The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical β-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with β-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.

Objective: To construct and compare the dynamic prediction models of the risk of mild cognitive impairment (MCI) in the elderly based on six different cognitive function scales. Methods: Based on longitudinal data from the Alzheimer's Disease Neuroimaging Initiative from 2005 to 2020, Mini-mental state examination (MMSE), functional activities questionnaire (FAQ), Alzheimer's disease assessment scale-cognitive (ADAS-Cog) 11, ADAS-Cog13, ADAS delayed word recall (ADASQ4), and Rey auditory verbal learning test (RAVLT)_immediate were used as longitudinal cognitive function evaluation indicators to assess the longitudinal changes in cognitive function. The joint model was used to analyze association between indicators variation trajectory and survival outcome MCI, and construct the risk prediction model of MCI in the elderly, the linear mixed model was constructed the longitudinal sub-model which described the evolution of a repeated measure over time, a proportional hazards model was constructed the survival sub-model, and the two sub-models were connected through the correlation parameter (α). The areas under the receiver operator characteristic curve (AUC) were used to evaluate the predictive efficacy of the model in the follow-up period of (t, t+Δt). The starting point t was selected at the 30^th, 42^nd, and 54^th month, and the Δt was selected as 15 and 21 months. Based on the prediction model, an example of the research object was selected for dynamic individual predictions of the risk of MCI. Results: Finally, 544 older adults (aged 60 years and above) with normal baseline cognitive status were included, of which 119 cases (21.9%) had MCI during the follow-up process were regarded as the case group, and 425 cases remained normal as the control group. The joint model suggests that the longitudinal trajectories of the six evaluation indicators are all related to the risk of MCI (P<0.001). The risk of MCI decreased by 32.3% (HR=0.677, 95%CI: 0.541-0.846) and 10.8% (HR=0.892, 95%CI: 0.865-0.919) for each one-point increase of MMSE and RAVLT_immediate longitudinal scores. The risk of MCI increased by 53.2% (HR=1.532, 95%CI: 1.393-1.686), 36.2% (HR=1.362, 95%CI: 1.268-1.462), 23.2% (HR=1.232, 95%CI: 1.181-1.285), and 85.1% (HR=1.851, 95%CI:1.629-2.104) for each one-point increase of FAQ, ADAS-Cog11, ADAS-Cog13, and ADASQ4 longitudinal scores. AUC results show that RAVLT_immediate (0.760 2) and ADASQ4 (0.755 8) have higher average prediction efficiency, followed by ADAS-Cog13 (0.743 7), ADAS-Cog11 (0.715 3), FAQ (0.700 8) and MMSE (0.629 5). ADASQ4 joint model was used to provide a dynamic individual prediction of the risk of MCI. The average probability of MCI after five years of follow-up and ten years of follow-up in the example individuals were 8% and 40%, respectively. Conclusions: The RAVLT_immediate and ADASQ4 scales, which are only for memory tests, have high accuracy in predicting the risk of MCI. Using the RAVLT_immediate and ADASQ4 scales as longitudinal cognitive function evaluation indicators to construct a joint model, the results can provide a basis for realizing MCI risk prediction for the elderly.
Aged ; Alzheimer Disease/psychology* ; Cognition ; Cognitive Dysfunction/epidemiology* ; Humans ; Middle Aged ; Neuropsychological Tests ; Risk Factors

