A novel dual-target Septin9 methylation assay for improved detection of early-stage colorectal cancer and high-grade intraepithelial neoplasia.

BACKGROUND: Colorectal cancer (CRC) ranks as the third most common malignancies in the world, and periodic examination of the patient is advantageous in reducing the mortality of CRC. The first blood-based Septin9 gene methylation assay which recognized by the US FDA for CRC examination was Epi proColon. However, this assay was not broadly applied in the current clinical guideline because of its relatively lower sensitivity in the detection of early-stage CRC. METHODS: This study aimed at developing a new multiplex Septin9 methylation assay (ColonUSK) which simultaneously evaluates two CpG-rich subregions in the promoter of the Septin9 gene and an internal control in a single reaction. ColonUSK proved increased sensitivity, with a detection limit as low as 12pg of the positive DNA compared with the Septin9 assay targeting one CpG-rich subregion. 1366 subjects were prospectively recruited from four comprehensive hospitals in China in an opportunistic screening study for assessing its value in CRC detection. Blind testing was developed to evaluate ColonUSK in comparison with clinical examination using clinical gold standard such as colonoscopy. RESULTS: The assay demonstrates clinical sensitivity for diagnosing colorectal cancer (CRC) and advanced adenoma at rates of 77.34% and 25.26%, respectively. Furthermore, ColonUSK exhibits a high degree of specificity for non-CRC cases (95.95%) clinically. Significantly, the detection rate of cases in high-grade intraepithelial neoplasia increased to 54.29%. The value for the assay in the Kappa test was 0.76, showing a high degree of consistency between ColonUSK and clinical gold standard. CONCLUSIONS: ColonUSK indicated moderate diagnostic value and could become a non-invasive detection way for CRC. The implementation of the ColonUSK assay has the capacity to markedly enhance CRC screening practices.

Trends and hotspots in gastrointestinal neoplasms risk assessment: A bibliometric analysis from 1984 to 2022.

BACKGROUND: Gastrointestinal neoplasm (GN) significantly impact the global cancer burden and mortality, necessitating early detection and treatment. Understanding the evolution and current state of research in this field is vital. AIM: To conducts a comprehensive bibliometric analysis of publications from 1984 to 2022 to elucidate the trends and hotspots in the GN risk assessment research, focusing on key contributors, institutions, and thematic evolution. METHODS: This study conducted a bibliometric analysis of data from the Web of Science Core Collection database using the "bibliometrix" R package, VOSviewer, and CiteSpace. The analysis focused on the distribution of publications, contributions by institutions and countries, and trends in keywords. The methods included data synthesis, network analysis, and visualization of international collaboration networks. RESULTS: This analysis of 1371 articles on GN risk assessment revealed a notable evolution in terms of research focus and collaboration. It highlights the United States' critical role in advancing this field, with significant contributions from institutions such as Brigham and Women's Hospital and the National Cancer Institute. The last five years, substantial advancements have been made, representing nearly 45% of the examined literature. Publication rates have dramatically increased, from 20 articles in 2002 to 112 in 2022, reflecting intensified research efforts. This study underscores a growing trend toward interdisciplinary and international collaboration, with the Journal of Clinical Oncology standing out as a key publication outlet. This shift toward more comprehensive and collaborative research methods marks a significant step in addressing GN risks. CONCLUSION: This study underscores advancements in GN risk assessment through genetic analyses and machine learning and reveals significant geographical disparities in research emphasis. This calls for enhanced global collaboration and integration of artificial intelligence to improve cancer prevention and treatment accuracy, ultimately enhancing worldwide patient care.

Current status and continuing medical education need for general practitioners in Tibet, China: a cross-sectional study.

