Flexocatalysis Enhances Tumor Photodynamic Therapy.

Photodynamic therapy (PDT) is long-standing suffered from elevated tumor interstitial fluid pressure (TIFP) and prevalent hypoxic microenvironment within the solid malignancies. Herein, sound-activated flexocatalysis is developed to overcome the dilemma of PDT through both enhancing tumor penetration of photosensitizers by reducing TIFP and establishing an oxygen-rich microenvironment. In detail, a Schottky junction is constructed by flexocatalyst MoSe2 nanoflowers and Pt. Subsequently, the Schottky junction is loaded with the photosensitizer indocyanine green (ICG) and encapsulated within tumor cytomembrane to constitute a bionic-flexocatalytic nanomedicine (MPI@M). After targeting the tumor, MPI@M orchestrates flexocatalytic water splitting in tumor interstitial fluid under acoustic stimulation to lower TIFP, which boosted the tumor penetration of ICG. Concurrently, the oxygen released from the flexocatalytic water splitting overcomes the limitation of hypoxia against PDT. Furthermore, superfluous singlet oxygen generated by PDT can induce mitochondrial dysfunction for further tumor cell apoptosis. After 60 min of flexocatalysis, both the 30% decrease of TIFP and the relieved tumor hypoxia are observed, significantly promoting the therapeutic effect of PDT. Consequently, MoSe2/Pt junction nanoflowers, with the excellent flexocatalytic performance, hold significant potential for future applications in biocatalytic cancer therapies.

Development of porous materials via protein/polysaccharides/polyphenols nanoparticles stabilized Pickering high internal phase emulsions for adsorption of Pb2+ and Cu2+ ions.

The porous materials (PM) were prepared by the Pickering high internal phase emulsion (PHIPE) template. Firstly, the nanoparticles named as ZHMNPs or MZHMNPs were fabricated based on zein, Hohenbuehelia serotina polysaccharides and Malus baccata (Linn.) Borkh polyphenols without or with Maillard reaction, the average particle sizes and zeta potentials of which were distributed in a range of 718.1-979.4 nm and -21.6-25.2 mV. ZHMNPs possessed the relatively uniform spherical morphology, while MZHMNPs were irregular in shape. With ZHMNPs or MZHMNPs serving as the stabilizers, the PHIPEs were prepared, and exhibited the good viscoelasticity and excellent storage and freeze-thaw stabilities. Based on above PHIPEs template, the constructed PM possessed the large specific surface area and uniform pore structure. Through the investigations of adsorption performances, PM showed the outstanding adsorption capacities on Pb2+ and Cu2+ ions regardless of dissolving in deionized water or simulated gastrointestinal digestive fluid. Furthermore, the results also showed that the pH, temperature and adsorbent dosage had certain impacts on the adsorption performances of PM on Pb2+ and Cu2+ ions.

The U-Shaped association between age and distant metastasis in patients with papillary thyroid carcinoma.

PURPOSE: To investigate the association between age distribution and synchronous distant metastasis of papillary thyroid carcinoma. METHOD: Patients with PTC who were treated from January 2013 to December 2018 at a single institute in a cancer referral center in China were retrospectively reviewed. A logistic regression model with restricted cubic splines (RCS) was used to examine the association between age at diagnosis and synchronous distant metastasis. RESULTS: A total of 111 patients (0.7%) were diagnosed with distant metastasis. The logistic regression model with RCS revealed a "U-shape" association between age and distant metastasis. The RCS curve suggested a U-shaped pattern. The multivariable regression analysis showed that patients in the age groups ≤21 years (OR 2.33, 95% CI 1.09-4.68, P = 0.022) and >55 years (OR 3.32, 95% CI 1.99-5.46, P < 0.001) had a significantly higher incidence of distant metastasis than patients in the age group of 22 to 55 years. CONCLUSIONS: A U-shaped association was observed between age at diagnosis and synchronous distant metastasis in papillary thyroid carcinoma patients.

Molecular Modeling of the Fluorination Effect on the Penetration of Nanoparticles across Lipid Bilayers.

