Long-term debridement effect of denervated large sacrococcygeal pressure injury: A case report.

RATIONALE: Complicated pressure injury in paraplegic patients is common and difficult to manage. Previous case studies have documented short-term management; however, little is known regarding suitable approaches to long-term clearing of extensive pressure injury in the sacrococcygeal area under denervation. PATIENT CONCERNS: A 53-year-old man was bedridden for 1.5 years owing to cervical vertebral fracture-dislocation (C5-C6), resulting in extensive sacrococcygeal pressure injury. DIAGNOSES: On admission, he presented with the injury complicated by infection (stage IV necrosis), and his vital signs were unstable. INTERVENTIONS: The infection was treated with a range of antibiotics, including clindamycin phosphate, metronidazole, cefoperazone sodium, and sulbactam sodium. Debridement of the pressure injury was performed, helping remove the necrotic tissue and stimulate tissue regeneration. OUTCOMES: The patient was discharged after 88 days of hospitalization. The extent of the pressure injury at discharge was reduced compared with that at admission. At 4-month follow-up, the injury was nearly healed, with no signs of any further complications. LESSONS: This case study suggests that wound debridement is a cost-effective and clinically efficacious approach to long-term complicated pressure injury management.

Fungicide-tolerant persister formation during cryptococcal pulmonary infection.

Bacterial persisters, a subpopulation of genetically susceptible cells that are normally dormant and tolerant to bactericides, have been studied extensively because of their clinical importance. In comparison, much less is known about the determinants underlying fungicide-tolerant fungal persister formation in vivo. Here, we report that during mouse lung infection, Cryptococcus neoformans forms persisters that are highly tolerant to amphotericin B (AmB), the standard of care for treating cryptococcosis. By exploring stationary-phase indicator molecules and developing single-cell tracking strategies, we show that in the lung, AmB persisters are enriched in cryptococcal cells that abundantly produce stationary-phase molecules. The antioxidant ergothioneine plays a specific and key role in AmB persistence, which is conserved in phylogenetically distant fungi. Furthermore, the antidepressant sertraline (SRT) shows potent activity specifically against cryptococcal AmB persisters. Our results provide evidence for and the determinant of AmB-tolerant persister formation in pulmonary cryptococcosis, which has potential clinical significance.

Galectin-7 Induction by EHMT2 Inhibition Enhances Immunity in Microsatellite Stability Colorectal Cancer.

BACKGROUND & AIMS: Although immunotherapy shows substantial advancement in colorectal cancer (CRC) with microsatellite instability high, it has limited efficacy for CRC with microsatellite stability (MSS). Identifying combinations that reverse immune suppression and prime MSS tumors for current immunotherapy approaches remains an urgent need. METHODS: An in vitro CRISPR screen was performed using coculture models of primary tumor cells and autologous immune cells from MSS CRC patients to identify epigenetic targets that could enhance immunotherapy efficacy in MSS tumors. RESULTS: We revealed EHMT2, a histone methyltransferase, as a potential target for MSS CRC. EHMT2 inhibition transformed the immunosuppressive microenvironment of MSS tumors into an immunomodulatory one by altering cytokine expression, leading to T-cell-mediated cytotoxicity activation and improved responsiveness to anti-PD1 treatment. We observed galectin-7 up-regulation upon EHMT2 inhibition, which converted a "cold" MSS tumor environment into a T-cell-inflamed one. Mechanistically, CHD4 repressed galectin-7 expression by recruiting EHMT2 to form a cotranscriptional silencing complex. Galectin-7 administration enhanced anti-PD1 efficacy in MSS CRC, serving as a potent adjunct cytokine therapy. CONCLUSIONS: Our findings suggest that targeting the EHMT2/galectin-7 axis could provide a novel combination strategy for immunotherapy in MSS CRC.

Left atrial enlargement and high uric acid level are risk factors for left atrial thrombus or dense spontaneous echo contrast in atrial fibrillation patients with low to moderate embolic risk assessed by CHA2DS2-VASC score.

