Identification and quantification of nine compounds in Fangwen Jiuwei decoction by liquid chromatography-mass spectrometry.

Fangwen Jiuwei Decoction is a traditional Chinese medicine preparation for the treatment of pneumonia developed by Shenzhen Bao'an Chinese Medicine Hospital, which shows remarkable clinical responses. Qualitative and quantitative analyses of the main active compounds are crucial for the quality control of traditional Chinese medicine prescription in clinical application. In this study, we identified nine active compounds essential for the pharmacological effects of Fangwen Jiuwei Decoction based on the analysis of the Network Pharmacology and relevant literature. Moreover, these compounds can interact with several crucial drug targets in pneumonia based on molecular docking. We applied high-performance liquid chromatography-tandem mass spectrometry method was established these nine active ingredients' qualitative and quantitative detections. The possible cleavage pathways of nine active components were determined based on secondary ions mass spectrometry. The results of high-performance liquid chromatography-tandem mass spectrometry were further validated, which show a satisfactory correlation coefficient (r > 0.99), recovery rate (≥93.31%), repeatability rate (≤5.62%), stability (≤7.95%), intra-day precision (≤6.68%), and inter-day precision (≤9.78%). The limit of detection was as low as 0.01 ng/ml. In this study, we established a high-performance liquid chromatography-tandem mass spectrometry method to qualitatively and quantitatively analyze the chemical components in the Fangwen Jiuwei Decoction extract.

Effectiveness of influenza vaccination on in-hospital death in older adults with respiratory diseases.

Influenza vaccination is associated with lower risk of hospitalization outcomes among older adults with respiratory diseases, but there is limited evidence by disease subtypes and patients' characteristics. This study included patients aged ≥60 years hospitalized for respiratory diseases from the Beijing Urban Employee Basic Medical Insurance database during 6 influenza seasons. Vaccination status was assessed by linking with the Beijing Elderly Influenza Vaccination database. Multi-variable logistic regression was performed to calculate effect estimates. After adjusting for measured and unmeasured confounders, influenza vaccination was associated with a lower risk of in-hospital death among older adults hospitalized for respiratory diseases (odds ratio [95% confidence interval], 0.70 [0.62-0.80]). The protective association was observed among patients with chronic obstructive pulmonary disease (0.67 [0.47-0.98]) as well as those with pneumonia or influenza (0.77 [0.64-0.93]). The protective association was stronger in younger patients (0.59 [0.43-0.81] for <75 and 0.72 [0.63-0.83] for ≥75) and those with fewer comorbidities (0.49 [0.16-1.62] for 0, 0.65 [0.50-0.86] for 1-2, and 0.72 [0.63-0.83] for ≥3 comorbidities). Influenza vaccination was associated with lower risk of in-hospital death among older patients hospitalized for respiratory diseases, with stronger associations in patients with younger age and fewer comorbidities.

We found that influenza vaccination was associated with lower risk of in-hospital death among older adults hospitalized for respiratory diseases. The associations were stronger in patients with younger age and fewer comorbidities. The study suggested that, in addition to prevent influenza itself, influenza vaccination may also prevent in-hospital death among patients with respiratory diseases.

Greenspace and mortality in the U.K. Biobank: Longitudinal cohort analysis of socio-economic, environmental, and biomarker pathways.

Exposure to natural greenspace benefits health through direct and indirect pathways: increasing physical activity, improving mental health, relieving social isolation, reducing exposure to extreme temperature, noise, and air pollution. Understanding the etiologic pathway of greenspace and health is needed. Here, we used a large cohort follow-up data from the U.K. Biobank to quantify the magnitude of behavioural factors, psychological factors, biomarkers/physiological measurements, co-morbid diseases, and environmental exposure as potential mediators in the relationship between greenspace and mortality. We estimated hazard ratios (HR) with Cox proportional hazards models, and undertook exploratory mediation analyses to quantify the relative contribution of five types of mediators. Our results indicate greenspace was strongly associated with lower mortality risks [per IQR of public greenspace (HR = 0.90 (95% CI 0.86-0.84)) and domestic gardens (HR = 0.91, (95% CI 0.88-0.94))]. The protective associations were especially pronounced among those with lower individual-level socioeconomic status or living in places with area-level deprivation. Exploratory mediation analysis detected benefits in pathways through reducing air pollution, relieving social isolation and depression, increased physical activity and time spent outdoor, better lung function (FEV1/FVC), and having higher serum vitamin D levels.

