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Bisphosphonates are considered an effective inhibitor of glutamine synthetase and thus can be used for treating tuberculosis (TB). However, its clinical benefit in TB remains unknown. We conducted a population-based cohort study by using the Taiwan National Health Insurance Research Database and TB databases of the Taiwan Centers for Disease Control. Patients with osteoporosis and a history of bone fracture from 2007 to 2014 were identified. Among them, bisphosphonate users and propensity score-matched nonusers were selected. A stratified multivariable Cox proportional hazard regression model was employed to investigate the independent predictors of TB. Among 218 908 patients with osteoporosis and bone fracture, 46 842 bisphosphonate users and 46 842 propensity score-matched nonusers were selected. Within the 2-year follow-up, 723 patients-348 in the user group and 375 in the nonuser group-developed TB. Bisphosphonate use was not an independent predictor of TB in the multivariable Cox proportional hazard model (adjusted hazard ratio, 0.86; 95%CI, 0.71-1.04); however, male sex, older age, being bedridden, and steroid use were independent risk factors. The real-world data revealed that bisphosphonate use did not protect patients with osteoporosis against TB.

Diabetes mellitus (DM) is highly comorbid with severe dengue diseases; however, the underlying mechanisms are unclear. Patients with DM have a 1.61-fold increased risk of developing dengue hemorrhagic fever. In search of host factors involved in dengue virus (DENV) infection, we used high-glucose (HG) treatment and showed that HG increased viral protein expression and virion release but had no effects on the early stages of viral infection. After HG stimulation, DENV-firefly luciferase-transfected assay and cellular replicon-based assay indicated increased viral translation, whereas using the glucose uptake inhibitor phloretin blocked this effect. HG treatment increased the translational factor poly(A)-binding protein (PABP) in a glucose transporter-associated, PI3K/AKT-regulated manner. Silencing PABP significantly decreased HG-prompted virion production. HG enhanced the formation of the PABP-eukaryotic translation initiation factor 4G complex, which is regulated by protein-disulfide isomerase. Hyperglycemia increased PABP expression, mortality rate, viral protein expression, and viral loads in streptozotocin-induced DM mice. Overall, hyperglycemic stress facilitates DENV infection by strengthening PABP-mediated viral translation.

Biomaterials for effective hemorrhage control are urgently needed in clinics as uncontrolled bleeding is associated with high mortality. Herein, we developed an injectable and in situ photo-crosslinkable hybrid hemostatic hydrogel by combining pectin methacrylate (PECMA) and gelatin methacryloyl (GelMA). This modular material system combines ionic- and photo-crosslinking chemistries to design interpenetrating networks (IPN) exhibiting tunable rheology, highly porous structure, and controllable swelling and mechanical properties. By simply changing the calcium (0–15 mM) and polymer (1.5–7%) content used for the sequential crosslinking of hydrogels via calcium gelation and UV-photopolymerization, it was possible to precisely modulate the injectability, degradation, and swelling ratio. Moreover, it is demonstrated that PECMA/GelMA hydrogels present good cytocompatibility and uniquely synergize the hemostatic properties of calcium ions on PECMA, the amine residues on GelMA, and the highly porous network toward rapid blood absorption and fast coagulation effect. An in vitro porcine skin bleeding model confirmed that the hydrogel could be directly injected into the wound and rapidly photo-crosslinked, circumventing the bleeding and decreasing the coagulation time by 39%. Importantly, the crosslinked hydrogel could be easily removed to prevent secondary wound injury. Overall, this injectable hybrid PECMA/GelMA hydrogel stands as a promising hemostatic material.

The data concerning the association between dengue viruses (DV) infection and autoimmune diseases (ADs) remain unclear and are scarce. This nationwide population-based cohort study assessed the risk of ADs among patients with DV infection. We analyzed Taiwanese medical data from the Registry of the National Notifiable Disease Reporting System of Taiwan’s Centers for Disease Control between 1998 and 2015 and identified patients with DV infection. From the entire general population data in the National Health Insurance Research Database, we randomly selected a comparison cohort that was individual matching by age, sex, residence, and index date. We analyzed the risk of ADs using a Cox proportional hazards regression model stratified by sex, age, and residence. We enrolled 29,365 patients with DV infection (50.68% men; mean age, 44.13 years) and 117,460 age-, sex-, and residence-matched controls in the present study. The incidence rates of organ-specific ADs were nonsignificantly higher in the DV cohort than in the non-DV control cohort. An approximately 70% lower risk of primary Sjogren syndrome (pSS) was evident in the DV cohort than in the non-DV control cohort with an adjusted hazard ratio of 0.30 (95% confidence interval 0.13–0.67) after adjusting for comorbidities in matched design. By contrast, the other systemic ADs were nonsignificantly lower in the DV cohort than in the non-DV control cohort. This nationwide long-term cohort study demonstrated that patients with DV infection had a lower risk of primary Sjogren syndrome than those without DV infection. Key Points• This retrospective, longitudinal cohort observational study shows that patients with DV infection had a lower risk of pSS than those without DV infection.• The DV cohort had an approximately 70% lower risk of pSS than the control group, with a multivariate-adjusted HR of 0.30.• On the basis of this result, we contended that DV infection has a protective effect that reduces the risk of pSS.

