Evidence linking COVID-19 and the health/well-being of children and adolescents: an umbrella review.

BACKGROUND: Experiences during childhood and adolescence have enduring impacts on physical and mental well-being, overall quality of life, and socioeconomic status throughout one's lifetime. This underscores the importance of prioritizing the health of children and adolescents to establish an impactful healthcare system that benefits both individuals and society. It is crucial for healthcare providers and policymakers to examine the relationship between COVID-19 and the health of children and adolescents, as this understanding will guide the creation of interventions and policies for the long-term management of the virus. METHODS: In this umbrella review (PROSPERO ID: CRD42023401106), systematic reviews were identified from the Cochrane Database of Systematic Reviews; EMBASE (OvidSP); and MEDLINE (OvidSP) from December 2019 to February 2023. Pairwise and single-arm meta-analyses were extracted from the included systematic reviews. The methodological quality appraisal was completed using the AMSTAR-2 tool. Single-arm meta-analyses were re-presented under six domains associated with COVID-19 condition. Pairwise meta-analyses were classified into five domains according to the evidence classification criteria. Rosenberg's FSN was calculated for both binary and continuous measures. RESULTS: We identified 1551 single-arm and 301 pairwise meta-analyses from 124 systematic reviews that met our predefined criteria for inclusion. The focus of the meta-analytical evidence was predominantly on the physical outcomes of COVID-19, encompassing both single-arm and pairwise study designs. However, the quality of evidence and methodological rigor were suboptimal. Based on the evidence gathered from single-arm meta-analyses, we constructed an illustrative representation of the disease severity, clinical manifestations, laboratory and radiological findings, treatments, and outcomes from 2020 to 2022. Additionally, we discovered 17 instances of strong or highly suggestive pairwise meta-analytical evidence concerning long-COVID, pediatric comorbidity, COVID-19 vaccines, mental health, and depression. CONCLUSIONS: The findings of our study advocate for the implementation of surveillance systems to track health consequences associated with COVID-19 and the establishment of multidisciplinary collaborative rehabilitation programs for affected younger populations. In future research endeavors, it is important to prioritize the investigation of non-physical outcomes to bridge the gap between research findings and clinical application in this field.

ZNF32 prevents the activation of cancer-associated fibroblasts through negative regulation of TGFB1 transcription in breast cancer.

Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related deaths in women worldwide. Cancer-associated fibroblasts (CAFs) are one of the fundamental cellular components of the tumor microenvironment and play a critical role in the initiation, progression, and therapy resistance of breast cancer. However, the detailed molecular mechanisms of CAFs activation from normal fibroblasts (NFs) are still not well understood. In the present study, we reported that ZNF32 expression in breast cancer cells was negatively correlated with CAF-related markers (FSP1, α-SMA, and FAP) in stromal fibroblasts, and loss of ZNF32 promoted the activation of CAFs, as evidenced by the enhanced proliferation and contractility of CAFs. ZNF32 deficiency-mediated fibroblast activation promoted the growth and metastasis of breast cancer cells in vitro and in vivo. Mechanistically, we demonstrated that ZNF32 inhibited TGFB1 transcription by directly binding to the -1968/-1962 region of the TGFB1 promoter, leading to the prevention of fibroblast activation. Altogether, our findings reveal an important mechanism by which ZNF32 suppression increases the transcription of the TGFB1 gene in breast cancer cells, and subsequently, elevated levels of secretory TGF-ß stimulate NFs transformation into CAFs, which in turn facilitates the malignant progression of breast cancer. Our data implicated ZNF32 as a potential therapeutic strategy against breast cancer.

Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell lung cancer.

The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR). Through an exogenous corona strategy, bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction. After intravenous injection, BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging. Bevacizumab is released from BCGN upon oxidation in tumor microenvironment, whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm. The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models. Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.

Optimization of polarization parameters for an LCVR polarization spectrometer under non-oversampling.

