An analysis of influencing factors of oral frailty in the elderly in the community.

OBJECTIVE: This study aimed to investigate the current situation of oral frailty (OF) in the elderly in the community in China and analyse its influencing factors. METHODS: Using convenience sampling, 380 elderly people from three communities in our city were selected as participants in the study. The Oral Frailty Index-8, the Frailty Scale, the Oral Health Assessment Tool, the Mini-nutritional Assessment Scale and the Pittsburgh Sleep Quality Index were used to investigate and analyse OF influencing factors. RESULTS: In this study, the 380 elderly participants were categorized into three groups: frailty, pre-frailty, and non-physical frailty, based on their responses to the questionnaires.The influencing factor analysis showed that age, gender, education level, frailty score, frailty stage, number of dentures, dry mouth, subjective chewing difficulty, oral health score and sleep quality were the influencing factors of OF in the elderly in the community (R2 = 0.712, F = 434.73, P < 0.05). The evaluation of the prediction results showed that the frailty score (area under the curve [AUC]: 0.751, 95% confidence interval [CI]: 0.683-0.862), subjective chewing difficulty (AUC: 0.765, 95% CI: 0.655-0.831) and sleep quality (AUC: 0.736, 95% CI: 0.652-0.781) had a higher predictive value for OF. CONCLUSION: The main OF influencing factors in the elderly in the community are age, gender, education level, physical frailty (PF) score, PF stage, number of dentures, dry mouth, subjective chewing difficulties, oral health score and sleep quality. Nursing staff should pay attention to the OF of the elderly in the community and take targeted intervention measures in time to reduce and control OF occurrence and progression.

Design, synthesis, in vitro and in vivo biological evaluation of pterostilbene derivatives for anti-inflammation therapy.

Pterostilbene (PST) is a naturally derived stilbene compound in grapes, blueberries, and other fruits. It is also a natural dietary compound with a wide range of biological activities such as antioxidant, anti-inflammatory, antitumor, and so on. Structural modifications based on the chemical scaffold of the pterostilbene skeleton are of great importance for drug discovery. In this study, pterostilbene skeletons were used to design novel anti-inflammatory compounds with high activity and low toxicity. A total of 30 new were found and synthesised, and their anti-inflammatory activity and safety were screened. Among them, compound E2 was the most active (against NO: IC50 = 0.7 µM) than celecoxib. Further studies showed that compound E2 exerted anti-inflammatory activity by blocking LPS-induced NF-κB/MAPK signalling pathway activation. In vivo experiments revealed that compound E2 had a good alleviating effect on acute colitis in mice. In conclusion, compound E2 may be a promising anti-inflammatory lead compound.

Calycosin inhibits triple-negative breast cancer progression through down-regulation of the novel estrogen receptor-α splice variant ER-α30-mediated PI3K/AKT signaling pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) is a heterogeneous carcinoma characterized by the most aggressive phenotype among all breast cancer subtypes. However, therapeutic options for TNBC patients have limited clinical efficacy due to lack of specific target and efficient targeted therapeutics. AIM: To investigate the biological characteristics of a novel estrogen receptor (ER)-α splice variant ER-α30 in breast cancer cells, and its possible role in the anticancer effects of calycosin, a typical phytoestrogen derived from the herbal plant Astragalus membranaceus, against TNBC. This may also provide a better understanding of the inhibitory activity of calycosin on TNBC progression. METHODS: Breast cancer tissues and para-cancer tissues were collected and analyzed for the expression levels of ER-α30 using immunohistochemistry (IHC), and its expression in two TNBC cell lines (MDA-MB-231 and BT-549) was detected by western blot and qRT-PCR assays. Then the alteration of cell viability, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT) in response to overexpression or knockdown of ER-α30 was separately determined by CCK-8, Hoechst 33258, wound healing, transwell and western blot assays in two TNBC cell lines. Next, the anticancer effects of calycosin on MDA-MB-231 cells were evaluated through CCK-8, colony formation, flow cytometry, Hoechst 33258 and western blot assays, along with the role of ER-α30 in these effects and the possible downstream targets of ER-α30. In addition, the in vivo experiments were carried out using MDA-MB-231 xenograft model intraperitoneally treated with calycosin. The volume and weight of xenograft tumor were measured to evaluate the in vivo anticancer activities of calycosin, while the corresponding changes of ER-α30 expression in tumor tissues were detected by IHC. RESULTS: It was demonstrated that the novel ER-α splice variant ER-α30 was primarily distributed in the nucleus of TNBC cells. Compared with normal breast tissues, ER-α30 expression was found in significantly higher levels in breast cancer tissues of ER- and progesterone receptor (PR)-negative subtype, so did in TNBC cell lines (MDA-MB-231 and BT-549) when compared to normal breast cell line MCF10A. Moreover, ER-α30 overexpression strikingly enhanced cell viability, migration, invasion and EMT progression and reduced apoptosis in TNBC cells, whereas shRNA-mediated knockdown of ER-α30 revealed the opposite results. Notably, calycosin suppressed the expression of ER-α30 in a dose-dependent manner, accompanied with the inhibition of TNBC growth and metastasis. A similar finding was observed for the xenografts generated from MDA-MB-231 cells. The treatment with calycosin suppressed the tumor growth and decreased ER-α30 expression in tumor tissues. Furthermore, this inhibition by calycosin was more pronounced in ER-α30 knockdown cells. Meanwhile, we found a positive relationship between ER-α30 and the activity of PI3K and AKT, which could also be inactivated by calycosin treatment. CONCLUSION: For the first time, it is demonstrated that the novel estrogen receptor-α splice variant ER-α30 could function as pro-tumorigenic factor in the context of TNBC by participating in cell proliferation, apoptosis, invasion and metastasis, thus it may serve as a potential therapeutic target for TNBC therapy. Calycosin could reduce the activation of ER-α30-mediated PI3K/AKT pathway, thereby inhibited TNBC development and progression, suggesting that calycosin may be a potential therapeutic option for TNBC.