Aims: To investigate the correlation and predictive value of left atrial diameter and blood uric acid levels with the occurrence of left atrial thrombus or dense spontaneous echo contrast in atrial fibrillation patients with low to moderate CHA2DS2-VASc scores. Methods and results: A total of 849 inpatients diagnosed with atrial fibrillation who had low to moderate CHA2DS2-VASc scores and complete transesophageal echocardiography were included in this study. Among them, 66 patients had left atrial thrombus or dense spontaneous echo contrast. When different models were used to correct other known risk factors, acid levels and abnormal left atrial diameter were identified as additional risk factors for left atrial thrombus or dense spontaneous echo contrast. The incidence of left atrial thrombus or dense spontaneous echo contrast was higher in patients with abnormal serum uric acid levels than in the control group (12.4% vs. 5.6%, p < 0.05), and this difference persisted after correcting the baseline data with propensity score matching (10.6% vs. 4.1%, p < 0.05). Abnormal left atrial diameter was another risk factor suggested by regression analysis, with an increased incidence of left atrial thrombus or dense spontaneous echo contrast in the abnormal left atrial diameter group compared to the control group, both before (18.0% vs. 3.5%, p < 0.05) and after (15.5% vs. 5.2%, p < 0.05) propensity score matching. The best predictive value was obtained by adding both abnormal serum uric acid levels and abnormal left atrial diameter. Conclusion: Left atrial enlargement and high uric acid levels increase the risk of left atrial thrombus or dense spontaneous echo contrast in atrial fibrillation patients with low to moderate CHA2DS2-VASc scores.

Dosage selection and effect evaluation of sodium pentobarbital in tree shrew anesthesia.

To achieve surgical anesthesia in animal experimentation, it is important to select the appropriate anesthetic dose. However, few studies have investigated the reasonable anesthetic dose in tree shrew (Tupaia belangeri). The aim of the study was to review the literature to determine the most commonly used anesthetic dose in tree shrew and to calculate the reasonable equivalent dose between tree shrew and rat based on the body surface area conversion. Two groups of 10 adult tree shrews each were anesthetized with 1% sodium pentobarbital through intraperitoneal injection separately at doses of 62 mg/kg (equivalent dose) and 40 mg/kg (reported dose). Anesthetic depth and times were assessed in addition to vital signs. The results showed that the dosage was quite different across studies, ranging from 15 mg/kg to 80 mg/kg, with 40 mg/kg being the most frequently reported dose. However, the group of tree shrews anesthetized with the commonly reported dose were unable to meet the requirements of surgery. In contrast, the equivalent dose (62 mg/kg, intraperitoneal injection with sodium pentobarbital) calculated by body surface area conversion could achieve an anesthetic time of 44.28 ± 3.95 min with no serious or fatal effects. During anesthetic monitoring, we found that sodium pentobarbital had an inhibitory effect on the blood pressure, pulse rate, respiratory rate and rectal temperature in tree shrews, especially on the respiratory rate. Thus, our study indicated that the use of the equivalent dose of sodium pentobarbital was effective in anesthetizing tree shrews.

Expression profile of circular RNAs in patients with unstable angina.

BACKGROUND: Circular RNAs (circRNAs) are a new class of noncoding RNAs, which interfere with gene transcription by absorbing microRNAs (miRNAs). OBJECTIVE: The expression profile and roles of circRNAs in unstable angina (UA) patients remains unclear. METHODS: An initial screening of circRNA expression by microarray analysis was performed using blood samples from three pairs of UA patients and matched healthy individuals. The differential expression of the chosen six circRNAs from the results of the microarray analysis was validated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The microarray results demonstrated that some circRNAs were markedly different in UA patients, when compared with matched healthy individuals. In these UA patients, 22 circRNAs were upregulated and six circRNAs were downregulated when a P-value of < 0.05 was considered as a cut-off level and the fold change was > 1.5. Among the six circRNAs chosen for further analysis, qRT-PCR identified that five of these were upregulated, and the remaining circRNA was downregulated. By comparing the outcome of the six candidate circRNAs between the circRNAs microarray assay and RT-PCR validation, it was found that four circRNAs (hsa_circ_0002229, hsa_circ_0005580, hsa_circ_0046667, and hsa_circ_0001451) had the same variation trend. CONCLUSION: The present study provided the expression profile of circRNAs in UA patients. Moreover, some circRNAs have the potential to be biomarkers for the detection of UA patients. Further studies with a larger population will focus on hsa_circ_0002229, hsa_circ_0005580, hsa_circ_0046667 and hsa_circ_0001451.