The spectral polarization measurement can obtain not only the spectral information of the target but also its polarization information, which can improve the detection and identification of the measured target. In the polarization spectrometer based on a liquid crystal variable retarder (LCVR) and acousto-optic tunable filter (AOTF), the LCVR is a core device for achieving fast and high-precision polarization detection. The AOTF is a new, to the best of our knowledge, filter device for spectral tuning. To reduce the sensitivity of an LCVR-based Stokes polarization spectrometer system to errors and Gaussian noise, and to maintain the advantage of fast electrical tuning of the system for spectral polarization detection, the phase retardation and azimuth angle of the polarization device LCVR is calculated and analyzed optimally under the minimum number of samples N=4 of the Stokes vector measurement method in this paper. The optimization algorithm considers the constraints, such as the number of types of LCVR phase retardation and the number of adjustments, and the azimuth and phase retardation to be optimized are searched for optimality step by step. The simulation results show that the number of adjustments of the phase retardation δ of LCVRs is only three times when four Stokes parameters are obtained. The LCVRs' number of species is four kinds (2×2). The condition number of the optimized measurement matrix is 1.742, which converges to the ideal condition number, the optimal azimuth angle (θ 1,θ 2) is (18.9°, 41.9°), and the optimal phase retardation δ is (179.9°, 156.6°, 0.4°, 46.3°). Its corresponding tetrahedral volume is closer to the ideal value. The optimized system is less sensitive to errors and Gaussian noise.

Medication therapy of high-dose methotrexate: An evidence-based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

AIMS: A lot of medication risks related to high-dose methotrexate (HDMTX) therapy still remain to be identified and standardized. This study aims to establish an evidence-based practice guideline for individualized medication of HDMTX. METHODS: The practice guideline was launched by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. The guideline was developed following the WHO handbook for guideline development and the methodology of evidence-based medicine (EBM). The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2017CN021). Systematic reviews were conducted to synthesize available evidence. A multicentre cross-sectional study was conducted using questionnaires to evaluate patients' perception and willingness concerning individualized medication of HDMTX. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the quality of evidence and to grade the strength of recommendations. RESULTS: Multidisciplinary working groups were included in this guideline, including clinicians, pharmacists, methodologists, pharmacologists and pharmacoeconomic specialists. A total of 124 patients were involved to integrate patient values and preferences. Finally, the guideline presents 28 recommendations, regarding evaluation prior to administration (renal function, liver function, pleural effusion, comedications, genetic testing), pre-treatment and routine dosing regimen, therapeutic drug monitoring (necessity, method, timing, target concentration), leucovorin rescue (initial timing, dosage regimen and optimization), and management of toxicities. Of these, 12 are strong recommendations. CONCLUSIONS: We developed an evidence-based practice guideline with respect to HDMTX medication using a rigorous and multidisciplinary approach. This guideline provides comprehensive and practical recommendations involving the whole process of HDMTX administration to health care providers.

Design and simulation analysis of the AOTF full-Stokes imaging spectropolarimeter.

In order to effectively improve the contrast of target identification, an acousto-optic tunable filter (AOTF) full-Stokes imaging spectropolarimeter is proposed, which can measure synchronously polarization information with each spectral band in real time. The full-Stokes vectors are obtained by the division-of-aperture polarization imaging system. The spectral bands are selected by RF of the AOTF electrically. Based on this system, a polarization error model is established, and the influence of the key polarization element angle error is analyzed. The results show that the measurement error increases with the increase of the polarization degree. When P=1, the influence of the azimuth angle error is greater than the retardance error under the same angle error. The results are helpful to find the variation law of the polarization error and provide a theoretical reference for the design of new types of full-Stokes imaging spectropolarimeters.

Poly(maleic anhydride-alt-1-octadecene)-based bioadhesive nanovehicles improve oral bioavailability of poor water-soluble gefitinib.

