Trophoblast cells serve as the foundation for placental development. We analyzed published multiomics sequencing data and found that trophoblast cells highly expressed RRS1 compared to primitive endoderm and epiblast. We used HTR-8/SVneo cells for further investigation, and Western blot and immunofluorescence staining confirmed that HTR-8/SVneo cells highly expressed RRS1. RRS1 was successfully knocked down in HTR-8/SVneo cells using siRNA. Using IncuCyte S3 live-cell analysis system based on continuous live-cell imaging and real-time data, we observed that proliferation, migration, and invasion abilities were all significantly decreased in RRS1-knockdown cells. RNA-seq revealed that knockdown of RRS1 affected the gene transcription, and upregulated pathways in extracellular matrix organization, DNA damage response, and intrinsic apoptotic signaling, downregulated pathways in embryo implantation, trophoblast cell migration, and wound healing. Differentially expressed genes were enriched in diseases related to placental development. Consistent with these findings, human chorionic villus samples collected from spontaneous abortion cases exhibited significantly reduced RRS1 expression compared to normal controls. Our results highlight the functional importance of RRS1 in human trophoblasts and suggest that its deficiency contributes to early pregnancy loss.
Humans ; Trophoblasts/physiology* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Female ; Pregnancy ; Abortion, Spontaneous/metabolism* ; Cell Line ; Placentation/genetics*

AIM:To investigate the effect of vaccarin(VAC)on endothelial dysfunction in type 2 diabetes mellitus(T2DM),and to uncover the underlying mechanisms.METHODS:(1)C57BL/6 mice received intraperitoneal injection of streptozotocin and were fed with a high-fat diet(21.8 kJ/kg,60%of the energy source was fat)to construct a T2DM mouse model.Thirty mice were randomly divided into control,T2DM and T2DM+VAC groups,with 10 mice in each group.The mice in T2DM+VAC group were given 1 mg/kg VAC via oral gavage for 6 weeks,while those in control and T2DM groups were given the same volume of PBS.The mRNA and protein expression levels of BCL2-interacting pro-tein 3(BNIP3),PTEN-induced kinase 1(PINK1)and parkin in the thoracic aorta were detected by RT-qPCR and West-ern blot.(2)Human umbilical vein endothelial cells(HUVECs)were stimulated by high glucose(HG;35 mmol/L glu-cose).Mitochondrial membrane potential,autophagy and mitochondrial superoxide levels were detected using JC-1,acri-dine orange(AO)and MitoSOX staining,respectively.RESULTS:Compared with control group,the mRNA and protein levels of BNIP3,PINK1 and parkin were significantly increased in the thoracic aorta of T2DM mice(P<0.05).Compared with T2DM group,the mRNA and protein levels of BNIP3,PINK1 and parkin in the thoracic aorta were significantly re-duced in T2DM+VAC group(P<0.05).The results of JC-1,AO and MitoSOX staining showed that VAC attenuated the decrease in mitochondrial membrane potential and the increase in autophagy and mitochondrial superoxide levels in HG-in-duced HUVECs.Treatment with VAC also inhibited HG-mediated mitochondrial damage in HUVECs after BNIP3 overex-pression.The effect of miR-570-3p mimic on mitochondrial damage was similar to VAC.RT-qPCR and Western blot showed that both miR-570-3p mimic and VAC significantly reduced the mRNA and protein levels of BNIP3,PINK1 and parkin.In contrast,inhibition of miR-570-3p exhibited the opposite effects.CONCLUSION:Treatment with VAC alle-viated endothelial dysfunction in T2DM by inhibiting HG-induced mitochondrial dysfunction through miR-570-3p/BNIP3.

This paper analyzes the literature on virtual reality(VR)technology interventions for autistic children published from 2014 to 2022.It shows that different VR systems in these studies have improved different symptoms of autism,and points out the feasibility of VR technology interventions for autistic children.

Alzheimer's disease(AD)is a common neurodegenerative disease with the main manifesta-tions of progressive cognitive dysfunction,behavioral disorders,and gradual decline of living ability.The etiology of AD is complex,and the pathogenesis of this disease remains controversial.Calcium signaling plays an impor-tant role in regulating neuronal activities,including neurotransmitter release,synaptic plasticity,memory stor-age,and neuronal apoptosis.Increasing studies have shown that neuronal calcium dyshomeostasis is a major path-ological factor in the occurrence and development of AD.This article reviews the role and research progress in in-tracellular calcium dyshomeostasis in AD,including the relationship between calcium homeostasis and amyloidβ,the role of calcium/calmodulin-dependent protein kinases in tau phosphorylation,calcium signaling path-ways,the relationship between calcium homeostasis and mitochondrial function,autophagy,and neuroinflamma-tion.

