Informal caregiving among people supporting a person with type 2 diabetes in rural communities of Northern Vietnam: A cross-sectional study of caregiver burdens.

OBJECTIVE: The prevalence of type 2 diabetes mellitus (T2DM) in Vietnam has doubled from 3% to 6% over the last decades, with potential consequences for persons with diabetes and their caregivers. This study aimed to assess caregiver burdens and factors associated with caregiver burden. METHOD: A cross-sectional study was conducted in 2019, using data from 1,241 informal caregivers (ICGs). Caregiver burden was scored from 0-32 using 8 questions from the Zarit Burden Interview (ZBI). Quantile regression analysis was used to identify factors associated with caregiver burden. RESULTS: The median score of the ZBI was 7.0 (Q1-Q3: 2.0-10.0), indicating that the burden among caregiver of persons with T2DM is not high. Quantile regression showed that the higher the monthly income, the lower the burden among caregivers (50% quantile and 75% quantile of burden: -0.004). Lower educational level (25%Q: 4.0, 50%Q; 3.0, 75%Q: 2.16), being a farmer (25%Q: 2.0) and providing care to other people besides the person with T2DM (25%Q: 2.0, 50%Q; 2.54, 75%Q: 1.66) were associated with higher burden on caregivers. CONCLUSION: The study found that caregivers facing additional life stressors, such as low income or other caregiving responsibilities, reported higher levels of burden. These findings could inform the development of interventions targeted at supporting informal caregivers in rural areas in low- and middle-income countries.

Analysis of the influencing factors of the scientific fitness literacy of nurses in the context of exercise and medicine integration.

OBJECTIVE: The present study aims to explore the influencing factors of the scientific fitness literacy of nurses and provide a strategic basis for literacy improvement. METHODS: A questionnaire on the influencing factors of scientific fitness literacy of nurses was designed by the group conducting the present study; the questionnaire was based on the socioecology model and the questionnaire preparation method. The general data questionnaire and the questionnaire on the influencing factors of scientific fitness literacy of nurses were adopted to investigate nurses in tertiary hospitals in order to analyze and discuss the influencing factors of their scientific fitness literacy. RESULTS: (1) The questionnaire on the influencing factors of the scientific fitness literacy of nurses comprised five dimensions and 36 items. The overall item-content validity index was 0.833-1.000, the scale-content validity index was 0.974, and the overall Cronbach's α coefficient was 0.955; (2) the results of the pairwise Pearson correlation analysis showed that all five dimensions were positively correlated with the scientific fitness literacy of nurses; and (3) the results of the multiple linear regression analysis revealed that five dimensions, as well as the existence of exercise habits in daily life, had a significant impact on the scientific fitness literacy of nurses (P < 0.001). CONCLUSION: The factors influencing the scientific fitness literacy of nurses involved all levels of the socioecological system. The methods of improving the awareness of the scientific fitness of nurses and providing opportunities for scientific fitness activities via the hospital played a critical role in literacy improvement. However, the lack of professional guidance and an atmosphere promoting scientific fitness might hinder literacy improvement.

Intracranial hemorrhage risk in patients with cerebral microbleeds after mechanical thrombectomy for acute ischemic stroke: a systematic review and meta-analysis.

Background and purpose intracranial hemorrhage risk in patients with cerebral microbleeds (CMBs) after mechanical thrombectomy for acute ischemic stroke (AIS) was investigated. We searched PubMed and Embase from inception to 29 August 2023 for relevant studies, calculated pooled odds ratio (ORs) of intracerebral hemorrhage (ICH) subtypes in AIS patients with CMB presence, 1-4 or ≥ 5 CMBs versus CMB absence, and with different CMB locations after mechanical thrombectomy. ICH subtypes included any ICH, symptomatic and asymptomatic ICH, hemorrhage outside infarct (including subarachnoid hemorrhage), hemorrhagic infarction, and parenchymal hemorrhage after mechanical thrombectomy. Five eligible studies enrolling 2051 patients were included. No significant association was shown between CMB locations (lobar, deep, infratentorial or mixed) and ICH risk. CMB presence or 1-4 CMBs did not significantly increase the risk of any ICH, symptomatic or asymptomatic ICH, ICH outside infarct, subarachnoid hemorrhage, hemorrhagic infarction, or parenchymal hemorrhage. CMBs ≥ 5 increased the risk of any ICH (OR 2.58, 95% CI 1.16-5.72), parenchymal hemorrhage (OR 3.38, 95% CI 1.43-7.97) and parenchymal hemorrhage-2 (OR 5.33, 2.05-13.86), without increasing hemorrhagic infarction or parenchymal haemorrhage-1 risk. After adjusted for possible confounding factors, increases in CMB burden were associated with hemorrhagic complications but not with symptomatic ICH. In AIS patients who received mechanical thrombectomy, no association was shown between CMB location and ICH risk. ICH risk was not significantly increased by CMB presence or 1-4 CMBs. ICH risk in patients with ≥ 5 CMBs requires further study.