BACKGROUND: The Tibetan area is one of China's minority regions with a shortage of general practice personnel, which requires further training and staffing. This research helps to understand the current condition and demand for general practitioner (GP) training in Tibetan areas and to provide a reference for promoting GP education and training. METHODS: We conducted a cross-sectional survey using stratified sampling targeting 854 GPs in seven cities within the Tibetan Autonomous Region, utilizing an online questionnaire. Achieving a high response rate of 95.1%, 812 GPs provided invaluable insights. Our meticulously developed self-designed questionnaire, available in both Chinese and Tibetan versions, aimed to capture a wide array of data encompassing basic demographics, clinical skills, and specific training needs of GPs in the Tibetan areas. Prior to deployment, the questionnaire underwent rigorous development and refinement processes, including expert consultation and pilot testing, to ensure its content validity and reliability. In our analysis, we employed descriptive statistics to present the characteristics and current training needs of GPs in the Tibetan areas. Additionally, chi-square tests were utilized to examine discrepancies in training needs across various demographic groups, such as age, job positions, and educational backgrounds of the participating GPs. RESULTS: The study was completed by 812 (812/854, 95.1%) GPs, of whom 62.4% (507/812) were female. The top three training needs were hypertension (81.4%, 661/812), pregnancy management (80.7%, 655/812), and treatment of related patient conditions and events (80.5%, 654/812). Further research shows that the training required by GPs of different ages in "puncturing, catheterization, and indwelling gastric tube use" (64.6% vs. 54.8%, p = 9.5 × 10- 6) varies statistically. GPs in various positions have different training needs in "community-based chronic disease prevention and management" (76.6% vs. 63.9%, p = 0.009). The training needs of GPs with different educational backgrounds in "debridement, suturing, and fracture fixation" (65.6% vs. 73.2%, p = 0.027) were also statistically significant. CONCLUSIONS: This study suggests the need for targeted continuing medical education activities and for updating training topics and content. Course developers must consider the needs of GPs, as well as the age, job positions, and educational backgrounds of GPs practicing in the Tibetan Plateau region. TRIAL REGISTRATION: Not applicable.

MnOxHy-modified CoMoP/NF nanosheet arrays as hydrogen evolution reaction and oxygen evolution reaction bifunctional catalysts under alkaline conditions.

It is widely acknowledged that interface engineering strategies can significantly enhance the activity of catalysts. In this study, we developed a CoMoP nanoarray directly grown in situ on a nickel foam (NF) substrate, with the interface structure formed through the electrodeposition of MnOxHy. The resulting heterostructure MnOxHy/CoMoP/NF exhibited remarkable hydrogen evolution reaction (HER) activity, achieving overpotentials as low as 61 and 138 mV at 10 and 100 mA cm-2, respectively. Moreover, MnOxHy/CoMoP/NF demonstrated efficient oxygen evolution reaction (OER) activity with an overpotential of 330 mV at 100 mA cm-2. Remarkably, MnOxHy/CoMoP/NF maintained its catalytic properties and structural integrity even after working continuously for 20 h facilitating the HER at 10 mA cm-2 and the OER at 100 mA cm-2. The Tafel slopes of the HER and OER were determined to be as small as 14 and 55 mV dec-1, respectively, confirming that the coupled interface conferred fast reaction kinetics on the catalyst. When applied in overall water splitting, MnOxHy/CoMoP/NF delivered a voltage of 1.91 V at 100 mA cm-2 with excellent stability. This study demonstrated the feasibility of utilizing a simple electrodeposition technique to fabricate a heterogeneous structure with bifunctional catalytic activity, establishing a solid foundation for diverse industrial applications.

Robust FeCoP nanoparticles grown on a rGO-coated Ni foam as an efficient oxygen evolution catalyst for excellent alkaline and seawater electrolysis.

Electrochemical water splitting is a potential green hydrogen energy generation technique. With the shortage of fresh water, abundant seawater resources should be developed as the main raw material for water electrolysis. However, since the precipitation reaction of chloride ions in seawater will compete with the oxygen evolution reaction (OER) and corrode the catalyst, seawater electrolysis is restricted by the decrease in activity, low stability, and selectivity. Rational design and development of efficient and stable catalysts is the key to seawater electrolysis. Herein, a high-activity bimetallic phosphide FeCoP, grown on a reduced graphene oxide (rGO)-protected Ni Foam (NF) substrate using FeCo Prussian Blue Analogue (PBA) as a template, was designed for application in alkaline natural seawater electrolysis. The OER activity confirmed that the formed FeCoP@rGO/NF has high electrocatalytic performance. In 1 M KOH and natural alkaline seawater, the overpotential was only 257 mV and 282 mV under 200 mA cm-2, respectively. It also demonstrated long-term stability up to 200 h. Therefore, this study provides new insight into the application of PBA as a precursor of bimetallic phosphide in the electrolysis of seawater at high current density.