OBJECTIVE: To determine the feasibility of conducting a full-scale randomized controlled trial (RCT) and investigate the basic information and safety of acupuncture for patients with chronic spontaneous urticaria (CSU). METHODS: A total of 80 participants with CSU from July 2018 to July 2019 were randomly assigned to receive active acupuncture (n=41) on a fixed prescription of acupoints or sham acupuncture (n=39) with superficial acupuncture on non-acupuncture points through the completely randomized design. Patients in both groups received 5 sessions per week for 2 weeks, and participants were followed for a further 2 weeks. Feasibility was assessed by recruitment and randomization rates, retention of participants, treatment protocol adherence, and the incidence of adverse events (AEs). The clinical primary outcome was the changes from baseline weekly urticaria activity scores (UAS7) after treatment at 2 weeks. Secondary outcomes included the Visual Analogue Scale (VAS) score of itching intensity, Dermatology Life Quality Index (DLQI), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA). RESULTS: A total of 80 participants were enrolled. The recruitment rate of 24.02%, randomization rate of 100%, a loss rate of 6.25%, and no obvious AEs were observed in either group. The decrease from baseline in the mean UAS7 total score at week 2 in the active acupuncture group was -8.63 (95%CI, -11.78 to -5.49) and -6.21 (95%CI, -9.43 to -2.98) in the sham acupuncture group for a between-group difference of -2.42 (95% CI, -6.93 to 2.07). The change in the DLQI, VAS of itching intensity, HAMA, and HAMD were a slightly better improvement trend in the active acupuncture group than the sham acupuncture group, but the between-group difference was not significant. CONCLUSIONS Active acupuncture had a better improvement trend in alleviating symptoms, improving quality of life and regulating the mood of anxiety and depression in patients with CSU than sham acupuncture. (Registration Nos. AMCTR-ICR-18000190 and ChiCTR2100054776).

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Objective:To summarize the construction and practice of the compulsory postgraduate course "reproductive genetics in gynecology and obstetrics" in Department of Gynecology and Obstetrics, Peking University, and to evaluate the teaching effect of this course.Methods:A total of 139 postgraduates who studied in Department of Obstetrics and Gynecology, Peking University, from 2019 to 2021 were enrolled as subjects, and a syllabus was constructed through a top-level design based on the "biological-psychological-social medicine pattern", with the teaching objectives of reproductive genetics theory, clinical translation, genetic counseling methods, and research advances. The teaching effect was evaluated by analyzing teaching assessment results, teaching evaluation feedback, and teaching achievements. SPSS 26.0 software was used to perform the t-test and the chi-square test. Results:The written test score, usual performance score, and total score of the postgraduate students in 2021 were higher than those in 2019 and 2020 [(73.50±8.19) vs. (70.94±14.90); (68.60±2.82) vs. (68.22±4.58); (90.58±4.18) vs. (89.49±7.60)], with significant differences in written test score and total score ( P<0.05). There was a high degree of satisfaction with the feedback of teaching, and 85.61% (119/139) of the students selected "great satisfaction"; in particular, there were increases in the degree of satisfaction with expanding research ideas and reflecting the advances in this discipline, but with no significant difference. There was a significant increase in the number of published articles. Conclusion:For the active implementation of the course of "Reproductive Genetics in Obstetrics and Gynecology", improving the teaching process in a planned and step-by-step way through a top-level design in advance can help to expand research ideas for future research work among postgraduates in obstetrics and gynecology and promote the sustainable development and improvement of the teaching of the emerging interdisciplinary discipline of reproductive genetics in obstetrics and gynecology.

