Construction and validation of serum Metabolic Risk Score for early warning of malignancy in esophagus.

Using noninvasive biomarkers to identify high-risk individuals prior to endoscopic examination is crucial for optimization of screening strategies for esophageal squamous cell carcinoma (ESCC). We conducted a nested case-control study based on two community-based screening cohorts to evaluate the warning value of serum metabolites for esophageal malignancy. The serum samples were collected at enrollment when the cases had not been diagnosed. We identified 74 differential metabolites and two prominent perturbed metabolic pathways, and constructed Metabolic Risk Score (MRS) based on 22 selected metabolic predictors. The MRS generated an area under the receiver operating characteristics curve (AUC) of 0.815. The model performed well for the within-1-year interval (AUC: 0.868) and 1-to-5-year interval (AUC: 0.845) from blood draw to diagnosis, but showed limited ability in predicting long-term cases (>5 years). In summary, the MRS could serve as a potential early warning and risk stratification tool for establishing a precision strategy of ESCC screening.

Effectiveness of Endoscopic Screening on Esophageal Cancer Incidence and Mortality: A 9-Year Report of the Endoscopic Screening for Esophageal Cancer in China (ESECC) Randomized Trial.

PURPOSE: To evaluate the effectiveness of endoscopic screening against incidence of and mortality from esophageal squamous cell carcinoma (ESCC). METHODS: From January 2012 to September 2016, we conducted a community-based cluster randomized controlled trial involving permanent residents age 45-69 years in a high-risk region for ESCC in northern China. A total of 668 targeted villages were randomly assigned in a 1:1 ratio to the screening group (offered Lugol's chromoendoscopy) or control group (no screening). Intention-to-treat and per-protocol analyses were performed to compare esophageal cancer (EC) incidence and mortality between the two groups. The per-protocol analysis adjusted for nonadherence to the screening procedure. RESULTS: A total of 33,847 participants were included in the analysis: 17,104 in the screening group, 15,165 (88.7%) of whom underwent screening, and 16,743 in the control group. During a maximum follow-up of 9 years, EC incidence in the screening and control groups were 60.9 and 72.5 per 100,000 person-years, respectively; mortality in the screening and control groups were 29.7 and 32.4 per 100,000 person-years, respectively. Compared with the control group, the incidence and mortality of the screening group reduced by 19% (adjusted hazard ratio [aHR], 0.81 [95% CI, 0.60 to 1.09]) and 18% (aHR, 0.82 [95% CI, 0.53 to 1.26]), respectively, in the intention-to-treat analysis; and by 22% (aHR, 0.78 [95% CI, 0.56 to 1.10]) and 21% (aHR, 0.79 [95% CI, 0.49 to 1.30]), respectively, in the per-protocol analysis. CONCLUSION: With a 9-year follow-up, our trial suggests that chromoendoscopic screening induces modest reductions in EC incidence and mortality. A more efficient strategy for EC screening and subsequent patient management should be established to guarantee the effectiveness of endoscopic screening.

Modulating the Catalytic Properties of Polyoxovanadates with Transition-Metal-Complex Units for Selective Oxidation of Sulfides.

Selective oxidation of sulfides to sulfoxides is of great significance in the synthesis of pharmaceuticals, desulfurization of fuels, and detoxification of sulfur mustard chemical warfare agents. Designing selective catalysts to achieve the efficient transformation of sulfides to sulfoxides is thus highly desired. Herein, we report three transition metal-complex-functionalized polyoxovanadates, [Zn2(BPB)2][V4O12]·0.5BPB·H2O (1), [Ni(BPB)(H2O)][V2O6]·2H2O (2), and [Co(HBPB)2][V4O12] (3) (BPB = 1,4-bis(pyrid-4-yl)benzene)), and explore their applications for selective oxidation of sulfides using H2O2 as an oxidant. All three compounds were catalytically effective for the oxidation of methyl phenyl sulfide to methyl phenyl sulfoxide, with 1 being best-performing with complete conversion and a selectivity of 96.7%. In the selective oxidation of a series of aromatic and aliphatic sulfides to corresponding sulfoxides, 1 also showed satisfactory performance; in particular, the chemical warfare agent stimulant 2-chloroethyl ethyl sulfide can be completely and selectively oxidized to the nontoxic 2-chloroethyl ethyl sulfoxide within 20 min at room temperature. Catalyst 1 can be recycled and reused at least six times with uncompromised performance. The perfect performance of 1 is attributed to the synergistic effect of coordinatively unsaturated V and Zn sites in bimetallic oxide, as revealed by comparative structural and catalytic studies.