Context At the end of life, chronic obstructive pulmonary disease (COPD) and lung cancer (LC) patients exhibit similar symptoms; however, a large-scale study comparing end-of-life health care utilization between these two groups has not been conducted in East Asia. Objectives To explore and compare end-of-life resource use during the last six months before death between COPD and LC patients. Methods Using data from the Taiwan National Health Insurance Research Database, we conducted a nationwide retrospective cohort study in COPD (n = 8640) and LC (n = 3377) patients who died between 1997 and 2013. Results The COPD decedents were more likely to be admitted to intensive care units (57.59% vs 29.82%), to have longer intensive care unit stays (17.59 vs 9.93 days), and to undergo intensive procedures than the LC decedents during their last six months; they were less likely to receive inpatient (3.32% vs 18.24%) or home-based palliative care (0.84% vs 8.17%) and supportive procedures than the LC decedents during their last six months. The average total medical cost during the last six months was approximately 18.42% higher for the COPD decedents than for the LC decedents. Conclusion Higher intensive health care resource use, including intensive procedure use, at the end of life suggests a focus on prolonging life in COPD patients; it also indicates an unmet demand for palliative care in these patients. Avoiding potentially inappropriate care and improving end-of-life care quality by providing palliative care to COPD patients are necessary.

Patients receiving hemodialysis (HD) are at risk of TB development. IGRA-positive patients showed significant decrease in quantitative IGRA result with alterations in CD3+CD4+CD45RO+, NK cell, and monocyte subsets immediately upon HD procedure. Our result suggested that the timing of IGRA testing is crucial in end-stage renal disease population.

Background Global pandemic resulted from the coronavirus disease-19 (COVID-19) demands mental health concerns on the affected population. We examine the time-course shift of psychological burden among suspected and confirmed COVID-19 patients. Methods Participants with suspected or confirmed COVID-19 were included in the cohort. Consecutive surveys were conducted upon hospital admission, discharge, and during outpatient follow-up by adapting the 5-item brief symptom rating scale (BSRS-5) assessing psychological symptoms including anxiety, depression, hostility, interpersonal sensitivity, and insomnia. The sixth measure to observe suicidal ideation was also included. Results A total of 109 eligible patients participated in the study, in which 83.49% reported no distress upon hospital admission, while 2.75%, 3.66%, and 10.1% patients were assessed as being with severe, moderate and mild psychological distress, respectively. Overall, age, sex, and history of contact did not significantly differ between patients with and without psychological distress. Multivariate logistic regression revealed that patients admitted during April–May (OR: 7.66, 95% CI: 1.46–40.28) and presented with symptoms including sore throat (OR: 4.24, 95% CI: 1.17–15.29) and malaise (OR: 5.24, 95% CI: 1.21–22.77) showed significantly higher risk of psychological distress. Cough symptom interestingly showed lower risk of emotional distress (OR: 0.25, 95% CI: 0.08–0.81). Subsequent surveys upon hospital discharge and during outpatient follow-up revealed steadily declining distress among all cohort. Conclusion At least 16.5% of our cohort reported psychological distress upon hospital admission, with distinct time-dependent decline. Access to mental health support, alongside with promoting positive activities for good mental health are pivotal for those directly affected.

Background Three-dimensional (3D) printing techniques have been used for anatomical models and surgical guiding instruments in orthopaedic surgery. The accuracy of these surgical guiding tools is important for obtaining good clinical outcomes. This study assessed the shape accuracy of an acrylonitrile butadiene styrene (ABS) canine tibia model printed using fused deposition modelling (FDM) and evaluated its morphological change after hydrogen peroxide (H2O2) gas plasma sterilisation. The tibias of six canine cadavers underwent computed tomography for 3D reconstruction. Tibia models were fabricated from ABS on a 3D printer through FDM. Reverse-engineering technology was used to compare morphological errors (root mean square; RMS) between the 3D-FDM models and virtual models segmented from original tibia images (3D-CT) and between the models sterilised with H2O2 gas plasma (3D-GAS) and 3D-FDM models on tibia surface and in cross-sections at: 5%, 15%, 25%, 50%, 75%, 85%, and 95% of the tibia length. Results The RMS mean ± standard deviation and average positive and negative deviation values for all specimens in G1 (3D-FDM vs. 3D-CT) were significantly higher than those in G2 (3D-GAS vs. 3D-FDM; P P