The fluorinated decorations have recently been widely used in many biomedical applications. However, the potential mechanism of the fluorination effect on the cellular delivery of nanoparticles (NPs) still remains elusive. In this work, we systemically explore the penetration of a perfluoro-octanethiol-coated gold NP (PF-Au NP) and, for comparison, an octanethiol-coated gold NP (OT-Au NP) across lipid bilayers. We also investigated the effect of these two types of NPs on the properties of lipid bilayers. Our findings indicate that the lipid type and the surface tension of the lipid bilayer significantly impact the penetration capabilities of the fluorinated gold NP. By examining the distribution of ligands on the surface of the two types of NPs in water and during the penetration process, we unveil their distinct penetration characteristics. Specifically, the PF-Au NP exhibits amphiphobic behavior (both hydrophobic and lipophobic), while the OT-Au NP exhibits solely hydrophobic characteristics. Finally, we observe that the penetration capabilities can be increased by adjusting the degree of fluorination of the ligands on the NP surface. Overall, this study provides useful physical insights into the unique properties of the fluorinated decorations in NP permeation.

The role of targeted therapy and/or immunotherapy therapy in anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a highly invasive malignant tumor with a poor prognosis. Traditional treatment methods have not been effective. However, advancements in targeted therapy and immunotherapy in recent years have shed new light on the management of ATC. The aim of this study was to examine the treatment plan and prognostic factors of ATC. METHODS: This study conducted a retrospective analysis of ATC patients who received treatment at our institution between 2000 and 2023 to evaluate the clinical characteristics, treatment methods, and factors influencing survival. Survival analysis was performed by the Kaplan‒Meier method and log-rank test, and multivariate analysis was performed using the Cox proportional hazard model. RESULTS: The 6-month and 1-year disease-specific OS rates were 49% and 29%, respectively. The presence of clinical symptoms and the timing of treatment significantly impacted patient prognosis (P < 0.05). Compared with surgery + radiotherapy/chemotherapy and only surgery, targeted therapy and targeted + immunotherapy represented an improved overall survival, The 6-month/1-year survival rates of which were 81%/61% and 91%/73% (P < 0.05), respectively. Multivariate analysis indicated that the symptoms at initial diagnosis, year of presentation, performance status and treatment plan were independent factors affecting the prognosis. The year of presentation (P = 0.048) and the treatment plan (P = 0.038) were significantly meaningful in predicting prognosis. CONCLUSION: Targeted therapy and targeted+immune therapy can effectively prolong the survival period of ATC patients. Symptoms at initial diagnosis and treatment plan have a significant impact on the prognosis.

The frequency of risk pathological characteristics in clinically low-risk papillary thyroid microcarcinoma suitable for active surveillance.

PURPOSE: Active surveillance has emerged as an initial management strategy for patients with low-risk papillary thyroid microcarcinoma (PTMC). The main objective of this research was to investigate the frequency of risk pathological characteristics among patients with clinically low-risk PTMC who are suitable for Active Surveillance. METHODS: A retrospective review was conducted on patients who underwent lobectomy for PTMC between January 2013 and December 2018. Patients with bilateral tumors, macroscopic multifocal tumors, macroscopic extrathyroidal extension (ETE), clinical lymph node metastases, macroscopic extranodal extension (ENE), distant metastases, a history of neck radiation or familial thyroid cancer were excluded. Pathological characteristics were collected from the postoperative pathological results. Aggressive variants, multifocality, ETE, lymphovascular invasion (LVI), perineural invasion (PNI), metastatic lymph nodes (LNs) ≥ 5, and ENE were defined as risk characteristics. RESULTS: The study included 4923 patients, of whom 1229 (25.0%) were male. The mean age was 43 years. A total of 2250 patients (45.7%) exhibited risk characteristics. Among them, 15 patients presented with aggressive variants, and 1813 patients (36.8%) had ETE. Multifocality, LVI, and PNI were observed in 551 (11.2%), 21 (0.4%), and 40 (0.8%) patients, respectively. A total of 139 patients (2.8%) had five or more metastatic LNs, and ENE was identified in 140 patients. Notably, 172 patients (3.5%) fulfilled the criteria for completion thyroidectomy, as they had aggressive variants, LVI, or five or more metastatic LNs. CONCLUSIONS: Nearly half of the patients diagnosed with clinically low-risk PTMC exhibited risk pathological characteristics, and a small proportion of patients met the criteria for completion thyroidectomy.

