Blocking Metallothionein-2 Expression by Copper-Doped Carbon Dots Induces Cellular Antioxidant System Collapse for Antitumor Therapy.

The insufficient antioxidant reserves in tumor cells play a critical role in reactive oxygen species (ROS)-mediated therapeutics. Metallothionein-2 (MT-2), an intracellular cysteine-rich protein renowned for its potent antioxidant properties, is intricately involved in tumor development and correlates with a poor prognosis. Consequently, MT-2 emerges as a promising target for tumor therapy. Herein, we present the development of copper-doped carbon dots (Cu-CDs) to target MT-2 to compromise the delicate antioxidant reserves in tumor cells. These Cu-CDs with high tumor accumulation and prolonged body retention can effectively suppress tumor growth by inducing oxidative stress. Transcriptome sequencing unveils a significant decrease in MT-2 expression within the in vivo tumor samples. Further mechanical investigations demonstrate that the antitumor effect of Cu-CDs is intricately linked to apolipoprotein E (ApoE)-mediated downregulation of MT-2 expression and the collapse of the antioxidant system. The robust antitumor efficacy of Cu-CDs provides invaluable insights into developing MT-2-targeted nanomedicine for cancer therapies.

Novel L-(CaP-ZnP)/SA Nanocomposite Hydrogel with Dual Anti-Inflammatory and Mineralization Effects for Efficient Vital Pulp Therapy.

Background: Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries and trauma-induced pulpitis. However, Mineral trioxide aggregate (MTA) as the most frequently used repair material, exhibits limited efficacy under inflammatory conditions. This study introduces an innovative nanocomposite hydrogel, tailored to simultaneously target anti-inflammation and dentin mineralization, aiming to efficiently preserve vital pulp tissue. Methods: The L-(CaP-ZnP)/SA nanocomposite hydrogel was designed by combining L-Arginine modified calcium phosphate/zinc phosphate nanoparticles (L-(CaP-ZnP) NPs) with sodium alginate (SA), and was characterized with TEM, SEM, FTIR, EDX, ICP-AES, and Zeta potential. In vitro, we evaluated the cytotoxicity and anti-inflammatory properties. Human dental pulp stem cells (hDPSCs) were cultured with lipopolysaccharide (LPS) to induce an inflammatory response, and the cell odontogenic differentiation was measured and possible signaling pathways were explored by alkaline phosphatase (ALP)/alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining, and Western blotting, respectively. In vivo, a pulpitis model was utilized to explore the potential of the L-(CaP-ZnP)/SA nanocomposite hydrogel in controlling pulp inflammation and enhancing dentin mineralization by Hematoxylin and eosin (HE) staining and immunohistochemistry staining. Results: In vitro experiments revealed that the nanocomposite hydrogel was synthesized successfully and presented desirable biocompatibility. Under inflammatory conditions, compared to MTA, the L-(CaP-ZnP)/SA nanocomposite hydrogel demonstrated superior anti-inflammatory and pro-odontogenesis effects. Furthermore, the nanocomposite hydrogel significantly augmented p38 phosphorylation, implicating the involvement of the p38 signaling pathway in pulp repair. Significantly, in a rat pulpitis model, the L-(CaP-ZnP)/SA nanocomposite hydrogel downregulated inflammatory markers while upregulating mineralization-related markers, thereby stimulating the formation of robust reparative dentin. Conclusion: The L-(CaP-ZnP)/SA nanocomposite hydrogel with good biocompatibility efficiently promoted inflammation resolution and enhanced dentin mineralization by activating p38 signal pathway, as a pulp-capping material, offering a promising and advanced solution for treatment of pulpitis.

Qualitative study on the problems and potential solution strategies for part-time clinical pharmacists' clinical services work in a tertiary hospital in China.

OBJECTIVE: To provide an initial understanding of problems and potential solution strategies for part-time clinical pharmacist work in China, and provide references for the training of part-time clinical pharmacists. METHODS: The study was conducted in a tertiary teaching hospital in China, and the project lasted 6 months. Phenomenological methods were used to guide the research design. Research data were obtained by conducting one-to-one semistructured interviews with part-time clinical pharmacists, and interview data were coded and analysed through thematic analysis. RESULTS: A total of 21 pharmacists were interviewed in a semistructured manner, and the results showed that following problems exist in the work of part-time clinical pharmacists: the existing professional knowledge is not adequate to meet the demands of clinical service; the career orientation of part-time clinical pharmacists is not clear; lack of professional self-confidence in clinical pharmacy practice; there is no suitable entry point to carry out pharmacy service work; it is difficult to communicate effectively, and for in addition, 17 potential solution strategies are proposed for the current problems, which can provide reference for the development of part-time clinical pharmacists' work. CONCLUSIONS: The work performed by part-time clinical pharmacists is currently immature and the strategies derived from this study may serve as potential solutions to resolve the part-time clinical pharmacy practice challenges.