[Periodontal health survey and analysis of influencing factors in 916 patients with type 2 diabetes].

PURPOSE: To investigate the periodontal health status of type 2 diabetes patients in the Endocrinology Department of Shanghai Sixth People's Hospital, to explore relevant influencing factors of chronic periodontitis, so as to provide epidemiological basis for targeted prevention and treatment of periodontal diseases in patients with type 2 diabetes. METHODS: Periodontal examination and questionnaire survey of patients with type 2 diabetes who visited the Endocrinology Department of Shanghai Sixth People's Hospital from November 2018 to December 2018 were conducted. Criteria in "Basic Methods for Oral Health Survey" recommended by WHO was referred to check and score the relevant periodontal indicators, including probing depth, bleeding on probing, attachment loss, calculus index, plaque index, etc. Sociodemographic information, diabetes history, periodontal health-related behaviors, and other information were collected through questionnaires. SPSS 22.0 software package was used for statistical analysis. RESULTS: Of the 916 patients with type 2 diabetes who participated in the survey, 670 patients with periodontitis were detected. The overall prevalence of periodontitis was 73.14%, and the number of missing teeth per capita was 4.85. The age of diabetic patients, the duration of diabetes, and the presence or absence of complications were risk factors for periodontitis. As the patients grew, the duration of the disease increased, and diabetes-related complications appeared, the prevalence of periodontitis in patients with diabetes increased significantly (P＜0.05). CONCLUSIONS: Periodontal health of patients with type 2 diabetes in the surveyed region is not optimistic. Early prevention and treatment of periodontitis is extremely important. It is necessary to pay attention to the periodontal health status of elderly patients with long-term disease and diabetes, and to carry out targeted oral prevention and health care work for this population.

Investigation Driven by Network Pharmacology on Potential Components and Mechanism of DGS, a Natural Vasoprotective Combination, for the Phytotherapy of Coronary Artery Disease.

Phytotherapy offers obvious advantages in the intervention of Coronary Artery Disease (CAD), but it is difficult to clarify the working mechanisms of the medicinal materials it uses. DGS is a natural vasoprotective combination that was screened out in our previous research, yet its potential components and mechanisms are unknown. Therefore, in this study, HPLC-MS and network pharmacology were employed to identify the active components and key signaling pathways of DGS. Transgenic zebrafish and HUVECs cell assays were used to evaluate the effectiveness of DGS. A total of 37 potentially active compounds were identified that interacted with 112 potential targets of CAD. Furthermore, PI3K-Akt, MAPK, relaxin, VEGF, and other signal pathways were determined to be the most promising DGS-mediated pathways. NO kit, ELISA, and Western blot results showed that DGS significantly promoted NO and VEGFA secretion via the upregulation of VEGFR2 expression and the phosphorylation of Akt, Erk1/2, and eNOS to cause angiogenesis and vasodilation. The result of dynamics molecular docking indicated that Salvianolic acid C may be a key active component of DGS in the treatment of CAD. In conclusion, this study has shed light on the network molecular mechanism of DGS for the intervention of CAD using a network pharmacology-driven strategy for the first time to aid in the intervention of CAD.

Analysis of the prevalence, risk factors, and clinical characteristics of osteoporosis in patients with essential hypertension.

