The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in ...colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
The objective of this retrospective study was to assess safety and comparative clinical effectiveness of laparoscopic inguinal hernia repair (LIHR) and robot-assisted inguinal hernia repair ...(RIHR) from multi-institutional experience in Taiwan.
Methods
Medical records from a total of eight hospitals were retrospectively collected and analyzed. Patients primarily diagnosed of inguinal hernia, recurrent inguinal hernia or incarceration groin hernia patients who either underwent laparoscopic or robot-assisted inguinal hernia repair between January 2018 and December 2022 were included in the study. Baseline characteristics, intra-operative and post-operative results were analyzed. To compare two cohorts, overlap weighting was employed to balance the significant inter-group differences. We also conducted subgroup analyses by state of a hernia (primary or recurrent/incarceration) and laterality (unilateral or bilateral) that indicated complexity of surgery.
Results
A total of 1,080 patients who underwent minimally invasive inguinal hernia repair from 8 hospitals across Taiwan were collected. Following the application of inclusion criteria, there were 279 patients received RIHR and 763 patients received LIHR. In the baseline analysis, RIHR was more often performed in recurrent/incarceration (RIHR 18.6% vs LIHR 10.3%,
p
= 0.001) and bilateral cases (RIHR 81.4 vs LIHR 58.3,
p
< 0.001). Suturing was dominant mesh fixation method in RIHR (RIHR 81% vs LIHR 35.8%,
p
< 0.001). More overweight patients were treated with RIHR (RIHR 58.8% vs LIHR 48.9%,
p
= 0.006). After overlap weighting, there were no significant difference in intraoperative and post-operative complications between RIHR and LIHR. Reoperation and prescription rates of pain medication (opioid) were significantly lower in RIHR than LIHR in overall group comparison (reoperation: RIHR 0% vs. LIHR 2.9%,
p
= 0.016) (Opioid prescription: RIHR 3.34 mg vs LIHR 10.82 mg,
p
= 0.001) while operation time was significantly longer in RIHR (OR time: RIHR 155.27 min vs LIHR 95.30 min, p < 0.001).
Conclusions
This real-world experience suggested that RIHR is a safe, and feasible option with comparable intra-operative and post-operative outcomes to LHIR. In our study, RIHR showed technical advantages in more complicated hernia cases with yielding to lower reoperation rates, and less opioid use.
Background
The coronavirus disease 2019 (COVID-19) pandemic is having a profound impact on the health and development of children worldwide. There is limited evidence on the impact of COVID-19 and ...its related school closures and disease-containment measures on the psychosocial wellbeing of children; little research has been done on the characteristics of vulnerable groups and factors that promote resilience.
Methods
We conducted a large-scale cross-sectional population study of Hong Kong families with children aged 2–12 years. Parents completed an online survey on family demographics, child psychosocial wellbeing, functioning and lifestyle habits, parent–child interactions, and parental stress during school closures due to COVID-19. We used simple and multiple linear regression analyses to explore factors associated with child psychosocial problems and parental stress during the pandemic.
Results
The study included 29,202 individual families; of which 12,163 had children aged 2–5 years and 17,029 had children aged 6–12 years. The risk of child psychosocial problems was higher in children with special educational needs, and/or acute or chronic disease, mothers with mental illness, single-parent families, and low-income families. Delayed bedtime and/or inadequate sleep or exercise duration, extended use of electronic devices were associated with significantly higher parental stress and more psychosocial problems among pre-schoolers.
Conclusions
This study identifies vulnerable groups of children and highlights the importance of strengthening family coherence, adequate sleep and exercise, and responsible use of electronic devices in promoting psychosocial wellbeing during the COVID-19 pandemic.
Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with ...current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.
Summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may ...contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant‐expressed miRNAs using real‐time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant‐expressed miRNAs was detected using real‐time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR‐145, miR‐224, miR‐513‐5p, miR‐150, miR‐516a‐5p, miR‐483‐5p and miR‐629, were found to be potentially abnormally expressed in SLE T cells. After validation, under‐expressed miR‐145 and over‐expressed miR‐224 were noted. We further found that STAT1 mRNA targeted by miR‐145 was over‐expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR‐224 was under‐expressed in SLE T cells. Transfection of Jurkat cells with miR‐145 suppressed STAT1 and miR‐224 transfection suppressed API5 protein expression. Over‐expression of miR‐224 facilitates activation‐induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR‐145 and miR‐224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation‐induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription‐1 (STAT)‐1 expression in patients with SLE.