Objective: To understand the transition rules of cognitive frailty and its influencing factors in the elderly in China and provide evidence for the early intervention of cognitive frailty. Methods: Data were retrospectively collected from China Health and Retirement Longitudinal Study with 3 round consecutive survey (2011, 2013, 2015) and the state of the subjects were classified into four categories: robust-normal cognitive, cognitive impairment, physical frailty, and cognitive frailty. A multi-state Markov model was established to explore the transition rules of cognitive frailty and its influencing factors. Results: A total of 3 470 older adults were included, and 350 (10.09%) had cognitive frailty at baseline. After two years, the probability of cognitive frailty in the cognitive impairment population was higher than that in people with physical frailty (31.6% vs. 7.6%). Persons with cognitive frailty were more likely to become physical frailty (29.7% vs. 15.6%). Being women (HR=1.599, 95%CI: 1.058-2.417), comorbidity (HR=3.035, 95%CI: 1.090-8.450), and depression (HR=1.678, 95%CI: 1.153-2.441) were the risk factors associated with cognitive frailty in the elderly, while being educated (HR=2.367, 95%CI: 1.567-3.575) was a protective factor for the transition of cognitive frailty to physical frailty. Conclusions: The prevalence of cognitive frailty is relatively high in the elderly in China. Those with cognitive impairment have a higher probability of cognitive frailty. Gender, education level, comorbidity, and depression are the main influencing factors for the occurrence and transition of cognitive frailty.
Aged ; China/epidemiology* ; Cognition ; Cognitive Dysfunction/epidemiology* ; Female ; Frail Elderly ; Frailty/epidemiology* ; Geriatric Assessment ; Humans ; Longitudinal Studies ; Male ; Retrospective Studies

OBJECTIVE: Polycystic ovary syndrome (PCOS), a common endocrine-metabolic dysfunction in reproductive-aged women, may be involved in compromised pregnancy and offspring outcomes. This study aimed to investigate whether maternal PCOS affects fetal growth, fetal development, and placental features. METHODS: This retrospective case-control study included 60 pregnant women with PCOS (PCOS group) and 120 healthy pregnant women without PCOS (control group). Fetal magnetic resonance imaging (MRI) was performed followed by an ultrasound examination and indications for imaging, including known or suspected fetal pathology, history of fetal abnormality in previous pregnancy or in a family member, and concern for placenta accreta. Fetal MRI images were analyzed for head circumference (HC), abdomen circumference (AC), lung-to-liver signal intensity ratio (LLSIR, a prenatal marker of fetal lung maturity), lengths of liver and kidney diameters in fetuses, and placental relative signal intensity on T2-weighted single-shot fast spin echo (SSFSE) imaging (rSI RESULTS: Compared to the control group, the PCOS group showed the following characteristics: (1) smaller biparietal diameter and femur length in fetuses (P=0.026 and P=0.005, respectively), (2) smaller HC in fetuses (evident after 32 weeks; P=0.044), (3) lower LLSIR and smaller dorsoventral length of liver in fetuses (evident before 32 weeks; P=0.005 and P=0.019, respectively), and (4) smaller placental thickness (evident before 32 weeks; P=0.017). No significant differences in placental rSI CONCLUSIONS There exist alterations of fetal growth, fetal development, and placental features from women with PCOS.

BACKGROUND: Long-term complications of cesarean section include placenta praevia, placenta accreta, cesarean scar pregnancy and uterine rupture. These life-threatening complications in pregnant women maybe result from the defects of endometrium and uterine smooth muscle as well as poorly formed decidua in the scar of cesarean section. Mesenchymal stem cells have the function of repairing tissue injuries, and the amount of cells homing to the site of injury may affect the effect of tissue repair. OBJECTIVE: To explore the distribution and homing of bone marrow mesenchymal stem cells from male rats into rat models of cesarean section. METHODS: Bone marrow mesenchymal stem cells isolated from male rats in vitro were cultured and identified. Female Wistar rats were randomized into two groups: cesarean section group and control group. Rats in the cesarean section group were given intravenous administration of bone marrow mesenchymal stem cells from male rats via the tail vein on day 21 after cesarean section, and non-operative rats in the control groups were given the same amount of bone marrow mesenchymal stem cells from male rats after natural delivery. Rats in the two groups were sacrificed on days 7 and 28 after cell injection. The distribution of bone marrow mesenchymal stem cells from male rats in tissues (including heart, lungs, livers, kidneys, and uterine scar) was detected by measurement of the SRY mRNA level using SPY-PCR. RESULTS AND CONCLUSION: In the cesarean section group, the SRY gene was most abundant in the lung, followed by the liver and the kidney on day 7 after injection, although the distribution of SRY gene in the heart and uterine scar was low; on day 28 after injection, the levels of SRY gene in the lung, liver and kidney decreased (P < 0.05), but had no significant changes in the heart and uterine scar (P > 0.05). In the control group, the distribution of SRY gene was similar to that in the cesarean section group on both days 7 and 28 after injection, and the levels of SRY gene in the heart and uterus were low. These findings reveal that allogeneic bone marrow mesenchymal stem cells implanted mainly distribute in tissues with abundant blood flow, including lungs, livers and kidneys. And the cell number decreases gradually over time. Since the amount of implanted cells in the heart and uterus is very low, the change with time is not obvious. Cesarean section injury has no impact on the distribution of bone marrow mesenchymal stem cells in pregnant rats and there is of course no increase in the homing and colonization of bone marrow mesenchymal stem cells in a cesarean scar.