BACKGROUND: The present study investigated the prevalence of osteoporosis (OP) among patients with essential hypertension (EH) in the Changchun community and analysed the correlation between EH and OP. METHODS: The study included 425 subjects with EH and 425 age- and sex-matched healthy controls. Bone mineral density (BMD) and serum creatinine (CR) levels were measured, and the subjects' current EH and OP statuses were surveyed to analyse the correlation between EH and OP. RESULTS: The EH group exhibited lower BMD and a higher rate of having OP than the control group, and this difference was statistically significant (p < 0.05). A significant sex difference in the BMD T-score was observed among the subjects (male: - 1.19 ± 1.55, female: - 1.70 ± 1.34). In both the EH group and the control group, the rate of having OP in females was greater than that in males. However, the OP prevalence among subjects with EH varied significantly by age, body weight, fracture history, nocturnal urination frequency, depression and anxiety status, duration of hypertension, and antihypertensive medication use (p < 0.05). Two-way analysis of variance suggested an effect of the interaction between different EH statuses and bone mass conditions on the serum CR values (F = 3.584, p = 0.028, bias η2 = 0.008). CONCLUSIONS: The prevalence of OP and low BMD were significantly higher among subjects with EH than among healthy controls. Additionally, the findings indicate that age, weight, fracture history, nocturnal urination frequency, depression and anxiety, duration of hypertension and antihypertensive drug use may be correlated to having OP in EH subjects, requiring further studies. Moreover, serum CR levels in subjects with different bone mass profiles were strongly influenced by the presence or absence of EH, and the serum CR levels differed significantly with the interaction of these two factors.

Tri-Branch Convolutional Neural Networks for Top-k Focused Academic Performance Prediction.

Academic performance prediction aims to leverage student-related information to predict their future academic outcomes, which is beneficial to numerous educational applications, such as personalized teaching and academic early warning. In this article, we reveal the students' behavior trajectories by mining campus smartcard records, and capture the characteristics inherent in trajectories for academic performance prediction. Particularly, we carefully design a tri-branch convolutional neural network (CNN) architecture, which is equipped with rowwise, columnwise, and depthwise convolutions and attention operations, to effectively capture the persistence, regularity, and temporal distribution of student behavior in an end-to-end manner, respectively. However, different from existing works mainly targeting at improving the prediction performance for the whole students, we propose to cast academic performance prediction as a top-k ranking problem, and introduce a top-k focused loss to ensure the accuracy of identifying academically at-risk students. Extensive experiments were carried out on a large-scale real-world dataset, and we show that our approach substantially outperforms recently proposed methods for academic performance prediction. For the sake of reproducibility, our codes have been released at https://github.com/ZongJ1111/Academic-Performance-Prediction.

Growth, Physiological, and Photosynthetic Responses of Xanthoceras sorbifolium Bunge Seedlings Under Various Degrees of Salinity.

Xanthoceras sorbifolium Bunge is priced for its medical and energetic values. The species also plays a key role in stabilizing ecologically fragile areas exposed to excess soil salinity. In this study, the effects of salinity on the growth, physiological, and photosynthetic parameters of X. sorbifolium Bunge were investigated. The X. sorbifolium seedlings were subjected to five salt treatments: 0 (control, CK), 70, 140, 210, and 280 mM of sodium chloride (NaCl) solutions. NaCl caused a decrease in plant height, specific leaf area, biomass, and root parameters. Leaf wilting and shedding and changes in root morphology, such as root length, root surface area, and root tips were observed. This study found that X. sorbifolium is tolerant to high salinity. Compared with the CK group, even if the concentration of NaCl was higher than 210 mM, the increase of the relative conductivity was also slow, while intercellular CO2 concentration had a similar trend. Moreover, NaCl stress caused an increase in the malondialdehyde (MDA), soluble proteins, and proline. Among the enzymes in the plant, the catalase (CAT) activity increases first and decreased with the increase in the intensity of NaCl stress, but the salt treatment had no significant effect on superoxide dismutase (SOD) activity. The peroxidase (POD) showed an increasing trend under salt stress. It was found that the photosynthesis of X. sorbifolium was notably impacted by saline stress. NaCl toxicity induced a noticeable influence on leaf net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), transpiration rate (E), and water use efficiency (Wue). As salt concentration increased, the content of chlorophyll decreased. It can be found that a low concentration of NaCl induced the increase of photosynthetic capacity but a high-intensity exposure to stress resulted in the reduction of photosynthetic efficiency and SOD activity, which had a positive correlation. In summary, salt-induced ionic stress primarily controlled root morphology, osmotic adjustment, and enzyme activities of salt-treated X. sorbifolium leaves, whereas the low salt load could, in fact, promote the growth of roots.

