Fraxetin inhibits proliferation and induces apoptosis of bladder cancer through the Akt pathway in vitro and in vivo.

Fraxetin, a natural compound extracted from the Chinese herb Cortex Fraxini, is reported to boast extensive antitumor properties in various cancers. However, whether fraxetin exhibited an anticancer effect on bladder cancer remains unknown. In this study, cell counting kit-8 was utilized to detect cell viability. Flow cytometry analysis was performed for cell apoptosis analysis. Western blot analysis and real-time PCR were used to ascertain gene expression analysis. A mouse bladder cancer xenograft model was established and subjected to fraxetin treatment. Fraxetin reduced the viability of bladder cancer cells, induced apoptosis in vitro, and inhibited the growth of bladder cancer in vivo. Fraxetin inhibited the Akt pathway in J82 cells. In conclusion, the growth inhibitory properties of fraxetin against bladder cancer may be mediated via an Akt inhibitory effect and cell apoptosis promotion.

Attrition in Conversational Agent-Delivered Mental Health Interventions: Systematic Review and Meta-Analysis.

BACKGROUND: Conversational agents (CAs) or chatbots are computer programs that mimic human conversation. They have the potential to improve access to mental health interventions through automated, scalable, and personalized delivery of psychotherapeutic content. However, digital health interventions, including those delivered by CAs, often have high attrition rates. Identifying the factors associated with attrition is critical to improving future clinical trials. OBJECTIVE: This review aims to estimate the overall and differential rates of attrition in CA-delivered mental health interventions (CA interventions), evaluate the impact of study design and intervention-related aspects on attrition, and describe study design features aimed at reducing or mitigating study attrition. METHODS: We searched PubMed, Embase (Ovid), PsycINFO (Ovid), Cochrane Central Register of Controlled Trials, and Web of Science, and conducted a gray literature search on Google Scholar in June 2022. We included randomized controlled trials that compared CA interventions against control groups and excluded studies that lasted for 1 session only and used Wizard of Oz interventions. We also assessed the risk of bias in the included studies using the Cochrane Risk of Bias Tool 2.0. Random-effects proportional meta-analysis was applied to calculate the pooled dropout rates in the intervention groups. Random-effects meta-analysis was used to compare the attrition rate in the intervention groups with that in the control groups. We used a narrative review to summarize the findings. RESULTS: The systematic search retrieved 4566 records from peer-reviewed databases and citation searches, of which 41 (0.90%) randomized controlled trials met the inclusion criteria. The meta-analytic overall attrition rate in the intervention group was 21.84% (95% CI 16.74%-27.36%; I2=94%). Short-term studies that lasted ≤8 weeks showed a lower attrition rate (18.05%, 95% CI 9.91%- 27.76%; I2=94.6%) than long-term studies that lasted >8 weeks (26.59%, 95% CI 20.09%-33.63%; I2=93.89%). Intervention group participants were more likely to attrit than control group participants for short-term (log odds ratio 1.22, 95% CI 0.99-1.50; I2=21.89%) and long-term studies (log odds ratio 1.33, 95% CI 1.08-1.65; I2=49.43%). Intervention-related characteristics associated with higher attrition include stand-alone CA interventions without human support, not having a symptom tracker feature, no visual representation of the CA, and comparing CA interventions with waitlist controls. No participant-level factor reliably predicted attrition. CONCLUSIONS: Our results indicated that approximately one-fifth of the participants will drop out from CA interventions in short-term studies. High heterogeneities made it difficult to generalize the findings. Our results suggested that future CA interventions should adopt a blended design with human support, use symptom tracking, compare CA intervention groups against active controls rather than waitlist controls, and include a visual representation of the CA to reduce the attrition rate. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42022341415; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022341415.

Instability in a carbon pool driven by multiple dissolved organic matter sources in a eutrophic lake basin: Potential factors for increased greenhouse gas emissions.