Revving the engine: PKB/AKT as a key regulator of cellular glucose metabolism.

Glucose metabolism is of critical importance for cell growth and proliferation, the disorders of which have been widely implicated in cancer progression. Glucose uptake is achieved differently by normal cells and cancer cells. Even in an aerobic environment, cancer cells tend to undergo metabolism through glycolysis rather than the oxidative phosphorylation pathway. Disordered metabolic syndrome is characterized by elevated levels of metabolites that can cause changes in the tumor microenvironment, thereby promoting tumor recurrence and metastasis. The activation of glycolysis-related proteins and transcription factors is involved in the regulation of cellular glucose metabolism. Changes in glucose metabolism activity are closely related to activation of protein kinase B (PKB/AKT). This review discusses recent findings on the regulation of glucose metabolism by AKT in tumors. Furthermore, the review summarizes the potential importance of AKT in the regulation of each process throughout glucose metabolism to provide a theoretical basis for AKT as a target for cancers.

A novel porous granular scaffold for the promotion of trabecular bone repair by time-dependent alteration of morphology.

Granular scaffolds have been extensively used in the clinic to repair irregular maxillofacial defects. There remain some challenges for the repair of trabecular structures in cancellous bone due to the reticular lamella-like morphology. In this study, we fabricated a novel granular scaffold by rational design of components with different degradation rates so that the morphology of the novel scaffold can evolve to match the growth period of bone cells. Here, polycaprolactone (PCL) was used to fabricate porous microspheres as a skeleton with slow degradation. The macropores were filled with quick degraded gelatin to form complete microspheres. Asynchronous degradation of the two components altered the morphology of the evolutive scaffold from compact to porous, gradually exposing the ridge-like skeletons. This scaffold reversed the decline of cellular adhesion to simple porous skeletons during the initial adhesion. Furthermore, the cells were able to grow into the pores and adhere onto the skeletons with an elongated cellular morphology, facilitating osteogenic differentiation. This novel scaffold was experimentally proven to promote the regeneration of alveolar bone along with a good percentage of bone volume and the formation of trabecular structures. We believe this morphology-evolved scaffold is highly promising for regenerative applications in the clinic.

Estrogen and Estrogen Receptor Modulators: Potential Therapeutic Strategies for COVID-19 and Breast Cancer.

Owing to the ongoing coronavirus disease 2019 (COVID-19) pandemic, we need to pay a particular focus on the impact of coronavirus infection on breast cancer patients. Approximately 70% of breast cancer patients express estrogen receptor (ER), and intervention therapy for ER has been the primary treatment strategy to prevent the development and metastasis of breast cancer. Recent studies have suggested that selective estrogen receptor modulators (SERMs) are a potential therapeutic strategy for COVID-19. With its anti-ER and anti-viral combined functions, SERMs may be an effective treatment for COVID-19 in patients with breast cancer. In this review, we explore the latent effect of SERMs, especially tamoxifen, and the mechanism between ER and virus susceptibility.

Superparamagnetic core-shell electrospun scaffolds with sustained release of IONPs facilitating in vitro and in vivo bone regeneration.

