Mn(iii)-mediated carbon-centered radicals generate an enhanced immunotherapeutic effect.

A strategy for designing cancer therapeutic nanovaccines based on immunogenic cell death (ICD)-inducing therapeutic modalities is particularly attractive for optimal therapeutic efficacy. In this work, a highly effective cancer therapeutic nanovaccine (denoted as MPL@ICC) based on immunogenic photodynamic therapy (PDT) was rationally designed and fabricated. MPL@ICC was composed of a nanovehicle of MnO2 modified with a host-guest complex using amino pillar[6]arene and lactose-pyridine, a prodrug of isoniazid (INH), and chlorine e6 (Ce6). The nanovaccine exhibited excellent biosafety, good targeting ability to hepatoma cells and enrichment at tumor sites. Most importantly, it could modulate the tumor microenvironment (TME) to facilitate the existence of Mn(iii) and Mn(iii)-mediated carbon-centered radical generation with INH released from the prodrug in situ to further strengthen ICD. This is the first report on Mn(iii)-mediated generation of carbon-centered radicals for successful anti-tumor immunotherapy using ICD, which provides a novel strategy for designing highly efficient cancer therapeutic nanovaccines.

Immune cell-derived exosomes as promising tools for cancer therapy.

Exosomes are nanoscale vesicles with a size of 30-150 nm secreted by living cells. They are vital players in cellular communication as they can transport proteins, nucleic acids, lipids, and etc. Immune cell-derived exosomes (imEXOs) have great potential for tumor therapy because they have many of the same functions as their parent cells. Especially, imEXOs display unique constitutive characteristics that are directly involved in tumor therapy. Herein, we begin by the biogenesis, preparation, characterization and cargo loading strategies of imEXOs. Next, we focus on therapeutic potentials of imEXOs from different kinds of immune cells against cancer from preclinical and clinical studies. Finally, we discuss advantages of engineered imEXOs and potential risks of imEXOs in cancer treatment. The advantages of engineered imEXOs are highlighted, including selective killing effect, effective tumor targeting, effective lymph node targeting, immune activation and regulation, and good biosafety.

Electrodeposition of Self-Supported High-Entropy Spinel Oxides for Stable Oxygen Evolution.

Spinel oxides have attracted increasing interest due to their excellent activity in the oxygen evolution reaction (OER). However, despite the high intrinsic OER activity, their poor electrical conductivity and weak structural stability prevented their application for a long time. These shortcomings can be solved by effectively adjusting the electronic structures of spinel oxides through a high-entropy strategy. Herein, a rapid two-step method was developed to prepare self-supported high-entropy spinel-type oxides on a carbon cloth (CC) to yield (Fe0.2Co0.2Ni0.2Mn0.2Cr0.2)3O4@CC (abbreviated as FeCoNiMnCr@CC). The unique electronic structure and stable crystal configuration of the resulting FeCoNiMnCr@CC materials required only an overpotential of 287 mV for the OER at a current density of 10 mA cm-2 coupled with excellent cyclic stability. In summary, the proposed high-entropy strategy looks promising for improving the catalytic performance of spinel oxides.

The reliability of a subtype-determining questionnaire in efficient benign paroxysmal positional vertigo diagnosis in geriatrics.

Introduction: Benign paroxysmal positional vertigo (BPPV), the most common cause of dizziness, especially for older adults, exposes patients to the lethal risk of falling. However, the diagnosis of BPPV in this population can be more elusive as they present few characteristic symptoms. Therefore, we explored the application of a subtype-determining questionnaire in BPPV diagnosis among the geriatric population. Methods: Patients were assigned to the aware and unaware groups. In the aware group, the technician would directly test the suspected canal indicated by the questionnaire, whereas, in the unaware group, the technician performed the regular positional test. The diagnostic parameters of the questionnaire were examined. Results: The accuracy, sensitivity, and specificity of questions 1-3 for diagnosing BPPV were 75.8, 77.6, and 74.7%, respectively. Question 4 demonstrated an accuracy of 75.6% in ascertaining the BPPV subtype, question 5 showed an accuracy of 75.6% in determining the affected side, and question 6 yielded an accuracy of 87.5% in distinguishing canalithiasis or cupulolithiasis. Examination time was shorter in the aware group than that in the unaware group (P < 0.05). No difference was found between the two groups for treatment time (P = 0.153). Conclusion: This subtype-determining questionnaire is practical in daily use and capable of providing instructive information for an efficient diagnosis in geriatric patients with BPPV.