Systematic Qualitative and Quantitative Analyses of Wenxin Granule via Ultra-High Performance Liquid Chromatography Coupled with Ion Mobility Quadrupole Time-of-Flight Mass Spectrometry and Triple Quadrupole-Linear Ion Trap Mass Spectrometry.

Wenxin granule (WXG) is a popular traditional Chinese medicine (TCM) preparation for the treatment of arrhythmia disease. Potent analytical technologies are needed to elucidate its chemical composition and assess the quality differences among multibatch samples. In this work, both a multicomponent characterization and quantitative assay of WXG were conducted using two liquid chromatography-mass spectrometry (LC-MS) approaches. An ultra-high performance liquid chromatography-ion mobility quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) approach combined with intelligent peak annotation workflows was developed to characterize the multicomponents of WXG. A hybrid scan approach enabling alternative data-independent and data-dependent acquisitions was established. We characterized 205 components, including 92 ginsenosides, 53 steroidal saponins, 14 alkaloids, and 46 others. Moreover, an optimized scheduled multiple reaction monitoring (sMRM) method was elaborated, targeting 24 compounds of WXG via ultra-high performance liquid chromatography-triple quadrupole linear ion trap mass spectrometry (UHPLC/QTrap-MS), which was validated based on its selectivity, precision, stability, repeatability, linearity, sensitivity, recovery, and matrix effect. By applying this method to 27 batches of WXG samples, the content variations of multiple markers from Notoginseng Radix et Rhizoma (21) and Codonopsis Radix (3) were depicted. Conclusively, we achieved the comprehensive multicomponent characterization and holistic quality assessment of WXG by targeting the non-volatile components.

Radiographic features and prognosis of early- and late-onset non-small cell lung cancer immune checkpoint inhibitor-related pneumonitis.

BACKGROUND: Immunotherapy is becoming a standard of care for non-small cell lung cancer (NSCLC). Checkpoint inhibitor-associated pneumonia (CIP) is a rare and potentially life-threatening event that can occur at any time during tumor immunotherapy. However, there may be differences in the radiological patterns and prognosis of CIP during different periods. This study aimed to investigate the radiographic features and prognosis of early- and late-onset immune-related pneumonitis. METHODS: We retrospectively analyzed the clinical data of 677 NSCLC patients receiving immunotherapy to identify 32 patients with CIP, analyzed the clinical and radiographic data, and summarized the radiological features and prognosis of early- and late-onset CIP. RESULTS: CIP had an incidence of 4.7%, a median onset time of 10 weeks, and a mortality of 28.1%. Among these, CIP included 14 early-onset cases, where grade ≥ 3 CIP accounted for 92.9%, main radiographic pattern was organizing pneumonia (OP)-like pattern, and mortality was 50.0%. We also identified 18 late-onset CIPs, where grade ≥ 3 CIP accounted for 50.0%, main radiographic pattern was nonspecific interstitial pneumonia (NSIP)-like pattern, and mortality was 11.1%. The overall survival rate of the early-onset group was significantly lower than that of the late-onset group (P < 0.05). CONCLUSION: Early-onset CIP cases were higher in the Common Terminology Criteria for Adverse Events (CTCAE v5.0) grade and mainly presented with an OP-like radiographic pattern; whereas, late-onset CIP cases were lower in CTCAE grade and mainly presented with an NSIP-like radiographic pattern. Finally, the prognosis of the early-onset CIP group was poorer than that of the late-onset CIP group. We believe that this study will be helpful for clinicians for making early diagnosis and deciding treatment modalities for patients with CIP.