Bone tissue engineering (BTE) is a promising approach to recover insufficient bone in dental implantations. However, the clinical application of BTE scaffolds is limited by their low mechanical strength and lack of osteoinduction. In an attempt to circumvent these limitations and improve osteogenesis, we introduced magnetic iron oxide nanoparticles (IONPs) into a core-shell porous electrospun scaffold and evaluated their impact on the physical, mechanical, and biological properties of the scaffold. We used poly(lactic-co-glycolic acid)/polycaprolactone/beta-tricalcium phosphate (PPT) scaffolds with and without γ-Fe2O3 encapsulation, namely PPT-Fe scaffolds and PPT scaffolds, respectively. The γ-Fe2O3 used in the PPT-Fe scaffolds was coated with polyglucose sorbitol carboxymethylether and was biocompatible. Structurally, PPT-Fe scaffolds showed uniform iron distribution encapsulated within the resorbable PPT scaffolds, and these scaffolds supported sustainable iron release. Furthermore, compared with PPT scaffolds, PPT-Fe scaffolds showed significantly better physical and mechanical properties, including wettability, superparamagnetism, hardness, tensile strength, and elasticity modulus. In vitro tests of rat adipose-derived mesenchymal stem cells (rADSCs) seeded onto the scaffolds showed increased expression of integrin ß1, alkaline phosphatase, and osteogenesis-related genes. In addition, enhanced in vivo bone regeneration was observed after implanting PPT-Fe scaffolds in rat calvarial bone defects. Thus, we can conclude that the incorporation of IONPs into porous scaffolds for long-term release can provide a new strategy for BTE scaffold optimization and is a promising approach that can offer enhanced osteogenic capacity in clinical applications.

Effect of nanoscale bioactive glass with radial spherical particles on osteogenic differentiation of rat bone marrow mesenchymal stem cells.

To validate the feasibility of two types of bioactive glass that contains spherical and radical spherical nano-sized particles in promoting bone repair, we hypothesize that radical spherical nano-sized particles have higher bone repair effectiveness than spherical one due to the physicochemical properties. We rigorously compared the physicochemical properties and bioactivities of these two types of bioactive glass. Specifically, we measured the size, surface morphology, concentration of ionic-dissolution products, bioactivity, and biological effects of two groups of bioactive glass on rat bone marrow mesenchymal stem cells (rBMSCs) and evaluate their effect on proliferation and osteogenic differentiation of rBMSCs in vitro. We observed that spherical nano-bioactive glass (SNBG) was spherical with smooth boundary, while the radial spherical nano-bioactive glass (RSNBG) had radial pore on the surface of particle boundary. When the two materials were immersed in simulated body fluid for 24 h, RSNBG produced more and denser hydroxyapatite carbonate than SNBG. The concentration of Ca and Si ions in RSNBG 24 h extract is higher than that of SNBG, while the concentration of P ions is lower. Proliferation, alkaline phosphatase (ALP) activity, intracellular Ca ion concentrations defined as the number of mineralized nodules produced, and the expression of osteogenic genes were significantly higher in rBMSCs co-cultured with 50 µg/mL RSNBG than SNBG. Overall, these results validated our hypothesis that RSNBG can provide better benefit than SNBG for inducing proliferation and osteogenic differentiation in rBMSCs, in turn suggested the feasibility of this RSNBG in further studies and utilization toward the ends of improved bone repair effectiveness.

Thermally induced self-agglomeration 3D scaffolds with BMP-2-loaded core-shell fibers for enhanced osteogenic differentiation of rat adipose-derived stem cells.

INTRODUCTION: Scaffold structure plays a vital role in cell behaviors. Compared with two-dimensional structure, 3D scaffolds can mimic natural extracellular matrix (ECM) and promote cell-cell and cell-matrix interactions. The combination of osteoconductive scaffolds and osteoinductive growth factors is considered to have synergistic effects on bone regeneration. MATERIALS AND METHODS: In this study, core-shell poly(lactide-co-glycolide) (PLGA)/polycaprolactone (PCL)-BMP-2 (PP-B) fibrous scaffolds were prepared through coaxial electrospinning. Next, we fabricated 3D scaffolds based on PP-B fibers with thermally induced self-agglomeration (TISA) method and compared with conventional PLGA/PCL scaffolds in terms of scaffold morphology and BMP-2 release behaviors. Then, rat adipose-derived stem cells (rADSCs) were seeded on the scaffolds, and the effects on cell proliferation, cell morphology, and osteogenic differentiation of rADSCs were detected. RESULTS: The results demonstrated that 3D scaffold incorporated with BMP-2 significantly increased proliferation and osteogenic differentiation of rADSCs, followed by PP-B group. CONCLUSION: Our findings indicate that scaffolds with 3D structure and osteoinductive growth factors have great potential in bone tissue engineering.

