Storage, Disposal, and Use of Opioids Among Cancer Patients in Central China: A Multi-Center Cross-Sectional Study.

OBJECTIVE: Unsafe opioid-related practices can lead to abuse, diversion, and accidental overdoses. In this study, we aimed to describe the patterns and beliefs regarding the storage, disposal, and use of opioids among Chinese patients with cancer in their home settings, which remain unclear. METHODS: A multicenter cross-sectional survey was conducted in Hubei Province from October 2022 to June 2023. We collected information on the storage, disposal, and use of opioids among cancer pain inpatients in the oncology department. Logistic regression was used to estimate the factors associated with unsafe disposal and use of opioids. RESULTS: The survey included 221 patients with a median age of 62 years. Only 3.2% stored their opioids under lock and key, and 49.8% were unaware of proper disposal methods. Nearly one-fifth (19.5%) reported having received information on the safe storage (14.0%) and/or disposal (10.0%) of opioids. A total of 44.3% reported unsafe use by sharing (1.8%), losing (4.1%), or taking opioids at a higher dose than prescribed (42.5%). Patients who did not receive information on the safe disposal of opioids (OR = 4.57, P = .0423), had a history of alcohol use (OR = 1.91, P = .0399), and used opioids other than morphine (OR = 2.31, P = .0461) had higher odds of unsafe disposal practices. Individuals with an associate degree/bachelor's degree or above were less likely to dispose of (OR = 0.36, P = .0261) and use (OR = 0.31, P = .0127) opioids unsafely. CONCLUSION: A significant proportion of Chinese patients with cancer exhibit unsafe practices in the storage, disposal, and use of opioids. The study highlights an urgent need for implementing routine education programs and drug "take-back" initiatives to improve opioid-related practices.

Application of nano-radiosensitizers in non-small cell lung cancer.

Radiotherapy stands as a cornerstone in the treatment of numerous malignant tumors, including non-small cell lung cancer. However, the critical challenge of amplifying the tumoricidal effectiveness of radiotherapy while minimizing collateral damage to healthy tissues remains an area of significant research interest. Radiosensitizers, by methods such as amplifying DNA damage and fostering the creation of free radicals, play a pivotal role in enhancing the destructive impact of radiotherapy on tumors. Over recent decades, nano-dimensional radiosensitizers have emerged as a notable advancement. Their mechanisms include cell cycle arrest in the G2/M phase, combating tumor hypoxia, and others, thereby enhancing the efficacy of radiotherapy. This review delves into the evolving landscape of nanomaterials used for radiosensitization in non-small cell lung cancer. It provides insights into the current research progress and critically examines the challenges and future prospects within this burgeoning field.

Current scenario and challenges of clinical pharmacists to implement pharmaceutical care in DRG/DIP payment hospitals in China: a qualitative interview study.

Purpose: The Diagnosis-Related Group (DRG) or Diagnosis-Intervention Packet (DIP) payment system, now introduced in China, intends to streamline healthcare billing practices. However, its implications for clinical pharmacists, pivotal stakeholders in the healthcare system, remain inadequately explored. This study sought to assess the perceptions, challenges, and roles of clinical pharmacists in China following the introduction of the DRG or DIP payment system. Methods: Qualitative interviews were conducted among a sample of clinical pharmacists. Ten semi-structured interviews were conducted, either online or face to face. Thematic analysis was employed to identify key insights and concerns related to their professional landscape under the DRG or DIP system. Results: Clinical pharmacists exhibited variable awareness levels about the DRG or DIP system. Their roles have undergone shifts, creating a balance between traditional responsibilities and new obligations dictated by the DRG or DIP system. Professional development, particularly concerning health economics and DRG-based or DIP-based patient care, was highlighted as a key need. There were calls for policy support at both healthcare and national levels and a revised, holistic performance assessment system. The demand for more resources, be it in training platforms or personnel, was a recurrent theme. Conclusion: The DRG or DIP system's introduction in China poses both opportunities and challenges for clinical pharmacists. Addressing awareness gaps, offering robust policy support, ensuring adequate resource allocation, and recognizing the evolving role of pharmacists are crucial for harmoniously integrating the DRG or DIP system into the Chinese healthcare paradigm.

