Gold Nano Frameworks with Mesopores for Synergistic Immune-Thermal Therapy in Hepatic Carcinoma: A Paradigm Shift in Immune Checkpoint Blockade.

Immune checkpoint blockade (ICB) therapy, while showing promise in various cancers, exhibits limited effectiveness in hepatic carcinoma due to the tumor's immunosuppressive microenvironment (TME) and challenges associated with immune cell infiltration. Efforts to transform the "cold" TME into an "inflamed" state, notably through chemo-immunotherapy, have sparked interest due to their potential to induce immunogenic cell death and augment the infiltration of cytotoxic T lymphocytes (CTLs). Nonetheless, the efficacy of chemo-immunotherapy is often compromised by suboptimal pharmacokinetics, poor tumor accumulation, and off-target toxicity. Herein, in response, we introduce an innovative, milder thermal therapeutic approach leveraging gold nano frameworks with mesopores for the targeted delivery of the immunostimulant imiquimod and NIR-II photothermal therapy. This strategy employs targeted molecule modifications to ensure precise tumor targeting, guided by photoacoustic imaging. Subsequent to mild thermal treatment, there is a release of immunogenic proteins (CRT and HSP90), enhancing tumor immunogenicity. Assisted by imiquimod, substantial CTL infiltration occurs, accompanied by pro-inflammatory factor release (TNF-α, IL-6), transforming M2 macrophages into the M1 phenotype. Ultimately, the proposed strategy combines PD-L1/PD-1 blockade, imiquimod and mild thermal treatment to synergistically enhance tumor immunogenicity, remodel the TME, and restrain hepatic carcinoma, making strides in ICB synergistic immune-thermal therapy.

NIR-II-Absorbing NDI Polymer with Superior Penetration Depth for Enhanced Photothermal Therapy Efficiency of Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinomas (HCC) have a high morbidity and mortality rate, and is difficult to cure and prone to recurrence when it has already developed. Therefore, early detection and efficient treatment of HCC is necessary. Methods: In this study, we synthesized a novel NDI polymer with uniform size, long-term stability, and high near-infrared two-zone (NIR-II) absorption efficiency, which can greatly enhance the effect of photothermal therapy (PTT) after intravenous injection into Huh-7-tumor bearing mice. Results: The in vitro and in vivo studies showed that NDI polymer exhibited excellent NIR-guided PTT treatment, and the antitumor effect was approximately 88.5%, with obvious antimetastatic effects. Conclusion: This study developed an NDI polymer-mediated integrated diagnostic and therapeutic modality for NIR-II fluorescence imaging and photothermal therapy.

Simultaneous screening of 33 restricted substances in polymer materials using pyrolysis/thermal desorption gas chromatography-mass spectrometry.

The purpose of this study was to offer a quick and efficient method to screen for multiple restricted additives in polymer materials. A solvent-free pyrolysis gas chromatography-mass spectrometry method was developed to simultaneously screen 33 restricted substances, comprising 7 phthalates, 15 bromine flame retardants, 4 phosphorus flame retardants, 4 ultraviolet stabilizers, and 3 bisphenols. The pyrolysis technique and temperatures affecting additive desorption were studied. Under optimized conditions, the instrument sensitivity was confirmed using in-house reference materials at concentrations of 100 mg/kg and 300 mg/kg. The linear range was between 100 and 1000 mg/kg in 26 compounds, and in the other compounds it was between 300 and 1000 mg/kg. In this study, in-house reference materials, certified reference materials, and proficiency testing samples were used for method verification. The relative standard deviation of this method was less than 15%, and recoveries ranged from 75.9 to 107.1% for most of the compounds, with a few exceeding 120%. Furthermore, the screening method was verified with 20 plastic products used in daily life and 170 recycled plastic particle samples from imports. The experimental results showed that phthalates were the main additives in plastic products, and among 170 recycled plastic particle samples, 14 samples were found to contain restricted additives. The main additives in recycled plastics were bis(2-ethylhexyl) phthalate, di-iso-nonyl phthalate, hexabromocyclododecane, and 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether at concentrations between 374 and 34785 mg/kg, except for some results that exceeded the maximum measured value of the instrument. Compared with traditional methods, an important advantage is that this method simultaneously tests for 33 additives without sample pretreatment, covering a variety of additives limited by laws and regulations, and therefore can provide more comprehensive and thorough inspections.

Hollow MnO2-Based Nanoprobes for Enhanced Photothermal/Photodynamic /Chemodynamic Co-Therapy of Hepatocellular Carcinoma.

