A carrier-free nanovaccine combined with cancer immunotherapy overcomes gemcitabine resistance.

Drug resistance is a significant challenge in cancer chemotherapy and is a primary factor contributing to poor recovery for cancer patients. Although drug-loaded nanoparticles have shown promise in overcoming chemotherapy resistance, they often carry a combination of drugs and require advanced design and manufacturing processes. Furthermore, they seldom approach chemotherapy-resistant tumors from an immunotherapy perspective. In this study, we developed a therapeutic nanovaccine composed solely of chemotherapy-induced resistant tumor antigens (CIRTAs) and the immune adjuvant Toll-like receptor (TLR) 7/8 agonist R848 (CIRTAs@R848). This nanovaccine does not require additional carriers and has a simple production process. It efficiently delivers antigens and immune stimulants to dendritic cells (DCs) simultaneously, promoting DCs maturation. CIRTAs@R848 demonstrated significant tumor suppression, particularly when used in combination with the immune checkpoint blockade (ICB) anti-PD-1 (αPD-1). The combined therapy increased the infiltration of T cells into the tumor while decreasing the proportion of regulatory T cells (Tregs) and modulating the tumor microenvironment, resulting in long-term immune memory. Overall, this study introduces an innovative strategy for treating chemotherapy-resistant tumors from a novel perspective, with potential applications in personalized immunotherapy and precision medicine.

Unplanned emergency department visits within 90 days of hip hemiarthroplasty for osteoporotic femoral neck fractures: Reasons, risks, and mortalities.

Objectives: Bipolar hemiarthroplasty is commonly performed to treat displaced femoral neck fractures in osteoporotic patients. This study aimed to assess the occurrence and outcomes of unplanned return visits to the emergency department (ED) within 90 days following bipolar hemiarthroplasty for displaced femoral neck fractures. Methods: The clinical data of 1322 consecutive patients who underwent bipolar hemiarthroplasty for osteoporotic femoral neck fractures at a tertiary medical center were analyzed. Data from the patients' electronic medical records, including demographic information, comorbidities, and operative details, were collected. The risk factors and mortality rates were analyzed. Results: Within 90 days after surgery, 19.9% of patients returned to the ED. Surgery-related reasons accounted for 20.2% of the patient's returns. Older age, a high Charlson comorbidity index score, chronic kidney disease, and a history of cancer were identified as significant risk factors for unplanned ED visits. Patients with uncemented implants had a significantly greater risk of returning to the ED due to periprosthetic fractures than did those with cemented implants (P = 0.04). Patients who returned to the ED within 90 days had an almost fivefold greater 1-year mortality rate (15.2% vs 3.1%, P < 0.001) and a greater overall mortality rate (26.2% vs 10.5%, P < 0.001). Conclusions: This study highlights the importance of identifying risk factors for unplanned ED visits after bipolar hemiarthroplasty, which may contribute to a better prognosis. Consideration should be given to the use of cemented implants for hemiarthroplasty, as uncemented implants are associated with a greater risk of periprosthetic fractures.

Comparison of minimally invasive transforaminal lumbar interbody fusion and midline lumbar interbody fusion in patients with spondylolisthesis.

BACKGROUND: This study aimed to compare surgical outcomes, clinical outcomes, and complications between minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) and midline lumbar interbody fusion (MIDLIF) in patients with spondylolisthesis. METHODS: This study retrospectively compared the patients who underwent MIS TLIF (n = 37) or MIDLIF (n = 50) for spinal spondylolisthesis. Data of surgical outcomes (postoperative one-year fusion rate and time to bony fusion), clinical outcomes (visual analog scale [VAS] for pain and Oswestry Disability Index [ODI] for spine function), and complications were collected and analyzed. RESULTS: There was more 2-level fusion in MIDLIF (46% vs. 24.3%, p = 0.038). The MIS TLIF and MIDLIF groups had similar one-year fusion rate and time to fusion. The MIDLIF group had significantly lower VAS at postoperative 3-months (2.2 vs. 3.1, p = 0.002) and postoperative 1-year (1.1 vs. 2.1, p = < 0.001). ODI was not significantly different. The operation time was shorter in MIDLIF (166.1 min vs. 196.2 min, p = 0.014). The facet joint violation is higher in MIS TLIF (21.6% vs. 2%, p = 0.009). The other complications were not significantly different including rate of implant removal, revision, and adjacent segment disease. CONCLUSION: In this study, postoperative VAS, operation time, and the rate of facet joint violation were significantly higher in the MIS TLIF group. Comparable outcomes were observed between MIDLIF and MIS TLIF in terms of fusion rate, time to fusion, and postoperative ODI score.