Impact of health literacy and social support on medication adherence in patients with hypertension: a cross-sectional community-based study.

BACKGROUND: Previous studies have examined the associations of health literacy and social support with medication adherence among patients with hypertension. However, limited evidence exists regarding the mechanisms underlying the relationship between these factors and medication adherence. PURPOSE: To explore the prevalence of medication adherence and its determinants in patients with hypertension in Shanghai. METHODS: A community-based cross-sectional study was conducted among 1697 participants with hypertension. We collected sociodemographic and clinical characteristics as well as data regarding health literacy, social support, and medication adherence using questionnaires. We examined interactions among the factors using a structural equation model. RESULTS: The participants included 654 (38.54%) patients with a low degree of medication adherence and 1043 (61.46%) patients with a medium/high degree of adherence. Social support directly influenced adherence (ß = 0.165, P < 0.001) and indirectly influenced adherence through health literacy (ß = 0.087, P < 0.001). Health literacy directly influenced adherence (ß = 0.291, P < 0.001). Education indirectly affected adherence through both social support (ß = 0.048, P < 0.001) and health literacy (ß = 0.080, P < 0.001). Moreover, there was a sequential mediating effect of social support and health literacy on the association between education and adherence (ß = 0.025, P < 0.001). After controlling for age and marital status, similar results were also obtained, indicating a good model fit. CONCLUSIONS: The degree of medication adherence among hypertensive patients needs to improve. Health literacy and social support had both direct and indirect effects on adherence, and thus, these factors should be considered as tools to improve adherence.

Dual inhibition of MYC and SLC39A10 by a novel natural product STAT3 inhibitor derived from Chaetomium globosum suppresses tumor growth and metastasis in gastric cancer.

Gastric cancer remains one of the most common deadly diseases and lacks effective targeted therapies. In the present study, we confirmed that the signal transducer and activator of transcription 3 (STAT3) is highly expressed and associated with a poor prognosis in gastric cancer. We further identified a novel natural product inhibitor of STAT3, termed XYA-2, which interacts specifically with the SH2 domain of STAT3 (Kd= 3.29 µM) and inhibits IL-6-induced STAT3 phosphorylation at Tyr705 and nuclear translocation. XYA-2 inhibited the viability of seven human gastric cancer cell lines with 72-h IC50 values ranging from 0.5 to 0.7 µΜ. XYA-2 at 1 µΜ inhibited the colony formation and migration ability of MGC803 (72.6% and 67.6%, respectively) and MKN28 (78.5% and 96.6%, respectively) cells. In the in vivo studies, intraperitoneal administration of XYA-2 (10 mg/kg/day, 7 days/week) significantly suppressed 59.8% and 88.8% tumor growth in the MKN28-derived xenograft mouse model and MGC803-derived orthotopic mouse model, respectively. Similar results were obtained in a patient-derived xenograft (PDX) mouse model. Moreover, XYA-2 treatment extended the survival of mice bearing PDX tumors. The molecular mechanism studies based on transcriptomics and proteomics analyses indicated that XYA-2 might exert its anticancer activity by synergistically inhibiting the expression of MYC and SLC39A10, two downstream genes of STAT3 in vitro and in vivo. Together, these findings suggested that XYA-2 may be a potent STAT3 inhibitor for treating gastric cancer, and dual inhibition of MYC and SLC39A10 may be an effective therapeutic strategy for STAT3-activated cancer.

Patterns of multimorbidity in community health centres in Shanghai, China: a retrospective, cross-sectional study based on outpatient data from 2014 to 2018.

