China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

Application of distal femoral 90° locking plate in children with supracondylar femoral fractures.

OBJECTIVE: This study aimed to assess the application value of distal femur 90° locking plate fixation for supracondylar femoral fractures (SFF) in children. PATIENTS AND METHODS: A total of 100 SFF children with or without diabetes who were enrolled in our hospital from January 2018 to January 2020 were randomized into a control group and a study group by the random number table method. The study group received distal femur locking plate fixation, and the control group adopted Kirschner wire (K wire) internal fixation. The primary outcomes of the two groups of children and the secondary outcomes of the diabetic patients were compared. RESULTS: The fracture union rate of the study group was significantly higher than that of the control group at 12 weeks, 16 weeks, 20 weeks and 24 weeks after the operation (p<0.05), while the rate showed no significant difference between the two groups at 28 weeks after the operation (p>0.05). The two groups showed similar operation time, intraoperative blood loss, intraoperative fluoroscopy time, and hospital stay (p>0.05). The study group yielded a more favorable outcome with regard to the Harris-Hip-Score (HHS) scores, HHS excellent-and-good rate, and Flynn scores satisfaction rate than the control group (p<0.001 or 0.05). The intracavitary pressure of the knee joint of the two groups presented a gradual decline with time, with remarkably lower results in the study group compared with the control group at 8 weeks and 16 weeks after the surgery (p<0.05), and differences at 24 weeks after the surgery did not come up to the statistical standard (p>0.05). Patients experienced fewer postoperative complications after locking plate fixation, as compared to those who received K wire treatment (p<0.05). Compared with the control group, the fracture union rate of diabetic children in the study group was significantly higher at 12 weeks, 16 weeks, and 20 weeks after surgery, respectively (p<0.05), while there was no significant difference between the two groups at 24 weeks and 28 weeks (p>0.05). CONCLUSIONS: The distal femur 90° locking plate fixation for diabetic children with SFF obviates the need for plate shaping and ensures firm fixation, with biomechanical design, promising efficacy, and few complications. The distal femur 90° locking plate fixation has better efficacy for children with diabetes. It shows great potential as the treatment of choice for diabetic children with SFF.

Correlation between APOE4 gene and gut microbiota in Alzheimer's disease.

Gut microbiota (GM) dysbiosis has been increasingly associated with Alzheimer's disease (AD). However, the association between APOE4, the most common genetic risk factor for sporadic AD, and GM in AD remains unclear. In this study, we conducted a comparative analysis of the GM of participants from China and the USA, with and without APOE4 genes and with or without AD (67 AD cases, 67 control cases). Our results revealed that the GM alpha diversity was not different between groups (AD_APOE4, Control_APOE4, AD_non-APOE4, and Control_non-APOE4) (419.031 ± 143.631 vs 391.091 ± 126.081, 351.086 ± 169.174 and 386.089 ± 177.200, respectively. P > 0.05). Interestingly, individuals in the AD_APOE4 group had different bacterial compositions and bacterial biomarkers. The Kruskal-Wallis rank sum test indicated that the abundances of many bacterial species in the AD_APOE4 patients differed from those in control individuals, including decreases in unclassified_g__Escherichia-Shigella (1.763 ± 6.73, 4.429 ± 11.13, 8.245 ± 16.55, and 5.69 ± 13.91 in four groups, respectively; P < 0.05), and unclassified_g_Clostridium_sensu_stricto_1 (0.1519 ± 0.348, 2.502 ± 5.913, 0.5146 ± 0.9487, 1.063 ± 3.428 in four groups, respectively; P < 0.05), and increases in gut_metagenome_g_Faecalibacterium (2.885 ± 4.47, 2.174 ± 3.957, 0.5765 ± 1.784, 1.582 ± 2.92 in four groups, respectively. P < 0.01) and unclassified_g_Bacteroides (3.875 ± 3.738, 2.47 ± 2.748, 2.046 ± 3.674, 3.206 ± 3.446 in four groups, respectively; P < 0.05). In the KEGG pathway level 2 analysis, we identified three significant differences in relative abundances of predicted functions between AD_APOE4 and AD_non-APOE4_carrier groups: neurodegenerative diseases (0.0007 ± 0.0005 vs 0.0009 ± 0.0004; P < 0.01), metabolism (0.0240 ± 0.0003 vs 0.0250 ± 0.0003; P < 0.05), and biosynthesis of other secondary metabolites (0.0094 ± 0.0002 vs 0.0090 ± 0.0002; P < 0.05). Receiver operating characteristic curves further demonstrated an area under the curve (AUC) of 0.74 for the discrimination of AD_APOE4_carrier and AD_non-APOE4_carrier individuals.