Associations between weight-adjusted-waist index and telomere length: Results from NHANES: An observational study.

Previous studies have demonstrated the connection between obesity and telomere length. A recently devised metric for determining obesity, the weight-adjusted-waist index (WWI), offers a distinct advantage in predicting fat and lean mass by depicting weight-independent abdominal adiposity. This article presents the results of the inaugural study on the relationship between WWI and telomere length in adult populations. The cross-sectional investigation analyzed data from 3479 participants from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2000. To inspect linear and nonlinear correlations, we adopted weighted multiple logistic regression analysis and smooth curve fit, respectively. In addition, threshold effects and subgroup analyses were accomplished. In the fully adapted model, a significant adverse association of WWI with telomere length was detected [ß = -0.02, 95% CI: (-0.03, -0.00), P value = 0.01]. The adverse correlation remained consistent across all subcategories. We also discovered an inverted U-shaped curve linking WWI and telomere length, with a conspicuous inflection point of 10.07 cm/√kg. For the first time, our research demonstrated strong links between WWI and telomere length. The inflection point suggests that controlling WWI within an optimum range might be essential for aging and health.

A Retrospective Comparison of Clinical Efficacy between Multimodal Analgesia and Patient-Controlled Epidural Analgesia in Patients Undergoing Total Knee Arthroplasty.

Background and Objectives: Adequate pain management during early rehabilitation is mandatory for improving the outcomes of patients undergoing total knee arthroplasty (TKA). Conventional pain management, mainly comprising opioids and epidural analgesia, may result in certain adverse effects such as dizziness, nausea, and motor blockade. We proposed a multimodal analgesic (MA) strategy involving the use of peripheral nerve block (NB), periarticular injection (PAI), and intravenous patient-controlled analgesia (IVPCA). This study compared the clinical efficacy and adverse effects of the proposed MA strategy and patient-controlled epidural analgesia (PCEA). Materials and Methods: We enrolled 118 patients who underwent TKA under spinal anesthesia. The patients followed either the MA protocol or received PCEA after surgery. The analgesic effect was examined using a numerical rating scale (NRS). The adverse effects experienced by the patients were recorded. Results: A lower proportion of patients in the MA group experienced motor blockade (6.45% vs. 22.98%) compared to those in the PCEA group on the first postoperative day. Furthermore, a lower proportion of patients in the MA group experienced numbness (18.52% vs. 43.33%) than those in the PCEA group on the first postoperative day. Conclusions: The MA strategy can be recommended for reducing the occurrence of motor blockade and numbness in patients following TKA. Therefore, the MA strategy ensures early rehabilitation while maintaining adequate pain relief.

Corrigendum: Sulforaphane promotes dendritic cell stimulatory capacity through modulation of regulatory molecules, JAK/STAT3- and microRNA-signaling.

[This corrects the article DOI: 10.3389/fimmu.2020.589818.].

Novel hollow α-Fe2O3 nanofibers with robust performance enabled multi-functional applications.

The synthetic strategies of achieving low-cost and high-performance nanofibers are of great significance in the field of catalysis and detection. In this work, a series of electrospun α-Fe2O3 nanofibers with hollow structure were prepared via combination technology of electrospinning, hydrothermal synthesis, and controlled calcination process. Especially, the influences of the crystal structure and morphology on the comprehensive properties of nanofibers have been explored in detail. The results indicated that α-Fe2O3 nanofibers could be obtained via the calcination at 600-800 °C. Rice-like α-Fe2O3 particles were observed to assemble a stable exoskeleton, supporting a robust tubular cavity. And this tubular structure turned gradually into groove-like structure as the calcination temperature increased, accompanied by tunable crystallization, specific surface area and magnetic property. Finally, combined with series of validation tests, including dye decolorization, electrochemical detection of trace cadmium ions and Fenton degradation of polyvinyl alcohol, the resultant α-Fe2O3 nanofibers have been demonstrated to show the potential application prospects.

