 211 patients with type 2 diabetes mellitus (T2DM) who were treated in Beijing Tongren Hospital from February to July 2019 were selected as the case group, including 72 patients with T2DM (T2DM group), 45 patients with DR (DR group), 49 patients with DN (DN group), 45 patients with DR and DN (DR+DN group); 76 healthy people were selected as the control group. The levels of serum VEGF and Hcy were measured in all subjects. The course of diabetes, body mass index, waist to hip ratio, fasting blood glucose, glycosylated hemoglobin (HbA 1c), triglyceride(TG), total cholesterol(TC), low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), urinary microalbumin/creatinine (ACR), urinary immunoglobulin G/creatinine (IGU/CR), urinary transferrin/creatinine (TRU/CR), urinary α1-microglobulin/creatinine (α1/CR), serum urea nitrogen, serum creatinine, hypersensitive C-reactive protein (hCRP) and erythrocyte sedimentation rate (ESR) were also observed in the case group. Results:The VEGF level of the T2DM group, DR group, DN group and DR+DN group was 90.02(61.24, 118.52), 124.38(81.50, 170.28), 133.19(78.84, 168.49), 124.08(79.82, 187.33)ng/ml respectively, which were significantly higher than that of the control group 50.31(21.10,67.74)ng/ml(all P<0.05); Compared with the T2DM group, the VEGF level in the DR group, DN group and DR+DN group increased significantly (all P<0.05). The level of Hcy in the DN group and DR+DN group [(12.58±3.66), (11.91±2.42) μmol/L, respectively] was higher than that in the control group [(10.44±2.09) μ mol/L], and the difference was statistically significant ( P<0.05). There was no statistically significant difference in VEGF and Hcy levels in different stages of DR ( U=264.00, t=-0.43, P>0.05). The Hcy level of DN patients in the group of massive proteinuria was higher than that in the group of microalbuminuria [(15.00±1.87) vs (11.79±3.76) μmol/L, t=-2.82, P=0.01].VEGF was positively correlated with ACR, TRU/CR and IGU/CR ( r=0.23, 0.19, 0.17, all P<0.05),while Hcy was positively correlated with serum urea nitrogen, serum creatinine, ACR, TRU/CR, IGU/CR and α 1/CR ( r=0.35, 0.44, 0.22, 0.19, 0.21, 0.29, all P<0.05). Conclusions:The level of VEGF in the serum of DR and DN patients increased, suggesting that VEGF may play a role in the development of DR and DN, but there was no significant difference in the level of VEGF in patients with different stages of DR and different urinary albumin excretion rate of DN.The level of serum Hcy in DN patients increased, and that was higher in massive proteinuria group, suggesting that serum Hcy may have clinical significance in the diagnosis and monitoring of DN.

Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I (DHP-I), was developed. In present study, the potential roles of renal organic anion transporters (OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated and in rabbits. Our results indicated that imipenem and cilastatin were substrates of hOAT1 and hOAT3. Cilastatin inhibited hOAT1/3-mediated transport of imipenem with IC values comparable to the clinical concentration, suggesting the potential to cause a clinical drug-drug interaction (DDI). Moreover, imipenem exhibited hOAT1/3-dependent cytotoxicity, which was alleviated by cilastatin and probenecid. Furthermore, cilastatin and probenecid ameliorated imipenem-induced rabbit acute kidney injury, and reduced the renal secretion of imipenem. Cilastatin and probenecid inhibited intracellular accumulation of imipenem and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells. Renal OATs, besides DHP-I, was also the target of interaction between imipenem and cilastatin, and contributed to the nephrotoxicity of imipenem. This therefore gives in part the explanation about the mechanism by which cilastatin protected against imipenem-induced nephrotoxicity. Thus, OATs can potentially be used as a therapeutic target to avoid the renal adverse reaction of imipenem in clinic.

Shanghai Jiao Tong University established the first biomedical science in China in 2016. Learning the successful experience from international universities can promote the development of this major. According to the comparison of cultivation program and curriculum system in different top universities at home and abroad, it was showed that Oxford University focused on the pluralism development of students, University of Technology Sydney paid attention to the combination of basis and clinical practice, and the University of Hong Kong stressed the integration of clinical practice, science and research, and transformation. Through the exploration of the details of educational system this university, we found that we mainly focused on five innovation ideas: building the basic knowledge, strengthening comprehensive basic knowledge teaching, stimulating students' interests towards biomedical science, developing their ability and promoting innovative education and training. Based on analysis of those cases, it is showed that the development of biomedical science in China should solve problems in curriculum integration and practical education of science and research, so as to achieve the goal to cultivate more talents in this major and boost the development and advances in the field of biomedical science.

Objective To evaluate the effect of sevoflurane on the electrophysiological stability of i-solated rat hearts subjected to hypothermic perfusion. Methods Clean-grade healthy adult male Sprague-Dawley rats, weighing 280-360 g, were heparinized and anesthetized with pentobarbital sodium. Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％CO2 at 37℃. Twenty-four Langendorff-perfused hearts were divided into 4 groups ( n=6 each) using a ran-dom number table method: control group ( C group ) , sevoflurane group ( S group ) , 32 ℃ hypothermia group ( H group) and 32℃ hypothermia plus sevoflurane group ( HS group) . After 15 min of equilibration, the isolated hearts were continuously perfused for 30 min with K-H solution at 37℃, with K-H solution con-taining 2. 3％ sevoflurane at 37 ℃, with K-H solution at 32 ℃, and with K-H solution containing 2. 3％sevoflurane at 32℃ in C, S, H and HS groups, respectively. Heart rate and monophasic action potential in three layers of the left ventricular anterior wall were recorded at 15 min of equilibration ( T0 ) and 30 of con-tinuous perfusion ( T2 ) , the transmural dispersion of repolarization ( TDR) were calculated, and the occur-rence of arrhythmia was observed. Results Compared with C and S groups, the heart rate was significantly decreased and TDR was enlarged at T1 , and the incidence of arrhythmia was increased in H and HS groups ( P<0. 05) . Compared with H group, TDR was significantly reduced at T1 , and the incidence of arrhythmia was decreased in HS group ( P<0. 05) . Conclusion Sevoflurane can improve the electrophysiological in-stability of isolated rat hearts subjected to hypothermic perfusion, and thus decrease the development of ar-rhythmia.

Human cytosolic sulfotransferase 2A1 (SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, arenobufagin (AB) was proved as a potential probe substrate for SULT2A1 with high sensitivity and specificity. Subsequently, the sulfation of AB was characterized by experimental and molecular docking studies. The sulfate-conjugated metabolite was identified as AB-3-sulfate. The sulfation of AB displayed a high selectivity for SULT2A1 which was confirmed by reaction phenotyping assays. The sulfation of AB by human liver cytosols and recombinant SULT2A1 both obeyed Michaelis-Menten kinetics, with similar kinetic parameters. Molecular docking was performed to understand the interaction between AB and SULT2A1, in which the lack of interaction with Met-137 and Tyr-238 of SULT2A1 made it possible to eliminate substrate inhibition of AB sulfation. Finally, the probe was successfully used to determine the activity of SULT2A1 and its isoenzymes in tissue preparations of human and laboratory animals.