Global Epidemiology of Gallstones in the 21st Century: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Gallstones are common and associated with substantial health and economic burden. We aimed to comprehensively evaluate the prevalence and incidence of gallstones in the 21st century. METHODS: We systematically searched PubMed and Embase to identify studies reporting the prevalence and/or incidence of gallstones between January 1, 2000, and November 18, 2023. Pooled prevalence and incidence were calculated using DerSimonian and Laird's random-effects model. We performed subgroup analyses and meta-regression based on age, sex, geographic location, population setting, and modality of detection to examine sources of heterogeneity. RESULTS: Based on 115 studies with 32,610,568 participants, the pooled prevalence of gallstones was 6.1% (95% CI, 5.6-6.5). Prevalence was higher in females vs males (7.6% vs 5.4%), in South America vs Asia (11.2% vs 5.1%), in upper-middle-income countries vs high-income countries (8.9% vs 4.0%), and with advancing age. On sensitivity analysis of population-based studies, the prevalence of gallstones was 5.5% (95% CI, 4.1-7.4; n = 44 studies), and when limiting subgroup analysis to imaging-based detection modalities, the prevalence was 6.7% (95% CI, 6.1-7.3; n = 101 studies). Prevalence has been stable over the past 20 years. Based on 12 studies, the incidence of gallstones was 0.47 per 100 person-years (95% CI, 0.37-0.51), without differences between males and females, and with increasing incidence in more recent studies. CONCLUSIONS: Globally, 6% of the population have gallstones, with higher rates in females and in South America. The incidence of gallstones may be increasing. Our findings call for prioritizing research on the prevention of gallstones.

Genotype analysis of rotaviruses isolated from children during a phase III clinical trial with the hexavalent rotavirus vaccine in China.

The oral hexavalent live human-bovine reassortant rotavirus vaccine (RV6) developed by Wuhan Institute of Biological Products Co., Ltd (WIBP) has finished a randomized, placebo-controlled phase III clinical trial in four provinces of China in 2021. The trail demonstrated that RV6 has a high vaccine efficacy against the prevalent strains and is safe for use in infants. During the phase III clinical trial (2019-2021), 200 rotavirus-positive fecal samples from children with RV gastroenteritis (RVGE) were further studied. Using reverse transcription-polymerase chain reaction and high-throughput sequencing, VP7 and VP4 sequences were obtained and their genetic characteristics, as well as the differences in antigenic epitopes of VP7, were analyzed in detail. Seven rotavirus genotypes were identified. The predominant rotavirus genotype was G9P [8] (77.0%), followed by prevalent strains G8P [8] (8.0%), G3P [8] (3.5%), G3P [9] (1.5%), G1P [8] (1.0%), G2P [4] (1.0%), and G4P [6] (1.0%). The amino acid sequence identities of G1, G2, G3, G4, G8, and G9 genotypes of isolates compared to the vaccine strains were 98.8%, 98.2%-99.7%, 88.4%-99.4%, 98.2%, 94.2%-100%, and 93.9%-100%, respectively. Notably, the vaccine strains exhibited high similarity in amino acid sequence, with only minor differences in antigenic epitopes compared to the Chinese endemic strains. This supports the potential application of the vaccine in preventing diseases caused by rotaviruses.