A hyaluronic acid modified cuprous metal-organic complex for reversing multidrug resistance via redox dyshomeostasis.

Multidrug resistance (MDR) which is often related to the overexpression of P-glycoprotein (P-gp) in drug-resistant cancer cells has been a major problem faced by current cancer chemotherapy. Reversing P-gp-related MDR by disrupting tumor redox homeostasis that regulates the expression of P-gp is a promising strategy. In this work, a hyaluronic acid (HA) modified nanoscale cuprous metal-organic complex (HA-CuTT) was developed to reverse P-gp-related MDR via two-way regulated redox dyshomeostasis, which was achieved by both Cu+-catalyzed generation of •OH and disulfide bonds-mediated depletion of glutathione (GSH). In vitro studies reveal that the DOX-loaded complex (HA-CuTT@DOX) has excellent targeting ability to HepG2-ADR cells due to the modification of HA and effectively induces redox dyshomeostasis in HepG2-ADR cells. Moreover, HA-CuTT@DOX can cause mitochondrial damage, decrease ATP level, and downregulate the P-gp expression, thereby leading to the reversal of MDR and the increased drug accumulation in HepG2-ADR cells. Importantly, in vivo experimental results show that it can achieve effective inhibition (89.6 %) of tumor growth in nude mice bearing HepG2-ADR cells. This is the first work to reverse P-gp-related MDR via two-way regulated redox dyshomeostasis based on a HA modified nanoscale cuprous metal-organic complex, providing a new therapeutic paradigm for effective treatment of MDR-related cancer.

An Innovative Tympanoplasty-Sleeve&Tongue Technique.

An innovative tympanoplasty method, blending the merits of traditional overlay and underlay techniques while avoiding the pitfalls. It enhances visualization, facilitates placement of the graft and preserves excellent blood supply, helps secure the fascia in place, as well as preserves the central-dented conical shape of the tympanic membrane. Laryngoscope, 133:3139-3143, 2023.

Significance of subtype-determining questionnaire in efficient diagnosis and treatment of BPPV.

BACKGROUND: Rapid recognition of benign paroxysmal positional vertigo (BPPV) matters in many ways, questionnaires evolve as a new alternative for diagnosis. A subtype-determining questionnaire is a more advanced but rarely studied type. OBJECTIVE: To explore the practicability of a subtype-determining questionnaire in facilitating diagnosis and treatment of BPPV. METHODS: A BPPV subtype-determining questionnaire was applied to vertiginous patients. All patients underwent the positional test, performed by one technician, who was either informed or uninformed about questionnaire results randomly. In the informed group, the technician checked the canal indicated by the questionnaire straightforwardly; in the uninformed group, she performed the conventional positional test. Diagnostic parameters of the questionnaire and disparities between the 2 groups were investigated. RESULTS: The accuracy, sensitivity, specificity of question 1-3 for diagnosing BPPV is 74.4%, 90.9%, 66.6% respectively. Question 4 shows an accuracy of 80.7% in determining BPPV subtype, question 5 yields an accuracy of 78.7% in ascertaining the affected side, question 6 exhibits an accuracy of 87.2% in deciding canalithiasis or cupulolithiasis. Both examination and treatment time were shorter in the informed group (p < .05). CONCLUSION: This subtype-determining questionnaire has appealing diagnostic ability. It provides valuable information that's conducive to fast diagnosis and efficient treatment of BPPV.

Nanococktail Based on Supramolecular Glyco-Assembly for Eradicating Tumors In Vivo.

The development of robust phototherapeutic strategies for eradicating tumors remains a significant challenge in the transfer of cancer phototherapy to clinical practice. Here, a phototherapeutic nanococktail atovaquone/17-dimethylaminoethylamino-17-demethoxygeldanamycin/glyco-BODIPY (ADB) was developed to enhance photodynamic therapy (PDT) and photothermal therapy (PTT) via alleviation of hypoxia and thermal resistance that was constructed using supramolecular self-assembly of glyco-BODIPY (BODIPY-SS-LAC, BSL-1), hypoxia reliever atovaquone (ATO), and heat shock protein inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG). Benefiting from a glyco-targeting and glutathione (GSH) responsive units BSL-1, ADB can be rapidly taken up by hepatoma cells, furthermore the loaded ATO and 17-DMAG can be released in original form into the cytoplasm. Using in vitro and in vivo results, it was confirmed that ADB enhanced the synergetic PDT and PTT upon irradiation using 685 nm near-infrared light (NIR) under a hypoxic tumor microenvironment where ATO can reduce O2 consumption and 17-DMAG can down-regulate HSP90. Moreover, ADB exhibited good biosafety, and tumor eradication in vivo. Hence, this as-developed phototherapeutic nanococktail overcomes the substantial obstacles encountered by phototherapy in tumor treatment and offers a promising approach for the eradication of tumors.

