Additional PD-1 inhibitor improves complete response to induction chemotherapy in locally advanced nasopharyngeal carcinoma.

Purpose: To investigate the treatment response and toxicity of the combination of induction chemotherapy (IC) and PD-1 inhibitor in locally advanced nasopharyngeal carcinoma (LANPC). Methods: Patients with stage III-IVA NPC who received IC or IC + PD-1 inhibitor were included. The chi-square test and multivariate logistic regression analysis were used for statistical analysis. Results: A total of 225 patients were identified, including 193 (85.8%) and 32 (14.2%) who received IC alone and IC + PD-1 inhibitor, respectively. The addition of PD-1 inhibitor to IC significantly improved the tumor response than those treated with IC alone. The complete response (CR), partial response, stable disease, and progressive disease rates of 4.7% vs. 31.3%, 69.4% vs. 62.5%, 24.9% vs. 6.3%, and 1.0% vs. 0% in patients receiving IC alone and IC + PD-1 inhibitor, respectively (P<0.001). The results of the multivariate logistic regression showed that receiving PD-1 inhibitor was an independent predictor influencing the CR rate of patients (odds ratio 9.814, P<0.001). The most common toxicity by using IC and PD-1 inhibitor was hematological toxicity. In terms of non-hematological toxicity, 7 (21.9%) patients experienced thyroid dysfunction and all of them were hyperthyroidism. No grade 5 toxicities were found. In those who received IC and PD-1 inhibitor, the one-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 100%, 96.9%, 96.9%, and 100%, respectively. Conclusion: The addition of PD-1 inhibitor to IC has promise as an effective treatment approach for LANPC. More studies are expected to provide further insights into the optimal use of this treatment strategy, paving the way for more personalized and effective treatment options for patients with LANPC.

Addition of nimotuzumab to concurrent chemoradiotherapy after induction chemotherapy improves outcomes of patients with locally advanced nasopharyngeal carcinoma.

Purpose: To investigate the survival outcomes and toxicities associated with the addition of nimotuzumab to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LANPC) patients who received induction chemotherapy (IC). Methods: Patients with stage III-IVA nasopharyngeal carcinoma who received IC and CCRT between January 2017 and October 2021 were retrospectively included. We aimed to compare the locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) between patients treated with CCRT+nimotuzumab and CCRT alone. Results: We included 411 patients in the analysis. Of these patients, 267 (65.0%) and 144 (35.0%) had CCRT+nimotuzumab and CCRT alone, respectively. Similar LRFS was found between those with and without nimotuzumab (92.9% vs. 92.6%, p = 0.855). The 3-year DMFS was 88.2% and 76.2% in those with and without nimotuzumab (p = 0.002). The 3-year DFS was 83.4% and 70.6% in those with and without nimotuzumab treatment (p = 0.003). The 3-year OS was 92.1% and 81.1% in those with and without nimotuzumab (p = 0.003). The multivariate Cox regression analysis indicated that the addition of nimotuzumab was independently associated with better DMFS (hazard ratio [HR] 0.606, p = 0.049), DFS (HR 0.613, p = 0.028), and OS (HR 0.497, p = 0.019). No significant differences in major toxicities were found between the two treatment arms, including hematologic toxicities, hepatoxicity, nephrotoxicity, gastrointestinal reactions, and mucositis (all p > 0.05). Conclusion: The addition of nimotuzumab to CCRT after IC in LANPC has shown promising results in improving treatment outcomes and acceptable toxicities.

Mesopic pupil indices as potential risk factors for glare disability after intraocular implantable collamer lens implantation: prospective study.