OBJECTIVE: Caring for patients with multimorbidity is an important part of primary care. It has become increasingly relevant that understanding the spectrum of multimorbidity will help general practitioners (GPs) acquire working knowledge and improve management skills. However, there was little research on characteristics of multimorbidity in primary care in China. This study aimed to identify the spectrum of frequency, proportion and ranking of multimorbidity patterns in adult patients seen at community health centres (CHCs) in Shanghai, China. DESIGN AND SETTING: This was an observational, retrospective, cross-sectional study analysis of outpatient data of 244 CHCs in Shanghai, China. PARTICIPANTS: Adult patients with chronic disease who visited Shanghai CHCs during 2014-2018 were selected from Shanghai CHC electronic medical records database using the International Classification of Diseases 10th Revision codes matched to the Second Version of International Classification of Primary Care codes. PRIMARY AND SECONDARY OUTCOME MEASURES: A number of adult patients with chronic disease were counted. Then frequency, proportion and rank of disease patterns of multimorbidity were analysed. RESULTS: Analysis of 301 651 158 electronic health records of 5 909 280 adult patients (54.2% females) found the multimorbidity proportion to be 81.2%. The prevalence of multimorbidity increased with age, which climbed from 43.7% among those aged 19-34 to 94.9% among those more than 80 years of age. The proportion of multimorbidity was higher in females (83.2%) than males (79.7%). Vascular and metabolic diseases were the most frequent diseases for patients over 45 years old. CONCLUSIONS: Multimorbidity has brought huge challenges to primary care practice in Shanghai. The Shanghai government should strengthen its support for the multitargeted prevention of chronic diseases and the improvement of GPs' management capabilities.

Conditions required to ensure successful detection and management of mild cognitive impairment in primary care: A Delphi consultation study in China.

Objective: Detection and management of mild cognitive impairment (MCI) in primary care has been recognized internationally as one of the strategies that can be employed to delay the development of dementia. However, little is known about what role primary care should play. This study aimed to develop a checklist of conditions necessary for successfully detecting and managing mild cognitive impairment in primary care in China. Methods: This study employed the Delphi method to establish expert consensus on the conditions required for successfully detecting and managing MCI in primary care in China. Twenty-four experts who specialized in general practice, public health, neuropsychology, or community health service management rated the importance of pre-defined conditions (44 items measuring providers' preparedness, patient engagement, and system support in line with the Chronic Care Model). The degree of consensus among the experts was measured using four indicators: median ≥ 4, mean ≥3.5, Co-efficient of Variance < 0.25, and retention in the checklist required ≥ 80% agreement with a rating of important or essential. The checklist and descriptions of the conditions were revised according to the experts' feedback and then sent out for repeated consultations along with a summary of the results of the previous round of consultations. Consensus was achieved after the second round of consultations, which was completed by 22 of the experts. Results: The experts endorsed a checklist of 47 conditions required for successful detection and management of MCI in primary care in China. These conditions were categorized into four domains: prepared general practitioners (17 items), engaged patients (15 items), organizational efforts (11 items), and environmental support (4 items). Conclusions: Successful detection and management of MCI in primary care in China requires a dedicated and competent workforce of general practitioners, as well as the engagement of patients and family caregivers. Adequate support from healthcare organizations, health system arrangements, and the broader society is needed to enable effective interactions between general practitioners and patients and efficient delivery of the services required to detect and manage MCI.

Evaluating the risk of hypertension in residents in primary care in Shanghai, China with machine learning algorithms.