PURPOSE: The effect of monotherapy in cancer is frequently influenced by the tumor's unique hypoxic microenvironment, insufficient drug concentration at the treatment site, and tumour cells' increased drug tolerance. In this work, we expect to design a novel therapeutic nanoprobe with the ability to solve these problems and improve the efficacy of antitumor therapy. METHODS: We have prepared a hollow manganese dioxide nanoprobes loaded with photosensitive drug IR780 for the photothermal/photodynamic/chemodynamic co-therapy of liver cancer. RESULTS: The nanoprobe demonstrates efficient thermal transformation ability under a single laser irradiation, and under the synergistic influence of photo heat, accelerates the Fenton/ Fenton-like reaction efficiency based on Mn2+ ions to produce more ·OH under the synergistic effect of photo heat. Moreover, the oxygen released under the degradation of manganese dioxide further promotes the ability of photosensitive drugs to produce singlet oxygen (ROS). The nanoprobe has been found to efficiently destroy tumour cells in vivo and in vitro experiments when used in combination with photothermal/photodynamic/ chemodynamic modes of treatment under laser irradiation. CONCLUSION: In all, this research shows that a therapeutic strategy based on this nanoprobe could be a viable alternative for cancer treatment in the near future.

Branched poly(ethylenimine) carbon dots-MnO2 nanosheets based fluorescent sensory system for sensing of malachite green in fish samples.

Malachite green (MG) is an organic dye compound that is frequently used as a fungicide and antiseptic in aquaculture. However, human or animal exposure to MG causes carcinogenic, teratogenic and mutagenic effects. Herein, a novel fluorescent assay was designed for the detection of MG using manganese dioxide nanosheets (MnO2 NS) as an energy acceptor to quench the fluorescence of branched poly(ethylenimine) carbon dots (BPEI-CDs) via Förster resonance energy transfer. When butyrylcholinesterase is introduced to form thiocholine in the presence of S-butyrylthiocholine iodide, MnO2 NS can be recovered by thiocholine to Mn2+, resulting in restoration of the fluorescence of BPEI-CDs. Exploiting these changes in fluorescence intensity in the above system, a fluorescence probe was successfully developed for the quantitative detection of MG. Besides, this assay was applied to fish samples, verifying the high potential for practical application of the proposed sensor for the monitoring of MG in aquatic products.

The preoperative elevated plasma fibrinogen level is associated with the prognosis of hilar cholangiocarcinoma.

PURPOSE: Elevated fibrinogen (Fbg) levels contribute to tumor progression and metastasis. However, little is known regarding the association of the clinicopathological characteristics and the prognosis of hilar cholangiocarcinoma (HC) with plasma fibrinogen. METHODS: Data on the plasma Fbg levels, clinicopathological characteristics, and overall survival were retrospectively collected. Plasma fibrinogen concentrations over 4.0 g/L were classified as hyperfibrinogen, elevated fibrinogen, or abnormal fibrinogen levels. We then analyzed the relationships among plasma fibrinogen level, clinicopathological features, and patient prognosis. RESULTS: A total of 171 HC patients were included. An elevated plasma fibrinogen level was associated with lymph-node metastasis (P < 0.001), the AJCC stage (P < 0.001), the surgical margin (P = 0.005), and vascular invasion (P = 0.027). Univariate analyses revealed that preoperative plasma fibrinogen (P < 0.001), operative blood loss (P = 0.044), vascular invasion (P < 0.001), CA19-9 (P = 0.003), surgical margin (P < 0.001), T stage (P < 0.001), histologic differentiation (P = 0.007), and lymph-node metastasis (P < 0.001) were associated with OS. The survival time of patients with high Fbg levels was shorter than that of patients with normal fibrinogen levels (P < 0.001). Furthermore, a multivariate analysis showed that fibrinogen was negatively and independently associated with the HC prognosis (P = 0.029). CONCLUSIONS: An elevated plasma Fbg level was associated with lymph-node metastasis, vascular invasion, the surgical margin, and the tumor stage, and the Fbg level might therefore be an independent factor associated with poor outcomes in HC patients.

[Determination of trace azo dyes in textile wastewater by liquid-liquid extraction and dispersive liquid-liquid microextraction coupled with gas chromatography-mass spectrometry].

