Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal, epithelial, and immune cells within the tumor microenvironment (TME). To enable the development of ...more efficacious therapies, we aim to study the heterogeneity, signatures of unique cell populations, and cell-cell interactions of non-immune and immune cell populations in 6 human papillomavirus (HPV)
and 12 HPV
HNSCC patient tumor and matched peripheral blood specimens using single-cell RNA sequencing. Using this dataset of 134,606 cells, we show cell type-specific signatures associated with inflammation and HPV status, describe the negative prognostic value of fibroblasts with elastic differentiation specifically in the HPV
TME, predict therapeutically targetable checkpoint receptor-ligand interactions, and show that tumor-associated macrophages are dominant contributors of PD-L1 and other immune checkpoint ligands in the TME. We present a comprehensive single-cell view of cell-intrinsic mechanisms and cell-cell communication shaping the HNSCC microenvironment.
Summary
Background
Few studies have examined the association between psoriasis and glomerulonephritis (GN) as well as chronic kidney disease (CKD).
Objectives
To determine the risk of CKD in patients ...with psoriasis and evaluate the impact of the severity of psoriasis, comorbidities and concomitant drugs on the risk of GN and CKD in patients with psoriasis.
Methods
We identified 4344 patients with psoriasis for the study cohort and randomly selected 13 032 subjects as a control cohort. Each subject was individually followed for up for 5 years to identify those who subsequently developed GN and CKD.
Results
After adjustment for traditional CKD risk factors, psoriasis was found to be independently associated with an increased risk of CKD during the follow‐up period hazard ratio (HR) 1·28; 95% confidence interval (CI) 1·14–1·44. The increased incidence of GN in patients with psoriasis (HR 1·50, 95% CI 1·24–1·81) may contribute to the positive association between psoriasis and CKD. Patients with mild and severe psoriasis had an increased risk of CKD and GN compared with the control cohort; the risk increased with severity. Patients with psoriasis and arthritis exhibited a higher risk of CKD than patients without arthritis (HR 1·62 vs. 1·26). Among drugs, nonsteroidal anti‐inflammatory drugs (NSAIDs) have the strongest association with CKD in patients with psoriasis (adjusted odds ratio 1·69, 95% CI 1·14–2·49).
Conclusions
Psoriasis was associated with a higher risk of developing CKD and GN. High severity, psoriatic arthritis involvement and concomitant NSAIDs use further increased the risk of CKD in patients with psoriasis.
What's already known about this topic?
There is an increased risk of multiple comorbidities in patients with psoriasis.
What does this study add?
Both mild and severe psoriasis presented an increased risk of chronic kidney disease (CKD) and glomerulonephritis, independent of traditional risk factors for CKD.
The development of CKD in patients with psoriasis was multifaceted. High severity, psoriatic arthritis involvement and concomitant nonsteroidal anti‐inflammatory drug use further increased the risk of CKD in patients with psoriasis.
To evaluate the efficacy of stent placement in the treatment of portal vein (PV) stenosis or occlusion in living donor liver transplant (LDLT) recipients, 468 LDLT records were reviewed. Sixteen (10 ...PV occlusions and 6 stenoses) recipients (age range, 8 months–59 years) were referred for possible interventional angioplasty (dilatation and/or stent) procedures. Stent placement was attempted in all. The approaches used were percutaneous transhepatic (n = 10), percutaneous transsplenic (n = 4), and intraoperative (n = 2). Technical success was achieved in 11 of 16 patients (68.8%). The sizes of the stents used varied from 7 mm to 10 mm in diameter. In the five unsuccessful patients, long‐term complete occlusion of the PV with cavernous transformation precluded catherterization. The mean follow‐up was 12 months (range, 3–24). The PV stent patency rate was 90.9% (10/11). Rethrombosis and occlusion of the stent and PV occurred in a single recipient who had a cryoperserved vascular graft to reconstruct the PV during the LDLT operation. PV occlusion of >1 year with cavernous transformation seemed to be a factor causing technical failure. In conclusion, early treatment of PV stenosis and occlusion by stenting is an effective treatment in LDLT. Percutaneous transhepatic and transsplenic, and intraoperative techniques are effective approaches depending on the situation.
Vascular stents in management of portal venous complications: percutaneous transhepatic and transplenic and intraoperative techniques can be effective in patients with portal venous complications, depending on the situation.
With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
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.
Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by ineffective hematopoiesis and leukemia progression. Racial differences may exist on clinical pictures and ...the molecular events leading to MDS, which are heterogeneous. To better define the clinical and cytogenetic features in Chinese patients, a retrospective multicentric study was performed in 508 MDS cases. Compared with Western countries, Chinese patients showed younger age (median: 49 vs 65-73 years), lower percentages of RARS (2.8 vs 6.6-15.3%), and CMML (5.2 vs 11.7-30.6%). Cytogenetically, among 367 cases with evaluable data, abnormal karyotypes were found in 136 cases, including 56 numerical and 80 structural changes. Incidences of single chromosome 5 and 7 abnormalities were lower than those in Western countries (2.2 vs 17.8-42.5%). However, complex cytogenetic aberrations and chromosome translocations were frequently observed and related to poor prognosis. Both multiple chromosome deletions and translocations were detected in advanced subtypes (RAEB and RAEB-T). Analysis of 200 cases revealed a higher incidence of hepatitis-B-virus infection than that in non-MDS population (21.00 vs 9.75%). This study further confirmed: (1) different genetic/environmental backgrounds between Asian and Western MDS populations; (2) a strong predictive value of cytogenetic abnormalities on disease outcome and involvement of genomic instability in leukemia clone development.
Sex controls have been performed in some farmed fish species because of significant growth differences between females and males. In yellow catfish (Pelteobagrus fulvidraco), adult males are three ...times larger than female adults. In this study, six Y- and X-linked amplified fragment length polymorphism fragments were screened by sex-genotype pool bulked segregant analysis and individual screening. Interestingly, sequence analysis identified two pairs of allelic genes, Pf33 and Pf62. Furthermore, the cloned flanking sequences revealed several Y- and X-specific polymorphisms, and four Y-linked or X-linked sequence characterized amplified region (SCAR) primer pairs were designed and converted into Y- and X-linked SCAR markers. Consequently, these markers were successfully used to identify genetic sex and YY super-males, and applied to all-male population production. Thus, we developed a novel and simple technique to help commercial production of YY super-males and all-male populations in the yellow catfish.
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.
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