Dynamic changes in water resources and comprehensive assessment of water resource utilization efficiency in the Aral Sea basin, Central Asia.

The Aral Sea Basin in Central Asia faces significant challenges in improving water utilization and treatment because of frequent transboundary river water disputes and shortages of water resources. However, the traditional water resource utilization efficiency (WRUE) assessment models generally have the defect of over-validating evaluation results. To solve this problem, this study used the Coefficient of Variation method to constrain the self-contained weights in the traditional Data Envelopment Analysis (DEA) to construct an improved CV-DEA model, and assessed the WRUE of the Aral Sea Basin countries during 2000-2018 and compared the WRUE with that of the countries in the Mekong River Basin and Northeast Asia, then explored the factors influencing water utilization. The conclusions were drawn: since 1960, the runoff from the upper Amu Darya and Syr Darya rivers increased significantly, while the runoff from the lower Amu Darya River into the Aral Sea declined. Meanwhile, the water area of the Aral Sea shrank from 2.56 × 104 km2 to 0.70 × 104 km2 in 2000-2018, with the Northern Aral Sea remaining stable while the southern part shrinking sharply. The WRUE of the Aral Sea Basin (0.599, on average) was higher than that of the Mekong River Basin (0.547) and lower than that of Northeast Asia (0.885). Kazakhstan and Uzbekistan had the highest WRUE of 0.819 and 0.685 respectively, and the WRUE in both two countries improved from 2000 to 2018. Tajikistan (0.495) and Turkmenistan (0.402) experienced decreases in WRUEs. The high input redundancy of agricultural water consumption was the main driving force affecting WRUE in the basin.

LncRNA SNHG1 alleviates myocardial ischaemia-reperfusion injury by regulating the miR-137-3p/KLF4/TRPV1 axis.

AIMS: Myocardial ischaemia-reperfusion injury (MIRI) contributes to serious myocardial injury and even death. Long non-coding RNAs (lncRNAs) have been reported to play pivotal roles in the occurrence and development of MIRI. Here, the detailed molecular mechanism of lncRNA SNHG1 in MIRI was explored. METHODS AND RESULTS: A cell model of MIRI was established through hypoxia/reoxygenation (H/R) stimulation. Cell viability and pyroptosis were evaluated utilizing MTT, PI staining, and flow cytometry. Interleukin (IL)-1ß and IL-18 secretion levels were examined by ELISA. The gene and protein expression were detected by RT-qPCR and western blot, respectively. Dual luciferase reporter gene, RIP and ChIP assays were performed to analyse the molecular interactions. The results showed that lncRNA SNHG1 overexpression alleviated H/R-induced HL-1 cell pyroptosis (all P < 0.05). LncRNA SNHG1 promoted KLF4 expression by sponging miR-137-3p. miR-137-3p silencing alleviated H/R-induced pyroptosis in HL-1 cells (all P < 0.05), which was abolished by KLF4 knockdown (all P < 0.05). KLF4 activated the AKT pathway by transcriptionally activating TRPV1 in HL-1 cells (all P < 0.05). TRPV1 knockdown reversed the alleviation of SNHG1 upregulation on H/R-induced pyroptosis in HL-1 cells (all P < 0.05). CONCLUSIONS: These results showed that lncRNA SNHG1 assuaged cardiomyocyte pyroptosis during MIRI progression by regulating the KLF4/TRPV1/AKT axis through sponging miR-137-3p. Our findings may provide novel therapeutic targets for MIRI.

Effects of temperature on cathepsin B, cathepsin D and acid phosphatase during embryo development of the hard tick Haemaphysalis longicornis.