Relationship between onset of eclampsia and AGTR1 gene polymorphisms.

OBJECTIVE: We aimed to study the correlations of angiotensin II receptor type 1 (AGTR1) gene polymorphisms with the occurrence and development of eclampsia. PATIENTS AND METHODS: A total of 200 pregnant women with eclampsia admitted to our hospital from January 1, 2017 to September 30, 2019 were collected as observation group and 200 normal pregnant women during the same period were recruited in the control group. Genome sequencing was performed to detect the AGTR1 gene polymorphisms in the two groups. Expression level of AGTR1 in both groups was detected. The influences of AGTR1 on clinical data of pregnant women with eclampsia were analyzed. RESULTS: There were no significant differences in age (p=0.545), height (p=0.738), weight (p=0.695) and hypertension (p=0.372) between observation group and control group. However, significant differences were found in the distributions of alleles at AGTR1 rs1799870 (p=0.002) and AGTR1 rs52936049 (p=0.047) between groups. The frequencies of T allele at rs1799870 and rs52936044 in observation group were higher than those in the control group. In addition, the distributions of AGTR1 gene genotypes at rs1799870 (p=0.012), rs144520513 (p=0.008) and rs529360494 (p p =0.036) in observation group differed from those in control group. Observation group had higher frequencies of TT genotype at rs1799870, GG genotype at rs144520513 and TG genotype at rs529360494 than those in control group. Besides, the frequency of CGG haplotype (p=0.008) of AGTR1 gene in observation group was notably lower than that in the control group, while the frequency of TGT haplotype (p=0.012) of AGTR1 gene in the former was remarkably higher than that in the latter. Moreover, the linkage disequilibrium between rs529360494 and rs144520513 of AGTR1 gene was relatively high (D'=0.623). AGTR1 gene polymorphism rs529360494 showed an evident relationship with the expression of AGTR1 gene, and the expression of AGTR1 in pregnant women with eclampsia who carried TG genotype was markedly reduced (p<0.05). Furthermore, AGTR1 gene polymorphism rs1799870 was associated with prothrombin time (PT) in pregnant women with eclampsia (p=0.046), and PT in those carrying genotype TC was shorter. Rs144520513 was related to the levels of triglyceride (TG) (p<0.001) and low-density lipoprotein (LDL) (p<0.001) in pregnant women with eclampsia, and TG and LDL levels were significantly lower. CONCLUSIONS: AGTR1 gene polymorphisms are closely associated with the onset and progression of eclampsia.

LncRNA MEG3 inhibits the growth, invasion and migration of Wilms' tumor via Wnt/ß-catenin pathway.

OBJECTIVE: Long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) has been identified to participate in the progression of malignant tumors. However, the role and function of MEG3 in Wilms' tumor (WT) remain unknown. Therefore, the aim of this study was to detect the role of MEG3 in the development of Wilms' tumor, and to explore the underlying mechanism. PATIENTS AND METHODS: Expression of MEG3 in WT tissues and blood samples were detected using quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between MEG3 level and clinicopathological character and histogenesis was analyzed. WT-CLS1 and WiT49 cells were cultured in vitro, and the influence of ectopic MEG3 expression was determined. Colony formation assay and Edu assay were employed to measure cell proliferation, while transwell assay and Matrigel assay were adopted to detect cell metastasis. Furthermore, Western blot was applied to explore the mechanism of MEG3 in WT. RESULTS: MEG3 was lowly expressed in WT tissues and blood samples (p<0.05). Over-expression of MEG3 significantly reduced the proliferation, invasion and migration of CLS1cells than control cells (p<0.05). However, inhibition of MEG3 in WiT49 cells significantly promoted cell growth and metastasis compared with cells in negative control group (p<0.05). In addition, MEG3 influenced the protein expression of ß-catenin by regulating the Wnt/ß-catenin pathway. CONCLUSIONS: MEG3 was low-expressed in WT tissues and blood samples. Meanwhile, it could inhibit the proliferation and metastasis of WT cells via wt/ß-catenin pathways. All our findings indicated that MEG3 served as a potential target for the diagnosis, treatment and prognosis prediction of WT.