[Associations of a mixture of eleven endocrine disruptors in human urine with the risk of papillary thyroid cancer].

OBJECTIVE: To examine the associations of human exposure to a mixture of 11 endocrine disruptors(EDCs) with the risk of papillary thyroid cancer(PTC), and to identify the priority of these EDCs. METHODS: EDCs were determined in fasting urine specimens to represent human exposure. Logistics regressions were performed to examine the associations between individual EDC and PTC risk. Bayes kernel machine regression was applied to examine the associations between the mixture of EDCs and PTC risk. Weighted quantile sum(WQS) regression and LASSO regression were performed to identify the main contributor. RESULTS: In the multivariate logistic regression model, after adjusting for a series of variables, 11 endocrine disruptors were statistically significantly correlated with the risk of PTC(P<0.05). In BKMR models, the mixture of EDCs was positively correlated with the risk of PTC(P<0.05). The weight and coefficient of mono(2-ethyl-5-hydroxyhexyl) phthalate(MEHHP) was 0.62 and 1.58 in WQS and LASSO models, respectively, which were much higher than those of the other EDCs. CONCLUSION: Combined exposure to o a variety of EDCs might promote the risk of PTC, and MEHHP was identified as the main contributor.

A prediction model for identifying high-risk lymph node metastasis in clinical low-risk papillary thyroid microcarcinoma.

BACKGROUND: The presence of high-volume lymph node metastasis (LNM) and extranodal extension (ENE) greatly increases the risk of recurrence in patients with low-risk papillary thyroid microcarcinoma (PTMC). The goal of this research was to analyze the factors that contribute to high-risk lymph node metastasis in patients with low-risk PTMC. METHODS: We analyzed the records of 7344 patients who were diagnosed with low-risk PTMC and treated at our center from January 2013 to June 2018.LNM with a high volume or ENE was classified as high-risk lymph node metastasis (hr-LNM). A logistic regression analysis was conducted to identify the risk factors associated with hr-LNM. A nomogram was created and verified using risk factors obtained from LASSO regression analysis, to predict the likelihood of hr-LNM. RESULTS: The rate of hr-LNM was 6.5%. LASSO regression revealed six variables that independently contribute to hr-LNM: sex, age, tumor size, tumor location, Hashimoto's thyroiditis (HT), and microscopic capsular invasion. A predictive nomogram was developed by integrating these risk factors, demonstrating its excellent performance. Upon analyzing the receiver operating characteristic (ROC) curve for predicting hr-LNM, it was observed that the area under the curve (AUC) had a value of 0.745 and 0.730 in the training and testing groups showed strong agreement, affirming great reliability. CONCLUSION: Sex, age, tumor size, tumor location, HT, and microscopic capsular invasion were determined to be key factors associated with hr-LNM in low-risk PTMC. Utilizing these factors, a nomogram was developed to evaluate the risk of hr-LNM in patients with low-risk PTMC.

Cascaded Antitumor Therapy Excited by Dual Nanozymes Based on Energy Restriction and Photocatalysis.

In nanocatalytic medicine, drugs can be transformed into toxic components through highly selective and highly specific catalytic reactions in the tumor microenvironment, avoiding toxic side effects on normal tissues. Due to the coexistence of Ce3+ and Ce4+, CeO2 is endowed with dual nanozyme activities. Herein, CeO2 nanoparticles served as templates to construct a biomimetic nanodrug delivery system (C/CeO2@M) by electrostatic adsorption of carbon quantum dots (CQDs) and coating a homologous tumor cytomembrane. After homologous targeting to tumors, the CQDs emitted 350-600 nm light under 660 nm laser irradiation by upconversion luminescence, which caused a CeO2-mediated photocatalytic reaction to generate reactive oxygen species. The catalase-like activity of CeO2-enabled converting excess H2O2 to O2, which not only alleviated tumor hypoxia and promoted intratumor drug delivery but also provided substrates for subsequent catalytic reactions. Meanwhile, the phosphatase activity of CeO2 could consume adenosine triphosphate (ATP) to block the energy supply for tumor cells, thus limiting cell proliferation and metastasis. The strategy of energy restriction and photocatalysis of dual nanozyme stimulation offers great potentials in enhancing drug penetration and eradicating solid tumors.