Severe hematuria due to vesical varices in a patient with portal hypertension: A case report.

BACKGROUND: Hematuria is one of the most common clinical symptoms for urologists and is typically observed in urinary system tumors, prostate hyperplasia, and urinary stone disease. Hematuria due to vesical varices is very rare, and only a few cases have been reported since 1989. We report the first case of vesical varices due to portal hypertension with aberrant development and functioning of the genitourinary system along with the complete diagnosis and treatment process. CASE SUMMARY: This patient was a 53-year-old man with a history of aberrant development of the genitourinary system and hepatitis B-associated cirrhosis. He was admitted to the emergency department with severe hematuria and bladder clot tamponade. Many abnormally dilated blood vessels were found surrounding the bladder in the pelvis by color Doppler ultrasound, contrast-enhanced computed tomography, and three-dimensional visualization technology. It was difficult to perform transurethral cystoscopy and hemostasis in this patient, so we performed open surgical bladder exploration for hemostasis and surgical devascularization around the bladder. CONCLUSION: Urologists should improve the understanding of the pathophysiology, clinical manifestations, diagnosis, and treatment of vesical varices. This case may be presented as a reference for the diagnosis and management of severe hematuria due to vesical varices.

Polyprenylated acylphloroglucinol meroterpenoids with PTP1B inhibition from Hypericum forrestii.

Three new polyprenylated acylphloroglucinol meroterpenoids, hyperiforins A-C (1-3), were isolated from Hypericum forrestii (Chittenden) N. Robson, together with twelve known analogues (4-15). Their structures were established by extensive physical and spectroscopic data analysis. Compounds 1, 2, 5, 7, and 13-15 showed potent inhibitory effects on protein tyrosine phosphatase 1B with IC50 values from 6.63 ± 2.40 to 14.21 ± 3.51 µM.

Chemical constituents with inhibition against TNF-α from Merrillanthus hainanensis.

Two new steroidal glycosides oxystauntoside A (1) and oxystauntoside B (2), together with sixteen known compounds (3-18) were isolated from the 95% ethanol extract of Merrillanthus hainanensis. Their structures were characterized by extensive spectroscopic analysis including NMR and mass spectra and single crystal X-ray crystallography. The absolute configuration of 1 and 2 were further determined by ECD calculations. All of these compounds were isolated from M. hainanensis for the first time. All the fractions and compounds were tested for the anti-inflammatory activity against the TNF-α factor. The ethyl acetate fraction showed the most potent inhibition (71.3%) at 10 µg/mL and compounds 5 (78.9%) and 9 (73.4%) in this fraction with both carboxyl and phenolic hydroxyl groups showed significant inhibition at 10 µM. Our study provided the first scientific report for the medicinal value of M. hainanensis.

Body surface area-based equivalent dose calculation in tree shrew.

Tree shrew (Tupaia belangeri) is a promising experimental animal in biomedical research, but the equivalent doses of drugs between tree shrew and human and other animals has not been explored, which hinders its further application in a wider scope. The main objective of this article is to provide a method of equivalent dose conversion between tree shrews and other species based on body surface area (BSA). BSA of tree shrews were measured by Image J software, and then the average Km value of tree shrews was figured out based on the body weights and BSA, then the conversion coefficients of equivalent dose among tree shrew and other species of experimental animals were calculated based known data. The Km value of tree shrews was 0.105 ± 0.001. Through BSA conversion, the equivalent dose for tree shrews (D-ts) relative to rats was obtained by formula: D-ts = 1.36 × D-a (rats weighing 200g as example), and the error was less than 10% when the BW of the tree shrew was 0.09 kg-0.15 kg. The coefficients of equivalent dose transferring from tree shrews to human and other species were calculated in article. These parameters could be used to determine a suitable dosing strategy for tree shrew studies.