Solvent- and Additive-Free Dehydrogenation of N-Heterocycles with Oxygen Catalyzed by Polyoxovanadate-Based Metal-Organic Frameworks.

N-heteroarenes are a family of organics with significant chemical and pharmaceutical applications. They are generally prepared by the catalytic oxidative dehydrogenation (ODH) of partially saturated N-heterocycles. In this work, we prepare and demonstrate the catalytic ODH applications of two polyoxovanadate-based metal-organic frameworks of the general formula {[MII(bibp)1.5][VV2O6]}·H2O (M = Ni 1, Co 2; bibp = 4,4'-bis(imidazol-1-ylmethyl)biphenyl). They are based on nonprecious metals, need no additives or organic solvents typically required for catalytic ODH, and utilize molecular O2 as the oxidant, thus possessing all the traits desirable for practical catalysis. Catalyst 1 shows tolerance for a range of substrates with different electronic and steric features, including 2,3-dihydro-1H-indole and tetrahydroquinolines substituted with various functional groups. Mechanistic studies supported primarily by evidence from electron paramagnetic resonance and X-ray photoelectron spectra suggest that the VV sites in 1 are catalytically responsible, first enabling the formation of the substrate-based radical species by a single electron transfer event while being converted into its mixed-valence form, followed by the production of the superoxide radical anion (O2•-) upon contact with O2. The reaction mixture containing O2•- and the initially formed substrate-based radical then undergoes a series of steps, including the hydrogen abstraction and formation of the hydroperoxyl radical, the production and tautomerization of the partially dehydrogenated intermediate, and finally a repeating cycle of the aforementioned steps, to achieve the high-yield conversion of substrates to the corresponding N-heteroarenes.

Additive-free selective oxidation of aromatic alcohols with molecular oxygen catalyzed by a mixed-valence polyoxovanadate-based metal-organic framework.

Selective oxidation of alcohols to aldehydes is an industrially significant chemical transformation. Herein, we report a mixed-valence polyoxovanadate-based metal-organic framework (MOF), (H2bix)5{[Cd(bix)2][VIV8VV7O36Cl]2}·3H2O (V-Cd-MOF), for catalyzing the additive-free oxidation of a series of aromatic alcohols with high selectivity and in nearly quantitative yield to the corresponding aldehydes with O2 as the oxidant. Experimental results, corroborated with density functional theory calculations, indicate that it is the synergistic operation of the dual active sites of the VIV-O-VV building units in the polyoxovanadate cluster that is responsible for the excellent catalytic performance observed: on the one hand, the exposed and readily accessible reduced VIV site is believed to activate O2, resulting in a reactive oxygen species for the subsequent activation and breaking of the substrate's Cα-H bond. On the other hand, the VV site coordinates with the alcoholic O atom to facilitate the cleavage of the O-H bond. The catalyst can be recycled by centrifugation and re-used at least five times with uncompromised performance. To our knowledge, V-Cd-MOF represents the first example of a polyoxometalate-based MOF catalyst for additive-free selective oxidation of alcohol to aldehyde with O2 as an oxidant.

Dextran-doxorubicin prodrug nanoparticles conjugated with CD147 monoclonal antibody for targeted drug delivery in hepatoma therapy.

Antibody-drug conjugates (ADCs) are a class of tumor cell-targeting drugs that have developed rapidly in recent years. From the perspective of further improving ADC targeting and developing natural macromolecules as drug carriers, it is still challenging and necessary to try new targeted drug delivery modalities. In this study, we have developed an antibody-modified prodrug nanoparticle based on biomacromolecule dextran (DEX) to delivery antitumour drug doxorubicin (DOX). Firstly, oxidized dextran (ODEX) and DOX were bonded to yield ODEX-DOX via Schiff base reaction, which can self-assemble into nanoparticles (NPs) carrying some aldehyde groups. Subsequently, the amino groups of CD147 monoclonal antibody were bound to the aldehyde groups on the surface of ODEX-DOX NPs, resulting in acid-responsive and antibody-modified CD147-ODEX-DOX NPs with relatively small particle size and high DOX loading. FT-IR, UV-Vis, HPLC, and 1H NMR were used to demonstrate the successful synthesis of polymer prodrug ODEX-DOX NPs and antibody-modified nanomedicine CD147-ODEX-DOX NPs. Dynamic light scattering (DLS) was used to evaluate the stability and the pH responsiveness of ODEX-DOX NPs in different media and tumour microenvironment. The in vitro total release content of DOX reached approximately 70% in PB 5.0 buffer solution after 103 h. Furthermore, the in vivo antitumour efficacy and biodistribution experiments confirmed that CD147-ODEX-DOX NPs could significantly inhibit the growth of HepG2 tumour. All of the results indicate that this acid-sensitive nanomedicine has higher safety and targeting effects. It promises to be an ideal strategy for future targeted drug delivery systems and anticancer therapies.