PURPOSE: To explore the influence of preoperative factors, including varying pupil sizes and refractive attributes, on postoperative glare disability in patients undergoing implantable collamer lens (ICL) implantation. SETTING: Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China. DESIGN: Prospective observational study. METHODS: The preoperative ocular characteristics and 6-month postoperative glare status in eligible patients who underwent EVO-Visian ICL V4c (VICMO) implantation were analyzed. The glare disability criteria encompassed a glare symptom score >6 and glare sensitivity exceeding 1:2.7. Logistic regression analysis was used to explore the relationship between the preoperative ocular parameters and post-ICL glare. RESULTS: The study included 95 patients (mean age, 26.04 ± 6.29 years), comprising 30 men (58 eyes) and 65 women (129 eyes). Multivariate analysis revealed a significant correlation between postoperative glare disability and increased spherical power in preoperative mesopic pupils (ß = -0.124, P = .039), as well as elevated cylinder power in preoperative mesopic (ß = -0.412, P = .009) and photopic pupils (ß = -0.430, P = .007). Moreover, a larger preoperative mesopic pupil diameter (ß = 0.561, P = .005) demonstrated a significant correlation with glare disability. CONCLUSIONS: Preoperative mesopic pupil dimensions and associated refractive parameters, such as sphere and cylinder, were correlated with glare disability, including the cylinder aspect in photopic pupils, which can assist clinicians in optimizing preoperative selection for ICL implantation, aiding in the anticipation of potential glare disability risks.

Metronomic S1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

Purpose: To investigate the efficacy and safety of using metronomic S1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods: We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses. Results: A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p<0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S1. The multivariate prognostic analysis revealed that metronomic S1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR] 0.074, p=0.010), DFS (HR 0.103, p=0.002) and OS (HR 0.127, P=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2. Conclusion: It is worth conducting a randomized controlled trial to assess the effect of metronomic S1 on survival outcomes and toxicities of LANPC.

Characterization of the monoclonal antibody and the immunodominant B-cell epitope of African swine fever virus pA104R by using mouse model.

The African swine fever virus (ASFV) structural protein pA104R is the only histone-like protein encoded by eukaryotic viruses. pA104R is an essential DNA-binding protein required for DNA replication and genome packaging of ASFV, which are vital for pathogen survival and proliferation. pA104R is an important target molecule for diagnosing, treating, and immune prevention of ASFV. This study characterized monoclonal antibodies (mAbs) against pA104R and found them to recognize natural pA104R in ASFV strains with different genotypes, showing high conservation. Confirmation analyses of pA104R epitopes using mAbs indicated the presence of immunodominant B-cell epitopes, and further characterization showed the high antigenic index and surface accessibility coefficients of the identified epitope. Furthermore, the pA104R protein functions through the polar interactions between the binding amino acid sites; however, these interactions may be blocked by the recognition of generated mAbs. Characterizing the immunodominant B-cell epitope of the ASFV critical proteins, such as pA104R, may contribute to developing sensitive diagnostic tools and vaccine candidate targets.IMPORTANCEAfrican swine fever (ASF) is a highly pathogenic, lethal, and contagious viral disease affecting domestic pigs and wild boars. As no effective vaccine or other treatments have been developed, the control of African swine fever virus (ASFV) relies heavily on virus detection and diagnosis. A potential serological target is the structural protein pA104R. However, the molecular basis of pA104R antigenicity remains unclear, and a specific monoclonal antibody (mAb) against this protein is still unavailable. In this study, mAbs against pA104R were characterized and found to recognize natural pA104R in ASFV strains with different genotypes. In addition, confirmation analyses of pA104R epitopes using mAbs indicated the presence of immunodominant B-cell epitopes, and further characterization showed the high antigenic index and surface accessibility coefficients of the identified epitope. Characteristics of the immunodominant B-cell epitope of ASFV proteins, such as pA104R, may contribute to developing sensitive diagnostic tools and identifying vaccine candidate targets.

Advancing sustainable seawater disinfection: Enhanced inactivation and mechanism of pulsed UV-LEDs irradiation on Tetraselmis sp.