Objective: The prevention of hypertension in primary care requires an effective and suitable hypertension risk assessment model. The aim of this study was to develop and compare the performances of three machine learning algorithms in predicting the risk of hypertension for residents in primary care in Shanghai, China. Methods: A dataset of 40,261 subjects over the age of 35 years was extracted from Electronic Healthcare Records of 47 community health centers from 2017 to 2019 in the Pudong district of Shanghai. Embedded methods were applied for feature selection. Machine learning algorithms, XGBoost, random forest, and logistic regression analyses were adopted in the process of model construction. The performance of models was evaluated by calculating the area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, accuracy and F1-score. Results: The XGBoost model outperformed the other two models and achieved an AUC of 0.765 in the testing set. Twenty features were selected to construct the model, including age, diabetes status, urinary protein level, BMI, elderly health self-assessment, creatinine level, systolic blood pressure measured on the upper right arm, waist circumference, smoking status, low-density lipoprotein cholesterol level, high-density lipoprotein cholesterol level, frequency of drinking, glucose level, urea nitrogen level, total cholesterol level, diastolic blood pressure measured on the upper right arm, exercise frequency, time spent engaged in exercise, high salt consumption, and triglyceride level. Conclusions: XGBoost outperformed random forest and logistic regression in predicting the risk of hypertension in primary care. The integration of this risk assessment model into primary care facilities may improve the prevention and management of hypertension in residents.

Rapid detection and classification of hongmu by atmospheric pressure ionization mass spectrometry.

Hongmu, a Chinese customary noun representing 29 kinds of wood species such as some Pterocarpus species (abbreviated as spp. hereinafter), Dalbergia spp. and Diospyros spp., is popular among Chinese people due to the furniture made from it. The slow regeneration of hongmu resources led to a decline in production, making hongmu prices high and illegal businesses profit from it. Therefore, it is necessary to identify and distinguish different varieties of hongmu for commercial trade. Herein, a cost-effective and rapid methodology was first developed via atmospheric pressure glow discharge mass spectrometry (APGD-MS) to classify three Dalbergia spp. and three Pterocarpus spp. Meanwhile, principal component analysis (PCA) was further applied to distinguish wood species and six kinds of hongmu extracts were able to be approximately separated into six units. Besides, hongmu could be clearly distinguished from their counterfeits, such as Guibourtia spp., using the method provided here. This method may provide a timely and necessary way for the determination of ingredients and identification of the authenticity of hongmu.

Challenges in detecting and managing mild cognitive impairment in primary care: a focus group study in Shanghai, China.

INTRODUCTION: Detection of mild cognitive impairment (MCI) is essential in slowing progression to dementia. Primary care plays a vital role in detecting and managing MCI. The chronic care model (CCM) provides effective methods to manage chronic diseases. OBJECTIVE: This study aimed to explore how MCI services are delivered in primary care in China. METHODS: Focus group interviews were conducted face to face among MCI stakeholders from six community health centres (CHCs) involved in the 'friendly community programme' in Shanghai, China. A total of 124 MCI stakeholders were interviewed, consisting of 6 groups (n=42) of general practitioners (GPs), 3 groups (n=18) of CHC managers, 4 groups (n=32) of people with MCI and 4 groups (n=32) of informal caregivers. Content and thematic analyses were performed using a combination of induction and deduction approaches. RESULTS: Three major themes emerged from the data corresponding to the CCM framework: hesitant patients, unprepared providers and misaligned environments. While the public are hesitant to seek medical attention for MCI problems, due to misunderstanding, social stigma and a lack of perceived benefits, GPs and CHCs are not well prepared either, due to lack of knowledge and a shortage of GPs, and a lack of policy, funding and information support. None of these issues can be addressed separately without tackling the others. CONCLUSION: This study combined the diverse perceptions of all the main stakeholders to detect and manage MCI in primary care settings in China. A vicious circle was found among the three interconnected CCM domains, creating a gridlock that should be addressed through a system's approach targeting all of the above-mentioned aspects.

S3I-201 derivative incorporating naphthoquinone unit as effective STAT3 inhibitors: Design, synthesis and anti-gastric cancer evaluation.