Endovascular thrombectomy with or without intravenous alteplase in acute stroke: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND PURPOSE: This study investigated clinical outcomes after direct endovascular thrombectomy (EVT) compared to bridging therapy (EVT with prior intravenous alteplase) in acute stroke within 4.5 h after onset. METHODS: PubMed and Embase were searched for eligible randomized controlled trials. The primary outcome was the rates of neurological functional independence defined as modified Rankin scale score 0-2 at 90 days, whose non-inferiority margin was set at - 15%, - 10%, - 6.5%, - 5%, and - 1.3% for its risk difference (RD). RESULTS: We included six studies enrolling 2334 participants. The crude cumulative rates of functional independence were 49.0% with direct EVT vs 50.9% with bridging therapy, without significant difference (Odd ratio [OR] = 0.93, 95% confidence interval [CI] 0.79-1.09) between two groups, where the pooled RD was - 2% (95% CI - 6 to 2%) whose lower 95% CI bound fell within non-inferiority margins of - 15%, - 10%, -6.5%, but not - 5% and - 1.3%. Between the two groups, no significant difference was found in excellent function rate (30.2% vs 30.6%, OR = 0.99, 95% CI 0.82-1.18) with RD of 0% (95% CI - 3 to 4%), mortality rate (16.0% vs 15.0%, OR = 1.08, 95% CI 0.86-1.35) with RD of 1% (95% CI - 2 to 4%), and symptomatic intracranial hemorrhage rate (4.3% vs 5.0%, OR = 0.86, 95% CI 0.58-1.27) with RD of 0% (95% CI - 2 to 1%). CONCLUSIONS: No statistical difference was found in functional and safety outcomes between direct EVT and bridging therapy groups in acute stroke within 4.5 h after symptom onset. EVT alone was non-inferior to bridging therapy for several, but not the more stringent, non-inferiority margins.

Clinical usefulness of linked color imaging in identifying Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Accurate diagnosis of Helicobacter pylori (H. pylori) infection status is a crucial premise for eradication therapy, as well as evaluation of risk for gastric cancer. Recent progress on imaging enhancement endoscopy (IEE) made it possible to not only detect precancerous lesions and early gastrointestinal cancers but also to predict H. pylori infection in real time. As a novel IEE modality, linked color imaging (LCI) has exhibited its value on diagnosis of lesions of gastric mucosa through emphasizing minor differences of color tone. AIM: To compare the efficacy of LCI for H. pylori active infection vs conventional white light imaging (WLI). METHODS: PubMed, Embase, Embase and Cochrane Library were searched up to the end of April 11, 2022. The random-effects model was adopted to calculate the diagnostic efficacy of LCI and WLI. The calculation of sensitivity, specificity, and likelihood ratios were performed; symmetric receiver operator characteristic (SROC) curves and the areas under the SROC curves were computed. Quality of the included studies was chosen to assess using the quality assessment of diagnostic accuracy studies-2 tool. RESULTS: Seven original studies were included in this study. The pooled sensitivity, specificity, positive likelihood rate, and negative likelihood rate of LCI for the diagnosis of H. pylori infection of gastric mucosa were 0.85 [95% confidence interval (CI): 0.76-0.92], 0.82 (95%CI: 0.78-0.85), 4.71 (95%CI: 3.7-5.9), and 0.18 (95%CI: 0.10-0.31) respectively, with diagnostic odds ratio = 26 (95%CI: 13-52), SROC = 0.87 (95%CI: 0.84-0.90), which showed superiority of diagnostic efficacy compared to WLI. CONCLUSION: Our results showed LCI can improve efficacy of diagnosis on H. pylori infection, which represents a useful endoscopic evaluation modality for clinical practice.

Efficacy, safety and immunogenicity of hexavalent rotavirus vaccine in Chinese infants.