Lakes serve as vital reservoirs of dissolved organic matter (DOM) and play pivotal roles in biogeochemical carbon cycles. However, the sources and compositions of DOM in freshwater lakes and their potential effects on lake sediment carbon pools remain unclear. In this study, seven inflowing rivers in the Lake Taihu basin were selected to explore the potential effects of multi-source DOM inputs on the stability of the lake sediment carbon pool. The results showed the high concentrations of dissolved organic carbon in the Lake Taihu basin, accompanied by a high complexity level. Lignins constituted the majority of DOM compounds, surpassing 40% of the total, while the organic carbon content was predominantly composed of humic acids (1.02-3.01 g kg-1). The high amounts of lignin oxidative cleavage led to CHO being the main molecular structure in the DOM of the seven rivers. The carbon constituents within the sediment carbon reservoir exhibited a positive correlation with dissolved CH4 and CO2, with a notable emphasis on humic acid and dissolved CH4 (R2 = 0.86). The elevated concentration of DOM, coupled with its intricate composition, contributed to the increases in dissolved greenhouse gases (GHGs). Experiments showed that the mixing of multi-source DOM can accelerate the organic carbon mineralization processes. The unit carbon emission efficiency was highest in the mixed group, reaching reached 160.9 µmol∙Cg-1, which also exhibited a significantly different carbon pool. The mixed decomposition of DOM from different sources influenced the roles of the lake carbon pool as source and sink, indicating that the multi-source DOM of this lake basin was a potential driving factor for increased carbon emissions. These findings have improved our understanding of the sources and compositions of DOM in lake basins and revealed their impacts on carbon emissions, thereby providing a theoretical basis for improving assessments of lake carbon emissions.

Conversational Agents in Health Care: Expert Interviews to Inform the Definition, Classification, and Conceptual Framework.

BACKGROUND: Conversational agents (CAs), or chatbots, are computer programs that simulate conversations with humans. The use of CAs in health care settings is recent and rapidly increasing, which often translates to poor reporting of the CA development and evaluation processes and unreliable research findings. We developed and published a conceptual framework, designing, developing, evaluating, and implementing a smartphone-delivered, rule-based conversational agent (DISCOVER), consisting of 3 iterative stages of CA design, development, and evaluation and implementation, complemented by 2 cross-cutting themes (user-centered design and data privacy and security). OBJECTIVE: This study aims to perform in-depth, semistructured interviews with multidisciplinary experts in health care CAs to share their views on the definition and classification of health care CAs and evaluate and validate the DISCOVER conceptual framework. METHODS: We conducted one-on-one semistructured interviews via Zoom (Zoom Video Communications) with 12 multidisciplinary CA experts using an interview guide based on our framework. The interviews were audio recorded, transcribed by the research team, and analyzed using thematic analysis. RESULTS: Following participants' input, we defined CAs as digital interfaces that use natural language to engage in a synchronous dialogue using ≥1 communication modality, such as text, voice, images, or video. CAs were classified by 13 categories: response generation method, input and output modalities, CA purpose, deployment platform, CA development modality, appearance, length of interaction, type of CA-user interaction, dialogue initiation, communication style, CA personality, human support, and type of health care intervention. Experts considered that the conceptual framework could be adapted for artificial intelligence-based CAs. However, despite recent advances in artificial intelligence, including large language models, the technology is not able to ensure safety and reliability in health care settings. Finally, aligned with participants' feedback, we present an updated iteration of the conceptual framework for health care conversational agents (CHAT) with key considerations for CA design, development, and evaluation and implementation, complemented by 3 cross-cutting themes: ethics, user involvement, and data privacy and security. CONCLUSIONS: We present an expanded, validated CHAT and aim at guiding researchers from a variety of backgrounds and with different levels of expertise in the design, development, and evaluation and implementation of rule-based CAs in health care settings.

Evaluating Conversational Agents for Mental Health: Scoping Review of Outcomes and Outcome Measurement Instruments.

BACKGROUND: Rapid proliferation of mental health interventions delivered through conversational agents (CAs) calls for high-quality evidence to support their implementation and adoption. Selecting appropriate outcomes, instruments for measuring outcomes, and assessment methods are crucial for ensuring that interventions are evaluated effectively and with a high level of quality. OBJECTIVE: We aimed to identify the types of outcomes, outcome measurement instruments, and assessment methods used to assess the clinical, user experience, and technical outcomes in studies that evaluated the effectiveness of CA interventions for mental health. METHODS: We undertook a scoping review of the relevant literature to review the types of outcomes, outcome measurement instruments, and assessment methods in studies that evaluated the effectiveness of CA interventions for mental health. We performed a comprehensive search of electronic databases, including PubMed, Cochrane Central Register of Controlled Trials, Embase (Ovid), PsychINFO, and Web of Science, as well as Google Scholar and Google. We included experimental studies evaluating CA mental health interventions. The screening and data extraction were performed independently by 2 review authors in parallel. Descriptive and thematic analyses of the findings were performed. RESULTS: We included 32 studies that targeted the promotion of mental well-being (17/32, 53%) and the treatment and monitoring of mental health symptoms (21/32, 66%). The studies reported 203 outcome measurement instruments used to measure clinical outcomes (123/203, 60.6%), user experience outcomes (75/203, 36.9%), technical outcomes (2/203, 1.0%), and other outcomes (3/203, 1.5%). Most of the outcome measurement instruments were used in only 1 study (150/203, 73.9%) and were self-reported questionnaires (170/203, 83.7%), and most were delivered electronically via survey platforms (61/203, 30.0%). No validity evidence was cited for more than half of the outcome measurement instruments (107/203, 52.7%), which were largely created or adapted for the study in which they were used (95/107, 88.8%). CONCLUSIONS: The diversity of outcomes and the choice of outcome measurement instruments employed in studies on CAs for mental health point to the need for an established minimum core outcome set and greater use of validated instruments. Future studies should also capitalize on the affordances made available by CAs and smartphones to streamline the evaluation and reduce participants' input burden inherent to self-reporting.