Ultraviolet light-emitting diodes (UV-LEDs), as a novel ultraviolet light source with flexible pulse mode, has gained significant attention for applications in water disinfection and food sterilization. This study investigated the comparative inactivation efficiency of Tetraselmis sp. with continuous and pulsed UV-LEDs irradiation, exploring different wavelengths, duty rates and pulse frequencies. The results reveal a significant enhancement in inactivation efficiency (p < 0.05) under pulsed conditions even at the same UV dose, with inactivation efficiency increasing as duty rate or pulse frequency decreases. The optimal conditions for achieving peak inactivation efficacy are identified as a duty rate of 50% and a pulse frequency of 5 Hz. Within this parameter space, pulsed irradiation leads to a remarkable 1.7-fold increase in inactivation efficiency at UV265 nm and a 1.5-fold increase at UV285 nm compared to continuous irradiation, respectively. Additionally, the disruptive impacts on photosynthetic performance are more pronounced with pulsed irradiation, particularly at the 5 Hz pulse frequency. In shed of these findings, the application of pulsed UV-LEDs irradiation emerges as a promising alternative to the conventional continuous UV disinfection methods in the area of seawater disinfection, offering higher disinfection efficacy and energy consumption.

Multi-crosslinked hydrogel built with hyaluronic acid-tyramine, thiolated glycol chitosan and copper-doped bioglass nanoparticles for expediting wound healing.

The migration of fibroblasts and endothelial cells is a critical determinant of wound-healing outcomes for skin injuries. Here, hyaluronic acid-tyramine (HAT) and thiolated glycol chitosan (TGC) conjugates were combined with copper-doped bioglass (ACuBG) nanoparticles to build a novel type of multi-crosslinked hydrogel for stimulating the migration of cells, and thus, expediting wound healing. The optimally devised HAT/TGC/ACuBG gels had markedly improved strength and stiffness compared to the gels built from either HAT or TGC while showing sufficient elasticity, which contributes to stimulating the migration of fibroblasts. The sustainable release of silicon and copper ions from the gels was found to jointly induce the migration of human umbilical vein endothelial cells. The results based on mouse full-thickness skin defects demonstrated that they were able to fully restore the skin defects with formation of complete appendages within two weeks, suggesting their promising potency for use in expediting wound healing.

Monitoring angiogenesis in skin autografts using photoacoustic microscopy.

BACKGROUND: Skin autografts have been broadly used to manage the skin and soft tissue defects. It is important for surgeons to assess the vitality of skin autografts via observing the angiogenesis. However, there is lack of reliable approach for giving the quantitative angiogenesis information on the skin autografts. Recently, photoacoustic microscopy imaging has attracted much attention based on its good performance in angiography. METHODS: In this study, we aim to monitor angiogenesis in skin autografts via PAM, and further verify its clinical potential for the early prediction of skin autografts clinical outcome. RESULTS AND CONCLUSIONS: The results indicate that PAM is a feasible, precise, high-resolution, noninvasive technique for the early prediction of necrosis of skin autografts via monitoring the angiogenesis, providing a promising tool for surgeons to use this surgical technology.

A Pilot Study of Anlotinib as a Combination Treatment in Advanced Nasopharyngeal Carcinoma.

AIMS: To investigate the short-term objective response and treatment toxicity of anlotinib as a combination treatment in patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (RM-NPC). METHODS: Patients with RM-NPC who received anlotinib as a combination treatment between March 2021 and July 2022 were retrospectively analyzed.The efficacy and safety of anlotinib as a combination treatment were analyzed. RESULTS: A total of 17 patients with RM-NPC were included in this study. Of these patients, 2 (11.8%) had local recurrence, 4 (23.5%) had cervical lymph node recurrence, and 11 (64.9%) had distant failure. The most common metastatic site was the liver (47.1%), followed by the lung (23.5%) and bone (23.5%). Anlotinib was given as first-line treatment in 3 patients (17.6%), second lines treatment in 7 patients (41.2%), and third to six-lines treatment in 7 patients (41.2%). All patients received anlotinib combined with chemotherapy and/or immunotherapy. One patient achieved a complete response (5.9%), 7 patients had a partial response (41.2%), 5 patients had stable disease (29.4%), and 4 patients had progressive disease (23.5%). The overall disease control rate and the overall response rate were 76.5% and 47.1%, respectively. The median progression-free survival was 8.1 months, and the median overall survival was not reached. The incidence of grade 3 adverse events was 30%. No unexpected side effects or treatment-related death were observed. CONCLUSION: Anlotinib, as a combination treatment, has a promising antitumor activity and a manageable safety profile in patients with RM-NPC. Our results add to the growing evidence that supports the benefits of combining antiangiogenic drugs in RM-NPC. Randomized controlled clinical trials investigating the evaluation of anlotinib are warranted.

