Monitoring ROS Responsive Fe3O4-based Nanoparticle Mediated Ferroptosis&Immunotherapy via 129Xe MRI.

The immune checkpoint blockade strategy has improved the survival rate of late-stage lung cancer patients. However, the low immune response rate limits the immunotherapy efficiency. Here, we report a ROS-responsive Fe3O4-based nanoparticle that undergoes charge reversal and disassembly in the tumor microenvironment, enhancing the uptake of Fe3O4 by tumor cells and triggering a more severe ferroptosis. In the tumor microenvironment, the nanoparticle rapidly disassembles and releases the loaded GOx and the immune-activating peptide Tuftsin under overexpressed H2O2. GOx can consume the glucose of tumor cells and generate more H2O2, promoting the disassembly of the nanoparticle and drug release, thereby enhancing the therapeutic effect of ferroptosis. Combined with Tuftsin, it can more effectively reverse the immune-suppressive microenvironment and promote the recruitment of effector T cells in tumor tissues. Ultimately, in combination with α-PD-L1, there is significant inhibition of the growth of lung metastases. Additionally, the hyperpolarized 129Xe method has been used to evaluate the Fe3O4 nanoparticle-mediated immunotherapy, where the ventilation defects in lung metastases have been significantly improved with complete lung structure and function recovered. The ferroptosis-enhanced immunotherapy combined with non-radiation evaluation methodology paves a new way for designing novel theranostic agents for cancer therapy.

Patient-specific QA for the HyperArc technique using gafchromic film with multiple calibration methods.

PURPOSE: This study aims to evaluate different methods for calibrating EBT-XD films to develop a precise pre-treatment verification method for stereotactic radiotherapy (SRT) patients using the HyperArc (HA, Varian Medical System) technique. METHODS: Gafchromic EBT-XD films were calibrated using three different approaches: manual calibration, EDW calibration, and PDD calibration. Films were digitalized with an Epson V850 Pro scanner applying the local scanning protocol. Three clinical treatment plans were selected for evaluation. Patient-specific QA films were irradiated in the Mobius MVP phantom and the STEEV phantom. Scanned film images were converted into dose images using the calibration curves. Gamma analysis was performed to compare film dose and TPS calculated dose with various criteria. RESULTS: The scan-to-scan variation was evaluated to be ≤ 0.2%. The accuracy of the calibration curves was verified and the deviation from the converted dose deviates ≤ 3% from the known delivered dose. The gamma passing rate for all calibration methods was found to be over 94% with clinically relevant criteria. EDW calibration demonstrated higher average gamma passing rates compared to the manual method for single target plans, which is 99% ± 1.2% and 98.8% ± 1.5%, respectively. PDD method demonstrated improved agreement for multiple targets with the result of 99.3% ± 0.8%. CONCLUSIONS: The three calibration methods were validated, and they produced accurate calibration curves for EBT-XD films to enable pre-treatment patient-specific QA for stereotactic radiotherapy.

Factors affecting the immunogenicity of influenza vaccines in human.

BACKGROUND: The influenza viruses pose a threat to human health and medical services, and vaccination is an important way to prevent infection. However, the effectiveness of influenza vaccines is affected by various aspects. This study aimed to explore factors related to the immune response to influenza vaccines. METHODS: The study was conducted from September 2019 to September 2021, and a total of 593 volunteers were recruited from the Center for Disease Control and Prevention in 3 provinces in China. The hemagglutination inhibition assay was used to measure antibody levels. The Chi-square test, multivariable logistic regression analysis, and sum-rank test were used to analyze the factors associated with influenza vaccine immune response. RESULTS: The Chi-square test showed that seroconversion rates and response rate were associated with age group, vaccination history, chronic conditions, the frequency of colds, and region (P < 0.05). The multivariable logistic regression analysis showed that age was an important factor that affected participants' seroconversion rates for A/H1N1, A/H3N2, B/Victoria, and response status (18-64 vs. ≤5: OR = 2.77, P < 0.001; ≥65 vs. ≤5: OR = 0.38, P = 0.01; 18-64 vs. ≤5: OR = 2.64, P = 0.03). Vaccination history was also an affecting factor for A/H1N1, B/Victoria, and response status (yes vs. no: OR = 0.4 / 0.44 / 0.25, P < 0.001). The frequency of colds and chronic conditions were also affecting factors for participants' seroconversion rates and response levels to different degrees. The sum-rank test showed that the fold changes for A/H1N1, B/Victoria, and B/Yamagata were associated with age group and vaccination history (P < 0.01). The fold changes for A/H3N2 were associated with the frequency of colds (P < 0.05), and those for B/Victoria were associated with gender and chronic conditions (P < 0.05). CONCLUSIONS: Vaccination history, age, health condition, and frequency of colds were important factors affecting the seroconversion rate of the influenza vaccine in human. There is a need for developing optimized vaccination strategies for vulnerable groups to improve the efficacy of influenza vaccines in human.

