A Dual-Cascade Activatable Near-Infrared Fluorescent Probe for Precise Intraoperative Imaging of Tumor.

Accurate intraoperative tumor delineation is critical to achieving successful surgical outcomes. However, conventional techniques typically suffer from poor specificity and low sensitivity and are time-consuming, which greatly affects intraoperative decision-making. Here, we report a cascade activatable near-infrared fluorescent (NIRF) probe IR780SS@CaP that can sequentially respond to tumor acidity and elevated glutathione levels for accurate intraoperative tumor localization. Compared with nonactivatable and single-factor activatable probes, IR780SS@CaP with a cascade strategy can minimize nonspecific activation and false positive signals in a complicated biological environment, affording a superior tumor-to-normal tissue ratio to facilitate the delineation of abdominal metastases. Small metastatic lesions that were less than 1 mm in diameter can be precisely identified by IR780SS@CaP and completely excised under NIRF imaging guidance. This study could benefit tumor diagnosis and image-guided tumor surgery by providing real-time information and reliable decision support, thus reducing the risk of both recurrence and complications to improve patient outcomes.

Assessing Postoperative Motor Risk in Insular Low-Grade Gliomas Patients: The Potential Role of Presurgery MRI Corticospinal Tract Shape Measures.

BACKGROUND: Insular low-grade gliomas (LGGs) are surgically challenging due to their proximity to critical structures like the corticospinal tract (CST). PURPOSE: This study aims to determine if preoperative CST shape metrics correlate with postoperative motor complications in insular LGG patients. STUDY TYPE: Retrospective. POPULATION: 42 patients (mean age 40.26 ± 10.21 years, 25 male) with insular LGGs. FIELD STRENGTH/SEQUENCE: Imaging was performed using 3.0 Tesla MRI, incorporating T1-weighted magnetization-prepared rapid gradient-echo, T2-weighted space dark-fluid with spin echo (SE), and diffusional kurtosis imaging (DKI) with gradient echo sequences, all integrated with echo planar imaging. ASSESSMENT: Shape metrics of the CST, including span, irregularity, radius, and irregularity of end regions (RER and IER, respectively), were compared between the affected and healthy hemispheres. Total end region radius (TRER) was determined as the sum of RER 1 and RER 2. The relationships between shape metrics and postoperative short-term (4 weeks) and long-term (>8 weeks) motor disturbances assessing by British Medical Research Council grading system, was analyzed using multivariable regression models. STATISTICAL TESTING: Paired t-tests compared CST metrics between hemispheres. Logistic regression identified associations between these metrics and motor disturbances. The models were developed using all available data and there was no independent validation dataset. Significance was set at P < 0.05. RESULTS: Short-term motor disturbance risk was significantly related to TRER (OR = 199.57). Long-term risk significantly correlated with IER 1 (OR = 59.84), confirmed as a significant marker with an AUC of 0.78. Furthermore, the CST on the affected side significantly had the greater irregularity, larger TRER and RER 1, and smaller span compared to the healthy side. DATA CONCLUSION: Preoperative evaluation of TRER and IER 1 metrics in the CST may serve as a tool for assessing the risk of postoperative motor complications in insular LGG patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Exploring MGMT methylation-driven structural connectivity changes in insular gliomas: a tractography and graph theoretical analysis.

OBJECTIVES: This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. METHODS: We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. RESULTS: The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. CONCLUSION: Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.

Efficacy of Acupuncture for Chronic Spontaneous Urticaria : A Randomized Controlled Trial.

BACKGROUND: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. OBJECTIVE: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. DESIGN: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994). SETTING: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. PARTICIPANTS: 330 participants diagnosed with CSU. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). MEASUREMENTS: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. RESULTS: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. LIMITATION: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. CONCLUSION: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province.

Post-Remedial Oxygen Supply: A New Perspective on Photodynamic Therapy to Suppress Tumor Metastasis.