The effects of temperature on the expression patterns and enzyme activity of cathepsin B (HlCatB), cathepsin D (HlCatD) and acid phosphatase (HlACP) during the embryo development of Haemaphysalis longicornis (bisexual population) were investigated in this study. Eggs were exposed to 20 °C (low temperature), 26 °C (normal temperature), and 30 °C (high temperature) immediately after laying, and collected on odd days of embryo development to measure HlCatB, HlCatD and HlACP gene expression using quantitative real-time PCR, as well as three enzyme activities using spectrophotometry. Then the associations between mRNA expression levels of three enzymes and their enzyme activities were assessed. Compared with normal temperature, the mRNA expression peaks of HlCatB were higher and appeared later at low and high temperatures and the activity of HlCatB increased on most days of embryonic development at high temperature. As for HlCatD, the expression peak appeared later at low temperature, but earlier at high temperature. The activity peaks of HlCatD were lower and appeared earlier at low and high temperatures. As for HlACP, the expression peak was higher and appeared later at low temperature, whereas it formed no prominent peak at high temperature. The activity peak of HlACP was higher at low temperature, but lower at high temperature. The linear regression analysis showed that activities of three enzymes were associated with their mRNA expression levels (P < 0.05). Three enzymes are involved in the embryo adaptation to temperature stress. Moreover, the mRNA expression level may be another factor affecting its enzyme activity.

Social Infrastructure and Street Networks as Critical Infrastructure for Aging Friendly Community Design: Mediating the Effect of Physical Activity.

Establishing an age-friendly environment at the community level is essential for promoting healthy aging. This study focused on the relationship between older adults and the community environment through their levels of satisfaction within it. We measured their physical activity (PA) in the community environment and three variables of community-level satisfaction: community environment (SCE), community social infrastructure (SSI), and community street networks (SSN). We analyzed 108 older adult participants in Suzhou using mediation analysis and multiple linear regression to investigate the relationship between physical activity and the community environment. The results of the mediation effect model showed that SCE, SSI, and SSN all affected the physical functions of older adults via the total amount of physical activity (TPA); SSI and SSN affected older adults' physical functions by affecting the total duration of moderate-intensity physical activity (MPA) and vigorous-intensity physical activity (VPA). In addition, SSI and SSN are related to the types of community facilities, street space quality, and accessibility. Our study provides valuable insights into optimizing aging-friendly neighborhoods through moderate-to-vigorous-intensity PAs at both the facility and street space levels.

Healthcare professionals' knowledge, attitude and practice towards National Centralized Drug Procurement policy in central China: A cross-sectional study.

Background: National Centralized Drug Procurement (NCDP), an ongoing government-led policy starting in 2019 in China, aimed at reducing drug costs. During the implementation of NCDP, healthcare professionals (HCPs) still have a certain degree of concern about the policy, which affects the clinical use of related drugs. Objective: This study aims to assess the level of knowledge, attitude and practice (KAP) of HCPs towards NCDP policy, together with the associated factors that determine their KAP. Methods: A cross-sectional study was conducted between September and November of 2021 in 30 hospitals in Hubei province in Central China. A self-designed online questionnaire including KAP towards NCDP policy was administered to HCPs. Logistic regression analysis was adopted to identify the factors associated with KAP. Results: A Total of, 742 HCPs completed the questionnaires. 43.4% of HCPs had good knowledge, 24.7% had a positive attitude, and 23.7% held good practice. Through multivariate logistic regression analysis, HCPs who are males, pharmacists, with senior professional titles and 6-10 years of professional working experience contributed to a higher knowledge level. Pharmacists and HCPs with good knowledge were more likely to have positive attitudes, while HCPs with higher education were less likely to have positive attitudes. Pharmacists, HCPs who had 11-20 years of professional working experience, worked in medium-size urban areas or had good knowledge were more likely to have good practice. Good practice is also associated with the positive attitude towards the efficacy of centralized-purchased medicines and impacts of NCDP policy. Conclusion: Only a small percentage of HCPs had good KAP towards NCDP policy. Pharmacists showed better KAP than physicians. The positive attitude towards the efficacy of centralized-purchased medicines and impacts of NCDP policy contributed to better practice. High-quality clinical evidence on the therapeutic effects and safety of the centralized-purchased drugs is needed.

