Four novel β-galactoside prodrugs were designed and synthesized from anthraquinones HAQ-OH and AQ-OH in an attempt to use the prodrugs to selectively release superoxide anion (O2−) in cancer cells and to achieve selected anticancer activity by utilizing the Warburg effect and the elevated level of β-galactosidase in certain cancer cells. Cellular assays showed that the prodrugs Gal-HAQ and Gal-AQ selectively inhibited the proliferation and induced apoptosis of ovarian cancer OVCAR-3 cells overexpressing β-galactosidase. Using O2− fluorescent probe, it was found that in OVCAR-3 cells Gal-HAQ and Gal-AQ could time-dependently release O2−, which was essential for their anticancer activity. Furthermore, it was found that Gal-HAQ and Gal-AQ were effective senolytics toward senescent cells overexpressing β-galactosidase without affecting the viability of corresponding non-senescent cells, further confirming the β-galactosidase-dependent cytotoxicity of the prodrugs. In conclusion, Gal-HAQ and Gal-AQ, which release O2− in response to β-galactosidase, are expected to serve as candidate prodrugs targeting cancer cells.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

Objective:To evaluate the feasibility of non-invasive prenatal testing (NIPT) for the screening of fetal chromosome aneuploidies in twin pregnancies.Methods:A total of 2 745 women with twin-pregnancies were subjected for NIPT screening. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried out on amniotic fluid samples from those with a high risk for fetal chromosome aneuploidies, and the diagnosis and pregnancy outcome were followed up. The sensitivity, specificity, positive predictive value and false positive rate of the NIPT were calculated.Results:Compared with other chromosomal abnormalities, NIPT had a higher efficacy for trisomy 21 and sex chromosomal aneuploidy (SCA) in twin pregnancies (with sensitivity being 100%, 100%, and specificity being 99.93%, 99.9%, respectively). It is difficult to evaluate the efficacy for trisomies 18 and 13 due to the limited data. For chromosome microdeletions and microduplications spanning 15 ~ 21 Mb, NIPT also had a certain detection rate. Compared with women with natural conception, NIPT had a higher detection rate for those with twin pregnancies by assisted reproduction ( P < 0.05). Conclusion:It is feasible to use NIPT for the detection of chromosome aneuploidies in women with twin pregnancies.

The environmental pollution and health hazards caused by the extensive use of organophosphorus flame retardants (OPFRs) have become a problem of wide concern around the world. As a typical OPFR, 2-ethylhexyl diphenyl phosphate (EHDPP) can be detected in water, atmosphere, soil and other environmental media. It widely exists in production and life and can accumulate in organisms, causing great risks the ecosystem and human health. This paper reviews the research of EHDPP domestically and abroad, and summarizes the physicochemical properties of EHDPP and the population situation of occupational exposure, environmental exposure, and population exposure in recent years. Besides, it summarizes the toxic effects and mechanisms of EHDPP, including acute toxicity, hepatotoxicity, neurotoxicity, reproductive and developmental toxicity, and carcinogenesis effects. This paper also proposes the future direction of toxicity and health risks of EHDPP, which provides a theoretical basis for further research on environmental hazards and safety evaluation of EHDPP.

With the core of "molecules and cells", the integrated curriculum group of School of Basic Medical Sciences, Lanzhou University, focuses on the transfer of life molecules, reorganizes teaching content, and integrates Medical Cell Biology, Biochemistry and Molecular Biology, and Medical Genetics to construct a new integrated course of Molecular Medicine. The curriculum group actively explores and practices the mode of medical integration through reconstruction of the curriculum system and optimization of the course content. On the basis of establishing the online course system, the group explores the diversified teaching methods and evaluation systems suitable for Molecular Medicine and discusses the problems in curriculum construction.

The environmental pollution and health hazards caused by the extensive use of organophosphorus flame retardants (OPFRs) have become a problem of wide concern around the world. As a typical OPFR, 2-ethylhexyl diphenyl phosphate (EHDPP) can be detected in water, atmosphere, soil and other environmental media. It widely exists in production and life and can accumulate in organisms, causing great risks the ecosystem and human health. This paper reviews the research of EHDPP domestically and abroad, and summarizes the physicochemical properties of EHDPP and the population situation of occupational exposure, environmental exposure, and population exposure in recent years. Besides, it summarizes the toxic effects and mechanisms of EHDPP, including acute toxicity, hepatotoxicity, neurotoxicity, reproductive and developmental toxicity, and carcinogenesis effects. This paper also proposes the future direction of toxicity and health risks of EHDPP, which provides a theoretical basis for further research on environmental hazards and safety evaluation of EHDPP.