Summary
Kefir treatment in ovariectomized (OVX) rats could significantly decrease the levels of bone turnover markers and prevent OVX-induced bone loss, deterioration of trabecular microarchitecture, ...and biomechanical dysfunction that may be due to increase intracellular calcium uptake through the TRPV6 calcium channel.
Introduction
Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to an increased fracture risk. The incidence of osteoporosis increases with age and occurs most frequently in postmenopausal women due to estrogen deficiency, as the balance between bone resorption and bone formation shifts towards increased levels of bone resorption. Among various methods of prevention and treatment for osteoporosis, an increase in calcium intake is the most commonly recommended preventive measure. Kefir is a fermented milk product made with kefir grains that degrade milk proteins into various peptides with health-promoting effects, including immunomodulating-, antithrombotic-, antimicrobial-, and calcium-absorption-enhancing bioactivities.
Methods
The aim of this study is to investigate the effect of kefir on osteoporosis prophylaxis in an ovariectomized rat model. A total of 56 16-week-old female Sprague-Dawley (SD) rats were divided into 7 experimental groups: sham (normal), OVX/Mock, OVX/1X kefir (164 mg/kg BW/day), OVX/2X kefir (328 mg/kg BW/day), OVX/4X kefir (656 mg/kg BW/day), OVX/ALN (2.5 mg/kg BW/day), and OVX/REBONE (800 mg/kg BW/day). After 12-week treatment with kefir, the bone physiology in the OVX rat model was investigated. Accordingly, the aim of this study was to investigate the possible transport mechanism involved in calcium absorption using the Caco-2 human cell line.
Results
A 12-week treatment with kefir on the OVX-induced osteoporosis model reduced the levels of C-terminal telopeptides of type I collagen (CTx), bone turnover markers, and trabecular separation (Tb. Sp.). Additionally, treatment with kefir increased trabecular bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and the biomechanical properties (hardness and modulus) of the distal femur with a dose-dependent efficacy. In addition, in in vitro assay, we found that kefir increased intracellular calcium uptake in Caco-2 cell through TRPV6 calcium channels and not through L-type voltage-operated calcium channels.
Conclusion
The protective effect of kefir in the OVX rat model may occur through increasing intracellular calcium uptake through the TRPV6 calcium channel.
Purpose The contribution of adjuvant chemotherapy after chemoradiation therapy (CRT) in nasopharyngeal cancer (NPC) remains controversial. Plasma Epstein-Barr virus (EBV) DNA is a potential biomarker ...of subclinical residual disease in NPC. In this prospective, multicenter, randomized controlled trial, we used plasma EBV DNA to identify patients with NPC at a higher risk of relapse for adjuvant chemotherapy. Patients and Methods Eligible patients with histologically confirmed NPC of Union for International Cancer Control stage IIB to IVB, adequate organ function, and no locoregional disease or distant metastasis were screened by plasma EBV DNA at 6 to 8 weeks after radiotherapy (RT). Patients with undetectable plasma EBV DNA underwent standard surveillance. Patients with detectable plasma EBV DNA were randomly assigned to either adjuvant chemotherapy with cisplatin and gemcitabine for six cycles (arm 1) or observation (arm 2). Patients were stratified for primary treatment (RT v CRT) and stage (II/III v IV). The primary end point was relapse-free survival (RFS). Results Seven hundred eighty-nine patients underwent EBV DNA screening. Plasma EBV DNA was undetectable in 573 (72.6%) and detectable in 216 (27.4%); 104 (13.2%) with detectable EBV DNA were randomly assigned to arms 1 (n = 52) and 2 (n = 52). After a median follow-up of 6.6 years, no significant difference was found in 5-year RFS rate between arms 1 and 2 (49.3% v 54.7%; P = .75; hazard ratio for relapse or death, 1.09; 95% CI, 0.63 to 1.89). The level of post-RT plasma EBV DNA correlated significantly with the hazards of locoregional failure, distant metastasis, and death. Conclusion In patients with NPC with detectable post-RT plasma EBV DNA, adjuvant chemotherapy with cisplatin and gemcitabine did not improve RFS. Post-RT plasma EBV DNA level should be incorporated as the selection factor in future clinical trials of adjuvant therapy in NPC.