Evaluating Ciliary Body Damage Induced by Blunt Low Speed Impact Using Finite Element Simulation.

PURPOSE: To evaluate the ciliary body mechanical load during low speed impact using finite element method to explain the mechanism of the cause of angle recession and cyclodialysis cleft. METHODS: Optical coherence tomography images were obtained to assess the patient's ciliary body angle recession. A finite element eye model was established based on Virginia Tech eye model with the consideration of dynamic impact of a projectile striking an eye. The mechanical properties of the ocular tissues were obtained from literatures. The stress and strain were evaluated. RESULTS: The stress distribution of the eye was calculated. The stress concentration at zonules was observed after 0.75 ms of the impact. The maximum stress at the cornea reached 3.8 MPa. The maximum stress at ciliary body was 57 KPa, which has high probability to cause ciliary body injury. The maximum stress at zonules was 0.98 MPa. The lateral expansion also reduces the forces transmitted along the sclera to the rear part of the eye. CONCLUSIONS: The eye under frontal impact will result in lateral expansion, which increase the stretch force of the lens, zonules and ciliary body. This mechanism can be seen as the protection for retina. The boundary of ciliary body is the most vulnerable position, where angle recession and cyclodialyses cleft will occur before retina damage occurrence. TRANSLATIONAL RELEVANCE: The finite element model explains the blunt low speed impact induced ciliary body related injuries, which enables us to assess the ocular injury for low energy impact and better diagnosis and treatment in clinics.

A case of polycystic ovary syndrome with inevitable miscarriage and multi-site venous thrombosis caused by hereditary protein C deficiency.

BACKGROUND: Polycystic ovarian syndrome (PCOS) affects up to 18% of reproductive-aged women and raises the risk of venous thromboembolic disease (VTE), due to metabolic features and an apparent fibrinolytic state. Recent studies have shown an increased risk of VTE (1.5- to 2-fold) in patients with PCOS as compared to those without PCOS. Mutations in the Protein C (PC) gene (PROC) lead to deficiency or dysfunction of the protein, Protein C deficiency is the main clotting physiological inhibitor of protein C cofactors, and is a risk factor for venous thrombosis, which can cause a variety of events, including miscarriage. This case report proposes a correlation between PCOS, protein C deficiency, venous thrombosis and inevitable miscarriage. CASE PRESENTATION: A 33-year-old Chinese woman was diagnosed with Polycystic Ovary Syndrome (PCOS) in 2015. During the course of treatment, she took ethinylestradiol and cyproterone acetate tablets for more than one year. In 2016, she was sent to a hospital for emergency care due to explosive thrombosis (thrombosis in multiple parts of the body and pulmonary thrombosis). In 2020, the patient became pregnant via natural means and came to our hospital for treatment. During the second trimester, she experienced an inevitable miscarriage. High-throughput sequencing (NGS) of peripheral blood lymphocytes revealed that the patient had a protein C deficiency resulting from a heterozygous mutation deletion of 572_574 in exon 7. CONCLUSION: PC deficiency in conjunction with PCOS and the concomitant use of oral contraceptive (COC) would increase the risk of VTE, especially in the early stages of COC use.