Exploring the Perceptions of mHealth Interventions for the Prevention of Common Mental Disorders in University Students in Singapore: Qualitative Study.

BACKGROUND: Mental health interventions delivered through mobile health (mHealth) technologies can increase the access to mental health services, especially among university students. The development of mHealth intervention is complex and needs to be context sensitive. There is currently limited evidence on the perceptions, needs, and barriers related to these interventions in the Southeast Asian context. OBJECTIVE: This qualitative study aimed to explore the perception of university students and mental health supporters in Singapore about mental health services, campaigns, and mHealth interventions with a focus on conversational agent interventions for the prevention of common mental disorders such as anxiety and depression. METHODS: We conducted 6 web-based focus group discussions with 30 university students and one-to-one web-based interviews with 11 mental health supporters consisting of faculty members tasked with student pastoral care, a mental health first aider, counselors, psychologists, a clinical psychologist, and a psychiatrist. The qualitative analysis followed a reflexive thematic analysis framework. RESULTS: The following 6 main themes were identified: a healthy lifestyle as students, access to mental health services, the role of mental health promotion campaigns, preferred mHealth engagement features, factors that influence the adoption of mHealth interventions, and cultural relevance of mHealth interventions. The interpretation of our findings shows that students were reluctant to use mental health services because of the fear of stigma and a possible lack of confidentiality. CONCLUSIONS: Study participants viewed mHealth interventions for mental health as part of a blended intervention. They also felt that future mental health mHealth interventions should be more personalized and capable of managing adverse events such as suicidal ideation.

Scope, Characteristics, Behavior Change Techniques, and Quality of Conversational Agents for Mental Health and Well-Being: Systematic Assessment of Apps.

BACKGROUND: Mental disorders cause substantial health-related burden worldwide. Mobile health interventions are increasingly being used to promote mental health and well-being, as they could improve access to treatment and reduce associated costs. Behavior change is an important feature of interventions aimed at improving mental health and well-being. There is a need to discern the active components that can promote behavior change in such interventions and ultimately improve users' mental health. OBJECTIVE: This study systematically identified mental health conversational agents (CAs) currently available in app stores and assessed the behavior change techniques (BCTs) used. We further described their main features, technical aspects, and quality in terms of engagement, functionality, esthetics, and information using the Mobile Application Rating Scale. METHODS: The search, selection, and assessment of apps were adapted from a systematic review methodology and included a search, 2 rounds of selection, and an evaluation following predefined criteria. We conducted a systematic app search of Apple's App Store and Google Play using 42matters. Apps with CAs in English that uploaded or updated from January 2020 and provided interventions aimed at improving mental health and well-being and the assessment or management of mental disorders were tested by at least 2 reviewers. The BCT taxonomy v1, a comprehensive list of 93 BCTs, was used to identify the specific behavior change components in CAs. RESULTS: We found 18 app-based mental health CAs. Most CAs had <1000 user ratings on both app stores (12/18, 67%) and targeted several conditions such as stress, anxiety, and depression (13/18, 72%). All CAs addressed >1 mental disorder. Most CAs (14/18, 78%) used cognitive behavioral therapy (CBT). Half (9/18, 50%) of the CAs identified were rule based (ie, only offered predetermined answers) and the other half (9/18, 50%) were artificial intelligence enhanced (ie, included open-ended questions). CAs used 48 different BCTs and included on average 15 (SD 8.77; range 4-30) BCTs. The most common BCTs were 3.3 "Social support (emotional)," 4.1 "Instructions for how to perform a behavior," 11.2 "Reduce negative emotions," and 6.1 "Demonstration of the behavior." One-third (5/14, 36%) of the CAs claiming to be CBT based did not include core CBT concepts. CONCLUSIONS: Mental health CAs mostly targeted various mental health issues such as stress, anxiety, and depression, reflecting a broad intervention focus. The most common BCTs identified serve to promote the self-management of mental disorders with few therapeutic elements. CA developers should consider the quality of information, user confidentiality, access, and emergency management when designing mental health CAs. Future research should assess the role of artificial intelligence in promoting behavior change within CAs and determine the choice of BCTs in evidence-based psychotherapies to enable systematic, consistent, and transparent development and evaluation of effective digital mental health interventions.