Enhanced bone regeneration and visual monitoring via superparamagnetic iron oxide nanoparticle scaffold in rats.

A main challenge for use of scaffolds in bone engineering involves non-invasive monitoring in vivo and enhanced bone regeneration. The tissue repair effect of superparamagnetic iron oxide nanoparticles (SPIONs) was demonstrated previously by our group. However, testing in vivo is needed to confirm in vitro results. Here, SPIONs loaded gelatin sponge (GS) was used as a scaffold (SPIONs-GS) and implanted in the incisor sockets of Sprague-Dawley rats. Incisor sockets filled with nothing and filled with GS served as controls. Rats were sacrificed at 2 and 4 weeks. A significant decrease in the signal intensity of T2-weighted magnetic resonance imaging (MRI) in the SPIONs-GS group was noted. Changes in image intensity of scaffolds (indicating scaffold degradation and interaction with host tissues) could be visually monitored over time. Microcomputed tomography showed that the SPIONs-GS group had more newly formed bone (64.44 ± 10.92 vs. 28.1 ± 4.49, p < .0001) and a better preserved alveolar ridge than blank control group at 4 weeks (0.962 ± 0.01 vs. 0.92 ± 0.01, p < .0001). Histology confirmed imaging results, showing good consistency in new bone formation and scaffold degradation. The number of SPIONs decreased rapidly with time due to quick degradation of GS, whereas the number of endocytic SPIONs in cells increased with time. These residual SPIONs, together with newly formed bone, could be detected by MRI at 4 weeks. Therefore, it was clear that SPIONs induced active osteogenesis. In conclusion, good visibility on MRI and enhanced regeneration of bone can be obtained by implanting SPIONs-GS in vivo without using an external magnetic field.

[Risk factors for ventilator-associated pneumonia in neonates and the changes of isolated pathogens].

OBJECTIVE: To study the risk factors for neonatal ventilator-associated pneumonia (VAP) and the changes of isolated pathogens in the last eight years. METHODS: The clinical data of 230 neonates who were admitted into the neonatal intensive care unit (NICU) and received mechanical ventilation for equal to or longer than 48 hrs in 2008 were retrospectively reviewed. The isolated pathogens were compared with those of eight years ago. RESULTS: The incidence of VAP (25.2%) in the year 2008 was lower than that of eight years ago (36.1%; P<0.05). The development of VAP was negatively correlated with the gestational age and the birth weight, but positively correlated with the duration of mechanical ventilation, intubation times, duration of hospitalization, presence of gastrointestinal bleeding and need for blood products transfusion. The main isolated pathogens were opportunistic antibiotics resistant bacteria, and the majority was gram negative bacilli (77%). The most frequently detected gram negative bacilli were Klebsiella (20%), Stenotrophomonas maltophilia (18%) and Acinetobacter (13%). Streptococcus mitis was the most frequently detected gram positive bacilli (14%). The distribution pattern of pathogens isolated in the same NICU eight years ago was somewhat different: Klebsiella (23%), Pseudomonas aeruginosa (17%), Acinetobacter (16%), Streptococcus mitis (11%), Fungi (1%) and Candida albicans (1%). CONCLUSIONS: The incidence of VAP is correlated with gestational age, birth weight, duration of mechanical ventilation and hospitalization, intubation times, presence of gastrointestinal bleeding and need for blood products transfusion. The main isolated pathogens are usually antibiotic resistant opportunistic bacteria. The detection rate of Stenotrophomonas maltophilia increased and that of Pseudomonas aeruginosa decreased when compared with eight years ago.

Nosocomial infection in an eye hospital: incidence and occurrence patterns.

PURPOSE: To describe the incidence and occurrence patterns of nosocomial infections in a large eye hospital over a 6-year period. METHODS: Medical records of 94,013 consecutive inpatients admitted to Zhongshan Ophthalmic Centre, Guangzhou, China, from 1996 to 2002, were reviewed. Demographic data and infection diagnoses were collected. Nosocomial infection was defined as an infection that was absent during preadmission assessments but detected at least 48 h after admission to the hospital, or occurred after surgical procedures performed within the hospital. RESULTS: The cumulative incidence of nosocomial infections over a 6-year period was 0.28%. The most common infections were acute conjunctivitis (45.5%) and upper respiratory tract infection (36.4%), followed by suppurative endophthalmitis (8.3%). Patients with acute conjunctivitis were predominantly adults aged from 15 to 59 years (60%), while patients with upper respiratory tract infection were predominantly children of 14 years or younger (74.0%), and those with endophthalmitis predominantly older persons 60 years or older (68.2%). Conditional pathogenic bacteria, mainly gram-positive, were responsible for most suppurative endophthalmitis cases. CONCLUSIONS: Although nosocomial infection incidence is relatively low in this eye hospital, our data suggest that different subgroups of patients are prone to certain types of infection. Specific preventive strategies targeting different subgroups of inpatients may further reduce the infection incidence.