Real-time visualization of skeletal muscle necrosis in mice and swine through NIR-II/I fluorescence imaging.

Avulsion often occurs in the limb due to heavy shearing forces which not only damage skeletal muscle but also main vessels, resulting in life-threatening muscle ischemia and necrosis. Defining muscle activity is vital for surgical repair. Currently, the color, capacity of blood, contractibility, and consistency (4C) are the primary principles for evaluating the activities of torn muscles. Based on clinical experiences, this standard turns out to be delayed diagnosis, which is not defined by specific parameters. Recently, near-infrared (NIR) fluorescence probes emitting within the second near-infrared window (NIR-II, 1000-1700 nm) have been widely used for non-invasive optical imaging because the tissue absorption and autofluorescence in the NIR-II region are negligible, thus allowing deeper penetration depths with micrometer-scale spatial resolution in vivo. As pathogenesis and development of muscle necrosis, necrosis-related protein may participate in this procedure. There is promising future for NIR-II to be used in evaluating muscle activity in avulsion. A new approach is developed based on experiments with mice and large animals (swine). Myoblasts were incubated with indocyanine green (ICG) to identify the necrosis muscles. The model of extremity damaged muscle was established for the real-time visualization and detection of developed necrosis muscle field under new equipment, both in balb/c mice (female) and long-haired swines. A visible NIR-II/I imaging system was first used in a large animal injured skeletal muscle-related model. Our NIR-II/I imaging system is suitable for evaluating the normal and injured skeletal muscle ICG cycle and pointing to the necrotic skeletal muscle tissue. NIR-II imaging is superior to NIR-I imaging in estimating skeletal muscle, best with 1100 nm filter. NIR-II fluorescence with 1100 nm filter is suitable for analyzing the progress of necrosis muscle tissue, leading to a new approach for intraoperative evaluation.

An injectable and adaptable hydrogen sulfide delivery system for modulating neuroregenerative microenvironment.

Peripheral nerve regeneration is a complex physiological process. Single-function nerve scaffolds often struggle to quickly adapt to the imbalanced regenerative microenvironment, leading to slow nerve regeneration and limited functional recovery. In this study, we demonstrate a "pleiotropic gas transmitter" strategy based on endogenous reactive oxygen species (ROS), which trigger the on-demand H2S release at the defect area for transected peripheral nerve injury (PNI) repair through concurrent neuroregeneration and neuroprotection processing. This H2S delivery system consists of an H2S donor (peroxyTCM) encapsulated in a ROS-responsive polymer (mPEG-PMet) and loaded into a temperature-sensitive poly (amino acid) hydrogel (mPEG-PA-PP). This multi-effect combination strategy greatly promotes the regeneration of PNI, attributed to the physiological effects of H2S. These effects include the inhibition of inflammation and oxidative stress, protection of nerve cells, promotion of angiogenesis, and the restoration of normal mitochondrial function. The adaptive release of pleiotropic messengers to modulate the tissue regeneration microenvironment offers promising peripheral nerve repair and tissue engineering opportunities.

Residual plasma Epstein-Barr virus DNA after intensity-modulated radiation therapy is associated with poor outcomes in nasopharyngeal carcinoma.

Aim: To investigate the effects of residual plasma Epstein-Barr virus (EBV) DNA levels after 3 months of intensity-modulated radiation therapy (IMRT) (postIMRT-EBV DNA) on prognosis in patients with nasopharyngeal carcinoma. Methods: Data from 300 patients were retrospectively collected for analysis. Results: Of these patients, 25 (8.3%) and 275 (91.7%) had positive and negative postIMRT-EBV DNA, respectively. Multivariate survival analysis showed that EBV DNA >688 IU/ml was independently associated with inferior distant metastasis-free survival (p = 0.003) and progression-free survival (p = 0.002). Moreover, postIMRT-EBV DNA was independently associated with inferior locoregional recurrence-free survival (hazard ratio: 4.325; p = 0.018), distant metastasis-free survival (hazard ratio: 10.226; p < 0.001) and progression-free survival (hazard ratio: 10.520; p < 0.001). Conclusion: Positive postIMRT-EBV DNA is a prognostic biomarker for nasopharyngeal carcinoma.