Tea polyphenols inhibit blooms caused by eukaryotic and prokaryotic algae.

With changes in global climate, blooms are becoming more frequent and difficult to control. Therefore, the selection of algal suppressor agents with effective inhibition and environmental safety is of paramount importance. One of the main treatment strategies is to inhibit the release of harmful algal toxins. Tea polyphenols (TP) are natural products that have been widely used in medicine, the environment, and other fields due to their antibacterial and antioxidant properties. To investigate their potential application in the treatment of algal blooms, TP were applied to three different microalgae. TP exhibited strong inhibitory effects towards all three microalgae. They stimulate the accumulation of ROS in algal cells, leading to lipid peroxidation and subsequent damage to the cell membrane, resulting in the rupture and necrosis of Cyclotella sp. and Chlorella vulgaris cells. Remarkably, it was observed that lower concentrations of TP exhibited the ability to induce apoptosis in M. aeruginosa cells without causing any structural damage. This outcome is particularly significant as it reduces the potential risk of microcystin release resulting from cell rupture. Overall, blooms dominated by different algae can be treated by adjusting the concentration of TP, a new algal suppressor, indicating strong potential treatment applications.

SRSF9 promotes colorectal cancer progression via stabilizing DSN1 mRNA in an m6A-related manner.

BACKGROUND: Serine/arginine-rich splicing factor 9 (SRSF9) is a classical RNA-binding protein that is essential for regulating gene expression programs through its interaction with target RNA. Whether SRSF9 plays an essential role in colorectal cancer (CRC) progression and can serve as a therapeutic target is largely unknown. Here, we highlight new findings on the role of SRSF9 in CRC progression and elucidate the underlying mechanism. METHODS: CRC cell lines and clinical tissue samples were used. qRT-PCR, Western blotting, immunohistochemistry (IHC), gain- and loss-of-function assays, animal xenograft model studies, bioinformatic analysis, methylated single-stranded RNA affinity assays, gene-specific m6A quantitative qRT-PCR, dual-luciferase reporter assays and RNA stability assays were performed in this study. RESULTS: The expression level of SRSF9 was higher in CRC cell lines than that in an immortal human intestinal epithelial cell line. Overexpression of SRSF9 was positively associated with lymph node metastasis and Dukes stage. Functionally, SRSF9 promoted cell proliferation, migration and invasion in vitro and xenograft growth. The results of bioinformatic analysis indicated that DSN1 was the downstream target of SRSF9. In CRC cells and clinical tissue samples, the expression of SRSF9 was positively associated with the expression of DSN1. Knockdown of DSN1 partially inhibited the SRSF9-induced phenotype in CRC cells. Mechanistically, we further found that SRSF9 is an m6A-binding protein and that m6A modifications were enriched in DSN1 mRNA in CRC cells. Two m6A modification sites (chr20:36773619-36773620 and chr20:36773645-chr20:36773646) in the SRSF9-binding region (chr20:36773597-36773736) of DSN1 mRNA were identified. SRSF9 binds to DSN1 in an m6A motif- and dose-dependent manner. SRSF9 modulates the expression of DSN1 in CRC cells. Such expression regulation was largely impaired upon methyltransferase METTL3 knockdown. Moreover, knockdown of SRSF9 accelerated DSN1 mRNA turnover, while overexpression of SRSF9 stabilized DSN1 mRNA in CRC cells. Such stabilizing was also weakened upon METTL3 knockdown. CONCLUSION: Overexpression of SRSF9 was associated with lymph node metastasis and Dukes stage in CRC. Knockdown of DSN1 eliminated the effects by SRSF9 overexpression in CRC. Our results indicated that SRSF9 functions as an m6A-binding protein (termed "reader") by enhancing the stability of DSN1 mRNA in m6A-related manner. Our study is the first to report that SRSF9-mediated m6A recognition has a crucial role in CRC progression, and highlights SRSF9 as a potential therapeutic target for CRC management.

Information needs and sources of information among people with depression and anxiety: a scoping review.