Signal transducer and activator of transcription 3 (STAT3) is a key regulator of many human cancers and has been widely recognized as a promising target for cancer therapy. A variety of small-molecule inhibitors have been developed for targeting STAT3, and some of them are now undergoing clinical trials. S3I-201, a known STAT3 inhibitor, may block STAT3 function in cancer cells by binding to the STAT3 SH2 domain to disrupt STAT3 protein complex formation. Using S3I-201 as a starting point for drug development, we synthesized a series of new STAT3 inhibitors 9a-x in this study by introducing naphthoquinone unit, a privileged fragment in STAT3 inhibitors. Most of the compounds exhibited strong anti-proliferation activity of gastric cancer cells (MGC803, MKN28, MNK1, and AGS). The representative compound 9n (SIL-14) could effectively inhibit the colony formation and migration of gastric cancer cells MGC803, arrest the cell cycle and induce MGC803 cell apoptosis at low micromolar concentrations in vitro. In addition, SIL-14 can also inhibit the phosphorylation of STAT3 protein and significantly decrease the expression of total STAT3, suggesting that it may exert anticancer effects by blocking the STAT3 signaling pathway. These results support that SIL-14 may be a promising STAT3 inhibitor for the further development of potential anti-gastric cancer candidates.

Comparison of clinical outcomes and risk factors for COVID-19 infection in cancer patients without anticancer treatment and noncancer patients.

Background: Previous studies have shown that cancer patients have higher rates of coronavirus disease 2019 (COVID-19) infection and mortality than noncancer patients. However, the differences between cancer patients undergoing regular follow-up without anticancer treatment and noncancer patients with COVID-19 have remained insufficiently investigated. Methods: A retrospective case-control study of 52 patients with COVID-19 infection was performed with a 1:3 matched proportion of cancer patients undergoing regular follow-up without anticancer treatment and noncancer patients. The demographic characteristics, clinical data, laboratory tests, treatment, and complications of patients were collected from medical records. Chi-square tests and univariate and multivariate regressions were performed to assess the differences between these two cohorts of COVID-19 patients with and without cancer and risk factors for severe events in COVID-19 patients. Results: Increased C-reactive protein (CRP) (>4 mg/L) (p = 0.015) and lactate dehydrogenase (LDH) (>243 IU/L) (p = 0.038) were identified as risk factors for severe events in all enrolled COVID-19 patients based on multivariate analysis, but cancer as a chronic disease (p = 1.000) was not identified as an independent risk factor for severe events in COVID-19 patients. Compared with noncancer patients, cancer patients had a significantly longer median hospitalization time (29 days vs. 19 days, p = 0.048) and a higher incidence of hypoalbuminemia complications (84.6 vs. 46.2%, p = 0.016). Conclusions: Increased CRP and LDH were risk factors for severe events in all enrolled COVID-19 patients, and an increased incidence of hypoalbuminemia complications and longer hospitalization were noted in COVID-19 cancer patients undergoing regular follow-up without anticancer treatment compared with noncancer patients.

Design, synthesis, and biological characterization of a potent STAT3 degrader for the treatment of gastric cancer.

Gastric cancer is a common malignant tumor that threatens human health, and its occurrence and development mechanism is a complex process involving multiple genes and multiple signals. Signal transducer and activator of transcription 3 (STAT3) has been elucidated as a promising target for developing anticancer drugs in gastric cancer. However, there is no FDA-approved STAT3 inhibitor yet. Herein, we report the design and synthesis of a class of STAT3 degraders based on proteolysis-targeting chimeras (PROTACs). We first synthesized an analog of the STAT3 inhibitor S3I-201 as a ligand, using the cereblon (CRBN)/cullin 4A E3 ligase ligand pomalidomide to synthesize a series of PROTACs. Among them, the SDL-1 achieves the degradation of STAT3 protein in vitro, and exhibits good anti-gastric cancer cell proliferation activity, inhibits invasion and metastasis of MKN1 cell, and induces MKN1 cell apoptosis and arrests cell cycle at the same time. Our study shows that SDL-1 is a potent STAT3 degrader and may serve as a potential anti-gastric cancer drug, providing ideas for further development of drugs for clinical use.

Application of Ultrasound-Guided Upper Trunk Brachial Plexus Block in Observation of Lower Shoulder Surgery.