CT-based quantification of trachea shape to detect invasion by thyroid cancer.

OBJECTIVE: This study aims to develop a CT-based method for quantifying tracheal shape and evaluating its ability to distinguish between cases with or without tracheal invasion in patients with thyroid carcinoma. METHODS: A total of 116 quantitative shape features, including 56 geometric moments and 60 bounding shape features, were defined. The tracheal lumen was semi-automatically defined with a CT threshold of less than - 500 HU. Three contiguous slices with the 1st, 2nd, and 3rd smallest trachea lumen areas were contiguously selected, and the appropriate number of slices to be included was determined. Fifty-six patients with differentiated thyroid carcinoma (DTC) invading the trachea and 22 patients with DTC but without invasion were retrospectively included. A receiver operating characteristic (ROC) curve was applied to select the representative shape features and determine the optimal threshold. RESULTS: 23.3%, 25.9%, and 24.1% of the features displayed an area under the ROC curve (AUC) ≥ 0.800 when derived from 1, 2, and 3 slices, respectively. Calculating feature values from two slices with the 1st and 2nd smallest tracheal lumen area were considered appropriate. Six final features, including 3 geometric moments and 3 bounding shape features, were selected to determine the tracheal invasion status of DTC and displayed AUCs of 0.875-0.918, accuracies of 0.821-0.891, sensitivities of 0.813-0.893, and specificities of 0.818-0.932, outperforming the visual evaluation results. CONCLUSIONS: Geometric moments and bounding shape features can quantify the tracheal shape and are reliable for identifying DTC tracheal invasion. The selected features quantified the extent of tracheal deformity in DTC patients with and without tracheal invasion. CLINICAL RELEVANCE STATEMENT: Six geometric features provide a non-invasive, semi-automated evaluation of the tracheal invasion status of thyroid cancer. KEY POINTS: • A novel method for quantifying tracheal shape using 56 geometric moments and 60 bounding shape features was developed. • Six features identify tracheal invasion by thyroid carcinoma. • The selected features quantified the extent of tracheal deformity in differentiated thyroid carcinoma patients with and without tracheal invasion.

Clinical factors associated with severe surgical complications in patients with hypopharyngeal cancer: a single-center case-cohort study.

BACKGROUND: Surgical complications are a major concern in the surgical treatment of hypopharyngeal cancer. OBJECTIVE: To identify clinical factors that predispose patients with hypopharyngeal cancer to severe surgical complications. MATERIALS AND METHODS: The data of 449 patients who were underwent surgery as a part of the initial treatment with curative intent or as salvage treatment were retrospectively reviewed. The Chi-square test and logistic regression were used to evaluate the association of different factors with severe surgical complications. RESULTS: The incidence of severe complications was 22% (99/449), and 10 patients (2.2%) experienced rupture of the carotid artery. Multivariate analysis identified T3/4 stage (p = .002, odds ratio (OR) = 1.58, 95% confidence interval (CI) 1.177-2.122), radiotherapy (RT) (p < .001, OR = 2.744, 95% CI 1.680-4.482), diabetes mellitus (DM) (p = .007, OR = 2.697, 95% CI 1.308-5.56), and nonprimary closure (p = .008, OR = 1.992, 95% CI 1.193-3.327) as significant risk factors for severe surgical complications. CONCLUSIONS AND SIGNIFICANCE: T3/4 stage, RT, nonprimary closure, and DM were independent predisposing factors for severe surgical complications in our study population of hypopharyngeal cancer patients. Taking measures to lower the tumor stage and simplify the surgical procedure may be crucial in reducing the incidence of severe surgical complications among these patients.