A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine (HRV) against rotavirus gastroenteritis (RVGE). A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV (n â€‹= â€‹3200) or placebo (n â€‹= â€‹3200) group. All the subjects received three oral doses of vaccine four weeks apart. The vaccine efficacy (VE) against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season. VE against severe RVGE, VE against RVGE hospitalization caused by serotypes contained in HRV, and VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated. All adverse events (AEs) were collected for 30 days after each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21% (95%CI: 53.31-79.69). VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36% (95%CI: 78.45-96.53) and 89.21% (95%CI: 64.51-96.72) respectively. VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88% (95%CI: 49.11-72.92), 85.51% (95%CI: 72.74-92.30) and 83.68% (95%CI: 61.34-93.11). Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable. There was no significant difference in incidences of SAEs in HRV and placebo groups. This study shows that this hexavalent reassortant rotavirus vaccine is an effective, well-tolerated, and safe vaccine for Chinese infants.

Single-centre empirical analysis of double-balloon enteroscopy in the diagnosis and treatment of small bowel diseases: A retrospective study of 466 cases.

BACKGROUND AND OBJECTIVE: The diagnosis and treatment of small bowel diseases (SBDs) has always been a challenge. The purpose of this study was to evaluate the value of double-balloon enteroscopy (DBE) in the diagnosis and treatment of small bowel diseases. METHOD: The clinical data of 466 patients who underwent double-balloon enteroscopy (DBE) in the Endoscope Center of Gastroenterology Department of the First People's Hospital of Yunnan Province from Jan. 2015 to Dec. 2020 were analysed retrospectively. The factors included age, sex, indications, endoscopic treatment results, pathological results, discharge diagnosis and so on. RESULTS: A total of 370 patients underwent 466 double-balloon enteroscopies, among whom 274 underwent one examination and 96 received two-way examinations (oral and transanal approaches). Abnormalities were detected in 299 cases, with a detection rate of 80.81% (299/370). The common indications were occult gastrointestinal bleeding (OGIB) (30.8%, 114/370) and abdominal pain (28.3%, 105/370). The diagnosis rates were 64.9% and 77.1%, respectively. The common positive findings included nonspecific inflammation/erosion (60 cases), ulcers (34 cases), diverticulum (32 cases), polyps (26 cases) and Crohn's disease (CD) (24 cases). The common tumours were lymphoma(12 cases), adenocarcinoma(11 cases) and stromal tumour(8 cases). Lymphoma was mostly located in the ileum, while stromal tumours and adenocarcinoma were mostly located in the duodenum and jejunum. The main endoscopic intervention measures were haemostasis and polypectomy, including haemostatic clip, argon plasma coagulation (APC), endoscopic mucosal resection (EMR), endoscopic trap resection, endoscopic foreign body extraction and other operations, without serious complications. CONCLUSION: DBE has a high success rate in the diagnosis and treatment of some SBDs, and it is a safe and effective management method.

Cell membrane coating integrity affects the internalization mechanism of biomimetic nanoparticles.

Cell membrane coated nanoparticles (NPs) have recently been recognized as attractive nanomedical tools because of their unique properties such as immune escape, long blood circulation time, specific molecular recognition and cell targeting. However, the integrity of the cell membrane coating on NPs, a key metrics related to the quality of these biomimetic-systems and their resulting biomedical function, has remained largely unexplored. Here, we report a fluorescence quenching assay to probe the integrity of cell membrane coating. In contradiction to the common assumption of perfect coating, we uncover that up to 90% of the biomimetic NPs are only partially coated. Using in vitro homologous targeting studies, we demonstrate that partially coated NPs could still be internalized by the target cells. By combining molecular simulations with experimental analysis, we further identify an endocytic entry mechanism for these NPs. We unravel that NPs with a high coating degree (≥50%) enter the cells individually, whereas the NPs with a low coating degree (<50%) need to aggregate together before internalization. This quantitative method and the fundamental understanding of how cell membrane coated NPs enter the cells will enhance the rational designing of biomimetic nanosystems and pave the way for more effective cancer nanomedicine.

Interfacial behavior of phospholipid monolayers revealed by mesoscopic simulation.

