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.

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.

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.

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 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).

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 investigate the application value of fiberoptic endoscopic evaluation of swallowing (FEES) in patients with dysphagia after stroke.Methods:A total of 200 patients with dysphagia who received treatment in Wenzhou Hospital of Traditional Chinese Medicine from January 2019 to December 2020 were included in this study. All patients underwent videofluoroscopic swallowing study (VFFS) and FEES. Examination results and the incidence of adverse reactions were compared between VFFS and FEES.Results:VFFS results revealed that oral food residue occurred in 122 patients, food leakage in 168 patients, food aspiration in 170 patients, epiglottis valley residue in 179 patients, pyriform sinus residue in 184 patients, cricopharyngeus muscle dysfunction in 61 patients, and abnormal esophageal peristalsis in 58 patients. FEES results revealed that food leakage occurred in 173 patients, food penetration in 151 patients, food aspiration in 180 patients, food retention in 166 patients, and vocal neoplasm in 21 patients. The incidence of adverse reactions generated in FEES was lower than that in VFFS (5.5% vs. 12.0%, χ2 = 5.29, P < 0.05). Conclusion:FEES has high sensitivity and safety in the detection of dysphagia after stroke, and it has important guiding significance for the treatment of dysphagia.

Objective:To investigate the expression levels of serum soluble triggering receptor expressed on myeloid cells 2(sTREM2)in patients with vascular dementia(VD)and its relationship with β-amyloid 1-42(Aβ1-42)and lipoprotein-associated phospholipase 2(Lp-PLA2), as well as its value in diagnosis and differential diagnosis.Methods:A total of 152 patients with ischemic stroke receiving routine treatment in our hospital from January 2018 to January 2020 were included and divided into a VD group(n=76)and a non-VD group(n=76)according to evaluation from subsequent visits at 3 months.General data, Mini-Mental State Examination Scale(MMSE), Hachinski Ischemic Scale(HIS)scores, and the levels of biochemical indicators were compared and analyzed for the two groups.Results:There were statistically significant differences in lesion size between the VD group and the non-VD group( P<0.05). The MMSE score in the VD group was significantly lower than that in the non-VD group.The HIS score, serum levels of sTREM2[(3.34±1.18)μg/L and(2.78±1.25)μg/L, t=2.121, P=0.036], Aβ1-42[(93.69±14.45)ng/L and(81.24±14.21)ng/L, t=4.003, P<0.001]and Lp-PLA2 levels[(58.67±14.15)μg/L and(43.18±13.86)μg/L, t=5.096, P<0.001]were significantly higher in patients with VD than in patients without VD( P<0.05). Serum sTREM2 was positively correlated with Aβ1-42( r=0.723, P<0.001)and Lp-PLA2( r=0.714, P<0.001), and Aβ1-42 was positively correlated with Lp-PLA2( r=0.698, P<0.001)in VD patients.The cut-off value, sensitivity, specificity, and area under the curve of serum sTREM2 for differentiating VD from non-VD were 3.96 μg/L, 81.30%, 78.40%, and 0.838, respectively. Conclusions:Serum sTREM2 is abnormally elevated in VD patients, and is significantly correlated with Aβ1-42 and LP-PLA2, thus STREM2 may be an indicator in the differential diagnosis of VD and non-VD.

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.