Plasma volume, cell volume, total blood volume and F factor in the tree shrew.

In this study, the physiological values of volumes of plasma, cells, total blood and the F blood factors were identified in 24 adult tree shrews (Tupaia belangeri; 12 male and 12 female; average BW of 123.9±19.19 g). The two-compartment model method of Evans Blue dye was used to obtain the plasma volume and the venous hematocrit was measured by microhematocrit method. To establish the relationship between body weight (BW) and blood volume of tree shrews, We performed linear fitting for these two datasets. Results were analyzed according to gender and weight (<120g vs.>120g). Statistical significance was assessed using the unpaired student t test and one-way ANOVA. The average volumes per 100g body weight of plasma, red blood cell (RBC) and total blood were 5.42±0.543, 3.24±0.445, and 8.66±0.680ml respectively. The mean body hematocrit, cardiac hematocrit, jugular vein hematocrit, femoral vein hematocrit, and tail vein hematocrit was 37.43±4.096, 39.72±3.219, 43.04±4.717, 40.84±3.041, and 38.71±3.442% respectively. The F cardiac was 0.94±0.072, F jugular vein 0.88±0.118, F femoral vein 0.92±0.111, and the F tail vein 0.97±0.117. Blood volume (ml) was 85.89103×BW (kg). This is the first study to provide the parameters of plasma volume, cell volume, total blood volume and F factor and a baseline for future research on blood physiology of tree shrews.

Chemotherapy-related cognitive impairment in patients with breast cancer based on MRS and DTI analysis.

The purpose of this study is to investigate chemotherapy-related cognitive impairment (CRCI) in breast cancer patients, analyze absolute concentration and structural changes of metabolites in different brain regions by multimodal neuroimaging technology, and explore correlation between them. Breast cancer patients with chemotherapy treatment group (Ctx+, N = 24) and control group without treatment (Ctx-, N = 20) underwent neuropsychological tests, multivoxel magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) before and after chemotherapy. Regions of interest (ROls) in magnetic resonance scan include bilateral posterior cingulate gyrus (PCG), bilateral dorsal thalamus (DT), bilateral lenticular nucleus (LN), bilateral posterior horn of the lateral ventricle paratrigonal white matter (PWM). In MRS, absolute concentrations of N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), total creatine (tCr), glutamine + glutamate (Glx) were quantified using LC Model and SAGE software. In DTI, we used fractional anisotropy (FA) and mean diffusivity (MD) to reflect white matter integrity. In Ctx+ patients, scores of functional assessment of cancer treatment cognition test (FACT-Cog), perceived cognitive impairments (PCI), impact of perceived impairments on quality of life (QOL), perceived cognitive abilities (PCA), auditory-verbal learning test (AVLT) recognition and clock drawing test (CDT) were lower than those before chemotherapy (p < 0.05). In MRS, Ctx+ patients had significantly lower NAA values in bilateral PCG, DT, respectively. The concentrations of tCr were observed to decline in bilateral PCG and right DT. Glx values decreased in right DT. Cho values decreased significantly in bilateral DT. In DTI, Ctx+ patients had lower FA values in bilateral PCG compared with patients before chemotherapy. Among imaging metrics and cognitive scores, positive correlations were observed between changes in AVLT recognition scores and changes in NAA values in bilateral PCG (left PCG: r = 0.470, p < 0.01; right PCG: r = 0.500, p < 0.01). Positive correlations were also found between changes in AVLT recognition and changes in FA values in bilateral PCG (left PCG: r = 0.513, p < 0.01; right PCG: r = 0.563, p < 0.01). Chemotherapy can lead to a decrease in memory function, accompanied by changes in brain metabolite concentration and white matter integrity in some parts of brain.

Hyperprins A and B, Two Complex Meroterpenoids from Hypericum przewalskii.