This study aims to ensure the wide application of ultrasound-guided superior brachial plexus block in shoulder surgery, solve the application problem of ultrasound-guided superior brachial plexus block in shoulder surgery, make up for severe postoperative pain after shoulder arthroscopy, and improve the patient's recovery ability. In this paper, 90 patients with shoulder arthroscopy were divided into 3 groups: A, B, and C. In recent years, with the rapid development of medicine, ultrasound-guided brachial plexus upper trunk block has been widely used in shoulder surgery. Shoulder arthroscopy is more and more used in the diagnosis and treatment of shoulder diseases because of its advantages of minimally invasive, safe, and rapid recovery. Compared with the traditional operation, it is found that the shoulder arthroscopic operation reduces the incision trauma through the microscope, but the shoulder operation involves more muscles and ligaments, so the perioperative pain of shoulder arthroscopic operation is still serious.

Perceived extrinsic barriers hinder community detection and management of mild cognitive impairment: a cross-sectional study of general practitioners in Shanghai, China.

BACKGROUND: General practitioners (GPs) play a critical role in community detection and management of mild cognitive impairment (MCI). Although adequate knowledge is essential, healthcare practice is shaped by intrinsic and extrinsic factors. This study aimed to test the mediating effect of perceived extrinsic barriers on the associations between knowledge, attitudes, and intended practice of GPs in community detection and management of MCI. METHODS: A cross-sectional study was conducted through an online survey of 1253 GPs sampled from 56 community health centres (CHCs) in Shanghai in 2021. Perceived extrinsic barriers were rated on a five-point Likert scale for patient engagement, working environment, and system context, respectively. A summed score was generated subsequently for each domain ranging from 0 to 100, with a higher score indicating higher barriers. The mediating effect of perceived extrinsic barriers (second-order) and the moderation effect of training on the association between MCI knowledge and practice scores, as well as the moderation effect of past experience on the association between MCI knowledge and extrinsic barriers, were tested through structural equation modelling (SEM) with a partial least square (PLS) approach. RESULTS: The study participants reported an average barrier score of 65.23 (SD = 13.98), 58.34 (SD = 16.95), and 60.37 (SD = 16.99) for patient engagement, working environment, and system context, respectively. Although knowledge had both direct and indirect (through attitudes) effects on intended practice, perceived extrinsic barriers negatively mediated (ß = - 0.012, p = 0.025) the association between knowledge and practice. Training moderated the effect of knowledge on practice (ß = - 0.066, p = 0.014). CONCLUSIONS: Perceived extrinsic barriers have a detrimental effect on the translation of knowledge into practice for community detection and management of MCI. The effect of training on practice declines when knowledge scores become higher.

Knowledge, attitudes, and practice of general practitioners toward community detection and management of mild cognitive impairment: a cross-sectional study in Shanghai, China.

BACKGROUND: General practitioners (GPs) are in a unique position for community detection and management of mild cognitive impairment (MCI). However, adequate knowledge, attitudes, and practice (KAP) are prerequisites for fulfilling such a role. This study aims to assess the MCI-related KAP of GPs in Shanghai, China. METHODS: An online survey was conducted on 1253 GPs who were recruited from 56 community health centres (CHCs) in Shanghai between April and May 2021. Knowledge (8 items), attitudes (13 items), and practice (11 items) were assessed using a scale endorsed by a panel of multidisciplinary experts. An average summed score was calculated and transformed into a score ranging from 0 to 100 for knowledge, attitudes, and practice, respectively. Adjusted odds ratios (AORs) were calculated for potential predictors of higher levels of KAP scores (with mean value as a cutoff point) through logistic modelling. The mediating role of attitudes on the association between knowledge and practice was tested using the PROCESS model 4 macro with 5000 bootstrap samples through linear regression modelling. RESULTS: A total of 1253 GPs completed the questionnaire, with an average score of 54.51 ± 18.18, 57.31 ± 7.43, and 50.05 ± 19.80 for knowledge, attitudes, and practice, respectively. More than 12% of respondents scored zero in knowledge, 28.4% tended not to consider MCI as a disease, and 19.1% completely rejected MCI screening. Higher levels of knowledge were associated with more favourable attitudes toward community management of MCI (AOR = 1.974, p < 0.001). Higher compliance with practice guidelines was associated with both higher levels of knowledge (AOR = 1.426, p < 0.01) and more favourable attitudes (AOR = 2.095, p < 0.001). The association between knowledge and practice was partially mediated by attitudes (p < 0.001). Training was associated with higher levels of knowledge (AOR = 1.553, p < 0.01), while past experience in MCI management was associated with more favourable attitudes (AOR = 1.582, p < 0.05) and higher compliance with practice guidelines (AOR = 3.034, p < 0.001). MCI screening qualification was associated with higher compliance with practice guidelines (AOR = 2.162, p < 0.05), but less favourable attitudes (AOR = 0.452, p < 0.05). CONCLUSION: The MCI knowledge of GPs in Shanghai is low, and is associated with less favourable attitudes toward MCI management and low compliance with practice guidelines. Attitudes mediate the association between knowledge and practice. Training is a significant predictor of knowledge. Further studies are needed to better understand how the attitudes of GPs in Shanghai are shaped by the environments in which they live and work.