Elimination of grain boundary resistance in vanadoborate electrolyte via the hydrogen-bond interaction of glycerol.

An effective method to eliminate grain boundary resistance of crystalline vanadoborate electrolyte was developed. This method involved the addition of glycerol to result in the formation of many hydrogen bonds between crystal grains, facilitating a rapid transfer of protons across grain boundaries. Using this method, the intrinsic conduction of vanadoborate electrolyte was fully reflected in its bulk materials, valuable for advancing our understanding of vanadoborate electrolytes and for promoting the application of these electrolytes.

Theoretical study on the vibrational spectra and potential energy curves for SiC (X3Π) and SiS (X1Σ+) molecules.

In this work, the vibrational constants (ωe,ωexe) calculated by the variational algebraic method (VAM) and some other molecular constants (De,re,Be,αe) were used to construct the improved Hulburt-Hirschfelder (IHH) analytical potential energy function (APEF). Not only that, but the calculated VAM potential points are used as the 'true' energies to determine the value of the variational parameter λ which is the pivotal fitting parameter in the IHH potential. With limited experimental data, high-precision IHH potential can be achieved by combining the VAM and the IHH APEF. This combination of the VAM and the IHH APEF is referred to be VAIHH APEF, which is employed to study the vibrational energies and potential energy curves (PECs) of SiC (X3Π) and SiS (X1Σ+) molecules, yielding full vibrational spectra and spectroscopic constants. The calculational results indicate that the VAIHH APEFs of SiC (X3Π) and SiS (X1Σ+) molecules are in good agreement with the experimental RKR potential points. Accurate PECs of SiC (X3Π) and SiS (X1Σ+) molecules imply that the VAIHH APEF is of high quality.

Update and validation of a diagnostic model to identify prevalent malignant lesions in esophagus in general population.

Background: Previous risk prediction models taking esophageal malignant lesions detected during endoscopy as the primary outcome are not always sufficient to identify prevalent cases which are "overlooked" at screening. We aimed to update and externally validate our previous risk prediction model for malignant esophageal lesions by redefining the predicted outcome. Methods: 15,192 individuals from the Endoscopic Screening for Esophageal Cancer in China randomized controlled trial (ESECC trial, NCT01688908) were included as the training set, and 4576 participants from another population-based esophageal squamous cell carcinoma (ESCC) screening cohort (Anyang Esophageal Cancer Cohort Study, AECCS) served as the external validation set. Lesions with severe dysplasia or worse diagnosed at chromoendoscopy or identified via follow-up within 1 year after screening were defined as main outcome. Logistic regressions were applied to reconstruct the questionnaire-based prediction model using information collected before screening, with Akaike Information Criterion to determine the model structure. Findings: The final prediction model included age and its quadratic term, family history of ESCC, low body mass index (≤22 kg/m2), use of coal or wood as main fuel for cooking, eating rapidly, and ingestion of leftover food. The area under the curve was 0·77 (95% CI: 0·73-0·80) and 0·71 (95% CI: 0·65-0·78) in the training and validation set. When screening the top 50% or 10% of high-risk individuals within population, the detection rates can be increased in both cohorts, as compared to universal screening. Interpretation: The described tool may promote the efficiency of current national screening programs for ESCC and contribute to a precision screening strategy in high-risk regions in China. Funding: This work was supported by the National Natural Science Foundation of China (82073626, 81773501), the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), the National Key R&D Program of China (2021YFC2500405), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (J200016), the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0204) and the Beijing Nova Program (Z201100006820093). Sponsors had no role in the study design, data collection, analysis, and interpretation of data.