An efficient method based on liquid-liquid extraction and dispersive liquid-liquid microextraction coupled with gas chromatography-mass spectrometry was developed for the determination of trace azo dyes in textile wastewater. The azo dyes were reduced to aromatic amines by sodium dithionite under alkaline conditions. The main pretreatment conditions that affected the extraction efficiency were optimized. Under the optimized experimental conditions, the linear ranges of this method were as follows:0.05-10 µg/L for 13 aromatic amines; 0.05-5 µg/L for 7 aromatic amines; and 20-100 µg/L for 2,4-diaminoanisole. The correlation coefficients were in the range of 0.996-0.999. The limits of detection reached 0.05 µg/L for all the 20 aromatic amines, and the detection limit of 2,4-diaminoanisole was 20 µg/L. Actual wastewater-spiked experiments involving printing, dyeing, and weaving showed that the average recoveries of the amines were in the range of 75.6%-115.1%. The developed method has high enrichment multiples and low detection limits, and it is suitable for the detection of trace levels of banned azo dyes in textile wastewater.

Lymphocyte to Monocyte Ratio Predicts Resectability and Early Recurrence of Bismuth-Corlette Type IV Hilar Cholangiocarcinoma.

BACKGROUND: The objective of our research was to investigate the value of the lymphocyte to monocyte ratio (LMR) and its dynamic changes (LMRc) in predicting tumor resectability and early recurrence of radiologically resectable type IV hilar cholangiocarcinoma (HC). METHODS: A total of 411 patients with radiologically resectable type IV HC were included. Data on their clinicopathologic characteristics, perioperative features, and survival outcomes were analyzed. Receiver operating characteristic (ROC) analysis was conducted to assess the ability of preoperative LMR (pre-LMR) to predict tumor resectability, and the ability of postoperative LMR (post-LMR) to discriminate between early and late recurrence. Survival curves were calculated using the Kaplan-Meier estimate. Univariate and multivariate logistic regression models were used to identify factors associated with resectability and early recurrence. RESULTS: Of 411 patients with potentially curative type IV HC, 254 underwent curative surgery. The optimal cutoff value of pre-LMR as an indicator of resectability was 3.67, and the optimal cutoff value of post-LMR for detecting early recurrence was 4.10. In the multivariate logistic regression model, CA19-9 > 200 U/mL, pre-LMR ≤ 3.67, and tumor size > 3 cm were found to be independent risk factors for poor resectability. Moreover, multivariate analysis showed that LMRc, resection margin, AJCC N stage, and lymphovascular invasion were independent risk factors associated with early recurrence. DISCUSSION: Pre-LMR is a valuable indicator of resectability and LMRc is a valuable predictor of early recurrence in patients with curative type IV HC.

A simple scoring system to predict early recurrence of Bismuth-Corlette type IV perihilar cholangiocarcinoma.

BACKGROUND: Early recurrence has been reported to be predictive of a poor prognosis for patients with perihilar cholangiocarcinoma (pCCA) after resection. The objective of our study was to construct a useful scoring system to predict early recurrence for Bismuth-Corlette type IV pCCA patients in clinic and to investigate the value of early recurrence in directing post-operative surveillance and adjuvant therapy. METHODS: In total, 244 patients who underwent radical resection for type IV pCCA were included. Data on clinicopathological characteristics, perioperative details and survival outcomes were analyzed. Survival curves were generated using the Kaplan-Meier method. Univariate and multivariate logistic-regression models were used to identify factors associated with early recurrence. RESULTS: Twenty-one months was defined as the cutoff point to distinguish between early and late recurrence. Univariate and multivariate analysis revealed that CA19-9 level >200 U/mL, R1 resection margin, higher N category and positive lymphovascular invasion were independent predictors of early recurrence. The scoring system was constructed accordingly. The early-recurrence rates of patients with scores of 0, 1, 2, 3, 4, and 5 were 23.9%, 38.7%, 60.0%, 78.6%, 83.4%, and 100%, respectively. Adjuvant therapy was significantly associated with higher overall survival rate for patients with early recurrence, but not for those with late recurrence. Patients in the early-recurrence group with scores ≥2 had better prognoses after adjuvant therapy. CONCLUSIONS: A simple scoring system using CA19-9 level, N category, resection margin and lymphovascular invasion status could predict early recurrence, and thus might direct post-operative surveillance and adjuvant therapy for patients with type IV pCCA.

Novel approach for the rapid screening of banned aromatic amines in dyed textiles using a chromogenic method.

A novel and simple method utilizing a chromogenic reaction on filter paper is introduced for the rapid screening of banned aromatic amines released from azo dyes. The proposed method involves the sample preparation protocols outlined by the current standard method and the chromogenic reaction of extracted aromatic amines on filter paper. Based on the principle of the reaction between primary amines and aldehydes, p-dimethylaminobenzaldehyde (DMAB) was used as the chromogenic reagent for the rapid screening of 24 carcinogenic aromatic amines and aniline without any chromatographic instruments under optimized experimental conditions. The detection limit for all the aromatic amines in this study was less than 15 mg/kg. A total of 727 dyed textile samples were analyzed using both the present standard method and the proposed method simultaneously. Using the proposed method, a total of 471 samples did not require further instrumental analysis, which can dramatically save instrumental detection time (61.2%), can decrease instrumental detection costs, and can avoid the use of large amounts of toxic reagents. The proposed method has been applied to detect banned aromatic amines in some inspection institutions and dye factories and has large social and economic benefits. Graphical abstract Chromogenic reaction methods.