MiR-640 inhibition alleviates acute liver injury via regulating WNT signaling pathway and LRP1.

OBJECTIVE: Acute liver injury (ALI) is associated with the Kupffer cells (KCs) inflammation and hepatocytes apoptosis. Previous studies have shown that miR-640 is a valid regulator of the Low-density lipoprotein receptor-related protein 1 (LRP 1) which expressed much lower in an inflammatory condition. However, it is unclear whether MiR-640 inhibition protects against ALI by the up-regulation of LRP 1. To explore the regulated mechanism of miR-640 on acute liver injury. MATERIALS AND METHODS: We analyzed the expression of miR-640 in different times of acute injured liver tissues. Lipopolysaccharide (LPS) was employed in provoking the KCs inflammation to injure liver. We used miR-640 mimic or inhibitor to improve or resist the function of miR-640 to explore miR-640 function to ALI via the target of LRP1. RESULTS: We showed that the expression of miR-640 markedly increased in LPS-induced acute injured liver tissues. LPS promoted the progress of ALI, and the inhibition of miR-640 could reverse the injured effects of LPS. Moreover, WNT signaling pathway and LRP1 were significantly enhanced by miR-640 inhibition. CONCLUSIONS: These results suggested that miR-640 promotes KCs inflammation via restraining LRP 1 and WNT signaling pathway. But inhibiting miR-640 prevents inflammation damage and ameliorates ALI. MiR-640 inhibition may become a novel target for the therapy of ALI in the future.

Diagnostic potential of urinary monocyte chemoattractant protein-1 for Alzheimer's disease and amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: The chemokine monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether urinary MCP-1 can distinguish patients with AD, patients with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) subjects. METHODS: A total of 754 participants, including 97 patients with AD, 50 patients with aMCI and 84 age- and sex-matched CN controls as well as a cohort of 523 CN subjects of different ages, were enrolled from five hospitals located in different areas of China. Urinary MCP-1 levels were determined using enzyme-linked immunosorbent assays. The correlations between urinary MCP-1 levels and cognition test scores or age were analysed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. RESULTS: In the cohort of CN subjects of different ages, urinary MCP-1 levels increased with ageing and were correlated with age. The urinary MCP-1 levels were higher in females than in males. In the cohort composed of patients with AD, aMCI and age- and sex-matched CN controls, urinary MCP-1 levels were significantly higher in patients with AD and aMCI than in CN controls. There were no differences in urine MCP-1 levels between the AD group and the aMCI group. The urinary MCP-1 levels were correlated with the Mini-Mental State Examination scores and age, and were able to differentiate patients with AD and aMCI from CN subjects. CONCLUSIONS: Urinary MCP-1 is a potential biomarker for the diagnosis of AD and aMCI.

Effect of miR-202-5p-mediated ATG7 on autophagy and apoptosis of degenerative nucleus pulposus cells.

OBJECTIVE: This study aimed to research the effect of miR-202-5p-mediated ATG7 on autophagy and apoptosis of degenerative nucleus pulposus cells. PATIENTS AND METHODS: The intervertebral disc nucleus pulposus (NP) tissue of patients with intervertebral disc degenerative disease and normal intervertebral disc nucleus pulposus (NP) tissue of patients with spinal fractures was collected as the research object. Normal NP cells and degenerative NP cells were isolated. Low expression of miR-202-5p and overexpression of ATG7 were carried out in degenerative NP cells. The expression of miR-202-5p and ATG7 mRNA was detected by RT-PCR. The expression of ATG7, LC3-II, Bax, and Bcl-2 proteins was detected by Western blot. The autophagy of cells was detected by MDC staining. The apoptosis of NP cells was detected by flow cytometry. The targeting relationship between miR-202-5p and ATG7 was detected by Dual-Luciferase reporter. RESULTS: In the degenerative NP tissues, miR-202-5p was highly expressed and ATG7 was low expressed. The inhibition of miR-202-5p expression can effectively promote autophagy of NP cells, increase the expression of ATG7 and LC3-II, inhibit the apoptosis of NP cells, inhibit the expression of pro-apoptotic proteins Bax, and promote the expression of pro-apoptotic proteins Bcl-2 proteins. The upregulation of ATG7 expression in degenerative NP cells alone had the same effect as the downregulation of miR-202-5p. The assay of the Dual-Luciferase reporter confirmed the targeting relationship between miR-202-5p and ATG7. CONCLUSIONS: MiR-202-5p can affect the autophagy and apoptosis of degenerative nucleus pulposus cells through targeted adjustment of ATG7, which may be a new therapeutic target for intervertebral disc degenerative diseases.