Adhering Low Surface Energy Materials without Surface Pretreatment via Ion-Dipole Interactions.

Low surface energy materials resist adhesion due to their chemical inertness and non-wetting properties. Herein, we report the creation of a transparent ionogel adhesive that uses ion-dipole interactions to achieve a higher bonding performance to polytetrafluoroethylene (PTFE) relative to most commercial glues. The ionogel adhesive is composed of a poly(hexafluorobutyl acrylate-co-methyl methacrylate) random copolymer and a hydrophobic ionic liquid. The prepared ionogel can adhere to various hydrophobic substrates, such as PTFE, polypropylene, and polyethylene, as well as hydrophilic glass, ceramics, and steel. The design strategy and adhesion behavior are well interpreted using the density functional theory calculations and molecular dynamics simulations. The straightforward ultraviolet-curing method, high optical clarity, versatile adhesion ability, and reversible adhesion capabilities make this high-performance adhesive a promising product for commercialization.

LPR: how different diagnostic tools shape the outcomes of treatment.

OBJECTIVE: To seek a deeper and more comprehensive understanding of two major diagnostic methods for laryngopharyngeal reflux by exploring whether and how differences exist before and after treatment between patients diagnosed by either Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) or 24-hour pH monitoring. MATERIALS AND METHODS: Two groups of patients who confirmed laryngopharyngeal reflux disease (LPRD) by either a combination of RSI and RFS (Questionnaire group, 35 patients) or 24-hour multichannel intraluminal impedance (MII) pH monitoring (pH Group, 23 patients) were recruited. All patients were prescribed esomeprazole 20 mg twice a day for 1 month. RSI, RFS, and acoustic parameters before and after treatment were compared between the two groups. Intrinsic correlations involving multiple parameters were investigated as well. RESULTS: Except for excess throat mucus (P = 0.019) and subglottic edema (P = 0.042), most RSI and RFS items before treatment were not significantly different between the Questionnaire and pH Groups, and nearly all such items in both groups exhibited distinct remission after therapy (P < 0.05). Absolute value of remission in RSI after treatment was more prominent in pH Group than in the Questionnaire group (P = 0.007). Jitter (P = 0.252), shimmer (P = 0.815), and harmonics-to-noise ratio (P = 0.117) descended to normal value after treatment. Moderate to high levels of correlation were found between the patient's original status and the absolute value of remission in most items of RSI and RFS as well as voice parameters. CONCLUSION: The 24-hour MII pH monitoring and a combination of RSI and RFS are quite competitive with each other in selecting LPRD patients. Although treatment worked out on nearly all the symptoms, laryngeal images and voice parameters, 24-hour MII pH seems to be more promising in a greater symptom relief. The extent of relief that can take place in most of the measurements is considerably determined by their initial status.

[Current situation and development in treatment of laryngopharyngeal reflux].

The mainstay of treatment of laryngopharyngeal reflux focuses on a concoction involving proton-pump inhibitor and modified beneficial behaviors, sometimes referring to medications like H2-R blocker etc. Therapeutic effect seems to be promising although may at times be challenged by conflict researches. Voice therapy and voice parameters emerge to provide a grand new perspective in treatment and evaluation of this disease.

[Deep neck abscesses accompanied by multiple underlying diseases: 2 case reports].

Patients who complained of pain, tenderness mass in neck, fever, limitation of mouth opening, pharyngalgia,dysphagia,with lab showing increased Neu, remarkably decreased PLT, upsurging Glu, urine-Glu, ALT, T-Bil, AFP, were finally diagnosed to suffer from deep neck abscesses after CT scanning. What was worth mentioning was that diabetes, hepatitis C, thrombocytopenia, and fungus infection added to the complexity of the treatment.