Photodynamic therapy (PDT) holds great promise in tumor therapy due to high safety, efficacy, and specificity. However, the risk of increased metastasis in hypoxic tumors after oxygen-dependent PDT remains underestimated. Here, we propose a post-PDT oxygen supply (POS) strategy to reduce the risk of metastasis. Herein, biocompatible and tumor-targeting Ce6@BSA and PFC@BSA nanoparticles were constructed for PDT and POS in a 4T1-orthotropic breast cancer model. PDT with Ce6@BSA nanoparticles increased tumor metastasis via the HIF-1α signaling pathway, whereas POS significantly reduced the PDT-triggered metastasis by blocking this pathway. Furthermore, POS, with clinical protocols and an FDA-approved photosensitizer (hypericin), and oxygen inhalation reduced PDT-induced metastasis. Our study findings indicate that PDT may increase the risk of tumor metastasis and that POS may solve this problem. POS can reduce the metastasis resulting not only from PDT but also from other oxygen-dependent treatments such as radiotherapy and sonodynamic therapy.

An Activatable Near-Infrared Fluorescent Probe for Precise Detection of the Pulmonary Metastatic Tumors: A Traditional Molecule Having a Stunning Turn.

An accurate detection of lung metastasis is of great significance for making better treatment choices and improving cancer prognosis, but remains a big challenge in clinical practice. In this study, we propose a reinventing strategy to develop a pH-activatable near-infrared (NIR) fluorescent nanoprobe, pulmonary metastasis tracer (denoted as PMT), based on assembly of NIR dye IR780 and calcium phosphate (CaP). By delicately tuning the intermolecular interactions during the assembly process and dye doping content, as well as the synthetic condition of probe, the fluorescence of PMT could be finely adjusted via the tumor acidity-triggered disassembly. Notably, the selected PMT9 could sharply convert subtle pH variations into a distinct fluorescence signal to generate high fluorescence ON/OFF contrast, dramatically reducing the background signals. Benefiting from such preferable features, PMT9 is able to precisely identify not only the tumor sites in orthotopic lung cancer models but also the pulmonary metastases in mice with remarkable signal-to-background ratio (SBR). This study provides a unique strategy to turn shortcomings of traditional dye IR780 during in vivo imaging into advantages and further expand the application of fluorescent probe to image lung associated tumor lesions.

A Potent Strategy of Combinational Blow Toward Enhanced Cancer Chemo-Photodynamic Therapy via Sustainable GSH Elimination.

Excessive glutathione (GSH), which is produced owing to abnormal metabolism of tumor cells, scavenges photo-induced reactive oxygen species (ROS) and consumes chemotherapeutic drugs, thereby attenuating the efficacy of photodynamic therapy and chemotherapy, respectively. Predominant strategies for GSH inhibition involve its chemical depletion, which only leads to a temporary therapeutic effect because GSH is replenished via various compensatory routes in tumor cells. Here, a versatile GSH-inhibiting nanosystem (termed PCNPs) for persistent synergistic therapy of cancer is reported. The porous skeleton of PCNPs allows easy encapsulation of buthionine sulfoximine (BSO) to sustainably suppress the biosynthesis of GSH. Thus, PCNPs not only demonstrate a prolonged release of BSO and improve drug utilization for efficient chemotherapy, but also act as an efficient photo-induced singlet oxygen radical generator that prevents the loss of ROS, thereby enhancing photodynamic therapy. In addition, the liposomal coating prevents cargo release in the blood, improves the accumulation of PCNPs at the tumor site, and promotes the cellular uptake of oxaliplatin and BSO. This strategy is applicable to ROS-based therapy and chemotherapy, which are suppressed by GSH, and may further enhance the synergistic effect of GSH-restrained therapy.

Rabies Virus-Inspired Metal-Organic Frameworks (MOFs) for Targeted Imaging and Chemotherapy of Glioma.