BACKGROUND: Previous studies have identified substantial unmet information needs in people with depression and anxiety. Sufficient information about the disorder, treatment, available services, and strategies for self-management is essential as it may influence quality of care and patients' quality of life. This scoping review aimed to provide a broad overview of information needs of people with depression and anxiety as well as the sources that they use to seek this information. METHODS: We included all primary research published in English that investigated information needs or information sources in people with depression or anxiety, with no restrictions imposed on the study design, location, setting, or participant characteristics. Six electronic databases (MEDLINE, Embase, PsycINFO, CINAHL, LISTA, Web of Science) and the grey literature (Google and Google Scholar) were searched for relevant studies published up to November 2021. Two reviewers independently screened articles and extracted data. Narrative synthesis was performed to identify key themes of information needs and information sources. Factors associated with information needs/sources such as demographic variables and symptom severity were also identified. RESULTS: Fifty-six studies (comprising 8320 participants) were included. Information needs were categorised into seven themes, including general facts, treatment, lived experience, healthcare services, coping, financial/legal, and other information. The most frequently reported needs in both people with depression and anxiety were general facts and treatment information. Subclinical samples who self-reported depressive/anxious symptoms appeared less interested in treatment information than patients with clinical diagnoses. Information sources were summarised into five categories: health professionals, written materials, media, interpersonal interactions, and organisational resources. Health professionals and media (including the internet) were the most frequently adopted and preferred sources. Although few studies have examined factors associated with information needs and information sources, there is preliminary evidence that symptom severity and disease subtypes are related to information needs/sources, whereas findings on demographic factors were mixed. CONCLUSIONS: Information needs appear to be high in people with depression and anxiety. Future research should examine differences between subgroups and associated factors such as the treatment course. Personalised information provision strategies are also needed to customise information according to individual needs and patient profiles. TRIAL REGISTRATION: The protocol of this scoping review was registered on Open Science Framework (OSF; link: https://doi.org/10.17605/OSF.IO/DF2M6 ).

Evaluation of the reliability of the criteria for assessing prescription quality in Chinese hospitals among pharmacists in China.

BACKGROUND: The reliability of Criteria for Assessing Prescription Quality in Chinese Hospitals (CAPQCH) has never been rigorously verified. This study was designed to verify the reliability of the CAPQCH among pharmacists in China. METHODS: Fourteen pharmacists, 5 from hospitals and 9 from the communities were recruited. We randomly selected 200 prescriptions, and made the testing prescriptions including appropriate and inappropriate testing prescriptions. Pharmacists assessed these testing prescriptions according to criteria in CAPQCH. Three test sets (Set 1, Set 2, and Set 3) were evaluated at 6-month intervals. Before administration of Set 3, pharmacists were informed that achievement on Set 3 would be reflected in their performance appraisal. We also evaluated the performance based on prescription comments before and after combining several confusing criteria. Cohen's Kappa statistic, Fleiss' Kappa statistic, and accuracy were employed to evaluate reliability among pharmacists. RESULTS: Median values of Cohen's Kappa were 0.61 in Set 1, 0.66 in Set 2, and 0.80 in Set 3; reliability is thus substantial. Our data indicate no significant differences between Set 1 and Set 2, whereas Set 3 indicates significantly improved performance. Moreover, combinations of confusing criteria contributed little to improvement of performance in prescription comments. CONCLUSION: Our results verified the reliability of CAPQCH application by working pharmacists. Adding performance based on prescription comments to personal appraisals was effective in improving the quality of prescription comments. These findings may be useful when future modification of the CAPQCH is considered. Moreover, this study contributes to improving the understanding of the prescription assessment situation in China.

Predictive value of the second-trimester fibronectin concentration for severe preeclampsia: A prospective nested case-control study in China.