Exploring the motivation of self-directed learning of hospital pharmacists: a multicentre qualitative study.

OBJECTIVE: Self-directed learning (SDL) has been embraced by the medical community as a core professional competency, with motivation considered a crucial component of SDL. However, little is known about how hospital pharmacists perceive motivation in SDL in the workplace. This study aimed to examine the intrinsic and external motivation of hospital pharmacists in SDL. DESIGN: This study employed a multicentre qualitative design, which lasted 13 months from May 2020 to June 2021. The interviews were audiorecorded, transcribed verbatim and analysed in NVivo V.12.0. Thematic analysis method was used to analyse the data. SETTING: The study took place in nine public hospitals located in urban areas of Henan Province. PARTICIPANTS: Sixteen hospital pharmacists were enrolled from the pharmacy departments of the sample hospitals, using a purposive sampling method. RESULTS: Sixteen one-on-one semistructured interviews were conducted, identifying intrinsic and extrinsic motivation in SDL for hospital pharmacists in the workplace. Intrinsic motivation includes curiosity and interest, achievement, self-efficacy and personal growth. Extrinsic motivation includes a more comprehensive set of elements, such as interpersonal motivations, work-related motivations and career-related motivations. CONCLUSIONS: Personal interests, the influence of surrounding individuals (directly or indirectly), work-related requirements and pressures, and professional development requirements and pressures are the main intrinsic or extrinsic motivations for SDL among hospital pharmacists in China. Future research may focus on these aspects to enhance the SDL competence of hospital pharmacists and other medical personnel.

Psychological Status, Influencing Factors and Intervention Countermeasures of Hospital Pharmacists in Extreme Working Environments in the Post-Pandemic Era--An Embedded Mixed Study.

Objective: The study explores the psychological state and related influences of hospital pharmacists enclosed in extreme work environments in the post-epidemic era, and also explores potential measures to alleviate negative emotions. Methods: An embedded mixed research methodology was used. In the qualitative research phase, semi-structured interviews were carried out with 30 pharmacists consistently confined to their work environments. The data were managed and analyzed using NVivo12 software. In the quantitative research phase, 146 pharmacists with experience in extreme work environments were selected, and the data were collected through questionnaires (GAD-7 and CD-RISC-25) and self-administered questions generated during the qualitative phase. The Shapiro-Wilk test was utilized to assess data normality. Spearman correlation was conducted to evaluate correlations among self-designed questions, resilience, and anxiety. Results: The results from interviews with 30 pharmacists revealed four factors influencing the psychological state of pharmacists in the post-epidemic era: personal factors, interpersonal relationships, environmental factors, and policy and public opinion. Mitigation measures for negative emotions encompass material security, life adjustment, epidemic prevention policy, public opinion information, and organizational management. The results of a quantitative study of 146 pharmacists showed that only 1% had severe anxiety, but the psychological resilience scores were generally low, and 62% had poor psychological resilience, with scores below 73. Simultaneously, it was observed that, except religious beliefs, factors influencing psychological status in extreme work environments were significantly negatively correlated with personal anxiety levels and significantly positively correlated with psychological resilience. Conclusion: Our study holds significance in unraveling the psychological aspects of pharmacists as healthcare workers. It also offers insights into how healthcare organizations respond to the negative emotions experienced by healthcare workers in emergencies or extreme environments.

What learning strategies are commonly used by hospital pharmacists in the process of self-directed learning? A multicentre qualitative study.

OBJECTIVE: As lifelong learners, hospital pharmacists must continually improve their self-directed learning skills. Reasonable learning strategies have been proven to enhance self-directed learning (SDL) significantly. Therefore, this study aims to investigate the SDL strategies used by hospital pharmacists in depth to provide them with a reference for the development of their SDL skills. SETTING: The study was conducted in three tertiary hospitals in Henan, China. DESIGN AND PARTICIPANTS: This study employed a multicentre qualitative design and lasted 12 months. One-on-one interviews and focus group discussions were used to collect data. All interviews were transcribed verbatim, and the interview data were analysed using the thematic analysis method. Purposive sampling was used to select interviewees (n=17) from three tertiary hospitals in Henan province in central China. RESULTS: After conducting data analysis, we summarised 12 learning strategies related to SDL, which were grouped into four themes: use of information resources, application of cognitive strategies, development of learning plans and use of learning platforms. CONCLUSION: The findings suggest that classic learning strategies, such as cognitive strategies and the development of learning plans, remain the cornerstones of hospital pharmacists' SDL abilities, while contemporary advances in information technology and changes in learning concepts have enriched the learning resources and learning platforms that are available to hospital pharmacists and have confronted contemporary hospital pharmacists with certain challenges.