This study was designed to investigate the effect of hypoxia on preeclampsia(PE)by modulating the Src/Siglec-6/SHP2 signaling pathway in the cytoplasm of trophoblast cells.Mouse model of PE was established in normal control and Siglec-6 knockdown mice by L-NAME administration,with aims of studying the changes in vascular diameter of spiral arteries in vivo and examining the expression levels of Siglec-6,p-Src,p-Shp2 and p-ERK1/2 proteins in mouse uterine vascular tissues.While,the effect of Src/Siglec-6/SHP2 on the invasive proliferation of trophoblast cells was explored by culturing human chorionic trophoblast cells HTR-8/SVneo with hypoxia in vitro.In vivo experimental assays showed that the diameter of spiral arteries was reduced in the Siglec-6 knockdown group of mice,and the expression levels of Siglec-6,p-Src,p-SHP2 and p-ERK1/2 proteins were significantly reduced.In vitro hypoxic HTR-8/SVneo cell model results revealed that Siglec-6 overexpression could promote trophoblast cell invasion and proliferation by regulating p-Src,p-SHP2,p-ERK1/2,MMP2,P53 and P21.While,suppression of Src and SHP2 eliminated Siglec-6 overexpression-mediated Siglec-6,p-Src,p-SHP2 and p-ERK1/2 expression,and inhibited the ability of Siglec-6 overexpression to mediate trophoblast invasion and proliferation.Taken together,Siglec-6 plays an important role in preeclampsia,and can alleviate preeclampsia by promoting trophoblast invasion and proliferation through the Src/SHP2 signalling pathway.

OBJECTIVE: To analyze the characteristics of genetic variants among children with refractory epilepsy (RE). METHODS: One hundred and seventeen children with RE who had presented at the Affiliated Jinhua Hospital of Zhejiang University School of Medicine from January 1, 2018 to November 21, 2019 were selected as the study subjects. The children were divided into four groups according to their ages of onset: < 1 year old, 1 ~ 3 years old, 3 ~ 12 years old, and >= 12 years old. Clinical data and results of trio-whole exome sequencing were retrospectively analyzed. RESULTS: In total 67 males and 50 females were included. The age of onset had ranged from 4 days to 14 years old. Among the 117 patients, 33 (28.21%) had carried pathogenic or likely pathogenic variants. The detection rates for the < 1 year old, 1 ~ 3 years old and >= 3 years old groups were 53.85% (21/39), 12.00% (3/25) and 16.98% (9/53), respectively, with a significant difference among the groups (χ² = 19.202, P < 0.001). The detection rates for patients with and without comorbidities were 33.33% (12/36) and 25.93% (21/81), respectively (χ² = 0.359, P = 0.549). Among the 33 patients carrying genetic variants, 27 were single nucleotide polymorphisms (SNPs) or insertion/deletions (InDels), and 6 were copy number variations (CNVs). The most common mutant genes were PRRT2 (15.15%, 5/33) and SCN1A (12.12%, 4/33). Among children carrying genetic variants, 72.73% (8/11) had attained clinical remission after adjusting the medication according to the references. CONCLUSION 28.21% of RE patients have harbored pathogenic or likely pathogenic variants or CNVs. The detection rate is higher in those with younger age of onset. PRRT2 and SCN1A genes are more commonly involved. Adjusting medication based on the types of affected genes may facilitate improvement of the remission rate.
Infant ; Female ; Male ; Humans ; Child ; Infant, Newborn ; Child, Preschool ; DNA Copy Number Variations ; Drug Resistant Epilepsy/genetics* ; Retrospective Studies ; Polymorphism, Single Nucleotide

Objective The combined detection of serum angiopoietin-like protein 8(ANGPTL8)and Vascular cell adhesion molecule-1(VCAM-1)levels was analyzed for the predictive value of cerebral vasospasm(CVS)after intracranial aneurysm embolization.Methods A total of 196 patients who underwent intracranial aneurysm embolization in our hospital from March 2019-March 2022 were selected as the study subjects,99 patients with CVS were in the CVS group,and 97 patients without CVS were in the non CVS group.Serum ANGPTL8 and VCAM-1 levels were detected by ELISA;the correlation between serum ANGPTL8 and VCAM-1 levels was analyzed by Pearson method,Logistic regression was used to analyze the influencing factors of CVS in patients undergoing intracranial aneurysm embolization;ROC curve was used to analyze the serum levels of ANGPTL8 and VCAM-1 to predict the cutoff value of CVS in patients undergoing intracranial aneurysm embolization;four grid table method was used to analyze the predictive value of ANGPTL8,VCAM-1 and their combination on the occurrence of CVS in patients undergoing intracranial aneurysm embolization.Results The differences between CVS and non-CVS groups were statistically significant in hypertension,Hunt-Hess grade,and Glasgow coma(GCS)scores(P＜0.05).The serum ANGPTL8 and VCAM-1 levels in the CVS group were significantly higher than those in the non-CVS group(P＜0.05).There was a positive correlation between serum ANGPTL8 and VCAM-1(r=0.468,P＜0.05).Multivariate analysis showed that high level of ANGPTL8(OR=3.652,95％CI:1.434-9.302),high level of VCAM-1(OR=2.619,95％CI:1.212-5.658),Hunt Hess grade Ⅲ-Ⅳ(OR=1.927,95％CI:1.104-3.362),GCS score of 3-8(OR=2.813,95％CI:1.257-6.295)were independent risk factors for CVS in patients undergoing intracranial aneurysm embolization.The AUC of serum ANGPTL8 level in predicting CVS in patients undergoing intracranial aneurysm embolization was 0.844,and the cut-off value was 189.233 U/L;the AUC of serum VCAM-1 level in predicting CVS in patients undergoing intracranial aneurysm embolization was 0.795,and the cutoff value was 17.984 mg/L.The accuracy,sensitivity and specificity of the combined prediction for CVS were 89.81％,93.94％and 85.57％,respectively,which were obviously higher than those of the single prediction.Conclusion The serum levels of ANGPTL8 and VCAM-1 in CVS group are obviously higher than those in non CVS group.The combination of the two has a high predictive value for CVS after intracranial aneurysm embolization.