The poor water solubility and inadequate oral bioavailability of gefitinib (Gef) remain a critical issue to achieve the therapeutic outcomes. Herein, we designed a poly(maleic anhydride-alt-1-octadecene) (PMA/C18) based lipid nanovehicle (PLN) to improve the intestinal absorption and oral bioavailability of poorly water-soluble Gef. PLN was nanometer-sized particles, and Gef was dispersed in the PLN formulation as amorphous or molecular state. At 4 h of oral administration, the tissue concentration of Gef in duodenum, jejunum, and ileum was profoundly enhanced 3.37-, 8.94-, and 8.09-fold by PLN when comparing to the counterpart lipid nanovehicle. Moreover, the oral bioavailability of Gef was significantly enhanced 2.48-fold by the PLN formulation when comparing to the free drug suspension. Therefore, this study provides an encouraging bioadhesive delivery platform to improve the oral delivery of poorly water-soluble drugs.

In Vivo Environment-Adaptive Nanocomplex with Tumor Cell-Specific Cytotoxicity Enhances T Cells Infiltration and Improves Cancer Therapy.

Drug delivery strategies possessing selectivity for cancer cells are eagerly needed in therapy of metastatic breast cancer. In this study, the chemotherapeutic agent, docetaxel (DTX), is conjugated onto heparan sulfate (HS). Aspirin (ASP), which has the activity of anti-metastasis and enhancing T cells infiltration in tumors, is encapsulated into the HS-DTX micelle. Then the cationic polyethyleneimine (PEI)-polyethylene glycol (PEG) copolymer binds to HS via electrostatic force, forming the ASP-loaded HS-DTX micelle (AHD)/PEI-PEG nanocomplex (PAHD). PAHD displays long circulation behavior in blood due to the PEG shell. Under the tumor microenvironment with weakly acidic pH, PEI-PEG separates from AHD, and the free cationic PEI-PEG facilitates the cellular uptake of AHD by increasing permeability of cell membranes. Then the overexpressed heparanase degrades HS, releasing ASP and DTX. PAHD shows specific toxicity toward tumor cells but not normal cells, with advanced activity of inhibiting tumor growth and lung metastasis in 4T1 tumor-bearing mice. The number of CD8+ T cells in tumor tissues is also increased. Therefore, PAHD can become an efficient drug delivery system for breast cancer treatment.

Rubus Occidentalis and its bioactive compounds against cancer: From molecular mechanisms to translational advances.

BACKGROUND: Cancer ranks as the second leading cause of death globally, imposing a significant public health burden. The rise in cancer resistance to current therapeutic agents underscores the potential role of phytotherapy. Black raspberry (BRB, Rubus Occidentalis) is a fruit rich in anthocyanins, ellagic acid, and ellagitannins. Accumulating evidence suggests that BRB exhibits promising anticancer effects, positioning it as a viable candidate for phytotherapy. PURPOSE: This article aims to review the existing research on BRB regarding its role in cancer prevention and treatment. It further analyzes the effective components of BRB, their metabolic pathways, and the potential mechanisms underlying the fruit's anticancer effects. METHODS: Ovid MEDLINE, EMBASE, Web of Science, and CENTRAL were searched through the terms of Black Raspberry, Raspberry, and Rubus Occidentali up to January 2023. Two reviewers performed the study selection by screening the title and abstract. Full texts of potentially eligible studies were retrieved to access the details. RESULTS: Out of the 767 articles assessed, 73 papers met the inclusion criteria. Among them, 63 papers investigated the anticancer mechanisms, while 10 conducted clinical trials focusing on cancer treatment or prevention. BRB was found to influence multiple cancer hallmarks by targeting various pathways. Decomposition of free radicals and regulation of estrogen metabolism, BRB can reduce DNA damage caused by reactive oxygen species. BRB can also enhance the function of nucleotide excision repair to repair DNA lesions. Through regulation of epigenetics, BRB can enhance the expression of tumor suppressor genes, inducing cell cycle arrest, and promoting apoptosis and pyroptosis. BRB can reduce the energy and nutrients supply to the cancer nest by inhibiting glycolysis and reducing angiogenesis. The immune and inflammatory microenvironment surrounding cancer cells can also be ameliorated by BRB, inhibiting cancer initiation and progression. However, the limited bioavailability of BRB diminishes its anticancer efficacy. Notably, topical applications of BRB, such as gels and suppositories, have demonstrated significant clinical benefits. CONCLUSION: BRB inhibits cancer initiation, progression, and metastasis through diverse anticancer mechanisms while exhibiting minimal side effects. Given its potential, BRB emerges as a promising phototherapeutic agent for cancer treatment.