Drug-induced liver injury associated with dacomitinib: A case report.

Dacomitinib, the second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been used as a first-line treatment in non-small cell lung cancer (NSCLC) patients harboring EGFR mutation. In this case, we report a patient with drug-induced liver injury (DILI) associated with the use of dacomitinib. A 59-year-old man with stage IV NSCLC was prescribed with dacomitinib; 37 days after dacomitinib administration, he was admitted to our hospital because of jaundice. Laboratory examinations revealed elevated serum levels of liver enzymes and bilirubin. Following the immediate discontinuation of dacomitinib, liver enzymes decreased but bilirubin continued to rise. Total bilirubin reached the peak (18-fold) on day 26 after dacomitinib termination and normalized on day 146 after dacomitinib discontinuation. A "probable" cause of DILI by dacomitinib was determined based on the Roussel Uclaf Causality Assessment Method. The severity of DILI was assessed as acute liver failure. To our knowledge, this is the first case of DILI caused by dacomitinib monotherapy in a real-world setting. Clinicians should pay particular attention to the possibility of DILI during dacomitinib treatment.

Voriconazole-induced severe skin allergy and neurological adverse event in a liver failure patient: A case report.

WHAT IS KNOWN AND OBJECTIVE: Triazole antifungal-associated severe skin allergy has received little attention. Here we report a case of an acute-on-chronic liver failure (ACLF) patient with diffused skin allergy pervading from the chest, abdomen, back, knees to perineum, with red colour and partially desquamation as well as a neurological adverse (insomnia) event after voriconazole treatment. CASE SUMMARY: A 40-year-old man with liver failure in our hospital had received voriconazole for invasive fungal infection therapy, and while waiting for liver transplantation exhibited a severe diffuse rash and a neurological adverse event. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first report of a liver failure patient who suffered a severe allergy accompanied with a neurological adverse event after voriconazole administration.

Integration of UPLC-QE-MS/MS and network pharmacology to investigate the active components and action mechanisms of tea cake extract for treating cough.

The active components and mechanisms of tea cake extract (TCE) were investigated for treating cough. The components of TCE were tentatively identified by ultrahigh-performance liquid chromatography coupled with Q-Exactive MS/MS (UPLC-QE-MS/MS), whose targets were obtained from the Swiss Target Prediction database and the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. Cough-related targets were retrieved from the Gene Cards and Online Mendelian Inheritance in Man database. After the intersection targets had been obtained, enrichment analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined, and the protein-protein interaction network and active compound-intersection target-KEGG pathway network were constructed. Core active compounds and their targets were validated with molecular docking. A total of 78 compounds were identified from TCE, including 24 flavonoids, 17 phenolic acids, 10 alkaloids, seven organic acids, five triterpenes, five amino acids, five coumarins, three carbohydrates, one anthraquinone and one other. A total of 347 intersection targets were obtained. The top five GO terms with the most significant P-values were responses to oxygen-containing compounds and organic substances, chemical and cellular responses to chemical stimulus, and regulation of biological quality. The top five KEGG pathways with the most significant P-values were: the PI3K-Akt signaling pathway, lipids and atherosclerosis, human cytomegalovirus infection, fluid shear stress and atherosclerosis, and proteoglycans in cancer. The top five core active compounds were quercetin, genistein, luteolin, kaempferol and emodin. The top five core targets were protein kinase B (Akt1), prostaglandin-endoperoxide synthase 2 (PTGS2), mitogen-activated protein kinase 1/3 (MAPK1/3) and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1). The top five core active compounds could stably bind to their targets with LibDockScores higher than 100. Tea cake extract plays the antitussive role via multiple components and targets. Core targets (AKT1, MAPK1, MAPK3 and PIK3R1) and core components (quercetin, genistein, luteolin and kaempferol) involved in the PI3K-Akt signaling pathway are worth more attention in subsequent validation experiments.