A mesoscopic model with molecular resolution is presented for dipalmitoyl phosphatidylcholine (DPPC) and palmitoyl oleoyl phosphatidylcholine (POPC) monolayer simulations at the air-water interface using many-body dissipative particle dynamics (MDPD). The parameterization scheme is rigorously based on reproducing the physical properties of water and alkane and the interfacial property of the phospholipid monolayer by comparison with experimental results. Using much less computing cost, these MDPD simulations yield a similar surface pressure-area isotherm as well as similar pressure-related morphologies as all-atom simulations and experiments. Moreover, the compressibility modulus, order parameter of lipid tails, and thickness of the phospholipid monolayer are quantitatively in line with the all-atom simulations and experiments. This model also captures the sensitive changes in the pressure-area isotherms of mixed DPPC/POPC monolayers with altered mixing ratios, indicating that the model is promising for applications with complex natural phospholipid monolayers. These results demonstrate a significant improvement of quantitative phospholipid monolayer simulations over previous coarse-grained models.

Polypharmacy among people living with type 2 diabetes mellitus in rural communes in Vietnam.

OBJECTIVES: People with diabetes are at high risk of polypharmacy owing to complex treatment of diabetes and comorbidities. Polypharmacy is associated with increased risk of adverse reactions and decreased compliance. Therefore, the objectives of this study were to assess polypharmacy in people with type 2 diabetes (T2D) and associated diabetes-related factors in rural areas in Vietnam. METHOD: People with T2D (n = 806) who had received treatment for diabetes at a district hospital were invited to participate in a questionnaire-based cross-sectional survey. Polypharmacy was defined as ≥5 types of medicine and assessed as a) prescription medicine and non-prescription/over the counter (OTC) medicine and b) prescription medicine and non-prescription/OTC, herbal and traditional medicine, and dietary supplement. Multiple logistic regression was used to investigate the association between polypharmacy and diabetes specific factors: duration, comorbidities and diabetes-related distress. RESULTS: Of the people with T2D, 7.8% had a medicine use corresponding to polypharmacy (prescription medicine and non-prescription/OTC), and 40.8% when herbal and traditional medicine, and dietary supplement were included. Mean number of medicine intake (all types of medicines and supplements) were 3.8±1.5. The odd ratios (ORs) of polypharmacy (medicine and supplements) increased with diabetes duration (<1-5 years OR = 1.66; 95%CI: 1.09-2.53 and >5 years OR = 1.74; 95%CI: 1.14-2.64 as compared to ≤1-year duration of diabetes), number of comorbidities (1-2 comorbidities: OR = 2.0; 95%CI: 1.18-3.42; ≥3 comorbidities: OR = 2.63;95%CI: 1.50-4.61 as compared to no comorbidities), and suffering from diabetes-related distress (OR = 1.49; 95%CI: 1.11-2.01) as compared to those without distress. CONCLUSIONS: In rural northern Vietnam, persons with longer duration of T2D, higher number of comorbidities and diabetes-related stress have higher odds of having a medicine use corresponding to polypharmacy. A high proportion of people with T2D supplement their prescription, non-prescription/OTC medicine with herbal and traditional medicine and dietary supplements.

Sequential macrophage transition facilitates endogenous bone regeneration induced by Zn-doped porous microcrystalline bioactive glass.

Macrophages play an important role in the immune microenvironment during bone healing, and sequential macrophage phenotypic transition could achieve superior osteogenic outcomes. Microcrystalline bioactive glasses (MCBGs) with osteoimmunomodulatory effects show potential in bone tissue regeneration. Zinc (Zn) has been approved to coordinate innate and adaptive immunity. Therefore, in this study, different amounts of ZnO were incorporated into microcrystalline bioactive glass to improve its immunomodulatory ability. The effect of Zn-MCBG ionic extracts on macrophage transition was studied, and the 5Zn-MCBG extracts could orchestrate sequential M1-to-M2 macrophage transition and promote the expression of proinflammatory and anti-inflammatory genes and cytokine expression to induce human bone marrow stromal cells (hBMSCs) osteogenic differentiation in vitro. Macroporous Zn-MCBG scaffolds containing mesopores were fabricated and showed good cell adhesion and feasible apatite formation when immersed in SBF in vitro. Furthermore, a rat calvarial defect model was used to confirm that the Zn-MCBG scaffold could modulate macrophage phenotypic transition and create a desirable osteogenic microenvironment to promote osteogenesis in vivo.