Gene transcription profile in mice vaccinated with ultraviolet-attenuated cercariae of Schistosoma japonicum reveals molecules contributing to elevated IFN-gamma levels.

Vaccination with ultraviolet-attenuated cercariae of Schistosoma japonicum induced protective immunity against challenge infection in experimental animal models. Our preliminary study on the transcription levels of IFN-gamma and IL-4 in splenic CD4+ T cells revealed that attenuated cercariae elicited predominantly a Th1 response in mice at the early stage, whereas normal cercariae stimulated primarily Th2-dependent responses. Further analysis on the gene profile of the skin-draining lymph nodes demonstrated that the levels of IFN-gamma were significantly higher in vaccinated mice than those in infected mice at day 4, 7 and 14 post-vaccination or post-infection. However, for IL-12 and IL-4, the potent inducers of Th1 and Th2 responses, respectively, as well as IL-10, there were no differences over the course of the experiment between the infected and vaccinated mice. To explore the underlying factors that may potentially contribute to elevated IFN-gamma in vaccinated mice, the mRNA profiles of the skin-draining lymph nodes at day 4 post-exposure were compared using oligonucleotide microarrays. Within the 847 probe sets with increased signal values, we focused on chemokines, cytokines and relevant receptors, which were validated by semi-quantitative RT-PCR. A comprehensive understanding of the immune mechanisms of attenuated cercariae-induced protection may contribute to developing efficient vaccination strategies against S. japonicum, especially during the early stage of infection.

[Clinical observation and nursing of direct cyclopexy].

PURPOSE: To investigate the proper nursing methods for patients with direct cyclopexy. METHODS: Thirty-four patients (34 eyes) undergone direct cycloepxy because of lower intraocular pressure (IOP) caused by traumatic cyclodialysis were given clinical observation and nursing. RESULTS: Thirty-two of the 34 eyes had normal IOP after 1 week to 6 months after operation. Among those, 5 cases were treated with the secondary surgery or argon laser phacocoagulation. Visual acuity was improved on 21 eyes and unimproved on 13 eyes. CONCLUSION: Direct cyclopexy is an effective treatment for patients with traumatic cyclodialysis. Ultrasound biomicroscopy (UBM) before surgery, careful observation of the IOP with correct directions, better psychological nursing and instructions for discharging are the important measures to successful surgery.

Removal of intralenticular magnetic foreign bodies with intraocular magnet.

PURPOSE: To investigate the possibility of conservation of the lens after removal of intralenticular magnetic foreign bodies with intraocular magnet. METHODS: Intralenticular magnetic foreign bodies of 15 patients were removed by using an intraocular magnet. The lens of each injury eye was conserved. Follow-up observation of these cases ranged from one to four years. RESULTS: The intralenticular magnetic foreign bodies of 15 patients were successfully removed. The lens of each injury eye was conserved and the transparence of the lens was properly maintained. Sizes of these foreign bodies were measured, ranging from 0.3 mm to 3 mm in diameter. The follow-up observation showed that the corrected visual acuity of 14 cases was not changed after operation. CONCLUSIONS: The intraocular magnet is very helpful for removal of magnetic foreign bodies from the transparent lens. This magnet allows removing of the foreign body by the surgeon and no damage to the lens was induced during the operation. Thus, maintenance of visual acuity of most of the patients can be achieved.

[Sympathetic ophthalmia caused by ocular penetration with endophthalmitis].

PURPOSE: To summarize the clinical features, diagnosis and treatment of sympathetic ophthalmia caused by ocular penetration with endophthalmitis. METHODS: Retrospective analysis was done on clinical data of 3 cases of sympathetic ophthalmia with ocular penetration and endophthalmitis. RESULTS: 5,253 cases of ocular penetration and fracture were hospitalized from 1993 to 2002, while 87 cases of sympathetic ophthalmia were found at the same period of time, with the ratio of 1.65%. 3 cases had history of ocular penetration with endophthalmitis. Fluorescein angiography indicated that these 3 cases had developed sympathetic ophthalmia. Microscopic examination showed that 1 case had typical histological changes of sympathetic ophthalmia. CONCLUSION: Sympathetic ophthalmia caused by ocular penetration with endophthalmitis is infrequent, but this situation should not be neglect.