Prospective randomized controlled trial comparing treatment efficacy and tolerance of picosecond alexandrite laser with a diffractive lens array and triple combination cream in female asian patients with melasma.

BACKGROUND: Recent evidence suggests melasma to be a photoaging disorder. Triple combination creams (TCC: fluocinolone acetonide 0.01%, hydroquinone 4% and tretinoin 0.05%) remain the gold standard treatment. Picosecond alexandrite laser treatment using a diffractive lens array (DLA) has been identified to be effective for improving photoaging conditions. OBJECTIVE: We aimed to compare the efficacy and tolerance of the picosecond alexandrite laser with those of DLA and TCC in female Asian patients with melasma. METHODS: Twenty-nine patients were randomly assigned to group A1 (3 laser sessions at 4-week intervals), A2 (5 laser sessions at 4-week intervals) or B (TCC daily for at least 8 weeks and then tapered until the final evaluation). The Melasma Area, Severity Index (MASI) score and VISIA were assessed at baseline, week 12 and week 20. By week 20, the follow-up periods for groups A1 and A2 were 3 months and 1 month, respectively. RESULTS: Nine, 11 and 6 participants in groups A1, A2 and B completed the study, respectively. MASI scores were significantly improved in all 3 groups at weeks 12 and 20. In groups A1, A2 and B, the improvement rates at week 20 were 53%, 38% and 50%, respectively. VISIA® analysis additionally revealed a significant improvement in spots, porphyria, pores and brown spots after 3 laser sessions (P < 0.05). Group A2 showed greater improvements than group A1 in terms of spots, wrinkles and pores; however, only red areas were significantly different (P < 0.001). All side-effects in the 3 groups were transient and gradually subsided after 1-3 months. CONCLUSION: Picosecond alexandrite laser treatment using DLA showed comparable efficacy with TCC for the treatment of melasma. Improvements in texture, spots, wrinkles and pores were observed in the laser groups. Patients with melasma lesions that exhibit telangiectasia may benefit from additional laser treatment sessions.

Correlations of LTα and NQO1 gene polymorphisms with childhood asthma.

OBJECTIVE: To explore the correlation of the lymphotoxin alpha (LTα) and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1) gene polymorphisms with childhood asthma. PATIENTS AND METHODS: A total of 102 asthma children (observation group) and 80 healthy children (control group) were enrolled. The information was collected via questionnaires and the polymorphisms of LTα rs2844484 and NQO1 rs2917666 were examined with the TaqMan-MGB probe. RESULTS: Observation group had higher constituent ratios of contact with animal furs, personal history of infection, personal history of allergy, familial infection history and familial allergic history than those of control group (p<0.05). However, there were no differences in age, sex, passive smoking, purchase of new furniture and mask wearing between the two groups (p>0.05). The frequency of LTα rs2844484 genotype AA was significantly higher than that of genotype AG and GG (p<0.01), and NQO1 rs2917666 genotype CC showed notably higher frequency than that of genotype CG and GG (p<0.05). The frequency of LTα rs2844484 A allele was significantly higher than that of G allele (p<0.01), while NQO1 rs2917666 C allele had remarkably higher frequency than G allele (p<0.05). The comparisons of the recessive and additive modes revealed differences between the two groups (p<0.05). However, we did not observe significant difference in dominant mode between the two groups (p>0.05). CONCLUSIONS: The risk factors for childhood asthma include the contact with animal furs, personal history of infection, personal history of allergy, familial infection history and familial allergic history. Polymorphisms of LTα and NQO1 genes are correlated with childhood asthma.

[Clinical efficacy and safety of specific immunotherapy for allergic rhinitis with cervical lymph node injection].