The willingness to use mobile health and its influencing factors among elderly patients with chronic heart failure in Shanghai, China.

OBJECTIVE: The purpose of this study was to explore the willingness of elderly patients with chronic heart failure to use mobile health for health management in Shanghai and analyze influencing factors. METHODS: The study was conducted from August 2020 to July 2021. A convenience sample of 181 elderly patients with chronic heart failure recruited from three tertiary hospitals and one health service center in Shanghai completed self-developed structured questionnaires. The data collected included demographic information, health status, knowing about mobile health, usage of mobile health, willingness to use mobile health for health management, and beliefs about mobile health. SPSS20.0 software was used for analyzing data. RESULTS: Eighty-four patients (46.4%) expressed their willingness to use mobile health. Logistic regression analyses showed that knowing about mobile health (OR = 16.30, p < 0.001), usage of mobile health (OR = 15.36, p < 0.001), self-rated health (good vs. poor: OR = 15.03, p = 0.003; neutral vs. poor: OR = 3.00, p = 0.006), perceived ease of use (OR = 3.86, p = 0.002), perceived usefulness (OR = 1.90, p < 0.001), and self-efficacy (OR = 1.43, p < 0.001) were important factors influencing the willingness to use mobile health. CONCLUSIONS: There is a need for developing user-friendly and useful mobile health for elderly patients with chronic heart failure. The participatory approach could be used to develop mobile health intervention. In addition, mobile health should be promoted, publicized, and trained among this group of population.

Functional role of the three conserved cysteines in the N domain of visual arrestin-1.

Arrestins specifically bind active and phosphorylated forms of their cognate G protein-coupled receptors, blocking G protein coupling and often redirecting the signaling to alternative pathways. High-affinity receptor binding is accompanied by two major structural changes in arrestin: release of the C-tail and rotation of the two domains relative to each other. The first requires detachment of the arrestin C-tail from the body of the molecule, whereas the second requires disruption of the network of charge-charge interactions at the interdomain interface, termed the polar core. These events can be facilitated by mutations destabilizing the polar core or the anchoring of the C-tail that yield "preactivated" arrestins that bind phosphorylated and unphosphorylated receptors with high affinity. Here we explored the functional role in arrestin activation of the three native cysteines in the N domain, which are conserved in all arrestin subtypes. Using visual arrestin-1 and rhodopsin as a model, we found that substitution of these cysteines with serine, alanine, or valine virtually eliminates the effects of the activating polar core mutations on the binding to unphosphorylated rhodopsin while only slightly reducing the effects of the C-tail mutations. Thus, these three conserved cysteines play a role in the domain rotation but not in the C-tail release.

Complete remission of platinum-refractory primary Fallopian tube carcinoma with third-line gemcitabine plus cisplatin: A case report and review of the literature.

Primary Fallopian tube carcinoma (PFTC) is a rare but highly aggressive disease. Currently, treatments are similar to those used in epithelial ovarian carcinoma (EOC), however, there are distinct differences between the two diseases. PFTC tends to recur in the retroperitoneal nodes and distant sites more often than EOC. Limited literature with regard to effective agents in platinum-resistant and -refractory (Pt-R) disease exists, particularly after two lines of consecutive treatment. In this case report, a 47-year-old female with PFTC exhibited recurrence in the liver after postoperative chemotherapy. The patient received paclitaxel and cisplatin combination as first-line chemotherapy and topotecan as a second-line treatment, which is considered platinum-refractory. After the second-line treatment failed, this patient received a gemcitabine plus cisplatin combination as third-line chemotherapy for a total of 6 cycles. The liver metastases regressed rapidly and completely. The patient's progression-free survival (PFS) was 10 months and overall survival (OS) was 45 months. In conclusion, gemcitabine and cisplatin combination is an effective regimen for refractory PFTC even after the failure of two previous lines of consecutive chemotherapy and this warrants further independent investigation.