Hyperprins A (1) and B (2), two polyprenylated acylphloroglucinol related meroterpenoids with undescribed carbon skeletons, were isolated from Hypericum przewalskii. Compound 1 possesses a new 6/6/6/6/5/5 hexacyclic system with an unprecedented tetracyclo[10.3.1.03,8.08,12]hexadecane motif. Compound 2 features a unique 6/8/6/6 tetracyclic scaffold. Their structures were determined by spectroscopic data, chemical method, and X-ray crystallography. Compound 1 showed antiproliferation activity against the MV-4-11 cell line, and the p-bromobenzoate derivative of 2 displayed PTP1B inhibition.

Inhibition of Long Noncoding RNA CRNDE Increases Chemosensitivity of Medulloblastoma Cells by Targeting miR-29c-3p.

Long noncoding RNA CRNDE (CRNDE) recently emerged as a carcinogenic promoter in various cancers including medulloblastoma. However, the functions and molecular mechanisms of CRNDE to the acquired drug resistance of medulloblastoma are still unclear. The transcript levels of CRNDE were examined in four medulloblastoma cell lines exposed to cisplatin treatment, and IC50 values were calculated. Effects of CRNDE knockdown or miR-29c-3p overexpression on cell viability, colony formation, apoptosis, migration, and invasion were assessed using the CCK-8, colony formation assay, flow cytometry, and Transwell assays, respectively. RNA pulldown and RNA-binding protein immunoprecipitation (RIP) were performed to confirm the molecular interactions between CRNDE and miR-29c-3p involved in medulloblastoma cells. The in vivo role of CRNDE knockdown or miR-29c-3p overexpression on tumor growth and apoptosis was evaluated in a xenograft mouse model of human medulloblastoma. The transcript levels of lncRNA CRNDE were significantly higher in cisplatin-treated tumor cells with higher IC50 values. Depletion of CRNDE inhibited tumor cell proliferation and colony formation, induced cell apoptosis, and suppressed migration and invasion in medulloblastoma cells. Moreover, overexpression of miR-29c-3p inhibited tumor cell proliferation and colony formation, migration, and invasion, and enhanced apoptosis and chemosensitivity to cisplatin. In addition, CRNDE was found to act as a miR-29c-3p sponge. Furthermore, in vivo experiments showed the CRNDE/miR-29c-3p interactions involved in medulloblastoma. Our study demonstrates that CRNDE acts as a critical mediator of proliferation, apoptosis, migration, invasion, and resistance to chemotherapeutics via binding to and negatively regulating miR-29c-3p in medulloblastoma cells. These results provide novel molecular targets for treatment of medulloblastoma.

BIN1 rs744373 variant shows different association with Alzheimer's disease in Caucasian and Asian populations.

BACKGROUND: The association between BIN1 rs744373 variant and Alzheimer's disease (AD) had been identified by genome-wide association studies (GWASs) as well as candidate gene studies in Caucasian populations. But in East Asian populations, both positive and negative results had been identified by association studies. Considering the smaller sample sizes of the studies in East Asian, we believe that the results did not have enough statistical power. RESULTS: We conducted a meta-analysis with 71,168 samples (22,395 AD cases and 48,773 controls, from 37 studies of 19 articles). Based on the additive model, we observed significant genetic heterogeneities in pooled populations as well as Caucasians and East Asians. We identified a significant association between rs744373 polymorphism with AD in pooled populations (P = 5 × 10- 07, odds ratio (OR) = 1.12, and 95% confidence interval (CI) 1.07-1.17) and in Caucasian populations (P = 3.38 × 10- 08, OR = 1.16, 95% CI 1.10-1.22). But in the East Asian populations, the association was not identified (P = 0.393, OR = 1.057, and 95% CI 0.95-1.15). Besides, the regression analysis suggested no significant publication bias. The results for sensitivity analysis as well as meta-analysis under the dominant model and recessive model remained consistent, which demonstrated the reliability of our finding. CONCLUSIONS: The large-scale meta-analysis highlighted the significant association between rs744373 polymorphism and AD risk in Caucasian populations but not in the East Asian populations.