Proton conductors with wide operating temperature domains achieved by applying a dual-modification strategy to MIL-101.

Developing an efficient strategy for obtaining proton conductors with wide working temperature domains is of great significance for the wide application of proton conductors. To date, proton conductors that have high proton conductivity from subzero temperatures to high temperatures above 100 °C have been very rare. Herein, we prepared two composites, H3PO4@MIL-101-SO3H(Cr) (1) and H2SO4@MIL-101-NH2(Al) (2) by applying a dual-modification strategy to functionalize MOF MIL-101, that is, incorporating acidic guest molecules into the channels of MIL-101 while modifying the MIL-101 backbone with functional groups. Both composites have high proton conductivity over a broad temperature domain (-40 °C to above 150 °C) due to the complementary conduction or synthetic conduction of the backbone functional group and acidic guest molecules in different temperature ranges. The proton conductivities of 1 are 0.9 × 10-1 S cm-1 at 65 °C and 95% RH, 7.5 × 10-5 S cm-1 at -40 °C and 1.4 × 10-2 S cm-1 at 150 °C. Further, the proton conductivities of 2 are 5.8 × 10-2 S cm-1 at 65 °C and 95% RH, 7.1 × 10-4 S cm-1 at -40 °C and 2.5 × 10-4 S cm-1 at 170 °C. All the proton conductivities of the two composites in three temperature domains (low, moderate and high temperature) are at a high level among those of reported proton conductors. Moreover, their proton conductivities have good stability and durability in the broad temperature region from subzero temperatures to high temperatures above 100 °C.

Hierarchically Ordered Macro-Microporous Polyoxometalate-Based Metal-Organic Framework Single Crystals.

Facile construction of ordered macroporous polyoxometalate-based metal-organic frameworks (POM@MOFs) to break the intrinsic microporous restriction is significant but remains challenging. On one hand, the POMs introduced improve the structural stability and modify the pores of MOFs, e.g., introducing functional catalytic and adsorptive units. Meanwhile, the acidic POMs severely affect the nucleation and growth of the POM@MOFs, resulting in complicated synthesis and difficult assembly control. Herein, a general approach has been developed to fabricate ordered macroporous POM@MOF single crystals, involving close-packed polystyrene (PS) nanosphere templates. The artificially selected polar solvents exerting strong solvent effect with POMs weaken the affinity between POMs and metal ions, thereby effectively stabilizing the precursors from assembly before filling into the PS template interstices. The weak alkaline carboxylate used regulates the in situ nucleation and growth of POM@MOFs through deprotonation of the ligands as well as coordinating modulation, affording a series of hierarchically cuboctahedral POM@MOF single crystals with ordered macropores (ca. 180 nm) and intrinsic micropores after template removal. The ordered macroporous structure and thinned microporous skeleton markedly improve mass diffusion properties, while the integral single-crystal lattice retains superior stability.

Health-seeking behavior and barriers to treatment of patients with upper gastrointestinal cancer detected by screening in rural China: real-world evidence from the ESECC trial.

BACKGROUND: To fully realize efficacy in cancer screening, timely and appropriate treatment for participants with malignant lesions is critical. However, the health-seeking behavior of patients with upper gastrointestinal (G.I.) cancer identified in population-level screening programs in China is unknown. METHODS: A community-based real-world investigation was conducted with 136 upper G.I. cancer patients detected in a large screening cohort in an area of high-risk for upper G.I. cancer in China. Using local medical claims data and semi-structured face-to-face interview, we collected information regarding the clinical treatment regimen and factors which result in the lack of timely and appropriate treatment. FINDINGS: The treatment records for 133 upper G.I. cancer patients were acquired. Among these, 48 (36•09%) patients did not receive treatment within three months of initial diagnosis, and treatment of early-stage cancer was more likely to be delayed. Sixteen patients did not seek further diagnostic testing due to their low health-awareness and socio-economic status. Another 20 participants proactively sought further diagnostic evaluation in health care facilities but were prevented from receiving further treatment due to low sensitivity of given diagnostic test(s), failure to recognize the significance of screening results, and/or lack of basic knowledge of diagnosis and treatment for early cancer on the part of clinicians. The treatment regimen offered to patients depended largely on the level of health care facilities they visited, and non-medical factors were the main reasons for choice of health care facilities. INTERPRETATION: A coordinated, system-based management strategy is urgently needed to support the design of upper G.I. cancer screening programs in rural populations in China. FUNDING: The Charity Project of the National Ministry of Health (201202014), the National Key R & D Program of China (2016YFC0901404), the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), and the National Natural Science Foundation of China (82073626).