DDX39B protects against sorafenib-induced ferroptosis by facilitating the splicing and cytoplasmic export of GPX4 pre-mRNA in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the main histological subtype of primary liver cancer and remains one of the most common solid malignancies globally. Ferroptosis was recently defined as an iron-catalyzed form of regulated necrosis. Because cancer cells exhibit higher iron requirements than noncancer cells, treatment with ferroptosis-inducing compounds may be a feasible strategy for cancer therapy. However, cancer cells develop acquired resistance to evade ferroptosis, and the mechanisms responsible for ferroptosis resistance are not fully clarified. In the current study, we reported that DDX39B was downregulated during sorafenib-induced ferroptosis in a dose- and time-dependent manner. Exogenous introduction of DDX39B ensured the survival of HCC cells upon exposure to sorafenib, while the opposite phenomenon was observed in DDX39B-silenced HCC cells. Mechanistically, we demonstrated that DDX39B increased GPX4 levels by promoting the splicing and cytoplasmic translocation of GPX4 pre-mRNA, which was sufficient to detoxify sorafenib-triggered excess lipid ROS production, lipid peroxidation accumulation, ferrous iron levels, and mitochondrial damage. Inhibition of DDX39B ATPase activity by CCT018159 repressed the splicing and cytoplasmic export of GPX4 pre-mRNA and synergistically assisted sorafenib-induced ferroptotic cell death in HCC cells. Taken together, our data uncover a novel role for DDX39B in ferroptosis resistance by modulating the maturation of GPX4 mRNA via a posttranscriptional approach and suggest that DDX39B inhibition may be a promising therapeutic strategy to enhance the sensitivity and vulnerability of HCC cells to sorafenib.

Thrombospondin-1 and prolyl 4-hydroxylase subunit alpha 3 as potential biomarkers of salivary gland fibrosis.

Background/purpose: Fibrosis is present in various physiologic and pathologic conditions of salivary glands (SGs). This study aimed to identify novel biomarkers of SG fibrosis by next-generation sequencing. Materials and methods: We established the SG fibrosis mouse model by excretory main duct ligation. Next-generation sequencing, differentially expressed gene (DEG) analysis, and gene set enrichment analysis was performed by comparing ligated and control SGs. We used algorithms of Cytohubba, molecular complex detection, Lasso logistic regression, and support vector machine to identify the key biomarkers. Selected key biomarkers were verified by the polymerase chain reaction and immunohistochemistry. We also retrieved and analyzed the key gene expression in the fibrosis of the heart, liver, lung, and kidney to ensure the generalization of key biomarkers in SG fibrosis. Results: Both interlobular and intralobular fibrosis was confirmed in the ligated SGs, with improved expressions of collagen I and transforming growth factor ß. Next-generation sequencing identified 2666 upregulated DEGs and 336 downregulated DEGs, which were highly enriched in the extracellular matrix-related pathways. Multiple algorithms identified 15 key biomarkers in SG fibrosis, including Thrombospondin-1 (THBS1) and Prolyl 4-Hydroxylase Subunit Alpha 3 (P4HA3). The mRNA and protein expression of THBS1 and P4HA3 was verified in mice. THBS1 was also highly expressed in lung and kidney fibrosis, whereas P4HA3 was upregulated in liver fibrosis. Conclusion: THBS1 and P4HA3 may be potential biomarkers for SG fibrosis. They may be also applicable in the diagnosis of multi-organ fibrosis.