Prognostic Significance of Primary Tumor Surgery in Adenoid Cystic Carcinoma Patients With Distant Metastases at Diagnosis: A Population-Based Database Analysis in Head and Neck Region.

Purpose: Adenoid cystic carcinoma (ACC) is an aggressive cancer that often leads to poor prognosis, especially when it has metastasized. The prognostic significance of primary tumor surgery (PTS) for ACC with distant metastasis (DM) at the time of diagnosis has not been extensively studied. Methods: Using data from the surveillance, epidemiology, and end results (SEER) database from 2010 to 2019, we identified patients with ACC in head and neck region and synchronous DM. We evaluated the effect of PTS on different patterns of metastasis using Kaplan-Meier analysis, log-rank tests, and multivariate Cox regression analysis to assess the therapeutic benefit of PTS in the overall cohort and various subgroups. Results: Of the 192 identified patients with synchronous metastatic ACC of head and neck, 91 (47.4%) underwent PTS. Patients who received PTS had significantly better survival than nonsurgical patients (median overall survival: 19 vs 43 months, P = .006). Cox regression analysis also showed that PTS was associated with improved survival (HR = .46, 95% CI: 0.42-0.88; P = .028). In sub-analyses, except for patients with liver metastases [overall survival (OS), P = .107, cancer-specific survival (CSS), P = .153], PTS consistently conferred significant survival benefits in patients with bone metastases (OS, P = .041, CSS, P = .065) and lung metastases (OS, P = .016, CSS, P = .027). PTS also led to better survival in patients who did not receive radiotherapy (median OS: 13 vs 52 months, P = .007). Conclusion: Our study suggests that PTS in metastatic ACC patients of head and neck improved overall and CSS, particularly in those with bone or lung metastases and those who did not receive radiotherapy. However, further prospective studies are needed to confirm these findings, and the indications for PTS in metastatic ACC should be carefully evaluated by a multidisciplinary board.

Hashimoto's thyroiditis is negatively associated with lymph node metastasis in PTMC.

PURPOSE: The association between Hashimoto's thyroiditis (HT) and lymph node metastasis (LNM) of papillary thyroid microcarcinoma (PTMC) remains poorly understood. We aimed to elucidate the impact of HT on PTMC and its association with LNM. METHODS: A retrospective cohort study was conducted at a single cancer referral center. Patients diagnosed with PTMC and complete clinicopathological results between January 2013 and June 2018 were included. Propensity score matching (PSM) and logistic regression analysis were performed to evaluate the difference in LNM characteristics between patients with and without HT. RESULTS: Among the 9929 PTMC patients, 2389 (24.1%) were pathologically diagnosed with HT. After PSM using variables including age, sex, primary tumor size, central neck dissection, extrathyroidal extension (ETE), gross ETE, multifocality and bilaterality, we identified 2324 pairs of patients for analysis. Patients with HT had a significantly lower incidence of LNM in the central neck (40.9% vs 56.2%, P < 0.001) and lateral neck (11.6% vs 14.2%, P = 0.016), a lower incidence of extranodal extension (ENE) (10.1% vs 17.0%, P < 0.001), fewer positive lymph nodes (median [IQR], 0 [0 to 2] vs 1 [0 to 3], P < 0.001), and a lower lymph node ratio (median [IQR], 0.00 [0.00 to 0.15] vs 0.12 [0.00 to 0.33], P < 0.001) than those without HT. Logistic regression analysis indicated that patients with HT had a significantly reduced risk of CLNM and LLNM compared to those without HT. CONCLUSIONS: Our study indicated a negative association between HT and LNM in PTMC.

A nomogram for predicting lateral lymph node metastasis in cN0 unifocal papillary thyroid microcarcinoma.