Safety and immunogenicity of a novel oral hexavalent rotavirus vaccine：a phase I clinical trial.

Background Rotavirus infections, prevalent in human populations, are caused mostly by group A viruses. Immunization against rotaviruses in infancy is currently the most effective and economical strategy to prevent rotavirus infection. This study evaluated the safety of a novel hexavalent rotavirus vaccine and analyzed its dose and immunogenicity.Methods This randomized, double-blinded, placebo-controlled phase I clinical trial enrolled healthy adults, toddlers, and infants in Zhengding County, Hebei Province, northern China. 40 adults and 40 children were assigned in a 2:1:1 ratio to receive one vaccine dose, placebo 1, and placebo 2, respectively. 120 6-12 week old infants were assigned equivalently into 3 groups. The infants in each group were assigned in a 2:1:1 ratio to receive three doses of vaccine, placebo 1, and placebo 2, at a 28-day interval. Adverse events (AEs) until 28 days after each dose and serious adverse events (SAEs) until 6 months after the third dose were reported. Virus shedding until 14 days after each dose in infants was tested. Geometric mean concentrations (GMCs) and seroconversion rates were measured for anti-rotavirus IgA by using an enzyme-linked immunosorbent assay (ELISA).Results The solicited and unsolicited AE frequencies and laboratory indexes were similar among the treatment groups. No vaccine-related SAEs were reported. The average percentage of rotavirus vaccine shedding in the infant vaccine groups was 5.00%. The post-3rd dose anti-rotavirus IgA antibody geometric mean concentrations (GMC) and seroconversion rate were higher in the vaccine groups than in the placebo groups.Conclusions The novel oral hexavalent rotavirus vaccine was generally well-tolerated in all adults, toddlers and infants, and the vaccine was immunogenic in infants.

Forkhead Box Q1 Is Critical to Angiogenesis and Macrophage Recruitment of Colorectal Cancer.

Angiogenesis and the tumor microenvironment (TME) play important roles in tumorigenesis. Forkhead box Q1 (FOXQ1) is a well-established oncogene in multiple tumors, including colorectal cancer (CRC); however, whether FOXQ1 contributes to angiogenesis and TME modification in CRC remains largely uncharacterized. Here, we demonstrate an essential role of FOXQ1-induced angiogenesis and macrophage recruitment in CRC that is related to its ability to promote the migration of endothelial cells and macrophages through activation of the EGF/PDGF pathway and the Twist1/CCL2 axis. We also provide evidence showing that the clinical significance between FOXQ1, Twist1, CCL2, and macrophage infiltration is associated with reduced 8-year survival in CRC patients. Our findings suggest FOXQ1 plays critical roles in the malignancy and progression of CRC, Therefore, FOXQ1 may serve as a therapeutic target for inhibiting angiogenesis and reducing macrophage recruitment in CRC.

Preparation and characterisation of a gellan gum-based hydrogel enabling osteogenesis and inhibiting Enterococcus faecalis.

Infections are the leading cause of failure of osteogenic material implantation. Antibiotic treatment, treatment with bone cement, or collagen sponge placement can result in drug resistance and difficulties in operation. To address this, gellan gum (GG) was selected in this study and prepared as an injectable hydrogel containing chlorhexidine (CHX) and nanohydroxyapatite (nHA) that overcomes these intractable problems. Scanning electron microscopy and micro-computed tomography revealed a three-dimensional polymeric network of the hydrogel. The hydrogel had excellent biocompatibility, as detected by cell counting kit-8 and Live/Dead assay. Bone marrow mesenchymal stem cells could be encapsulated into the network, showing that the structure was suitable for cell growth. Additionally, loading the hydrogel with nHA improved its mechanical, biodegradable, and osteogenic properties. Quantitative alkaline phosphatase and Alizarin Red S staining validated its osteogenic ability. Furthermore, antibacterial activity assessment showed that the hydrogel loaded with 50 µg/mL CHX inhibited Enterococcus faecalis in a concentration-dependent manner. Thus, we report an injectable GG-based hydrogel with superior antibacterial effect against E. faecalis and osteogenesis, which holds promise for treating infectious bone defects caused by refractory periradicular periodontitis.