Prevalence of toothache in Chinese adults aged 65 years and above.

OBJECTIVES: To investigate the prevalence of toothache and its risk indicators in the older Chinese population. METHODS: National cross-sectional survey data on 25 048 Chinese people ≥65 years in 2011, 2014 and 2018 survey year were analysed and then pooled. Chi-square test was used to examine the differences in prevalence among specific subgroups. Multivariate modified Poisson regression analyses with robust error variances were used to detect related factors and prevalence ratios (PR) were calculated. RESULTS: The prevalence of toothache was 16.3% (95% CI: 15.5%-17.1%), 12.8% (95% CI: 12.0%-13.7%) and 16.0% (95% CI: 15.3%-16.7%) in years 2011, 2014 and 2018. In the pooled multivariate Poisson regression model, factors associated with toothache were female (PR: 1.27, 95% CI: 1.18-1.37), younger age (PR: 1.84, 95% CI: 1.63-2.09), currently married and living with spouse (PR: 1.08, 95% CI: 1.01-1.15), current living in urban area (PR:1.12, 95% CI: 1.06-1.20), enough financial support (PR: 0.69, 95% CI: 0.65-0.74), having chronic disease (PR: 1.46, 95% CI: 1.35, 1.57), higher sugar intake (PR: 1.10, 95% CI: 1.03-1.17), salty flavour (PR:1.15, 95% CI: 1.07-1.23), smoking (PR: 1.14, 95% CI:1.06-1.23) or drinking (PR: 1.17, 95% CI: 1.09-1.25), with denture (PR: 1.15, 95% CI: 1.08-1.22) and higher toothbrushing frequency (PR: 1.25-1.50). CONCLUSIONS: More than one in ten older Chinese population had toothache, and it was related to age, gender, socioeconomic status, behaviour and oral health status. Lifestyle interventions should be taken to avoid the occurrence of the toothache.

Correction: Combination of PEG-decorated black phosphorus nanosheets and immunoadjuvant for photoimmunotherapy of melanoma.

Correction for 'Combination of PEG-decorated black phosphorus nanosheets and immunoadjuvant for photoimmunotherapy of melanoma' by Shiyu Wan et al., J. Mater. Chem. B, 2020, 8, 2805-2813.

Human serum albumin-based doxorubicin prodrug nanoparticles with tumor pH-responsive aggregation-enhanced retention and reduced cardiotoxicity.

Doxorubicin (DOX) is a widely-used anticancer drug, but its cardiotoxicity severely hampers its potency in chemotherapy. Herein, human serum albumin (HSA) is engaged as a biocompatible nanocarrier to load a pH-sensitive DOX prodrug, DMDOX, generating HSA-DMDOX nanoparticles via self-assembly driven by hydrophobic interactions. HSA-DMDOX disperses well in a physiological environment (∼40 nm) but aggregates in a tumor acidic microenvironment (pH 6.5, ∼140 nm) owing to the hydrophobicity increase of DMDOX by protonation of carboxylic groups. In vitro anticancer study showed that HSA-DMDOX exhibited enhanced cellular uptake by 4T1 cells and superior cytotoxicity in comparison to HSA-DOX nanoparticles. In vivo study suggested that HSA-DMDOX achieved long blood circulation, aggregation enhanced tumor retention, comparable antitumor efficacy and reduced cardiotoxicity relative to free DOX. Our work presents a facile and effective approach to delivering anthracyclines by HSA-based tumor pH-responsive nanoparticles with aggregation-enhanced tumor retention and reduced toxicity.

Combination of PEG-decorated black phosphorus nanosheets and immunoadjuvant for photoimmunotherapy of melanoma.