AIM: To evaluate the value of the second-trimester fibronectin concentration, alone and in combination with other markers (e.g., mean arterial pressure, inhibin A), in the identification of women who subsequently develop severe preeclampsia. METHODS: For this prospective nested case-control study, serum from pregnant women (gestational age 15-22 weeks) who underwent routine Down syndrome screening was analyzed. The women were tracked to delivery and assigned to the severe preeclampsia or control group, according to whether they developed severe preeclampsia. Each woman who later developed severe preeclampsia was paired with five healthy women with pregnancies of similar gestational age (± 1 week). Fibronectin, inhibin A, human chorionic gonadotropin, placental growth factor, cysteine, and homocysteine concentrations were measured in 44 cases in the severe preeclampsia group and 220 cases in the control group. The body mass index and mean arterial pressure were calculated. All results were compared between the two groups. Logistic regression analysis and receiver operating characteristic curve construction were conducted for markers differing significantly between two groups. RESULTS: The second-trimester fibronectin value was positively correlated with severe preeclampsia and predicted 67.7% of severe preeclampsia cases. The combination of fibronectin, inhibin A, and mean arterial pressure predicted 76.7% of severe preeclampsia cases; predictive values for combinations of fibronectin with mean arterial pressure or inhibin A were 75.4% and 74.6%, respectively. Combination with these other markers increased the predictive value of fibronectin. In addition, fibronectin was more powerful for the late severe preeclampsia and severe preeclampsia without fetal growth restriction subgroups. CONCLUSIONS: The second-trimester fibronectin concentration can be used to predict severe preeclampsia.

[Analysis of results of concurrent hearing and deafness genetic screening and follow up of 33 911 newborns].

OBJECTIVE: To analyze the results of concurrent hearing and deafness genetic screening and follow up of newborns. METHODS: In total 33 911 babies born to 5 designated hospitals in Nanshan District of Shenzhen city from October 2017 to December 2019 were included. All subjects underwent concurrent hearing and deafness genetic screening covering 21 variants of 4 genes including GJB2, SLC26A4, GJB3 and Mt12SrRNA. For those with positive results, Sanger sequencing was carried out for confirmation. RESULTS: 93.32% subjects passed the first-round hearing screening, and 87.01% passed the recheck testing. The overall detection rate was 4.18%. The detection rates for GJB2, SLC26A4, GJB3 and Mt12srRNA variants were 1.98%, 1.58%, 0.37% and 0.25%, respectively. 126 and 84 subjects were found with high risk for delayed-onset and drug-induced hearing loss, respectively. In addition, 4 and 5 subjects were found to harbor homozygous/compound heterozygous variants of the GJB2 and SLC26A4 genes, respectively. Concurrent screening showed that subjects (with heterozygous variants) who did not passed the two round hearing test were as follows: GJB2 with 6.75% in the first round and 2.61% in the second round testing, SLC26A4 (3.3%/1.2%), GJB3 (0.72%/0.14%) and 12SrRNA (0.36%/Nil), respectively. Moreover, the No-pass rate in the subjects with homozygous or compound variants in single gene, heterozygous variant in single gene, heterozygous variant in multiple genes, and homozygous variant in GJB3 gene were significantly higher than the subjects with negative results of genetic screening. CONCLUSION: Concurrent newborn genetic screening can enhance the effectiveness of hearing screening and enable earlier identification and intervention for children with hearing impairment. Follow-up can improve the diagnostic rate for children who are positive for the concurrent screening. Nevertheless, genetic and hearing screening cannot replace the diagnostic testing. It is necessary to conduct comprehensive analysis for the results of genetic and hearing screening and radiological examinations. Sanger sequencing and next-generation sequencing are critical for ascertain the diagnosis.

Sevoflurane prevents vulnerable plaque disruption in apolipoprotein E-knockout mice by increasing collagen deposition and inhibiting inflammation.

BACKGROUND: Sevoflurane may reduce the occurrence of major adverse cardiovascular events (MACCEs) in surgical patients, although the mechanisms are poorly understood. We hypothesised that sevoflurane stabilises atherosclerotic plaques by inhibiting inflammation and enhancing prolyl-4-hydroxylase α1 (P4Hα1), the rate-limiting subunit for the P4H enzyme essential for collagen synthesis. METHODS: We established a vulnerable arterial plaque model in apolipoprotein E-knockout mice (ApoE-/-) fed a high-fat diet that underwent daily restraint/noise stress, with/without a single prior exposure to sevoflurane for 6 h (1-3%; n=30 per group). In vitro, smooth muscle cells (SMCs) were incubated with tumour necrosis factor-alpha in the presence/absence of sevoflurane. Immunohistochemistry, immunoblots, and mRNA concentrations were used to quantify the effect of sevoflurane on plaque formation, expression of inflammatory cytokines, P4Hα1, and collagen subtypes in atherosclerotic plaques or isolated SMCs. RESULTS: In ApoE-/- mice, inhalation of sevoflurane 1-3% for 6 h reduced the aortic plaque size by 8-29% in a dose-dependent manner, compared with control mice that underwent restraint stress alone (P<0.05); this was associated with reduced macrophage infiltration and lower lipid concentrations in plaques. Sevoflurane reduced gene transcription and protein expression levels of pro-inflammatory cytokines (≥69-75%; P<0.05) and matrix metalloproteinases (≥39-65%; P<0.05) at both gene transcription and protein levels, compared with controls. Sevoflurane dose dependently increased Types I and III collagen deposition through enhanced protein expression of P4Hα1, both in vivo and in vitro (0.7-3.3-fold change; P<0.05). CONCLUSIONS: Sevoflurane dose dependently promotes plaque stabilisation and decreases the incidence of plaque disruption in ApoE-/- mice by increasing collagen deposition and inhibiting inflammation. These mechanisms may contribute to sevoflurane reducing MACCE.