Estimating cancer survival and prevalence with the Medical-Insurance-System-based Cancer Surveillance System (MIS-CASS): An empirical study in China.

BACKGROUND: We aimed to establish a new approach for surveillance of cancer prevalence and survival in China, based on the Medical-Insurance-System-based Cancer Surveillance System (MIS-CASS). METHODS: We constructed a standard procedure for data collection, cleaning, processing, linkage, verification, analysis, and estimation of cancer prevalence and survival (including both actual observations and model estimates) by conjoint use of medical insurance claims data and all-cause death surveillance data. As a proof-of-principle study, we evaluated the performance of this surveillance approach by estimating the latest prevalence and survival for upper gastrointestinal cancers in Hua County, a high-risk region for oesophageal cancer in China. FINDINGS: In Hua County, the age-standardised relative 5-year survival was 39·2% (male: 36·8%; female: 43·6%) for oesophageal cancer and 33·3% (male: 29·6%; female: 43·4%) for stomach cancer. For oesophageal cancer, better survival was observed in patients of 45-64 years compared with national average estimates, and women of <75 years had better survival than men. The 5-year prevalence rate in Hua County was 99·8/100,000 (male: 105·9/100,000; female: 93·3/100,000) for oesophageal cancer and 41·5/100,000 (male: 57·4/100,000; female: 24·5/100,000) for stomach cancer. For both of these cancers, the prevalence burden peaked at 65-79 years. The model estimates for survival and prevalence were close to the observations in real investigation, with a relative difference of less than 4·5%. INTERPRETATION: This novel approach allows accurate estimation of cancer prevalence and survival with a short delay, which has great potential for regular use in general Chinese populations, especially those not covered by cancer registries. FUNDING: The National Key R&D Program of China (2016YFC0901404), the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), the National Natural Science Foundation of China (82073626), the Taikang Yicai Public Health and Epidemic Control Fund (TKYC-GW-2020), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (J200016), and the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0204).

Hollow Lindqvist-like-Shaped {V6} Cluster-Based Metal-Organic Framework for the Highly Efficient Detoxification of Mustard Gas Simulant.

A polyoxovanadate-based nickel-organic framework, [Ni(bib)2]{V2O6}({V6}-MOF, bib = 1,4-bis(1H-imidazoly-1-yl)benzene), was facilely prepared under gentle hydrothermal conditions and structurally characterized. Single-crystal X-ray diffraction analysis indicates that the {V6} cluster in the {V6}-MOF is constructed of two VO5 tetragonal pyramids and four VO4 tetrahedrons via the apex sharing of O atoms, presenting a hollow Linqvist-like structure, which is different from these reported hexanuclear vanadium clusters. The {V6}-MOF not only expands the structure of polyoxovanadates (POVs) but also catalyzes the rapid detoxification of mustard gas simulant (2-chloroethyl ethyl sulfide, CEES) at 25 °C. The catalytic results were determined by means of GC, GC-MS, and 1H NMR. Using {V6}-MOF as a heterogeneous catalyst, CEES underwent catalyzed oxidation to only nontoxic product 2-chloroethyl ethyl sulfoxide (CEESO) within 40 min, and the conversion and selectivity were almost 100%. In addition, {V6}-MOF exhibits high sustainability, and no obvious reductions in conversion and selectivity are observed after five runs.

The Incidence of Lymphoma in Beijing: Comparing Results from MIS-CASS (2019) and Beijing Cancer Registry (2017).

INTRODUCTION: This study aimed to evaluate the performance of the Medical-Insurance-System-based Cancer Surveillance System (MIS-CASS) in estimating cancer incidence by comparing the results with the Beijing Cancer Registry (BCR), which is one of the highest-quality population-based cancer registries in China. METHODS: Using lymphoma as an example, we extracted relevant claims data from the administrative systems of medical insurance in Beijing (2012-2020) and estimated the most current lymphoma incidence in Beijing (2019) using a standard data processing procedure. The absolute number of new cases, crude incidence rate, and age-standardized incidence rate of lymphoma were compared with the latest data reported by the BCR (2017). RESULTS: Both lymphoma incidence rates and age distribution of new cases estimated based on MIS-CASS were similar to the BCR data (crude incidence rate: 9.8/100,000 vs. 10.6/100,000). However, because MIS-CASS included more designated hospitals and covered a larger local stationary population irrespective of household registration (hukou), the absolute number of incident lymphoma cases identified by MIS-CASS was 39.1% higher than that reported by the BCR (2,002 vs. 1,439). CONCLUSIONS: The MIS-CASS approach reflected the actual cancer burden in a more complete and timely manner as compared with the current BCR, providing new insights for improving cancer surveillance strategies in China.