NIR-triggered photodynamic therapy of traumatic heterotopic ossification with a type II collagen-targeted photosensitizer.

Traumatic heterotopic ossification (HO) represents an intractable sequela following trauma with no currently effective prophylaxis or treatment. Photodynamic therapy (PDT) is a non-invasive treatment for various proliferative diseases. However, the specific effects of PDT on HO development remain unclear. In this study, the therapeutic potential of a near-infrared (NIR) probe-WL-808, composed of type II collagen-binding peptide (WYRGRL) and a PDT photosensitizer (IR-808), was evaluated for the innovative HO-targeted PDT approach. In vitro studies indicated that WL-808 could induce chondrocyte apoptosis and inhibit cell viability through ROS generation under NIR excitation. In vivo, the efficacy of WL-808-mediated PDT was tested on the tenotomy HO model mice. WL-808 specifically targeted the type II collagen cartilaginous template of HO, promoting cell apoptosis and enhancing extracellular matrix (ECM) degradation under 808 nm NIR excitation, which inhibited the final ectopic bone formation. Moreover, no obvious toxicity or side effects were detected after treatment with WL-808. Taken together, WL-808-mediated PDT significantly diminished ectopic cartilage and subsequent bone formation, providing a new perspective for HO prophylaxis and treatment.

The effect of Tuina based on the concept of hip-knee-ankle conjugation in patients with chronic ankle instability: study protocol for a randomized controlled trial.

Background: Chronic ankle instability (CAI) is a common sports injury disease and characterized by limited mobility, perceived instability and muscle weakness, combined treatment of hip-knee-ankle is a common rehabilitation method. Tuina, as a traditional Chinese manual therapy, is usually used for CAI, but many of them only focus on the local ankle joint rather than the combination of hip and knee joint. Therefore, we have designed a randomized controlled trial (RCT) to investigate the effects of Tuina base on the concept of hip-knee-ankle conjugation on the stability and balance of lower limbs and ankle function in patients with CAI. Methods: We have designed a randomized controlled trial. A total of 72 participants with CAI will be randomly divided into functional training groups and hip-knee-ankle Tuina combined with functional training group in a 1:1 ratio. Participants in control group will receive 8 sessions of functional training (30 min per session, twice a week for 4 weeks). Participants in intervention group will receive 8 sessions of Tuina combined with functional training (twice a week for 4 weeks). The primary outcomes include the Y-Balance Test (YBT) and Cumberland Ankle Instability Tool (CAIT). The Secondary outcomes include the Foot and Ankle Ability Measure (FAAM) and ankle range of motion (ROM). The outcome assessments will be conducted before the first intervention and after the last intervention. Discussion: The aim of this study is to explore a safe and effective manipulation program and serve as reference for clinical treatment of CAI and expect to provide the necessary theoretical and practical support to our future research. Clinical Trial Registration: Chinese Clinical Trail Registry ChiCTR2300068274.

Xerostomia: An easily ignored symptom induced by induction chemotherapy in patients with nasopharyngeal carcinoma.

BACKGROUND: To investigate the prevalence and predictive factors of xerostomia during induction chemotherapy (IC) in patients with nasopharyngeal carcinoma (NPC). METHODS: We prospectively enrolled NPC patients who received IC between October 2020 and October 2021. The Visual Analogue Scale (VAS) and Xerostomia Inventory (XI) were used to evaluate the condition of xerostomia. The volume of the submandibular gland (SMG) was also calculated before and after IC. RESULTS: Fifty-two patients were enrolled in this study. Of these patients, 32.7% (n = 17) experienced xerostomia before IC. There were 32 (61.5%) patients suffered from xerostomia after IC, including 21 (40.4%) patients with newly diagnosed xerostomia after IC and 11 (21.1%) patients complained their xerostomia aggravated in those with xerostomia before IC. The median XI scores increased from 11 (standard deviation [SD], 2.930) to 18 (SD 3.995), 16 (SD 3.605), and 17 (SD 4.331) after the first, second, and third cycles of IC, respectively. The median score of VAS also increased from 0 to 4 during the following three cycles of IC. In those with IC-related xerostomia, the SMG volume after IC was significantly decreased compared with those without IC-related xerostomia (P = 0.001). The reduction of the SMG volume after IC was the independent risk factor for xerostomia (P = 0.002). CONCLUSION: Approximately two-thirds of NPC patients suffered from IC-related xerostomia and patients with a reduction of SMG volume after IC had a higher risk of xerostomia.