Long-chain alkanol-alkyl carboxylic acid-based low-viscosity hydrophobic deep eutectic solvents for one-pot extraction of anthraquinones from Rhei Radix et Rhizoma.

Natural long-chain alkanol and alkyl carboxylic acid were used to prepare novel hydrophobic deep eutectic solvents (HDESs). These HDESs are liquid at room temperature and have low viscosity (<12.26 mPa‧s), low polarity (lower than that of methanol, ChCl-based deep eutectic solvents and other reported HDESs), and low density (<0.928 g/mL). A simple one-pot method based on a novel HDES-water two-phase extraction system was constructed for the extraction of weak-polarity bioactive components, anthraquinones, from Rhei Radix et Rhizoma. This HDES-based new extraction method does not consume hazardous organic solvents and can obtain a total anthraquinone yield of 21.52 mg/g, which is close to that obtained by the Chinese pharmacopoeia method (21.22 mg/g) and considerably higher than those by other reported HDESs-based extraction methods (14.20-20.09 mg/g, p < 0.01). The high extraction yield can be mainly attributed to the severe destruction of the RRR cell walls by the extraction system and the excellent dissolving ability of novel HDESs for anthraquinones.

Association Between Drug Treatments and the Incidence of Liver Injury in Hospitalized Patients With COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) has led to the emergence of global health care. In this study, we aimed to explore the association between drug treatments and the incidence of drug-induced liver injury (DILI) in hospitalized patients with COVID-19. A retrospective study was conducted on 5113 COVID-19 patients in Hubei province, among which 395 incurred liver injury. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models. The results showed that COVID-19 patients who received antibiotics (HR 1.97, 95% CI: 1.55-2.51, p < 0.001), antifungal agents (HR 3.10, 95% CI: 1.93-4.99, p < 0.001) and corticosteroids (HR 2.31, 95% CI: 1.80-2.96, p < 0.001) had a higher risk of DILI compared to non-users. Special attention was given to the use of parenteral nutrition (HR 1.82, 95% CI: 1.31-2.52, p < 0.001) and enteral nutrition (HR 2.71, 95% CI: 1.98-3.71, p < 0.001), which were the risk factors for liver injury. In conclusion, this study suggests that the development of DILI in hospitalized patients with COVID-19 needs to be closely monitored, and the above-mentioned drug treatments may contribute to the risk of DILI.

Knowledge, Attitude and Practice of Hospital Pharmacists in Central China Towards Adverse Drug Reaction Reporting: A Multicenter Cross-Sectional Study.

Background: Healthcare professionals' knowledge and attitudes towards adverse drug reactions (ADRs) and ADR reporting play a significant role in pharmacovigilance. This study aims to investigate the gap between knowledge and practice in ADR reporting among hospital pharmacists. Methods: This study is a multi-center, cross-sectional study based on a questionnaire survey. A semi-structured questionnaire was developed including knowledge, attitudes, and practices (KAP) towards ADR reporting. From October to November 2021, questionnaires were filled out on the internet by hospital pharmacists from a central province of China. The data analysis used a one-way ANOVA to analyze the differences between the pharmacist's characteristics and knowledge and attitude, respectively. The ordinal logistic regression method was used to analyze the predictors of practice. Results: A total of 1,026 valid questionnaires from 512 medical institutions were collected. It was found that 88.8% of participants have a clear understanding of the ADR definition, while 59.6% of them have misunderstandings about the reporting time of new and serious adverse reactions. Most pharmacists showed positive attitudes towards ADR reporting. Higher education background, higher professional title, attending training, and clinical pharmacist resulted in higher knowledge scores. Higher education background, shorter working years, attending training, and from non-tertiary hospital related to higher attitude scores. In terms of practice, age, hospital type, working years, training, and pharmacist type all have significant associations with practice scores. Pharmacists' knowledge score and attitude score were significant predictors of practice score with OR being 1.19 (95% CI: 1.06, 1.33) and 1.04 (95% CI: 1.005, 1.07). Conclusion: Although most hospital pharmacists showed positive attitudes towards ADR reporting, their knowledge and practice were still insufficient. Hospital pharmacists' knowledge and attitude are associated with their practice towards ADR reporting. The training had a significant impact on the pharmacist's knowledge, attitude, and practice.