Hepatic paragonimiasis: a single-center retrospective analysis of 32 cases in Mainland China.

BACKGROUND: In paragonimiasis, the lungs and pleural cavity are the major target organs, and the central nervous system can also be affected. The liver is an organ in which ectopic paragonimiasis rarely occurs. Because the symptoms and examinations in hepatic paragonimiasis (HP) are not typical, the disease is often misdiagnosed in the clinic. METHODS: From February 2008 to March 2015, our department accepted 32 patients who presented with a liver mass upon ultrasound and computed tomography imaging and in whom the source of the mass could not be identified upon numerous further diagnostic tests. We ultimately obtained surgical biopsies of their lesions for pathological examination. We analysed the clinical data of these cases, along with their disease characteristics, the diagnostic strategies employed and their treatment experiences. Additionally, we performed patient follow-up for a period of 6-12 months. RESULTS: All patients underwent half/partial hepatectomy and were diagnosed with HP upon pathological examination. They recovered well after surgery and their original symptoms were markedly improved without recurrence. The liver functions of the patients reached normal levels before discharge and no additional liver lesions were found upon diagnostic imaging. CONCLUSION: The diagnosis of HP based on clinical manifestations, laboratory tests or image examination is difficult and only pathologic analysis of biopsies could confirm HP. Surgical treatment not only removes lesions, but also allows for pathologic biopsy. This study encompasses the largest number of HP patients to date, but the surgical outcomes require further research and long-term follow-up.

[Determination of free carcinogenic aromatic amines in textiles by ultra-performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry].

A method of ultra-performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry (UPLC-LTQ/Orbitrap MS) was used to determine 24 free carcinogenic aromatic amines in textiles. The main factors influencing the method, including the extraction solvent, the extraction temperature and the extraction time, were optimized. Under the optimized experimental conditions, the analytes were extracted by dichloromethane for 10 min and loaded into a ZORBAX SB-C18 column (150 mm x 2.1 mm, 5 µm) with a gradient elution of methanol and 0.1% aqueous formic acid solution, and finally detected by LTQ/Orbitrap MS. The screening and quantitative analysis were carried out by the accurate mass of quasi-molecular ion and the peak in extracted chromatogram with accurate mass respectively. The correlation coefficients (R2) were higher than 0.99. The recoveries were 87.8%-105.6% with the RSDs were 1.6%-3.4%. The limits of detection were 0.5-1 µg/kg, and the limits of quantification were 1.5-3 µg/kg. The proposed method was applied to 14 textile samples containing spandex. 4,4'-Diaminodiphenylmethane was determined in five samples and the contents were 0.21-25.6 mg/kg. The results indicate that the developed method is a simple, efficient, precise and reliable technique for the determination of free carcinogenic aromatic amines in textiles.

[Determination of carcinogenic aromatic amines derived from azo colorants in plastic components of electrical and electronic products by high performance liquid chromatography-mass spectrometry].

A study for the simultaneous determination of 21 primary aromatic amines derived from the reduction of the azo colorants in plastic components of electrical and electronic products was conducted. Organic solvents were used to dissolve or swell the plastics to release the azo dyes existing in the plastic components. The azo colorants were reduced to aromatic amines under strong reducing condition of dithionite. Aromatic amines were extracted with methyl tert-butyl ether. Methanol-water (1: 1, v/v) was used to concentrate the extract to constant-volume for HPLC-MS analysis. The analytes were separated on a ZORBAX Eclipse XDB C18 column using the gradient elution with acetonitrile and 0.1% (v/v) formic acid aqueous solution at a flow rate of 0.6 mL/min. The analyte confirmation was performed using retention time and characteristic ions in selected ion monitoring (SIM) mode. The correlation coefficients (r) of all the standard curves were more than 0.998, and the limits of quantification of the analytes were 0.5 mg/kg. The recoveries were 60.1% - 129.5% for the 21 aromatic amines with the RSDs not more than 14.0% except for a few compounds. The results showed that the banned azo colorants in the plastic products can be analyzed qualitatively and quantitatively through reductive conversion into aromatic amines. In addition, this method has high accuracy and good precision.

[Determination of hexabromocyclododecane in coatings by gas chromatography-mass spectrometry].