The blood-brain barrier (BBB) restricts access to the brain of more than 98 % of therapeutic agents and is largely responsible for treatment failure of glioblastoma multiforme (GBM). Therefore, it is of great importance to develop a safe and efficient strategy for more effective drug delivery across the BBB into the brain. Inspired by the extraordinary capability of rabies virus (RABV) to enter the central nervous system, we report the development and evaluation of the metal-organic framework-based nanocarrier MILB@LR, which closely mimicked both the bullet-shape structure and surface functions of natural RABV. MILB@LR benefited from a more comprehensive RABV-mimic strategy than mimicking individual features of RABV and exhibited significantly enhanced BBB penetration and brain tumor targeting. MILB@LR also displayed superior inhibition of tumor growth when loaded with oxaliplatin. The results demonstrated that MILB@LR may be valuable for GBM targeting and treatment.

Theoretical Study of the Histidine-catalyzed Asymmetric Aldol Reaction of Acetone and Benzaldehyde.

The mechanism of histidine-catalyzed asymmetrical aldol reaction of acetone with benzaldehyde was studied by using B3LYP method of density functional theory at the levels of 6-31G(d,p) and cc-pvdz basis sets. The calculation results showed that the reaction mechanism included four steps: (I) nucleophilic attack of histidine on acetone to form alcohol intermediate Inter-A through the transition state TS1 (considered a rate control step because the activation energy (49.95 kcal/mol) was relatively high); (II) dehydration of the alcohol intermediate to form the cis- or trans-enamine through the transition states TS3 and TS4 with the energy barriers of 36.12 and 38.15 kcal/mol; (III) electrophilic addition of cis-enamine or trans-enamine with benzaldehyde to form imine Inter-C or Inter-E through the transition states TS8, TS9, TS10, and TS11 (energy barriers 18.43, 22.34, 13.24, and 13.24 kcal/mol, respectively); (IV) after combination of the imine intermediate with water through the transition states TS12, TS13, TS14, and TS15 (energy barriers 22.79, 34.6, 28.2, 25.12 kcal/mol, respectively), removal of the histidine catalys to obtain the final S or R aldol product. Through analyzing the potential energy profile of reaction, we found that the histidine-catalyzed reaction of acetone with benzaldehyde was more energetically favorable to obtain the R-product (ee value >99%). Solvent effects computed with a polarizable continuum model (PCM) indicated that the DMSO and water can reduce the reaction energy barrier.

[Clinical characteristics and GAA gene mutation in children with glycogen storage disease type II: an analysis of 3 cases].

Glycogen storage disease type II (GSD II) is an autosomal recessive disorder caused by a deficiency of the lysosomal glycogen-hydrolyzing enzyme acid α-glucosidase (GAA) and can affect multiple systems including the heart and skeletal muscle. The aim of this study was to investigate three children with GSD II confirmed by GAA gene analysis and to report their clinical characteristics and gene mutations. One case was classified as infantile-onset GSD II, and two cases as late-onset GSD II. The infantile-onset patient (aged 4 months) showed no weight increase and had dyspnea, muscle hypotonia, and increased alanine aminotransferase and creatine kinase; echocardiography showed hypertrophic cardiomyopathy. The late-onset patients (aged 8 years and 13 years respectively) showed persistently elevated liver enzymes; one of them had recurrent respiratory tract infection and restrictive ventilation disorder, and the other case showed significantly increased creatase but normal electromyographic findings. Peripheral blood genetic testing for GAA gene showed six pathogenic mutations in the three cases, and the mutations c.2738C>T and c.568C>T had not been reported. Therefore, peripheral blood genetic testing for GAA gene is an effective diagnostic method.

Prenatal diagnosis of Berry syndrome by fetal echocardiography: a case report.

We report a case in which Berry syndrome is diagnosed by fetal echocardiography. Fetal echocardiography showed that the ascending aorta, main pulmonary artery, left pulmonary artery, and right pulmonary artery were presented as a vascular complexity in the three vessels and pulmonary arterial branches view.

High-temperature inhibition of biosynthesis and transportation of anthocyanins results in the poor red coloration in red-fleshed Actinidia chinensis.