Photoimmunotherapy, which combines local photothermal therapy (PTT) with immunological stimulation, is a promising modality for cancer treatment. Herein, we have reported a photothermal-immunotherapy of melanoma using pegylated black phosphorus nanosheets (BP-PEG NSs) and imiquimod (R837) as the photothermal conversion agent and the immunoadjuvant, respectively. The photothermal stability of BP NSs was remarkably enhanced after the modification of poly(ethylene glycol) (PEG) by electrostatic interactions. The in situ generation of tumor-associated antigens by PTT elicited a strong immune response in the presence of R837, achieving a photoimmunotherapy of B16 melanoma. This photoimmunotherapy stimulated a stronger immune response both in vitro and in vivo than monotherapy, inducing a much greater release of cytokines such as IL-6, IL-12, and TNF-α. In vivo antitumor studies in B16 tumor-bearing mice demonstrated that photoimmunotherapy showed the best tumor inhibition effects. Our study suggested that BP-PEG NS-based PTT primed with an immunoadjuvant can be used for synergistic photoimmunotherapy of melanomas.

Leveraging a polycationic polymer to direct tunable loading of an anticancer agent and photosensitizer with opposite charges for chemo-photodynamic therapy.

Herein, we reported a primary amine containing polycationic polymer to load an oppositely charged anticancer drug (doxorubicin, DOX) and a photosensitizer (chlorin e6, Ce6) for combinational chemo-photodynamic therapy. The electrostatic interactions as well as other multiple interactions between the polymer and payloads endowed the drug-loaded nanoparticles with excellent stability. Moreover, the electrostatic attraction between the cationic polymer and anionic Ce6 dictated that Ce6 had higher loading efficiency than DOX. DOX showed pH-responsive drug release owing to the increased solubility of protonated DOX and reduced interaction with the partially protonated polymer under acidic conditions. In contrast, Ce6 showed pH-insensitive release because of the smaller change in solubility and the intense interactions between Ce6 and the polymer. Synergistic chemo/photodynamic therapy of 4T1 cancer cells was achieved by light-triggered reactive oxygen species (ROS)-mediated enhanced cellular uptake and effective endo/lysosomal escape of drug-loaded nanoparticles. Our study demonstrated that the polycationic polymer could act as a robust carrier for differential loading and release of oppositely charged cargos for combinational therapy.

A dithiocarbamate-based H2O2-responsive prodrug for combinational chemotherapy and oxidative stress amplification therapy.

Here, we report the rational design of a H2O2-responsive diethyldithiocarbamate (DTC)-based prodrug, which chelated Cu(ii) to form Cu(DTC)2 with a high anticancer activity in a tumor-microenvironment and induced oxidative stress amplification, showing superior antitumor toxicity to disulfiram.

Highly Stable, Coordinated Polymeric Nanoparticles Loading Copper(II) Diethyldithiocarbamate for Combinational Chemo/Chemodynamic Therapy of Cancer.

Disulfiram (DSF) has excellent in vitro anticancer activity in the presence of Cu(II). The anticancer mechanism studies have demonstrated that copper(II) diethyldithiocarbamate, Cu(DDC)2, is the crucial DSF's metabolite exhibiting anticancer activity. In this paper, highly stable polymeric nanoparticles were fabricated via a coordination strategy between Cu(II) and carboxylic groups in poly(ethylene glycol)- b-poly(ester-carbonate) (PEC) for efficient loading of Cu(DDC)2, which was generated by the in situ reaction of DSF and Cu(II). The properties of nanoparticles such as drug loading contents, sizes, and morphologies could be tuned by varying the feeding ratios of DSF, Cu(II), and PEC. These Cu(II)/DDC-loaded nanoparticles showed excellent stability in both neutral and weak acidic solutions and under dilution. In vitro anticancer study established that Cu(II)/DDC-loaded nanoparticles could enable a combination therapy of Cu(DDC)2-based chemotherapy and chemodynamic therapy mediated by bioavailable Cu(II) that was not in the form of Cu(DDC)2. The in vivo antitumor results demonstrated that the Cu(II)/DDC-loaded nanoparticles showed superior antitumor efficacy to DSF/Cu(II). Our study provided a facile and effective strategy of highly stable coordination-mediated polymeric nanoparticles for combinational therapy of cancer.