Inhibition of STAT3 Signaling Pathway by Terphenyllin Suppresses Growth and Metastasis of Gastric Cancer.

Gastric cancer is a common type of malignant tumor with a relatively poor prognosis and presents a serious threat to global health. Signal Transducer and Activator of Transcription-3 (STAT3) has been strongly implicated in many cancers, and its constitutive activation promotes growth, angiogenesis, inflammation, and immune evasion. Therefore, considerable efforts have been put into developing effective and safe STAT3 inhibitors. In this study, we performed a virtual screening by molecular docking and found that terphenyllin, a marine-derived natural product, directly interacted with STAT3. We further found that terphenyllin inhibited the phosphorylation and activation of STAT3 and decreased the protein levels of STAT3-dependent target genes, including c-Myc and Cyclin D1. Subsequently, we demonstrated that terphenyllin exerted its potent anticancer efficacy against gastric cancer in vitro and in vivo. Terphenyllin concentration-dependently inhibited growth, proliferation, and colony formation and induced cell cycle arrest and apoptosis of gastric cancer cells in vitro. Moreover, terphenyllin treatment suppressed the tumor growth and metastasis in a gastric cancer orthotopic mouse model without notable toxicity in vivo. Taken together, our results indicated that terphenyllin exerts its anticancer activity by inhibiting the STAT3 signaling pathway and may serve as a potent STAT3 inhibitor for gastric cancer treatment.

Characterization of a bioactive meroterpenoid isolated from the marine-derived fungus Talaromyces sp.

A new meroterpenoid, taladrimanin A (1), was isolated from a marine-derived fungus Talaromyces sp. HM6-1-1, together with eleven biogenetically related compounds (2-12). A plausible biosynthetic pathway for the meroterpenoids (1-4) was proposed. The planar structure of 1 was assigned by HRESIMS and NMR. Its relative configuration was established by quantum chemical NMR calculation of two possible isomers and analyzed by DP4 + method. Finally, X-ray diffraction unambiguously confirmed the relative configuration and revealed the absolute configuration of compound 1. 2-12 were assigned by comparing their NMR data with those reported in the literature. 1 was the first drimane-type meroterpenoid with a C10 polyketide unit bearing an 8R-configuration. In the bioactive assay, 1 exhibited antitumor activity against gastric cancer cells MGC803 and MKN28; it also inhibited the colony formation and induced apoptosis in MGC803 cells both in a concentration-dependent manner. Additionally, 1 displayed selective antibacterial activity against Staphylococcus aureus 6538P, and low activities towards strains of Vibrio parahaemolyticus and Escherichia coli in this study. KEY POINTS: • Twelve compounds were obtained from Talaromyces sp., including four meroterpenoids, one of which was new. • The new compound taladrimanin A (1) inhibits the growth of gastric cancer cells MGC803 and MKN28 as well as the pathogenic bacteria Staphylococcus aureus 6538P. • The biosynthetic pathway of the meroterpenoids was proposed.