The Mechanism of Lung and Intestinal Injury in Acute Pancreatitis: A Review.

Acute pancreatitis (AP), as a common cause of clinical acute abdomen, often leads to multi-organ damage. In the process of severe AP, the lungs and intestines are the most easily affected organs aside the pancreas. These organ damages occur in succession. Notably, lung and intestinal injuries are closely linked. Damage to ML, which transports immune cells, intestinal fluid, chyle, and toxic components (including toxins, trypsin, and activated cytokines to the systemic circulation in AP) may be connected to AP. This process can lead to the pathological changes of hyperosmotic edema of the lung, an increase in alveolar fluid level, destruction of the intestinal mucosal structure, and impairment of intestinal mucosal permeability. The underlying mechanisms of the correlation between lung and intestinal injuries are inflammatory response, oxidative stress, and endocrine hormone secretion disorders. The main signaling pathways of lung and intestinal injuries are TNF-α, HMGB1-mediated inflammation amplification effect of NF-κB signal pathway, Nrf2/ARE oxidative stress response signaling pathway, and IL-6-mediated JAK2/STAT3 signaling pathway. These pathways exert anti-inflammatory response and anti-oxidative stress, inhibit cell proliferation, and promote apoptosis. The interaction is consistent with the traditional Chinese medicine theory of the lung being connected with the large intestine (fei yu da chang xiang biao li in Chinese). This review sought to explore intersecting mechanisms of lung and intestinal injuries in AP to develop new treatment strategies.

What Is the Role of Pharmacists in Treating COVID-19 Patients? The Experiences and Expectations of Front Line Medical Staff.

Aims: The study aimed to understand the role and the core values of pharmacists and the professional expectations of medical staff for pharmacists in treating COVID-19 patients from the perspectives of the frontline medical staff. The findings help to understand and provide a reference for the career growth path of future pharmacists. Methods: A phenomenological method was used to conduct in-depth interviews with frontline medical staff working in isolation wards during COVID-19. The interview data were analyzed, and the themes were extracted. Results: Pharmacists played a positive role in ensuring the supply of non-routinely stocked drugs, including traditional Chinese medicine preventative preparations, providing drug information and medication consultation for complex patients, and identifying adverse drug reactions. However, at present, the integration of pharmacists and nurses is poor with inadequate communication, and the pharmaceutical care activities provided to physicians were still not comprehensive. Conclusions: The level of pharmaceutical care provided by pharmacists needs to be further strengthened. Frontline medical teams generally have high professional expectations for pharmacists, including expecting pharmacists to become drug therapy experts. They expect pharmacists to fully participate in clinical decision-making, especially playing a central role in managing drug interactions, contraindications, and other clinical uses of drugs.

Impact of timing on in-patient outcomes of complete repair of tetralogy of Fallot in infancy: an analysis of the United States National Inpatient 2005-2011 database.

BACKGROUND: This study aimed to investigate whether age at complete repair of tetralogy of Fallot (TOF) impacts postoperative morbidity and length of hospital stay in infants less than 365 days of age. METHODS: The United States Nationwide Inpatient Sample was searched for infants 0-365 days of age that underwent complete repair of TOF between 2005 and 2011. Patients were categorized based on age at time of repair: 0-30 days; 31-90 days; 91-180 days; > 180 days. RESULTS: A total of 1112 infants were included in the study. Multivariate analysis showed the risk of postoperative complications was 40% lower in infants ≥91 days old at the time of repair as compared to those ≤30 days old. In addition, children > 30 days old at the time of repair had a significantly shorter length of hospital stay than those aged ≤30 days. In the subgroup with elective repair, older age was associated with a shorter length of hospital stay as compared to those ≤30 days old at repair, while association between age at complete repair of TOF and postoperative complication was not significant among the groups after adjusting for confounders. CONCLUSIONS: In children < 1 year old, postoperative complications and length of hospital stay are affected by the timing of complete repair of TOF.