A coarse-grained study on mechanical behaviors of diamond-like carbon based on machine learning.

Diamond-like carbon (DLC) films have broad application potential due to their high hardness, high wear resistance, and self-lubricating properties. However, considering that DLC films are micron-scale, neither finite element methods nor macroscopic experiments can reveal their deformation and failure mechanisms. Here we propose a coarse-grained molecular dynamics (CGMD) approach which expands the capabilities of molecular dynamics simulations to uniaxial tensile behavior of DLC films at a higher scale. The Tersoff potential is modified by high-throughput screening calculations for CGMD. Given this circumstance, machine learning (ML) models are employed to reduce the high-throughput computational cost by 86%, greatly improving the efficiency of parameter optimization in second- and fourth-order CGMD. The final obtained coarse-grained tensile curves fit well with that of the all-atom curves, showing that the ML-based CGMD method can investigate DLC films at higher scales while saving a large number of computational resources, which is important for promoting the research and production of high-performance DLC films.

Risk factors of early thyroid dysfunction after definitive radiotherapy in nasopharyngeal carcinoma patients.

BACKGROUND: To explore the patterns and risk factors of early thyroid dysfunction in nasopharyngeal carcinoma (NPC) patients within 1 year after intensity-modulated radiation therapy (IMRT). METHODS: Patients with NPC who received definitive IMRT between April 2016 and April 2020 were included. All patients had normal thyroid function before definitive IMRT. The chi-square test, Student's T-test, Mann-Whitney U test, Kaplan-Meier method, receiver operating characteristics curve, and Cox proportional hazard analysis were used for statistical analysis. RESULTS: A total of 132 NPC patients were identified. Of these patients, 56 (42.4%) had hypothyroidism and 17 (12.9%) had hyperthyroidism. The median time to hypothyroidism and hyperthyroidism was 9 months (range, 1-12 months) and 1 month (range, 1-6 months) after definitive IMRT, respectively. In patients with hypothyroidism, 41 (73.2%) had subclinical hypothyroidism and 15 (26.8%) had clinical hypothyroidism. In those with hyperthyroidism, 12 patients (70.6%) had subclinical hyperthyroidism, and five patients (29.4%) had clinical hyperthyroidism. Age, clinical stage, thyroid volume, and V45 were independent risk factors for early radiation-induced hypothyroidism within 1 year after IMRT. Patients aged <47 years, stage III/IV disease, or pre-irradiation thyroid volume < 14 cm3 had higher risks of developing hypothyroidism. CONCLUSION: Primary subclinical hypothyroidism was the most common subtype of early thyroid dysfunction in NPC patients within 1 year after IMRT. Age, clinical stage, thyroid volume, and V45 were independent risk factors for early radiation-induced hypothyroidism in NPC patients.

Deep-penetration functionalized cuttlefish ink nanoparticles for combating wound infections with synergetic photothermal-immunologic therapy.