Developing a Peptide That Inhibits DNA Repair by Blocking the Binding of Artemis and DNA Ligase IV to Enhance Tumor Radiosensitivity.

PURPOSE: Artemis and DNA Ligase IV are 2 critical elements in the nonhomologous end joining pathway of DNA repair, acting as the nuclease and DNA ligase, respectively. Enhanced cellular radiosensitivity by inhibition of either protein contributes to a promising approach to develop molecular targeted radiosensitizers. The interaction between Artemis and DNA Ligase IV is required for the activation of Artemis as nuclease at 3'overhang DNA; thus, we aim to generate an inhibitory peptide targeting the interaction between Artemis and DNA Ligase IV for novel radiosensitizer development. METHODS AND MATERIALS: We synthesized the peptide BAL, which consists of the interaction residues of Artemis to DNA Ligase IV. The radiosensitization effect of BAL was evaluated by colony formation assay. The effects of BAL on radiation-induced DNA repair were evaluated with Western blotting and immunofluorescence. The effects of BAL on cell proliferation, cell cycle arrest, and cell apoptosis were assessed via CCK-8 and flow cytometry assays. The potential synergistic effects of BAL and irradiation in vivo were investigated in a xenograft mouse model. RESULTS: The generated peptide BAL blocking the interaction between Artemis and DNA Ligase IV significantly enhanced the radiosensitivity of GBC-SD and HeLa cell lines. BAL prolonged DNA repair after irradiation; BAL and irradiation showed synergistic effects on cell proliferation, cell cycle, and cell apoptosis, and these functions are all DNA Ligase IV-related. Finally, we confirmed the endogenous radiosensitization effect of BAL in a xenograft mouse model. CONCLUSIONS: The inhibitory peptide BAL targeting the binding of Artemis and DNA Ligase IV successfully functions as a novel radiosensitizer that delays DNA repair and synergizes with irradiation to inhibit cell proliferation, induce cell cycle arrest, and promote cell apoptosis.

Physical Activity, Blood Pressure Control, and Health-Related Quality of Life Among Hypertensive Individuals: A Cross-Sectional Study in Jiangsu Province, China.

Hypertension has become one of the most serious chronic diseases that threaten public health. Regulating self-management is considered a priority and in which physical activity plays a vital role. Based on the Fifth National Health Service Survey (NHSS, 2013), a total of 6079 patients with hypertension were investigated by stratified cluster random sampling. This study explored the relationships between blood pressure control and physical activity, and health-related quality of life (HRQoL). Tobit regression and generalized linear regression analysis were used to explore the relationships among participants' socioeconomic characteristics, health behaviors, and HRQoL. The results showed that 4712 respondents (77.51%) had no problems in any aspect, but the proportion of respondents with problems increased significantly with age (P for trend <.001). Blood pressure control was significantly correlated with the health utility value (P < .001). Patients who participated in physical activity and maintained normal daily blood pressure also showed higher health utility value. Physical activity was significantly related to blood pressure control and HRQoL. Therefore, regular physical activity is recommended for hypertensive residents to improve HRQoL.

Hierarchical WSe2 nanoflower as a cathode material for rechargeable Mg-ion batteries.

Transition metal dichalcogenides (TMDs) have emerged as a promising material in the energy field due to their unique structural arrangement. In this work, ordered flower-like WSe2 nanosheet was synthesized through simple one-step hydrothermal method, and its cathode application for rechargeable Mg-ion batteries was assessed. The WSe2 cathode exhibits a high reversible capacity above 265 mAh g-1 at 50 mA g-1, excellent cycling life of 90% initial capacitance that can be ceaselessly harvested for 100 cycles at 50 mA g-1, and superior rate capability of 70% initial capacitance maintained even at the current density of 500 mA g-1. This work paves the way for the application of WSe2 cathode in Mg-ion and other rechargeable batteries.