Development and validation of a questionnaire-based risk scoring system to identify individuals at high risk for gastric cancer in Chinese populations.

OBJECTIVE: This study aimed to develop and validate a risk scoring system to identify high-risk individuals carrying malignant lesions in stomach for tailored gastric cancer screening. METHODS: A gastric cancer risk scoring system (GC-RSS) was developed based on questionnaire-based predictors for gastric cancer derived from systematic literature review. To assess the capability of this system for discrimination, risk scores for 8,214 and 7,235 outpatient subjects accepting endoscopic examination in two endoscopy centers, and 32,630 participants in a community-based cohort in China were calculated to plot receiver operating characteristic curves and generate area under the curve (AUC). To evaluate the performance of GC-RSS, the screening proportion, sensitivity and detection rate ratio compared to universal screening were used under different risk score cutoff values. RESULTS: GC-RSS comprised nine predictors including advanced age, male gender, low body mass index (<18.5 kg/m2), family history of gastric cancer, cigarette smoking, consumption of alcohol, preference for salty food, irregularity of meals and consumption of preserved food. This tool performed well in determining the risk of malignant gastric lesions with AUCs of 0.763, 0.706 and 0.696 in three validation sets. When subjects with risk scores ≥5 were evaluated with endoscopy, nearly 50% of these endoscopies could be saved with a detection rate of over 1.5 times achieved. When the cutoff was set at 8, only about 10% of subjects with the highest risk would be offered endoscopy, and detection rates for gastric cancer could be increased 2-4 fold compared to universal screening. CONCLUSIONS: An effective questionnaire-based GC-RSS was developed and validated. This tool may play an important role in establishing a tailored screening strategy for gastric cancer in China.

CD147 Monoclonal Antibody Targeted Reduction-Responsive Camptothecin Polyphosphoester Nanomedicine for Drug Delivery in Hepatocellular Carcinoma Cells.

In the treatment of tumor-targeted small-molecule anti-cancer drugs, antibody-mediated therapies, especially for antibody-drug conjugates (ADCs), have revealed great latent force. However, the therapeutic drugs provided by ADCs possess limitation. Considering that the combination of antibodies and nano-drugs can broaden their applicability in the field of tumor treatment, herein, we developed an antibody conjugated polymeric prodrug nanoparticles SAE-PEG-b-PBYP-ss-CPT for targeted camptothecin (CPT) delivery to liver tumor cells. The diblock copolymer was composed of PEG and biodegradable polyphosphoester (PBYP) containing alkynyl groups in the side chain. A derivative of CPT (CPT-ss-N3) was bonded to the PBYP via "click" reaction. The diethyl squarate (SAE) in the terminal of PEG chain was used as a functional group to bond with CD147 monoclonal antibody (CD147 mAb). The particle size and size distribution of the both nanoparticles, with antibody binding (namely CD147-CPT NPs) and without antibody (abbreviated as CPT-loaded NPs), were measured by dynamic light scattering (DLS). The morphologies of both two kinds of nanoparticles were observed by transmission electron microscope (TEM). The results of X-ray photoelectron spectroscopy (XPS) showed that CD147 mAb had been coupled to the surface of CPT-loaded NPs. Endocytosis test indicated that CD147-CPT NPs had higher uptake rate and accumulation in HepG2 cells than those of CPT-loaded NPs without antibodies, due to CD147 mAb can specifically bind to CD147 protein overexpressed in HepG2 cells. We establish a method to bond monoclonal antibodies to anti-cancer polymeric prodrugs, and endow biodegradable polymeric prodrugs with precise targeting functions to liver cancer cells.

Fabrication of aminated poly(glycidyl methacrylate)-based polymers for co-delivery of anticancer drugs and the p53 gene.