Objective: To evaluate the clinical efficacy and safety of intralymphatic immunotherapy with cervical lymph node injection for allergic rhinitis. Method: A retrospective analysis of 81 patients with allergic rhinitis(AR) who had received specific immunotherapy with cervical lymph node injection in 2016 in the first people's Hospital of Foshan was conducted. The neck lymph node immunotherapy under the guidance of color Doppler ultrasound consisted of three sessions, and in each session 50 Tu(Arog) was delivered. The scores of nasal and ocular symptoms, drug score and adverse reactions during treatment were recorded before and after treatment, and the efficacy and safety were observed. Result: Before treatment, the nasal symptoms score of 81 AR cases of mite allergy was 7.00±1.65. After 1,2 and 3 sessions of cervical lymph node immune therapy and 1 year after completion of treatment, the nasal symptom scores were 4.37±1.88, 4.26±1.80, 4.22±1.80, and 4.09±2.10,respectively, which were significantly lower than that before treatment(P<0.01). The quality of life score was 53.68±9.28 before treatment, which decreased to 23.01±13.28 one year after treatment, and the difference was statistically significant(P<0.01). The drug score was 3.27±1.17 before treatment, which decreased to 1.00±1.05 1 years after treatment, and the difference was statistically significant(P<0.01). During treatment and 1-year follow-up, only 8 cases had mild local reactions, and no systemic adverse reactions occurred. Conclusion: Cervical lymph node injection specific immunotherapy can significantly relieve the symptoms of dust mite allergic rhinitis. The treatment is effective and safe, and greatly shortens the duration of immune treatment.

Long non-coding RNA 00152 promotes cell proliferation in cervical cancer via regulating miR-216b-5p/HOXA1 axis.

OBJECTIVE: Several studies demonstrated that aberrant lncRNA expression contributes to cervical cancer (CC) development and progression. LINC00152, a novel lncRNA, has been identified as an oncogene involved in various cancers. In the present study, we aim to investigate the expression pattern, clinical significance, potential functional roles, and regulatory mechanism of LINC00152 in CC. PATIENTS AND METHODS: The transcription levels of LINC00152, miR-216b-5p, and HOXA1 in CC tissues and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). LINC00152 knockdown in CC cells was conducted by transfecting the LINC00152-specific siRNA. The cell proliferation ability was evaluated by the Cell Counting Kit-8 (CCK-8) assay. Cell cycle and apoptosis analysis were assessed by flow cytometry. The target relation among LINC00152, miR-216b-5p, and HOXA1 were measured using the dual-luciferase reporter assay. The protein levels of HOXA1 in CC cells were determined by Western blot. RESULTS: LINC00152 was up-regulated in CC tissues and cell lines. The high expression level of LINC00152 was positively correlated with poor prognosis and histologic grade in CC. The silence of LINC00152 could inhibit the proliferation of CC cells through inducing the cell cycle arrest at G0/G1 phase and promote apoptosis in vitro. Mechanically, we demonstrated that LINC00152 could modulate the proliferation of CC cells through elevating HOXA1 expression level via sponging miR-216b-5p based on bioinformatics analysis and experimental validation. CONCLUSIONS: Our findings revealed a novel molecular mechanism underlying LINC00152 modulating CC progression through the miR-216b-5p/HOXA1 pathway, suggesting that LINC00152 might potentially act as an effective diagnostic marker and therapeutic target for cervical cancer.

Effects of long non-coding RNA NEAT1 on sepsis-induced brain injury in mice via NF-κB.

OBJECTIVE: The aim of this study was to investigate the effect of long non-coding ribonucleic acid (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) on sepsis-induced brain injury in mice through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). MATERIALS AND METHODS: The mouse model of sepsis was established by cecal ligation and puncture induction. The relative expression levels of NEAT1 and NF-κB in brain tissues of mice in healthy group and sepsis group were determined via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blotting, respectively. Subsequently, the expression of NEAT1 was silenced by transfection of small interfering RNAs (siRNAs). Meanwhile, its effect on NF-κB expression was detected. To further explore the effect of sepsis on brain injury, the content of brain water and the expression levels of apoptosis-related proteins, including B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX), in mice of healthy group, sepsis group, and sepsis + si-NEAT1 group were measured. Furthermore, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to detect the proliferation and apoptosis of nerve cells. RESULTS: The relative expression levels of NEAT1 and NF-κB were significantly increased in the brain tissues of septic mice (p<0.01). Si-NEAT1 transfection significantly decreased the expressions of NEAT1 and NF-κB in brain tissues of septic mice (p<0.05). The content of brain water in mice of sepsis group was evidently increased (p<0.05). However, si-NEAT1 treatment remarkably reduced this content (p<0.05). In addition, sepsis markedly decreased the activity of nerve cells (p<0.05). However, si-NEAT1 could significantly increase the activity of nerve cells in septic mice (p<0.05). Moreover, si-NEAT1 notably decreased the expression of BAX (p<0.05), whereas it increased the expression of Bcl-2 (p<0.05). The results of apoptosis detection revealed that sepsis remarkably promoted the apoptosis of mouse nerve cells (p<0.05). In addition, si-NEAT1 transfection could evidently alleviate the apoptosis of nerve cells in septic mice (p<0.05). CONCLUSIONS: LncRNA NEAT1 promotes brain injury in septic mice by positively regulating NF-κB. However, si-NEAT1 transfection can reduce this injury.