Reporting inconsistency between published conference abstracts and article abstracts of randomised controlled trials in prosthodontics presented at IADR general sessions.

Background: There is commonly a discrepancy between conference abstracts and published article abstracts in prosthodontic randomized controlled trials (RCTs), which may mislead the scholars those attend conferences. Objective: To identify the characteristics predicting inconsistency between conference abstracts and published article abstracts in prosthodontic RCTs. Methods: The conference abstracts of prosthodontic RCTs presented at the IADR general sessions from 2002 to 2015 were searched. Electronic searches of MEDLINE, EMBASE, the Cochrane Library, and Google Scholar databases were conducted to match full-text publications for conference abstracts. Two investigators extracted basic characteristics and assessed the consistency and reporting quality independently and in duplicate. The linear regression model was used to analyze the predictors of inconsistency. Results: A total of 147 conference abstracts were matched with published articles. Results for the secondary outcome measure, Statistical analysis, and precision measure were less than 50% consistent, and even nearly 5% of the studies had opposite conclusions. Multiple linear regression analysis showed that three factors were correlated with lower inconsistency, including continent of origin (p = 0.011), presentation type (p = 0.017), and difference in reporting quality (p = 0.013). Conclusion: Conference attendees should cautiously treat the findings of the conference abstracts. Researchers should improve the precision of the information delivered at conferences. We recommend the authors of RCTs to explain the primary difference between conference abstracts and article abstracts.

Specific inhibitor of Smad3 (SIS3) alleviated submandibular gland fibrosis and dysfunction after dominant duct ligation in mice.

Background/purpose: Chronic obstructive sialadenitis (COS) is a condition that severely reduced patients' quality of life. This study aimed to analyze the effects of SIS3, a specific inhibitor of small mothers against decapentaplegic 3 (SMAD3), on the submandibular gland (SMG) dysfunction, fibrosis, and inflammation. Materials and methods: The dominant duct in the SMG was ligated in mice, followed by intraperitoneal injection of SIS3 (2 mg/kg/day) or Dimethyl sulfoxide (DMSO) saline for 7 days. In the sham group, this duct was surgically identified but not ligated. Saliva flow, histological structure, fibrosis, Transforming growth factor-ß1 (TGF-ß)/SMAD3 signaling, and inflammatory cytokines, were analyzed. Results: SIS3 rescued ligation-induced SMG dysfunction and improved the saliva flow rate compared to DMSO. SIS3 alleviated acinar atrophy and ductal dilation and maintained the morphology of the basal membrane. SIS3 reduces interlobular and intralobular fibrosis and collagen deposition. We observed reduced SMAD3 phosphorylation and TGF-ß expression. The SIS3 group showed downregulation of np_5318 and miR-21 and upregulation of miR-29 b compared to the DMSO group. Moreover, SIS3 controlled the inflammatory cytokine release, including interleukin-6 and interleukin-1ß. Conclusion: SIS3 protected duct-ligated SMGs against fibrosis and dysfunction by inhibiting the TGF-ß/SMAD3 signaling and inflammatory cytokine expression. SIS3 may serve as a promising treatment for chronic obstructive sialadenitis.

Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells.

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.

Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry.