Objective To analyze and discuss the epidemiological characteristics and drug resistance of pathogenic bacteria of infective endocarditis in Nanjing in the past five years, and to provide reference for the prevention and treatment of infective endocarditis. Methods A total of 220 infective endocarditis cases in Nanjing area from 2015 to 2020 were included in the analysis. The distribution characteristics of pathogens were collected and analyzed. Information on drug resistance was also collected, and the potential relationship between pathogen distribution and drug resistance was explored. Statistical analysis was performed using SPSS 19.0. Results The ratio of male to female patients included in this study was 143:77, and most of them were aged from 41 to 60 years old. There were 195 patients with underlying cardiac diseases (88.64%). A total of 1132 pathogenic bacteria were detected in the blood samples of all 220 patients, among which 1 007 were mainly gram-positive bacteria (88.96%): 725 strains of Streptococcus viridans (725/1 132, 64.05%), 124 strains of Staphylococcus aureus (124/1 132, 10.95%), 96 strains of Staphylococcus epidermidis (96/1 132, 8.48%), and 62 strains (62/1 132, 5.48%) of others (Staphylococcus human, etc.); the main gram-negative bacteria ( a total of 125 strains , 11.04%) were 73 strains of Pseudomonas aeruginosa (73/1 132, 6.45%) and 52 strains of Escherichia coli (52/1 132, 4.59%). Among the strains isolated from subjects of different ages and genders, the distribution difference was consistent with the total trend, and there was no significant difference (all P>0.05). Among gram-positive bacteria, Streptococcus was sensitive to antibiotics such as penicillin, oxacillin, and vancomycin. Staphylococcus aureus and S. epidermidis were sensitive to vancomycin and resistant to oxacillin and penicillin. Gram-negative bacteria were less resistant to amikacin and meropenem. All these differences were statistically significant (all P<0.05). Conclusion For patients with infective endocarditis, antibiotics should be selected reasonably according to the type of pathogenic bacteria and the corresponding drug resistance characteristics.

After decades of development,protein and peptide drugs have now grown into a major drug class in the marketplace.Target identification and validation are crucial for the discovery of protein and peptide drugs,and bioinformatics prediction of targets based on the characteristics of known target proteins will help improve the efficiency and success rate of target selection.However,owing to the developmental history in the pharmaceutical industry,previous systematic exploration of the target spaces has mainly focused on traditional small-molecule drugs,while studies related to protein and peptide drugs are lacking.Here,we systematically explore the target spaces in the human genome specifically for protein and peptide drugs.Compared with other proteins,both suc-cessful protein and peptide drug targets have many special characteristics,and are also significantly different from those of small-molecule drugs in many aspects.Based on these features,we develop separate effective genome-wide target prediction models for protein and peptide drugs.Finally,a user-friendly web server,Predictor Of Protein and Peptide drugs'therapeutic Targets(POPPIT)(http://poppit.ncpsb.org.cn/),is established,which provides not only target prediction specifically for protein and peptide drugs but also abundant annotations for predicted targets.

Objective:To understand the characters of norovirus infection in children with acute diarrhea in Beijing from 2014 to 2019.Methods:Fecal specimens were collected from children with acute diarrhea visiting the hospital affiliated to the Capital Institute of Pediatrics from April 2014 to December 2019 for norovirus screening by reverse transcription-polymerase chain reaction (RT-PCR). Then RdRp gene and VP1 gene of norovirus (NoV) were amplified and sequenced from positive specimens and then genotyped by Norovirus Genotyping Tool 2.0.Results:Fecal specimens were collected from 2 577 cases with acute diarrhea and tested for NoV RNA in this study, of which 484 cases (18.78%, 484/2 577) were positive for NoV. NoV infection can occur all year round, with obvious seasonal distribution, the epidemic peak is in autumn and winter. There was no gender difference in the detection of NoV ( χ2=1.77, P=0.183). 399 specimens genotyped by VP1 gene with 98.25% (392/399) being GII and GII.4 Sydney as the mainly genotype (52.13%, 208/399), followed by GII.3 (19.8%, 79/399) and GII.2 (18.5%, 74/399). Then 267 specimens also were genotyped by RdRp region, which revealed that the main genotype was GII.P31 (57.3 %, 153/267), followed by GII.P12 (15.36%, 41/267) and GII.P16 (14.98 %, 40/267). Dual-typing revealed that various combination strains, GII.4 Sydney[P31] (53.18%, 142/267) as the major combination, followed by GII.3[P12] and GII.2[P16] (15.36%, 41/267 and 10.49%, 28/267). While GII.3[P12] showed a downward trend, GII.4 Sydney[P16] increased gradually. Conclusions:Norovirus is an important pathogen of acute diarrhea in children in Beijing, from 2014 to 2019, with various prevalent genotypes.