Investigation of the characteristics of medication errors and adverse drug reactions using pharmacovigilance data in China.

The aim of this study was to investigate the characteristics of medication errors (MEs) and adverse drug reactions (ADRs) using data from the spontaneous reporting system, which is helpful to understand the actual situation of MEs in China. Data from 2015 in a south distinct in Shanghai were gathered from the spontaneous reporting system and analyzed. The general information, cause of errors, severity, primary diseases, involved system and organs, symptoms, and suspected drugs were investigated. A total of 1290 adverse drug events (ADEs), including 1079 ADRs and 211 MEcs (MEs causing ADE), were reported. Older patients suffered from both ADRs and MEcs (age distribution and dosage form were different between ADRs and MEcs). The main causes of errors were inappropriate usage and dosage of drugs and inappropriate indication selection. Most ADR and MEc cases were mild; the possibility of developing a severe adverse event was quite low. The distribution of the top 10 system and organs, and symptoms involved was significantly different between ADRs and MEcs, with J01 drugs (antibacterials for systemic use) being the leading cause in both. Our results suggested that a direct analysis of data from the spontaneous reporting system is a reliable, and convenient method to investigate MEs and ADRs, despite the existing limitations, and contributes to further understanding the current situation of MEs and ADRs in China.

Ozone (O3) elicits neurotoxicity in spinal cord neurons (SCNs) by inducing ER Ca(2+) release and activating the CaMKII/MAPK signaling pathway.

Ozone (O3) is widely used in the treatment of spinal cord related diseases. Excess or accumulation of this photochemical air can however be neurotoxic. In this study, in vitro cultured Wister rat spinal cord neurons (SCNs) were used to investigate the detrimental effects and underlying mechanisms of O3. Ozone in a dose-dependent manner inhibited cell viability at a range of 20 to 500 µg/ml, with the dose at 40 µg/ml resulting in a decrease of cell viability to 75%. The cell death after O3 exposure was related to endoplasmic reticulum (ER) calcium (Ca(2+)) release. Intracellular Ca(2+) chelator, ER stabilizer (inositol 1,4,5-trisphosphate receptor (IP3R) antagonist and ryanodine receptor (RyR) antagonist) and calcium/calmodulin-dependent protein kinase II (CaMKII) antagonist could effectively block Ca(2+) mobilization and inhibit cell death following 40 µg/ml O3 exposure. In addition, ER Ca(2+) release due to O3 exposure enhanced phospho-p38 and phospho-JNK levels and apoptosis of SCNs through activating CaMKII. Based on these results, we confirm that ozone elicits neurotoxicity in SCNs via inducing ER Ca(2+) release and activating CaMKII/MAPK signaling pathway. Therefore, physicians should get attention to the selection of treatment concentrations of oxygen/ozone. And, approaches, such as chelating intracellular Ca(2+) and stabilizing neuronal Ca(2+) homeostasis could effectively ameliorate the neurotoxicity of O3.

A network analysis of food flows within the United States of America.

The world food system is globalized and interconnected, in which trade plays an increasingly important role in facilitating food availability. We present a novel application of network analysis to domestic food flows within the USA, a country with global importance as a major agricultural producer and trade power. We find normal node degree distributions and Weibull node strength and betweenness centrality distributions. An unassortative network structure with high clustering coefficients exists. These network properties indicate that the USA food flow network is highly social and well-mixed. However, a power law relationship between node betweenness centrality and node degree indicates potential network vulnerability to the disturbance of key nodes. We perform an equality analysis which serves as a benchmark for global food trade, where the Gini coefficient = 0.579, Lorenz asymmetry coefficient = 0.966, and Hoover index = 0.442. These findings shed insight into trade network scaling and proxy free trade and equitable network architectures.

Effects of supplementing coated methionine in a high plant-protein diet on growth, antioxidant capacity, digestive enzymes activity and expression of TOR signaling pathway associated genes in gibel carp, Carassius auratus gibelio.