BACKGROUND: Identifying risk factors for occult lateral lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of lateral neck dissection (LND). The objective of this study was to develop a nomogram for predicting the probability of LLNM in patients with cN0 unifocal PTMC. METHODS: We conducted a retrospective analyzed a total of 4872 patients with cN0 unifocal PTMC who were treated at our center from January 2013 to June 2018. Logistic regression analysis was used to determine the risk factors for LLNM, and a nomogram was constructed based on these risk factors. RESULTS: The rate of LLNM was 3.2%. Tumors located in the upper lobe(odds ratio [OR] = 2.56, 95% confidence interval [CI] 1.80-3.62; p < 0.001) and size greater than 7 mm (OR = 2.59, 95% CI 1.85-3.62; p < 0.001) had a significantly higher risk of LLNM compared to tumors in the lower or middle lobe and size less than or equal to 7 mm. Tumors with extrathyroidal extension (ETE) had a significantly higher risk of LLNM (OR = 1.41, 95% CI 1.01-1.99; p = 0.044). The presence of three or more central lymph node metastases (CLNMs) (OR = 5.84, 95% CI 3.83-8.93; p < 0.001) or one or two CLNMs (OR = 2.91, 95% CI 1.93-4.42; p < 0.001) also increased the risk of LLNM compared to having no CLNMs. A nomogram incorporating these risk factors was developed, and the receiver operating characteristic (ROC) curve demonstrated an area under the curve (AUC) of 0.777, indicating a high degree of predictive accuracy. CONCLUSION: Tumor location in the upper lobe, greater than 7 mm in size, ETE, and CLNMs, especially three or more, were independent risk factors for LLNM in cN0 unifocal PTMC. The nomogram based on these factors exhibited favorable predictive value and consistency.

Hybrid source translation scanning mode for interior tomography.

Interior tomography is a promising technique that can be used to image large objects with high acquisition efficiency. However, it suffers from truncation artifacts and attenuation value bias due to the contribution from the parts of the object outside the ROI, which compromises its ability of quantitative evaluation in material or biological studies. In this paper, we present a hybrid source translation scanning mode for interior tomography, called hySTCT-where the projections inside the ROI and outside the ROI are finely sampled and coarsely sampled respectively to mitigate truncation artifacts and value bias within the ROI. Inspired by our previous work-virtual projection-based filtered backprojection (V-FBP) algorithm, we develop two reconstruction methods-interpolation V-FBP (iV-FBP) and two-step V-FBP (tV-FBP)-based on the linearity property of the inverse Radon transform for hySTCT reconstruction. The experiments demonstrate that the proposed strategy can effectively suppress truncated artifacts and improve the reconstruction accuracy within the ROI.

Fourteen years old as the best age cutoff to differentiate prepubertal from pubertal papillary thyroid carcinoma.

BACKGROUND: It is unclear whether differences in clinical presentation and/or prognosis exist between prepubertal papillary thyroid cancer (PTC) and pubertal PTC. At present, there is a lack of definition for the appropriate cutoff age to define prepubertal PTC. METHODS: This study retrospectively reviewed 227 pediatric PTC patients (aged ≤18 years) who underwent initial surgery from March 2000 to December 2018. The median duration of follow-up was 85 months (range, 8-258). RESULTS: The age range was basically linearly related to multiple risk factors, such as T3-T4 disease, distant metastasis. Age (p = 0.032) was an independent risk factor for recurrence and persistent disease. Patients aged <14 years had obviously higher rates of extensive disease. The 10-year disease-free survival (DFS) rate of patients aged <14 years was 59.5% and that of patients aged ≥14 years was 82.6% (p = 0.004). CONCLUSIONS: Fourteen years of age may be an appropriate cutoff to differentiate prepubertal PTC from pubertal PTC.

A case-control study of urinary concentrations of bisphenol A, bisphenol F, and bisphenol S and the risk of papillary thyroid cancer.

The incidence of thyroid cancer (TC), especially papillary thyroid cancer (PTC), has dramatically increased globally. Whereas some endocrine disruptors have been linked to neoplastic processes, the associations between human exposure to bisphenol analogs and the risk of TC remain unclear. This present case-control study examined the associations between the urinary concentrations of bisphenol A (BPA) and other bisphenols, namely bisphenol F (BPF) and bisphenol S (BPS), and the risk of PTC. After adjusting for confounders and creatinine standardization, significantly positive associations were observed for BPF (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.27-2.54), but negative associations observed for BPA (OR = 0.38, 95% CI = 0.19-0.77) and BPS (OR = 0.63, 95% CI = 0.43-0.93), in the total population. However, after stratification by age and smoking, statistical significance was retained only in non-smoking women, suggesting the adverse effects of BPF exposure on PTC risk, especially in women. These findings require replication and confirmation in further research.