Case report: Surgical treatment of McCune-Albright syndrome with hyperthyroidism and retrosternal goiter: A case report and literature review.

Introduction: McCune-Albright syndrome (MAS) is a low-incidence syndrome consisting of the clinical triad of fibrous structural dysplasia of bone, endocrine disease, and skin pigmentation. Thyroid dysfunction is the second most common endocrine dysregulation in MAS. However, there are no treatment guidelines for MAS complicated with hyperthyroidism. Notably, no case of MAS complicated with retrosternal goiter and hyperthyroidism has been reported to our knowledge. Case presentation: We report a 27-year-old man with MAS who developed the typical triad of bone fibrous dysplasia, skin pigmentation and hyperthyroidism, complaining of recent fast-growing neck mass and difficulty in breathing. Hyperthyrodism was under control by Thiamazole, and computed tomography showed an enlarged thyroid extending retrosternally. We performed a total thyroidectomy on the patient. At the 1-year follow-up, the patient's dyspnea, hyperthyroidism, and bone pain were all significantly alleviated. Review: We searched the literature for previous case reports concerning MAS patients complicated with thyroid dysregulation. A total of 17 articles and 22 patients were identified to form our database. Among them, 9 studies clearly mentioned surgical intervention in 11 patients, and prognoses were also reported. Surgery was the most common intervention chosen and indicated a satisfactory prognosis. Conclusion: We report a rare case of MAS patient complicated with retrosternal goiter and hyperthyroidism. Our review provides an overview of MAS cases requiring interventions on thyroid function, and total thyroidectomy should be a proper treatment for these patients.

The association between gallstone disease (GSD) and hip fracture: a nationwide population-based study.

Objectives: Despite the high prevalence of gallstone disease (GSD), the shared risk factors of GSD and osteoporosis, and the known association between hip fracture and hepatobiliary diseases, the association between hip fracture and GSD is not currently clear. Therefore, we performed a nationwide population-based study to investigate the association between GSD and hip fracture to determine the impact of cholecystectomy on the risk of fracture.Methods: In this study, we assessed all subjects in the longitudinal health insurance database (LHID) between 2000 and 2011, excluding those subjects aged >20 years old and those with a previous history of hip fracture (ICD-9-CM 820). Among those that were included, subjects with at least two or more outpatient visits or with one record of hospitalization under the coding of GSD (ICD-9-CM code: 574) were allocated to the GSD cohort. The remaining subjects were designated to the control cohort. All participants were followed till the onset of hip fracture, withdrawal from the NHI, or the end of 2013.Results: We found that the cumulative incidence of hip fracture was higher in the GSD cohort than in the control cohort (log-rank test: p-value < 0.01). After adjustment, the GSD patients had a 1.21-fold risk of hip fracture compared to control subjects (aHR = 1.21, 95% CI = 1.21-1.30). Comparison between those subjects without GSD and those without cholecystectomy revealed that the risk of hip fracture was higher among GSD patients that had not undergone cholecystectomy (aHR = 1.17, 95% CI = 1.06-1.29) or those that had undergone cholecystectomy (aHR = 1.22, 95% CI = 1.06-1.41).Conclusion: Based upon these results, we concluded that GSD was associated with an increased risk of hip fracture regardless of whether the patient had undergone cholecystectomy.

Sulforaphane Promotes Dendritic Cell Stimulatory Capacity Through Modulation of Regulatory Molecules, JAK/STAT3- and MicroRNA-Signaling.