OBJECTIVETo explore role of MIER3 gene in the development and progression of human colorectal carcinoma (CRC) and analyze the proteins that interact with MIER3 using bioinformatic techniques.

METHODSMIER3 mRNA and protein expressions were detected in 8 CRC biopsy samples and paired adjacent tissues using real-time PCR and Western blotting. A recombinant eukaryotic expression vector pcDNA3-MIER3 was constructed and its effect on the proliferation and invasion of CRC cells were tested using CCK8 assay and Transwell migration assay. Bioinformatic methods were used to predict and analyze MIER3-interacting proteins.

RESULTSMIER3 was obviously down-regulated in the 8 CRC tissues as compared with the paired adjacent tissues. In human CRC cell line DLD1, MIER3 overexpression induced by transfection of the cells with pcDNA3-MIER3 significantly inhibited the cell proliferation and suppressed cell invasiveness in vitro. Bioinformatics analyses indicated that NAT9 was a potential MIER3-interacting protein and MIER3 was probably associated with tumor susceptibility.

CONCLUSIONMIER3, which is obviously down-regulated in CRC tissues, is closely associated with the proliferation and invasion of CRC, and NAT9 protein is a probable MIER3-interacting protein.

OBJECTIVETo construct a eukaryotic expression vector of transmembrane-4-L-six-family-1 (TM4SF1) gene and study its effect on the migration and invasion of colorectal cancer cells.

METHODSA pair of specific primers of TM4SF1 gene (GenBank: BC034145.1) was used to acquire the open reading frame of TM4SF1 by RT-PCR. The amplified sequence was ligated to a PEZ-M29 vector, which, after identification, was transiently transfected in colorectal cancer cell lines HCT116 and DLD1. Western blotting and immunocytochemistry were used to analyze the transfection efficiency, and scratch and Transwell tests were performed to analyze the changes in the migration and invasion of HCT116 and DLD1 cells after transfection.

RESULTSCell scratch and Transwell assays revealed that transfection with the recombinant plasmid, PEZ-M29/TM4SF1, caused up-regulated expression of TM4SF1 and promoted the migration and invasion of HCT116 and DLD1 cells.

CONCLUSIONOur results demonstrated that TM4SF1 is closely related to the invasion and metastasis of colorectal cancer cells in vitro.

Antigens, Surface ; biosynthesis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Colorectal Neoplasms ; pathology ; Genetic Vectors ; HCT116 Cells ; Humans ; Neoplasm Proteins ; biosynthesis ; Transfection