Klebsiella pneumoniae-caused liver abscess (KLA) is an emerging infectious disease. However, factors other than K1-specific loci that contribute to the pathogenesis of this disease have not been ...identified. pLVPK is a 219,385-bp plasmid of K. pneumoniae CG43, an invasive K2 strain associated with KLA. We aimed in this study to evaluate the involvement of pLVPK in K. pneumoniae virulence and its clinical significance in abscess formation. A pLVPK-cured CG43 was isolated and its virulence was examined in a mouse model. The prevalence of pLVPK-derived loci terW, iutA, rmpA, silS, and repA was investigated in 207 clinical isolates by screening with specific primers. Loss of pLVPK abolished the ability of K. pneumoniae to disseminate into extraintestinal sites and, consequently, attenuated abscess formation in mice. Primary K. pneumoniae abscess isolates (n = 94) were more likely to be terW ⁺-iutA ⁺-rmpA ⁺-silS ⁺ than those related to non-abscess infections (n = 113) (62% vs. 27%; p < 0.0001). Logistic regression analysis indicated that the presence of the terW-rmpA-iutA-silS loci was a significant risk factor (odds ratio, 4.12; 95% confidence interval, 2.02-8.4; p < 0.0001) for abscess formation. pLVPK is a determinant for K. pneumoniae virulence and infection with strains carrying the pLVPK-derived terW-rmpA-iutA-silS loci may predispose patients to abscess formation.
Viable aerosols in the airflow may increase the risk of occupants contracting diseases. Natural ventilation is common in buildings and is accompanied by re-entry airflow during the ventilation ...process. If the re-entry airflow contains toxic or infectious species, it may cause potential harm to residents. One of the Covid-19 outbreaks occurred in a public residential building at Luk Chuen House (LC-House) in Hong Kong. It is highly suspected that the outbreak of the disease is related to the re-entry airflow. The study attempts to explain and discuss possible causes of the outbreak. In order to understand the impact of airflow on the outbreak, a public residential building similar to LC-House was used in the study. Two measurements M − I and M − II with the same settings were conducted for a sampling unit in the corridor under low and strong wind conditions respectively. The sampling unit and the tracer gas carbon dioxide (CO2) were used to simulate the index unit and infectious contaminated airflow respectively. The CO2 concentrations of the unit and corridor were measured simultaneously. Two models of Traditional Single-zone model (TSZ-model) and New Dual-zone model (NDZ-model) were used in the analysis. By comparing the ACH values obtained from the two models, it is indicated that the re-entry airflow of the unit is related to the corridor wind speeds and this provides a reasonable explanation for the outbreak in LC-House, and believes that the results can help understand the recent frequent cluster outbreaks in other residential buildings.
•The dual-zone model can more accurately describe the ventilation of the room.•The newly introduced fade-index shows the airflow characteristics of the corridor.•The integration of TSZ-model and NDZ-model can quantify re-entry airflow.•Re-entry airflow is a wind speed depending sub-airflow in ventilation.•Re-entry airflow cannot be neglected during studying Covid-19 spread in buildings.
More than 100,000 genetic variants are reported to cause Mendelian disease in humans, but the penetrance-the probability that a carrier of the purported disease-causing genotype will indeed develop ...the disease-is generally unknown. We assess the impact of variants in the prion protein gene (PRNP) on the risk of prion disease by analyzing 16,025 prion disease cases, 60,706 population control exomes, and 531,575 individuals genotyped by 23andMe Inc. We show that missense variants in PRNP previously reported to be pathogenic are at least 30 times more common in the population than expected on the basis of genetic prion disease prevalence. Although some of this excess can be attributed to benign variants falsely assigned as pathogenic, other variants have genuine effects on disease susceptibility but confer lifetime risks ranging from <0.1 to ~100%. We also show that truncating variants in PRNP have position-dependent effects, with true loss-of-function alleles found in healthy older individuals, a finding that supports the safety of therapeutic suppression of prion protein expression.
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