Introduction: The broccoli isothiocyanate sulforaphane was shown to inhibit inflammation and tumor progression, also in pancreatic cancer, while its effect on tumor immunity is poorly understood. We investigated the immunoregulatory effect of sulforaphane on human dendritic cells alone and in presence of pancreatic tumor antigens, as well as underlying molecular mechanisms. Methods: Sulforaphane-treated human dendritic cells were matured in vitro with a cytokine cocktail, and the expression of regulatory molecules was examined by flow cytometry. The subsequent T-cell response was analyzed by T-cell proliferation assay and CD25 expression. To confirm the findings, dendritic cells pulsed with pancreatic cancer-derived tumor antigens were used. To identify the involved pathway- and microRNA-signaling in sulforaphane-treated dendritic cells, inhibitors of various signaling pathways, western blot analysis, microRNA array, and bioinformatic analysis were applied. Results: Sulforaphane modulated the expression of the costimulatory CD80, CD83 and the suppressive B7-H1 molecules on dendritic cells and thereby promoted activation of T cells. The effect was verified in presence of pancreatic tumor antigens. Phosphorylation of STAT3 in dendritic cells was diminished by sulforaphane, and the inhibition of JAK/STAT3 led to downregulation of B7-H1 expression. Among the identified top 100 significant microRNA candidates, the inhibition of miR-155-5p, important for the expression of costimulatory molecules, and the induction of miR-194-5p, targeting the B7-H1 gene, were induced by sulforaphane. Conclusion: Our findings demonstrate that sulforaphane promotes T-cell activation by dendritic cells through the modulation of regulatory molecules, JAK/STAT3- and microRNA-signaling in healthy conditions and in context of pancreatic cancer-derived antigens. They explore the immunoregulatory properties of sulforaphane and justify further research on nutritional strategies in the co-treatment of cancer.

The Incidence and Risk Factors of Hip Fracture after Liver Transplantation (LT): A Nationwide Population-Based Study.

BACKGROUND: Osteoporosis and fragility fracture are the major complications after liver transplantation (LT). The aim of the study was to determine the incidence and risk factors of hip fracture after LT. METHODS: We conducted a retrospective population-based cohort study, enrolling the patients receiving LT between January 1999 and December 2010. Control subjects were randomly matched to every recipient by age and sex by 1 : 10 ratios. RESULTS: During the follow-up period, 17 recipients (0.77%) and 70 (0.32%) control subjects suffered from hip fractures. The incident rates (per 10000 person-years) were 21.49 for recipients and 7.52 for controls (adjusted hazard ratio = 2.71; 95% confidence interval = 1.21-6.05). The cumulative incidence of hip fracture was significantly higher among the recipients (p < 0.0001). Among the recipients, the subjects aged >65 years at transplantation and with pretransplant steroid use are more susceptible to posttransplant hip fracture. Immunosuppressive agents did not significantly affect the risk of hip fracture among recipients. CONCLUSIONS: Liver transplantation is a risk factor for hip fractures. Aged >65 years at transplantation and pretransplant steroid use are risk factors for posttransplant hip fractures among the recipients.

Detection of perioperative cancer antigen 72-4 in gastric juice pre- and post-distal gastrectomy and its significances.

Gastric carcinoma is one of the most common malignancies nowadays, and caner antigen 72-4 (CA 72-4) in gastric juice has been rarely studied. To compare CA 72-4 in gastric juice pre- and post-distal gastrectomy (DG) and analyze its possible significances, we selected 64 patients diagnosed with gastric carcinoma who underwent DG and collected their perioperative gastric juice samples whose contents of CA 72-4 were detected. We found that CA 72-4 in gastric juice pre-gastrectomy is significantly higher among patients in advanced stages and correlated with tumor TNM classification (P < 0.01), within which tumor size, levels of gastric wall invaded, and number of metastatic lymph nodes are significant influencing factors (P < 0.05); CA 72-4 in gastric juice post-gastrectomy is significantly higher than that pre-surgery (P < 0.01), and it is significantly correlated with tumor TNM classification and radical degree (P < 0.01), and regards the sum of distances from tumor to two cutting edges and the classification of cutting edge as significant impact factors (P < 0.05); nine patients whose CA 72-4 in gastric juice rose post-DG show features indicating poor prognosis; the difference of CA 72-4 in gastric juice between pre- and post-gastrectomy is significantly correlated with tumor TNM classification and radical degree (P < 0.05), and regards tumor size, levels of gastric walls invaded, the sum of distances from tumor to two cutting edges and the classification of cutting edge as significant influential factors (P < 0.05). We conclude that CA 72-4 in gastric juice pre- and post-gastrectomy can provide us with much information about tumor and radical gastrectomy and that CA 72-4 in gastric juice post-gastrectomy and the difference of CA 72-4 in gastric juice between pre- and post-gastrectomy may indicate prognosis.