A method has been developed for the determination of hexabromocyclododecane (HBCD) in fire proof coatings by gas chromatography-mass spectrometry (GC-MS). The sample was extracted with dichloromethane and purified through an organic membrane before analysis with GC-MS. The characteristic fragments (m/z 157, 239, 319, 401) and the quantitative ion (m/z 239) were selected. With the optimized conditions, the good linear relationship was obtained between the peak area and the mass concentration of HBCD in the range of 5 to 100 mg/L with the correlation coefficient more than 0. 999. The spiked recoveries in the coatings of acrylic and epoxy resins were 92.9% - 116.3% with the RSDs not more than 8%. The LOD (S/N > or = 3) of HBCD was 30 microg/g, and the LOQ (S/N > or = 10) was 100 microg/g, which were much lower than the international maximum residue limit. The method is simple, quick, accurate and precise, which can meet the requirements of the European Commission Regulation (EC) No. 1907/2006 and Norway PoHS instruction (Prohibition on Certain Hazardous Substances in Consumer Products) for the determination of HBCD. It is suitable for the analysis of HBCD in fire proof coatings.

[Screening and confirmation of carcinogenic dyes in textiles by high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry].

A method of high performance liquid chromatography-linear ion trap/Orbitrap high resolution mass spectrometry (HPLC-LTQ/Orbitrap MS) was used to screen and confirm carcinogenic dyes in textiles. The analytes were extracted from textile samples with pyridine/water (1/1, v/v) in a water bath under controlled conditions (95 degrees C, 150 r/min), and then filtered with a 0.22 microm polytetrafluoroetylene (PTFE) membrane. The eluates were separated on a CAPCELL PAK C18 column (100 mm x 2.0 mm, 5 microm) using gradient elution with acetonitrile/ 5 mmol/L ammonium acetate aqueous solution containing 0.01% formic acid (in positive mode) and acetonitrile/5 mmol/L ammonium acetate aqueous solution (in negative mode), and finally detected by HPLC-LTQ/Orbitrap MS in ESI modes. Full scan experiments were performed over the range of m/z 200-800. The screening and quantitative analysis were carried out by the accurate mass of quasi-molecular ion and the peak area in extracted chromatogram with accurate mass, respectively. The confirmatory analysis for target compounds was performed with the retention time and qualitative fragments obtained by data-dependent scan mode. Under the optimal conditions, nine carcinogenic dyes were routinely detected with mass accuracy below 5 x 10(-6) (5 ppm), and good linearities were provided in their respective linear ranges with correlation coefficients higher than 0.99. The limits of detection were in the range of 0.125-25 mg/kg. The average recoveries at three spiked levels were in the range of 62.13%116.28% with the relative standard deviations (RSDs) lower than 15%. The proposed method was applied to screen and confirm the nine carcinogenic dyes in textile samples. It is convenient and reliable.

[Determination of phthalic acid esters in textiles by solid phase extraction-gas chromatography].

A method was established for the simultaneous determination of some phthalic acid esters, namely, dimethyl phthalate (DMP), diethyl phthalate (DEP), dipropyl phthalate (DPrP), dibutyl phthalate (DBP), diamyl phthalate (DAP), dihexyl phthalate (DHP), benzyln-butyl phthalate (BBP), di-(2-ethylhexyl) phthalate (DEHP), dicyclohexyl phthalate (DCHP), di-n-octyl phthalate (DNOP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) in textiles by solid phase extraction (SPE) coupled with gas chromatography (GC). The phthalic acid esters in textiles were extracted by Soxhlet extraction with hexane, the extracts were then cleaned up and enriched by a strong anion exchange (SAX) SPE cartridge. The parameters affecting the purification efficiency of SPE cartridge, such as solvent conditioning, rinsing, and elution, were studied. Conditioning with 5 mL hexane and rinsing with 3 mL isooctane were proved to be the optimal conditions. Of the several solvent ratios (ethylacetate in hexane) used for selective elution of phthalic acid esters from the SAX SPE cartridge, the 15% (v/v) content for ethylacetate in hexane gave the best result. Under the optimized conditions, the recoveries of phthalic acid esters for spiked standards (n=7) were 86.3%-102.7%, and the relative standard deviations (RSDs) were less than 5%. In this method the detection limits for DMP, DEP, DPrP, DBP, DAP, BBP, DCHP, DEHP, DNOP were all below 1 mg/kg, and the detection limits for DINP and DIDP were 1.74 mg/kg and 1.55 mg/kg respectively. This SPE-GC method is sensitive, accurate and suitable for the analysis of phthalate environmental hormones in textiles.