This study explored the impacts of supplementation of different levels of coated methionine (Met) in a high-plant protein diet on growth, blood biochemistry, antioxidant capacity, digestive enzymes activity and expression of genes related to TOR signaling pathway in gibel carp (Carassius auratus gibeilo). A high-plant protein diet was formulated and used as a basal diet and supplemented with five different levels of coated Met at 0.15, 0.30, 0.45, 0.60 and 0.75%, corresponding to final analyzed Met levels of 0.34, 0.49, 0.64, 0.76, 0.92 and 1.06%. Three replicate groups of fish (initial mean weight, 11.37 ± 0.02 g) (20 fish per replicate) were fed the test diets over a 10-week feeding period. The results indicated that with the increase of coated Met level, the final weight, weight gain (WG) and specific growth rate initially boosted and then suppressed, peaking at 0.76% Met level (P< 0.05). Increasing dietary Met level led to significantly increased muscle crude protein content (P< 0.05) and reduced serum alanine aminotransferase activity (P< 0.05). Using appropriate dietary Met level led to reduced malondialdehyde concentration in hepatopancreas (P< 0.05), improved superoxide dismutase activity (P< 0.05), and enhanced intestinal amylase and protease activities (P< 0.05). The expression levels of genes associated with muscle protein synthesis such as insulin-like growth factor-1, protein kinase B, target of rapamycin and eukaryotic initiation factor 4E binding protein-1 mRNA were significantly regulated, peaking at Met level of 0.76% (P< 0.05). In conclusion, supplementing optimal level of coated Met improved on fish growth, antioxidant capacity, and the expression of TOR pathway related genes in muscle. The optimal dietary Met level was determined to be 0.71% of the diet based on quadratic regression analysis of WG.

Microbiome in gynecologic malignancies: a bibliometric analysis from 2012 to 2022.

Microbiome and microbial dysbiosis have been proven to be involved in the carcinogenesis and treatment of gynecologic malignancies. However, there is a noticeable gap in the literature, as no comprehensive papers have covered general information, research status, and research frontiers in this field. This study addressed this gap by exploring the relationship between the gut and female reproductive tract (FRT) microbiome and gynecological cancers from a bibliometric perspective. Using VOSviewer 1.6.18, CiteSpace 6.1.R6, and HistCite Pro 2.1 software, we analyzed data retrieved from the Web of Science (WOS) Core Collection (WoSCC) database. Our dataset, consisting of 204 articles published from 2012 to 2022, revealed a consistent and upward publication trend. The United States and the United Kingdom were the primary driving forces, attributed to their prolificacy, high-quality output, and extensive cooperation. The University of Arizona Cancer Center, which is affiliated with the United States, ranked first among the top ten most prolific institutions. Frontiers in Cellular and Infection Microbiology emerged as the leading publisher. Herbst-Kralovetz MM led as the most productive author. Mitra A was the most influential author. Cervical cancer is notably associated with the microbiome, while endometrial and ovarian cancers are receiving increased attention in the last year. Intersections between the gut microbiome and estrogen are of growing importance. Current research focuses on identifying specific microbial species for etiological diagnosis, while frontiers mainly focus on the anticancer potential of microorganisms, such as regulating the effects of immune checkpoint inhibitors. In conclusion, this study sheds light on a novel and burgeoning direction of research, providing a one-stop overview of the microbiome in gynecologic malignancies. Its findings aim to help young researchers to identify research directions and future trends for ongoing investigations.

pH/glutathione-responsive theranostic nanoprobes for chemoimmunotherapy and magnetic resonance imaging of ovarian cancer cells.

The integration of immunotherapy and standard chemotherapy holds great promise for enhanced anticancer effects. In this study, we prepared a pH- and glutathione (GSH)-sensitive manganese-doped mesoporous silicon (MMSNs) based drug delivery system by integrating paclitaxel (PTX) and anti-programmed cell death-ligand 1 antibody (aPD-L1), and encapsulating with polydopamine (PDA) for chemoimmunosynergic treatment of ovarian cancer cells. The nanosystem was degraded in response to the tumor weakly acidic and reductive microenvironment. The Mn2+ produced by degradation can be used as a contrast agent for magnetic resonance (MR) imaging to provide visual exposure to tumor tissue. The released PTX can not only kill tumor cells directly, but also induce immunogenic death (ICD) of tumor cells, which can play a synergistic therapeutic effect with aPD-L1. Therefore, our study is expected to provide a promising strategy for improving the efficacy of cancer immunotherapy and the detection rate of cancer.