Borate bioactive glass prevents zoledronate-induced osteonecrosis of the jaw by restoring osteogenesis and angiogenesis.

OBJECTIVES: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of systemic nitrogen-containing bisphosphonate (N-BP) administration, which leads to osteonecrosis, pain, and infection. Despite much effort, effective remedies are yet to be established. This study aimed to investigate potential recovery effect of borate bioactive glass (BBG) in vitro and in vivo. METHODS: The effect of BBG on zoledronate-treated bone marrow mesenchymal cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) was explored by cell counting kit-8, EdU assay, flow cytometry, alkaline phosphatase staining, alizarin red staining, angiogenesis experiment, and real-time quantitative polymerase chain reaction. The preventive effect of BBG on zoledronate-induced osteonecrosis of the jaw in rat model was examined by micro-CT, HE staining, and immunohistochemistry. RESULTS: Exposure of BBG to BMSCs and HUVECs increased cell proliferation and restored their osteogenesis and angiogenesis potential in vitro. The BRONJ lesions were satisfactorily repaired and bone mineral density, bone volume/tissue volume, trabecula number, OCN-positive cells, and CD31-positive cells were increased in the BBG-treated groups compared with saline-treated groups. CONCLUSIONS: Exposure of BMSCs and HUVECs to BBG restores osteogenesis and angiogenesis inhibited by zoledronate. BBG successfully restores extraction socket healing of BRONJ in rat model.

miR-129-5p inhibits proliferation, migration, and invasion in rectal adenocarcinoma cells through targeting E2F7.

microRNAs (miRNAs), a kind of small noncoding RNAs, are considered able to regulate expression of genes and mediate RNA silencing. miR-129-5p was shown to be a cancer-related miRNA. However, the influence of miR-129-5p in rectal adenocarcinoma (READ) development remains to be determined. Based on the TCGA data, downregulation of miR-129-5p in READ samples was observed. Manual restoration of the miR-129-5p in SW1463 and SW480 cell lines significantly inhibited invasion, migration, and proliferation of READ cell lines, while the apoptosis ability was enhanced. Meanwhile, we found E2F7 acted as a potential target of miR-129-5p and was upregulated in READ samples. E2F7 upregulation reversed the repression of miR-129-5p on READ development. Finally, in vivo experiments showed that inhibition of tumor growth in nude mice was achieved through upregulating miR-129-5p. Overall, our findings suggest increasing of miR-129-5p leads to the suppression of READ progression through regulating the expression of E2F7, which may provide novel insights into the treatment of READ.

Nanoparticle translocation across the lung surfactant film regulated by grafting polymers.

Nanoparticle-based pulmonary drug delivery has gained significant attention due to its ease of administration, increased bioavailability, and reduced side effects caused by a high systemic dosage. After being delivered into the deep lung, the inhaled nanoparticles first interact with the lung surfactant lining layer composed of phospholipids and surfactant proteins and then potentially cause the dysfunction of the lung surfactant. Conditioning the surface properties of nanoparticles with grafting polymers to avoid these side effects is of crucial importance to the efficiency and safety of pulmonary drug delivery. Herein, we perform coarse-grained molecular simulations to decipher the involved mechanism responsible for the translocation of the polymer-grafted Au nanoparticles across the lung surfactant film. The simulations illustrate that conditioning of the grafting polymers, including their length, terminal charge, and grafting density, can result in different translocation processes. Based on the energy analysis, we find that these discrepancies in translocation stem from the affinity of the nanoparticles with the lipid tails and heads and their contact with the proteins, which can be tuned by the surface polarity and surface charge of the nanoparticles. We further demonstrate that the interaction between the nanoparticles and the lung surfactant is related to the depletion of the lipids and proteins during translocation, which affects the surface tension of the surfactant film. The change in the surface tension in turn affects the nanoparticle translocation and the collapse of the surfactant film. These results can help understand the adverse effects of the nanoparticles on the lung surfactant film and provide guidance to the design of inhaled nanomedicines for improved permeability and targeting.