Objective To investigate the changes of caries susceptibility factors during the transition from caries-free to caries in three-year-old children.Methods The study included 144 caries-free children aged 34-38 months.All participants underwent clinical examination and full-mouth supragingival plaque collection.Survey of children's oral health behaviors involving feeding habits and oral health care was also taken from children' s parents of all participants.The children were reexamined 6 and 12 months later.According to the potential changes of caries status in twelve months follow up,all the participants were divided into three groups:caries-free group (caries free children in twelve months follow up),caries at 6-month group(children who were found with caries or cavities fillings at six months review) and caries at 12-month group(children who were caries free at six months but found with caries or cavities fillings at twelve months).Streptococcus mutans (Sm)and Streptococcus sobrinus (Ss) loads were compared among the three groups by real time fluorescence quantitative polymerase chain reaction (FQ-PCR).Results One hundred and thirty children completed twelve months review,the dropout rate was 9.7％ (14/144).At the end of twelve months follow up,the number of children in caries-free group,caries at 6-month group and caries at 12-month group was 58,44 and 28 respectively.The changes of oral behavioral habits in caries-free group,caries at 6-month group and caries at 12-month group during twelve months follow up were not significantly different(P ＞0.05).At baseline,the frequency of sweets consumption and eating sweets before sleeping in caries-free group was significantly lower than that in caries at 6-month group and caries at 12-month group (P ＜ 0.001).At baseline,the quantity of Sm and Ss in caries at 6-month group [copy number of Sm:(6.33 ± 2.21) × 103,copy number of Ss:(1.99 ±0.45) × 103] was significantly higher than that in the caries-free group [copy number of Sm:(5.81 ± 2.43) × 103,copy number of Ss:(1.34 ± 0.53) × 103] (P ＜ 0.05).There was no significant difference in the quantity of Sm and Ss in the caries-free group and caries at 12-month group(P ＞ 0.05).At six months,the quantity of Sm and Ss in caries at 12-month group was significantly higher than that in the caries-free group although both groups of children were caries-free at six months (P ＜ 0.05).Conclusions The quantity of Sm and Ss increased six months before the caries onset in three-year-old children.High frequency sweets consumption and eating sweets before sleeping were important susceptibility factors for caries onset in the future.

Objective To construct a eukaryotic expression vector of transmembrane-4-L-six-family-1 (TM4SF1) gene and study its effect on the migration and invasion of colorectal cancer cells. Methods A pair of specific primers of TM4SF1 gene (GenBank: BC034145.1) was used to acquire the open reading frame of TM4SF1 by RT-PCR. The amplified sequence was ligated to a PEZ-M29 vector, which, after identification, was transiently transfected in colorectal cancer cell lines HCT116 and DLD1. Western blotting and immunocytochemistry were used to analyze the transfection efficiency, and scratch and Transwell tests were performed to analyze the changes in the migration and invasion of HCT116 and DLD1 cells after transfection. Results Cell scratch and Transwell assays revealed that transfection with the recombinant plasmid, PEZ-M29/TM4SF1, caused up-regulated expression of TM4SF1 and promoted the migration and invasion of HCT116 and DLD1 cells. Conclusion Our results demonstrated that TM4SF1 is closely related to the invasion and metastasis of colorectal cancer cells in vitro.

Objective To construct a eukaryotic expression vector of transmembrane-4-L-six-family-1 (TM4SF1) gene and study its effect on the migration and invasion of colorectal cancer cells. Methods A pair of specific primers of TM4SF1 gene (GenBank: BC034145.1) was used to acquire the open reading frame of TM4SF1 by RT-PCR. The amplified sequence was ligated to a PEZ-M29 vector, which, after identification, was transiently transfected in colorectal cancer cell lines HCT116 and DLD1. Western blotting and immunocytochemistry were used to analyze the transfection efficiency, and scratch and Transwell tests were performed to analyze the changes in the migration and invasion of HCT116 and DLD1 cells after transfection. Results Cell scratch and Transwell assays revealed that transfection with the recombinant plasmid, PEZ-M29/TM4SF1, caused up-regulated expression of TM4SF1 and promoted the migration and invasion of HCT116 and DLD1 cells. Conclusion Our results demonstrated that TM4SF1 is closely related to the invasion and metastasis of colorectal cancer cells in vitro.