Abatacept alleviates rheumatoid arthritis development by inhibiting migration of fibroblast-like synoviocytes via MAPK pathway.

OBJECTIVE: To investigate whether Abatacept could regulate the occurrence and progression of rheumatoid arthritis (RA) by mediating cell migration of fibroblast-like synoviocytes (FLS) via mitogen-activated protein kinase (MAPK) pathway. PATIENTS AND METHODS: Levels of MMP1, MMP3 and MMP13 in RA-FLS treated with Abatacept or MAPK pathway inhibitor were detected by quantitative Real-time-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The regulatory effect of Abatacept on MAPK pathway was detected by Western blot. Transwell assay was performed to access the role of Abatacept in regulating cell migration of RA-FLS. RESULTS: Abatacept treatment remarkably downregulated levels of MMP1, MMP3 and MMP13 in FLS, which were confirmed by qRT-PCR and ELISA. Migratory ability of FLS was inhibited by Abatacept treatment. Western blot results suggested that Abatacept treatment downregulated MAPK pathway-related genes in FLS. The effects of Abatacept on MMPs expressions and cell migration were partially reversed by SB203580 treatment, the MAPK pathway inhibitor. CONCLUSIONS: Abatacept inhibits FLS migration and MMPs expressions via inhibiting MAPK pathway, thereby inhibiting RA development.

Outcomes of Heart Transplant Recipients With Preexisting Malignancies.

BACKGROUND: Ensuring careful selection of heart transplant recipients with pretransplant malignancies (PTM) has been suggested in several retrospective studies. However, cancer survival rates continue to increase and we still lack outcomes data on PTM patients who have undergone heart transplantation (HT) within the Asian region. Herein we report pretransplant characteristics and outcomes among PTM patients with HT. METHODS: A total of 354 patients underwent HT from January 2004 to January 2016. Eight of these patients had a history malignancy that was being treated before transplantation. Posttransplant outcomes and clinical characteristics were collected and possible prognostic factors analyzed. RESULTS: The median age of the patients with a preexisting malignancy was 60 years. The PTM group included 5 males and 3 females, with a median duration of follow-up of 43 months. In this group there were 2 patients with lymphoma after chemotherapy, 1 with colon cancer postoperatively, and 1 was on chemotherapy. In the other 4 patients, nasopharyngeal cancer, thyroid cancer, breast cancer, and endometrial cancer were identified, and each had undergone treatment. Only 1 premalignancy patient, with nasopharyngeal cancer, had disease recurrence. The 5-year overall survival of these patients was 50.0 ± 17.7%, but 5-year survival for those without PTM was 68.7 ± 2.0%. CONCLUSION: PTM was 2.3% in our cohort. PTM is associated with an increased risk of all-cause mortality. Thus, our findings suggest careful consideration when selecting PTM patients for HT.

MiR-203 is essential for the shift from osteogenic differentiation to adipogenic differentiation of mesenchymal stem cells in postmenopausal osteoporosis.