In plants, the role of anthocyanins trafficking in response to high temperature has been rarely studied, and therefore poorly understood. Red-fleshed kiwifruit has stimulated the world kiwifruit industry owing to its appealing color. However, fruit in warmer climates have been found to have poor flesh coloration, and the factors responsible for this response remain elusive. Partial correlation and regression analysis confirmed that accumulative temperatures above 25 °C (T25) was one of the dominant factors inhibiting anthocyanin accumulation in red-fleshed Actinidia chinensis, 'Hongyang'. Expression of structural genes, AcMRP and AcMYB1 in inner pericarp sampled from the two high altitudes (low temperature area), was notably higher than the low altitude (high temperature area) during fruit coloration. AcMYB1 and structural genes coordinate expression supported the MYB-bHLH (basic helix-loop-helix)-WD40 regulatory complex mediated downregulation of anthocyanin biosynthesis induced by high temperatures in kiwifruit. Moreover, cytological observations using the light and transmission electronic microscopy showed that there were a series of anthocyanic vacuolar inclusion (AVI)-like structures involved in their vacuolization process and dissolution of the pigmented bodies inside cells of fruit inner pericarp. Anthocyanin transport was inhibited by high temperature via retardation of vacuolization or reduction in AIV-like structure formation. Our findings strongly suggested that complex multimechanisms influenced the effects of high temperature on red-fleshed kiwifruit coloration.

Genetic diversity and evolution of two capsid protein genes of citrus tristeza virus isolates from China.

The genetic diversity and population structure of citrus tristeza virus (CTV) isolates from China were investigated based on partial sequences spanning the C-terminal end of p61 and the complete sequences of the CPm and CP genes. Phylogenetic analysis revealed five known groups (RB, T30, T36, HA and VT) and one new group (VI) consisting of only Chinese CTV isolates. Incongruent phylogenetic trees coupled with recombination analysis suggested several recombination events in the CPm gene. Positive selection was detected at codon 9 of CPm and codons 31, 41 and 68 of CP. The widespread CTV subpopulation AT-1 found in China has a unique amino acid insertion at the C-terminus of p61, which could increase CTV population complexity with implications for the evolutionary history of the virus. Our results suggest relevant roles for gene flow, purifying selection and recombination in shaping the CTV population in China.

Levels, composition profiles and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in sludge from ten textile dyeing plants.

As components of synthetic dyes, polycyclic aromatic hydrocarbons (PAHs) are present as contaminants in textile dyeing sludge due to the recalcitrance in wastewater treatment process, which may pose a threat to environment in the process of sludge disposal. In order to evaluate PAHs in textile dyeing sludge, comprehensive investigation comprising 10 textile dyeing plants was undertaken. Levels, composition profiles and risk assessment of 16 EPA-priority PAHs were analyzed in this study. The total concentrations of 16 PAHs (∑16 PAHs) varied from 1463 ± 177 ng g(-1) to 16,714 ± 1,507 ng g(-1) with a mean value of 6386 ng g(-1). The composition profiles of PAHs were characterized by 3- and 4-ring PAHs, among which phenanthrene, anthracene and fluoranthene were the most dominant components. The mean benzo[a]pyrene equivalent (BaPeq) concentration of ∑16 PAHs in textile dyeing sludge was 423 ng g(-1), which was 2-3 times higher than concentrations reported for urban soil. According to ecological risk assessment, the levels of PAHs in the textile dyeing sludge may cause a significant risk to soil ecosystem after landfill or dumping on soil.

Light-Activated In Situ Vaccine with Enhanced Cytotoxic T Lymphocyte Infiltration and Function for Potent Cancer Immunotherapy.

In situ cancer vaccination is an attractive strategy that stimulates protective antitumor immunity. Cytotoxic T lymphocytes (CTLs) are major mediators of the adaptive immune defenses, with critical roles in antitumor immune response and establishing immune memory, and are consequently extremely important for in situ vaccines to generate systemic and lasting antitumor efficacy. However, the dense extracellular matrix and hypoxia in solid tumors severely impede the infiltration and function of CTLs, ultimately compromising the efficacy of in situ cancer vaccines. To address this issue, a robust in situ cancer vaccine, Au@MnO2 nanoparticles (AMOPs), based on a gold nanoparticle core coated with a manganese dioxide shell is developed. The AMOPs modulated the unfavorable tumor microenvironment (TME) to restore CTLs infiltration and function and efficiently induced immunogenic cell death. The Mn2+-mediated stimulator of the interferon genes pathway can be activated to further augment the therapeutic efficacy of the AMOPs. Thus, the AMOPs vaccine successfully elicited long-lasting antitumor immunity to considerably inhibit primary, recurrent, and metastatic tumors. This study not only highlights the importance of revitalizing CTLs efficacy against solid tumors but also makes progress toward overcoming TME barriers for sustained antitumor immunity.