Bioorthogonal chemistry reactions occur in physiological conditions without interfering with normal physiological processes. Through metabolic engineering, bioorthogonal groups can be tagged onto cell membranes, which selectively attach to cargos with paired groups via bioorthogonal reactions. Due to its simplicity, high efficiency, and specificity, bioorthogonal chemistry has demonstrated great application potential in drug delivery. On the one hand, bioorthogonal reactions improve therapeutic agent delivery to target sites, overcoming off-target distribution. On the other hand, nanoparticles and biomolecules can be linked to cell membranes by bioorthogonal reactions, providing approaches to developing multi-functional drug delivery systems (DDSs). In this review, we first describe the principle of labeling cells or pathogenic microorganisms with bioorthogonal groups. We then highlight recent breakthroughs in developing active targeting DDSs to tumors, immune systems, or bacteria by bioorthogonal chemistry, as well as applications of bioorthogonal chemistry in developing functional bio-inspired DDSs (biomimetic DDSs, cell-based DDSs, bacteria-based and phage-based DDSs) and hydrogels. Finally, we discuss the difficulties and prospective direction of bioorthogonal chemistry in drug delivery. We expect this review will help us understand the latest advances in the development of active targeting and multi-functional DDSs using bioorthogonal chemistry and inspire innovative applications of bioorthogonal chemistry in developing smart DDSs for disease treatment.

Severe Thrombocytopenia Caused by Vancomycin in the Intensive Care Unit: A Case Report.

Thrombocytopenia can cause substantial morbidity and mortality in critically ill patients. There are multiple etiology factors and various mechanisms associated with thrombocytopenia, of which drug-induced thrombocytopenia (DITP) deserves attention. Herein, we describe a case of severe thrombocytopenia during intensive care unit (ICU) hospitalization that was likely to be associated with vancomycin. By revealing the process of identifying this case of DITP and reviewing relevant clinical studies, a risk alert of vancomycin-related severe hematotoxicity should be considered.

Walking Dead Tumor Cells for Targeted Drug Delivery Against Lung Metastasis of Triple-Negative Breast Cancer.

Lung metastasis is challenging in patients with triple-negative breast cancer (TNBC). Surgery is always not available due to the dissemination of metastatic foci and most drugs are powerless because of poor retention at metastatic sites. TNBC cells generate an inflamed microenvironment and overexpress adhesive molecules to promote invasion and colonization. Herein, "walking dead" TNBC cells are developed through conjugating anti-PD-1 (programmed death protein 1 inhibitor) and doxorubicin (DOX)-loaded liposomes onto cell corpses for temporal chemo-immunotherapy against lung metastasis. The walking dead TNBC cells maintain plenary tumor antigens to conduct vaccination effects. Anti-PD-1 antibodies are conjugated to cell corpses via reduction-activated linker, and DOX-loaded liposomes are attached by maleimide-thiol coupling. This anchor strategy enables rapid release of anti-PD-1 upon reduction conditions while long-lasting release of DOX at inflamed metastatic sites. The walking dead TNBC cells improve pulmonary accumulation and local retention of drugs, reprogram the lung microenvironment through damage-associated molecular patterns (DAMPs) and PD-1 blockade, and prolong overall survival of lung metastatic 4T1 and EMT6-bearing mice. Taking advantage of the walking dead TNBC cells for pulmonary preferred delivery of chemotherapeutics and checkpoint inhibitors, this study suggests an alternative treatment option of chemo-immunotherapy to augment the efficacy against lung metastasis.

Intramuscular Expression of Plasmid-Encoded FVII-Fc Immunoconjugate for Tumor Immunotherapy by Targeting Tumoral Blood Vessels and Cells.