OBJECTIVE: The purpose of this study was to investigate how miR-203 promotes osteogenic differentiation of bone marrow mesenchymal cells (BMSCs) by regulating its target gene DKK1, thereby inhibiting the occurrence of osteoporosis. PATIENTS AND METHODS: A total of 60 cases with postmenopausal osteoporosis and 40 cases of normal individuals were recruited. The expression of miR-203 in serum of all cases was detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The capacity of osteogenesis and adipogenic differentiation of MSCs was determined by alizarin red staining and oil red staining, respectively. Transfection of miR-203 mimics and miR-203 inhibitor were mediated by Liposomes, and then the MSCs were induced osteogenic and adipogenic differentiation. MiR-203 mimic was co-transfected with wild-type or mutant DKK1 for luciferase reporter gene detection. In the osteoporosis model of rats, the tibia was taken for micro-CT examination of bone mineral density (BMD) and bone volume/structural parameters (BV/TV), while the femur was taken for the measurement of absorption parameters (Ob.S)./BS) and the number of osteoclasts per circumference of bone (N.Oc/B.Pm). RESULTS: The expression level of miR-203 was significantly lower in patients with postmenopausal osteoporosis than that in normal individuals. The osteogenic capacity of BMSCs in these patients was reduced, while their adipogenic capacity was enhanced. MiR-203 promoted the expression of osteogenic genes and inhibited that of adipogenic genes. Knockdown of miR-203 decreased the level of osteogenic related genes but increased that of adipogenic related genes, while overexpression of miR-203 led to the opposite results. Furthermore, miR-203 inhibited the protein expression of DKK1. In addition, bone density and bone volume/structural parameters were lower in ovariectomized rats than those in normal rats. Meanwhile, bone resorption parameters and the number of osteoclasts per bone circumference in ovariectomized rats were higher than those in normal rats. CONCLUSIONS: MiR-203 can promote osteogenic differentiation of mesenchymal stem cells by downregulating the gene expression of DKK1.

A study on related factors of hemodynamic depression in carotid artery stenting.

OBJECTIVE: To investigate the pathogenesis and related factors of carotid artery stenting (CAS) related to hemodynamic depression (HD). PATIENTS AND METHODS: 433 CAS patients were admitted to our hospital and were selected from Jan 2013 to Jun 2016. We set up the HD diagnostic criteria for CAS and observed the whole morphology of vessels to classify carotid atherosclerotic plaques. We analyzed cerebral angiography and placed temporary cardiac pacemaker via femoral vein in order to prepare carotid artery stenting. We determined the general situation of HD after CAS according to the results. RESULTS: 38 patients received temporary placement of cardiac temporary pacemakers, and 241 patients (59.80%) developed HD. 403 patients were divided into HD group and non HD group and results suggested there was no significant difference between the two groups except for diabetes (p>0.05). Also, bilateral carotid stenting was performed in 26 patients (6.45%), and the HD group was significantly higher than that in non HD group (p<0.05). HD group had 31 MACCE cases, and non HD group had 2 MACCE cases. There was no occurrence of adverse cardiovascular events in this study. CONCLUSIONS: Cardiac temporary pacemaker may be one of the effective approaches to improve HD after CAS and reduce perioperative MACCE.

SPARCL1 suppresses osteosarcoma metastasis and recruits macrophages by activation of canonical WNT/ß-catenin signaling through stabilization of the WNT-receptor complex.

Metastasis significantly reduces the survival rate of osteosarcoma (OS) patients. Therefore, identification of novel targets remains extremely important to prevent metastasis and treat OS. In this report, we show that SPARCL1 is downregulated in OS by epigenetic methylation of promoter DNA. In vitro and in vivo experiments revealed that SPARCL1 inhibits OS metastasis. We further demonstrated that SPARCL1-activated WNT/ß-catenin signaling by physical interaction with various frizzled receptors and lipoprotein receptor-related protein 5/6, leading to WNT-receptor complex stabilization. Activation of WNT/ß-catenin signaling contributes to the SPARCL1-mediated inhibitory effects on OS metastasis. Furthermore, we uncovered a paracrine effect of SPARCL1 on macrophage recruitment through activated WNT/ß-catenin signaling-mediated secretion of chemokine ligand5 from OS cells. These findings suggest that the targeting of SPARCL1 as a new anti-metastatic strategy for OS patients.

Blood-derived amyloid-ß protein induces Alzheimer's disease pathologies.

The amyloid-ß protein (Aß) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aß deposited in the brain originates from the brain tissue itself. However, Aß is generated in both brain and peripheral tissues. Whether circulating Aß contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aß originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aß plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aß accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aß can enter the brain, form the Aß-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aß metabolism in both the brain and the periphery.