Aminated poly(glycidyl methacrylate)s-based polymers for gene delivery not only can reduce toxicity and improve solubility, but can improve gene transfection efficiency and reduce protein aggregation. In this study, we first prepared poly(glycidyl methacrylate) (PGMA) via reversible addition-fragmentation chain transfer (RAFT) polymerization, and then the obtained PGMA homopolymer was post-modified with ethanol amine (EA), 1-amino-2-propanol (AP), 3-(dibutylamino)propylamine (DA) and N-(2-hydroxyethyl)ethylenediamine (HA), respectively, to yield four kinds of PGMA-based gene vectors containing hydroxyl groups (abbreviated as PGEA, PGAP, PGDA and PGHA). The effects of the different side chains and hydroxyl groups on the biological properties of these four cationic polymers were investigated. We found that the transfection efficiency of the PGHA/p53 complex was higher than those of the other three polymer/gene complexes through MTT assay and laser scanning confocal microscopy. Hence, we chose HA for further post-modification to fabricate a cationic copolymer, PCL-ss-P(PEGMA-co-GHA) (abbreviated as PGHAP), via a combination of ring opening polymerization (ROP) and RAFT copolymerization. The PCL-ss-P(PEGMA-co-GHA) amphiphilic copolymer could self-assemble into nanoparticles, which could be used to encapsulate anticancer drug doxorubicin (DOX) and compress the p53 gene to form the DOX-loaded PCL-ss-P(PEGMA-co-GHA)/p53 complex (abbreviated as DPGHAP/p53). The gel retardation assay showed that p53 gene could be well immobilized and remained stable under the electronegative conditions. MTT assay showed that the DPGHAP/p53 complex had a significant antitumor effect on A549 cells and H1299 cells compared with free DOX or/and p53 gene therapy alone. Furthermore, the test results from live cell imaging systems revealed that the DPGHAP/p53 complexes could effectively deliver DOX and the p53 gene into A549 cells. Therefore, the constructed cationic polymer PCL-ss-P(PEGMA-co-GHA) has potential application prospects as a co-vector of anticancer drugs and genes.

Estimating cancer incidence based on claims data from medical insurance systems in two areas lacking cancer registries in China.

BACKGROUND: We aimed to establish a Medical-Insurance-System-based Cancer Surveillance System (MIS-CASS) in China and evaluate the completeness and timeliness of this system through reporting cancer incidence rates using claims data in two regions in northern and southern China. METHODS: We extracted claims data from medical insurance systems in Hua County of Henan Province, and Shantou City in Guangdong Province in China from Jan 1, 2012 to Jun 30, 2019. These two regions have been considered to be high risk regions for oesophageal cancer. We developed a rigorous procedure to establish the MIS-CASS, which includes data extraction, cleaning, processing, case ascertainment, privacy protection, etc. Text-based diagnosis in conjunction with ICD-10 codes were used to determine cancer diagnosis. FINDINGS: In 2018, the overall age-standardised (Segi population) incidence rates (ASR World) of cancer in Hua County and Shantou City were 167·39/100,000 and 159·78/100,000 respectively. In both of these areas, lung cancer and breast cancer were the most common cancers in males and females respectively. Hua County is a high-risk region for oesophageal cancer (ASR World: 25·95/100,000), whereas Shantou City is not a high-risk region for oesophageal cancer (ASR World: 11·43/100,000). However, Nanao island had the highest incidence of oesophageal cancer among all districts and counties in Shantou (ASR World: 36·39/100,000). The age-standardised male-to-female ratio for oesophageal cancer was lower in Hua County than in Shantou (1·69 vs. 4·02). A six-month lag time was needed to report these cancer incidences for the MIS-CASS. INTERPRETATION: MIS-CASS efficiently reflects cancer burden in real-time, and has the potential to provide insight for improvement of cancer surveillance in China. FUNDING: The National Key R&D Program of China (2016YFC0901404), the Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals (XXZ0204), the Sanming Project of Shenzhen (SZSM201612061), and the Shantou Science and Technology Bureau (190829105556145, 180918114960704).

A universal strategy for fabrication and morphology control of polyoxometalate-based metal-organic frameworks.

A novel method is proposed to fabricate polyoxometalate-based metal-organic frameworks (POM@MOFs) by using the ability of POMs to oxidize metals to cations. The morphology-controlled growth of POM@MOFs (NENU-n) is achieved in the absence of any modulators and an effect of polyoxoanion charge number on morphology is observed.