The challenge of wound infections post-surgery and open trauma caused by multidrug-resistant bacteria poses a constant threat to clinical treatment. As a promising antimicrobial treatment, photothermal therapy can effectively resolve the problem of drug resistance in conventional antibiotic antimicrobial therapy. Here, we report a deep-penetration functionalized cuttlefish ink nanoparticle (CINP) for photothermal and immunological therapy of wound infections. CINP is decorated with zwitterionic polymer (ZP, namely sulfobetaine methacrylate-methacrylate copolymer) to form CINP@ZP nanoparticles. Natural CINP is found to not only exhibit photothermal destruction of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), but also trigger macrophages-related innate immunity and enhance their antibacterial functions. The ZP coating on the surface of CINP enables nanoparticles to penetrate into deeply infected wound environment. In addition, CINP@ZP is further integrated into the thermosensitive Pluronic F127 gel (CINP@ZP-F127). After in situ spraying gel, CINP@ZP-F127 is also documented notable antibacterial effects in mice wound models infected with MRSA and E. coli. Collectively, this approach combining of photothermal therapy with immunotherapy can promote delivery efficiency of nanoparticles to the deep foci of infective wounds, and effectively eliminate wound infections.

Prognostic effect of residual plasma Epstein-Barr viral DNA after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: To assess the prognostic effect of plasma Epstein-Barr virus (EBV) DNA load after induction chemotherapy (postIC -EBV DNA) on survival outcomes in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: Patients who were diagnosed with LA-NPC between August 2017 and October 2021 were included. The chi-squared test, receiver operating characteristic, Kaplan-Meier survival analysis, and Cox proportional hazard model were used for statistical analysis. RESULTS: We included 172 patients with EBV DNA-positive LA-NPC in this study. There were 35.5% (n = 61) of patients had plasma residual EBV DNA after induction chemotherapy (IC). Patients with higher EBV DNA before IC (p < 0.001) and advanced nodal stage (p = 0.031) were significantly related to a higher rate of residual postIC -EBV DNA. Patients with detectable postIC -EBV DNA had inferior 3-year locoregional relapse-free survival (LRFS) (86.7% vs. 96.9%, p = 0.020), distant metastasis-free survival (DMFS) (76.8% vs. 94.2%, p < 0.001), disease-free survival (DFS) (68.2% vs. 91.1%, p < 0.001), and overall survival (OS) (87.8% vs. 97.9%, p = 0.044) compared to those with undetectable postIC -EBV DNA. The multivariate prognostic analyses showed that detectable postIC -EBV DNA was the independent prognostic factor related to LRFS (p = 0.032), DMFS (p = 0.010), and DFS (p = 0.004) than those with undetectable postIC -EBV DNA. Pretreatment EBV DNA load had no prognostic effect in the multivariate analyses. CONCLUSIONS: The monitoring of plasma postIC -EBV DNA has improved prognostication in LA-NPC. Our findings suggest that postIC -EBV DNA may be a robust indicator to identify the optimal candidate for intensive treatment.

Tumor-targeted AIE polymeric micelles mediated immunogenic sonodynamic therapy inhibits cancer growth and metastasis.

Aggregation-induced emission luminogens (AIEgens) exhibit potent sonosensitivity in nanocarriers compared with conventional organic sonosensitizers owing to the strong fluorescence emission in the aggregated state. However, the premature drug leakage and ineffective tumor targeting of current AIE nanosonosensitizers critically restrict their clinical applications. Here, an AIEgen-based sonosensitizer (AIE/Biotin-M) with excellent sonosensitivity was developed by assembling salicylaldazine-based amphiphilic polymers (AIE-1) and 4T1 tumor-targeting amphiphilic polymers (DSPE-PEG-Biotin) for the effective delivery of salicylaldazine to 4T1 tumor tissues, aiming to mediate immunogenic SDT. In vitro, AIE/Biotin-M were highly stable and generated plentiful singlet oxygen (1O2) under ultrasound (US) irradiation. After AIE/Biotin-M targeted accumulation in the tumor, upon US irradiation, the generation of 1O2 not only led to cancer cell death, but also elicited a systemically immune response by causing the immunogenic cell death (ICD) of cancer cells. In addition to mediating SDT, AIE/Biotin-M could chelate and reduce Fe3+, Cu2+ and Zn2+ by salicylaldazine for inhibiting neovascularization in tumor tissues. Ultimately, AIE/Biotin-M systemically inhibited tumor growth and metastasis upon US irradiation. This study presents a facile approach to the development of AIE nanosonosensitizers for cancer SDT.