Regulation of Glandular Size and Phytoalexin Biosynthesis by a Negative Feedback Loop in Cotton.

Plants have evolved diverse defense mechanisms encompassing physical and chemical barriers. Cotton pigment glands are known for containing various defense metabolites, but the precise regulation of gland size to modulate defense compound levels remains enigmatic. Here, it is discovered that the VQ domain-containing protein JAVL negatively regulates pigment gland size and the biosynthesis of defense compounds, while the MYC2-like transcription factor GoPGF has the opposite effect. Notably, GoPGF directly activates the expression of JAVL, whereas JAVL suppresses GoPGF transcription, establishing a negative feedback loop that maintains the expression homeostasis between GoPGF and JAVL. Furthermore, it is observed that JAVL negatively regulates jasmonate levels by inhibiting the expression of jasmonate biosynthetic genes and interacting with GoPGF to attenuate its activation effects, thereby maintaining homeostatic regulation of jasmonate levels. The increased expression ratio of GoPGF to JAVL leads to enlarged pigment glands and elevated jasmonates and defense compounds, enhancing insect and pathogen resistance in cotton. These findings unveil a new mechanism for regulating gland size and secondary metabolites biosynthesis, providing innovative strategies for strengthening plant defense.

The Uptake and Distribution Evidence of Nano- and Microplastics in vivo after a Single High Dose of Oral Exposure.

Objective: Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo. Methods: Fluorescent microspheres (100 nm, 3 µm, and 10 µm) were given once at a dose of 200 mg/(kg∙body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings. Results: In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group ( P < 0.05). In the 3 µm group, the FI only increased in the lung at 2 h ( P < 0.05). In the 10 µm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h ( P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed. Conclusion: Nanoplastics translocated rapidly to observed organs/tissues through blood circulation; however, only small amounts of MPs could penetrate the organs.

[Roles of cardiac mast cells and Toll-like receptor 4 in viral myocarditis among mice].

OBJECTIVE: To investigate the role and significance of cardiac mast cells and Toll-like receptor 4 (TLR4) in the development and progression of viral myocarditis (VMC). METHODS: Forty-eight Balb/c mice were randomly divided into a control group (n=24) and a model group (n=24). Coxsackievirus B3 was intraperitoneally injected into the model group mice to establish a VMC model. In each group, cardiac tissues were collected from 8 mice at 7, 14 and 28 days after the model was established. The cardiac tissues were stained with hematoxylin and eosin as well as Masson trichrome to observe pathological changes in cardiac tissues. The number and degranulation of cardiac mast cells at each time point were measured and evaluated by toluidine blue staining and transmission electron microscopy. The mRNA and protein expression of TLR4 in cardiac tissues was measured by RT-PCR and immunohistochemistry. In the model group, the correlation between number of cardiac mast cells and mRNA expression of TLR4 at all time points was analyzed. RESULTS: The model group had significantly higher pathological scores of cardiac tissues than the control group at all time points (P<0.05). The myocardial collagen volume fraction in the model group at 28 days was significantly higher than in the control group at all time points and higher than in the model group at 7 and 14 days (P<0.05). At each time point, the model group had a significantly increased number of mast cells (P<0.05), and significantly increased mRNA and protein expression of TLR4 (P<0.05) compared with the control group. In the model group, the number of cardiac mast cells was positively correlated with the mRNA expression of TLR4 at all time points (R²=0.877, P<0.05). CONCLUSIONS: Mice with VMC have significantly increased numbers of cardiac mast cells and expression of TLR4 compared with control mice at all time points, suggesting that mast cells and TLR4 may play important roles in the inflammatory response and fibrosis of VMC.