This study evaluated the effect of chitosan, poly vinyl alcohol (PVA) and poly (2-hydroxyethyl methacrylate) (pHEMA) on delaying the human fibroblast senescence. Cells could form suspending multicellular spheroids on these biomaterials, but only chitosan was capable of decreasing the SA β-gal activity and increasing the proliferation ability of senescent fibroblasts. Therefore, in addition to the structure of multicellular spheroids, chitosan itself should play an important role in delaying fibroblast senescence. The main difference of senescence-related protein expressions for cells cultured on chitosan, PVA and pHEMA occurred on the TGF-β signaling pathway. In addition to the intracellular TGF-β expression, the extracellular TGF-β expression was also downregulated. Chitosan with cationic amino structure was assumed to bind with anionic TGF-β by forming polyelectrolyte complexes. This assumption was demonstrated by directly adding chitosan into the medium to downregulate the cell TGF-β expression and further to delay cell senescence, indicating TGF-β signaling pathway was involved in the chitosan-mediating fibroblast senescence process. Finally, the delaying cell senescence ability of chitosan increased with increasing the amount of amino groups in chitosan and its ionization degree. In summary, these results provide important information for considering the application of chitosan in the future cell therapy and regeneration medicine.

An ideal in vitro drug screening model is important for the drug development. In addition to monoculture systems, 3 dimensional (3D) coculture systems are extensively used to simulate the in vivo tumor microenvironment as cell-cell and cell-extracellular matrix interactions within the tumor tissues can be mimicked. In this study, in vitro 3D suspension coculture multicellular spheroids with core/shell cell distribution were developed on chitosan-coated surfaces. Based on the characteristic of chitosan inhibiting cell adhesion, SW620 (colon cancer cell line), 3A6 (mesenchymal stem-like cell line) and Hs68 (foreskin fibroblast line) cells could aggregate to form 3D coculture spheroids with intimate cell contacts. When cells were cocultured on chitosan, 3A6 and Hs68 cells always located in the core of spheroids and were completely enveloped by SW620 cells due to their N-cadherin protein expression following the differential adhesion hypothesis. The core cells could be the feeder layers to stimulate the shell SW620 cells to enhance their mitochondria activity. Moreover, 3D coculture core/shell multicellular spheroids could enhance the resistance of SW620 cells against the cytotoxicity effect of chemotherapy drugs. To sum up, based on the specificity of the core/shell coculture multicellular spheroids, a novel in vitro tumor model was proposed in this study.

CD44, a cell-surface glycoprotein, plays an important role in cell proliferation, adhesion, migration, and other biological functions, which are related with the physiological and pathologic activities of cells. Especially, CD44 is extensively expressed within adult bone marrow and has been considered as an important marker for some cancer stem cells (CSCs) in various types of tumors. Therefore, it is essential to understand the variations in CD44 expression of stem cells and cancer cells for further clinical applications. In this paper, CD44 expression was assessed on a human colon cancer cell line (SW620), a human mesenchymal stem-like cell line (3A6), and a human foreskin fibroblast line (Hs68). We used chitosan to establish a suspension culture model to develop multicellular spheroids to mimic a three-dimension (3D) in vivo environment. Obviously, CD44 expression on 3A6 and SW620 cells was dynamic and diverse when they were in the aggregated state suspended on chitosan, while Hs68 cells were relatively stable. Furthermore, we discuss how to regulate CD44 expression of 3A6 and SW620 cells by the interactions between cell and cell, cell and chitosan, as well as cell and microenvironment. Finally, the possible mechanism of chitosan to control CD44 expression of cells is proposed, which may lead to the careful use of chitosan for potential clinical applications.

The advantages of Thermo-Raman spectroscopy are the identification of structure and the ability to monitor the transformation of a sample in a heating process. In this work, Raman spectra were taken continuously from xerogel TiO2 in a heating process similar to that in TGA/DTA. The variation in Raman spectra showed the phase transformation from xerogel to amorphous TiO2 and then to anatase and rutile successively was consistent with the peaks in TGA for a weight loss of 25% at 82°C and two extra endothermic peaks in DTA at 382 and 573°C. However, the transformation from anatase to rutile at 573°C was not complete.