Tissue factor (TF) has been confirmed to be specifically expressed by vascular endothelial cells (VECs) in solid tumors and certain types of malignant tumor cells. Coagulation factor VII (FVII) can specifically bind to TF with high affinity, so the FVII-TF interaction provides an ideal target for tumor therapy. Expression of proteins in skeletal muscles is a simple and economical avenue for continuous production of therapeutic molecules. However, it is difficult to treat solid tumors till now due to the limited number of therapeutic proteins produced by the intramuscular gene expression system. Herein, we strived to explore whether anti-tumor effects can be achieved via intramuscular delivery of a plasmid encoding a FVII-guided immunoconjugate (Icon) molecule by a previously established Pluronic L64/electropulse (L/E) technique. Our study exhibited several interesting outcomes. 1) The mouse light chain of FVII (mLFVII) molecule could guide red fluorescent protein (RFP) to accumulate predominantly at tumor sites in a TF-dependent manner. 2) Intramuscular expression of mLFVII-hFc (human IgG1 Fc) Icon could significantly inhibit the growth of both liver and lung cancers in nude mice, and the inhibition extent was proportional to the level of tumor-expressed TF. 3) The number of blood vessels and the amount of blood flow in tumors were significantly decreased in mLFVII-hFc Icon-treated mice. 4) This immunotherapy system did not display obvious side effects. Our study provided an efficient and economical system for tumor immunotherapy by targeting both blood vessels and tumor cells. It is also an open system for synergistic therapy by conveniently integrating other anticancer regimens.

The implementation of a FIP guidance for COVID-19: insights from a nationwide survey.

BACKGROUND: The International Pharmaceutical Federation (FIP) has established an interim guidance of coronavirus disease 2019 (COVID-19) for pharmacists worldwide. The aim of this study was to identify the implementation of FIP guidance in China and provide applicable strategies for further actions. METHODS: A nationwide cross-sectional survey on Chinese pharmacists was distributed electronically through groups of WeChat between 9 December 2020 and 18 December 2020. The 29-item questionnaire for the survey was designed based on the FIP guidance and knowledge, attitudes, and practices (KAP) framework. RESULTS: A total of 237 responses from 237 pharmacists (69.20% females) were received. Most pharmacists (81.86%) participated in work related to COVID-19. Respondents referred to other guidelines or consensus more than they did to FIP guidance. Most participants were qualified for the knowledge-based questions regarding COVID-19 (67.51%), had positive attitudes towards pharmacists' roles and actions (61.18%), and were qualified in the practices of prevention measures, infection risk monitoring, and pharmacists' advice (50.63%). Several factors were revealed as having impact on pharmacists' KAP, such as the relevance of participating in work related to COVID-19, work entailments, and information source. CONCLUSIONS: The FIP guidance has a certain degree of dissemination and implementation in China, which can be improved through effective actions directed towards impact factors.

Optimal Management of the Public and Patients by Pharmacists in the Era of COVID-19: An Evidence-Based Review and Practical Recommendations.

Purpose: Currently, managing the public and patients during the COVID-19 pandemic is constituting a health care challenge worldwide. Patient-oriented management is of crucial importance to promote emergency preparedness and response. This study aims to formulate an integrated pharmacist management strategy of the public and patients and to provide evidence-based and practical references. Methods: Evidence-based review and practical analysis were utilized. First, PubMed, EMBASE and Chinese database were searched. Studies about patient management in major public health emergencies were included. Second, the Chinese experience of patient management was analyzed and identified. Finally, combining evidence-based and practical analysis, the pharmacist management strategy of the public and patients was researched and summarized. Results: Regarding the home quarantine period, pharmacist management services should include medication guidance, guidance on risk monitoring, sanitation measures education, health management guidance and psychological support. Regarding the outpatient visit period, pharmacists should participate in the control of in-hospital infections and provide physician-pharmacist joint clinic services, pharmacy clinic services, medication therapy management, medication consultation services, drug supply guarantee and drug dispensing services. Regarding the hospitalization period, pharmacist management services should include monitoring and evaluating the safety and efficacy of medications, providing strengthened care for special populations and other pharmaceutical care. For non-hospitalized or discharged patients, pharmacist management services should include formulating medication materials and establishing pharmacy management files for discharged patients. Conclusion: An evidence-based, patient-centered and entire-process-integrated pharmacist management strategy of the public and patients is established, which remedies the gaps in the existing patient management and can be implemented to support pharmacists' contributions to COVID-19 pandemic control.