The efficacy of cryogenic plasma tonsillectomy in the treatment of obstructive sleep apnea-hypopnea syndrome in children: A meta-analysis.

BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) refers to the apnea and hypopnea caused by partial or complete obstruction of the upper airway collapse during sleep. The cryogenic plasma tonsillectomy is mostly used for the clinical treatment of children with OSAHS. AIMS: The objective of this meta-analysis is to investigate the clinical efficacy of cryogenic plasma tonsillectomy for OSAHS in children. MATERIALS & METHODS: The literature search was conducted through China National Knowledge Infrastructure (CNKI), Wanfang Database, Embase, PubMed, and Web of Science databases. The search was from the establishment of each database to June 2022. Randomized controlled trials (RCTs) meeting the criteria for partial/total cryo-plasma tonsillectomy for treating patients with obstructive sleep apnea-hypopnea syndrome in children were included, with data extracted. The meta-analysis was performed using the Stata 16.0 and Review Manager 5.4. Seven RCTs were included in this study. RESULTS: The results showed that the partial/complete cryo-plasma tonsillectomy in the experimental group had a better therapeutical effective rate than the control group of patients treated with conventional surgery [Odds ratio (OR) = 2.181, 95% CI: 1.306-3.645, P < 0.05]. Also, in terms of postoperative adverse reactions, the number of adverse reactions in the experimental group was significantly lower than in the control group (OR = 0.445, 95% CI: 0.287-0.689, P = 0.001). The analysis of surgical efficacy showed that the operative time, intraoperative blood loss, and postoperative pain score were all significantly lower than those of the control group. Furthermore, further analysis of the apnea-hypopnea index (AHI) and the lowest oxygen saturation (LSaO2) of the two groups showed that the cryo-plasma tonsillectomy treatment had higher LSaO2 levels than conventional treatment [Standardized mean difference (SMD) = 0.380, 95% CI: 0.094-0.667, P = 0.009]. CONCLUSION: The application of cryo-plasma tonsillectomy can significantly improve the treatment effect of OSAHS, reducing adverse reactions.

Sonodynamic-immunomodulatory nanostimulators activate pyroptosis and remodel tumor microenvironment for enhanced tumor immunotherapy.

Rationale: Spatiotemporal control of pyroptosis has a profound impact on cancer immunotherapy. Owing to the precise spatiotemporal control and reduction in the side effects of ultrasound (US), sonodynamic therapy (SDT) is expected to be a promising mean to activate pyroptosis. Furthermore, the pyroptosis-initiated immune response can be amplified by enhanced lymphocyte infiltration occurring due to extracellular matrix (ECM) depletion. Therefore, it is highly desirable to develop a sonodynamic-immunomodulatory strategy to amplify pyroptosis-mediated tumor immunotherapy by remodeling of the tumor microenvironment, thereby enhancing tumor immunotherapy. Methods: We reported a potent strategy based on a sonosensitizer, which is composed of LY364947-loaded porous coordination network (PCN-224) camouflaged with a red blood cell (RBC) membrane and evaluated pyroptosis activation, collagen depletion, immunocyte infiltration, and adaptive immune response during the pyroptosis-initiated immune response in vitro and in vivo. Results: The sonosensitizer generated reactive oxygen species (ROS) under US irradiation and initiated the caspase-3 apoptotic signaling pathway, which is regarded as the key upstream activator of gasdermin E (GSDME)-mediated pyroptosis. During the subsequent anti-tumor immune response mediated by pyroptosis, LY364947 loosened the ECM structure via collagen depletion, resulting in enhanced T-lymphocyte infiltration and nearly complete eradication of tumors in a mouse model with the formation of immunological memory. Conclusion: Our findings indicate that sonodynamic-immunomodulatory pyroptotic strategy exhibits robust anti-tumor immune efficacy as well as provides novel insights into the role of pyroptosis in cancer immunology.