MoS2 nanoflower-mediated enhanced intratumoral penetration and piezoelectric catalytic therapy.

The absence of lymphatic vessels in tumors leads to the retention of interstitial fluid, and the formation of an inverse pressure difference between the tumor and blood vessels hinders drug delivery deep into the tumor, which leads to tumor recurrence and metastasis. Therefore, we designed a novel strategy to downregulate tumor interstitial fluid pressure (TIFP) by water splitting in the tumor interstitium based on piezoelectric catalysis nanomedicine. First, the chemotherapeutic drug doxorubicin (DOX) was loaded on the piezoelectric catalytic material MoS2 and then encapsulated with tumor cell membrane (CM) to obtain MD@C. MD@C could not only target the tumor through homologous targeting but, more importantly, also triggered piezoelectric catalytic water splitting under ultrasound (US) stimulation; as a result, the TIFPs of U14 and PAN02 tumor-bearing mice were reduced to 57.14% and 45.5%, respectively, and the tumor inhibition rates of MD@C were 96.75% and 99.21%, which increased the perfusion of blood-derived drugs in the tumors. Moreover, the hydroxyl radicals generated by piezoelectric catalysis could effectively inhibit the growth of tumors in combination with DOX. Consequently, the piezoelectric catalytic water splitting strategy of MD@C can enhance drug delivery, providing a new universal platform for the treatment of solid malignant tumors.

A nomogram to predict lateral lymph node metastases in lateral neck in patients with medullary thyroid cancer.

Background: Medullary thyroid cancer (MTC) can only be cured by surgery, but the management of lateral lymph nodes is controversial, especially for patients with cN0+cN1a. To address this challenge, we developed a multivariate logistic regression model to predict lateral lymph node metastases (LNM). Methods: We retrospectively collected clinical data from 124 consecutive MTC patients who underwent initial surgery at our institution. The data of 82 patients (from 2010 to 2018) and 42 patients (from January 2019 to November 2019) were used as the training set for building the model and as the test set for validating the model, respectively. Results: In the training group, the multivariate analyses indicated that male and MTC patients with higher preoperative basal calcitonin levels were more likely to have lateral LNM (P = 0.007 and 0.005, respectively). Multifocal lesions and suspected lateral LNM in preoperative ultrasound (US) were independent risk factors (P = 0.032 and 0.002, respectively). The identified risk factors were incorporated into a multivariate logistic regression model to generate the nomogram, which showed good discrimination (C-index = 0.963, 95% confidence interval [CI]: 0.9286-0.9972). Our model was validated with an excellent result in the test set and even superior to the training set (C-index = 0.964, 95% CI: 0.9121-1.000). Conclusion: Higher preoperative basal calcitonin level, male sex, multifocal lesions, and lateral lymph node involvement suspicion on US are risk factors for lateral LNM. Our model and nomogram will objectively and accurately predict lateral LNM in patients with MTC.

Molecular Simulation Studies on the Interactions of Bilirubin at Different States with a Lipid Bilayer.

The unconjugated bilirubin (BR) may penetrate through the cell membrane and cause a severe cytotoxicity. However, the molecular mechanism underlying the penetration of BR into the cell membrane is still largely unknown. In this work, we systematically investigate the interaction of BR and a lipid bilayer under different conditions by using all-atom molecular dynamics simulations. It is found that BR at the Z,Z conformation can easily enter into the interior of the lipid bilayer due to its hydrophobicity. However, when BR transforms from the Z,Z conformation to the E,E conformation (after the blue-light emission), its penetration ability is greatly reduced (especially at its ionized state). This study may offer useful physical insights into the effect of phototherapy on the penetration behavior and the cytotoxicity of the unconjugated BR.